Ongoing Oxidative Stress Causes Subclinical Neuronal Dysfunction in the Recovery Phase of EAE

PubMed Central

Radbruch, Helena; Bremer, Daniel; Guenther, Robert; Cseresnyes, Zoltan; Lindquist, Randall; Hauser, Anja E.; Niesner, Raluca

2016-01-01

Most multiple sclerosis (MS) patients develop over time a secondary progressive disease course, characterized histologically by axonal loss and atrophy. In early phases of the disease, focal inflammatory demyelination leads to functional impairment, but the mechanism of chronic progression in MS is still under debate. Reactive oxygen species generated by invading and resident central nervous system (CNS) macrophages have been implicated in mediating demyelination and axonal damage, but demyelination and neurodegeneration proceed even in the absence of obvious immune cell infiltration, during clinical recovery in chronic MS. Here, we employ intravital NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX1–4, DUOX1, 2) and, thus, to identify the cellular source of oxidative stress in the CNS of mice affected by experimental autoimmune encephalomyelitis (EAE) in the remission phase of the disease. This directly affects neuronal function in vivo, as monitored by cellular calcium levels using intravital FRET–FLIM, providing a possible mechanism of disease progression in MS. PMID:27014271

Linear Combinations of Multiple Outcome Measures to Improve the Power of Efficacy Analysis ---Application to Clinical Trials on Early Stage Alzheimer Disease

PubMed Central

Xiong, Chengjie; Luo, Jingqin; Morris, John C; Bateman, Randall

2018-01-01

Modern clinical trials on Alzheimer disease (AD) focus on the early symptomatic stage or even the preclinical stage. Subtle disease progression at the early stages, however, poses a major challenge in designing such clinical trials. We propose a multivariate mixed model on repeated measures to model the disease progression over time on multiple efficacy outcomes, and derive the optimum weights to combine multiple outcome measures by minimizing the sample sizes to adequately power the clinical trials. A cross-validation simulation study is conducted to assess the accuracy for the estimated weights as well as the improvement in reducing the sample sizes for such trials. The proposed methodology is applied to the multiple cognitive tests from the ongoing observational study of the Dominantly Inherited Alzheimer Network (DIAN) to power future clinical trials in the DIAN with a cognitive endpoint. Our results show that the optimum weights to combine multiple outcome measures can be accurately estimated, and that compared to the individual outcomes, the combined efficacy outcome with these weights significantly reduces the sample size required to adequately power clinical trials. When applied to the clinical trial in the DIAN, the estimated linear combination of six cognitive tests can adequately power the clinical trial. PMID:29546251

Recent progress in MEMS technology development for military applications

NASA Astrophysics Data System (ADS)

Ruffin, Paul B.; Burgett, Sherrie J.

2001-08-01

The recent progress of ongoing efforts at the Army Aviation and Missile Command (AMCOM) to develop microelectromechanical systems (MEMS) technology for military applications is discussed in this paper. The current maturity level of low cost, low power, micro devices in industry, which range from simple temperature and pressure sensors to accelerometers in airbags, provides a viable foundation for the development of rugged MEMS devices for dual-use applications. Early MEMS technology development efforts at AMCOM emphasized inertial MEMS sensors. An Army Science and Technology Objective (STO) project was initiated to develop low cost inertial components with moderate angular rate sensor resolution for measuring pitch and yaw of missile attitude and rotational roll rate. Leveraging the Defense Advanced Research Projects Agency and other Government agencies has resulted in the development of breadboard inertial MEMS devices with improved robustness. During the past two years, MEMS research at AMCOM has been expanded to include environmental MEMS sensors for missile health monitoring, RF-MEMS, optical MEMS devices for beam steering, and micro-optic 'benches' for opto-electronics miniaturization. Additionally, MEMS packaging and integration issues have come into focus and are being addressed. Selected ongoing research efforts in these areas are presented, and some horizon MEMS sensors requirements for Army and law enforcement are presented for consideration.

Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy

PubMed Central

Waddington Cruz, Márcia; Amass, Leslie; Keohane, Denis; Schwartz, Jeffrey; Li, Huihua; Gundapaneni, Balarama

2016-01-01

Abstract Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and −7.8 (−44.3, 28.8) kg/m2 × g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis. Trial Registration: ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002. PMID:27494299

Evaluating Fluorscence-Based Metrics for Early Detection of ...

EPA Pesticide Factsheets

Summary: This paper discusses the results of an ongoing Water Research Foundation project on developing a fluorescence sensor system for early detection of distribution system nitrification Summary: This paper discusses the results of an ongoing Water Research Foundation project on developing a fluorescence sensor system for early detection of distribution system nitrification

Ongoing Progress in Spacecraft Controls

NASA Technical Reports Server (NTRS)

Ghosh, Dave (Editor)

1992-01-01

This publication is a collection of papers presented at the Mars Mission Research Center workshop on Ongoing Progress in Spacecraft Controls. The technical program addressed additional Mars mission control problems that currently exist in robotic missions in addition to human missions. Topics include control systems design in the presence of large time delays, fuel-optimal propulsive control, and adaptive control to handle a variety of unknown conditions.

Prostate cancer diagnostics: Clinical challenges and the ongoing need for disruptive and effective diagnostic tools.

PubMed

Sharma, Shikha; Zapatero-Rodríguez, Julia; O'Kennedy, Richard

The increased incidence and the significant health burden associated with carcinoma of the prostate have led to substantial changes in its diagnosis over the past century. Despite technological advancements, the management of prostate cancer has become progressively more complex and controversial for both early and late-stage disease. The limitations and potential harms associated with the use of prostate-specific antigen (PSA) as a diagnostic marker have stimulated significant investigation of numerous novel biomarkers that demonstrate varying capacities to detect prostate cancer and can decrease unnecessary biopsies. However, only a few of these markers have been approved for specific clinical settings while the others have not been adequately validated for use. This review systematically and critically assesses ongoing issues and emerging challenges in the current state of prostate cancer diagnostic tools and the need for disruptive next generation tools based on analysis of combinations of these biomarkers to enhance predictive accuracy which will benefit clinical diagnostics and patient welfare. Copyright © 2016. Published by Elsevier Inc.

Geriatric trauma.

PubMed

Adams, Sasha D; Holcomb, John B

2015-12-01

The landscape of trauma is changing due to an aging population. Geriatric patients represent an increasing number and proportion of trauma admissions and deaths. This review explores recent literature on geriatric trauma, including triage criteria, assessment of frailty, fall-related injury, treatment of head injury complicated by coagulopathy, goals of care, and the need for ongoing education of all surgeons in the care of the elderly. Early identification of high-risk geriatric patients is imperative to initiate early resuscitative efforts. Geriatric patients are typically undertriaged because of their baseline frailty being underappreciated; however, centers that see more geriatric patients do better. Rapid reversal of anticoagulation is important in preventing progression of brain injury. Anticipation of difficult disposition necessitates early involvement of physical therapy for rehabilitation and case management for appropriate placement. Optimal care of geriatric trauma patients will be based on the well established tenets of trauma resuscitation and injury repair, but with distinct elements that address the physiological and anatomical challenges presented by geriatric patients.

Pluripotent cell models of fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.

PubMed

Suzuki, Naoya M; Niwa, Akira; Yabe, Miharu; Hira, Asuka; Okada, Chihiro; Amano, Naoki; Watanabe, Akira; Watanabe, Ken-Ichiro; Heike, Toshio; Takata, Minoru; Nakahata, Tatsutoshi; Saito, Megumu K

2015-04-01

Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF. ©AlphaMed Press.

Child neurology: Brachial plexus birth injury: what every neurologist needs to know.

PubMed

Pham, Christina B; Kratz, Johannes R; Jelin, Angie C; Gelfand, Amy A

2011-08-16

While most often transient, brachial plexus birth injury can cause permanent neurologic injury. The major risk factors for brachial plexus birth injury are fetal macrosomia and shoulder dystocia. The degree of injury to the brachial plexus should be determined in the neonatal nursery, as those infants with the most severe injury--root avulsion--should be referred early for surgical evaluation so that microsurgical repair of the plexus can occur by 3 months of life. Microsurgical repair options include nerve grafts and nerve transfers. All children with brachial plexus birth injury require ongoing physical and occupational therapy and close follow-up to monitor progress.

Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease

PubMed Central

Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald

2015-01-01

Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

Quantitative structural MRI for early detection of Alzheimer’s disease

PubMed Central

McEvoy, Linda K; Brewer, James B

2011-01-01

Alzheimer’s disease (AD) is a common progressive neurodegenerative disorder that is not currently diagnosed until a patient reaches the stage of dementia. There is a pressing need to identify AD at an earlier stage, so that treatment, when available, can begin early. Quantitative structural MRI is sensitive to the neurodegeneration that occurs in mild and preclinical AD, and is predictive of decline to dementia in individuals with mild cognitive impairment. Objective evidence of ongoing brain atrophy will be critical for risk/benefit decisions once potentially aggressive, disease-modifying treatments become available. Recent advances have paved the way for the use of quantitative structural MRI in clinical practice, and initial clinical use has been promising. However, further experience with these measures in the relatively unselected patient populations seen in clinical practice is needed to complete translation of the recent enormous advances in scientific knowledge of AD into the clinical realm. PMID:20977326

Emotion episodes during psychotherapy sessions among women newly diagnosed with gynecological cancers.

PubMed

Myers Virtue, Shannon; Manne, Sharon L; Darabos, Kathleen; Heckman, Carolyn J; Ozga, Melissa; Kissane, David; Rubin, Stephen; Rosenblum, Norman

2015-09-01

The aim of this study was to describe emotion episodes during early and late psychotherapy sessions among women newly diagnosed with gynecological cancer and to examine whether the total number of emotion episodes during early and later sessions was associated with baseline psychological distress, dispositional emotion expressivity, and patient-rated therapeutic progress. The study utilized data from an ongoing study examining the efficacy of two psychotherapy interventions, a coping and communication intervention and a supportive counseling intervention, for women diagnosed with gynecological cancer. Emotion episode coding was completed for the first and sixth psychotherapy sessions for each patient randomized to receive psychotherapy (N = 173). Patients completed baseline survey measures of psychological distress and dispositional emotional expressivity and post-session ratings of therapeutic progress. The average number of emotion episodes was 7.4 in the first session and 5.2 episodes in the sixth session. In both sessions, the majority of emotion episodes contained only negative emotions and focused on a cancer-related topic. A higher number of emotion episodes in the first session was associated with higher psychological distress reported in the baseline survey (p = 0.02). A higher number of emotion episodes in the sixth session was associated with a higher number of emotion episodes in the first session (p < 0.001) and higher patient-rated progress as rated in the sixth session (p = 0.016). The findings highlight the importance of expressed emotions, particularly negative emotions about cancer-related topics, in therapeutic progress during psychotherapy among women diagnosed with gynecological cancer. Copyright © 2014 John Wiley & Sons, Ltd.

Development and initial validation of the Classification of Early-Onset Scoliosis (C-EOS).

PubMed

Williams, Brendan A; Matsumoto, Hiroko; McCalla, Daren J; Akbarnia, Behrooz A; Blakemore, Laurel C; Betz, Randal R; Flynn, John M; Johnston, Charles E; McCarthy, Richard E; Roye, David P; Skaggs, David L; Smith, John T; Snyder, Brian D; Sponseller, Paul D; Sturm, Peter F; Thompson, George H; Yazici, Muharrem; Vitale, Michael G

2014-08-20

Early-onset scoliosis is a heterogeneous condition, with highly variable manifestations and natural history. No standardized classification system exists to describe and group patients, to guide optimal care, or to prognosticate outcomes within this population. A classification system for early-onset scoliosis is thus a necessary prerequisite to the timely evolution of care of these patients. Fifteen experienced surgeons participated in a nominal group technique designed to achieve a consensus-based classification system for early-onset scoliosis. A comprehensive list of factors important in managing early-onset scoliosis was generated using a standardized literature review, semi-structured interviews, and open forum discussion. Three group meetings and two rounds of surveying guided the selection of classification components, subgroupings, and cut-points. Initial validation of the system was conducted using an interobserver reliability assessment based on the classification of a series of thirty cases. Nominal group technique was used to identify three core variables (major curve angle, etiology, and kyphosis) with high group content validity scores. Age and curve progression ranked slightly lower. Participants evaluated the cases of thirty patients with early-onset scoliosis for reliability testing. The mean kappa value for etiology (0.64) was substantial, while the mean kappa values for major curve angle (0.95) and kyphosis (0.93) indicated almost perfect agreement. The final classification consisted of a continuous age prefix, etiology (congenital or structural, neuromuscular, syndromic, and idiopathic), major curve angle (1, 2, 3, or 4), and kyphosis (-, N, or +) variables, and an optional progression modifier (P0, P1, or P2). Utilizing formal consensus-building methods in a large group of surgeons experienced in treating early-onset scoliosis, a novel classification system for early-onset scoliosis was developed with all core components demonstrating substantial to excellent interobserver reliability. This classification system will serve as a foundation to guide ongoing research efforts and standardize communication in the clinical setting. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Antisense Therapy in Neurology

PubMed Central

Lee, Joshua J.A.; Yokota, Toshifumi

2013-01-01

Antisense therapy is an approach to fighting diseases using short DNA-like molecules called antisense oligonucleotides. Recently, antisense therapy has emerged as an exciting and promising strategy for the treatment of various neurodegenerative and neuromuscular disorders. Previous and ongoing pre-clinical and clinical trials have provided encouraging early results. Spinal muscular atrophy (SMA), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), Fukuyama congenital muscular dystrophy (FCMD), dysferlinopathy (including limb-girdle muscular dystrophy 2B; LGMD2B, Miyoshi myopathy; MM, and distal myopathy with anterior tibial onset; DMAT), and myotonic dystrophy (DM) are all reported to be promising targets for antisense therapy. This paper focuses on the current progress of antisense therapies in neurology. PMID:25562650

Electroactive polymer-based devices for e-textiles in biomedicine.

PubMed

Carpi, Federico; De Rossi, Danilo

2005-09-01

This paper describes the early conception and latest developments of electroactive polymer (EAP)-based sensors, actuators, electronic components, and power sources, implemented as wearable devices for smart electronic textiles (e-textiles). Such textiles, functioning as multifunctional wearable human interfaces, are today considered relevant promoters of progress and useful tools in several biomedical fields, such as biomonitoring, rehabilitation, and telemedicine. After a brief outline on ongoing research and the first products on e-textiles under commercial development, this paper presents the most highly performing EAP-based devices developed by our lab and other research groups for sensing, actuation, electronics, and energy generation/storage, with reference to their already demonstrated or potential applicability to electronic textiles.

Restrictive Versus Massive Fluid Resuscitation Strategy (REFILL study), influence on blood loss and hemostatic parameters in obstetric hemorrhage: study protocol for a randomized controlled trial.

PubMed

de Lange, Natascha; Schol, Pim; Lancé, Marcus; Woiski, Mallory; Langenveld, Josje; Rijnders, Robbert; Smits, Luc; Wassen, Martine; Henskens, Yvonne; Scheepers, Hubertina

2018-03-06

Postpartum hemorrhage (PPH) is associated with maternal morbidity and mortality and has an increasing incidence in high-resource countries, despite dissemination of guidelines, introduction of skills training, and correction for risk factors. Current guidelines advise the administration, as fluid resuscitation, of almost twice the amount of blood lost. This advice is not evidence-based and could potentially harm patients. All women attending the outpatient clinic who are eligible will be informed of the study; oral and written informed consent will be obtained. Where there is more than 500 ml blood loss and ongoing bleeding, patients will be randomized to care as usual, fluid resuscitation with 1.5-2 times the amount of blood loss or fluid resuscitation with 0.75-1.0 times the blood loss. Blood loss will be assessed by weighing all draping. A blood sample, for determining hemoglobin concentration, hematocrit, thrombocyte concentration, and conventional coagulation parameters will be taken at the start of the study, after 60 min, and 12-18 h after delivery. In a subgroup of women, additional thromboelastometric parameters will be obtained. Our hypothesis is that massive fluid administration might lead to a progression of bleeding due to secondary coagulation disorders. In non-pregnant individuals with massive blood loss, restrictive fluid management has been shown to prevent a progression to dilution coagulopathy. These data, however, cannot be extrapolated to women in labor. Our objective is to compare both resuscitation protocols in women with early, mild PPH (blood loss 500-750 ml) and ongoing bleeding, taking as primary outcome measure the progression to severe PPH (blood loss > 1000 ml). Netherlands Trial Register, NTR 3789 . Registered on 11 January 2013.

From Cheerleader to Coach: The Developmental Progression of Bedside Teachers in Giving Feedback to Early Learners.

PubMed

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

2015-11-01

Medical students learn clinical skills at the bedside from teaching clinicians, who often learn to teach by teaching. Little is known about the process of becoming an effective clinical teacher. Understanding how teaching skills and approaches change with experience may help tailor faculty development for new teachers. Focusing on giving feedback to early learners, the authors asked: What is the developmental progression of clinician-teachers as they learn to give clinical skills feedback to medical students? This qualitative study included longitudinal interviews with clinician-teachers over five years in a new clinical skills teaching program for preclinical medical students. Techniques derived from grounded theory were used for initial analyses. The current study focused on one theme identified in initial analyses: giving feedback to students. Transcript passages were organized by interview year, coded, and discussed in year clusters; thematic codes were compared and emergent codes developed. Themes related to giving feedback demonstrated a dyadic structure: characteristic of less experienced teachers versus characteristic of experienced teachers. Seven dominant dyadic themes emerged, including teacher as cheerleader versus coach, concern about student fragility versus understanding resilience, and focus on creating a safe environment versus challenging students within a safe environment. With consistent teaching, clinical teachers demonstrated progress in giving feedback to students in multiple areas, including understanding students' developmental trajectory and needs, developing tools and strategies, and adopting a dynamic, challenging, inclusive team approach. Ongoing teaching opportunities with targeted faculty development may help improve clinician-teachers' feedback skills and approaches.

Emerging Therapies in Metastatic Prostate Cancer.

PubMed

Sonnenburg, Daniel W; Morgans, Alicia K

2018-04-11

In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy. A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects. Multiple ongoing clinical trials are investigating novel hormonal therapies and combinations of chemotherapy, targeted small molecules, immunotherapy, and radiopharmaceuticals. Progress continues to be made in the treatment of metastatic prostate cancer, and ongoing clinical trials continue to investigate novel agents and approaches to treatment.

Anaplastic lymphoma kinase inhibitors in brain metastases from ALK+ non-small cell lung cancer: hitting the target even in the CNS.

PubMed

Klempner, Samuel J; Ou, Sai-Hong Ignatius

2015-06-01

The paradigm shift occurring in non-small cell lung cancer (NSCLC) is encapsulated by the management of patients harboring oncogenic anaplastic lymphoma kinase (ALK) rearrangements. The unprecedented improvements in patient outcomes resulting from ALK-directed therapy have led to the appreciation of patterns of disease progression. Early studies have suggested that some tyrosine kinase inhibitors (TKIs), including ALK TKIs, inefficiently penetrated the blood brain barrier. With the increasing appreciation of the CNS as a sanctuary site in ALK TKI-treated patients, there is increasing focus and importance on the prevention and control of CNS metastases in ALK-rearranged NSCLC. The spectrum of CNS activity is variable among the currently available ALK TKI therapies and further studies are ongoing. In the following review we discuss the ability of current and future ALK inhibitors (ALK-i) to control and prevent CNS progression in patients with ALK-rearranged NSCLC. The potential implications for TKI sequencing and important future research directions are discussed.

Role of pirfenidone in the management of pulmonary fibrosis.

PubMed

Meyer, Keith C; Decker, Catherine A

2017-01-01

Pulmonary fibrosis is associated with a number of specific forms of interstitial lung disease (ILD) and can lead to progressive decline in lung function, poor quality of life, and, ultimately, early death. Idiopathic pulmonary fibrosis (IPF), the most common fibrotic ILD, affects up to 1 in 200 elderly individuals and has a median survival that ranges from 3 to 5 years following initial diagnosis. IPF has not been shown to respond to immunomodulatory therapies, but recent trials with novel antifibrotic agents have demonstrated lessening of lung function decline over time. Pirfenidone has been shown to significantly slow decline in forced vital capacity (FVC) over time and prolong progression-free survival, which led to its licensing by the United States Food and Drug Administration (FDA) in 2014 for the treatment of patients with IPF. However, pirfenidone has been associated with significant side effects, and patients treated with pirfenidone must be carefully monitored. We review recent and ongoing clinical research and experience with pirfenidone as a pharmacologic therapy for patients with IPF, provide a suggested approach to incorporate pirfenidone into a treatment algorithm for patients with IPF, and examine the potential of pirfenidone as a treatment for non-IPF forms of ILD accompanied by progressive pulmonary fibrosis.

Progress towards early detection services for infants with hearing loss in developing countries

PubMed Central

Olusanya, Bolajoko O; Swanepoel, De Wet; Chapchap, Mônica J; Castillo, Salvador; Habib, Hamed; Mukari, Siti Z; Martinez, Norberto V; Lin, Hung-Ching; McPherson, Bradley

2007-01-01

Background Early detection of infants with permanent hearing loss through infant hearing screening is recognised and routinely offered as a vital component of early childhood care in developed countries. This article investigates the initiatives and progress towards early detection of infants with hearing loss in developing countries against the backdrop of the dearth of epidemiological data from this region. Methods A cross-sectional, descriptive study based on responses to a structured questionnaire eliciting information on the nature and scope of early hearing detection services; strategies for financing services; parental and professional attitudes towards screening; and the performance of screening programmes. Responses were complemented with relevant data from the internet and PubMed/Medline. Results Pilot projects using objective screening tests are on-going in a growing number of countries. Screening services are provided at public/private hospitals and/or community health centres and at no charge only in a few countries. Attitudes amongst parents and health care workers are typically positive towards such programmes. Screening efficiency, as measured by referral rate at discharge, was generally found to be lower than desired but several programmes achieved other international benchmarks. Coverage is generally above 90% but poor follow-up rates remain a challenge in some countries. The mean age of diagnosis is usually less than six months, even for community-based programmes. Conclusion Lack of adequate resources by many governments may limit rapid nationwide introduction of services for early hearing detection and intervention, but may not deter such services altogether. Parents may be required to pay for services in some settings in line with the existing practice where healthcare services are predominantly financed by out-of-pocket spending rather than public funding. However, governments and their international development partners need to complement current voluntary initiatives through systematic scaling-up of public awareness and requisite manpower development towards sustainable service capacities at all levels of healthcare delivery. PMID:17266763

The MEarth Project: Finding the Best Targets for Atmospheric Characterization with JWST

NASA Astrophysics Data System (ADS)

Berta-Thompson, Z.

2014-04-01

If we want to directly observe the radius, orbit, mass, and atmosphere of a small, cool, habitable exoplanet, our best opportunity is to find such a planet transiting a small, cool, nearby M dwarf star. The MEarth Project is an ongoing all-sky survey for Earth-like planets transiting the closest, smallest M dwarfs in the Galaxy. MEarth aims to find good targets for atmospheric characterization with JWST and the next generation of enormous ground-based telescopes. This poster provides a status update on the MEarth Project, including the progress we've made over the past five years with 8 telescopes in the Northern hemisphere and promising early results from our new installation of 8 more telescopes in the Southern hemisphere.

Biomolecularmodeling and simulation: a field coming of age

PubMed Central

Schlick, Tamar; Collepardo-Guevara, Rosana; Halvorsen, Leif Arthur; Jung, Segun; Xiao, Xia

2013-01-01

We assess the progress in biomolecular modeling and simulation, focusing on structure prediction and dynamics, by presenting the field’s history, metrics for its rise in popularity, early expressed expectations, and current significant applications. The increases in computational power combined with improvements in algorithms and force fields have led to considerable success, especially in protein folding, specificity of ligand/biomolecule interactions, and interpretation of complex experimental phenomena (e.g. NMR relaxation, protein-folding kinetics and multiple conformational states) through the generation of structural hypotheses and pathway mechanisms. Although far from a general automated tool, structure prediction is notable for proteins and RNA that preceded the experiment, especially by knowledge-based approaches. Thus, despite early unrealistic expectations and the realization that computer technology alone will not quickly bridge the gap between experimental and theoretical time frames, ongoing improvements to enhance the accuracy and scope of modeling and simulation are propelling the field onto a productive trajectory to become full partner with experiment and a field on its own right. PMID:21226976

Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

PubMed

Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

2016-05-01

HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization. Copyright © 2016 Elsevier Inc. All rights reserved.

Progress in European CELSS activities

NASA Technical Reports Server (NTRS)

Skoog, A. I.

1987-01-01

The European Controlled Ecological Life Support System (CELSS) activities started in the late 1970's with system analysis and feasibility studies of Biological Life Support Systems (BLSS). The initiation for CELSS came from the industry side in Europe, but since then planning and hardware feasibility analyses have been initiated also from customer/agency side. Despite this, it is still too early to state that a CELSS program as a concerted effort has been agreed upon in Europe. However, the general CELSS objectives were accepted as planning and possible development goals for the European effort for manned space activities, and as experimental planning topics in the life sciences community for the next decades. It is expected that ecological life support systems can be tested and implemented on a space station towards the end of this century or early in the next. For the European activities a possible scenario can be projected based on ongoing life support system development activities and the present life sciences goals.

Molecular profiles of finasteride effects on prostate carcinogenesis.

PubMed

Li, Jin; Kim, Jeri

2009-06-01

Our inability to distinguish between low-grade prostate cancers that pose no threat and those that can kill compels newly diagnosed early prostate cancer patients to make decisions that may negatively affect their lives needlessly for years afterward. To reliably stratify patients into different risk categories and apply appropriate treatment, we need a better molecular understanding of prostate cancer progression. Androgen ablation therapy and 5-alpha reductase inhibitors reduce dihydrotestosterone levels and increase apoptosis. Because of the differing biological potentials of tumor cells, however, these treatments may, in some cases, worsen outcome by selecting for or inducing adaptation of stronger androgen receptor signaling pathways. Reduced dihydrotestosterone also may be associated with altered survival pathways. Complicating treatment effects further, molecular adaptation may be accelerated by interactions between epithelial and stromal cells. The hypothesis that early prostate cancer cells with differing biological potential may respond differently to finasteride treatment is worth testing. Ongoing studies using a systems biology approach in a preoperative prostate cancer setting are testing this hypothesis toward developing more-rational clinical interventions.

Souvenaid®: a new approach to management of early Alzheimer's disease.

PubMed

Ritchie, C W; Bajwa, J; Coleman, G; Hope, K; Jones, R W; Lawton, M; Marven, M; Passmore, P

2014-03-01

Synaptic loss correlates closely with cognitive deficits in Alzheimer's disease and represents a new target for intervention. Souvenaid® is the first medical nutrition product to be designed to support synapse formation and function in early Alzheimer's disease, and has undergone an extensive, 12-year development programme. The relatively large amount of clinical data available for Souvenaid® is unusual for a medical nutrition product. Souvenaid® contains omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid), uridine (as uridine monophosphate) and choline which are nutritional precursors required for synaptic membrane phospholipid synthesis, together with phospholipids and other cofactors. Souvenaid® has demonstrated cognitive benefits in patients with mild Alzheimer's disease but not in patients with mild-to-moderate Alzheimer's disease. Two randomised, double-blind, controlled trials (duration 12 and 24 weeks) in patients with mild Alzheimer's disease untreated with acetylcholinesterase inhibitors and/or memantine have demonstrated that Souvenaid® is well tolerated and improves episodic memory performance. The daily intake of Souvenaid® has not been associated with any harmful effects or interactions with medications and none are anticipated. The ongoing, 24-month, European Union-funded LipiDiDiet trial in subjects with prodromal Alzheimer's disease is evaluating the potential benefits of Souvenaid® on memory and in slowing progression to Alzheimer's dementia. If Souvenaid® induces synaptogenesis and improved synaptic function, it may provide benefits in other clinical conditions characterised by neurodegeneration. A number of trials are ongoing and planned to evaluate the potential wider benefits of Souvenaid®.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

PubMed

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H Irene

2014-02-01

To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Technologic developments in the field of photonics for the detection of urinary bladder cancer.

PubMed

Palmer, Scott; Sokolovski, Sergei G; Rafailov, Edik; Nabi, Ghulam

2013-12-01

Bladder cancer is a common cause of morbidity and mortality worldwide in an aging population. Each year, thousands of people, mostly men, are diagnosed with this disease, but many of them present too late to receive optimal treatment. As with all cancers, early diagnosis of bladder cancer significantly improves the efficacy of therapy and increases survival and recurrence-free survival rates. Ongoing research has identified many limitations about the sensitivity of standard diagnostic procedures in detecting early-stage tumors and precancerous changes. The consequences of this are often tumor progression and increased tumor burden, leading to a decrease in patient quality of life and a vast increase in treatment costs. The necessity for improved early detection of bladder cancer has spurred on research into novel methods that use a wide range of biological and photonic phenomena. This review will broadly discuss standard detection methodologies and their major limitations before covering novel photonic techniques for early tumor detection and staging, assessing their diagnostic accuracy for flat and precancerous changes. We will do so in the context of both cystoscopic examination and the screening of voided urine and will also touch on the concept of using photonic technology as a surgical tool for tumor ablation. Copyright © 2013 Elsevier Inc. All rights reserved.

Can women determine the success of early medical termination of pregnancy themselves?

PubMed

Cameron, S T; Glasier, A; Johnstone, A; Dewart, H; Campbell, A

2015-01-01

To determine the outcome of early medical termination of pregnancy (TOP) among women who choose a "self assessment" follow up comprising a self-performed low sensitivity urine pregnancy test with instructions on signs/symptoms that mandate contacting the TOP service. A retrospective review of computer databases of 1726 women choosing self-assessment after early medical TOP (<9 weeks) in the UK. The main outcome measures were (a) number of women choosing self-assessment, (b) contact rates with TOP service and (c) time to presentation with an ongoing pregnancy (failed TOP). Ninety-six percent of women having an early medical TOP and going home to expel the pregnancy chose self-assessment. Two percent of women made unscheduled visits to the TOP service. One hundred and eighty-eight women (11%) telephoned the service about concerns related to complications or the success of treatment. There were eight ongoing pregnancies (0.5%; 95% confidence interval 0.2-0.9%). Four were detected within 4 weeks of treatment; the remainder were not detected until one or more missed menses after the procedure. Most women having an early medical TOP, who go home to expel the pregnancy, choose self-assessment. Relatively few women make unscheduled visits or telephone the TOP service. Most ongoing pregnancies are recognized at an early stage, although late presentation (as with all methods of follow up) does still occur. If women are given clear instructions on how and when to conduct a urine pregnancy test and on signs/symptoms that mandate contacting the TOP service, then they can confirm the success of early medical TOP themselves. Late presentation due to failure to recognize an ongoing pregnancy is rare. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical progression in Parkinson disease and the neurobiology of axons.

PubMed

Cheng, Hsiao-Chun; Ulane, Christina M; Burke, Robert E

2010-06-01

Despite tremendous growth in recent years in our knowledge of the molecular basis of Parkinson disease (PD) and the molecular pathways of cell injury and death, we remain without therapies that forestall disease progression. Although there are many possible explanations for this lack of success, one is that experimental therapeutics to date have not adequately focused on an important component of the disease process, that of axon degeneration. It remains unknown what neuronal compartment, either the soma or the axon, is involved at disease onset, although some have proposed that it is the axons and their terminals that take the initial brunt of injury. Nevertheless, this concept has not been formally incorporated into many of the current theories of disease pathogenesis, and it has not achieved a wide consensus. More importantly, in view of growing evidence that the molecular mechanisms of axon degeneration are separate and distinct from the canonical pathways of programmed cell death that mediate soma destruction, the possibility of early involvement of axons in PD has not been adequately emphasized as a rationale to explore the neurobiology of axons for novel therapeutic targets. We propose that ongoing degeneration of axons, not cell bodies, is the primary determinant of clinically apparent progression of disease, and that future experimental therapeutics intended to forestall disease progression will benefit from a new focus on the distinct mechanisms of axon degeneration.

[Effect of different nutritional support on pancreatic secretion in acute pancreatitis].

PubMed

Achkasov, E E; Pugaev, A V; Nabiyeva, Zh G; Kalachev, S V

To develop and justify optimal nutritional support in early phase of acute pancreatitis (AP). 140 AP patients were enrolled. They were divided into groups depending on nutritional support: group I (n=70) - early enteral tube feeding (ETF) with balanced mixtures, group II (n=30) - early ETF with oligopeptide mixture, group III (n=40) - total parenteral nutrition (TPN). The subgroups were also isolated depending on medication: A - Octreotide, B - Quamatel, C - Octreotide + Quamatel. Pancreatic secretion was evaluated by using of course of disease, instrumental methods, APUD-system hormone levels (secretin, cholecystokinin, somatostatin, vasointestinal peptide). ETF was followed by pancreas enlargement despite ongoing therapy, while TPN led to gradual reduction of pancreatic size up to normal values. α-amylase level progressively decreased in all groups, however in patients who underwent ETF (I and II) mean values of the enzyme were significantly higher compared with TPN (group III). Secretin, cholecystokinin and vasointestinal peptide were increasing in most cases, while the level of somatostatin was below normal in all groups. Enteral tube feeding (balanced and oligopeptide mixtures) contributes to pancreatic secretion compared with TPN, but this negative impact is eliminated by antisecretory therapy. Dual medication (Octreotide + Quamatel) is more preferable than monotherapy (Octreotide or Quamatel).

Neglected evidence in idiopathic pulmonary fibrosis and the importance of early diagnosis and treatment.

PubMed

Cottin, Vincent; Richeldi, Luca

2014-03-01

In idiopathic pulmonary fibrosis (IPF), some facts or concepts based on substantial evidence, whilst implicit for learned subspecialists, have previously been neglected and/or not explicitly formulated or made accessible to a wider audience. IPF is strongly associated with cigarette smoking and is predominantly a disease of ageing. However, its cause(s) remain elusive and, thus, it is one of the most challenging diseases for the development of novel effective and safe therapies. With the approval of pirfenidone for patients with mild-to-moderate IPF, an earlier diagnosis of IPF is a prerequisite for earlier treatment and, potentially, improvement of the long-term clinical outcome of this progressive and ultimately fatal disease. An earlier diagnosis may be achieved in IPF by promoting thin-slice chest high-resolution computed tomography screening of interstitial lung disease as a "by-product" of large-scale lung cancer screening strategies in smokers, but other techniques, which have been neglected in the past, are now available. Lung auscultation and early identification of "velcro" crackles has been proposed as a key component of early diagnosis of IPF. An ongoing study is exploring correlations between lung sounds on auscultation obtained using electronic stethoscopes and high-resolution computed tomography patterns.

Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer.

PubMed

Lampaki, Sofia; Lazaridis, George; Zarogoulidis, Konstantinos; Kioumis, Ioannis; Papaiwannou, Antonis; Tsirgogianni, Katerina; Karavergou, Anastasia; Tsiouda, Theodora; Karavasilis, Vasilis; Yarmus, Lonny; Darwiche, Kaid; Freitag, Lutz; Sakkas, Antonios; Kantzeli, Angeliki; Baka, Sofia; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul

2015-01-01

Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the opportunity for a definitive answer of the role of tyrosine kinase inhibitors in induction treatment before chemo-radiotherapy or in early disease adjuvant therapy.

Early antiretroviral therapy: rationale, protease inhibitor-sparing regimens and once daily dosing.

PubMed

Gatell, J M

1998-01-01

In 1998 it seems reasonable and widely accepted that all human immunodeficiency virus type 1 (HIV-1)-infected patients willing to be treated may benefit from receiving antiretroviral therapy. Only those with undetectable plasma HIV-1 RNA, normal CD4 lymphocyte counts and lack of markers of immunological system activation may be possible exceptions. The rationale supporting the early initiation of antiretroviral therapy are (i) data on viral dynamics; (ii) preliminary data pointing toward a better and a quicker restoration of immune function when treatment is initiated in very early stages (during or within a few weeks or months of acute symptomatic or asymptomatic HIV-1 infection); (iii) the lack of a stable viral load set-point even in patients in the early stages (CD4 > 500 cells/mm3) who have a very low viral load (< 5000 copies/ml); (iv) the relatively high likelihood of clinical progression at mid-term of the approximately 50-75% of patients in very early disease stages (CD4 > 500 cells/mm3) who have a plasma viral load above 5000 to 10,000 HIV-1 RNA copies/ml; (v) data from the Spanish Earth-1 study, which used a composite endpoint (virological, immunological or clinical progression), demonstrating that even in these very early stages of HIV-1 disease any antiretroviral therapy (double or triple combination) was better than no treatment. Even in early disease stages, a triple combination is needed to achieve a durable and profound virological and immunological response. In addition, the combination of stavudine plus didanosine has several advantages and can be considered one of the best double nucleoside combinations to combine with a protease inhibitor or with a non-nucleoside reverse transcriptase inhibitor. The INCAS study and the preliminary results of the ongoing Spanish SCAN study have demonstrated the possibility of protease inhibitor-sparing combinations for initial antiretroviral treatment, at least in selected patient subsets, such as those with a relatively low baseline viral load. Furthermore, components of these protease inhibitor-sparing combinations such as didanosine or nevirapine are suitable for once daily administration.

The MEarth Project: Status Update and the Commissioning of a Brand New Telescope Array in the Southern Hemisphere

NASA Astrophysics Data System (ADS)

Berta-Thompson, Zachory K.; Irwin, Jonathan; Charbonneau, David; Newton, Elisabeth R.; Dittmann, Jason

2014-06-01

The MEarth Project is an ongoing all-sky survey for Earth-like planets transiting the closest, smallest M dwarfs. MEarth aims to find good targets for atmospheric characterization with JWST and the next generation of enormous ground-based telescopes. MEarth's yearly data releases, containing precise light curves of nearby mid-to-late M dwarfs, provide a unique window into the photometric variability of the stars that will forever be among the most interesting targets in the search for potentially habitable exoplanets. We present a status update on the MEarth Project, including a detailed map of the progress we’ve made so far with 8 telescopes in the Northern hemisphere and promising early results from our new installation of 8 more telescopes in the Southern hemisphere.

Automated Attitude Sensor Calibration: Progress and Plans

NASA Technical Reports Server (NTRS)

Sedlak, Joseph; Hashmall, Joseph

2004-01-01

This paper describes ongoing work a NASA/Goddard Space Flight Center to improve the quality of spacecraft attitude sensor calibration and reduce costs by automating parts of the calibration process. The new calibration software can autonomously preview data quality over a given time span, select a subset of the data for processing, perform the requested calibration, and output a report. This level of automation is currently being implemented for two specific applications: inertial reference unit (IRU) calibration and sensor alignment calibration. The IRU calibration utility makes use of a sequential version of the Davenport algorithm. This utility has been successfully tested with simulated and actual flight data. The alignment calibration is still in the early testing stage. Both utilities will be incorporated into the institutional attitude ground support system.

Early diagnostic of concurrent gear degradation processes progressing under time-varying loads

NASA Astrophysics Data System (ADS)

Guilbault, Raynald; Lalonde, Sébastien

2016-08-01

This study develops a gear diagnostic procedure for the detection of multi- and concurrent degradation processes evolving under time-varying loads. Instead of a conventional comparison between a descriptor and an alarm level, this procedure bases its detection strategy on a descriptor evolution tracking; a lasting descriptor increase denotes the presence of ongoing degradation mechanisms. The procedure works from time domain residual signals prepared in the frequency domain, and accepts any gear conditions as reference signature. To extract the load fluctuation repercussions, the procedure integrates a scaling factor. The investigation first examines a simplification assuming a linear connection between the load and the dynamic response amplitudes. However, while generally valuable, the precision losses associated with large load variations may mask the contribution of tiny flaws. To better reflect the real non-linear relation, the paper reformulates the scaling factor; a power law with an exponent value of 0.85 produces noticeable improvements of the load effect extraction. To reduce the consequences of remaining oscillations, the procedure also includes a filtering phase. During the validation program, a synthetic wear progression assuming a commensurate relation between the wear depth and friction assured controlled evolutions of the surface degradation influence, whereas the fillet crack growth remained entirely determined by the operation conditions. Globally, the tested conditions attest that the final strategy provides accurate monitoring of coexisting isolated damages and general surface deterioration, and that its tracking-detection capacities are unaffected by severe time variations of external loads. The procedure promptly detects the presence of evolving abnormal phenomena. The tests show that the descriptor curve shapes virtually describe the constant wear progression superimposed on the crack length evolution. At the tooth fracture, the mean values of the residual signal evince strong perturbations, while after this episode, the monitoring curves continue signaling the ongoing wear process.

Overview of Play: Its Uses and Importance in Early Intervention/Early Childhood Special Education

ERIC Educational Resources Information Center

Lifter, Karin; Foster-Sanda, Suzanne; Arzamarski, Caley; Briesch, Jacquelyn; McClure, Ellen

2011-01-01

Play is a natural activity of early childhood, which has great relevance to the fields of early intervention, early childhood special education, and early childhood education. Within these fields, ongoing tensions persist in how play is described and used. These tensions compromise activities of assessment, intervention, and curriculum development…

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2016-02-01

14. ABSTRACT Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive...pugilistica 3, 11 or ‘punch drunk’ syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain...Progress to date: To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing

Left ventricular remodeling leads to heart failure in mice with cardiac-specific overexpression of VEGF-B167: echocardiography and magnetic resonance imaging study.

PubMed

Lottonen-Raikaslehto, Line; Rissanen, Riina; Gurzeler, Erika; Merentie, Mari; Huusko, Jenni; Schneider, Jurgen E; Liimatainen, Timo; Ylä-Herttuala, Seppo

2017-03-01

Cardiac-specific overexpression of vascular endothelial growth factor (VEGF)-B 167 is known to induce left ventricular hypertrophy due to altered lipid metabolism, in which ceramides accumulate to the heart and cause mitochondrial damage. The aim of this study was to evaluate and compare different imaging methods to find the most sensitive way to diagnose at early stage the progressive left ventricular remodeling leading to heart failure. Echocardiography and cardiovascular magnetic resonance imaging were compared for imaging the hearts of transgenic mice with cardiac-specific overexpression of VEGF-B 167 and wild-type mice from 5 to 14 months of age at several time points. Disease progression was verified by molecular biology methods and histology. We showed that left ventricular remodeling is already ongoing at the age of 5 months in transgenic mice leading to heart failure by the age of 14 months. Measurements from echocardiography and cardiovascular magnetic resonance imaging revealed similar changes in cardiac structure and function in the transgenic mice. Changes in histology, gene expressions, and electrocardiography supported the progression of left ventricular hypertrophy. Longitudinal relaxation time in rotating frame (T 1 ρ ) in cardiovascular magnetic resonance imaging could be suitable for detecting severe fibrosis in the heart. We conclude that cardiac-specific overexpression of VEGF-B 167 leads to left ventricular remodeling at early age and is a suitable model to study heart failure development with different imaging methods. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

PubMed Central

Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

The future for follow-up of gynaecological cancer in Europe. Summary of available data and overview of ongoing trials.

PubMed

Leeson, S C; Beaver, K; Ezendam, N P M; Mačuks, R; Martin-Hirsch, P L; Miles, T; Jeppesen, M M; Jensen, P T; Zola, P

2017-03-01

After completing treatment, most patients follow a pre-determined schedule of regular hospital outpatient appointments, which includes clinical examinations, consultations and routine tests. After several years of surveillance, patients are transferred back to primary care. However, there is limited evidence to support the effectiveness and efficiency of this approach. This paper examines the current rationale and evidence base for hospital-based follow-up after treatment for gynaecological cancer. We investigate what alternative models of care have been formally evaluated and what research is currently in progress in Europe, in order to make tentative recommendations for a model of follow-up. The evidence base for traditional hospital based follow-up is limited. Alternative models have been reported for other cancer types but there are few evaluations of alternative approaches for gynaecological cancers. We identified five ongoing European studies; four were focused on endometrial cancer patients and one feasibility study included all gynaecological cancers. Only one study had reached the reporting stage. Alternative models included nurse-led telephone follow-up and comparisons of more intensive versus less intensive regimes. Outcomes included survival, quality of life, psychological morbidity, patient satisfaction and cost effectiveness of service. More work is needed on alternative strategies for all gynaecological cancer types. New models will be likely to include risk stratification with early discharge from secondary care for early stage disease with fast track access to specialist services for suspected cancer recurrence or other problems. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronological changes in the eighth cranial nerve compound action potential (CAP) in experimental endolymphatic hydrops: the effects of altering the polarity of click sounds.

PubMed

Morizono, Tetsuo; Kondo, Tsuyoshi; Yamano, Takafumi; Miyagi, Morimichi; Shiraishi, Kimio

2009-02-01

Using a guinea pig model of experimental endolymphatic hydrops, click sounds of altered polarity showed different latencies and amplitudes in hydropic compared with normal cochleae. Latency changes appeared as early as 1 week after endolymphatic obstruction. This method can help diagnose endolymphatic hydrops. The goal of the study was to develop an objective electrophysiological diagnosis of endolymphatic hydrops. Endolymphatic hydrops were created surgically in guinea pigs. The latency and the amplitude of the eighth cranial nerve compound action potential (CAP) for click sounds of altered polarity were measured up to 8 weeks after the surgery. At early stages after surgery, the latency for condensation clicks became longer, and at later stages the latencies for both condensation and rarefaction became longer. The discrepancy in the latencies for rarefaction and condensation click sounds (rarefaction minus condensation) became larger by the first week after surgery, but no further discrepancy occurred thereafter. Compared with latency changes, amplitude changes in the CAP were rapid and progressive following surgery, suggesting ongoing damage to hair cells.

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

Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

PubMed

Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

2016-09-01

To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

A review of nateglinide in the management of patients with type 2 diabetes

PubMed Central

Tentolouris, Nicholas; Voulgari, Christina; Katsilambros, Nicholas

2007-01-01

Impaired insulin secretion occurs early in the pathogenesis of type 2 diabetes mellitus (T2DM) and is chronic and progressive, resulting initially in impaired glucose tolerance (IGT) and eventually in T2DM. As most patients with T2DM have both insulin resistance and insulin deficiency, therapy for T2DM should aim to control not only fasting, but also postprandial plasma glucose levels. While oral glucose-lowering treatment with metformin and thiazolidinediones corrects fasting plasma glucose, these agents do not address the problem of mealtime glucose spikes that have been shown to trigger atherogenic processes. Nateglinide is a derivative of the amino acid D-phenylalanine, which acts directly on the pancreatic β-cells to stimulate insulin secretion. Nateglinide monotherapy controls significantly mealtime hyperglycemia and results in improved overall glycemic control in patients with T2DM by reducing glycosylated hemoglobin (HbA1c) levels. The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents. In prediabetic subjects with IGT, nateglinide restores early insulin secretion and reduces postprandial hyperglycemia. Nateglinide has an excellent safety and tolerability profile and provides a lifetime flexibility that other antidiabetic agents could not accomplish. The aim of this review is to identify nateglinide as an effective “gate-keeper” in T2DM, since it restores early-phase insulin secretion and prevents mealtime glucose spikes throughout the day and to evaluate the results of ongoing research into its potential role in delaying the progression to overt diabetes and reducing its complications and mortality. PMID:18200800

Orientation Discrimination with Macular Changes Associated with Early AMD

PubMed Central

Bedell, Harold E.; Tong, Jianliang; Woo, Stanley Y.; House, Jon R.; Nguyen, Tammy

2010-01-01

Purpose Age-related macular degeneration (AMD) is a condition that progressively reduces central vision in elderly individuals, resulting in a reduced capacity to perform many daily activities and a diminished quality of life. Recent studies identified clinical treatments that can slow or reverse the progression of exudative (wet) AMD and ongoing research is evaluating earlier interventions. Because early diagnosis is critical for an optimal outcome, the goal of this study is to assess psychophysical orientation discrimination for randomly positioned short line segments as a potential indicator of subtle macular changes in eyes with early AMD. Methods Orientation discrimination was measured in a sample of 74 eyes of patients aged 47 to 82 years old, none of which had intermediate or advanced AMD. Amsler-grid testing was performed as well. A masked examiner graded each eye as level 0, 1, 2, or 3 on a streamlined version of the Age-Related Eye Disease Study (AREDS) scale for AMD, based on the presence and extent of macular drusen or retinal pigment epithelium (RPE) changes. Visual acuity in the 74 eyes ranged from 20/15 to 20/40+1, with no significant differences among the grading levels. Humphrey 10–2 and Nidek MP-1 micro-perimetry were used to assess retinal sensitivity at test locations 1° from the locus of fixation. Results Average orientation-discrimination thresholds increased systematically from 7.4° to 11.3° according to the level of macular changes. In contrast, only 3 of 74 eyes exhibited abnormalities on the Amsler grid and central-field perimetric defects occurred with approximately equal probability at all grading levels. Conclusions In contrast to Amsler grid and central-visual-field testing, psychophysical orientation discrimination has the capability to distinguish between eyes with and without subtle age-related macular changes. PMID:19319009

Fabry disease: Review and experience during newborn screening.

PubMed

Hsu, Ting-Rong; Niu, Dau-Ming

2018-05-01

Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Heterozygous females can develop vital organ damage that in turn causes severe morbidity and mortality; these symptoms may be as severe as those in affected males. For the treatable disease, this review aims to raise awareness of early recognition and further management of FD based on newborn screening. As newborn screening for FD has been implemented worldwide, it allows the early detection of individuals with Fabry mutations. Based on screening studies, the prevalence of the later-onset type FD is much higher than that of classical type FD. Newborn screening studies have also revealed that patients with FD may develop insidious but ongoing irreversible organ damage. The timing of enzyme replacement therapy, which is able to stabilize the progression of disease, is important in order to prevent irreversible organ damage. Therapies that may become available in the future include pharmacological chaperones and substrate reduction therapy, both of which are still under investigation as ways of improving the health of individuals with FD. Copyright © 2017 Elsevier Inc. All rights reserved.

InTASC Model Core Teaching Standards and Learning Progressions for Teachers 1.0: A Resource for Ongoing Teacher Development

ERIC Educational Resources Information Center

Council of Chief State School Officers, 2013

2013-01-01

The Council of Chief State School Officers (CCSSO), through its Interstate Teacher Assessment and Support Consortium (InTASC), offers this set of combined resources that define and support ongoing teacher effectiveness to ensure students reach college and career ready standards. This document includes the "InTASC Model Core Teaching…

High expression of AID and active class switch recombination might account for a more aggressive disease in unmutated CLL patients: link with an activated microenvironment in CLL disease.

PubMed

Palacios, Florencia; Moreno, Pilar; Morande, Pablo; Abreu, Cecilia; Correa, Agustín; Porro, Valentina; Landoni, Ana Ines; Gabus, Raul; Giordano, Mirta; Dighiero, Guillermo; Pritsch, Otto; Oppezzo, Pablo

2010-06-03

Interaction of chronic lymphocytic leukemia (CLL) B cells with tissue microenvironment has been suggested to favor disease progression by promoting malignant B-cell growth. Previous work has shown expression in peripheral blood (PB) of CLL B cells of activation-induced cytidine deaminase (AID) among CLL patients with an unmutated (UM) profile of immunoglobulin genes and with ongoing class switch recombination (CSR) process. Because AID expression results from interaction with activated tissue microenvironment, we speculated whether the small subset with ongoing CSR is responsible for high levels of AID expression and could be derived from this particular microenvironment. In this work, we quantified AID expression and ongoing CSR in PB of 50 CLL patients and characterized the expression of different molecules related to microenvironment interaction. Our results show that among UM patients (1) high AID expression is restricted to the subpopulation of tumoral cells ongoing CSR; (2) this small subset expresses high levels of proliferation, antiapoptotic and progression markers (Ki-67, c-myc, Bcl-2, CD49d, and CCL3/4 chemokines). Overall, this work outlines the importance of a cellular subset in PB of UM CLL patients with a poor clinical outcome, high AID levels, and ongoing CSR, whose presence might be a hallmark of a recent contact with the microenvironment.

The First Year: A Cultural Shift towards Improving Student Progress

ERIC Educational Resources Information Center

Jobe, Rebecca L.; Spencer, Martha; Hinkle, Jessica P.; Kaplan, Jonathan A.

2016-01-01

Student attrition has been a primary focus among higher education institutions for nearly 50 years, yet overall retention and graduation rates continue to be of significant concern. Despite increased attention, ongoing struggles of colleges and universities to effectively address potential barriers to student progress are well-documented. Part of…

HIV and neurocognitive dysfunction.

PubMed

Spudich, Serena

2013-09-01

The spectrum of HIV-associated neurocognitive disorder (HAND) has been dramatically altered in the setting of widely available effective antiretroviral therapy (ART). Once culminating in dementia in many individuals infected with HIV, HAND now typically manifests as more subtle, though still morbid, forms of cognitive impairment in persons surviving long-term with treated HIV infection. Despite the substantial improvement in severity of this disorder, the fact that neurologic injury persists despite ART remains a challenge to the community of patients, providers and investigators aiming to optimize quality of life for those living with HIV. Cognitive dysfunction in treated HIV may reflect early irreversible CNS injury accrued before ART is typically initiated, ongoing low-level CNS infection and progressive injury in the setting of ART, or comborbidities including effects of treatment which may confound the beneficial reduction in viral replication and immune activation effected by ART.

Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: current status and future directions.

PubMed

Ocaña, Alberto; Amir, Eitan

2009-12-01

Aberrant activation of HER2 through overexpression has been shown to play an important role in some breast cancers. Therapies against this receptor including the monoclonal antibody, trastuzumab, or the small tyrosine kinase inhibitor, lapatinib have shown to improve the prognosis of such patients. Despite overexpressing HER2, some patients do not respond to these targeted treatments or progress after a short period of time. Irreversible tyrosine kinase inhibitors have been developed to bypass several pathways that could be involved in this resistance. In vitro, these agents have been shown to be more potent and to prolong target inhibition. Clinical development of these agents is ongoing and early results are promising. This review will describe the biologic rationale that justifies the development of these agents in breast cancer focusing on the current status and future directions.

HIV and mycobacteria.

PubMed

Procop, Gary W

2017-07-01

The importance of mycobacteria as opportunistic pathogens, particularly members of the M. avium complex (MAC), in patients with progressive HIV infection was recognized early in the AIDS epidemic. It took longer to appreciate the global impact and devastation that would result from the deadly synergy that exists between HIV and M. tuberculosis. This HIV/M. tuberculosis co-pandemic is ongoing and claiming millions of lives every year. In addition to MAC, a number of other non-tuberculous mycobacteria have been recognized as opportunistic pathogens in HIV-infected individuals; some of these are more commonly encountered (e.g., M. kansasii) than others (M. haemophilum and M. genevense). Finally, there are challenges to concomitantly treating the HIV and the infecting Mycobacterium species, because of antimicrobial resistance, therapeutic side-effects and the complex pharmacologic interactions of the antiretroviral and antimycobacterial multidrug therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety and efficacy of pharmacologic thromboprophylaxis following blunt head injury: a systematic review.

PubMed

Reeves, Fairleigh; Batty, Lachlan; Pitt, Veronica; Chau, Marisa; Pattuwage, Loyal; Gruen, Russell L

2013-10-01

Patients with blunt head injury are at high risk of venous thromboembolism. However, pharmacologic thromboprophylaxis (PTP) may cause progression of intracranial hemorrhage, and clinicians must often weigh up the risks and benefits. This review aimed to determine whether adding PTP to mechanical prophylaxis confers net benefit or harm and the optimal timing, dose, and agent for PTP in patients with blunt head injury. We searched MEDLINE, EMBASE, The Cochrane Library Central Register of Controlled Trials (CENTRAL), and www.clinicaltrials.gov on April 24, 2013, to identify controlled studies and ongoing trials that assessed the efficacy or safety of thromboprophylaxis interventions in the early management of head-injured patients. Studies were classified based on types of interventions and comparisons, and the quality of included studies was assessed using Cochrane risk-of-bias tool and the Newcastle-Ottawa Quality Assessment Scale. We intended to undertake a meta-analysis if studies were sufficiently similar. Sixteen studies met the inclusion criteria, including four randomized controlled trials. At least two randomized controlled trials were at high risk of bias owing to inadequate randomization and concealment of allocation, and observational studies were potentially confounded by substantial differences between comparison groups. Heterogeneity of included studies precluded meta-analysis. Results were mixed, with some studies supporting and others refuting addition of PTP to mechanical interventions. Little evidence was available about dose or choice of agent. The safety and efficacy of early PTP in patients without early progression of hemorrhage is unclear. There is currently insufficient evidence to guide thromboprophylaxis in patients with blunt head injury. Standardized definitions and outcome measurements would facilitate comparison of outcomes across future studies. Studies in mixed populations should report head-injured specific subgroup data. Future randomized controlled trials should investigate the efficacy and safety of early pharmacologic prophylaxis in addition to mechanical intervention. Systematic review, level IV.

The Changing Landscape of Smoldering Multiple Myeloma: A European Perspective

PubMed Central

Fernández de Larrea, Carlos; Leleu, Xavier; Heusschen, Roy; Zojer, Niklas; Decaux, Olivier; Kastritis, Efstathios; Minnema, Monique; Jurczyszyn, Artur; Beguin, Yves; Wäsch, Ralph; Palumbo, Antonio; Dimopoulos, Meletios; Mateos, Maria Victoria; Ludwig, Heinz; Engelhardt, Monika

2016-01-01

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammopathy of undetermined significance to multiple myeloma (MM), based on higher levels of circulating monoclonal immunoglobulin and bone marrow plasmocytosis without end-organ damage. Until a Spanish study reported fewer MM-related events and better overall survival among patients with high-risk SMM treated with lenalidomide and dexamethasone, prior studies had failed to show improved survival with earlier intervention, although a reduction in skeletal-related events (without any impact on disease progression) has been described with bisphosphonate use. Risk factors have now been defined, and a subset of ultra-high-risk patients have been reclassified by the International Myeloma Working Group as MM, and thus will require optimal MM treatment, based on biomarkers that identify patients with a >80% risk of progression. The number of these redefined patients is small (∼10%), but important to unravel, because their risk of progression to overt MM is substantial (≥80% within 2 years). Patients with a high-risk cytogenetic profile are not yet considered for early treatment, because groups are heterogeneous and risk factors other than cytogenetics are deemed to weight higher. Because patients with ultra-high-risk SMM are now considered as MM and may be treated as such, concerns exist that earlier therapy may increase the risk of selecting resistant clones and induce side effects and costs. Therefore, an even more accurate identification of patients who would benefit from interventions needs to be performed, and clinical judgment and careful discussion of pros and cons of treatment initiation need to be undertaken. For the majority of SMM patients, the standard of care remains observation until development of symptomatic MM occurs, encouraging participation in ongoing and upcoming SMM/early MM clinical trials, as well as consideration of bisphosphonate use in patients with early bone loss. Implications for Practice: Smoldering multiple myeloma is an early stage of myeloma disease and is diagnosed before any symptoms occur. Recent research has redefined the diagnostic criteria for multiple myeloma, offering new insights into testing and classification of this malignancy. Risk factors have now been defined and three biomarkers have been validated that are able to identify patients presenting a high risk of progression toward a symptomatic disease. These biomarkers will help physicians to identify high-risk patients who may benefit from optimal treatment. This article summarizes the views of a European panel of hematologists on the implicated changes in patient care. PMID:26921288

CaMKIIα underlies spontaneous and evoked pain behaviors in Berkeley sickle cell transgenic mice.

PubMed

He, Ying; Chen, Yan; Tian, Xuebi; Yang, Cheng; Lu, Jian; Xiao, Chun; DeSimone, Joseph; Wilkie, Diana J; Molokie, Robert E; Wang, Zaijie Jim

2016-12-01

Pain is one of the most challenging and stressful conditions to patients with sickle cell disease (SCD) and their clinicians. Patients with SCD start experiencing pain as early as 3 months old and continue having it throughout their lives. Although many aspects of the disease are well understood, little progress has been made in understanding and treating pain in SCD. This study aimed to investigate the functional involvement of Ca/calmodulin-dependent protein kinase II (CaMKIIα) in the persistent and refractory pain associated with SCD. We found that nonevoked ongoing pain as well as evoked hypersensitivity to mechanical and thermal stimuli were present in Berkeley sickle cell transgenic mice (BERK mice), but not nonsickle control littermates. Prominent activation of CaMKIIα was observed in the dorsal root ganglia and spinal cord dorsal horn region of BERK mice. Intrathecal administration of KN93, a selective inhibitor of CaMKII, significantly attenuated mechanical allodynia and heat hyperalgesia in BERK mice. Meanwhile, spinal inhibition of CaMKII elicited conditioned place preference in the BERK mice, indicating the contribution of CaMKII in the ongoing spontaneous pain of SCD. We further targeted CaMKIIα by siRNA knockdown. Both evoked pain and ongoing spontaneous pain were effectively attenuated in BERK mice. These findings elucidated, for the first time, an essential role of CaMKIIα as a cellular mechanism in the development and maintenance of spontaneous and evoked pain in SCD, which can potentially offer new targets for pharmacological intervention of pain in SCD.

EPA releases progress report on hydraulic fracturing study

NASA Astrophysics Data System (ADS)

Showstack, Randy

2013-01-01

The U.S. Environmental Protection Agency (EPA) provided a 21 December progress report on its ongoing national study about the potential impacts of hydraulic fracturing on drinking water resources. The agency said that a draft of the congressionally requested study will be released in 2014 for public and peer review and that its progress report does not draw conclusions about the potential impacts of hydraulic fracturing, often referred to as fracking.

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

PubMed Central

Müller, Sören; Agnihotri, Sameer; Shoger, Karsen E.; Myers, Max I.; Chaparala, Srilakshmi; Villanueva, Clarence R.; Chattopadhyay, Ansuman; Butterfield, Lisa H.; Okada, Hideho; Pollack, Ian F.

2018-01-01

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns. PMID:29618666

32 CFR 326.17 - Exemptions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... piece of information in the early stages of an investigation. In some cases, it is only after the... investigation on that individual is taking place, and might weaken the on-going investigation, reveal... might in itself provide an answer to that individual relating to an on-going investigation. The conduct...

Progress in the improved lattice calculation of direct CP-violation in the Standard Model

NASA Astrophysics Data System (ADS)

Kelly, Christopher

2018-03-01

We discuss the ongoing effort by the RBC & UKQCD collaborations to improve our lattice calculation of the measure of Standard Model direct CP violation, ɛ', with physical kinematics. We present our progress in decreasing the (dominant) statistical error and discuss other related activities aimed at reducing the systematic errors.

The Impact of Task Difficulty and Performance Scores on Student Engagement and Progression

ERIC Educational Resources Information Center

Lynch, Raymond; Patten, James Vincent; Hennessy, Jennifer

2013-01-01

Background: This article considers the impact of differential task difficulty on student engagement and progression within an Irish primary school context. Gaining and maintaining student engagement during learning tasks such as homework is a significant and understandable on-going challenge for teachers. The findings of this study hold the…

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2015-02-01

Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive neurological and...11 or ‘punch drunk’ syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain injuries 15-17...To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing efforts include

Evolving concepts of heredity and genetics in orthodontics.

PubMed

Carlson, David S

2015-12-01

The field of genetics emerged from the study of heredity early in the 20th century. Since that time, genetics has progressed through a series of defined eras based on a number of major conceptual and technical advances. Orthodontics also progressed through a series of conceptual stages over the past 100 years based in part on the ongoing and often circular debate about the relative importance of heredity (nature) and the local environment (nurture) in the etiology and treatment of malocclusion and dentofacial deformities. During the past 20 years, significant advancements in understanding the genomic basis of craniofacial development and the gene variants associated with dentofacial deformities have resulted in a convergence of the principles and concepts in genetics and in orthodontics that will lead to significant advancement of orthodontic treatments. Fundamental concepts from genetics and applied translational research in orthodontics provide a foundation for a new emphasis on precision orthodontics, which will establish a modern genomic basis for major improvements in the treatment of malocclusion and dentofacial deformities as well as many other areas of concern to orthodontists through the assessment of gene variants on a patient-by-patient basis. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Early Course of Inflammatory Bowel Disease in a Population-Based Inception Cohort Study From 8 Countries in Asia and Australia.

PubMed

Ng, Siew C; Zeng, Zhirong; Niewiadomski, Ola; Tang, Whitney; Bell, Sally; Kamm, Michael A; Hu, Pinjin; de Silva, H Janaka; Niriella, Madunil A; Udara, W S A A Yasith; Ong, David; Ling, Khoon Lin; Ooi, Choon Jin; Hilmi, Ida; Lee Goh, Khean; Ouyang, Qin; Wang, Yu Fang; Wu, Kaichun; Wang, Xin; Pisespongsa, Pises; Manatsathit, Sathaporn; Aniwan, Satimai; Limsrivilai, Julajak; Gunawan, Jeffri; Simadibrata, Marcellus; Abdullah, Murdani; Tsang, Steve W C; Lo, Fu Hang; Hui, Aric J; Chow, Chung Mo; Yu, Hon Ho; Li, Mo Fong; Ng, Ka Kei; Ching, Jessica Y L; Chan, Victor; Wu, Justin C Y; Chan, Francis K L; Chen, Minhu; Sung, Joseph J Y

2016-01-01

The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

The PD-1 pathway as a therapeutic target to overcome immune escape mechanisms in cancer.

PubMed

Henick, Brian S; Herbst, Roy S; Goldberg, Sarah B

2014-12-01

Immunotherapy is emerging as a powerful approach in cancer treatment. Preclinical data predicted the antineoplastic effects seen in clinical trials of programmed death-1 (PD-1) pathway inhibitors, as well as their observed toxicities. The results of early clinical trials are extraordinarily promising in several cancer types and have shaped the direction of ongoing and future studies. This review describes the biological rationale for targeting the PD-1 pathway with monoclonal antibodies for the treatment of cancer as a context for examining the results of early clinical trials. It also surveys the landscape of ongoing clinical trials and discusses their anticipated strengths and limitations. PD-1 pathway inhibition represents a new frontier in cancer immunotherapy, which shows clear evidence of activity in various tumor types including NSCLC and melanoma. Ongoing and upcoming trials will examine optimal combinations of these agents, which should further define their role across tumor types. Current limitations include the absence of a reliable companion diagnostic to predict likely responders, as well as lack of data in early-stage cancer when treatment has the potential to increase cure rates.

Space nuclear safety program. Progress report, October-December 1984

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

George, T.G.

1986-05-01

This quarterly report covers studies related to the use of /sup 238/PuO/sub 2/ in radioisotope power systems carried out for the Office of Special Nuclear Projects of the US Department of Energy by Los Alamos National Laboratory. Most of the studies discussed are ongoing; the results and conclusions described may change as the work progresses.

Attachment Theory and Primary Caregiving

ERIC Educational Resources Information Center

Colmer, Kaye; Rutherford, Lynne; Murphy, Pam

2011-01-01

Offering intensive parent support programs within an early childhood setting recognises that early childhood educators are uniquely placed to form highly supportive and ongoing relationships with children and their families as part of their everyday work. This feature of early childhood programs can be utilised to include educators as partners in…

Rethinking Early Education

ERIC Educational Resources Information Center

Celeste, Eric

2017-01-01

The National Association for the Education of Young Children (NAEYC) says in its current policy paper that, for high-quality early education to exist outside of tiny islands across the country, the following must be addressed: (1) teacher preparation; (2) ongoing professional learning; and (3) disparity in early education teacher pay. To achieve…

Stakeholders' Perspectives on Preclinical Testing for Alzheimer's Disease.

PubMed

Arias, Jalayne J; Cummings, Jeffrey; Grant, Alexander Rae; Ford, Paul J

2015-01-01

Progress towards validating amyloid beta as an early indicator of Alzheimer's disease (AD) heightens the need for evaluation of stakeholders' perspectives of the benefits and harms of preclinical testing in asymptomatic individuals. Investigators conducted and analyzed 14 semi-structured interviews with family members of patients diagnosed with AD. Participants reported benefits, including the potential to seek treatment, make lifestyle changes, and prepare for cognitive impairment. Participants identified harms, including social harms, adverse life decisions, and psychological harms. Nine participants reported either a "positive global perspective" or a "positive global perspective (qualified)." Results from this study characterized stakeholders' perspectives on the potential benefits and harms of clinical use of preclinical testing for AD. Investigators used data from this study to develop a framework that contributes to ongoing discussions that will evaluate widespread adoption of preclinical testing and will inform future research. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Beyond the classroom: a case study of immigrant safety liaisons in residential construction.

PubMed

Ochsner, Michele; Marshall, Elizabeth G; Martino, Carmen; Pabelón, Marién Casillas; Kimmel, Louis; Rostran, Damaris

2012-01-01

Latino day laborers often work at dangerous construction sites with little power to change conditions. We describe the development, implementation, and early-stage results of a program to train immigrant day laborers as safety liaisons. These are construction workers prepared to recognize and respond to health and safety hazards. Based in Newark, NJ, the project involves collaboration between New Labor, a membership-based worker center, and university researchers and labor educators. Safety liaisons undergo training and receive ongoing support for their roles. Both qualitative and quantitative data are collected to monitor progress. Although lacking in formal authority, safety liaisons have prompted improvements at specific sites, filed OSHA complaints, and developed a local worker council. Participatory training methods, opportunities for leadership outside the classroom, and participation in project planning have strengthened liaisons' effectiveness, leadership skills, and commitment. The safety liaison approach could be adapted by worker centers and their partner organizations.

Research Spotlight: Model suggests path to ending the ongoing Haitian cholera epidemic

NASA Astrophysics Data System (ADS)

Schultz, Colin

2011-05-01

Since early November 2010 a deadly cholera epidemic has been spreading across the Caribbean nation of Haiti, killing thousands of people and infecting hundreds of thousands. While infection rates are being actively monitored, health organizations have been left without a clear understanding of exactly how the disease has spread across Haiti. Cholera can spread through exposure to contaminated water, and the disease travels over long distances if an infected individual moves around the country. Using representations of these two predominant dispersion mechanisms, along with information on the size of the susceptible population, the number of infected individuals, and the aquatic concentration of the cholera-causing bacteria for more than 500 communities, Bertuzzo et al. designed a model that was able to accurately reproduce the progression of the Haitian cholera epidemic. (Geophysical Research Letters, doi:10.1029/2011GL046823, 2011)

Genetic heterogeneity in Usher syndrome.

PubMed

Keats, Bronya J B; Savas, Sevtap

2004-09-15

Mutations in seven different genes have been associated with Usher syndrome, and an additional four loci have been mapped. The identified genes encode myosin VIIa, harmonin (a PDZ-domain protein), cadherin 23, protocadherin 15, sans (a scaffold-like protein), usherin and clarin. Three clinical types of Usher syndrome have been described: USH1 patients have severe to profound congenital hearing loss, vestibular dysfunction, and retinal degeneration beginning in childhood, those with USH2 have moderate to severe congenital hearing loss, normal vestibular function, and later onset of retinitis pigmentosa, and USH3 patients have progressive hearing loss, which distinguishes them from the other two types. The shaker-1, waltzer, Ames waltzer, and Jackson shaker mice provide murine models for four of the genetic forms of Usher syndrome. Ongoing studies are enabling early diagnosis of Usher syndrome in children who present with hearing loss, thus providing time to prepare for the onset of visual loss. Copyright 2004 Wiley-Liss, Inc.

Managing Air Quality - Ongoing Evaluation of Progress

EPA Pesticide Factsheets

Describes the importance of evaluating if air quality programs are achieving the desired results to inform environmental program managers, regulated industry and the public, and provides EPA examples.

Factors Influencing Early Feeding of Foods and Drinks Containing Free Sugars-A Birth Cohort Study.

PubMed

Ha, Diep H; Do, Loc G; Spencer, Andrew John; Thomson, William Murray; Golley, Rebecca K; Rugg-Gunn, Andrew J; Levy, Steven M; Scott, Jane A

2017-10-23

Early feeding of free sugars to young children can increase the preference for sweetness and the risk of consuming a cariogenic diet high in free sugars later in life. This study aimed to investigate early life factors influencing early introduction of foods/drinks containing free sugars. Data from an ongoing population-based birth cohort study in Australia were used. Mothers of newborn children completed questionnaires at birth and subsequently at ages 3, 6, 12, and 24 months. The outcome was reported feeding (Yes/No) at age 6-9 months of common foods/drinks sources of free sugars (hereafter referred as foods/drinks with free sugars). Household income quartiles, mother's sugar-sweetened beverage (SSB) consumption, and other maternal factors were exposure variables. Analysis was conducted progressively from bivariate to multivariable log-binomial regression with robust standard error estimation to calculate prevalence ratios (PR) of being fed foods/drinks with free sugars at an early age (by 6-9 months). Models for both complete cases and with multiple imputations (MI) for missing data were generated. Of 1479 mother/child dyads, 21% of children had been fed foods/drinks with free sugars. There was a strong income gradient and a significant positive association with maternal SSB consumption. In the complete-case model, income Q1 and Q2 had PRs of 1.9 (1.2-3.1) and 1.8 (1.2-2.6) against Q4, respectively. The PR for mothers ingesting SSB everyday was 1.6 (1.2-2.3). The PR for children who had been breastfed to at least three months was 0.6 (0.5-0.8). Similar findings were observed in the MI model. Household income at birth and maternal behaviours were significant determinants of early feeding of foods/drinks with free sugars.

Network for Early Onset Cystic Kidney Diseases—A Comprehensive Multidisciplinary Approach to Hereditary Cystic Kidney Diseases in Childhood

PubMed Central

König, Jens Christian; Titieni, Andrea; Konrad, Martin; Bergmann, C.

2018-01-01

Hereditary cystic kidney diseases comprise a complex group of genetic disorders representing one of the most common causes of end-stage renal failure in childhood. The main representatives are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet–Biedl syndrome, and hepatocyte nuclear factor-1beta nephropathy. Within the last years, genetic efforts have brought tremendous progress for the molecular understanding of hereditary cystic kidney diseases identifying more than 70 genes. Yet, genetic heterogeneity, phenotypic variability, a lack of reliable genotype–phenotype correlations and the absence of disease-specific biomarkers remain major challenges for physicians treating children with cystic kidney diseases. To tackle these challenges comprehensive scientific approaches are urgently needed that match the ongoing “revolution” in genetics and molecular biology with an improved efficacy of clinical data collection. Network for early onset cystic kidney diseases (NEOCYST) is a multidisciplinary, multicenter collaborative combining a detailed collection of clinical data with translational scientific approaches addressing the genetic, molecular, and functional background of hereditary cystic kidney diseases. Consisting of seven work packages, including an international registry as well as a biobank, NEOCYST is not only dedicated to current scientific questions, but also provides a platform for longitudinal clinical surveillance and provides precious sources for high-quality research projects and future clinical trials. Funded by the German Federal Government, the NEOCYST collaborative started in February 2016. Here, we would like to introduce the rationale, design, and objectives of the network followed by a short overview on the current state of progress. PMID:29497606

Network for Early Onset Cystic Kidney Diseases-A Comprehensive Multidisciplinary Approach to Hereditary Cystic Kidney Diseases in Childhood.

PubMed

König, Jens Christian; Titieni, Andrea; Konrad, Martin

2018-01-01

Hereditary cystic kidney diseases comprise a complex group of genetic disorders representing one of the most common causes of end-stage renal failure in childhood. The main representatives are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet-Biedl syndrome, and hepatocyte nuclear factor-1beta nephropathy. Within the last years, genetic efforts have brought tremendous progress for the molecular understanding of hereditary cystic kidney diseases identifying more than 70 genes. Yet, genetic heterogeneity, phenotypic variability, a lack of reliable genotype-phenotype correlations and the absence of disease-specific biomarkers remain major challenges for physicians treating children with cystic kidney diseases. To tackle these challenges comprehensive scientific approaches are urgently needed that match the ongoing "revolution" in genetics and molecular biology with an improved efficacy of clinical data collection. Network for early onset cystic kidney diseases (NEOCYST) is a multidisciplinary, multicenter collaborative combining a detailed collection of clinical data with translational scientific approaches addressing the genetic, molecular, and functional background of hereditary cystic kidney diseases. Consisting of seven work packages, including an international registry as well as a biobank, NEOCYST is not only dedicated to current scientific questions, but also provides a platform for longitudinal clinical surveillance and provides precious sources for high-quality research projects and future clinical trials. Funded by the German Federal Government, the NEOCYST collaborative started in February 2016. Here, we would like to introduce the rationale, design, and objectives of the network followed by a short overview on the current state of progress.

Structural elements of the Sulu Sea, Philippines

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

Hinz, K.; Block, M.; Kudrass, H.R.

1994-07-01

The structure and tectonic history of the Sulu Sea are described on the basis of seismic reflection data combined with the findings of onshore and offshore geological studies, and the results of ODP Leg 124 drilling. Closing of a hypothetical Mesozoic proto-South China Sea associated with the formation of oceanic crustal splinters in the late Eocene followed by southward subduction and, in turn, progressive collision of the north Palawan continental terrane with the micro-continental Borneo plate since the middle Miocene, resulted in the formation of the structurally complex Sulu-Borneo collision belt. The latter comprises north Sabah, southern and central Palawan,more » and the northwest Sulu basin. Fracturing of the Borneo micro-continental plate into the Sulu and Cagayan ridges initiated the opening of the southeast Sulu basin during the late Oligocene through the early Miocene. Collision of the north Palawan continental terrane with Cagayan Ridge in the late early Miocene and oblique collision of these blocks with the central Philippines resulted in the still ongoing closing of the southeast Sulu basin since the middle or late Miocene. Closing of the southeast Sulu basin began with the formation of an oceanic crustal slab.« less

NGST Yardstick Integrated Science Instrument Module (ISIM) Feasibility Study

NASA Astrophysics Data System (ADS)

Greenhouse, M. A.; Dipirro, M.; Federline, B.; Gardner, Jonathan P.; Guy, P.; Hagopian, J.; Hein, J.; Jurotich, M.; Lawrence, J.; Martineau, B.; Mather, J. C.; Mentzell, E.; Satyapal, S.; Stanley, D.; Teplitz, H. I.; Travis, J.; Bely, P.; Petro, L. D.; Stockman, P.; Burg, R.; Bitzel, R.

1998-12-01

We display portions of the baseline design concept for the NGST Integrated Science Instrument Module (ISIM). This ISIM design is under ongoing development for integration with the "Yardstick" and other NGST 8 m architectures that are intended for packaging in an EELV or Ariane 5 meter class fairing. The goals of this activity are to: [1] demonstrate mission science feasibility, [2] identify ISIM technology challenge areas, [3] assess ISIM engineering and cost feasibility, [5] identify ISIM/NGST interface constraints, and [6] enable smart customer procurement of the ISIM. In this poster, we display a snap shot of work in progress including: optical design, opto-mechanical layout, thermal modeling, focal plane array design, and electronics design. Ongoing progress can be monitored via ISIM team web site: http://ngst.gsfc.nasa.gov/

A decade of aquatic invasive species (AIS) early detection method development in the St. Louis River estuary

EPA Science Inventory

As an invasion prone location, the St. Louis River Estuary (SLRE) has been a case study for ongoing research to develop the framework for a practical Great Lakes monitoring network for early detection of aquatic invasive species (AIS). Early detection, however, necessitates findi...

Patterns of Practice: Case Studies of Early Childhood Education & Family Engagement in Community Schools

ERIC Educational Resources Information Center

Jacobson, Linda; Rollins, S. Kwesi; Brown, Janet; Naviasky, Heather

2016-01-01

This "Patterns of Practice: Case Studies of Early Childhood Education & Family Engagement in Community Schools" report updates the community school case studies through a description of ongoing developments in Cincinnati, OH; Evansville, IN; Multnomah County, OR; and Tulsa, OK and adds to that knowledge base of early learning and…

An Examination of the Influence of Institutional Context on Academic Progress Rates at Division I Institutions: A Multilevel Approach

ERIC Educational Resources Information Center

McLaughlin, Jacqueline Elaine

2012-01-01

The growing attention given to intercollegiate athletics in recent years amid ongoing controversies highlights the importance of closely examining the implementation and impact of sports policy on college campuses. In an attempt to improve the academic performance and retention of student-athletes, the Academic Progress Rate (APR) was implemented…

Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

PubMed Central

Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

2015-01-01

Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

Aftershocks of Chile's Earthquake for an Ongoing, Large-Scale Experimental Evaluation

ERIC Educational Resources Information Center

Moreno, Lorenzo; Trevino, Ernesto; Yoshikawa, Hirokazu; Mendive, Susana; Reyes, Joaquin; Godoy, Felipe; Del Rio, Francisca; Snow, Catherine; Leyva, Diana; Barata, Clara; Arbour, MaryCatherine; Rolla, Andrea

2011-01-01

Evaluation designs for social programs are developed assuming minimal or no disruption from external shocks, such as natural disasters. This is because extremely rare shocks may not make it worthwhile to account for them in the design. Among extreme shocks is the 2010 Chile earthquake. Un Buen Comienzo (UBC), an ongoing early childhood program in…

"Till Death Do Us Part": A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb.

PubMed

Omais, Saad; Jaafar, Carine; Ghanem, Noël

2018-01-01

Adult neurogenesis (AN) is an ongoing developmental process that generates newborn neurons in the olfactory bulb (OB) and the hippocampus (Hi) throughout life and significantly contributes to brain plasticity. Adult neural stem and progenitor cells (aNSPCs) are relatively limited in number and fate and are spatially restricted to the subventricular zone (SVZ) and the subgranular zone (SGZ). During AN, the distinct roles played by cell cycle proteins extend beyond cell cycle control and constitute key regulatory mechanisms involved in neuronal maturation and survival. Importantly, aberrant cell cycle re-entry (CCE) in post-mitotic neurons has been strongly linked to the abnormal pathophysiology in rodent models of neurodegenerative diseases with potential implications on the etiology and progression of such diseases in humans. Here, we present an overview of AN in the SVZ-OB and olfactory epithelium (OE) in mice and humans followed by a comprehensive update of the distinct roles played by cell cycle proteins including major tumors suppressor genes in various steps during neurogenesis. We also discuss accumulating evidence underlining a strong link between abnormal cell cycle control, olfactory dysfunction and neurodegeneration in the adult and aging brain. We emphasize that: (1) CCE in post-mitotic neurons due to loss of cell cycle suppression and/or age-related insults as well as DNA damage can anticipate the development of neurodegenerative lesions and protein aggregates, (2) the age-related decline in SVZ and OE neurogenesis is associated with compensatory pro-survival mechanisms in the aging OB which are interestingly similar to those detected in Alzheimer's disease and Parkinson's disease in humans, and (3) the OB represents a well suitable model to study the early manifestation of age-related defects that may eventually progress into the formation of neurodegenerative lesions and, possibly, spread to the rest of the brain. Such findings may provide a novel approach to the modeling of neurodegenerative diseases in humans from early detection to progression and treatment as well.

Early College High School Initiative. Evaluation Year End Report: 2003?2004

ERIC Educational Resources Information Center

Berger, Andrea R.; Cole, Susan; Melton, Janet; Safran, Stephanie; Vogel, Tyler; Walton, Laura; Adelman, Nancy; Hall, Catherine; Keating, Kaelie Knowles; Murray, Samantha; Nielsen, Natalie; Schaffner, Monika

2005-01-01

This is the first year-end report produced as part of the on-going evaluation of the Bill & Melinda Gates Foundation's Early College High School Initiative. The program provides funding and support for the establishment of Early College High Schools, which are organized to allow all enrolled students the opportunity to earn a high school diploma…

Starting Smart: How Early Experiences Affect Brain Development. An Ounce of Prevention Fund Paper.

ERIC Educational Resources Information Center

Ounce of Prevention Fund.

Recent research has provided great insight into the impact of early experience on brain development. It is now believed that brain growth is highly dependent upon early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring…

Embedded Professional Development and Classroom-Based Early Reading Intervention: Early Diagnostic Reading Intervention through Coaching

ERIC Educational Resources Information Center

Amendum, Steven J.

2014-01-01

The purpose of the current mixed-methods study was to investigate a model of professional development and classroom-based early reading intervention implemented by the 1st-grade teaching team in a large urban/suburban school district in the southeastern United States. The intervention provided teachers with ongoing embedded professional…

Investigating Alternatives to the Fish Early Life-Stage Test: A Strategy for Discovering and Annotating Adverse Outcome Pathways for Early Fish Development

EPA Science Inventory

The fish early life-stage (FELS) test (OECD Test Guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an on-going effort to develop efficient and cost-effec...

Assessing Early Communication Skills at 12 Months: A Retrospective Study of Autism Spectrum Disorder

ERIC Educational Resources Information Center

Swain, Nathaniel Robert; Eadie, Patricia Ann; Prior, Margot Ruth; Reilly, Sheena

2015-01-01

Background: Early identification of Autism Spectrum Disorder (ASD) is currently limited by the absence of reliable biological markers for the disorder, as well as the reliability of screening and assessment tools for children aged between 6 and 18 months. Ongoing research has demonstrated the importance of early social communication skills in…

HYPERGLYCOSYLATED HUMAN CHORIONIC GONADOTROPIN AS AN EARLY PREDICTOR OF PREGNANCY OUTCOMES AFTER IN VITRO FERTILIZATION

PubMed Central

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H. Irene

2014-01-01

Objective To determine if hyperglycosylated hCG (hhCG), produced by invasive trophoblasts, measured as early as 9 days after egg retrieval can predict ongoing pregnancies (OP) after in vitro fertilization and fresh embryo transfer (IVF-ET). Design Cohort Setting Academic ART center Patients Consecutive patients undergoing IVF-ET Interventions Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Outcome Ongoing pregnancy (OP) beyond 9 weeks of gestation Results OP (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. D9 hhCG levels >110 pg/mL was 96% specific for OP, yielding a positive predictive value of 95%. Compared to D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67). Diagnostic test characteristics were similar between D16 hhCG and hCG levels. Conclusions In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable. HhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. At this early assessment, hhCG is superior to traditional hCG and highly predictive of ongoing pregnancies. PMID:24355054

Optical and infrared masers

NASA Technical Reports Server (NTRS)

1973-01-01

Ongoing research progress in the following areas is described: (1) tunable infrared light sources and applications; (2) precision frequency and wavelength measurements in the infrared with applications to atomic clocks; (3) zero-degree pulse propagation in resonant medium; (4) observation of Dicke superradiance in optically pumped HF gas; (5) unidirectional laser amplifier with built-in isolator; and (6) progress in infrared metal-to-metal point contact tunneling diodes.

Modifiable lifestyle and social factors affect chronic kidney disease in high-risk individuals with type 2 diabetes mellitus.

PubMed

Dunkler, Daniela; Kohl, Maria; Heinze, Georg; Teo, Koon K; Rosengren, Annika; Pogue, Janice; Gao, Peggy; Gerstein, Hertzel; Yusuf, Salim; Oberbauer, Rainer; Mann, Johannes F E

2015-04-01

This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes.

Lysosomal acid lipase deficiency--an under-recognized cause of dyslipidaemia and liver dysfunction.

PubMed

Reiner, Željko; Guardamagna, Ornella; Nair, Devaki; Soran, Handrean; Hovingh, Kees; Bertolini, Stefano; Jones, Simon; Ćorić, Marijana; Calandra, Sebastiano; Hamilton, John; Eagleton, Terence; Ros, Emilio

2014-07-01

Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease caused by deleterious mutations in the LIPA gene. The age at onset and rate of progression vary greatly and this may relate to the nature of the underlying mutations. Patients presenting in infancy have the most rapidly progressive disease, developing signs and symptoms in the first weeks of life and rarely surviving beyond 6 months of age. Children and adults typically present with some combination of dyslipidaemia, hepatomegaly, elevated transaminases, and microvesicular hepatosteatosis on biopsy. Liver damage with progression to fibrosis, cirrhosis and liver failure occurs in a large proportion of patients. Elevated low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels are common features, and cardiovascular disease may manifest as early as childhood. Given that these clinical manifestations are shared with other cardiovascular, liver and metabolic diseases, it is not surprising that LAL-D is under-recognized in clinical practice. This article provides practical guidance to lipidologists, endocrinologists, cardiologists and hepatologists on how to recognize individuals with this life-limiting disease. A diagnostic algorithm is proposed with a view to achieving definitive diagnosis using a recently developed blood test for lysosomal acid lipase. Finally, current management options are reviewed in light of the ongoing development of enzyme replacement therapy with sebelipase alfa (Synageva BioPharma Corp., Lexington, MA, USA), a recombinant human lysosomal acid lipase enzyme. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Scriptotherapy: A Technique for Conflict Resolution.

ERIC Educational Resources Information Center

Johnson, Roy E.

Part 1 of this dissertation contains an introductory chapter entitled, "The Children Shout Fight Fight," in which the written analytical process named Scriptotherapy is discussed. In Chapter 1, "Early Adolescence an Ongoing Process," early adolescent growth and development, the process of moral development, temperament types…

Approaches to Legacy System Evolution.

DTIC Science & Technology

1997-12-01

such as migrating legacy systems, to more distributed open environments. This framework draws out the important global issues early in the planning...ongoing system evolution initiatives, for drawing out important global issues early in the planning cycle using the checklists as a guide, and for

Practical treatment strategies for patients with Alzheimer's disease.

PubMed

Christensen, Daniel D; Lin, Peter

2007-12-01

With the "baby boomers" entering retirement and beyond and the life expectancy of the entire population increasing, the burden of Alzheimer's Disease (AD) grows alarmingly greater. Over 5 million people in the United States currently have AD, and that number could triple by 2050. The financial impact of caring for these patients is substantial. Estimates of direct and indirect costs are as high as $148 billion per year. In addition to its substantial economic impact, AD has devastating effects on patients and their families. Alzheimer's disease begins with gradual memory loss and progresses to personality change, behavioral disturbance, loss of executive function, and loss of the ability to perform basic activities of daily living, including eating, walking, dressing, and grooming. These impairments strain families and caregivers and create challenges to the care and safety of the patient as well as threaten the health and well-being of the caregiver. As the number of patients diagnosed with AD increases, there is an ever-growing need for early diagnosis, which often is first observed in the primary care setting. While AD cannot be reversed or stopped, disease progression can be delayed and quality of life enhanced with early diagnosis and treatment. Early and accurate diagnosis has become increasingly important and will become even more so with the anticipated new generation of medications. Though several consensus statements on diagnosis and treatment of AD have been developed, few primary care physicians routinely follow evidence-based guidelines in their clinical practices. A 2006 survey conducted by the American Academy of Family Physicians identified a moderate to high level of need for education on AD in a majority of respondents. This article illustrates the primary care management of AD beginning with diagnosis and concluding with autopsy. Enhancing diagnostic and treatment skills in primary care will promote earlier diagnosis, improved patient management, and ongoing research into this increasingly important dilemma of aging.

NASA and The Semantic Web

NASA Technical Reports Server (NTRS)

Ashish, Naveen

2005-01-01

We provide an overview of several ongoing NASA endeavors based on concepts, systems, and technology from the Semantic Web arena. Indeed NASA has been one of the early adopters of Semantic Web Technology and we describe ongoing and completed R&D efforts for several applications ranging from collaborative systems to airspace information management to enterprise search to scientific information gathering and discovery systems at NASA.

A Learning Progression for Elementary Students' Functional Thinking

ERIC Educational Resources Information Center

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

2017-01-01

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

A real-time cabled observatory on the Cascadia subduction zone

NASA Astrophysics Data System (ADS)

Vidale, J. E.; Delaney, J. R.; Toomey, D. R.; Bodin, P.; Roland, E. C.; Wilcock, W. S. D.; Houston, H.; Schmidt, D. A.; Allen, R. M.

2015-12-01

Subduction zones are replete with mystery and rife with hazard. Along most of the Pacific Northwest margin, the traditional methods of monitoring offshore geophysical activity use onshore sensors or involve conducting infrequent oceanographic expeditions. This results in a limited capacity for detecting and monitoring subduction processes offshore. We propose that the next step in geophysical observations of Cascadia should include real-time data delivered by a seafloor cable with seismic, geodetic, and pressure-sensing instruments. Along the Cascadia subduction zone, we need to monitor deformation, earthquakes, and fluid fluxes on short time scales. High-quality long-term time series are needed to establish baseline observations and evaluate secular changes in the subduction environment. Currently we lack a basic knowledge of the plate convergence rate, direction and its variations along strike and of how convergence is accommodated across the plate boundary. We also would like to seek cycles of microseismicity, how far locking extends up-dip, and the transient processes (i.e., fluid pulsing, tremor, and slow slip) that occur near the trench. For reducing risk to society, real-time monitoring has great benefit for immediate and accurate assessment through earthquake early warning systems. Specifically, the improvement to early warning would be in assessing the location, geometry, and progression of ongoing faulting and obtaining an accurate tsunami warning, as well as simply speeding up the early warning. It would also be valuable to detect strain transients and map the locked portion of the megathrust, and detect changes in locking over the earthquake cycle. Development of the US portion of a real-time cabled seismic and geodetic observatory should build upon the Ocean Observatories Initiative's cabled array, which was recently completed and is currently delivering continuous seismic and pressure data from the seafloor. Its implementation would require substantial initial and ongoing investments from federal and state governments, private partners and the academic community but would constitute a critical resource in mitigating the hazard both through improved earthquake and tsunami warning and an enhanced scientific understanding of subduction processes in Cascadia.

A Learning Progressions Approach to Early Algebra Research and Practice

ERIC Educational Resources Information Center

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

2015-01-01

We detail a learning progressions approach to early algebra research and how existing work around learning progressions and trajectories in mathematics and science education has informed our development of a four-component theoretical framework consisting of: a curricular progression of learning goals across big algebraic ideas; an instructional…

Preventing progression from arthralgia to arthritis: targeting the right patients.

PubMed

van Steenbergen, Hanna W; da Silva, José A Pereira; Huizinga, Tom W J; van der Helm-van Mil, Annette H M

2018-01-01

Early treatment is associated with improved outcomes in patients with rheumatoid arthritis (RA), suggesting that a 'window of opportunity', in which the disease is most susceptible to disease-modifying treatment, exists. Autoantibodies and markers of systemic inflammation can be present long before clinical arthritis, and maturation of the immune response seems to coincide with the development of RA. The pre-arthritis phase associated with symptoms such as as joint pain without clinical arthritis (athralgia) is now hypothesized to fall within the aforementioned window of opportunity. Consequently, disease modulation in this phase might prevent the occurrence of clinically apparent arthritis, which would result in a persistent disease course if untreated. Several ongoing proof-of-concept trials are now testing this hypothesis. This Review highlights the importance of adequate risk prediction for the correct design, execution and interpretation of results of these prevention trials, as well as considerations when translating these findings into clinical practice. The patients' perspectives are discussed, and the accuracy with which RA development can be predicted in patients presenting with arthralgia is evaluated. Currently, the best starting position for preventive studies is proposed to be the inclusion of patients with an increased risk of RA, such as those identified as fulfilling the EULAR definition of 'arthralgia suspicious for progression to RA'.

ALK-targeted therapy for lung cancer: ready for prime time.

PubMed

Husain, Hatim; Rudin, Charles M

2011-06-01

Lung cancer remains the leading cause of cancer-related death in the United States. Ongoing research into the molecular basis of lung cancer has yielded insight into various critical pathways that are deregulated in lung tumorigenesis, and in particular key driver mutations integral to cancer cell survival and proliferation. One of the most recent examples of this has been definition of translocations and functional dysregulation of the anaplastic lymphoma kinase (ALK) gene in a subset of patients with non-small-cell lung cancer. The pace of research progress in this area has been remarkable: chromosomal rearrangements involving this gene in lung cancer were first reported in 2007 by a team of investigators in Japan. Less than 3 years later, an early-phase clinical trial of a targeted ALK inhibitor has yielded impressive responses in patients with advanced lung cancer containing ALK rearrangements, and mechanisms of acquired resistance to ALK-targeted therapy are being reported. A definitive study randomizing patients with ALK-mutant lung cancer to crizotinib (also known as PF-02341066 or 1066) versus standard therapy has recently completed enrollment.Taken together, these data describe a trajectory of research progress from basic discovery science to real-world implementation that should serve as a model for future integration of preclinical and clinical therapeutic research.

Magnetization-prepared rapid acquisition with gradient echo magnetic resonance imaging signal and texture features for the prediction of mild cognitive impairment to Alzheimer's disease progression.

PubMed

Martinez-Torteya, Antonio; Rodriguez-Rojas, Juan; Celaya-Padilla, José M; Galván-Tejada, Jorge I; Treviño, Victor; Tamez-Peña, Jose

2014-10-01

Early diagnoses of Alzheimer's disease (AD) would confer many benefits. Several biomarkers have been proposed to achieve such a task, where features extracted from magnetic resonance imaging (MRI) have played an important role. However, studies have focused exclusively on morphological characteristics. This study aims to determine whether features relating to the signal and texture of the image could predict mild cognitive impairment (MCI) to AD progression. Clinical, biological, and positron emission tomography information and MRI images of 62 subjects from the AD neuroimaging initiative were used in this study, extracting 4150 features from each MRI. Within this multimodal database, a feature selection algorithm was used to obtain an accurate and small logistic regression model, generated by a methodology that yielded a mean blind test accuracy of 0.79. This model included six features, five of them obtained from the MRI images, and one obtained from genotyping. A risk analysis divided the subjects into low-risk and high-risk groups according to a prognostic index. The groups were statistically different ([Formula: see text]). These results demonstrated that MRI features related to both signal and texture add MCI to AD predictive power, and supported the ongoing notion that multimodal biomarkers outperform single-modality ones.

The Lancet Countdown: tracking progress on health and climate change.

PubMed

Watts, Nick; Adger, W Neil; Ayeb-Karlsson, Sonja; Bai, Yuqi; Byass, Peter; Campbell-Lendrum, Diarmid; Colbourn, Tim; Cox, Peter; Davies, Michael; Depledge, Michael; Depoux, Anneliese; Dominguez-Salas, Paula; Drummond, Paul; Ekins, Paul; Flahault, Antoine; Grace, Delia; Graham, Hilary; Haines, Andy; Hamilton, Ian; Johnson, Anne; Kelman, Ilan; Kovats, Sari; Liang, Lu; Lott, Melissa; Lowe, Robert; Luo, Yong; Mace, Georgina; Maslin, Mark; Morrissey, Karyn; Murray, Kris; Neville, Tara; Nilsson, Maria; Oreszczyn, Tadj; Parthemore, Christine; Pencheon, David; Robinson, Elizabeth; Schütte, Stefanie; Shumake-Guillemot, Joy; Vineis, Paolo; Wilkinson, Paul; Wheeler, Nicola; Xu, Bing; Yang, Jun; Yin, Yongyuan; Yu, Chaoqing; Gong, Peng; Montgomery, Hugh; Costello, Anthony

2017-03-18

The Lancet Countdown: tracking progress on health and climate change is an international, multidisciplinary research collaboration between academic institutions and practitioners across the world. It follows on from the work of the 2015 Lancet Commission, which concluded that the response to climate change could be "the greatest global health opportunity of the 21st century". The Lancet Countdown aims to track the health impacts of climate hazards; health resilience and adaptation; health co-benefits of climate change mitigation; economics and finance; and political and broader engagement. These focus areas form the five thematic working groups of the Lancet Countdown and represent different aspects of the complex association between health and climate change. These thematic groups will provide indicators for a global overview of health and climate change; national case studies highlighting countries leading the way or going against the trend; and engagement with a range of stakeholders. The Lancet Countdown ultimately aims to report annually on a series of indicators across these five working groups. This paper outlines the potential indicators and indicator domains to be tracked by the collaboration, with suggestions on the methodologies and datasets available to achieve this end. The proposed indicator domains require further refinement, and mark the beginning of an ongoing consultation process-from November, 2016 to early 2017-to develop these domains, identify key areas not currently covered, and change indicators where necessary. This collaboration will actively seek to engage with existing monitoring processes, such as the UN Sustainable Development Goals and WHO's climate and health country profiles. The indicators will also evolve over time through ongoing collaboration with experts and a range of stakeholders, and be dependent on the emergence of new evidence and knowledge. During the course of its work, the Lancet Countdown will adopt a collaborative and iterative process, which aims to complement existing initiatives, welcome engagement with new partners, and be open to developing new research projects on health and climate change. Copyright © 2017 Elsevier Ltd. All rights reserved.

Childhood Psychosocial Cumulative Risks and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study

PubMed Central

Hakulinen, Christian; Pulkki-Råback, Laura; Elovainio, Marko; Kubzansky, Laura D.; Jokela, Markus; Hintsanen, Mirka; Juonala, Markus; Kivimäki, Mika; Josefsson, Kim; Hutri-Kähönen, Nina; Kähönen, Mika; Viikari, Jorma; Keltikangas-Järvinen, Liisa; Raitakari, Olli T

2015-01-01

Objective Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity as well as having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression. Methods Participants were 2265 men and women (age range: 24-39 years in 2001) from the on-going Cardiovascular Risk in Young Finns study whose carotid IMT were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life-events, parental health behavior family, socioeconomic status, and childhood emotional environment). Results The cumulative risk score was associated with higher IMT in 2007 (b=.004; se=.001; p<.001) and increased IMT progression from 2001 to 2007 (b=.003; se=.001; p=.001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life-events was associated with higher IMT in 2001 (b=.007; se=.003; p=.016) and poorer parental health behavior predicted higher IMT in 2007 (b=.004; se=.002; p=.031) after adjustment for age, sex and childhood cardiovascular risk factors. Conclusions Early life psychosocial environment influences cardiovascular risk later in life and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood. PMID:26809108

Childhood Psychosocial Cumulative Risks and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study.

PubMed

Hakulinen, Christian; Pulkki-Råback, Laura; Elovainio, Marko; Kubzansky, Laura D; Jokela, Markus; Hintsanen, Mirka; Juonala, Markus; Kivimäki, Mika; Josefsson, Kim; Hutri-Kähönen, Nina; Kähönen, Mika; Viikari, Jorma; Keltikangas-Järvinen, Liisa; Raitakari, Olli T

2016-01-01

Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity and having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression. Participants were 2265 men and women (age range, 24-39 years in 2001) from the ongoing Cardiovascular Risk in Young Finns study whose carotid IMTs were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life events, parental health behavior family, socioeconomic status, and childhood emotional environment). The cumulative risk score was associated with higher IMT in 2007 (b = 0.004, standard error [SE] = 0.001, p < .001) and increased IMT progression from 2001 to 2007 (b = 0.003, SE = 0.001, p = .001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status, and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life events was associated with higher IMT in 2001 (b = 0.007, SE = 0.003, p = .016) and poorer parental health behavior predicted higher IMT in 2007 (b = 0.004, SE = 0.002, p = .031) after adjustment for age, sex, and childhood cardiovascular risk factors. Early life psychosocial environment influences cardiovascular risk later in life, and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood.

NASA/MSFC FY-81 Atmospheric Processes Research Review

NASA Technical Reports Server (NTRS)

Turner, R. E. (Compiler)

1981-01-01

Progress in ongoing research programs and future plans for satellite investigations into global weather, upper atmospheric phenomena, and severe storms and local weather are summarized. Principle investigators and publications since June 1980 are listed.

Program Updates - San Antonio River Basin

EPA Pesticide Factsheets

This page will house updates for this urban waters partnership location. As projects progress, status updates can be posted here to reflect the ongoing work by partners in San Antonio working on the San Antonio River Basin.

Progress in Evaluating Quantitative Optical Gas Imaging

EPA Science Inventory

Development of advanced fugitive emission detection and assessment technologies that facilitate cost effective leak and malfunction mitigation strategies is an ongoing goal shared by industry, regulators, and environmental groups. Optical gas imaging (OGI) represents an importan...

'Chronophilia': Entries of Erotic Age Preference into Descriptive Psychopathology.

PubMed

Janssen, Diederik F

2015-10-01

A scientific nomenclature of erotic age preferences informed the mid- through late nineteenth century joint appearance of homosexuality and sexual abuse of minors on the medico-legal scene. Yet, even in the twenty-first century, legal, psychiatric and culture-critical dimensions of related terms are rarely cleanly distinguished. Review of primary sources shows the ongoing Western suspension of notions of 'sick desire', alongside and beyond the medicalisation of homosexuality, between metaphor, legal interdiction and postulated psychopathology. Virtually all early attention to erotic age preference occurred in the context of emergent attention to erotic gender preference. Age of attraction and age difference centrally animate modern homosexuality's pre-modern past; its earliest psychiatric nomenclature and typologies (1844-69); its early aetiologies stipulating degrees of sexual differentiation (1890 s); its concomitant sub-classification (1896-1914); its earliest psychophysiological tests (1950s); and, finally, its post-psychiatric, social scientific typologies (1980s). Several identifications of 'paedophilia' were seen throughout the 1890 s but as a trope it gained cultural momentum only during, and as a seemingly intriguing corollary of, the progressive depsychiatricisation of homosexuality across the Anglo-European world (late 1950s through 1980s). Early twentieth century sources varied in having it denote (1) a distinct perversion, thus possible 'complication' of sexual inversion (2) a discrete corollary of psychosexual differentiation akin to gender preference (3) a distinct subtype of fetishism, thus a likely imprint of early seduction (4) a more intricate expression of erotic symbolism or psychosexual complex or (5) a taste answering to culture, a lack of it, or a libertine disregard for it.

Oncogenic LINE-1 Retroelements Sustain Prostate Tumor Cells and Promote Metastatic Progression

DTIC Science & Technology

2015-10-01

elements in prostate cancer contribute to its progression by activating oncogenic DNA sequences, or silencing tumor suppressor like sequences. We have...prostate cancer cells. Experiments are ongoing to determine if PIWIL-1 expression in prostate cancer cells will reduce their growth, thereby providing...proof of principle for future gene-based therapeutics for this cancer . 15. SUBJECT TERMS Prostate cancer , LINE-1, PIWIL-1, retrotransposons 16

Trauma-Focused CBT for Youth who Experience Ongoing Traumas

PubMed Central

Cohen, Judith A.; Mannarino, Anthony P.; Murray, Laura A.

2011-01-01

Many youth experience ongoing trauma exposure, such as domestic or community violence. Clinicians often ask whether evidence-based treatments containing exposure components to reduce learned fear responses to historical trauma are appropriate for these youth. Essentially the question is, if youth are desensitized to their trauma experiences, will this in some way impair their responding to current or ongoing trauma? The paper addresses practical strategies for implementing one evidence-based treatment, Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for youth with ongoing traumas. Collaboration with local therapists and families participating in TF-CBT community and international programs elucidated effective strategies for applying TF-CBT with these youth. These strategies included: 1) enhancing safety early in treatment; 2) effectively engaging parents who experience personal ongoing trauma; and 3) during the trauma narrative and processing component focusing on a) increasing parental awareness and acceptance of the extent of the youths’ ongoing trauma experiences; b) addressing youths’ maladaptive cognitions about ongoing traumas; and c) helping youth differentiate between real danger and generalized trauma reminders. Case examples illustrate how to use these strategies in diverse clinical situations. Through these strategies TF-CBT clinicians can effectively improve outcomes for youth experiencing ongoing traumas. PMID:21855140

Effect of acarbose to delay progression of carotid intima-media thickness in early diabetes.

PubMed

Patel, Y R; Kirkman, M S; Considine, R V; Hannon, T S; Mather, K J

2013-10-01

The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Progressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects. Copyright © 2013 John Wiley & Sons, Ltd.

Nutritional Modulation of Age-Related Macular Degeneration

PubMed Central

Weikel, Karen A; Taylor, Allen

2012-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/wk of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available. PMID:22503690

Notification: Municipal Sewer Systems - Consent Decree Progress and Challenges

EPA Pesticide Factsheets

Project #OPE-FY14-0045, August 6, 2014. The EPA OIG plans to begin preliminary research on the EPA's ongoing enforcement initiative focused on keeping raw sewage and contaminated stormwater out of our nation's waters.

DOT's Restructuring - Limited Progress in Streamlining Field Office Structure

DOT National Transportation Integrated Search

1998-04-30

The report characterizes two ongoing efforts in the Department involving our : analysis of opportunities to collocate field offices on an intermodal basis, and : FHWA's examination of its regional office structure. Although many aspects of : our effo...

Coast Guard : budget challenges for 2001 and beyond

DOT National Transportation Integrated Search

2000-03-15

The testimony today, which is based on recently completed and ongoing work, addresses two topics: (1) the Coast Guard's progress in justifying and managing its Deepwater Project and (2) opportunities for improving the Coast Guard's operating efficien...

Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma.

PubMed

Hao, Yoshiteru; Numata, Kazushi; Ishii, Tomohiro; Fukuda, Hiroyuki; Maeda, Shin; Nakano, Masayuki; Tanaka, Katsuaki

2017-05-07

To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test ( P = 0.002). The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs.

Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma

PubMed Central

Hao, Yoshiteru; Numata, Kazushi; Ishii, Tomohiro; Fukuda, Hiroyuki; Maeda, Shin; Nakano, Masayuki; Tanaka, Katsuaki

2017-01-01

AIM To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. METHODS Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. RESULTS During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test (P = 0.002). CONCLUSION The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs. PMID:28533668

Four Methods for Engaging Young Children as Environmental Education Researchers

ERIC Educational Resources Information Center

Green, Carie

2017-01-01

This article contributes to the ongoing dialogue regarding what it means to engage young children as active researchers in Early Childhood Environmental Education (ECEE) and Early Childhood Education for Sustainability (ECEfS). Drawing from a participatory and phenomenological framework, this paper considers the advantages, challenges, and…

Parenting Behaviours and Children's Development from Infancy to Early Childhood: Changes, Continuities and Contributions

ERIC Educational Resources Information Center

Gutman, Leslie Morrison; Feinstein, Leon

2010-01-01

This study investigated trajectories of parenting behaviours and children's development from infancy to early childhood, associations between parenting behaviours and children's development and how these associations vary according to socioeconomic indicators. Mothers and children were examined from an ongoing longitudinal study of families…

Making Space for Place-Making Pedagogies: Stretching Normative Mandated Literacy Curriculum

ERIC Educational Resources Information Center

Comber, Barbara

2011-01-01

In an era of normative standardised literacy curriculum continuing to make space for culturally responsive literacy pedagogy is on ongoing challenge for early childhood educators. Collaborative participatory research and ethnographic studies of teachers who accomplish innovative and inclusive early childhood education in culturally diverse high…

Potential Developmental and Early Life Health Effects of Nanomaterials: Data Gaps and Research Needs for Risk Assessment

EPA Science Inventory

Although research examining the toxicology of nanomaterials has been ongoing for many years, early studies largely focus on respiratory effects, and are limited by lack of appropriate dose metrics and a limited understanding of the role of the physicochemical properties of nanoma...

Supporting Early Childhood Teachers in Guinea-Bissau

ERIC Educational Resources Information Center

Portugal, Maria Gabriela; Aveleira, Ana Paula

2009-01-01

This article presents a reflective report on a project aiming to strengthen educators and improve early childhood education in Guinea-Bissau--one of the poorest countries on the African continent, where preschool teachers have no training and have to face several ongoing difficulties. Helping these Guinea-Bissau teachers to focus on curriculum…

Effects of Acarbose to Delay Progression of Carotid Intima-Media Thickness in Early Diabetes

PubMed Central

Patel, YR; Kirkman, MS; Considine, RV; Hannon, TS; Mather, KJ

2014-01-01

Background The antidiabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. Methods The Early Diabetes Intervention Program (EDIP) was a randomized trial of acarbose versus placebo, in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 hours after a 75g oral glucose load, and mean HbA1c 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Results Progressive increases in IMT were seen in both treatment groups, but this was reduced in participants randomized to acarbose (p=0.047). In age, sex and smoking-adjusted analyses IMT progression was associated with greater fasting and OGTT-excursion glucose, fasting insulin, cholesterol, and glycated LDL concentrations. IMT progression was reduced with study-related changes in weight, insulin, and nonesterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Conclusions Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects. PMID:23908125

Chronic kidney disease guideline implementation in primary care: a qualitative report from the TRANSLATE CKD study

PubMed Central

Vest, Bonnie M.; York, Trevor R.M.; Sand, Jessica; Fox, Chester H.; Kahn, Linda S.

2016-01-01

Background Primary care physicians (PCPs) are optimally situated to identify and manage early-stage chronic kidney disease (CKD). Nonetheless, studies have documented suboptimal PCP understanding, awareness, and management of early CKD. The TRANSLATE CKD study is an ongoing national mixed-methods cluster randomized control trial that examines the implementation of evidence-based guidelines for CKD into primary care practice. Methods As part of mixed-methods process evaluation, semi-structured interviews were conducted by phone with 27 providers participating in the study. Interviews were audio-taped and transcribed. Thematic content analysis was used to identify themes. Themes were categorized according to the four domains of Normalization Process Theory (NPT). Results Identified themes illuminated the complex work undertaken in primary care practices to manage CKD. Barriers to guideline implementation were identified in each of the four NPT domains, including: 1) lack of knowledge and understanding around CKD (coherence), 2) difficulties engaging providers and patients in CKD management (cognitive participation), 3) limited time and competing demands (collective action), and 4) challenges obtaining and utilizing data to monitor progress (reflexive monitoring). Conclusions Addressing the barriers to implementation with concrete interventions at the levels at which they occur, informed by NPT, will ultimately improve the quality of CKD patient care. PMID:26355134

The International Thymic Malignancy Interest Group thymic initiative: a state-of-the-art study of thymic malignancies.

PubMed

Detterbeck, Frank; Korst, Robert

2014-01-01

Thymic malignancies are relatively rare tumors. A general lack of knowledge, misconceptions about benignancy, confusion about the definition of terms, and variability in reporting of outcomes have further hampered progress in these diseases. The International Thymic Malignancy Interest Group has emerged to counter these challenges and has brought together a worldwide multidisciplinary community determined to improve outcomes for these patients. Although the organization is young (initiated in 2010), major early accomplishments have created a foundation and infrastructure for scientific research. These include consensus definitions of terms, an unprecedented global database, development of practical clinical resources and, together with the International Association for the Study of Lung Cancer, development of proposals for the first formal stage classification of these malignant tumors. Many articles have been published or are under way, and a second phase of projects building on the early success is proceeding. The greatest accomplishment of the International Thymic Malignancy Interest Group lies in the establishment of an open culture of collaboration and the engagement of a broad group of individuals united by a common mission. It is a testament to what can be achieved, despite ongoing and inherent challenges, by determination and a collective effort. Copyright © 2014 Elsevier Inc. All rights reserved.

Work Change in Multiple Sclerosis as Motivated by the Pursuit of Illness-Work-Life Balance: A Qualitative Study.

PubMed

Vijayasingham, Lavanya; Jogulu, Uma; Allotey, Pascale

2017-01-01

Individuals with multiple sclerosis have a tendency to make early decisions for work change, even in reversible, episodic, or mild disease stages. To better understand how a multiple sclerosis (MS) diagnosis influences perceptions of work and motivations for work changes, we conducted a hermeneutic phenomenology study to explore the work lives of ten individuals with MS in Malaysia. The interpretive analysis and cumulative narratives depict an overarching change in their concept of ideal work and life aspirations and how participants make preemptive work changes to manage illness-work-life futures in subjectively meaningful ways. Discussions on their integrated pursuit of finding dynamic and subjective illness-work-life balance include reconciling the problem of hard work and stress on disease activity and progress, making positive lifestyle changes as health management behaviour, and the motivational influence of their own life and family roles: the consideration of their spouses, parents, and children. At an action level, work change was seen as moral and necessary for the management of illness futures. Our findings contribute insights on how individual perceptions and holistic life management decisions contribute to on-going and disrupted work trajectories, which can inform practice and policy on early interventions to support continued employment.

Chronic Kidney Disease Guideline Implementation in Primary Care: A Qualitative Report from the TRANSLATE CKD Study.

PubMed

Vest, Bonnie M; York, Trevor R M; Sand, Jessica; Fox, Chester H; Kahn, Linda S

2015-01-01

Primary care physicians (PCPs) are optimally situated to identify and manage early stage chronic kidney disease (CKD). Nonetheless, studies have documented suboptimal PCP understanding, awareness, and management of early CKD. The TRANSLATE CKD study is an ongoing national, mixed-methods, cluster randomized control trial that examines the implementation of evidence-based guidelines for CKD into primary care practice. As part of the mixed-methods process evaluation, semistructured interviews were conducted by phone with 27 providers participating in the study. Interviews were audio-taped and transcribed. Thematic content analysis was used to identify themes. Themes were categorized according to the 4 domains of Normalization Process Theory (NPT). Identified themes illuminated the complex work undertaken to manage CKD in primary care practices. Barriers to guideline implementation were identified in each of the 4 NPT domains, including (1) lack of knowledge and understanding around CKD (coherence), (2) difficulties engaging providers and patients in CKD management (cognitive participation), (3) limited time and competing demands (collective action), and (4) challenges obtaining and using data to monitor progress (reflexive monitoring). Addressing the barriers to implementation with concrete interventions at the levels at which they occur, informed by NPT, will ultimately improve the quality of CKD patient care. © Copyright 2015 by the American Board of Family Medicine.

Work Change in Multiple Sclerosis as Motivated by the Pursuit of Illness-Work-Life Balance: A Qualitative Study

PubMed Central

Jogulu, Uma

2017-01-01

Individuals with multiple sclerosis have a tendency to make early decisions for work change, even in reversible, episodic, or mild disease stages. To better understand how a multiple sclerosis (MS) diagnosis influences perceptions of work and motivations for work changes, we conducted a hermeneutic phenomenology study to explore the work lives of ten individuals with MS in Malaysia. The interpretive analysis and cumulative narratives depict an overarching change in their concept of ideal work and life aspirations and how participants make preemptive work changes to manage illness-work-life futures in subjectively meaningful ways. Discussions on their integrated pursuit of finding dynamic and subjective illness-work-life balance include reconciling the problem of hard work and stress on disease activity and progress, making positive lifestyle changes as health management behaviour, and the motivational influence of their own life and family roles: the consideration of their spouses, parents, and children. At an action level, work change was seen as moral and necessary for the management of illness futures. Our findings contribute insights on how individual perceptions and holistic life management decisions contribute to on-going and disrupted work trajectories, which can inform practice and policy on early interventions to support continued employment. PMID:29348937

Recent advances in multidisciplinary management of hepatocellular carcinoma

PubMed Central

Gomaa, Asmaa I; Waked, Imam

2015-01-01

The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

Retinopathy predicts progression of fasting plasma glucose: An Early Diabetes Intervention Program (EDIP) Analysis

PubMed Central

Patel, Yash R.; Kirkman, M. Sue; Considine, Robert V; Hannon, Tamara S; Mather, Kieren J

2017-01-01

Background Retinopathy is increasingly recognized in prediabetic populations, and may herald increased risk of metabolic worsening. The Early Diabetes Intervention Program (EDIP) evaluated worsening of glycemia in screen-detected Type 2 diabetes, following participants for up to 5 years. Here we have evaluated whether the presence of retinopathy at the time of detection of diabetes was associated with accelerated progression of glycemia. Methods We prospectively studied 194 participants from EDIP with available baseline retinal photographs. Retinopathy was determined at baseline using 7-field fundus photography and defined as an Early Treatment of Diabetic Retinopathy Study Scale grading score of ≥20. Results At baseline, 12% of participants had classical retinal lesions indicating retinopathy. In univariate Cox proportional hazard analysis, the presence of retinopathy at baseline was associated with a doubled risk of progression of fasting plasma glucose (HR 2.02; 95% CI 1.05–3.89). The retinopathy effect was robust to individual adjustment for age and glucose, the most potent determinants of progression in EDIP. Conclusion Retinopathy was associated with increased risk of progression of fasting plasma glucose among adults with screen-detected, early diabetes. Early detection of retinopathy may help individualize more aggressive therapy to prevent progressive metabolic worsening in early diabetes. PMID:28003103

Association of Systemic Inflammatory and Anti-inflammatory Responses with Adverse Outcomes in Acute Pancreatitis: Preliminary Results of an Ongoing Study.

PubMed

Sharma, Deepesh; Jakkampudi, Aparna; Reddy, Ratnakar; Reddy, Panyala Balakumar; Patil, Aasish; Murthy, H V V; Rao, G Venkat; Reddy, D Nageshwar; Talukdar, Rupjyoti

2017-12-01

This paper reports preliminary data of an ongoing study that evaluates the association of systemic inflammatory response (SIRS) with early severe acute pancreatitis (ESAP) and compensatory anti-inflammatory response syndrome (characterized by HLA-DR down-regulation) with infected pancreatic necrosis (IPN). Consecutive patients presenting within 72 h of symptom onset with organ dysfunction and/or local complications were included. Following parameters were recorded: demographics, etiology, SIRS, APACHE II, creatinine, BUN. Circulating IL-8, IL-6, IL-10, TNF-alpha concentrations and expression of HLA-DR and IL-10 by qRT-PCR in PBMCs were measured. Strength of associations of cytokine concentration and HLA-DR/IL-10 expression with outcomes was expressed as Hedges' G and relative risk (95% CI). Twenty-eight patients (10 MSAP; 18 SAP) fulfilled inclusion criteria. Twelve patients had ESAP and eight presented with organ failure. Admission SIRS worsened in eight (28.6%) patients over 48 h. Sixteen (57.1%) patients developed primary IPN. Twenty-one (75%) patients had HLA-DR down-regulation during the first week, which persisted to the second week in 12 (42.9%) patients. IL-8, IL-6, and TNF-α progressively increased from healthy controls to MAP to MSAP to SAP. IL-6 and TNF-α was higher in the patients who developed ESAP (p = 0.01 and 0.05, respectively). Patients who died within the first week also had a significantly elevated concentration of IL-6 and TNF-α (p = 0.02 and 0.01, respectively). The relative risk (95% CI) of developing primary IPN with persistent HLA-DR down-regulation till the second week of illness was 11.3 (1.6-82.4; p = 0.01). Our study objectively demonstrates significant association of ESAP and early mortality with primary cytokine response, and development of IPN with persistent HLA-DR down-regulation.

Putting The "Yee-Hah!" In Astronomy Outreach: Professional Development Through The ASP "Sky Rangers" Project

NASA Astrophysics Data System (ADS)

Manning, Jim; Gurton, S.; Hurst, A.

2010-05-01

The Astronomical Society of the Pacific is conducting a NASA-funded professional development program to help increase astronomy education and outreach capacity at national parks, nature centers, and other outdoor and environmental centers--venues that still have a dark night sky as a natural resource and a yen to interpret it for their visitors. Through online workshops and on-site workshops at national parks, the ASP staff, working in conjunction with partners from the National Park Service, National Association for Interpretation, and the Association of Science and Technology Centers, provides materials and training focusing on the sky. Participants become part of ASP's "Astronomy from the Ground Up" informational education community of practice, with ongoing options to hone their new skills. The presenter will report on early progress and lessons learned, as well as future plans, as the ASP and its partners work to help wilderness and nature interpreters put a little more "yee-hah!" in their visitor presentations aimed at the sky.

Ongoing Cerebral Vasculitis During Treatment of Rocky Mountain Spotted Fever.

PubMed

Sun, Lisa R; Huisman, Thierry A G M; Yeshokumar, Anusha K; Johnston, Michael V

2015-11-01

Rocky Mountain spotted fever is a tickborne infection that produces a systemic small-vessel vasculitis; its prognosis is excellent if appropriate treatment is initiated early. Because the advent of effective antirickettsial therapies predates the widespread use of brain magnetic resonance imaging, there are limited data on the effect of untreated Rocky Mountain spotted fever infection on neuroimaging studies. We describe a 7-year-old girl with delayed treatment of Rocky Mountain spotted fever who suffered severe neurological impairment. Serial brain magnetic resonance images revealed a progressive "starry sky appearance," which is proposed to result from the same small vessel vasculitis that causes the characteristic skin rash of this infection. Neurological injury can continue to occur despite specific antirickettsial therapy in Rocky Mountain spotted fever. This child's clinical features raise questions about the optimal management of this infection, particularly the utility of immune modulating therapies in cases of delayed treatment and neurological involvement. Copyright © 2015 Elsevier Inc. All rights reserved.

Compressing climate model simulations: reducing storage burden while preserving information

NASA Astrophysics Data System (ADS)

Hammerling, Dorit; Baker, Allison; Xu, Haiying; Clyne, John; Li, Samuel

2017-04-01

Climate models, which are run at high spatial and temporal resolutions, generate massive quantities of data. As our computing capabilities continue to increase, storing all of the generated data is becoming a bottleneck, which negatively affects scientific progress. It is thus important to develop methods for representing the full datasets by smaller compressed versions, which still preserve all the critical information and, as an added benefit, allow for faster read and write operations during analysis work. Traditional lossy compression algorithms, as for example used for image files, are not necessarily ideally suited for climate data. While visual appearance is relevant, climate data has additional critical features such as the preservation of extreme values and spatial and temporal gradients. Developing alternative metrics to quantify information loss in a manner that is meaningful to climate scientists is an ongoing process still in its early stages. We will provide an overview of current efforts to develop such metrics to assess existing algorithms and to guide the development of tailored compression algorithms to address this pressing challenge.

Hematoma Expansion Following Acute Intracerebral Hemorrhage

PubMed Central

Brouwers, H. Bart; Greenberg, Steven M.

2013-01-01

Intracerebral hemorrhage, the most devastating form of stroke, has no specific therapy proven to improve outcome by randomized controlled trial. Location and baseline hematoma volume are strong predictors of mortality, but are non-modifiable by the time of diagnosis. Expansion of the initial hematoma is a further marker of poor prognosis that may be at least partly preventable. Several risk factors for hematoma expansion have been identified, including baseline ICH volume, early presentation after symptom onset, anticoagulation, and the CT angiography spot sign. Although the biological mechanisms of hematoma expansion remain unclear, accumulating evidence supports a model of ongoing secondary bleeding from ruptured adjacent vessels surrounding the initial bleeding site. Several large clinical trials testing therapies aimed at preventing hematoma expansion are in progress, including aggressive blood pressure reduction, treatment with recombinant factor VIIa guided by CT angiography findings, and surgical intervention for superficial hematomas without intraventricular extension. Hematoma expansion is so far the only marker of outcome that is amenable to treatment and thus a potentially important therapeutic target. PMID:23466430

Developing new products in cystic fibrosis: needs and obstacles for activities of small and middle-sized companies.

PubMed

Schlangen, Miriam; Reimann, Andreas L G

2011-06-01

Small and middle-sized enterprises (SMEs) can make important contributions to medical progress through the development of new safe and effective drugs that address the greatest unmet needs of patients. Regulatory inconsistencies across agencies in various countries, however, remain major challenges in cystic fibrosis (CF) drug development. Clear and consistent treatment guidelines, well educated clinical trial sites, a patient registry and grant funding for early development programs are important success-factors for an efficient development process. SMEs developing products for CF need partners in the CF community to assist with disease education and awareness for ongoing clinical trials. SMEs should collaborate and communicate with the CF community in a legally compliant way to take a patient-centric approach to drug design, development and administration. Furthermore, they can help to develop educational tools and fund medical education activities to increase the understanding of the underlying defects and mechanisms of CF disease. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

James, K.H.

A prolific hydrocarbon province extends across the northern margin of South America from Colombia to east of Trinidad. Two key components are a world-class source rock, formed on a regional Late Cretaceous passive margin, and a complex tectonic setting in which a variety of structural and stratigraphic traps, reservoirs, seals and hydrocarbon kitchens have evolved through time. Convergence between the Farallon and Caribbean plates with South America culminated in the late Cretaceous-early Palaeogene with emplacement of Colombia`s Central Cordillera in the west and a nappe-foreland basin system in the north. Regional hydrocarbon generation probably occurred below associated basins. Subsequent obliquemore » convergence between the Caribbean and South America, partitioned into strike-slip and compressional strain, generated an eastward migrating and ongoing uplift-foredeep (kitchen) system from central Venezuela to Trinidad. Similarly, oblique interaction of western Colombia with the Nazca Plate caused segmentation of the earlier orogen, northward extrusion of elements such as the Maracaibo Block, and eastward migration of uplift progressively dividing earlier kitchens into localized foredeeps.« less

Current therapeutic landscape for advanced gastroesophageal cancers

PubMed Central

Lopez, Anthony; Harada, Kazuto; Mizrak Kaya, Dilsa

2018-01-01

Treatment of advanced gastroesophageal cancers remains challenging for clinicians, patients, and caregivers alike. Despite considerable research, the therapeutic armamentarium is restricted and hardly personalized. In the first-line setting, trastuzumab with a fluoropyrimidine and platinum agent is the standard-of-care in patients with HER2-positive tumor. For the others, a platinum-based doublet (preferably with oxaliplatin) is recommended. Three-drug cytotoxic regimens should be reserved for exceptional cases where patients have good performance status. Triple combinations produce higher toxicity and provide marginal advantage. In the second line setting, the combination of paclitaxel and ramucirumab is preferred over all others. Currently, nothing is approved in the 3rd or later line. Nivolumab has resulted in an improved benefit in an Asian trial. Early trials of TAS-102, STAT3 inhibitors, anti-claudin 18.2 and other immune checkpoint inhibitors (alone or in combination) are ongoing. However, development of reproducible biomarkers for patient enrichment is critical for future progress. PMID:29666801

From planes to brains: parallels between military development of virtual reality environments and virtual neurological surgery.

PubMed

Schmitt, Paul J; Agarwal, Nitin; Prestigiacomo, Charles J

2012-01-01

Military explorations of the practical role of simulators have served as a driving force for much of the virtual reality technology that we have today. The evolution of 3-dimensional and virtual environments from the early flight simulators used during World War II to the sophisticated training simulators in the modern military followed a path that virtual surgical and neurosurgical devices have already begun to parallel. By understanding the evolution of military simulators as well as comparing and contrasting that evolution with current and future surgical simulators, it may be possible to expedite the development of appropriate devices and establish their validity as effective training tools. As such, this article presents a historical perspective examining the progression of neurosurgical simulators, the establishment of effective and appropriate curricula for using them, and the contributions that the military has made during the ongoing maturation of this exciting treatment and training modality. Copyright © 2012. Published by Elsevier Inc.

Integrated nonlinear photonics. Emerging applications and ongoing challenges - A mini review

DOE PAGES

Hendrickson, Scott M.; Foster, Amy C.; Camacho, Ryan M.; ...

2014-11-26

In this paper, we provide a review of recent progress in integrated nonlinear photonics with a focus on emerging applications in all-optical signal processing, ultra-low-power all-optical switching, and quantum information processing.

Discriminant analysis forecasting model of first trimester pregnancy outcomes developed by following 9,963 infertile patients after in vitro fertilization.

PubMed

Yi, Yan; Li, Xihong; Ouyang, Yan; Lin, Ge; Lu, Guangxiu; Gong, Fei

2016-05-01

To investigate a forecasting method developed to predict first trimester pregnancy outcomes using the first routine ultrasound scan for early pregnancy on days 27-29 after ET and to determine whether to perform a repeated scan several days later based on this forecasting method. Prospective analysis. Infertile patients at an assisted reproductive technology center. A total of 9,963 patients with an early singleton pregnancy after in vitro fertilization (IVF)-ET. None. Ongoing pregnancy >12 weeks of gestation. The classification score of ongoing pregnancy was equal to (1.57 × Maternal age) + (1.01 × Mean sac diameter) + (-0.19 × Crown-rump length) + 25.15 (if cardiac activity is present) + 1.30 (if intrauterine hematomas are present) - 47.35. The classification score of early pregnancy loss was equal to (1.66 × Maternal age) + (0.84 × Mean sac diameter) + (-0.38 × Crown-rump length) + 8.69 (if cardiac activity is present) + 1.60 (if intrauterine hematomas are present) - 34.77. In verification samples, 94.44% of cases were correctly classified using these forecasting models. The discriminant forecasting models are accurate in predicting first trimester pregnancy outcomes based on the first scan for early pregnancy after ET. When the predictive result is ongoing pregnancy, a second scan can be postponed until 11-14 weeks if no symptoms of abdominal pain or vaginal bleeding are present. When the predictive results suggest early pregnancy loss, repeated scans are imperative to avoid a misdiagnosis before evacuating the uterus. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Recovery collapse coincident with ongoing carbon cycle perturbations following the Permian-Triassic mass extinction

NASA Astrophysics Data System (ADS)

Petsios, E.; Bottjer, D. J.

2016-12-01

The Permian-Triassic mass extinction, the largest extinction of the Phanerozoic, is attributed to volcanic outgassing from the Siberian Traps and the resulting climate change. Ongoing volcanism in the Early Triassic is implicated for continued carbon cycle instability following the initial event, reflected in large inorganic carbon isotope excursions throughout the 5 Mya interval. Recent paleoecological studies have shown that timing of recovery from the extinction in the Early Triassic is highly complex, differing between regions, with documented cases of "early" recovery in some environments. The importance of specific environmental factors, such as oxygen levels and sea surface temperatures, in aiding or hindering recovery following the extinction is the topic of ongoing study. Here we present an ecological survey of marine benthic communities from the Lower Triassic Blacktail Creek outcrop of the Dinwoody Formation, correlated bed-for-bed with inorganic carbon isotope values. We observe incipient recovery as communities show increasing richness and evenness throughout the section, followed by a `collapse' with a return of high dominance, low richness fauna coincident with large δ13Ccarb shifts. We observe a statistically significant correlation between the magnitude of δ13Ccarb excursions and benthic community complexity over a stratigraphic section, implying a shared causal mechanism acting at the local scale. The globally correlatable nature of these observed carbon isotope shifts, as well as an absence of lithologic evidence for oxygen limitation, points to thermal stress brought on by pulses of volcanism as the shared cause between recovery collapse and carbon cycle perturbations. We propose that the "early" recovery at Blacktail Creek was truncated by recurrent greenhouse gas induced thermal spikes, highlighting the interplay of local and global environmental conditions in expediting or hindering Early Triassic recovery.

PRELIMINARY RESULTS OF A PROSPECTIVE FEASIBILITY PILOT STUDY OF “GEMPOX” (GEMCITABINE, OXALIPLATIN, AND PACLITAXEL) IN PEDIATRIC AND ADULT PATIENTS WITH REFRACTORY OR RECURRENT CENTRAL NERVOUS SYSTEM (CNS) GERM CELL TUMORS (GCT): THE INTERNATIONAL CNS GCT CONSORTIUM TRIAL, CNS GCT-4

PubMed Central

Finlay, Jonathan L.; Liu, Yin; Haley, Kelley; Erdreich-Epstein, Anat; Rushing, Teresa; Grimm, John; Wong, Kenneth E.; Kiehna, Erin; Krieger, Mark D.; Gilles, Floyd; Badie, Benham; D'Apuzzo, Massimo; Dhall, Girish

2014-01-01

BACKGROUND: The optimal management of patients with recurrent CNS GCT, especially those with non-germinomatous (mixed malignant) GCT (MMGCT), remains unclear. Preliminary results are presented on the response rate, toxicity and early outcomes of a re-induction regimen of gemcitabine, oxaliplatin and paclitaxel (GEMPOX) administered, in responsive patients, prior to myeloablative chemotherapy and autologous hematopoietic cell rescue (HDCx + AuHCR). METHODS: Since December 2004, 13 recurrent or refractory patients (12 MMGCT, 1 germinoma; 12 males; mean age 16.5 years, range 7-34 years) have been treated with up to 4 cycles of gemcitabine (800 mg/m2), oxaliplatin (100 mg/m2) and paclitaxel (170 mg/m2), administered on one day at 14 days intervals. RESULTS: Of 13 patients, five were treated on a preceding feasibility pilot with 1-3 cycles of GEMPOX, and seven have been formally enrolled on an ongoing prospective multi-center trial. Six patients achieved complete remissions (tumor marker and/or imaging studies), five achieved partial remissions and two developed progressive disease (PD) while on GEMPOX; one patient with PD after 1 cycle had pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma.; the second patient, with pure pineal choriocarcinoma, progressed following the second cycle of GEMPOX. Eleven of the 13 patents subsequently underwent HDCx + AuHCR. Six of them subsequently received irradiation. Transient hepatotoxicity and pancytopenia were the most commonly observed toxicities. Other toxicities included: paclitaxel anaphylaxis (1), transient encephalopathy (1), peripheral neuropathy (1), hyperesthesia (4), mucositis (2) and electrolyte imbalances (3). Four of the 12 patients with MMGCT continue alive and disease-free for 8+ , 10+ , 14+ and 16+ months since discontinuation of all therapy. One patient (with pure yolk sac tumor) relapsed in a loco-regional extra-CNS location (cavernous and ethmoid/sphenoid sinuses) and remains alive with progressive disease on therapy now 12+ months post-HDCx + AuHCR. CONCLUSIONS: GEMPOX appears to be an effective re-induction regimen for patients with recurrent CNS MMGCT, with acceptable toxicities. The ongoing multi-center, international trial should confirm this and demonstrate the contribution of GEMPOX towards improved survival when followed by HDCx + AuHCR with or without further irradiation, in the setting of minimal residual disease. SECONDARY CATEGORY: Pediatrics.

Early Detection of Progressive Adolescent Idiopathic Scoliosis: A Severity Index.

PubMed

Skalli, Wafa; Vergari, Claudio; Ebermeyer, Eric; Courtois, Isabelle; Drevelle, Xavier; Kohler, Remi; Abelin-Genevois, Kariman; Dubousset, Jean

2017-06-01

Early detection of progressive adolescent idiopathic scoliosis (AIS) was assessed based on 3D quantification of the deformity. Based on 3D quantitative description of scoliosis curves, the aim is to assess a specific phenotype that could be an early detectable severity index for progressive AIS. Early detection of progressive scoliosis is important for adapted treatment to limit progression. However, progression risk assessment is mainly based on the follow up, waiting for signs of rapid progression that generally occur during the growth peak. Sixty-five mild scoliosis (16 boys, 49 girls, Cobb Angle between 10 and 20°) with a Risser between 0 and 2 were followed from their first examination until a decision was made by the clinician, either considering the spine as stable at the end of growth (26 patients) or planning to brace because of progression (39 patients). Calibrated biplanar x-rays were performed and 3D reconstructions of the spine allowed calculating six local parameters related to main curve deformity. For progressive curve 3D phenotype assessment, data were compared with those previously assessed for 30 severe scoliosis (Cobb Angle > 35°), 17 scoliosis before brace (Cobb Angle > 29°) and 53 spines of nonscoliosis subjects. A predictive discriminant analysis was performed to assess similarity of mild scoliosis curves either to those of scoliosis or nonscoliosis spines, yielding a severity index (S-index). S-index value at first examination was compared with clinical outcome. At the first exam, 53 out of 65 predictions (82%) were in agreement with actual clinical outcome. Approximately, 89% of the curves that were predicted as progressive proved accurate. Although still requiring large scale validation, results are promising for early detection of progressive curves. 2.

Bridging from Cells to Cognition in Autism Pathophysiology: Biological Pathways to Defective Brain Function and Plasticity

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

Anderson, Matthew; Hooker, Brian S.; Herbert, Martha

We review evidence to support the model that autism may begin when a maternal environmental, infectious, or autoantibody insult causes inflammation which increases reactive oxygen species (ROS) production in the fetus, leading to fetal DNA damage (nuclear and mitochondrial), and that these inflammatory and oxidative stressors persist beyond early development (with potential further exacerbations), producing ongoing functional consequences. In organs with a high metabolic demand such as the central nervous system, the continued use of mitochondria with DNA damage may generate additional ROS which will activate the innate immune system leading to more ROS production. Such a mechanism would self-sustainmore » and possibly progressively worsen. The mitochondrial dysfunction and altered redox signal transduction pathways found in autism would conspire to activate both astroglia and microglia. These activated cells can then initiate a broad-spectrum proinflammatory gene response. Neurons may have acquired receptors for these inflammatory signals to inhibit neuronal signaling as a protection from excitotoxic damage during various pathologic insults (e.g., infection). In autism, over-zealous neuroinflammatory responses could not only influence neural developmental processes, but may more significantly impair neural signaling involved in cognition in an ongoing fashion. This model makes specific predictions in patients and experimental animal models and suggests a number of targets sites of intervention. Our model of potentially reversible pathophysiological mechanisms in autism motivates our hope that effective therapies may soon appear on the horizon.« less

A call to arms: economic barriers to optimal dialysis care.

PubMed

McFarlane, P A; Mendelssohn, D C

2000-01-01

Epidemic growth rates and the enormous cost of dialysis pressure end-stage renal disease (ESRD) delivery systems around the world. Payers of dialysis services can constrain costs through (1) limiting access to dialysis, (2) reducing the quality of dialysis, and (3) placing constraints on modality distribution. In order to secure the necessary resources for ESRD care, we propose that the nephrology community consider the following suggestions: First, future leaders in dialysis should acquire additional advanced training in innovative pathways such as health care economics, business and health care administration, and health care policy. Second, the international nephrology community must strongly engage in ongoing advocacy for accessible, high quality, cost-effective care.Third, efforts should be made to better define and then implement optimal dialysis modality distributions that maximize patient outcomes but limit unnecessary costs. Fourth, industry should be encouraged to lower the unit cost of dialysis, allowing for improved access to dialysis, especially in developing countries. Fifth, research should be encouraged that seeks to identify measures that will reduce dialysis costs but will not impair quality of care. Finally, early referral of patients with progressive renal disease to nephrology clinics, empowerment of informed patient choice of dialysis modality, and proper and timely access creation should be encouraged and can be expected to help limit overall expenditures. Ongoing efforts in these areas by the nephrology community will be essential if we are to overcome the challenges of ESRD growth in this new decade.

The Early Communication Indicator for Infants and Toddlers: Early Head Start Growth Norms from Two States

ERIC Educational Resources Information Center

Greenwood, Charles R.; Walker, Dale; Buzhardt, Jay

2010-01-01

The Early Communication Indicator (ECI) is a measure relevant to intervention decision making and progress monitoring for infants and toddlers. With increasing recognition of the importance of quality early childhood education and intervention for all children, measurement plays an important role in documenting children's progress and outcomes of…

Louisiana Standards for Programs Serving Four-Year-Old Children: Bulletin.

ERIC Educational Resources Information Center

Picard, Cecil J.

As part of Louisiana's efforts to expand and improve the quality of its early childhood programs, a committee of educators from across the state collaborated to develop standards for programs serving 4-year-olds. This guide presents program standards to assist the ongoing development, evaluation, and improvement of early childhood center-based…

78 FR 53187 - Early Scoping Notification for the Alternatives Analysis of the GA 400 Transit Initiative in...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... (MARTA) issue this early scoping notice to advise other agencies and the public that they intend to... the public and agency officials to help support the ongoing alternatives analysis and system planning... considered, the transportation problems that are being addressed by the alternatives analysis study, public...

Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

ERIC Educational Resources Information Center

Hawley, Theresa

Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

Research on a Community-Initiated Preschool Program. Final Report.

ERIC Educational Resources Information Center

Davies, Norma

This report describes and anlayzes the second year operations of an ongoing successful parent initiated and directed nursery school. Included are: (1) a brief review of relevant issues in early childhood education, such as parent participation and community control in education; (2) a short history of the program's inception and early development;…

Encouraging a Culture of Research in Practicing Teachers in Singapore

ERIC Educational Resources Information Center

Ebbeck, Marjory; Chan, Yvonne Yoke Yin; Yim, Hoi Yin Bonnie

2011-01-01

Upgrading the status of early childhood teaching and improving job satisfaction are areas of concern to practitioners, policy makers and other stakeholders in the early childhood field. Ways to upgrade practicing teachers, including their involvement in research, is an on-going challenge. This paper reports on a research in Singapore where a…

Beginning Teacher Induction in Secondary Schools: A Best Practice Case Study

ERIC Educational Resources Information Center

Kearney, Sean

2017-01-01

Beginning teacher induction is becoming an increasingly popular process in acculturating teachers to their new careers. The problems that teachers face early in their careers are well known, and effective and ongoing induction is one of the foremost practices for alleviating the pressures that teachers face early in their careers. While induction…

From Parents to Partners: Building a Family-Centered Early Childhood Program

ERIC Educational Resources Information Center

Keyser, Janis

2006-01-01

Partnering with parents is essential if an early childhood program is to succeed. "From Parents to Partners" explores the reasons and methods for developing ongoing partnerships with parents and other family members. It also provides the tools and strategies needed to build the communication and support networks within which these partnerships…

Readiness Matters! The 2015-2016 Kindergarten Readiness Assessment Report

ERIC Educational Resources Information Center

Maryland State Department of Education, 2016

2016-01-01

As part of Maryland's ongoing commitment to early learning and school readiness, a comprehensive new Kindergarten Readiness Assessment (KRA) was administered for the second time. This assessment is part of the new Ready for Kindergarten: Maryland's Early Childhood Comprehensive Assessment System (R4K) that was developed to align to the state's…

More than Letters: Literacy Activities for Preschool, Kindergarten, and First Grade.

ERIC Educational Resources Information Center

Moomaw, Sally; Hieronymus, Brenda

Noting that the early enjoyment of reading and writing provides a foundation for a lifetime of ongoing learning, this book details a literacy curriculum for preschool, kindergarten, and first grade. Chapter 1 describes the stages of writing development and discusses how early childhood teachers can facilitate emergent reading and writing. Chapter…

The Evaluation of an Early Childhood Teacher Preparation Program: An Action Research Project

ERIC Educational Resources Information Center

Ragno, Kerry Sullivan

2013-01-01

The purpose of this dissertation was to evaluate the effectiveness of an Early Childhood Development Associate of Applied Science (AAS) degree program at one community college as part of an ongoing action research project. Prior to this dissertation study, external and internal barriers prevented the associate degree program stakeholders from…

Why Are There Developmental Stages in Language Learning? A Developmental Robotics Model of Language Development.

PubMed

Morse, Anthony F; Cangelosi, Angelo

2017-02-01

Most theories of learning would predict a gradual acquisition and refinement of skills as learning progresses, and while some highlight exponential growth, this fails to explain why natural cognitive development typically progresses in stages. Models that do span multiple developmental stages typically have parameters to "switch" between stages. We argue that by taking an embodied view, the interaction between learning mechanisms, the resulting behavior of the agent, and the opportunities for learning that the environment provides can account for the stage-wise development of cognitive abilities. We summarize work relevant to this hypothesis and suggest two simple mechanisms that account for some developmental transitions: neural readiness focuses on changes in the neural substrate resulting from ongoing learning, and perceptual readiness focuses on the perceptual requirements for learning new tasks. Previous work has demonstrated these mechanisms in replications of a wide variety of infant language experiments, spanning multiple developmental stages. Here we piece this work together as a single model of ongoing learning with no parameter changes at all. The model, an instance of the Epigenetic Robotics Architecture (Morse et al 2010) embodied on the iCub humanoid robot, exhibits ongoing multi-stage development while learning pre-linguistic and then basic language skills. Copyright © 2016 Cognitive Science Society, Inc.

Progress of Icelandic Lava Flows Charted by NASA EO-1 Spacecraft

NASA Image and Video Library

2014-09-09

On the night of Sept. 6, 2014 NASA Earth Observing 1 EO-1 spacecraft observed the ongoing eruption at Holuhraun, Iceland. Partially covered by clouds, this scene shows the extent of the lava flows that have been erupting.

Review of ongoing clinical trials in non-small cell lung cancer: a status report for 2009 from the ClinicalTrials.gov website.

PubMed

Subramanian, Janakiraman; Madadi, Anusha R; Dandona, Monica; Williams, Kristina; Morgensztern, Daniel; Govindan, Ramaswamy

2010-08-01

Several new agents are being tested in clinical trials for patients with non-small cell lung cancer (NSCLC). A survey of ongoing clinical trials in NSCLC in the ClinicalTrials.gov website would help identify areas that require further attention in the future. We conducted a survey of ongoing clinical trials on NSCLC registered in the ClinicalTrials.gov website. The advanced search option was applied using the terms "non small cell lung cancer," "open studies," "interventional," and "adults 18 years or older." Of the 493 eligible trials, 77 (15.6%) were phase III, 92 (18.7%) were phase I, and 240 (48.7%) were phase II trials. Universities were listed as the primary sponsor for 224 (45.4%) trials and pharmaceutical industry for 166 (33.7%) trials. Majority of the trials were multicenter studies (56.8%) and were being conducted exclusively within the United States (51.3%). A large proportion of phase II and III clinical trials (77.2%) were focused on patients with advanced-stage disease. The most frequently used end points were progression-free survival (27.1%) followed by tumor response rate (22.9%) and overall survival (16.6%). Although biomarker analysis was included in 185 (37.5%) trials, only 39 (7.9%) trials used biomarkers for patient selection. Progression-free survival is the end point most commonly used to assess the effectiveness of experimental regimens, and biomarker-based patient selection is rarely used in ongoing clinical trials for NSCLC.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

PubMed

Eckstrand, C D; Sparger, E E; Pitt, K A; Murphy, B G

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

PubMed Central

Sparger, E. E.; Pitt, K. A.

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs. PMID:28384338

Factors Influencing Early Feeding of Foods and Drinks Containing Free Sugars—A Birth Cohort Study

PubMed Central

Ha, Diep H.; Do, Loc G.; Spencer, Andrew John; Golley, Rebecca K.; Rugg-Gunn, Andrew J.; Levy, Steven M.

2017-01-01

Early feeding of free sugars to young children can increase the preference for sweetness and the risk of consuming a cariogenic diet high in free sugars later in life. This study aimed to investigate early life factors influencing early introduction of foods/drinks containing free sugars. Data from an ongoing population-based birth cohort study in Australia were used. Mothers of newborn children completed questionnaires at birth and subsequently at ages 3, 6, 12, and 24 months. The outcome was reported feeding (Yes/No) at age 6–9 months of common foods/drinks sources of free sugars (hereafter referred as foods/drinks with free sugars). Household income quartiles, mother’s sugar-sweetened beverage (SSB) consumption, and other maternal factors were exposure variables. Analysis was conducted progressively from bivariate to multivariable log-binomial regression with robust standard error estimation to calculate prevalence ratios (PR) of being fed foods/drinks with free sugars at an early age (by 6–9 months). Models for both complete cases and with multiple imputations (MI) for missing data were generated. Of 1479 mother/child dyads, 21% of children had been fed foods/drinks with free sugars. There was a strong income gradient and a significant positive association with maternal SSB consumption. In the complete-case model, income Q1 and Q2 had PRs of 1.9 (1.2–3.1) and 1.8 (1.2–2.6) against Q4, respectively. The PR for mothers ingesting SSB everyday was 1.6 (1.2–2.3). The PR for children who had been breastfed to at least three months was 0.6 (0.5–0.8). Similar findings were observed in the MI model. Household income at birth and maternal behaviours were significant determinants of early feeding of foods/drinks with free sugars. PMID:29065527

‘Chronophilia’: Entries of Erotic Age Preference into Descriptive Psychopathology

PubMed Central

Janssen, Diederik F.

2015-01-01

A scientific nomenclature of erotic age preferences informed the mid- through late nineteenth century joint appearance of homosexuality and sexual abuse of minors on the medico-legal scene. Yet, even in the twenty-first century, legal, psychiatric and culture-critical dimensions of related terms are rarely cleanly distinguished. Review of primary sources shows the ongoing Western suspension of notions of ‘sick desire’, alongside and beyond the medicalisation of homosexuality, between metaphor, legal interdiction and postulated psychopathology. Virtually all early attention to erotic age preference occurred in the context of emergent attention to erotic gender preference. Age of attraction and age difference centrally animate modern homosexuality’s pre-modern past; its earliest psychiatric nomenclature and typologies (1844–69); its early aetiologies stipulating degrees of sexual differentiation (1890s); its concomitant sub-classification (1896–1914); its earliest psychophysiological tests (1950s); and, finally, its post-psychiatric, social scientific typologies (1980s). Several identifications of ‘paedophilia’ were seen throughout the 1890s but as a trope it gained cultural momentum only during, and as a seemingly intriguing corollary of, the progressive depsychiatricisation of homosexuality across the Anglo-European world (late 1950s through 1980s). Early twentieth century sources varied in having it denote (1) a distinct perversion, thus possible ‘complication’ of sexual inversion (2) a discrete corollary of psychosexual differentiation akin to gender preference (3) a distinct subtype of fetishism, thus a likely imprint of early seduction (4) a more intricate expression of erotic symbolism or psychosexual complex or (5) a taste answering to culture, a lack of it, or a libertine disregard for it. PMID:26352305

Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy.

PubMed

Elliott, Cameron A; Gross, Donald W; Wheatley, B Matt; Beaulieu, Christian; Sankar, Tejas

2016-09-01

Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre-surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the contralateral hippocampus after surgery suggests the possibility of an early post-operative imaging marker to predict surgical outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

“Till Death Do Us Part”: A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb

PubMed Central

Omais, Saad; Jaafar, Carine; Ghanem, Noël

2018-01-01

Adult neurogenesis (AN) is an ongoing developmental process that generates newborn neurons in the olfactory bulb (OB) and the hippocampus (Hi) throughout life and significantly contributes to brain plasticity. Adult neural stem and progenitor cells (aNSPCs) are relatively limited in number and fate and are spatially restricted to the subventricular zone (SVZ) and the subgranular zone (SGZ). During AN, the distinct roles played by cell cycle proteins extend beyond cell cycle control and constitute key regulatory mechanisms involved in neuronal maturation and survival. Importantly, aberrant cell cycle re-entry (CCE) in post-mitotic neurons has been strongly linked to the abnormal pathophysiology in rodent models of neurodegenerative diseases with potential implications on the etiology and progression of such diseases in humans. Here, we present an overview of AN in the SVZ-OB and olfactory epithelium (OE) in mice and humans followed by a comprehensive update of the distinct roles played by cell cycle proteins including major tumors suppressor genes in various steps during neurogenesis. We also discuss accumulating evidence underlining a strong link between abnormal cell cycle control, olfactory dysfunction and neurodegeneration in the adult and aging brain. We emphasize that: (1) CCE in post-mitotic neurons due to loss of cell cycle suppression and/or age-related insults as well as DNA damage can anticipate the development of neurodegenerative lesions and protein aggregates, (2) the age-related decline in SVZ and OE neurogenesis is associated with compensatory pro-survival mechanisms in the aging OB which are interestingly similar to those detected in Alzheimer's disease and Parkinson's disease in humans, and (3) the OB represents a well suitable model to study the early manifestation of age-related defects that may eventually progress into the formation of neurodegenerative lesions and, possibly, spread to the rest of the brain. Such findings may provide a novel approach to the modeling of neurodegenerative diseases in humans from early detection to progression and treatment as well. PMID:29593485

Chronic pancreatitis.

PubMed

Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

2017-09-07

Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

PubMed Central

Barrientos, Jacqueline C.; Barr, Paul M.; Flinn, Ian W.; Burger, Jan A.; Tran, Anh; Clow, Fong; James, Danelle F.; Graef, Thorsten; Friedberg, Jonathan W.; Rai, Kanti; O’Brien, Susan

2015-01-01

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. PMID:25755291

1H NMR Spectroscopy-Based Metabolomic Assessment of Uremic Toxicity, with Toxicological Outcomes, in Male Rats Following an Acute, Mid-Life Insult from Ochratoxin A

PubMed Central

Mantle, Peter G.; Nicholls, Andrew W.; Shockcor, John P.

2011-01-01

Overt response to a single 6.25 mg dose of ochratoxin A (OTA) by oral gavage to 15 months male rats was progressive loss of weight during the following four days. Lost weight was restored within one month and animals had a normal life-span without OTA-related terminal disease. Decline in plasma OTA concentration only commenced four days after dosing, while urinary excretion of OTA and ochratoxin alpha was ongoing. During a temporary period of acute polyuria, a linear relationship between urine output and creatinine concentration persisted. Elimination of other common urinary solutes relative to creatinine was generally maintained during the polyuria phase, except that phosphate excretion increased temporarily. 1H NMR metabolomic analysis of urine revealed a progressive cyclic shift in the group principal components data cluster from before dosing, throughout the acute insult phase, and returning almost completely to normality when tested six months later. Renal insult by OTA was detected by 1H NMR within a day of dosing, as the most sensitive early indicator. Notable biomarkers were trimethylamine N-oxide and an aromatic urinary profile dominated by phenylacetylglycine. Tolerance of such a large acute insult by OTA, assessed by rat natural lifetime outcomes, adds a new dimension to toxicology of this xenobiotic. PMID:22069722

Detection of early changes in lung cell cytology by flow-systems analysis techniques. Progress report, January 1--December 31, 1978. [Resulting from exposure to toxic agents associated with production and use of synthetic fuels from oil shale and coal

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

Steinkamp, J.A.; Wilson, J.S.; Svitra, Z.V.

1979-02-01

This report summarizes ongoing experiments to develop cytological and biochemical indicators for measuring damage to respiratory tract cells of experimental animals exposed by inhalation to environmental toxic agents. The specific goal is to apply flow cytometric methods to analyze and detect changes in lung epithelium as a function of exposure to toxic agents associated with the production and utilization of synthetic fuels from oil shale and coal. During the past 6 months, hamsters were exposed to raw and spent oil shale particulates, silica dust, and ozone, and DNA content measurements were performed on lung cell samples. Although initial shale exposuresmore » did not yield the expected results, recent data show atypical changes in DNA content per cell distributions. Ozone exposures also were expanded to include DNA measurements and cytology, ranging up to 72 h postexposure. Progress was achieved in developing a new method for quantitating pulmonary macrophage phagocytosis in rats using micron-sized fluorescent spheres. New methods for determining alkaline phosphatase, DNA content, and protein also were under development. Plans are to continue developing cytological and biochemical markers for measuring atypical cellular changes, including macrophage function, and to emphasize exposing experimental animals to particulates and gaseous agents for studying dose-damage relationships.« less

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

PubMed Central

Lim, Jun Wei; Dillon, John; Miller, Michael

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. PMID:25024592

Magnetization-prepared rapid acquisition with gradient echo magnetic resonance imaging signal and texture features for the prediction of mild cognitive impairment to Alzheimer’s disease progression

PubMed Central

Martinez-Torteya, Antonio; Rodriguez-Rojas, Juan; Celaya-Padilla, José M.; Galván-Tejada, Jorge I.; Treviño, Victor; Tamez-Peña, Jose

2014-01-01

Abstract. Early diagnoses of Alzheimer’s disease (AD) would confer many benefits. Several biomarkers have been proposed to achieve such a task, where features extracted from magnetic resonance imaging (MRI) have played an important role. However, studies have focused exclusively on morphological characteristics. This study aims to determine whether features relating to the signal and texture of the image could predict mild cognitive impairment (MCI) to AD progression. Clinical, biological, and positron emission tomography information and MRI images of 62 subjects from the AD neuroimaging initiative were used in this study, extracting 4150 features from each MRI. Within this multimodal database, a feature selection algorithm was used to obtain an accurate and small logistic regression model, generated by a methodology that yielded a mean blind test accuracy of 0.79. This model included six features, five of them obtained from the MRI images, and one obtained from genotyping. A risk analysis divided the subjects into low-risk and high-risk groups according to a prognostic index. The groups were statistically different (p-value=2.04e−11). These results demonstrated that MRI features related to both signal and texture add MCI to AD predictive power, and supported the ongoing notion that multimodal biomarkers outperform single-modality ones. PMID:26158047

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia.

PubMed

Brown, Jennifer R; Barrientos, Jacqueline C; Barr, Paul M; Flinn, Ian W; Burger, Jan A; Tran, Anh; Clow, Fong; James, Danelle F; Graef, Thorsten; Friedberg, Jonathan W; Rai, Kanti; O'Brien, Susan

2015-05-07

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. © 2015 by The American Society of Hematology.

Mechanisms of fibrosis in acute liver failure.

PubMed

He, Yingli; Jin, Li; Wang, Jing; Yan, Zhi; Chen, Tianyan; Zhao, Yingren

2015-07-01

Acute liver failure (ALF) is a condition with high mortality and morbidity. Fibrosis in chronic liver disease was extensively researched, whereas fibrosis and underlying mechanism in acute liver failure remains unclear. Hepatitis B virus related ALF patients were recruited to investigate if there was ongoing fibrosis by liver histology and liver stiffness measurement(LSM) analysis as well as fibrosis markers assay. Sera HMGB1 were kinetically detected in progression and remission stage of ALF. Hepatic stellate cell(HSC) activation by HMGB1 was explored by testing mRNA and protein level of α-SMA and collagen 1a1 by using qPCR and western blot. Autophagy induction by HMGB1 was explored by LC3-II conversion, autophagy flux and fluorescence. Firstly, ongoing fibrosis in progression stage of ALF was confirmed by histological analysis, LS measurement as well as fibrosis markers detection. HSC activation and autophagy induction in explanted liver tissue also revealed. Next, kinetic monitoring sera HMGB1 revealed elevated HMGB1 in progression stage of ALF vs HBsAg carrier, and drop back to base level in remission stage. Thirdly, rHMGB1 dose dependently activated HSCs, as indicated by increased mRNA and proteins level in α-SMA and collagen 1a1. Moreover, autophagy was induced in HSC treated with rHMGB1, as illustrated by increased LC3 lipidation, elevated autophagy flux and GFP-LC3 puncta. Acute liver failure is accompanied by ongoing fibrosis, HSC activation and autophagy induction. Increased HMGB1 activates HSC via autophagy induction. Those findings integrate HMGB1, HSCs activation, autophagy into a common framework that underlies the fibrosis in ALF. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Taking an Evaluative Stance to Decision-Making about Professional Development Options in Early Childhood Education and Care

ERIC Educational Resources Information Center

Brownlee, Joanne Lunn; Sumsion, Jennifer; Irvine, Susan; Berthelsen, Donna; Farrell, Ann; Walsh, Kerryann; Ryan, Sharon; Mulhearn, Gerry

2015-01-01

This article builds on our ongoing work in conceptualising an "evaluative stance" framework to assist in understanding how leaders in the field of early childhood education and care (ECEC) make decisions about the selection of professional development options for themselves and their staff. It introduces the notion that evaluative…

Early Intervention and Juvenile Delinquency Prevention: Evidence from the Chicago Longitudinal Study

ERIC Educational Resources Information Center

Mann, Emily A.; Reynolds, Arthur J.

2006-01-01

This study investigated the role of an early educational intervention and child-, family-, peer-, and school-level predictors on court-reported juvenile delinquency. Data were provided from the Chicago Longitudinal Study, an ongoing investigation of the scholastic and social development of more than 1,500 low-income youths (93% of whom were…

Children Placed at Risk for Learning and Behavioral Difficulties: Implementing a School-Wide System of Early Identification and Intervention.

ERIC Educational Resources Information Center

O'Shaughnessy, Tam E.; Lane, Kathleen L.; Gresham, Frank M.; Beebe-Frankenberger, Margaret E.

2003-01-01

This article describes a school-wide system of early identification and intervention for children recognized as being at risk for learning and behavior difficulties. Suggested guidelines for implementing such a program include: evaluating existing theory, knowledge, and practice; providing ongoing professional development; creating a school-wide…

Early Communication Strategies: Using Video Analysis to Support Teachers Working with Preverbal Pupils

ERIC Educational Resources Information Center

Anderson, Carolyn

2006-01-01

Carolyn Anderson is a speech and language therapist who is currently working as a senior lecturer at the University of Strathclyde. In this article she provides an early account of her ongoing research into communication between teachers and pupils with severe and complex learning disabilities. Video recordings were made of teacher-pupil…

Variations in Chinese Parental Perceptions of Early Childhood Education Quality

ERIC Educational Resources Information Center

Hu, Bi Ying; Zhou, Yisu; Li, Kejian

2017-01-01

As consumers of Early Childhood Education and Care (ECEC), Chinese parents play a crucial role in the ongoing process of monitoring, evaluating, and improving the quality of ECEC in China. This study used questionnaires to solicit parental feedback on the importance of, and their quality ratings for, aspects of ECEC. The researchers used a random…

"Safe Spaces"? Sites of Bilingualism for Young Learners in Home, School and Community

ERIC Educational Resources Information Center

Conteh, Jean; Brock, Avril

2011-01-01

Drawing together the work of two researchers engaged in ongoing, longitudinal research with practitioners in early years and bilingual complementary settings, this article argues that bilingual learners in the early years need and are entitled to particular kinds of "safe spaces" to succeed in their education. Historical and policy contexts, and…

The Synergistic Effect of Teaching a Combined Explicit Movement and Phonological Awareness Program to Preschool Aged Students

ERIC Educational Resources Information Center

Callcott, Deborah; Hammond, Lorraine; Hill, Susan

2015-01-01

While movement is critical to young children's development, there is an ongoing debate about the time devoted to teaching movement in early childhood classrooms. Nevertheless, research has established a link between specific precursor motor skills and early literacy development. This study investigated the synergistic effect of practising specific…

Sex-Specific Relationships among Attachment Security, Social Values, and Sensation Seeking in Early Adolescence: Implications for Adolescents' Externalizing Problem Behaviour

ERIC Educational Resources Information Center

Sarracino, Diego; Presaghi, Fabio; Degni, Silvia; Innamorati, Marco

2011-01-01

In early adolescence, attachment security reflects not only the quality of ongoing relationships with parents, but also how adolescents process social relationships with "others"--that is, their "social value orientation"--with possible implications for adolescents' risk-taking. In this study, a sample of Italian early…

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

PubMed

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

2006-07-01

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

Basic Writing and the Conflict over Language

ERIC Educational Resources Information Center

Fox, Tom

2015-01-01

David Bleich's exploration of language conflicts in the university in "The Materiality of Language: Gender, Politics, and the University" helps explain the ongoing struggle over basic writing as between two radically different understandings of language. Progressive educators and writing teachers see language as rhetorical and…

Dyscalculia in Harrow

ERIC Educational Resources Information Center

Messenger, Chris; Emerson, Jane; Bird, Ronit

2007-01-01

In this article, the authors offer three definitions of dyscalculia, then describe the background and initial progress of the Harrow Dyscalculia Project. Their project in Harrow is associated with ongoing research into numeracy and brain development led by Brian Butterworth, Professor of Cognitive Neuropsychology at UCL. Pupils from Harrow schools…

Ongoing data reduction, theoretical studies, and supporting research in magnetospheric physics

NASA Technical Reports Server (NTRS)

Scarf, F. L.; Greenstadt, E. W.

1982-01-01

The investigators published a very large number of space science research papers, and in almost all cases these papers involved correlative multi-spacecraft studies. A tabulation of these research papers is provided. Quarterly progress reports for the second contractual period are included.

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

ClinicalTrials.gov

2017-05-11

Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

Motor, cognitive, and functional declines contribute to a single progressive factor in early HD.

PubMed

Schobel, Scott A; Palermo, Giuseppe; Auinger, Peggy; Long, Jeffrey D; Ma, Shiyang; Khwaja, Omar S; Trundell, Dylan; Cudkowicz, Merit; Hersch, Steven; Sampaio, Cristina; Dorsey, E Ray; Leavitt, Blair R; Kieburtz, Karl D; Sevigny, Jeffrey J; Langbehn, Douglas R; Tabrizi, Sarah J

2017-12-12

To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group data from randomized double-blind clinical trials. We studied Unified Huntington Disease Rating Scale (UHDRS) and non-UHDRS clinical measures and brain measures of progressive atrophy in 1,668 individuals with early HD followed up prospectively for up to 30 to 36 months of longitudinal clinical follow-up. The results demonstrated that a composite measure of motor, cognitive, and global functional decline best characterized clinical progression and was most strongly associated with brain measures of progressive corticostriatal atrophy. Use of a composite motor, cognitive, and global functional clinical outcome measure in HD provides an improved measure of clinical progression more related to measures of progressive brain atrophy and provides an opportunity for enhanced clinical trial efficiency relative to currently used individual motor, cognitive, and functional outcome measures. © 2017 American Academy of Neurology.

Hyperemesis Gravidarum (HG)

MedlinePlus

... of vomiting (e.g. gastric ulcers, esophageal bleeding, malnutrition, etc.) may also contribute to and worsen ongoing ... vomiting include debilitating fatigue, gastric irritation, ketosis, and malnutrition. Aggressive care early in pregnancy is very important ...

Clinical Trials | Division of Cancer Prevention

Cancer.gov

Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis

PubMed Central

Saas, Philippe; Bonnefoy, Francis; Toussirot, Eric; Perruche, Sylvain

2017-01-01

Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft-versus-host disease. However, whether early-stage apoptotic cell infusion can be used to treat ongoing inflammatory disorders has not been reported extensively. Recently, we have provided evidence that early-stage apoptotic cell infusion is able to control, at least transiently, ongoing collagen-induced arthritis. This beneficial therapeutic effect is associated with the modulation of antigen-presenting cell functions mainly of macrophages and plasmacytoid dendritic cells, as well as the induction of collagen-specific regulatory CD4+ T cells (Treg). Furthermore, the efficacy of this approach is not altered by the association with two standard treatments of rheumatoid arthritis (RA), methotrexate and tumor necrosis factor (TNF) inhibition. Here, in the light of these observations and recent data of the literature, we discuss the mechanisms of early-stage apoptotic cell infusion and how this therapeutic approach can be transposed to patients with RA. PMID:29062314

Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis.

PubMed

Saas, Philippe; Bonnefoy, Francis; Toussirot, Eric; Perruche, Sylvain

2017-01-01

Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft- versus -host disease. However, whether early-stage apoptotic cell infusion can be used to treat ongoing inflammatory disorders has not been reported extensively. Recently, we have provided evidence that early-stage apoptotic cell infusion is able to control, at least transiently, ongoing collagen-induced arthritis. This beneficial therapeutic effect is associated with the modulation of antigen-presenting cell functions mainly of macrophages and plasmacytoid dendritic cells, as well as the induction of collagen-specific regulatory CD4 + T cells (Treg). Furthermore, the efficacy of this approach is not altered by the association with two standard treatments of rheumatoid arthritis (RA), methotrexate and tumor necrosis factor (TNF) inhibition. Here, in the light of these observations and recent data of the literature, we discuss the mechanisms of early-stage apoptotic cell infusion and how this therapeutic approach can be transposed to patients with RA.

The role of early magnetic resonance imaging in predicting survival on bevacizumab for recurrent glioblastoma: Results from a prospective clinical trial (CABARET).

PubMed

Field, Kathryn M; Phal, Pramit M; Fitt, Greg; Goh, Christine; Nowak, Anna K; Rosenthal, Mark A; Simes, John; Barnes, Elizabeth H; Sawkins, Kate; Cher, Lawrence M; Hovey, Elizabeth J; Wheeler, Helen

2017-09-15

Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival. Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard. For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors. In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017;123:3576-82. © 2017 American Cancer Society. © 2017 American Cancer Society.

Early life trauma, depression and the glucocorticoid receptor gene--an epigenetic perspective.

PubMed

Smart, C; Strathdee, G; Watson, S; Murgatroyd, C; McAllister-Williams, R H

2015-12-01

Hopes to identify genetic susceptibility loci accounting for the heritability seen in unipolar depression have not been fully realized. Family history remains the 'gold standard' for both risk stratification and prognosis in complex phenotypes such as depression. Meanwhile, the physiological mechanisms underlying life-event triggers for depression remain opaque. Epigenetics, comprising heritable changes in gene expression other than alterations of the nucleotide sequence, may offer a way to deepen our understanding of the aetiology and pathophysiology of unipolar depression and optimize treatments. A heuristic target for exploring the relevance of epigenetic changes in unipolar depression is the hypothalamic-pituitary-adrenal (HPA) axis. The glucocorticoid receptor (GR) gene (NR3C1) has been found to be susceptible to epigenetic modification, specifically DNA methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life. In this paper we discuss the progress that has been made by studies that have investigated the relationship between depression, early trauma, the HPA axis and the NR3C1 gene. Difficulties with the design of these studies are also explored. Future efforts will need to comprehensively address epigenetic natural histories at the population, tissue, cell and gene levels. The complex interactions between the epigenome, genome and environment, as well as ongoing nosological difficulties, also pose significant challenges. The work that has been done so far is nevertheless encouraging and suggests potential mechanistic and biomarker roles for differential DNA methylation patterns in NR3C1 as well as novel therapeutic targets.

High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

PubMed

de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

2018-05-09

Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Using Current Literature Selections to Nurture the Development of Kindness in Young Children

ERIC Educational Resources Information Center

Zeece, Pauline Davey

2009-01-01

Learning to display kindness and compassion for others is a critical and ongoing developmental process and an important part of young children's evolving social competence (Han and Kemple in "Early Child Educ J" 34(3):241-246, 2006; Moore in "Early Child Educ Today" 19(3):36-44, 2004). The capacity to care emanates from physical and psychological…

Dale Avenue School Early Childhood Education Center Project. Research Bulletin, Volume I, No. 2, February 1971.

ERIC Educational Resources Information Center

Paterson Board of Education, NJ.

Described is an on-going 1970-71 urban early childhood education project serving 120 pre-kindergarten and 120 kindergarten culturally disadvantaged children in Paterson, New Jersey. Discussed are the program rationale based on the importance of preschool experience and the need for a model demonstration project. Purposes of the special project are…

Early Determinants of Postsecondary Education Participation and Degree Attainment: Findings from an Inner-City Minority Cohort

ERIC Educational Resources Information Center

Ou, Suh-Ruu; Reynolds, Arthur J.

2014-01-01

Early determinants of college attendance and degree attainment for economically disadvantaged minority youth were examined in the present study. The study sample (n = 1,379) was drawn from the Chicago Longitudinal Study (CLS), an ongoing investigation of a panel of low-income minority children born in 1980, growing up in high-poverty neighborhoods…

Getting on the Same Page: Identifying Goals for Technology Use in Early Childhood Education. Policy Brief

ERIC Educational Resources Information Center

Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

2014-01-01

Technology use among young children is increasingly a fact of life, and establishing a clear set of goals that are broadly accepted by stakeholders is critical to planning for the successful integration of technology into early childhood education (ECE). However, debates about the role of technology in ECE settings are ongoing, with some…

MSFC Skylab lessons learned

NASA Technical Reports Server (NTRS)

1974-01-01

Key lessons learned during the Skylab Program that could have impact on on-going and future programs are presented. They present early and sometimes subjective opinions; however, they give insights into key areas of concern. These experiences from a complex space program management and space flight serve as an early assessment to provide the most advantage to programs underway. References to other more detailed reports are provided.

Using AVIRIS to assess hemlock abundance and early decline in the Catskills, New York

Treesearch

Jennifer Pontius; Richard Hallett; Mary Martin

2005-01-01

In order to aid land managers in monitoring and controlling the ongoing hemlock woolly adelgid outbreak, more accurate landscape scale tools are required to locate the hemlock resource, identify infestation and spot early decline. To this end, NASA's Airborne Visible Infra-red Imaging Spectrometer was flown over the infestation front in the Catskills region of New...

Music Play Zone II: Deepening Parental Empowerment as Music Guides for Their Young Children

ERIC Educational Resources Information Center

Koops, Lisa Huisman

2012-01-01

With the intent of facilitating musical development of children enrolled in early childhood music courses, the purpose of this research was to describe the ongoing use of an online social networking site by parents of preschool children. Six families attended a 45-min early childhood music class each week for 10 weeks and responded to assignments…

Making Benchmark Testing Work

ERIC Educational Resources Information Center

Herman, Joan L.; Baker, Eva L.

2005-01-01

Many schools are moving to develop benchmark tests to monitor their students' progress toward state standards throughout the academic year. Benchmark tests can provide the ongoing information that schools need to guide instructional programs and to address student learning problems. The authors discuss six criteria that educators can use to…

Thematic Teaching in Action

ERIC Educational Resources Information Center

Loughran, Sandra B.

2005-01-01

This article describes "thematic teaching," defined as a process of integrating and linking multiple elements of a curriculum in an ongoing exploration of many different aspects of a topic or subject. Thematic teaching is about students actively constructing their own knowledge. In classrooms where successful thematic work is in progress,…

RAEGE Project Update: Yebes Observatory Broadband Receiver Ready for VGOS

NASA Astrophysics Data System (ADS)

IGN Yebes Observatory staff

2016-12-01

An update of the deployment and activities at the Spanish/Portuguese RAEGE project (``Atlantic Network of Geodynamical and Space Stations'') is presented. While regular observations with the Yebes radio telescope are on-going, technological developments about receivers for VGOS are progressing at the Yebes laboratories.

Early childhood growth failure and the developmental origins of adult disease: Do enteric infections and malnutrition increase risk for the metabolic syndrome?

PubMed Central

DeBoer, Mark D.; Lima, Aldo A. M.; Oría, Reinaldo B.; Scharf, Rebecca J.; Moore, Sean R.; Luna, Max A.; Guerrant, Richard L.

2012-01-01

Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses–and potentially young children—undergo adaptive epigenetic changes with longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following malnutrition. In the developing world there remains a high degree of nutritional stunting—linear growth failure due to inadequate calories that may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption from intestinal mucosa changes now termed “environmental enteropathy.” Emerging evidence links early childhood diarrhea and/or growth failure with increased CVD risk factors in later life, including dyslipidemia, hypertension and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation or both. Given increases in CVD in developing areas of the world, associations between childhood malnutrition, early life infections and increased CVD risk factors underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide. PMID:23110643

Stereotactic radiotherapy for early lung cancer: Evidence-based approach and future directions

PubMed Central

Chehade, Samer; Palma, David A.

2015-01-01

Aim To review key studies evaluating stereotactic radiotherapy in the setting of early-stage non-small cell lung cancer (NSCLC) for inoperable or high-risk patients, and discuss areas of ongoing research and clinical trials. Background The use of stereotactic radiotherapy for the treatment of early stage non-small cell lung cancer (NSCLC) has increased rapidly over the past decade. Numerous studies have reported outcomes for patients treated with SBRT who are unfit for surgical resection, or at high risk of surgical complications. Materials and methods A narrative review. Results The preponderance of evidence suggests that SBRT is associated with excellent local control (∼90% at 3 years) and a favorable toxicity profile. In patients with higher operative risks, such as the elderly and patients with severe COPD, SBRT may provide a less-toxic treatment than surgery with similar oncologic outcomes. Ongoing studies are evaluating the use of SBRT for locally advanced or oligometastatic NSCLC. Conclusions A large body of evidence now exists to support the use of SBRT for early-stage NSCLC. Decisions regarding the optimal choice of treatment should be individualized, and made in the context of a multidisciplinary team. PMID:26696779

The viability of transplanting organs from donors who underwent cardiopulmonary resuscitation: A systematic review.

PubMed

West, Stephen; Soar, Jasmeet; Callaway, Clifton W

2016-11-01

To identify reports of patients who underwent cardiopulmonary resuscitation (CPR) prior to solid organ donation and compare recipient and organ function outcomes to those that did not undergo CPR. Donation after restoration of circulation then progressing to death and those donating with on-going CPR who would have otherwise have termination of efforts were both included. Systematic review. Clinical studies comparing the outcome of patients and organs retrieved from donors who underwent CPR with those that did not require CPR. Full-text articles were searched on EmBASE, MEDLINE, Cochrane Database of Systematic Reviews and the Cochrane Register of Controlled Trials. Twenty-two observational studies were included. There were 12,206 adult and 2552 paediatric organ transplantation identified. Comparing donation after restoration of circulation there was no difference in immediate, one year, and five-year graft function. Donation with on-going CPR was associated with reduced immediate graft function for both renal and hepatic transplantation, however long term function was not different. CPR does not appear to adversely affect graft function. Patients who have restored circulation after resuscitation and subsequently progress to death should be evaluated for organ donation. Those with on-going CPR should be considered for hepatic and renal transplantation but there may be worse initial graft function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Preliminary Investigations of the Application of the Early Communication Indicator (ECI) for Infants and Toddlers

ERIC Educational Resources Information Center

Greenwood, Charles R.; Carta, Judith J.; Walker, Dale; Hughes, Kere; Weathers, Mary

2006-01-01

Early interventionists are accountable for the progress of children receiving their services. Technically adequate measures of the progress of individual children are needed. While the Early Communication Indicator (ECI) for infants and toddlers is one such measure, data to support its use are limited to a single research report. In this…

Beyond Subprime Learning: Accelerating Progress in Early Education. Policy Brief

ERIC Educational Resources Information Center

Bornfreund, Laura; McCann, Clare; Williams, Conor; Guernsey, Lisa

2014-01-01

Earlier this year, in "Subprime Learning: Early Education in America since the Great Recession," the current state of early education in the U.S. was surveyed by examining progress over the last five years . It was found that while the public, political, and research consensus is stronger than ever, the field remains in dire need of…

Hardware Progress Made in the Early Flight Fission Test Facilities (EFF-TF) To Support Near-Term Space Fission Systems

NASA Astrophysics Data System (ADS)

Van Dyke, Melissa; Martin, James

2005-02-01

The NASA Marshall Space Flight Center's Early Flight Fission Test Facility (EFF-TF), provides a facility to experimentally evaluate nuclear reactor related thermal hydraulic issues through the use of non-nuclear testing. This facility provides a cost effective method to evaluate concepts/designs and support mitigation of developmental risk. Electrical resistance thermal simulators can be used to closely mimic the heat deposition of the fission process, providing axial and radial profiles. A number of experimental and design programs were underway in 2004 which include the following. Initial evaluation of the Department of Energy Los Alamos National Laboratory 19 module stainless steel/sodium heat pipe reactor with integral gas heat exchanger was operated at up to 17.5 kW of input power at core temperatures of 1000 K. A stainless steel sodium heat pipe module was placed through repeated freeze/thaw cyclic testing accumulating over 200 restarts to a temperature of 1000 K. Additionally, the design of a 37- pin stainless steel pumped sodium/potassium (NaK) loop was finalized and components procured. Ongoing testing at the EFF-TF is geared towards facilitating both research and development necessary to support future decisions regarding potential use of space nuclear systems for space exploration. All efforts are coordinated with DOE laboratories, industry, universities, and other NASA centers. This paper describes some of the 2004 efforts.

Using Neuroplasticity-Based Auditory Training to Improve Verbal Memory in Schizophrenia

PubMed Central

Fisher, Melissa; Holland, Christine; Merzenich, Michael M.; Vinogradov, Sophia

2009-01-01

Objective Impaired verbal memory in schizophrenia is a key rate-limiting factor for functional outcome, does not respond to currently available medications, and shows only modest improvement after conventional behavioral remediation. The authors investigated an innovative approach to the remediation of verbal memory in schizophrenia, based on principles derived from the basic neuroscience of learning-induced neuroplasticity. The authors report interim findings in this ongoing study. Method Fifty-five clinically stable schizophrenia subjects were randomly assigned to either 50 hours of computerized auditory training or a control condition using computer games. Those receiving auditory training engaged in daily computerized exercises that placed implicit, increasing demands on auditory perception through progressively more difficult auditory-verbal working memory and verbal learning tasks. Results Relative to the control group, subjects who received active training showed significant gains in global cognition, verbal working memory, and verbal learning and memory. They also showed reliable and significant improvement in auditory psychophysical performance; this improvement was significantly correlated with gains in verbal working memory and global cognition. Conclusions Intensive training in early auditory processes and auditory-verbal learning results in substantial gains in verbal cognitive processes relevant to psychosocial functioning in schizophrenia. These gains may be due to a training method that addresses the early perceptual impairments in the illness, that exploits intact mechanisms of repetitive practice in schizophrenia, and that uses an intensive, adaptive training approach. PMID:19448187

d-Amino acids in molecular evolution in space - Absolute asymmetric photolysis and synthesis of amino acids by circularly polarized light.

PubMed

Sugahara, Haruna; Meinert, Cornelia; Nahon, Laurent; Jones, Nykola C; Hoffmann, Søren V; Hamase, Kenji; Takano, Yoshinori; Meierhenrich, Uwe J

2018-07-01

Living organisms on the Earth almost exclusively use l-amino acids for the molecular architecture of proteins. The biological occurrence of d-amino acids is rare, although their functions in various organisms are being gradually understood. A possible explanation for the origin of biomolecular homochirality is the delivery of enantioenriched molecules via extraterrestrial bodies, such as asteroids and comets on early Earth. For the asymmetric formation of amino acids and their precursor molecules in interstellar environments, the interaction with circularly polarized photons is considered to have played a potential role in causing chiral asymmetry. In this review, we summarize recent progress in the investigation of chirality transfer from chiral photons to amino acids involving the two major processes of asymmetric photolysis and asymmetric synthesis. We will discuss analytical data on cometary and meteoritic amino acids and their potential impact delivery to the early Earth. The ongoing and future ambitious space missions, Hayabusa2, OSIRIS-REx, ExoMars 2020, and MMX, are scheduled to provide new insights into the chirality of extraterrestrial organic molecules and their potential relation to the terrestrial homochirality. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca. Copyright © 2018 Elsevier B.V. All rights reserved.

Reality Check Algorithm for Complex Sources in Early Warning

NASA Astrophysics Data System (ADS)

Karakus, G.; Heaton, T. H.

2013-12-01

In almost all currently operating earthquake early warning (EEW) systems, presently available seismic data are used to predict future shaking. In most cases, location and magnitude are estimated. We are developing an algorithm to test the goodness of that prediction in real time. We monitor envelopes of acceleration, velocity, and displacement; if they deviate significantly from the envelope predicted by Cua's envelope gmpe's then we declare an overfit (perhaps false alarm) or an underfit (possibly a larger event has just occurred). This algorithm is designed to provide a robust measure and to work as quickly as possible in real-time. We monitor the logarithm of the ratio between the envelopes of the ongoing observed event and the envelopes derived from the predicted envelopes of channels of ground motion of the Virtual Seismologist (VS) (Cua, G. and Heaton, T.). Then, we recursively filter this result with a simple running median (de-spiking operator) to minimize the effect of one single high value. Depending on the result of the filtered value we make a decision such as if this value is large enough (e.g., >1), then we would declare, 'that a larger event is in progress', or similarly if this value is small enough (e.g., <-1), then we would declare a false alarm. We design the algorithm to work at a wide range of amplitude scales; that is, it should work for both small and large events.

[Psychologic management of extreme prematurity].

PubMed

Granboulan, V; Danan, C; Dassieu, G; Janaud, J C; Durand, B

1995-05-01

The ongoing progress in neonatal intensive care is modifying the psychic context of prematurity for all the partners, infants as well as parents and physicians. Comfort and prognosis of preterm infants have much improved. Since newborns under 24 weeks of gestational age are now surviving, they spend approximately half the duration of pregnancy out of the maternal uterus. All the psychological issues of such an early separation have to be considered, including the developmental outcome of a sensorial environment which is quite different from the intra-uterine one. Research has been developing in this field. The cooperation between neonatalogists and psychologists has been profitable to parents. Problems linked to the separation, such as difficulty in representing the infant, are no more frequent owing to the attention paid to the mother-child bond and subsequent early contacts. What is forward now is the impact of an hyper technical world of intensive care on the parents, and of the strange aspect of the tiny baby surrounded by engines and tubes. Such an overpresence of reality often results in a reaction of traumatic daziness among parents. The cooperation of the whole staff is necessary for the resumption of an imaginary process of psychic functioning. Finally, the survival of very-low-birth-weight infants confronts the neonatalogists with some delicate ethical questions. Psychiatrists and psychologists might have an important part to play in aiding the profession in its sorting out of these ethical issues.

Current oncologic concepts and emerging techniques for imaging of head and neck squamous cell cancer

PubMed Central

Sadick, Maliha; Schoenberg, Stefan O.; Hoermann, Karl; Sadick, Haneen

2012-01-01

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and currently they account for 5% of all malignancies worldwide. Inspite of ongoing developments in diagnostic imaging and new therapeutic options, HNSCC still represents a multidisciplinary challenge. One of the most important prognostic factors in HNSCC is the presence of lymph node metastases. Patients with confirmed nodal involvement have a considerable reduction of their 5-year overall survival rate. In the era of individually optimised surgery, chemotherapy and intensity modulated radiotherapy, the main role of pre- and posttherapeutic imaging remains cancer detection at an early stage and accurate follow-up. The combined effort of early diagnosis and close patient monitoring after surgery and/or radio-chemotherapy influences disease progression and outcome predicition in patients with HNSCC. This review article focuses on currrent oncologic concepts and emerging tools in imaging of head and neck squamous cell cancer. Besides the diagnostic spectrum of the individual imaging modalities, their limitations are also discussed. One main part of this article is dedicated to PET-CT which combines functional and morphological imaging. Furthermore latest developments in MRI are presented with regard to lymph node staging and response prediction. Last but not least, a clinical contribution in this review explains, which information the head and neck surgeon requires from the multimodality imaging and its impact on operation planning. PMID:23320060

Tentorial dural arteriovenous fistula presenting as myelopathy: Case series and review of literature

PubMed Central

Gross, Robert; Ali, Rushna; Kole, Max; Dorbeistein, Curtis; Jayaraman, Mahesh V; Khan, Muhib

2014-01-01

Dural arteriovenous fistula (DAVF) is a rare type of cerebral arteriovenous malformation. Common presenting symptoms are related to hemorrhage. However, rarely these patients may present with myelopathy. We present two cases of DAVF presenting as rapidly progressive myelopathy. Two treatment options are available: microsurgical interruption of the fistula and endovascular embolization. These treatment options of DAVFs have improved significantly in the last decade. The optimal treatment of DAVFs remains controversial, and there is an ongoing debate as to whether primary endovascular or primary microsurgical treatment is the optimal management for these lesions. However, despite treatment a high percentage of patients are still left with severe disability. The potential for functional ambulation in patients with DAVF is related to the time of intervention. This emphasizes the important of early diagnosis and early intervention in DAVF. The eventual outcome may depend on several factors, such as the duration of symptoms, the degree of disability before treatment, and the success of the initial procedure to close the fistula. The usage of magnetic resonance imaging and selective angiography has significantly improved the ability to characterize DAVFs, however, these lesions remain inefficiently diagnosed. If intervention is delayed even prolonged time in rehabilitation does not change the grave prognosis. This review outlines the presentation, classication and management of DAVF as well as discussing patient outcomes. PMID:25516869

Omega-3 fatty acids, inflammation and angiogenesis: basic mechanisms behind the cardioprotective effects of fish and fish oils.

PubMed

Massaro, M; Scoditti, E; Carluccio, M A; Campana, M C; De Caterina, R

2010-02-25

Atherosclerosis is now widely accepted to be an inflammatory disease, characterized by degenerative as well as proliferative changes and extracellular accumulation of lipid and cholesterol, in which an ongoing inflammatory reaction plays an important role both in initiation and progression/destabilization, converting a chronic process into an acute disorder. Neovascularization has also been recognized as an important process for the progression/destabilization of atherosclerotic plaques. In fact, vulnerable atherosclerotic plaques prone to rupture are characterized by an enlarged necrotic core, containing an increased number of vasa vasorum, apoptotic macrophages, and more frequent intraplaque haemorrhage. Various functional roles have been assigned to intimal microvessels, however the relationship between the process of angiogenesis and its causal association with the progression and complications of atherosclerosis are still challenging and controversial. In the past 30 years, the dietary intake of omega-3 (n-3) polyunsaturated fatty acids--mainly derived from fish--has emerged as an important way to modify cardiovascular risk through beneficial effects on all stages of atherosclerosis, including plaque angiogenesis. This review specifically focuses on the modulating effects of n-3 fatty acids on molecular events involved in early and late atherogenesis, including effects on endothelial expression of adhesion molecules, as well as pro-inflammatory and pro-angiogenic enzymes. By accumulating in endothelial membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of several genes through an attenuation of activation of the nuclear factor-kappaB system of transcription factors. This occurs secondary to decreased generation of intracellular reactive oxygen species. This series of investigations configures a clear example of nutrigenomics--i.e., how nutrients may affect gene expression, ultimately affecting a wide spectrum of human diseases.

Integrated versus fragmented implementation of complex innovations in acute health care.

PubMed

Woiceshyn, Jaana; Blades, Kenneth; Pendharkar, Sachin R

Increased demand and escalating costs necessitate innovation in health care. The challenge is to implement complex innovations-those that require coordinated use across the adopting organization to have the intended benefits. We wanted to understand why and how two of five similar hospitals associated with the same health care authority made more progress with implementing a complex inpatient discharge innovation whereas the other three experienced more difficulties in doing so. We conducted a qualitative comparative case study of the implementation process at five comparable urban hospitals adopting the same inpatient discharge innovation mandated by their health care authority. We analyzed documents and conducted 39 interviews of the health care authority and hospital executives and frontline managers across the five sites over a 1-year period while the implementation was ongoing. In two and a half years, two of the participating hospitals had made significant progress with implementing the innovation and had begun to realize benefits; they exemplified an integrated implementation mode. Three sites had made minimal progress, following a fragmented implementation mode. In the former mode, a semiautonomous health care organization developed a clear overall purpose and chose one umbrella initiative to implement it. The integrative initiative subsumed the rest and guided resource allocation and the practices of hospital executives, frontline managers, and staff who had bought into it. In contrast, in the fragmented implementation mode, the health care authority had several overlapping, competing innovations that overwhelmed the sites and impeded their implementation. Implementing a complex innovation across hospital sites required (a) early prioritization of one initiative as integrative, (b) the commitment of additional (traded off or new) human resources, (c) deliberate upfront planning and continual support for and evaluation of implementation, and (d) allowance for local customization within the general principles of standardization.

Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

PubMed Central

Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R.; Birx, Deborah L.; Ratto-Kim, Silvia; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Hu, Haitao

2016-01-01

Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548

Towards the next generation of climate change assessment: learning from past experiences to inform a sustainable future

NASA Astrophysics Data System (ADS)

Mach, K. J.; Field, C. B.

2017-12-01

Over decades, assessment by the Intergovernmental Panel on Climate Change and many others has bolstered understanding of the climate problem: unequivocal warming, pervasive impacts, and serious risks from continued high emissions of heat-trapping gases. Societies are increasingly responding with early actions to decarbonize energy systems and prepare for impacts. This emerging era of climate solutions creates a need for new approaches to assessment that emphasize learning from ongoing real-world experiences and that help close the gap between aspirations and the pace of progress. Against this backdrop, the presentation will take stock of recent advances and challenges in assessment, especially drawing from analysis of climate change assessment. Four assessment priorities will be considered: (1) integrating diverse evidence including quantitative and qualitative results, (2) applying rigorous expert judgment in evaluating knowledge and uncertainties, (3) exploring widely ranging futures and their connections to ongoing choices and actions, and (4) incorporating interactions among experts and decision-makers in assessment processes. Across these assessment priorities, the presentation will critique both opportunities and pitfalls, outlining possibilities for future experimentation, innovation, and learning. It will evaluate, in particular, lessons from risk-based approaches; strategies for transparently acknowledging persistent uncertainties and contested priorities; ways to minimize biases and foster creativity in expert judgments; scenario-based assessment of surprises, deep uncertainties, and decision-making implications; and opportunities for broadening the conception of expertise and engaging different decision-makers and stakeholders. Overall, these approaches can advance assessment products and processes as a basis for sustained dialogue supporting decision-making.

Teaching the Teachers: Physical Science for the Non-Scientific

NASA Astrophysics Data System (ADS)

Michels, D. J.; Pickert, S. M.; Montrose, C. J.; Thompson, J. L.

2004-12-01

The Catholic University of America, in collaboration with the Solar Physics Branch of the Naval Research Laboratory and the Goddard Space Flight Center, has begun development of an experimental, inquiry-driven and standards-referenced physical science course for undergraduate, pre-service K-8 teachers. The course is team-taught by faculty from the University's Departments of Education and Physics and NRL solar physics research personnel. Basic physical science concepts are taught in the context of the Sun and Sun-Earth Connections, through direct observation, web-based solar data, and images and movies from ongoing space missions. The Sun can illuminate, in ways that cannot be duplicated with comparable clarity in the laboratory, the basics of magnetic and gravitational force fields, Newton's Laws, and light and optics. The immediacy of the connection to ongoing space research and live mission data serves as well to inspire student interest and curiosity. Teaching objectives include pedagogical methods, especially hands-on and observational experiences appropriate to the physics content and the K-8 classroom. The CUA Program, called TOPS! (Top Teachers of Physical Science!) has completed its first year of classroom experience; the first few batches of Program graduates should be in K-8 classrooms in time to capitalize on the motivational opportunities offered by the 2007-2008 IHY and IPY. We present data on the attitudinal and scientific progress of fifteen pre-service Early Childhood and Elementary Education majors as they experienced, many for the first time, the marvels of attractive and repulsive forces, live observations of solar system dynamics, access to real-time satellite data and NASA educational resources.

Myths and realities about the recovery of L׳Aquila after the earthquake

PubMed Central

Contreras, Diana; Blaschke, Thomas; Kienberger, Stefan; Zeil, Peter

2014-01-01

There is a set of myths which are linked to the recovery of L׳Aquila, such as: the L׳Aquila recovery has come to a halt, it is still in an early recovery phase, and there is economic stagnation. The objective of this paper is threefold: (a) to identify and develop a set of spatial indicators for the case of L׳Aquila, (b) to test the feasibility of a numerical assessment of these spatial indicators as a method to monitor the progress of a recovery process after an earthquake and (c) to answer the question whether the recovery process in L׳Aquila stagnates or not. We hypothesize that after an earthquake the spatial distribution of expert defined variables can constitute an index to assess the recovery process more objectively. In these articles, we aggregated several indicators of building conditions to characterize the physical dimension, and we developed building use indicators to serve as proxies for the socio-economic dimension while aiming for transferability of this approach. The methodology of this research entailed six steps: (1) fieldwork, (2) selection of a sampling area, (3) selection of the variables and indicators for the physical and socio-economic dimensions, (4) analyses of the recovery progress using spatial indicators by comparing the changes in the restricted core area as well as building use over time; (5) selection and integration of the results through expert weighting; and (6) determining hotspots of recovery in L׳Aquila. Eight categories of building conditions and twelve categories of building use were identified. Both indicators: building condition and building use are aggregated into a recovery index. The reconstruction process in the city center of L׳Aquila seems to stagnate, which is reflected by the five following variables: percentage of buildings with on-going reconstruction, partial reconstruction, reconstruction projected residential building use and transport facilities. These five factors were still at low levels within the core area in 2012. Nevertheless, we can conclude that the recovery process in L׳Aquila did not come to a halt but is still ongoing, albeit being slow. PMID:26779431

Ongoing clinical trials of PD-1 and PD-L1 inhibitors for lung cancer in China.

PubMed

Liu, Si-Yang; Wu, Yi-Long

2017-07-05

Compared to chemotherapy, promising results have been obtained by blocking the PD-1 pathway using antibodies that inhibit programmed cell death protein 1 (PD-1) or programmed cell death protein ligand 1 (PD-L1). Furthermore, global researchers and doctors are exploring how to optimize this immunotherapy in 270 clinical studies. However, Chinese clinical trials of these agents remain in the early stages. We summarize the ongoing international and domestic clinical trials using PD-1 and PD-L1 inhibitors to treat lung cancer. This information can help researchers better understand the active and approved clinical trials in China, as well as the ongoing research regarding PD-1 and PD-L1 inhibitors.

Public reporting helped drive quality improvement in outpatient diabetes care among Wisconsin physician groups

PubMed Central

Smith, Maureen A.; Wright, Alexandra; Queram, Christopher; Lamb, Geoffrey C.

2012-01-01

Public reporting on the quality of ambulatory health care is growing, but knowledge of how physician groups respond to such reporting has not kept pace. We examined responses to public reporting on the quality of diabetes care in 409 primary care clinics within seventeen large, multispecialty physician groups. We determined that a focus on publicly reported metrics, along with participation in large or externally sponsored projects, increased a clinic’s implementation of diabetes improvement interventions. Clinics were also more likely to implement interventions in more recent years. Public reporting helped drive both early implementation of a single intervention and ongoing implementation of multiple simultaneous interventions. To fully engage physician groups, accountability metrics should be structured to capture incremental improvements in quality, thereby rewarding both early and ongoing improvement activities. PMID:22392668

HOMER CITY MULTISTREAM COAL CLEANING DEMONSTRATION: A PROGRESS REPORT

EPA Science Inventory

The report gives an overview of ongoing testing and evaluation of the Homer City Coal Cleaning Plant, built to enable the Homer City Power Complex to meet sulfur dioxide (SO2) emission levels mandated by the State of Pennsylvania and the U.S. Government. The plant was constructed...

Applications of aerospace technology

NASA Technical Reports Server (NTRS)

Rouse, D. J.; Brown, J. N., Jr.; Cleland, John; Lehrman, Stephen; Trachtman, Lawrence; Wallace, Robert; Winfield, Daniel; Court, Nancy; Maggin, Bernard; Barnett, Reed

1987-01-01

Highlights are presented for the Research Triangle Institute (RTI) Applications Team activities over the past quarter. Progress in fulfilling the requirements of the contract is summarized, along with the status of the eight add-on tasks. New problem statements are presented. Transfer activities for ongoing projects with the NASA Centers are included.

Enhancing Family Engagement in Interventions for Mental Health Problems in Youth

ERIC Educational Resources Information Center

Herman, Keith C.; Borden, Lindsay A.; Hsu, Chinghui; Schultz, Tia R.; Carney, Megan Strawsine; Brooks, Connie M.; Reinke, Wendy M.

2011-01-01

Much progress has been made in helping families improve their relationships and provide effective environments for their children. However, an ongoing challenge in implementing these practices is to actively engage families in interventions for youth. Most effective treatments for youth require some level of caregiver involvement. Research has…

What Principals Should Know about Building and Maintaining Teams

ERIC Educational Resources Information Center

Turk, Randall L.; Wolff, Krista; Waterbury, Christopher; Zumalt, Jon

2002-01-01

A field study conducted by 8 students and a faculty supervisor of a principal preparation program determined that individual and team reflection resulted in shared learning from team training and ongoing team activities. An industrial concept known as value-chain teams has implications for monitoring student progress from kindergarten through…

Implementing RTI[superscript 2]: Reports from the Field. Policy Brief

ERIC Educational Resources Information Center

Dawkins, Shardae

2014-01-01

Starting in 2014-15, districts across the state of Tennessee must implement a Response to Instruction and Intervention (RTI[superscript 2]) plan. RTI[superscript 2] is an instructional framework which provides ongoing monitoring of student performance and progress through the use of universal student screeners and interventions targeted at…

Environmental Education in the Developing World.

ERIC Educational Resources Information Center

Connor, James V.

This paper attempts to explore how developing nations can best respond to the request of the United Nations General Assembly to examine their ongoing programs and policies for environmental impact, and to report regularly to the General Assembly on the progress being made towards the objectives of "environmentally sound and sustainable…

Secondary School Transition: Planning for Success.

ERIC Educational Resources Information Center

Hemphill, Rae

Parents of adolescents with attention deficit disorders are offered suggestions for easing the transition of their teen from elementary to secondary school. Careful scheduling of classes with the guidance counselor to "fit" the individual teen's needs is urged. The importance of ongoing communication with the school concerning class progress,…

Dissociative Identity Disorder in Felonious Offenders: Two Case Studies.

ERIC Educational Resources Information Center

Culiner, Ty

1997-01-01

Describes the case studies of two inmates detained in a maximum security prison having been diagnosed with Dissociative Identity Disorder and receiving individual therapy. Although treatment is ongoing, mid-treatment progress indicates the treatment is successful and the prognosis is excellent. Accentuates the practicality and rewards of working…

Sustaining Professional Learning Communities through Teacher Leadership

ERIC Educational Resources Information Center

Jennings, Karen

2013-01-01

Professional learning communities (PLCs), with their attributes of shared values, high expectations, and collaboration, have the potential to change school culture. The 4 elementary schools in this study have been unable to sustain ongoing, effective teamwork, resulting in a failure to attain adequate progress, and in 2 schools, in the placement…

(Re)constructing Ideals of Multicultural Education through "Grow Your Own Teachers"

ERIC Educational Resources Information Center

Madda, Christina L.; Schultz, Brian D.

2009-01-01

Reflecting on the current status of multicultural education in higher education institutions, we examine "Grow Your Own Teachers," a progressive, innovative program that not only embodies and enacts major principles of multicultural education, but also represents an ongoing effort to redefine and revitalize multicultural education within…

"Future Proofing" Faculty: The Struggle To Create Technical Lifelong Learners.

ERIC Educational Resources Information Center

Nay, Fred W.; Malm, Loren D.; Malone, Bobby G.; Oliver, Brad E.; Saunders, Nancy G.; Thompson, Jay C., Jr.

College faculty can avoid investing valuable time and resources in inappropriate technologies by staying in step with technological progress. A "future proof" approach to technology recognizes and welcomes small failures, considering them part of the ongoing process of absorbing technology into the learning process. Future proofing attempts to…

Technology and Motor Ability Development

ERIC Educational Resources Information Center

Wang, Lin; Lang, Yong; Luo, Zhongmin

2014-01-01

As a new member joining the technology family, active video games have been developed to promote physical exercise. This working-in-progress paper shares an ongoing project on examining the basic motor abilities that are enhanced through participating in commercially available active video games. [For the full proceedings see ED557181.

Framework for Evaluating Habitat Restoration Success with Respect to Fish Habitat- and Population-related Beneficial Use Impairments

EPA Science Inventory

A major challenge of evaluating restoration progress is establishing a cause-effect relationship between observed changes in fish abundance and ongoing aquatic habitat restoration. Since 1979, fish populations within the St. Louis River Area of Concern, which were severely degrad...

A Program Evaluation of a Literacy Initiative for Students with Moderate to Severe Disabilities

ERIC Educational Resources Information Center

De La Cruz, Carrie F.

2009-01-01

Recently the National Reading Panel concluded that systematic and direct instruction in phonological awareness, phonics, fluency, vocabulary, and comprehension that is informed by ongoing assessments of student progress results in positive student achievement (NICHHD, 2002). For students with moderate to severe disabilities and students with…

Destabilization of Lead Pipe Scales in a Long-Term Vacant Home in Cincinnati

EPA Science Inventory

this presentation covers an ongoing study at a Cincinnati house, following the progression of lead release from a lead service line with different amounts of stagnation time and water use. This presentation is essentially the same as the talk cleared for AWWA ACE 2017, with some...

Progress in High Throughput Exposure Assessment for Prioritizing Human Exposure to Environmental Chemicals (SRA)

EPA Science Inventory

For thousands of chemicals in commerce, there is little or no information about exposure or health and ecological effects. The US Environmental Protection Agency (USEPA) has ongoing research programs to develop and evaluate models that use the often minimal chemical information a...

77 FR 65676 - Federal Advisory Committee; Defense Health Board (DHB) Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... DEPARTMENT OF DEFENSE Office of the Secretary Federal Advisory Committee; Defense Health Board (DHB) Meeting AGENCY: Department of Defense (DoD). ACTION: Notice of meeting. SUMMARY: Pursuant to the... addition, the DHB will report on the progress of its ongoing review of the effects of the obesity epidemic...

AGOR 28: SIO Shipyard Representative Bi-Weekly Progress Report

DTIC Science & Technology

2015-02-26

2 • Pilot House – Electrical and joiner work is ongoing, however carpenters are waiting for HVAC to finish before Norac...STD Report - TEST REPORT ( 320-001-2 MCCS Design Verification Test Report)(R/ASR) 108/0 AGOR27 A059 STD Report - STUDENT GUIDES ( DI-059 (Student

In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series.

PubMed

Xu, Melody J; Wu, Susan; Daud, Adil I; Yu, Siegrid S; Yom, Sue S

2018-05-30

Patients with metastatic Merkel cell carcinoma (mMCC) who experience disease progression on immunotherapy have limited additional standard options. Given evidence of synergism between radiation therapy (RT) and immunotherapy, two patients progressing on PD-1 inhibition were referred for short-course RT. Two patients were found to have progressive mMCC on PD-1 inhibitor therapy and were treated with single-fraction palliative RT. Both patients were observed to have local control at irradiated regions, as well as durable abscopal response at unirradiated, out-of-field, sites of metastatic disease. Short-course RT is a compelling strategy that could be a means to augment response in patients with mMCC who show progression on immune checkpoint blockade. Ongoing clinical trials are investigating the relationship between RT and immunotherapy in mMCC.

An Exploratory Survey of Digital Libraries on the World Wide Web: Art and Literature of the Early Italian Renaissance.

ERIC Educational Resources Information Center

McKibben, Suzanne J.

This study assessed the ongoing development of digital libraries (DLs) on the World Wide Web. DLs of art and literature were surveyed for selected works from the early Italian Renaissance in order to gain insight into the current trends prevalent throughout the larger population of DLs. The following artists and authors were selected for study:…

Kei hea te Ora? The Whereabouts of the Health of Children in the Early Childhood Curriculum of Aotearoa New Zealand

ERIC Educational Resources Information Center

Gibbons, Andrew

2015-01-01

The policies and practices of early childhood teaching in Aotearoa New Zealand have been an ongoing site of political, economic, social and cultural contestation. Competing values and beliefs regarding experiences of both the child and the teacher have been central to the contesting. Helen May (2001, 2009) tracks these tensions through the waxing…

CGH’s Third Year with NCI: Progress, Partnerships, & Possibilities

Cancer.gov

The Center for Global Health is embarking on its third year within the National Cancer Institute, and I am pleased with the extraordinary progress and achievements made in this time by our dedicated staff members.  CGH has established new, and strengthened ongoing, initiatives and programs with great success, including the regional Leadership Forums for Cancer Control Planning, the United States – Latin America Cancer Research Network, and the regional Grant Writing Workshops.  CGH has also developed several funding opportunities in collaboration with partners across NIH and our stakeholders.

Indoor chemistry: research opportunities and challenges.

PubMed

Nazaroff, W W; Goldstein, A H

2015-08-01

In this editorial, we have highlighted key research opportunities and challenges in four topical themes for indoor chemistry: human occupants as agents influencing indoor chemistry; oxidative chemistry; surface phenomena; and semivolatile organic compounds. In each case, enough prior work has been done to demonstrate the importance of the theme and to create a foundation for future studies. Extensive achievements and ongoing progress in (outdoor) atmospheric chemistry—both in the analytical methods developed and in the scientific knowledge created—also contribute to a strong foundation from which to achieve rapid research progress in this exciting new domain.

Progress in thermomechanical control of steel plates and their commercialization

PubMed Central

Nishioka, Kiyoshi; Ichikawa, Kazutoshi

2012-01-01

The water-cooled thermomechanical control process (TMCP) is a technology for improving the strength and toughness of water-cooled steel plates, while allowing control of the microstructure, phase transformation and rolling. This review describes metallurgical aspects of the microalloying of steel, such as niobium addition, and discusses advantages of TMCP, for example, in terms of weldability, which is reduced upon alloying. Other covered topics include the development of equipment, distortions in steel plates, peripheral technologies such as steel making and casting, and theoretical modeling, as well as the history of property control in steel plate production and some early TMCP technologies. We provide some of the latest examples of applications of TMCP steel in various industries such as shipbuilding, offshore structures, building construction, bridges, pipelines, penstocks and cryogenic tanks. This review also introduces high heat-affected-zone toughness technologies, wherein the microstructure of steel is improved by the addition of fine particles of magnesium-containing sulfides and magnesium- or calcium-containing oxides. We demonstrate that thanks to ongoing developments TMCP has the potential to meet the ever-increasing demands of steel plates. PMID:27877477

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents.

PubMed

Choi, Chang-Ik

2016-08-27

Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis.

PubMed

Dolei, Antonina

2018-01-01

Two human endogenous retroviruses of the HERV-W family are proposed as multiple sclerosis (MS) co-factors: MS-associated retrovirus (MSRV) and ERVWE1, whose env proteins showed several potentially neuropathogenic features, in vitro and in animal models. Phase II clinical trials against HERV-Wenv are ongoing. HERV-W/MSRV was repeatedly found in MS patients, in striking parallel with MS stages, active/remission phases, and therapy outcome. The HERV-Wenv protein is highly expressed in active MS plaques. Early MSRV presence in spinal fluids predicted worst MS progression 10 years in advance. Effective anti-MS therapies strongly reduced MSRV/Syncytin-1/HERV-W expression. The Epstein-Barr virus (EBV) activates HERV-W/MSRV in vitro and in vivo, in patients with infectious mononucleosis and controls with high anti-EBNA1-IgG titers. Thus, the two main EBV/MS links (infectious mononucleosis and high anti-EBNA1-IgG titers) are paralleled by activation of HERV-W/MSRV. It is hypothesized that EBV may act as initial trigger of future MS, years later, by activating MSRV, which would act as direct neuropathogenic effector, before and during MS.

SUDI prevention: a review of Maori safe sleep innovations for infants.

PubMed

Abel, Sally; Tipene-Leach, David

2013-08-02

Recent research and policy around sudden unexpected death in infancy (SUDI) have emphasised the place of safe sleeping practices within SUDI prevention strategies. Maori SUDI prevention workers have focussed on innovations around the safe sleep environment for some time now, as they have grappled with difficult to change and disproportionately high Maori SUDI rates. The wahakura (a flax bassinet modelled on a traditional Maori infant sleeping item) was developed in 2006 aiming to mitigate some of the risks of bedsharing with vulnerable infants, in particular infants exposed to maternal smoking in pregnancy. Early wahakura projects in Gisborne and Hawke's Bay showed high acceptability, effectiveness as an infant health promotion vehicle but difficulty maintaining a low/no cost supply for vulnerable families. The Hawke's Bay project revealed two pathways forward: the need for robust research to ensure the safety of the wahakura and the exploration of financially viable and more readily available alternatives. Work on both pathways is currently in progress around the country, signalling New Zealand's ongoing contribution to SUDI prevention and its potential contribution to knowledge and practices applicable to indigenous and other marginalised communities worldwide.

Radial Velocity Survey of T Tauri Stars in Taurus-Auriga

NASA Astrophysics Data System (ADS)

Crockett, Christopher; Mahmud, N.; Huerta, M.; Prato, L.; Johns-Krull, C.; Hartigan, P.; Jaffe, D.

2009-01-01

Is the frequency of giant planet companions to young stars similar to that seen around old stars? Is the "brown dwarf desert" a product of how low-mass companion objects form, or of how they evolve? Some models indicate that both giant planets and brown dwarfs should be common at young ages within 3 AU of a primary star, but migration induced by massive disks drive brown dwarfs into the parent stars, leaving behind proportionally more giant planets. Our radial velocity survey of young stars will provide a census of the young giant planet and brown dwarf population in Taurus-Auriga. In this poster we present our progress in quantifying how spurious radial velocity signatures are caused by stellar activity and in developing models to help distinguish between companion induced and spot induced radial velocity variations. Early results stress the importance of complementary observations in both visible light and NIR. We present our technique to determine radial velocities by fitting telluric features and model stellar features to our observed spectra. Finally, we discuss ongoing observations at McDonald Observatory, KPNO, and the IRTF, and several new exoplanet host candidates.

Optical Frequency Stabilization and Optical Phase Locked Loops: Golden Threads of Precision Measurement

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

Taubman, Matthew S.

Stabilization of lasers through locking to optical cavities, atomic transitions, and molecular transitions has enabled the field of precision optical measurement since shortly after the invention of the laser. Recent advances in the field have produced an optical clock that is orders of magnitude more stable than those of just a few years prior. Phase locking of one laser to another, or to a frequency offset from another, formed the basis for linking stable lasers across the optical spectrum, such frequency chains exhibiting progressively finer precision through the years. Phase locking between the modes within a femtosecond pulsed laser hasmore » yielded the optical frequency comb, one of the most beautiful and useful instruments of our time. This talk gives an overview of these topics, from early work through to the latest 1E-16 thermal noise-limited precision recently attained for a stable laser, and the ongoing quest for ever finer precision and accuracy. The issues of understanding and measuring line widths and shapes are also studied in some depth, highlighting implications for servo design for sub-Hz line widths.« less

Probabilistic Mass Growth Uncertainties

NASA Technical Reports Server (NTRS)

Plumer, Eric; Elliott, Darren

2013-01-01

Mass has been widely used as a variable input parameter for Cost Estimating Relationships (CER) for space systems. As these space systems progress from early concept studies and drawing boards to the launch pad, their masses tend to grow substantially, hence adversely affecting a primary input to most modeling CERs. Modeling and predicting mass uncertainty, based on historical and analogous data, is therefore critical and is an integral part of modeling cost risk. This paper presents the results of a NASA on-going effort to publish mass growth datasheet for adjusting single-point Technical Baseline Estimates (TBE) of masses of space instruments as well as spacecraft, for both earth orbiting and deep space missions at various stages of a project's lifecycle. This paper will also discusses the long term strategy of NASA Headquarters in publishing similar results, using a variety of cost driving metrics, on an annual basis. This paper provides quantitative results that show decreasing mass growth uncertainties as mass estimate maturity increases. This paper's analysis is based on historical data obtained from the NASA Cost Analysis Data Requirements (CADRe) database.

Understanding emerging treatment paradigms in rheumatoid arthritis

PubMed Central

2011-01-01

Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed – and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice. PMID:21624182

Understanding emerging treatment paradigms in rheumatoid arthritis.

PubMed

Breedveld, Ferdinand C; Combe, Bernard

2011-05-25

Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed - and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice.

An Integrated MRI and MRS Approach to Evaluation of Multiple Sclerosis with Cognitive Impairment

NASA Astrophysics Data System (ADS)

Liang, Zhengrong; Li, Lihong; Lu, Hongbing; Huang, Wei; Tudorica, Alina; Krupp, Lauren

Magnetic resonance imaging and spectroscopy (MRI/MRS) plays a unique role in multiple sclerosis (MS) evaluation, because of its ability to provide both high image contrast and significant chemical change among brain tissues. The image contrast renders the possibility of quantifying the tissue volumetric and texture variations, e.g., cerebral atrophy and progressing speed, reflecting the ongoing destructive pathologic processes. Any chemical change reflects an early sign of pathological alteration, e.g., decreased N-acetyl aspartate (NAA) in lesions and normal appearing white matter, related to axonal damage or dysfunction. Both MRI and MRS encounter partial volume (PV) effect, which compromises the quantitative capability, especially for MRS. This work aims to develop a statistical framework to segment the tissue mixtures inside each image element, eliminating theoretically the PV effect, and apply the framework to the evaluation of MS with cognitive impairment. The quantitative measures from MRI/MRS neuroimaging are strongly correlated with the qualitative neuropsychological scores of Brief Repeatable Battery (BRB) test on cognitive impairment, demonstrating the usefulness of the PV image segmentation framework in this clinically significant problem.

Progress in thermomechanical control of steel plates and their commercialization

NASA Astrophysics Data System (ADS)

Nishioka, Kiyoshi; Ichikawa, Kazutoshi

2012-04-01

The water-cooled thermomechanical control process (TMCP) is a technology for improving the strength and toughness of water-cooled steel plates, while allowing control of the microstructure, phase transformation and rolling. This review describes metallurgical aspects of the microalloying of steel, such as niobium addition, and discusses advantages of TMCP, for example, in terms of weldability, which is reduced upon alloying. Other covered topics include the development of equipment, distortions in steel plates, peripheral technologies such as steel making and casting, and theoretical modeling, as well as the history of property control in steel plate production and some early TMCP technologies. We provide some of the latest examples of applications of TMCP steel in various industries such as shipbuilding, offshore structures, building construction, bridges, pipelines, penstocks and cryogenic tanks. This review also introduces high heat-affected-zone toughness technologies, wherein the microstructure of steel is improved by the addition of fine particles of magnesium-containing sulfides and magnesium- or calcium-containing oxides. We demonstrate that thanks to ongoing developments TMCP has the potential to meet the ever-increasing demands of steel plates.

Amyloidosis: Pathogenesis and New Therapeutic Options

PubMed Central

Merlini, Giampaolo; Seldin, David C.; Gertz, Morie A.

2011-01-01

The systemic amyloidoses are a group of complex diseases caused by tissue deposition of misfolded proteins that results in progressive organ damage. The most common type, immunoglobulin light chain amyloidosis (AL), is caused by clonal plasma cells that produce misfolded light chains. The purpose of this review is to provide up-to-date information on diagnosis and treatment options for AL amyloidosis. Early, accurate diagnosis is the key to effective therapy, and unequivocal identification of the amyloidogenic protein may require advanced technologies and expertise. Prognosis is dominated by the extent of cardiac involvement, and cardiac staging directs the choice of therapy. Treatment for AL amyloidosis is highly individualized, determined on the basis of age, organ dysfunction, and regimen toxicities, and should be guided by biomarkers of hematologic and cardiac response. Alkylator-based chemotherapy is effective in almost two thirds of patients. Novel agents are also active, and trials are ongoing to establish their optimal use. Treatment algorithms will continue to be refined through controlled trials. Advances in basic research have led to the identification of new drug targets and therapeutic approaches, which will be integrated with chemotherapy in the future. PMID:21483018

HAWCPol: a first-generation far-infrared polarimeter for SOFIA

NASA Astrophysics Data System (ADS)

Dowell, C. Darren; Cook, Brant T.; Harper, D. Al; Lin, Lung-Sheng; Looney, Leslie W.; Novak, Giles; Stephens, Ian; Berthoud, Marc; Chuss, David T.; Crutcher, Richard M.; Dotson, Jessie L.; Hildebrand, Roger H.; Houde, Martin; Jones, Terry J.; Krejny, Megan; Lazarian, Alexandre; Moseley, S. Harvey; Tassis, Kostas; Vaillancourt, John E.; Werner, Michael W.

2010-07-01

We describe our ongoing project to build a far-infrared polarimeter for the HAWC instrument on SOFIA. Far-IR polarimetry reveals unique information about magnetic fields in dusty molecular clouds and is an important tool for understanding star formation and cloud evolution. SOFIA provides flexible access to the infrared as well as good sensitivity to and angular resolution of continuum emission from molecular clouds. We are making progress toward outfitting HAWC, a first-generation SOFIA camera, with a four-band polarimeter covering 50 to 220 microns wavelength. We have chosen a conservative design which uses quartz half-wave plates continuously rotating at ~0.5 Hz, ball bearing suspensions, fixed wire-grid polarizers, and cryogenic motors. Design challenges are to fit the polarimeter into a volume that did not originally envision one, to minimize the heating of the cryogenic optics, and to produce negligible interference in the detector system. Here we describe the performance of the polarimeter measured at cryogenic temperature as well as the basic method we intend for data analysis. We are on track for delivering this instrument early in the operating lifetime of SOFIA.

Gang homicides - five U.S. cities, 2003-2008.

PubMed

2012-01-27

Gang homicides account for a substantial proportion of homicides among youths in some U.S. cities; however, few surveillance systems collect data with the level of detail necessary to gang homicide prevention strategies. To compare characteristics of gang homicides with nongang homicides, CDC analyzed 2003-2008 data from the National Violent Death Reporting System (NVDRS) for five cities with high levels of gang homicide. This report describes the results of that analysis, which indicated that, consistent with similar previous research, a higher proportion of gang homicides than other homicides involved young adults and adolescents, racial and ethnic minorities, and males. Additionally, the proportion of gang homicides resulting from drug trade/use or with other crimes in progress was consistently low in the five cities, ranging from zero to 25%. Furthermore, this report found that gang homicides were more likely to occur with firearms and in public places, which suggests that gang homicides are quick, retaliatory reactions to ongoing gang-related conflict. These findings provide evidence for the need to prevent gang involvement early in adolescence and to increase youths' capacity to resolve conflict nonviolently.

Statistical physics of language dynamics

NASA Astrophysics Data System (ADS)

Loreto, Vittorio; Baronchelli, Andrea; Mukherjee, Animesh; Puglisi, Andrea; Tria, Francesca

2011-04-01

Language dynamics is a rapidly growing field that focuses on all processes related to the emergence, evolution, change and extinction of languages. Recently, the study of self-organization and evolution of language and meaning has led to the idea that a community of language users can be seen as a complex dynamical system, which collectively solves the problem of developing a shared communication framework through the back-and-forth signaling between individuals. We shall review some of the progress made in the past few years and highlight potential future directions of research in this area. In particular, the emergence of a common lexicon and of a shared set of linguistic categories will be discussed, as examples corresponding to the early stages of a language. The extent to which synthetic modeling is nowadays contributing to the ongoing debate in cognitive science will be pointed out. In addition, the burst of growth of the web is providing new experimental frameworks. It makes available a huge amount of resources, both as novel tools and data to be analyzed, allowing quantitative and large-scale analysis of the processes underlying the emergence of a collective information and language dynamics.

Progress and challenges in understanding planar cell polarity signaling.

PubMed

Axelrod, Jeffrey D

2009-10-01

During development, epithelial cells in some tissues acquire a polarity orthogonal to their apical-basal axis. This polarity, referred to as planar cell polarity (PCP), or tissue polarity, is essential for the normal physiological function of many epithelia. Early studies of PCP focused on insect epithelia (Lawrence, 1966 [1]), and the earliest genetic analyses were carried out in Drosophila (Held et al., 1986; Gubb and Garcia-Bellido, 1982 [2,3]). Indeed, most of our mechanistic understanding of PCP derives from the ongoing use of Drosophila as a model system. However, a range of medically important developmental defects and physiological processes are under the control of PCP mechanisms that appear to be at least partially conserved, driving considerable interest in studying PCP both in Drosophila and in vertebrate model systems. Here, I present a model of the PCP signaling mechanism based on studies in Drosophila. I highlight two areas in which our understanding is deficient, and which lead to current confusion in the literature. Future studies that shed light on these areas will substantially enhance our understanding of the fascinating yet challenging problem of understanding the mechanisms that generate PCP.

Genetic Landscape of Auditory Dysfunction.

PubMed

Bowl, Michael R; Brown, S D M

2018-05-02

Over the past 25 years, human and mouse genetics research together has identified several hundred genes essential for mammalian hearing, leading to a greater understanding of the molecular mechanisms underlying auditory function. However, from the number of still as yet uncloned human deafness loci and the findings of large-scale mouse mutant screens, it is clear we are still far from identifying all of the genes critical for auditory function. In particular, while we have made great progress in understanding the genetic bases of congenital and early-onset hearing loss, we have only just begun to elaborate upon the genetic landscape of age-related hearing loss. With an aging population and a growing literature suggesting links between age-related hearing loss and neuropsychiatric conditions, such as dementia and depression, understanding the genetics and subsequently the molecular mechanisms underlying this very prevalent condition is of paramount importance. Increased knowledge of genes and molecular pathways required for hearing will ultimately provide the foundation upon which novel therapeutic approaches can be built. Here we discuss the current status of deafness genetics research and the ongoing efforts being undertaken for discovery of novel genes essential for hearing.

Endpoints for Pre-Dementia AD Trials: A Report from the EU/US/CTAD Task Force

PubMed Central

Vellas, B.; Bateman, R.; Blennow, K.; Frisoni, G.; Johnson, K.; Katz, R.; Langbaum, J.; Marson, D.; Sperling, R.; Wessels, A.; Salloway, S.; Doody, R.; Aisen, P.

2015-01-01

For Alzheimer’s disease treatment trials that focus on the pre-dementia stage of disease, outcome measures are needed that will enable assessment of disease progression in patients who are clinically normal. The EU/US CTAD Task Force, an international collaboration of investigators from industry, academia, non-profit foundations, and regulatory agencies, met in Philadelphia, Pennsylvania, USA, on November 19, 2014 to discuss existing and novel outcome assessments that may be useful in pre-dementia trials. Composite measures that assess changes in episodic memory, executive function, global cognition, and global function have recently been developed by a number of groups and appear to be sensitive at this stage. Functional measures that involve real-life complex tasks also appear to capture early subtle changes in pre-dementia subjects and have the advantage of representing clinically meaningful change. Patient reported outcomes and novel CSF and imaging biomarkers have also shown promise. More studies are needed to validate all of these tests in the pre-dementia population. Many of them have been incorporated as exploratory measures in ongoing or planned trials. PMID:26247004

Creating an Ofsted Story: The Role of Early Years Assessment Data in Schools' Narratives of Progress

ERIC Educational Resources Information Center

Bradbury, Alice; Roberts-Holmes, Guy

2017-01-01

This paper explores the growing importance of measures of progress in judgements of schools' effectiveness in England, with a focus on the role of the early years (settings for children aged 2-5) in providing data for these measures. Qualitative data from a research project involving three diverse school-based and pre-compulsory early years…

Examining the Technical Adequacy of Progress Monitoring Using Early Writing Curriculum-Based Measures

ERIC Educational Resources Information Center

Hampton, David D.; Lembke, Erica S.

2016-01-01

The purpose of this study was to examine 4 early writing measures used to monitor the early writing progress of 1st-grade students. We administered the measures to 23 1st-grade students biweekly for a total of 16 weeks. We obtained 3-min samples and conducted analyses for each 1-min increment. We scored samples using 2 different methods: correct…

Adolescent Deviant Peer Clustering as an Amplifying Mechanism Underlying the Progression from Early Substance Use to Late Adolescent Dependence

ERIC Educational Resources Information Center

Van Ryzin, Mark J.; Dishion, Thomas J.

2014-01-01

Background: Early substance use co-occurs with youths' self-organization into deviant peer groups in which substance use is central to social interaction. We hypothesized that the social dynamics of deviant peer groups amplify the risk of progressing from early use to later dependence, and that this influence occurs over and above escalations…

Arterial hypertension and skin allergy are risk factors for progression from dengue to dengue hemorrhagic fever: a case control study.

PubMed

Teixeira, Maria Glória; Paixão, Enny S; Costa, Maria da Conceição N; Cunha, Rivaldo V; Pamplona, Luciano; Dias, Juarez P; Figueiredo, Camila A; Figueiredo, Maria Aparecida A; Blanton, Ronald; Morato, Vanessa; Barreto, Maurício L; Rodrigues, Laura C

2015-05-01

Currently, knowledge does not allow early prediction of which cases of dengue fever (DF) will progress to dengue hemorrhagic fever (DHF), to allow early intervention to prevent progression or to limit severity. The objective of this study is to investigate the hypothesis that some specific comorbidities increase the likelihood of a DF case progressing to DHF. A concurrent case-control study, conducted during dengue epidemics, from 2009 to 2012. Cases were patients with dengue fever that progressed to DHF, and controls were patients of dengue fever who did not progress to DHF. Logistic regression was used to estimate the association between DHF and comorbidities. There were 490 cases of DHF and 1,316 controls. Among adults, progression to DHF was associated with self-reported hypertension (OR = 1.6; 95% CI 1.1-2.1) and skin allergy (OR = 1.8; 95% CI 1.1-3.2) with DHF after adjusting for ethnicity and socio-economic variables. There was no statistically significant association between any chronic disease and progression to DHF in those younger than 15 years. Physicians attending patients with dengue fever should keep those with hypertension or skin allergies in health units to monitor progression for early intervention. This would reduce mortality by dengue.

Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.

PubMed

Duncan, Jhodie Rubina; Dick, Alec Lindsay Ward; Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

2012-01-01

Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T₂-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence.

Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson's disease: the PPMI cohort.

PubMed

Simuni, Tanya; Caspell-Garcia, Chelsea; Coffey, Christopher S; Weintraub, Daniel; Mollenhauer, Brit; Lasch, Shirley; Tanner, Caroline M; Jennings, Danna; Kieburtz, Karl; Chahine, Lana M; Marek, Kenneth

2018-01-01

To examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson's disease (PD) compared with healthy controls (HC). Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging. 423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1-42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy. This study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1-42 level is an important finding that will have to be replicated in other cohorts. ClinicalTrials.gov identifier: NCT01141023. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The mid- to late-Holocene environmental evolution at the marsh of Vravron (Attiki, SE Greece): a multidisciplinary approach

NASA Astrophysics Data System (ADS)

Triantaphyllou, M. V.; Kouli, K.; Tsourou, T.; Koukousioura, O.; Pavlopoulos, K.; Dermitzakis, M. D.

2009-04-01

The Vravron bay, in the vicinity of the homonym archaeological site is a marshy area located on the eastern coast of Attiki peninsula (eastern Greece). Vravron was inhabited already since the Early/ Middle Neolithic, although it's mainly known from the famous Archaic and Classical sanctuary of Vravronia Artemis. A sediment core from the marshy deposits of Vravron was submitted to detailed palynological, micropaleontological and sedimentological analyses, in order to investigate the environmental evolution of the area since approx. 3000 BC (AMS 14C). Benthic foraminifera and ostracoda assemblages were used to trace the depositional environment of the sequence: open shallow marine conditions with constant input of fresh water due to the influx of Erasinos River are recorded until 400BC, confirming the existence of the natural port known from a Mycenaean legend, while repeated flooding events recorded between 400BC and 50 AD should be linked with the destruction of the famous sanctuary of Artemis and the abandonment of the area. Around 50 AD the ongoing progression of Erasinos River resulted in the gradual development of lagoonal environment that after 1300AD got isolated from the sea becoming progressively a fresh water marsh. Pollen assemblages included representatives from all modern phytogeographic zones, indicating the complexity of the plant communities in the area and outlined the vegetation development since the Early Bronze Age. Even if human presence has been continuously recorded, its impact on natural environment appears profound only during the Mycenaean times, when cereal cultivation seems to be the main rural activity and after 1300AD, when a remarkable rise in like ploughing and herding evidence marks the introduction of the Arvanites population in the area. The establishment of the Vravronia Artemis sanctuary during the Geometric times coincides with a turnover in agricultural activities, as cereal cultivation is neglected and olive groves are amplified.

Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

PubMed Central

Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

2012-01-01

Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T2-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence. PMID:23028622

Dietary Sodium Modulation of Aldosterone Activation and Renal Function During the Progression of Experimental Heart Failure Miller: Dietary Sodium and Early Heart Failure

PubMed Central

Miller, Wayne L.; Borgeson, Daniel D.; Grantham, J. Aaron; Luchner, Andreas; Redfield, Margaret M.; Burnett, John C.

2015-01-01

Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression. PMID:25823360

An automated, broad-based, near real-time public health surveillance system using presentations to hospital Emergency Departments in New South Wales, Australia.

PubMed

Muscatello, David J; Churches, Tim; Kaldor, Jill; Zheng, Wei; Chiu, Clayton; Correll, Patricia; Jorm, Louisa

2005-12-22

In a climate of concern over bioterrorism threats and emergent diseases, public health authorities are trialling more timely surveillance systems. The 2003 Rugby World Cup (RWC) provided an opportunity to test the viability of a near real-time syndromic surveillance system in metropolitan Sydney, Australia. We describe the development and early results of this largely automated system that used data routinely collected in Emergency Departments (EDs). Twelve of 49 EDs in the Sydney metropolitan area automatically transmitted surveillance data from their existing information systems to a central database in near real-time. Information captured for each ED visit included patient demographic details, presenting problem and nursing assessment entered as free-text at triage time, physician-assigned provisional diagnosis codes, and status at departure from the ED. Both diagnoses from the EDs and triage text were used to assign syndrome categories. The text information was automatically classified into one or more of 26 syndrome categories using automated "naïve Bayes" text categorisation techniques. Automated processes were used to analyse both diagnosis and free text-based syndrome data and to produce web-based statistical summaries for daily review. An adjusted cumulative sum (cusum) was used to assess the statistical significance of trends. During the RWC the system did not identify any major public health threats associated with the tournament, mass gatherings or the influx of visitors. This was consistent with evidence from other sources, although two known outbreaks were already in progress before the tournament. Limited baseline in early monitoring prevented the system from automatically identifying these ongoing outbreaks. Data capture was invisible to clinical staff in EDs and did not add to their workload. We have demonstrated the feasibility and potential utility of syndromic surveillance using routinely collected data from ED information systems. Key features of our system are its nil impact on clinical staff, and its use of statistical methods to assign syndrome categories based on clinical free text information. The system is ongoing, and has expanded to cover 30 EDs. Results of formal evaluations of both the technical efficiency and the public health impacts of the system will be described subsequently.

Agricultural innovations in Morocco's cannabis industry.

PubMed

Chouvy, Pierre-Arnaud; Macfarlane, Jennifer

2018-06-06

Cannabis cultivation in Morocco's mountainous Rif region is undergoing its most profound development since mass production of hashish began in the early 1980s. The adoption of high-yielding varieties of cannabis, modern agricultural practices, and modern hashish production techniques began in the mid-2000s and accelerated after the mid-2010s, with the result that more potent and varied cannabis derivatives are now being produced and that increased quantities of highly potent hashish are seized in Europe. This research was initiated to answer a simple research question: how, and to what extent, is the illegal cannabis industry modernizing in Morocco, now that we know that it explains the THC increase in hashish seized in Europe? To answer this question in the context of a lack of literature and quantitative data, empirical fieldwork was undertaken in cannabis fields and hashish-producing farms in Morocco in July and October 2017. A mostly qualitative approach to data collection was employed through participatory rural appraisals (discussions, interviews, direct observations). As such, this work builds predominantly upon primary research. Fieldwork showed that, subsequent to very localized, experimental beginnings in the early 2000s, the progressive and varied adoption of agricultural innovations at the cultivation and production stages has spread throughout the Rif during the 2010s. Interviews and direct observations conducted in the field indicate that the ongoing adoption of modern farming techniques has enabled the production of high-quality hashish and potent modern extracts. The still ongoing modernization and professionalization of the Moroccan cannabis industry is a testimony of the country's leading position in global hashish production. What the future holds for Moroccan cannabis growers is difficult to predict. How legalization processes manifest themselves in Moroccan and European policies, and how upcoming developments will affect the social, economic, political and ecological stability of the region, remains largely unknown. However, the spread of cannabis cultivation in the Rif is clearly pushing economic and environmental limits, and there is an obvious need for innovations that mitigate such pressures. Copyright © 2018 Elsevier B.V. All rights reserved.

FOUR-YEAR INCIDENCE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION: THE LOS ANGELES LATINO EYE STUDY

PubMed Central

Varma, Rohit; Foong, Athena W.P.; Lai, Mei-Ying; Choudhury, Farzana; Klein, Ronald; Azen, Stanley P.

2011-01-01

Purpose To estimate 4-year incidence and progression of early and advanced age-related macular degeneration (AMD). Design Population-based cohort study. Methods A comprehensive ophthalmologic examination including stereoscopic fundus photography was performed on adult Latinos at baseline and follow-up. Photographs were graded using a modified Wisconsin Age-Related Maculopathy Grading System. For estimations of incidence and progression of AMD, the Age Related Eye Disease Study Scale was used. Main outcome measures are incidence and progression of early AMD (drusen type, drusen size, and retinal pigmentary abnormalities) and advanced AMD (exudative AMD and geographic atrophy). Results 4,658/6100 (76%) completed the follow-up examination. The 4-year incidence of early AMD was 7.5% (95%CI:6.6,8.4) and advanced AMD was 0.2% (95%CI:0.1,0.4). Progression of any AMD occurred in 9.3% (95%CI:8.4,10.3) of at-risk participants. Incidence and progression increased with age. Incidence of early AMD in the second eye (10.8%) was higher than incidence in the first eye (6.9%). Baseline presence of soft indistinct large drusen≥250μm in diameter was more likely to predict the 4-year incidence of pigmentary abnormalities, geographic atrophy, and exudative AMD than smaller or hard or soft distinct drusen. Conclusions Age-specific incidence and progression of AMD in Latinos are lower than in non-Hispanic whites. While incident early AMD is more often unilateral, the risk of its development in the second is higher than in the first eye. Older persons and those with soft indistinct large drusen had a higher risk of developing advanced AMD compared to those who were younger and did not have soft indistinct large drusen. PMID:20399926

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

Zavarin, Mavrik; Joseph, C.

This progress report (Level 4 Milestone Number M4FT-16LL080303052) summarizes research conducted at Lawrence Livermore National Laboratory (LLNL) within the Crystalline Disposal R&D Activity Number FT-16LL080303051 and Crystalline International Collaborations Activity Number FT-16LL080303061. The focus of this research is the interaction of radionuclides with Engineered Barrier System (EBS) and host rock materials at various physico-chemical conditions relevant to subsurface repository environments. They include both chemical and physical processes such as solubility, sorption, and diffusion. The colloid-facilitated transport effort focused on preparation of a draft manuscript summarizing the state of knowledge and parameterization of colloid-facilitated transport mechanisms in support of reactive transportmore » and performance assessment models for generic crystalline repositories. This draft manuscript is being submitted as a level 3 milestone with LANL as the primary author. LLNL’s contribution to that effort is summarized only briefly in the present report. A manuscript summarizing long-term U(VI) diffusion experiments through bentonite backfill material was recently accepted for publication; the contents of that manuscript are summarized in the present report. The Np(IV) diffusion experiments were started mid-year and are ongoing. The completion of these experiments is planned for early FY17. Our progress in quantifying Np(IV) diffusion in bentonite backfill is summarized in the present report. Our involvement with the NEA TDB project was summarized in a recent Argillite Disposal activity report. It is not included in this report.« less

How to define responders in osteoarthritis

PubMed Central

Cooper, Cyrus; Adachi, Jonathan D.; Bardin, Thomas; Berenbaum, Francis; Flamion, Bruno; Jonsson, Helgi; Kanis, John A.; Pelousse, Franz; Lems, Willem F.; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Reiter, Susanne; Reginster, Jean-Yves; Rizzoli, René; Bruyère, Olivier

2013-01-01

Background Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain, functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of other joint structures. Scope Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis, review current regulatory guidelines for the conduct of clinical trials, and examine the concept of responder analyses for improving drug evaluation in osteoarthritis. Findings The ESCEO considers that the major challenges in DMOAD development are the absence of a precise definition of the disease, particularly in the early stages, and the lack of consensus on how to detect structural changes and link them to clinically meaningful endpoints. Responder criteria should help identify progression of disease and be clinically meaningful. The ideal criterion should be sensitive to change over time and should predict disease progression and outcomes such as joint replacement. Conclusion The ESCEO considers that, for knee osteoarthritis, clinical trial data indicate that radiographic joint space narrowing >0.5 mm over 2 or 3 years might be a reliable surrogate measure for total joint replacement. On-going research using techniques such as magnetic resonance imaging and biochemical markers may allow the identification of these patients earlier in the disease process. PMID:23557069

Hyper-excitability of brainstem pathways in cerebral palsy.

PubMed

Smith, Allison Teresa; Gorassini, Monica Ann

2018-06-27

Individuals with cerebral palsy (CP) experience impairments in the control of head and neck movements, suggesting dysfunction in brainstem circuitry. To examine if brainstem circuitry is altered in CP we compared reflexes evoked in the sternocleidomastoid (SCM) muscle by trigeminal nerve stimulation in adults with CP and age/sex-matched controls. Increasing the intensity of trigeminal nerve stimulation produced progressive increases in the long-latency suppression of ongoing SCM EMG in controls. In contrast, participants with CP showed progressively increased facilitation around the same reflex window, suggesting heightened excitability of brainstem pathways. We also examined if there was altered activation of cortico-brainstem pathways in response to pre-natal injury of the brain. Motor-evoked potentials (MEPs) in the SCM that were conditioned by a prior trigeminal afferent stimulation were more facilitated in CP compared to controls, especially in ipsilateral MEPs that are likely mediated by cortico-reticulospinal pathways. In some participants with CP, but not in controls, a combined trigeminal nerve and cortical stimulation near threshold intensities produced large, long-lasting responses in both the SCM and biceps brachii muscles. We propose that the enhanced excitatory responses evoked from trigeminal and cortical inputs in CP are produced by heightened excitability of brainstem circuits, resulting in the augmented activation of reticulospinal pathways. Enhanced activation of reticulospinal pathways in response to early injury of the corticospinal tract may provide a compensated activation of the spinal cord, or alternatively, contribute to impairments in the precise control of head and neck functions.

Cyclin-Dependent Kinase Inhibitors for the Treatment of Breast Cancer: Past, Present, and Future.

PubMed

DiPippo, Adam J; Patel, Neelam K; Barnett, Chad M

2016-06-01

Treatment of metastatic breast cancer (MBC) that is resistant to endocrine therapy presents a significant clinical challenge. The well-known role of cell cycle dysregulation in these patients is partly mediated by cyclin-dependent kinase (CDK) activity. Specific cyclin and CDK complexes regulate cell cycle progression by managing the transition through the cell cycle, and inhibition of CDKs represents an important target for novel agents. First-generation CDK inhibitors (e.g., flavopiridol) were relatively nonselective and had an unacceptable toxicity profile in early trials. Second-generation CDK inhibitors were designed to target the CDK4 and CDK6 (CDK4/6) pathway and have shown promising clinical activity with an acceptable toxicity profile in patients with MBC. Palbociclib is a first-in-class CDK4/6 inhibitor that was granted accelerated U.S. Food and Drug Administration approval in combination with letrozole for the treatment of MBC in the first-line setting (February 2015) as well as in combination with fulvestrant for MBC that had progressed on previous endocrine therapy (February 2016). Other CDK4/6 inhibitors, including ribociclib and abemaciclib, are under investigation as monotherapy and in combination with endocrine or anti-human epidermal growth receptor 2 therapy for the treatment of MBC. Ongoing clinical trials should provide additional information to guide the appropriate use of these agents and identify patient populations that could derive the most benefit. © 2016 Pharmacotherapy Publications, Inc.

Cellular regeneration strategies for macular degeneration: past, present and future.

PubMed

Chichagova, Valeria; Hallam, Dean; Collin, Joseph; Zerti, Darin; Dorgau, Birthe; Felemban, Majed; Lako, Majlinda; Steel, David H

2018-05-01

Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.

Endemism in the moss flora of North America.

PubMed

Carter, Benjamin E; Shaw, Blanka; Shaw, A Jonathan

2016-04-01

Identifying regions of high endemism is a critical step toward understanding the mechanisms underlying diversification and establishing conservation priorities. Here, we identified regions of high moss endemism across North America. We also identified lineages that contribute disproportionately to endemism and document the progress of efforts to inventory the endemic flora. To understand the documentation of endemic moss diversity in North America, we tabulated species publication dates to document the progress of species discovery across the continent. We analyzed herbarium specimen data and distribution data from the Flora of North America project to delineate major regions of moss endemism. Finally, we surveyed the literature to assess the importance of intercontinental vs. within-continent diversification for generating endemic species. Three primary regions of endemism were identified and two of these were further divided into a total of nine subregions. Overall endemic richness has two peaks, one in northern California and the Pacific Northwest, and the other in the southern Appalachians. Description of new endemic species has risen steeply over the last few decades, especially in western North America. Among the few studies documenting sister species relationships of endemics, recent diversification appears to have played a larger role in western North America, than in the east. Our understanding of bryophyte endemism continues to grow rapidly. Large continent-wide data sets confirm early views on hotspots of endemic bryophyte richness and indicate a high rate of ongoing species discovery in North America. © 2016 Botanical Society of America.

They're Only Young Once.

ERIC Educational Resources Information Center

Skupa, Leanne

1983-01-01

Recent graduates can be counted on to maintain ongoing interest in their college if involved early and in a variety of alumni activities. Possibilities include athletic events, special events, tours, educational programs, parties, and outdoor and service activities. (MSE)

Scientific Basis for Biotech Crops

EPA Science Inventory

Efforts to change the genetic makeup of plants have been ongoing since the beginning of agriculture, thousands of years ago. Early plant improvements relied on simply cross-breeding cultivars with desired traits. Advancements in mutation breeding through chemicals and radiation ...

Developing a Measure of Scientific Literacy for Middle School Students

ERIC Educational Resources Information Center

Fives, Helenrose; Huebner, Wendy; Birnbaum, Amanda S.; Nicolich, Mark

2014-01-01

Scientific literacy reflects "a broad and functional understanding of science for general education purposes" (DeBoer, [DeBoer, G. E., 2000], p. 594). Herein, we present the ongoing development of the Scientific Literacy Assessment (SLA), a work-in-progress measure to assess middle school students' (ages 11-14) scientific literacy.…

Tracking Behavioral Progress within a Children's Mental Health System: The Vermont Community Adjustment Tracking System.

ERIC Educational Resources Information Center

Bruns, Eric J.; Burchard, John D.; Froelich, Peter; Yoe, James T.; Tighe, Theodore

1998-01-01

Describes the Vermont Community Adjustment Tracking System (VT-CATS), which utilizes four behavioral instruments to allow intensive, ongoing, and interpretable behavioral assessment of a service system's most challenging children and adolescents. Also explains the adjustment indicator checklists and the ability of VT-CATS to address agencies'…

Tracking Learners' Progress: Adopting a Dual "Corpus cum Experimental Data" Approach

ERIC Educational Resources Information Center

Meunier, Fanny; Littre, Damien

2013-01-01

The article discusses the potential of combining learner corpus research with experimental studies in order to fine-tune the understanding of learner language development. It illustrates the complementarity of the two methodological approaches with data from an ongoing study of the acquisition of the English tense and aspect system by French…

Evaluating public participation in environmental decision-making: EPA's superfund community involvement program.

Treesearch

Susan Charnley; Bruce Engelbert

2005-01-01

This article discusses an 8-year, ongoing project that evaluates the Environmental Protection Agency's Superfund community involvement program. The project originated as a response to the Government Performance and Results Act, which requires federal agencies to articulate program goals, and evaluate and report their progress in meeting those goals. The evaluation...

Creating a Learning Environment for Pre-Service Teachers.

ERIC Educational Resources Information Center

Diggs, Laura L.

This paper presents statistics from ongoing research on a unique learning environment developed at the University of Missouri-Columbia College of Education (MU-CoE). MU-CoE has developed a new approach to space devoted to learning, not teaching. This new concept of progressive learning and performance support integrates interactive networked…

ACSM Fitness Book: A Proven Step-By-Step Program from the Experts. Third Edition.

ERIC Educational Resources Information Center

American Coll. of Sports Medicine, Indianapolis, IN.

This offers advice on the health benefits of regular physical activity. It includes a scientifically proven fitness test to determine one's starting point and monitor ongoing progress, offering step-by-step instructions, sample programs, and insights on nutrition, weight control, motivation, and overcoming setbacks. Seven chapters examine: (1)…

Quality and Utility of the Multi-Tiered Instruction Self-Efficacy Scale

ERIC Educational Resources Information Center

Barnes, Susan K.; Burchard, Melinda S.

2011-01-01

Response to Intervention (RTI) is an educational approach that integrates ongoing assessment of individual student progress with targeted instruction. Administrators and teachers in P-12 schools expressed a need for colleagues in higher education to provide training to general education pre-service and in-service teachers in selecting appropriate…

The Evolution of Preservice Science Teachers' Concerns about Teaching.

ERIC Educational Resources Information Center

Zielinski, Edward J.; Preston, Denise D.

As primary agents involved in reform and innovation in preparation programs, teacher educators require ongoing evaluation of the impacts of change. This paper reports a study to determine preservice teachers' concerns as they progressed through a traditional teacher preparation program and changes in their concerns that may have been attributed to…

The Progress and Promise of the Reading for Understanding Research Initiative

ERIC Educational Resources Information Center

Douglas, Karen M.; Albro, Elizabeth R.

2014-01-01

Decades of reading research have improved our understanding of the ways that young children learn how to read and of the component skills that support the ongoing development of reading and reading comprehension. However, while these investments have transformed reading instruction and reading outcomes for many learners, too many children are not…

Second Annual Progress Report on Radiation Tolerance of Controlled Fusion Welds in High Temperature Oxidation Resistant FeCrAl Alloys

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

Field, Kevin G.; Gussev, Maxim N.; Yamamoto, Yukinori

2016-12-30

The present report summarizes and discusses the current results and on-going activity towards developing a modern, nuclear grade FeCrAl alloy designed to have enhanced radiation tolerance and weldability under the Department of Energy (DOE) Nuclear Energy Enabling Technologies (NEET) program.

Canadian Schools in Transition: Moving from Dual Education Systems to Inclusive Schools.

ERIC Educational Resources Information Center

Lupart, Judy; Webber, Charles

2002-01-01

This article analyzes the many meanings of school restructuring and highlights the ongoing nature of school reform in Canadian schools. Following a selective chronology of general and special education reform, it attempts to capture what appear to be the key features of school reform and progressive inclusion. (Contains references.) (Author/CR)

A Progress Report on an Exploratory Mathematics Course: Incorporating a Programming Component

ERIC Educational Resources Information Center

Goldberg, Robert; Waxman, Jerry

2004-01-01

This paper reports on an ongoing effort to incorporate a programming component into exploratory mathematics courses and analyzes some of the many practical considerations required for successfully managing such a course in large lecture hall classes. Two pedagogical paradigms (top-down and bottom-up) are compared and contrasted for teaching Visual…

Rural vs. Suburban Residential Choice: A Progress Report. Technical Report 107A.

ERIC Educational Resources Information Center

Gray, Morris J.; And Others

As part of an ongoing investigation to determine the locational behavior of single-family-housing residents on the metropolitan fringe, a pilot study was conducted which simulated residential choice by asking respondents to rate the economy, convenience, and desirability of rural housing descriptions relative to a standard suburban residence. Four…

Nuclear Energy Research Initiative (NERI) Program. 2nd Quarterly Technical Progress Report

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

NONE

2000-02-22

The research activities have been underway. We have located a large body of source material from aerospace, shipbuilding and manufacturing businesses that is serving the basis for identifying improvement methodologies. Our work on developing the three models proposed to capture the extent of the improvement possibilities has been ongoing.

The Progress and Promise of the Reading for Understanding Research Initiative

ERIC Educational Resources Information Center

Douglas, Karen M.; Albro, Elizabeth R.

2014-01-01

Decades of reading research have improved our understanding of the ways that young children learn how to read and of the component skills that support the ongoing development of reading and reading comprehension. But while these investments have transformed reading instruction and reading outcomes for many learners, too many children are not…

Service-Learning's Ongoing Journey as a Method of Instruction: Implications for School-Based Agricultural Education

ERIC Educational Resources Information Center

Roberts, Richie; Edwards, M. Craig

2015-01-01

American education's journey has witnessed the rise and fall of various progressive education approaches, including service-learning. In many respects, however, service-learning is still undergoing formation and adoption as a teaching method, specifically in School-Based, Agricultural Education (SBAE). For this reason, the interest existed to…

Don't Sweat the Big Stuff: Academic Innovation in All Shapes and Sizes

ERIC Educational Resources Information Center

Halfond, Jay A.

2011-01-01

Faculty don't give themselves enough credit for innovation and creative thinking within higher education. The soap operas of entrenched faculty, factions divided over trivia, professors protecting their sub-disciplines, lengthy and convoluted approval processes, and ongoing acrimony and melodrama all overshadow progress made without fanfare. The…

From Reflective Practice to Practical Wisdom: Toward a Post-Foundational Teacher Education

ERIC Educational Resources Information Center

Eryaman, Mustafa Yunus

2007-01-01

The author situates this paper within ongoing debates in related areas such as reflective practice, critical pedagogy, practical wisdom and critical theory. First, the author identifies some of the problems in the present notions of reflective teaching and progressive teacher education. The analyzes and compares the traditional-technical and…

The Alabama Counseling Association: A Legacy of Community and Professional Service

ERIC Educational Resources Information Center

Clark, Eddie, Jr.

2007-01-01

The Alabama Counseling Association (ALCA) has an ongoing plan for professional growth and development reflective of the multiple counseling professions and the diversity of its members. Based on the development and history of the organization, this research project was designed to assess ALCA's progress toward achieving its stated outcome goals. A…

Reconsidering Arthur Bestor and the Cold War in Social Education.

ERIC Educational Resources Information Center

Weltman, Burton

2000-01-01

Explores the development of Arthur Bestor's ideas and his differences with progressives during the 1950's. Contends their differences, exacerbated by the Cold War, were matters of emphasis not principles. Concludes that ongoing post-Cold War battles among liberal social educators should be resolved in favor of their common social and educational…

76 FR 12996 - Advisory Committee for Biological Sciences; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

.... Purpose of Meeting: The Advisory Committee for BIO provides advice, recommendations, and oversight... that make up BIO. Agenda: Items on the agenda include the NSF and BIO FY 2012 budget request, the 2010 America Competes Act, and a progress report on BIO's ongoing experiments in innovation. In addition, the...

Space nuclear safety program

NASA Astrophysics Data System (ADS)

George, T. G.

1990-02-01

This quarterly report describes studies related to the use of Pu(238)O sub 2 in radioisotope power systems, carried out of the Office of Defense Energy Programs and Special Applications of the U.S. Department of Energy by Los Alamos National Laboratory. The studies are ongoing; the results and conclusions described may change as the work progresses.

The U.S. EPA ToxCast Program: Moving from Data Generation to Application (SOT Tox21 update symposium presentation)

EPA Science Inventory

The U.S. EPA ToxCast program is entering its tenth year. Significant learning and progress have occurred towards collection, analysis, and interpretation of the data. The library of ~1,800 chemicals has been subject to ongoing characterization (e.g., identity, purity, stability...

Measuring Family System Characteristics in Families Caring for Dementia Patients.

ERIC Educational Resources Information Center

Niederehe, George; And Others

This paper describes an ongoing study evaluating families that provide in-home care to elderly relatives wth dementia. Characteristics of the study, which include a focus on progressive senile dementia, use of a clinical approach, longitudinal design, descriptive nature, focus on the dyad of patient and primary caregiver, and use of videotaping…

A practical guide to exercise training for heart failure patients.

PubMed

Smart, Neil; Fang, Zhi You; Marwick, Thomas H

2003-02-01

Exercise training has been shown to improve exercise capacity in patients with heart failure. We sought to examine the optimal strategy of exercise training for patients with heart failure. Review of the published data on the characteristics of the training program, with comparison of physiologic markers of exercise capacity in heart failure patients and healthy individuals and comparison of the change in these characteristics after an exercise training program. Many factors, including the duration, supervision, and venue of exercise training; the volume of working muscle; the delivery mode (eg, continuous vs. intermittent exercise), training intensity; and the concurrent effects of medical treatments may influence the results of exercise training in heart failure. Starting in an individually prescribed and safely monitored hospital-based program, followed by progression to an ongoing and progressive home program of exercise appears to be the best solution to the barriers of anxiety, adherence, and "ease of access" encountered by the heart failure patient. Various exercise training programs have been shown to improve exercise capacity and symptom status in heart failure, but these improvements may only be preserved with an ongoing maintenance program.

Core principles of assessment in competency-based medical education.

PubMed

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

2017-06-01

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

N-acetylaspartate and neurofilaments as biomarkers of axonal damage in patients with progressive forms of multiple sclerosis.

PubMed

Trentini, Alessandro; Comabella, Manuel; Tintoré, Mar; Koel-Simmelink, Marleen J A; Killestein, Joep; Roos, Birthe; Rovira, Alex; Korth, Carsten; Ottis, Philipp; Blankenstein, Marinus A; Montalban, Xavier; Bellini, Tiziana; Teunissen, Charlotte E

2014-12-01

Primary and secondary progressive forms of multiple sclerosis (PPMS and SPMS) have different pathological characteristics. However, it is unknown whether neurodegenerative mechanisms are shared. We measured cerebrospinal fluid (CSF) levels of neurofilament (Nf) light and heavy isoforms and N-acetylaspartic acid (NAA) in 21 PP, 10 SPMS patients and 15 non-inflammatory neurological disease controls (NINDC). Biomarkers were related to Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) over a long period of follow-up [median (interquartile range) 9 (5.5-12.5) years] in 19 PPMS and 4 SPMS patients, and to T2 lesion load, T1 lesion load, and brain parenchymal fraction at the time of lumbar puncture. Nf light was higher in PPMS (p < 0.005) and Nf heavy was increased in both SPMS and PPMS (p < 0.05 and p < 0.01) compared to NINDC, but were comparable between the two MS subtypes. Nf heavy was a predictor of the ongoing disability measured by MSSS (R(2) = 0.17, β = 0.413; p < 0.05). Conversely, Nf light was the only predictor of the EDSS annual increase (R(2) = 0.195, β = 0.441; p < 0.05). The frequency of abnormal biomarkers did not differ between the two MS progressive subtypes. Our data suggest that PP and SPMS likely share similar mechanisms of axonal damage. Moreover, Nf heavy can be a biomarker of ongoing axonal damage. Conversely, Nf light can be used as a prognostic marker for accumulating disability suggesting it as a good tool for possible treatment monitoring in the progressive MS forms.

"Because if You Don't Put the Top On, It Will Spill": A Longitudinal Study of Sibling Teaching in Early Childhood

ERIC Educational Resources Information Center

Howe, Nina; Della Porta, Sandra; Recchia, Holly; Ross, Hildy

2016-01-01

Naturalistic dyadic sequences of teaching and learning involving older and younger siblings were investigated in 39 middle-class dyads over a 2-year period in early childhood. Siblings were observed during ongoing interactions in the home setting for 6 90-min sessions at both Time 1 (older sibling "M" age = 4.4 years; younger sibling…

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

PubMed

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Stereometric parameters change vs. Topographic Change Analysis (TCA) agreement in Heidelberg Retina Tomography III (HRT-3) early detection of clinical significant glaucoma progression.

PubMed

Dascalu, A M; Cherecheanu, A P; Stana, D; Voinea, L; Ciuluvica, R; Savlovschi, C; Serban, D

2014-01-01

to investigate the sensitivity and specificity of the stereometric parameters change analysis vs. Topographic Change Analysis in early detection of glaucoma progression. 81 patients with POAG were monitored for 4 years (GAT monthly, SAP at every 6 months, optic disc photographs and HRT3 yearly). The exclusion criteria were other optic disc or retinal pathology; topographic standard deviation (TSD>30; inter-test variation of reference height>25 μm. The criterion for structural progression was the following: at least 20 adjacent super-pixels with a clinically significant decrease in height (>5%). 16 patients of the total 81 presented structural progression on TCA. The most useful stereometric parameters for the early detection of glaucoma progression were the following: Rim Area change (sensitivity 100%, specificity 74.2% for a "cut-off " value of -0.05), C/D Area change (sensitivity 85.7%, specificity 71.5% for a "cut off " value of 0.02), C/D linear change (sensitivity 85.7%, specificity 71.5% for a "cut-off " value of 0.02), Rim Volume change (sensitivity 71.4%, specificity 88.8% for a "cut-off " value of -0.04). RNFL Thickness change (<0) was highly sensitive (82%), but less specific for glaucoma progression (45,2%). Changes of the other stereometric parameters have a limited diagnostic value for the early detection of glaucoma progression. TCA is a valuable tool for the assessment of the structural progression in glaucoma patients and its inter-test variability is low. On long-term, the quantitative analysis according to stereometric parameters change is also very important. The most relevant parameters to detect progression are RA, C/D Area, Linear C/D and RV.

Early Statin Use and the Progression of Alzheimer Disease: A Total Population-Based Case-Control Study.

PubMed

Lin, Feng-Cheng; Chuang, Yun-Shiuan; Hsieh, Hui-Min; Lee, Tzu-Chi; Chiu, Kuei-Fen; Liu, Ching-Kuan; Wu, Ming-Tsang

2015-11-01

The protective effect of statin on Alzheimer disease (AD) is still controversial, probably due to the debate about when to start the use of statin and the lack of any large-scale randomized evidence that actually supports the hypothesis. The purpose of this study was to examine the protective effect of early statin use on mild-to-moderate AD in the total Taiwanese population.This was a total population-based case-control study, using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The study patients were those with newly diagnosed dementia (ICD-9 290.x) and prescribed any acetylcholinesterase inhibitors (AChEI) from the Taiwan National Health Insurance dataset in 1997 to 2008. The newly diagnosed eligible mild-to-moderate AD patients were traced from the dates of their index dates, which was defined as the first day to receive any AChEI treatment, back to 1 year (exposure period) to categorize them into AD with early statin use and without early statin use. Early statin use was defined as patients using statin before AChEI treatment. Alzheimer disease patients with early statin use were those receiving any statin treatment during the exposure period. Then, we used propensity-score-matched strategy to match these 2 groups as 1:1. The matched study patients were followed-up from their index dates. The primary outcome was the discontinuation of AChEI treatment, indicating AD progression.There were 719 mild-to-moderate AD-paired patients with early statin use and without early statin use for analyses. Alzheimer disease progression was statistically lower in AD patients with early statin use than those without (P = 0.00054). After adjusting for other covariates, mild-to-moderate AD patients with early stain use exhibited a 0.85-risk (95% CI = 0.76-0.95, P = 0.0066) to have AD progression than those without.Early statin use was significantly associated with a reduction in AD progression in mild-to-moderate AD patients. The future randomized trial studies can confirm our findings.

Early low-grade gastric MALToma rarely transforms into diffuse large cell lymphoma or progresses beyond the stomach and regional lymph nodes.

PubMed

Liu, Ting-Yun; Dei, Pei-Han; Kuo, Sung-Hsin; Lin, Chung-Wu

2010-06-01

Gastric mucosa-associated lymphoid tissue lymphoma (MALToma) usually presents at an early stage involving only the stomach and/or regional lymph nodes. Although a sequential transformation from low-grade gastric MALToma (GM) to high-grade GM to secondary diffuse large B-cell lymphoma (DLBCL) is commonly assumed, documented cases of transformation are rare. We aim to determine the frequency of transformation. We identified 55 early low-grade GMs, 18 early high-grade GMs, and 13 advanced GMs at the National Taiwan University Hospital from 1995 to 2005. The median follow-up time was 59 months. We found that only one early low-grade GM and two early high-grade GMs transformed into secondary DLBCLs and progressed outside the stomach and regional lymph nodes. Significantly, we identified 13 low-grade GMs that were refractory to Helicobacter eradication therapy or relapsed after initial response. All 13 cases had been followed-up for at least 3 years without development of secondary DLBCLs. The frequency of transformation for early low-grade GM was less than 2% (1/55). Although two lymphoma-unrelated mortalities were identified, none of the 55 patients with early-low grade GMs died of the disease. Compared with chronic lymphocytic leukemia, which has a 16% transformation rate and a median transformation time of 24 months, we conclude that early low-grade GM rarely transforms into secondary DLBCL or progresses beyond the stomach. Without transformation or progression, patients with early low-grade GM rarely die of the disease and should be treated conservatively. Copyright (c) 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

Rehabilitation and education are underutilized for mild stroke and TIA sufferers.

PubMed

Faux, Steven G; Arora, Pooja; Shiner, Christine T; Thompson-Butel, Angelica G; Klein, Linda A

2018-06-01

Transient ischemic attack (TIA) and mild stroke represent a large proportion of cerebrovascular events, at high risk of being followed by recurrent, serious events. The importance of early education addressing risk management, secondary prevention and lifestyle modifications is the centerpiece of further stroke prevention. However, delivering education and rehabilitation to this population can be complex and challenging. Via synthesis of a narrative review and clinical experience, we explore the unique and inherent complexities of rehabilitation management and education provision for patients following mild stroke and TIA. A considerable proportion of TIA/mild stroke survivors have ongoing rehabilitation needs that are poorly addressed. The need for rehabilitation in these patients is often overlooked, and available assessment tools lack the sensitivity to identify common subtle impairments in cognition, mood, language and fatigue. Active and accessible education interventions need to be initiated early after the event, and integrated with ongoing rehabilitation management. Priority areas in need of future development in this field are highlighted and discussed. Implications for rehabilitation Survivors of mild stroke and TIA have ongoing unmet rehabilitation needs and require a unique approach to rehabilitation and education. Rehabilitation needs are difficult to assess and poorly addressed in this cohort, where available assessment tools lack the sensitivity required to identify subtle impairments. Education needs to be initiated early after the event and involve active engagement of the patient in order to improve stroke knowledge, mood and motivate adherence to lifestyle modifications and secondary prevention. Rehabilitation physicians are currently an underutilized resource, who should be more involved in the management of all patients following TIA or mild stroke.

Recent progress in chemical and chemoenzymatic synthesis of carbohydrates.

PubMed

Muthana, Saddam; Cao, Hongzhi; Chen, Xi

2009-12-01

The important roles that carbohydrates play in biological processes and their potential application in diagnosis, therapeutics, and vaccine development have made them attractive synthetic targets. Despite ongoing challenges, tremendous progresses have been made in recent years for the synthesis of carbohydrates. The chemical glycosylation methods have become more sophisticated and the synthesis of oligosaccharides has become more predictable. Simplified one-pot glycosylation strategy and automated synthesis are increasingly used to obtain biologically important glycans. On the other hand, chemoenzymatic synthesis continues to be a powerful alternative for obtaining complex carbohydrates. This review highlights recent progress in chemical and chemoenzymatic synthesis of carbohydrates with a particular focus on the methods developed for the synthesis of oligosaccharides, polysaccharides, glycolipids, and glycosylated natural products.

Recent Progress in Chemical and Chemoenzymatic Synthesis of Carbohydrates

PubMed Central

Muthana, Saddam; Cao, Hongzhi; Chen, Xi

2011-01-01

Summary The important roles that carbohydrates play in biological processes and their potential application in diagnosis, therapeutics, and vaccine development have made them attractive synthetic targets. Despite ongoing challenges, tremendous progresses have been made in recent years for the synthesis of carbohydrates. The chemical glycosylation methods have become more sophisticated and the synthesis of oligosaccharides has become more predictable. Simplified one-pot glycosylation strategy and automated synthesis are increasingly used to obtain biologically important glycans. On the other hand, chemoenzymatic synthesis continues to be a powerful alternative for obtaining complex carbohydrates. This review highlights recent progress in chemical and chemoenzymatic synthesis of carbohydrates with a particular focus on the methods developed for the synthesis of oligosaccharides, polysaccharides, glycolipids, and glycosylated natural products. PMID:19833544

[What's new in pediatric dermatology].

PubMed

Czernielewski, Justine; Hohl, Daniel

2015-04-01

Progress in paediatric dermatology is achieved in both research and therapeutic fields. In infectiology, scabies and bed bugs are a scourge for dermatologists, with an important recent outbreak. This article describes the fundamental clinical signs to look for, when suspecting such diagnosis. Hair dermatoscopy seems to be also very precious as a new tool for the diagnosis of ringworm. Regarding eczemas, atopic dermatitis is supported by S. Aureus's skin colonization, the target of eradication of new products in ongoing studies. We will also explain the role of Hemangiol, recently marketed in Switzerland for the treatment of haemangiomas. Alternative beta blockers have also a large number of ongoing projects in the dermatological vascular diseases field. Other various news is to be discovered....

Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure.

PubMed

Miller, Wayne L; Borgeson, Daniel D; Grantham, J Aaron; Luchner, Andreas; Redfield, Margaret M; Burnett, John C

2015-02-01

Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: (i) high sodium [250 mEq (5.8 g) per day, n =6]; (ii) standard sodium [58 mEq (1.3 g) per day, n =6]; and (iii) sodium restriction [11 mEq (0.25 g) per day, n =6]. During the 38-day study, haemodynamics, renal function, plasma renin activity (PRA), and aldosterone were measured. Changes in haemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups; however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.

Lung Cancers Associated with Cystic Airspaces: Underrecognized Features of Early Disease.

PubMed

Sheard, Sarah; Moser, Joanna; Sayer, Charlie; Stefanidis, Konstantinos; Devaraj, Anand; Vlahos, Ioannis

2018-01-01

Early lung cancers associated with cystic airspaces are increasingly being recognized as a cause of delayed diagnoses-owing to data gathered from screening trials and encounters in routine clinical practice as more patients undergo serial imaging. Several morphologic subtypes of cancers associated with cystic airspaces exist and can exhibit variable patterns of progression as the solid elements of the tumor grow. Current understanding of the pathogenesis of these malignancies is limited, and the numbers of cases reported in the literature are small. However, several tumor cell types are represented in these lesions, with adenocarcinoma predominating. The features of cystic airspaces differ among cases and include emphysematous bullae, congenital or fibrotic cysts, subpleural blebs, bronchiectatic airways, and distended distal airspaces. Once identified, these cystic lesions pose management challenges to radiologists in terms of distinguishing them from benign mimics of cancer that are commonly seen in patients who also are at increased risk of lung cancer. Rendering a definitive tissue-based diagnosis can be difficult when the lesions are small, and affected patients tend to be in groups that are at higher risk of requiring biopsy or resection. In addition, the decision to monitor these cases can add to patient anxiety and cause the additional burden of strained departmental resources. The authors have drawn from their experience, emerging evidence from international lung cancer screening trials, and large databases of lung cancer cases from other groups to analyze the prevalence and evolution of lung cancers associated with cystic airspaces and provide guidance for managing these lesions. Although there are insufficient data to support specific management guidelines similar to those for managing small solid and ground-glass lung nodules, these data and guidelines should be the direction for ongoing research on early detection of lung cancer. © RSNA, 2018.

The reorganization of functional architecture in the early-stages of Parkinson's disease.

PubMed

Tuovinen, Noora; Seppi, Klaus; de Pasquale, Francesco; Müller, Christoph; Nocker, Michael; Schocke, Michael; Gizewski, Elke R; Kremser, Christian; Wenning, Gregor K; Poewe, Werner; Djamshidian, Atbin; Scherfler, Christoph; Seki, Morinobu

2018-05-01

The study aim was to identify longitudinal abnormalities of functional connectivity and its relation with motor disability in early to moderately advanced stages of Parkinson's disease patients. 3.0T structural and resting-state functional MRI was performed in healthy subjects (n = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2 ± 1.2 years at baseline with a clinical follow-up of 1.5 ± 0.3 years. Resting-state fMRI analysis included region-to-region connectivity in correlation with UPDRS-III scores and computation of Global Efficiency and Degree Centrality. At baseline, patients' connectivity increased between the cerebellum and somatomotor network, and decreased between motor regions (Rolandic operculum, precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate connectivity. At 1.5 years follow-up, connectivity remained altered in the same regions identified at baseline. The cerebellum showed additional hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala compared to controls. These differences correlated with UPDRS-III scores. Seed-based connectivity revealed increased involvement of the default mode network with precentral gyrus in patients at follow-up investigation. Resting-state fMRI identified marked disturbances of the overall architecture of connectivity in Parkinson's disease. The noted alterations in cortical motor areas were associated with cerebellar hyperconnectivity in early to moderately advanced stages of Parkinson's disease suggesting ongoing attempts of recovery and compensatory mechanism for affected functions. The potential to identify connectivity alterations in regions related to both motor and attentional functions requires further evaluation as an objective marker to monitor disease progression, and medical, as well as surgical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exposure to Alcohol Content in Movies and Initiation of Early Drinking Milestones.

PubMed

Jackson, Kristina M; Janssen, Tim; Barnett, Nancy P; Rogers, Michelle L; Hayes, Kerri L; Sargent, James

2018-01-01

Exposure to alcohol content in movies has been shown to be associated with adolescent use of alcohol, including earlier onset. This study examined the influence of movie alcohol exposure on subsequent alcohol onset, considering the social context (whether the movie was viewed with a friend or parent). We examined whether media's influence holds across a spectrum of early drinking milestones: sipping (but not consuming a full drink of) alcohol, consuming a full drink of alcohol, and engaging in heavy episodic drinking (HED). Data were taken from a sample of 882 middle school youth (52% female; 24% non-White) enrolled in an ongoing study on alcohol initiation and progression. Exposure to alcohol content in films was measured using a method that combines content analysis and random assignment of movie titles to youth surveys. The hazard of initiating alcohol use (sip, full drink, HED) as a function of exposure was estimated using survival analysis. Associations were adjusted for demographic, personality, and social influence factors known to be associated with both movie exposure and alcohol use. Exposure to alcohol content was common. Hours of exposure prospectively predicted earlier onset of alcohol involvement across all outcomes. Viewing movies with friends appeared to augment the media exposure effect, in contrast to viewing movies with parents, which was not a significant predictor of initiation. Exposure to alcohol in films is involved in the entry into early stages of alcohol involvement. Findings support further investigation into the role of the media in underage drinking, especially in the context of consuming media with friends and peers. Limiting media exposure and/or stronger Federal Trade Commission oversight of movie ratings should be a priority for preventing underage drinking. Copyright © 2017 by the Research Society on Alcoholism.

Optimal Timing of Delivery among Low-Risk Women with Prior Caesarean Section: A Secondary Analysis of the WHO Multicountry Survey on Maternal and Newborn Health.

PubMed

Ganchimeg, Togoobaatar; Nagata, Chie; Vogel, Joshua P; Morisaki, Naho; Pileggi-Castro, Cynthia; Ortiz-Panozo, Eduardo; Jayaratne, Kapila; Mittal, Suneeta; Ota, Erika; Souza, João Paulo; Mori, Rintaro

2016-01-01

To investigate optimal timing of elective repeat caesarean section among low-risk pregnant women with prior caesarean section in a multicountry sample from largely low- and middle-income countries. Secondary analysis of a cross-sectional study. Twenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health. 29,647 women with prior caesarean section and no pregnancy complications in their current pregnancy who delivered a term singleton (live birth and stillbirth) at gestational age 37-41 weeks by pre-labour caesarean section, intra-partum caesarean section, or vaginal birth following spontaneous onset of labour. We compared the rate of short-term adverse maternal and newborn outcomes following pre-labour caesarean section at a given gestational age, to those following ongoing pregnancies beyond that gestational age. Severe maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality. Odds of neonatal morbidity and intra-hospital early neonatal mortality were 0.48 (95% confidence interval [CI] 0.39-0.60) and 0.31 (95% CI 0.16-0.58) times lower for ongoing pregnancies compared to pre-labour caesarean section at 37 weeks. We did not find any significant change in the risk of severe maternal outcomes between pre-labour caesarean section at a given gestational age and ongoing pregnancies beyond that gestational age. Elective repeat caesarean section at 37 weeks had higher risk of neonatal morbidity and mortality compared to ongoing pregnancy, however risks at later gestational ages did not differ between groups.

RISA progress in the development of drought indicators to support decision making

NASA Astrophysics Data System (ADS)

Close, S.; Simpson, C.

2015-12-01

Communities around the country are increasingly recognizing the need to plan for water shortages and long-term drought. To build preparedness and help communities manage risk, researchers funded by NOAA's National Integrated Drought Information System (NIDIS) Coping with Drought initiative through the Regional Integrated Sciences and Assessments (RISA) program are working to better understand these impacts across the country and work with communities and resource managers to develop adaptation strategies that meet their needs. The Coping with Drought initiative supports research involving the use of climate predictions and forecast information in decision-making across a range of sectors including agriculture, natural and water resources management, and public health. As a component of this initiative, the RISA program supported research and engagement to develop indicators of drought designed to be of most use to managers and planners grappling with severe and in some cases ongoing drought in their regions. Indicators are being developed for coastal ecosystems in the Carolinas, water management in California, and native communities in Arizona. For instance, the California Nevada Applications Program (CNAP) RISA developed a percentile-based indicator system for analyzing historic droughts and characterizing the ongoing California drought. And in the Southwest, the Climate Assessment for the Southwest (CLIMAS) RISA has been working with the Hopi community on drought monitoring and planning to develop the first-ever Hopi Quarterly Drought Status Report which integrates scientific and local knowledge about drought. This presentation will discuss RISA's role in developing drought indicators based on engagement with decision makers and how this work fits into the larger role that RISAs are playing in the development of the NIDIS Regional Drought Early Warning Systems across the U.S.

Curriculum-Based Measurement Performance Indicators: A Tool for Undergraduate Calculus Students to Inform and Direct Their Learning Behavior

ERIC Educational Resources Information Center

Sturges, Linda W.

2010-01-01

The present study investigated the extent to which providing students with individualized performance feedback informed and directed their learning behavior. Individualized performance feedback was delivered to students using curriculum-based measurement progress indicators, either as a visual representation of ongoing performance in the form of a…

The Social World, the Creative Self, and the Ongoing Achievement of Freedom

ERIC Educational Resources Information Center

Mayer, Susan Jean

2017-01-01

As an educator, Maxine Greene returned repeatedly to the dynamic transaction that John Dewey had theorized between a vital social world and individual creativity. With Dewey, she viewed mutually transformative relations with others as the wellspring of all personal growth and social progress and as key to achieving a form of freedom that both…

The Pipeline and Student Perceptions of Schooling: Good News and Bad News.

ERIC Educational Resources Information Center

Moses, Michele S.; And Others

The existence of a math/science "ipieline" in public schooling is well documented in which the number of female students, students with lower socioeconomic status, and students of color in proportion to white males in advanced math and science progressively shrinks during high school. As part of an ongoing gender equity project, separate versions…

Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy

ERIC Educational Resources Information Center

Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

2009-01-01

Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

Gamification of Learning and Teaching in Schools--A Critical Stance

ERIC Educational Resources Information Center

Buck, Marc Fabian

2017-01-01

The ongoing transformation of learning and teaching is one facet of the progressing digitalization of all aspects of life. Gamification's aim is to change learning for the better by making use of the motivating effects of (digital) games and elements typical of games, like experience points, levelling, quests, rankings etc. Especially in the light…

An Evaluation of the Chicago Public Schools' Efforts To Relieve Student Overcrowding at Elementary Schools. Progress Report.

ERIC Educational Resources Information Center

Valdez, Virginia

To address the inadequate condition of school buildings across the city, the Chicago Public Schools (CPS) established a Capital Improvement Program (CIP) in 1996, an ongoing plan for reviewing and upgrading CPS infrastructure over 5 years. Capital projects include additions, annexes, new replacement schools, and new area schools. This report…

Teacher Effectiveness in the Formative Use of a Mathematical Assessment

ERIC Educational Resources Information Center

Collette, Lisa Audrey

2012-01-01

In current research literature, formative assessment has been identified as having the potential for tracking student progress to ensure high-stakes test preparedness. Formative assessment has several shades of meaning. This study defines it as an ongoing process that utilizes all of the moment-by-moment day-by-day pieces of data that can be…

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…

Preconditions for Post-Employment Learning: Preliminary Results from Ongoing Research

ERIC Educational Resources Information Center

Salter, Linda

2011-01-01

This article describes the first phase of a two-phase, mixed-method study. The study, now in progress, explores how and to what extent willingness to engage in learning in mature adulthood is influenced by prior experiences and specific individual personality variables, such as perceived locus of control and degree of self-efficacy. Study…

Final Report of Activities for International Women's Year in the Department of Health, Education, and Welfare.

ERIC Educational Resources Information Center

Department of Health, Education, and Welfare, Washington, DC. Federal Women's Bureau.

Descriptions are given of mission-oriented or programmatic activities for or of concern to women, ongoing or initiated by the Department of Health, Education and Welfare during International Women's Year. Extensive comments are made about background and progress of programs, research, workshops, and other activities in the following eight…

When Is 100% Not 100%? The Use of Safe Harbor to Make Adequate Yearly Progress

ERIC Educational Resources Information Center

Polikoff, Morgan S.; Wrabel, Stephani L.

2013-01-01

Debate over the design of state and federal accountability systems is an important ongoing issue for policy makers. As we move toward next-generation accountability through No Child Left Behind's (NCLB) waivers and reauthorization drafts, it is important to understand the implementation and effects of key elements of prior accountability systems.…

Putting Faces on the Data: What Great Leaders Do!

ERIC Educational Resources Information Center

Sharratt, Lyn; Fullan, Michael

2012-01-01

Students are people--not data. Assessment data can bury you or give you focused information on how to reach every student. "Putting Faces on the Data" shows how to develop a common language for sharing all students' progress with all teachers and leaders and how to use ongoing assessment to inform instruction. Based on worldwide research from more…

"Monkey in a Cage": The Complicated Loyalties of Mid-Level Academic Women Working in Higher Education

ERIC Educational Resources Information Center

Vongalis-Macrow, Athena

2012-01-01

Loyalty raises a dilemma for women's career progression and leadership because it signals confidence in the organisation, despite the ongoing constraints that organisations present for women and their leadership aspirations. The research investigates women's loyalty in the context of higher education. Focussing on a select group of mid-level…

Assessment without Testing: Using Performance Measures Embedded in a Technology-Based Instructional Program as Indicators of Reading Ability

ERIC Educational Resources Information Center

Mitchell, Alison; Baron, Lauren; Macaruso, Paul

2018-01-01

Screening and monitoring student reading progress can be costly and time consuming. Assessment embedded within the context of online instructional programs can capture ongoing student performance data while limiting testing time outside of instruction. This paper presents two studies that examined the validity of using performance measures from a…

3 CFR 8853 - Proclamation 8853 of August 31, 2012. National Ovarian Cancer Awareness Month, 2012

Code of Federal Regulations, 2013 CFR

2013-01-01

... lives to ovarian cancer. They are mothers and daughters, sisters and grandmothers, community members and... provider. To learn more, visit www.Cancer.gov. Ongoing progress in science and medicine is moving us... condition. Ovarian cancer affects the lives of far too many women every year, and the tragedy it leaves in...

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

Kartsaklis, Christos; Civario, G

This paper discusses an ongoing progress regarding the development of a Java-based library for rapid kernel prototyping in NVIDIA PTX and PTX instruction scheduling. It is aimed at developers seeking total control of emitted PTX, highly parametric emission of, and tunable instruction reordering. It is primarily used for code development at ICHEC but is also hoped that NVIDIA GPU community will also find it beneficial.

An ECG Lab Project for Teaching Signal Conditioning Systems in a Master's Degree in Mechatronic Engineering

ERIC Educational Resources Information Center

Martín, Francisco Javier Ferrero; Martínez, Alberto López; Llopis, Marta Valledor; Rodriguez, Juan Carlos Campo; Viejo, Cecilio Blanco; Vershinin, Yuri A.

2015-01-01

Ongoing technological progress in measurement systems triggered the development of an in­novative, hands-on teaching program to help students toward a fuller understanding of recent changes in the field. This paper presents a lab project that links theoretical principles with the practical issues of signal conditioning systems. This is…

A Humanistic Approach to Criterion Referenced Testing.

ERIC Educational Resources Information Center

Wilson, H. A.

Test construction is not the strictly logical process that we might wish it to be. This is particularly true in a large on-going project such as the National Assessment of Educational Progress (NAEP). Most of the really deep questions can only be answered by the exercise of well-informed human judgment. Criterion-referenced testing is still a term…

The Techy Teacher/Using Data to Personalize Learning

ERIC Educational Resources Information Center

Tucker, Catlin

2015-01-01

Technology makes it easier than ever for educators to generate meaningful, ongoing data to inform their teaching, track student progress, and personalize learning. When the author began to explore how she could use technology to quickly assess student skills, data became exciting and took on a new role in her teaching practice. Now she uses data…

Competences of Mathematical Modelling of High School Students

ERIC Educational Resources Information Center

Sekerak, Josef

2010-01-01

Thanks to technological progress the world becomes more and more complicated. People stand in front of new and difficult problems that need to be solved. These are problems, the solutions of which are not universal, and cannot be learned. Many solutions require specific data that cannot be learned, as new data is part of the ongoing generation of…

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

PubMed

Bendaly, Edmond; Dalal, Anand A; Culver, Kenneth; Galebach, Philip; Bocharova, Iryna; Foster, Rebekah; Sasane, Medha; Macalalad, Alexander R; Guérin, Annie

2017-05-01

This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and 10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8 months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to assess the gastrointestinal tolerability of ceritinib 450 and 600 mg with low-fat meals. Novartis Pharmaceutical Corporation.

Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinson's Disease

PubMed Central

Vezoli, Julien; Fifel, Karim; Leviel, Vincent; Dehay, Colette; Kennedy, Henry; Cooper, Howard M.; Gronfier, Claude; Procyk, Emmanuel

2011-01-01

Background It is increasingly recognized that non-motor symptoms are a prominent feature of Parkinson's disease and in the case of cognitive deficits can precede onset of the characteristic motor symptoms. Here, we examine in 4 monkeys chronically treated with low doses of the neurotoxin MPTP the early and long-term alterations of rest-activity rhythms in relationship to the appearance of motor and cognitive symptoms. Methodology/Principal Findings Behavioral activity recordings as well as motor and cognitive assessments were carried out continuously and in parallel before, during and for several months following MPTP-treatment (12–56 weeks). Cognitive abilities were assessed using a task that is dependent on the functional integrity of the fronto-striatal axis. Rest-activity cycles were monitored continuously using infrared movement detectors of locomotor activity. Motor impairment was evaluated using standardized scales for primates. Results show that MPTP treatment led to an immediate alteration (within one week) of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only became apparent 3 to 5 weeks after initiating chronic MPTP administration. In three of the four animals studied, clinical scores returned to control levels 5–7 weeks following cessation of MPTP treatment. In contrast, both cognitive deficits and chronobiological alterations persisted for many months. Levodopa treatment led to an improvement of cognitive performance but did not affect rest-activity rhythms in the two cases tested. Conclusions/Significance Present results show that i) changes in the rest activity cycles constituted early detectable consequences of MPTP treatment and, along with cognitive alterations, characterize the presymptomatic stage; ii) following motor recovery there is a long-term persistence of non-motor symptoms that could reflect differential underlying compensatory mechanisms in these domains; iii) the progressive MPTP-monkey model of presymptomatic ongoing parkinsonism offers possibilities for in-depth studies of early non-motor symptoms including sleep alterations and cognitive deficits. PMID:21887350

Imaging the Hot Stellar Content of Early Type Galaxies

NASA Astrophysics Data System (ADS)

Bertola, Francesco

1991-07-01

WE PROPOSE TO IMAGE WITH THE FOC IN THE F/96 CONFIGURATION FIVE EARLY TYPE GALAXIES IN FOUR PASSBANDS CENTERED AT 1500 A, 2200 A, 2800 A AND 3400 A. WHEN COUPLED WITH PHOTOMETRY OBTAINED FROM THE GROUND OUR OBSERVATIONS WILL ALLOW US TO DERIVE COMPLETE SED OF THESE GALAXIES AS A FUNCTION OF THE DISTANCE FROM THE CENTER. THIS IS A KEY STEP TOWARDS THE UNDERSTANDING OF STELLAR POPULATIONS - IN PARTICULAR THE ONE RESPONSIBLE FOR THE UV EMISSION - IN EARLY TYPE GALAXIES AND WILL PROVIDE IMPORTANT INSIGHT IN THEIR FORMATION AND EVOLUTION. WE PLAN TO OBSERVE NGC 1399, NGC 2681, NGC 4552, NGC 5018 AND NGC 4627 WHICH SAMPLE A WIDE RANGE OF INTRINSIC PROPERTIES AS INDICATED BY PREVIOUS IUE OBSERVATIONS. FOR NGC 4627 THERE IS EVIDENCE OF ONGOING STAR FORMATION AND THE HST WILL BE ABLE TO SHOW THE CHARACTERISTIC CLUMPINESS. NGC 2681 HAD A STARBUST OF AGE GREATER THAN 1 GYR. NGC 4552 IS ONE OF THE MOST METAL RICH GALAXY KNOWN. NGC 1399 HAS THE SAME METALLICITY AND LUMINOSITY OF THE PREVIOUS GALAXY BUT IS A MUCH STRONGER X-RAY EMITTER. NGC 5018 IS A VERY GOOD CANDIDATE FOR ONGOING STAR FORMATION. WE BELIEVE IN THIS WAY WE CAN OBTAIN SED FOR THE TWO-DIMENSIONAL IMAGES OF EARLY TYPE GALAXIES FROM BROAD BAND IMAGING ALONE. THE CALIBRATION OF OUR FILTER SYSTEM WILL ALLOW US TO APPLY IT TO THE BIDIMENSIONAL ANALYSIS OF THE GENERAL SAMPLE OF EARLY TYPE GALAXIES.

Revisiting a Progressive Pedagogy. The Developmental-Interaction Approach. SUNY Series, Early Childhood Education: Inquiries and Insights.

ERIC Educational Resources Information Center

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

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

Shuttle Risk Progression by Flight

NASA Technical Reports Server (NTRS)

Hamlin, Teri; Kahn, Joe; Thigpen, Eric; Zhu, Tony; Lo, Yohon

2011-01-01

Understanding the early mission risk and progression of risk as a vehicle gains insights through flight is important: . a) To the Shuttle Program to understand the impact of re-designs and operational changes on risk. . b) To new programs to understand reliability growth and first flight risk. . Estimation of Shuttle Risk Progression by flight: . a) Uses Shuttle Probabilistic Risk Assessment (SPRA) and current knowledge to calculate early vehicle risk. . b) Shows impact of major Shuttle upgrades. . c) Can be used to understand first flight risk for new programs.

The early Earth Observing System reference handbook: Earth Science and Applications Division missions, 1990-1997

NASA Technical Reports Server (NTRS)

1990-01-01

Prior to the launch of the Earth Observing System (EOS) series, NASA will launch and operate a wide variety of new earth science satellites and instruments, as well as undertake several efforts collecting and using the data from existing and planned satellites from other agencies and nations. These initiatives will augment the knowledge base gained from ongoing Earth Science and Applications Division (ESAD) programs. This volume describes three sets of ESAD activities -- ongoing exploitation of operational satellite data, research missions with upcoming launches between now and the first launch of EOS, and candidate earth probes.

Semantic-Web Technology: Applications at NASA

NASA Technical Reports Server (NTRS)

Ashish, Naveen

2004-01-01

We provide a description of work at the National Aeronautics and Space Administration (NASA) on building system based on semantic-web concepts and technologies. NASA has been one of the early adopters of semantic-web technologies for practical applications. Indeed there are several ongoing 0 endeavors on building semantics based systems for use in diverse NASA domains ranging from collaborative scientific activity to accident and mishap investigation to enterprise search to scientific information gathering and integration to aviation safety decision support We provide a brief overview of many applications and ongoing work with the goal of informing the external community of these NASA endeavors.

Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival

PubMed Central

Henkel, Jenny S; Beers, David R; Wen, Shixiang; Rivera, Andreana L; Toennis, Karen M; Appel, Joan E; Zhao, Weihua; Moore, Dan H; Powell, Suzanne Z; Appel, Stanley H

2013-01-01

In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression. To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T-lymphocytes from patients were assessed by flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, TGF-β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients. A 3.5-year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at collection and predictive of future rapid progression and attenuated survival. Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients. PMID:23143995

Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

PubMed

Shiroyama, Takayuki; Suzuki, Hidekazu; Tamiya, Motohiro; Tamiya, Akihiro; Tanaka, Ayako; Okamoto, Norio; Nakahama, Kenji; Taniguchi, Yoshihiko; Isa, Shun-Ichi; Inoue, Takako; Imamura, Fumio; Atagi, Shinji; Hirashima, Tomonori

2018-01-01

Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27-87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil-to-lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44-5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Case management considerations of progressive dementia in a home setting.

PubMed

Pierce, Mary Ellen

2010-01-01

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

The cost-utility of open prostatectomy compared with active surveillance in early localised prostate cancer

PubMed Central

2014-01-01

Background There is an on-going debate about whether to perform surgery on early stage localised prostate cancer and risk the common long term side effects such as urinary incontinence and erectile dysfunction. Alternatively these patients could be closely monitored and treated only in case of disease progression (active surveillance). The aim of this paper is to develop a decision-analytic model comparing the cost-utility of active surveillance (AS) and radical prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk prostate cancer. Methods A Markov model comparing PE and AS over a lifetime horizon was programmed in TreeAge from a German societal perspective. Comparative disease specific mortality was obtained from the Scandinavian Prostate Cancer Group trial. Direct costs were identified via national treatment guidelines and expert interviews covering in-patient, out-patient, medication, aids and remedies as well as out of pocket payments. Utility values were used as factor weights for age specific quality of life values of the German population. Uncertainty was assessed deterministically and probabilistically. Results With quality adjustment, AS was the dominant strategy compared with initial treatment. In the base case, it was associated with an additional 0.04 quality adjusted life years (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of €6,883 per patient (2011 prices). Considering only life-years gained, PE was more effective with an incremental cost-effectiveness ratio of €96,420/life year gained. Sensitivity analysis showed that the probability of developing metastases under AS and utility weights under AS are a major sources of uncertainty. A Monte Carlo simulation revealed that AS was more likely to be cost-effective even under very high willingness to pay thresholds. Conclusion AS is likely to be a cost-saving treatment strategy for some patients with early stage localised prostate cancer. However, cost-effectiveness is dependent on patients’ valuation of health states. Better predictability of tumour progression and modified reimbursement practice would support widespread use of AS in the context of the German health care system. More research is necessary in order to reliably quantify the health benefits compared with initial treatment and account for patient preferences. PMID:24721557

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

PubMed Central

Acharya, Sunil; Xu, Jia; Wang, Xiao; Jain, Shalini; Wang, Hai; Zhang, Qingling; Chang, Chia-Chi; Bower, Joseph; Arun, Banu; Seewaldt, Victoria; Yu, Dihua

2016-01-01

Tamoxifen and aromatase inhibitors (AIs) have shown efficacy in prevention of estrogen receptor-positive (ER+) breast cancer; however, there exists no proven prevention strategy for estrogen receptor-negative (ER-) breast cancer. Up to 40% of ER- breast cancers have human epidermal growth factor receptor 2 overexpression (HER2+), suggesting HER2 signaling might be a good target for chemoprevention for certain ER- breast cancers. Here, we tested the feasibility of the HER2-targeting agent lapatinib in prevention and/or early intervention of an ER-/HER2+ early-stage breast disease model. We found that lapatinib treatment forestalled the progression of atypical ductal hyperplasia (ADH)-like acini to ductal carcinoma in situ (DCIS)-like acini in ER-/HER2+ human mammary epithelial cells (HMECs) in 3D culture. Mechanistically, we found that inhibition of HER2/Akt signaling by lapatinib led to downregulation of GLUT4 and a reduced glucose uptake in HER2-overexpressing cells, resulting in decreased proliferation and increased apoptosis of these cells in 3D culture. Additionally, our data suggest that HER2-driven glycolytic metabolic dysregulation in ER-/HER2+ HMECs might promote early-stage breast disease progression, which can be reversed by lapatinib treatment. Furthermore, low-dose lapatinib treatment, starting at the early stages of mammary grand transformation in the MMTV-neu* mouse model, significantly delayed mammary tumor initiation and progression, extended tumor-free survival, which corresponded to effective inhibition of HER2/Akt signaling and downregulation of GLUT4 in vivo. Taken together, our results indicate that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. PMID:27293993

Best Practices in e-Assessment

ERIC Educational Resources Information Center

Buzetto-More, Nicole A.; Alade, Ayodele Julius

2006-01-01

According to Martell and Calderon (2005), assessment is an ongoing process that involves planning, discussion, consensus building, reflection, measuring, analyzing, and improving based on the data and artifacts gathered about a learning objective. Impacting education from early childhood through graduate studies, the assessment movement is based…

Reggio Social Capital

ERIC Educational Resources Information Center

Stejzygier, Aneta

2009-01-01

The paper presents the social capital as the essential element of success of the Reggio Emilia preschools known for their unique approach to the early childhood education. The collaborative effort is introduced through examples of the currently ongoing "Reggio Narrates" project of Reggio preschools, the "Dialogue with the…

Effect of disease stage on progression of hydroxychloroquine retinopathy.

PubMed

Marmor, Michael F; Hu, Julia

2014-09-01

Hydroxychloroquine sulfate retinopathy can progress after the drug is stopped. It is not clear how this relates to the stage of retinopathy or whether early screening with modern imaging technology can prevent progression and visual loss. To determine the relationship between progression of retinopathy and the severity of disease using objective data from optical coherence tomography and assess the value of early screening for the toxic effects of hydroxychloroquine. Clinical findings in patients with hydroxychloroquine retinopathy were monitored with repeated anatomical and functional examinations for 13 to 40 months after the drug was stopped in a referral practice in a university medical center. Eleven patients participated, with the severity of toxic effects categorized as early (patchy parafoveal damage shown on field or objective testing), moderate (a 50%-100% parafoveal ring of optical coherence tomography thinning but intact retinal pigment epithelium), and severe (visible bull's-eye damage). Visual acuity, white 10-2 visual field pattern density plots, fundus autofluorescence, spectral-density optical coherence tomography cross sections, thickness (from cube diagrams), and ellipsoid zone length. Visual acuity and visual fields showed no consistent change. Fundus autofluorescence showed little or no change except in severe cases in which the bull's-eye damage expanded progressively. Optical coherence tomography cross sections showed little visible change in early and moderate cases but progressive foveal thinning (approximately 7 μm/y) and loss of ellipsoid zone (in the range of 100 μm/y) in severe cases, which was confirmed by quantitative measurements. The measurements also showed some foveal thinning (approximately 4 μm/y) and deepening of parafoveal loss in moderate cases, but the breadth of the ellipsoid zone remained constant in both early and moderate cases. A few cases showed a suggestion of ellipsoid zone improvement. Patients with hydroxychloroquine retinopathy involving the retinal pigment epithelium demonstrated progressive damage on optical coherence tomography for at least 3 years after the drug was discontinued, including loss of foveal thickness and cone structure. Cases recognized before retinal pigment epithelium damage retained foveal architecture with little retinal thinning. Early recognition of hydroxychloroquine toxic effects before any fundus changes are visible, using visual fields and optical coherence tomography (along with fundus autofluorescence and multifocal electroretinography as indicated), will greatly minimize late progression and the risk of visual loss.

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

PubMed

Pichler, Raimund H; de Boer, Ian H

2010-08-01

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

An ongoing process: a qualitative study of how the alcohol-dependent free themselves of addiction through progressive abstinence.

PubMed

Yeh, Mei-Yu; Che, Hui-Lian; Wu, Shu-Mei

2009-11-24

Most people being treated for alcoholism are unable to successfully quit drinking within their treatment programs. In few cases do we know the full picture of how abstinence is achieved in Taiwan. We tracked processes of abstinence in alcohol-dependency disorders, based on study evidence and results. This research explores the process of recovery from the viewpoint of the alcohol-dependent. Semi-structured interviews were conducted in two different settings, using purpose sampling, during 2003-2004. The data were analyzed using content analysis. Participants were 32 adults, purposefully selected from an Alcoholics Anonymous group and a psychiatric hospital in North Taiwan. We found that the abstinence process is an ongoing process, in which the alcohol-dependent free themselves of addiction progressively. This process never ends or resolves in complete recovery. We have identified three stages in the struggle against alcoholism: the Indulgence, Ambivalence and Attempt (IAA) cycle, in which the sufferer is trapped in a cycle of attempting to give up and failing; the Turning Point, in which a Personal Nadir is reached, and the Ongoing Process of abstinence, in which a constant effort is made to remain sober through willpower and with the help of support groups. We also discuss Influencing Factors that can derail abstinence attempts, pushing the sufferer back into the IAA cycle. This study provides important points of reference for alcohol and drug service workers and community healthcare professionals in Taiwan, casting light on the abstinence process and providing a basis for intervention or rehabilitation services.

An ongoing process: A qualitative study of how the alcohol-dependent free themselves of addiction through progressive abstinence

PubMed Central

2009-01-01

Background Most people being treated for alcoholism are unable to successfully quit drinking within their treatment programs. In few cases do we know the full picture of how abstinence is achieved in Taiwan. We tracked processes of abstinence in alcohol-dependency disorders, based on study evidence and results. This research explores the process of recovery from the viewpoint of the alcohol-dependent. Methods Semi-structured interviews were conducted in two different settings, using purpose sampling, during 2003-2004. The data were analyzed using content analysis. Participants were 32 adults, purposefully selected from an Alcoholics Anonymous group and a psychiatric hospital in North Taiwan. Results We found that the abstinence process is an ongoing process, in which the alcohol-dependent free themselves of addiction progressively. This process never ends or resolves in complete recovery. We have identified three stages in the struggle against alcoholism: the Indulgence, Ambivalence and Attempt (IAA) cycle, in which the sufferer is trapped in a cycle of attempting to give up and failing; the Turning Point, in which a Personal Nadir is reached, and the Ongoing Process of abstinence, in which a constant effort is made to remain sober through willpower and with the help of support groups. We also discuss Influencing Factors that can derail abstinence attempts, pushing the sufferer back into the IAA cycle. Conclusion This study provides important points of reference for alcohol and drug service workers and community healthcare professionals in Taiwan, casting light on the abstinence process and providing a basis for intervention or rehabilitation services. PMID:19930698

Cost and Schedule Benchmarks for Defense Acquisition Contracts

DTIC Science & Technology

1994-09-01

and schedule deviations early Knepp & S -curves for cost S -curves couldn’t Stroble/1993 control be used Terry & EAC Indices SCI-based EAC is...completed and on-going contracts from the early 1970’ s to date. Some of the fields in the database used in determining the status of cost overruns and...Measurement Data (Christensen, 1992:20). Christensen Article David S . Christensen published an analysis of cost overruns on DoD acquisition contracts

How African American and Hispanic High School Students in an Urban Charter High School May Benefit from the Early College High School Model of Receiving College Credits?

ERIC Educational Resources Information Center

Pitchford-Nicholas, Gloria Jean

2015-01-01

The preparedness of students to enter college is an ongoing issue of national concern. The purpose of the study was to conduct a mixed method descriptive case study to answer the question: "How African-American and Hispanic High School Students in an Urban Charter High School may benefit from the Early College High School Model of receiving…

Technical Adequacy of Early Numeracy Curriculum-Based Progress Monitoring Measures for Kindergarten and First-Grade Students

ERIC Educational Resources Information Center

Hampton, David D.; Lembke, Erica S.; Lee, Young-Sun; Pappas, Sandra; Chiong, Cynthia; Ginsburg, Herbert P.

2012-01-01

The purpose of this study was to examine six early numeracy measures used to monitor the mathematics progress of kindergarten and first-grade students. Seventy-one kindergarten students and 75 first-grade students were administered the measures each week. Delayed-alternate form reliability was adequate for instructional decision making on some…

Early Childhood Education in Pakistan--Progress and Challenges

ERIC Educational Resources Information Center

Shami, Pervez A.

2009-01-01

This paper is on Early Childhood Education (ECE)--a goal of Education For All (EFA), assesses the progress of Pakistan's efforts and strategies mainly during post Dakar period 2001-02 to 2005-06 and the major challenges being encountered. The information includes analysis of National Educational Data on ECE in the light of policies and plans, EFA…

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

PubMed

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

2015-02-01

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

Abnormal-induced theta activity supports early directed-attention network deficits in progressive MCI.

PubMed

Deiber, Marie-Pierre; Ibañez, Vicente; Missonnier, Pascal; Herrmann, François; Fazio-Costa, Lara; Gold, Gabriel; Giannakopoulos, Panteleimon

2009-09-01

The electroencephalography (EEG) theta frequency band reacts to memory and selective attention paradigms. Global theta oscillatory activity includes a posterior phase-locked component related to stimulus processing and a frontal-induced component modulated by directed attention. To investigate the presence of early deficits in the directed attention-related network in elderly individuals with mild cognitive impairment (MCI), time-frequency analysis at baseline was used to assess global and induced theta oscillatory activity (4-6Hz) during n-back working memory tasks in 29 individuals with MCI and 24 elderly controls (EC). At 1-year follow-up, 13 MCI patients were still stable and 16 had progressed. Baseline task performance was similar in stable and progressive MCI cases. Induced theta activity at baseline was significantly reduced in progressive MCI as compared to EC and stable MCI in all n-back tasks, which were similar in terms of directed attention requirements. While performance is maintained, the decrease of induced theta activity suggests early deficits in the directed-attention network in progressive MCI, whereas this network is functionally preserved in stable MCI.

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.

Adolescent Literacy Programs: Costs of Implementation. Final Report from Carnegie Corporation of New York's Council on Advancing Adolescent Literacy

ERIC Educational Resources Information Center

Levin, Henry M.; Catlin, Doran; Elson, Alex

2010-01-01

Many educators and researchers have proposed reforms for dealing with the ongoing adolescent literacy crisis. Progress in strengthening young people's literacy now depends on schools a) choosing appropriate programs and b) implementing them consistently and effectively. Yet the history of school reform is littered with reforms that were adopted…

Developing a Multi Sensor Scanning System for Hardwood Inspection and Processing

Treesearch

Richard W. Conners; D.Earl Kline; Philip A. Araman

1995-01-01

For the last few years the authors as part of the Center for Automated Processing of Hardwoods have been attempting to develop a multiple sensor hardwood defect detection system. This development activity has been ongoing for approximately 6 years, a very long time in the commercial development world. This paper will report the progress that has been made and will...

Nested ocean models: Work in progress

NASA Technical Reports Server (NTRS)

Perkins, A. Louise

1991-01-01

The ongoing work of combining three existing software programs into a nested grid oceanography model is detailed. The HYPER domain decomposition program, the SPEM ocean modeling program, and a quasi-geostrophic model written in England are being combined into a general ocean modeling facility. This facility will be used to test the viability and the capability of two-way nested grids in the North Atlantic.

The Burden of Responsibility: Elite Students' Understandings of Civic Participation in Singapore

ERIC Educational Resources Information Center

Sim, Jasmine B.-Y.

2012-01-01

Elder statesman Lee Kuan Yew maintains that a society ruled by elites is necessary to provide for high growth and social progress. Elitism conjures a class divide; an ongoing concern is a disconnection between elite and the citizens it has to represent. In the tradition of political socialization, and using the case study approach, this article…

Innovative Research into Practice in Support Centers for College Athletes: Implications for the Academic Progress Rate Initiative

ERIC Educational Resources Information Center

Comeaux, Eddie

2015-01-01

Concerns about the educational experiences of Division I athletes are pervasive. Finding meaningful ways to strike a healthy balance between athletics and academics has been an ongoing struggle for colleges and universities, and this article emphasizes the need for and value of innovation in current practices. The article introduces the Career…

Effects of a Prototypical Training Program on the Implementation of Systematic Observational Data Collection on IEP Objectives for the Core Deficits of Autism Spectrum Disorders

ERIC Educational Resources Information Center

Harkins, Jessica L.

2013-01-01

Legal mandates and best practice recommendations for the education of students with autism spectrum disorders (ASD) emphasize the importance of systematic, ongoing observational data collection in order to monitor progress and demonstrate accountability. The absence of such documentation in decision-making on instructional objectives indicates a…

Therapeutic touch and dementia care: an ongoing journey.

PubMed

Doherty, Donna; Wright, Stephen; Aveyard, Barry; Sykes, Meg

2006-12-01

Touch is considered a core aspect of care provision and therapeutic relationships. Therapeutic touch allows nurses to facilitate healing and forge therapeutic relationships through touch or non-touch and maintain channels of communication often lost in dementia as the disease progresses. This article reports the findings of a research project to examine the effectiveness of therapeutic touch in dementia care.

State of the Art of Language Learning Design Using Mobile Technology: Sample Apps and Some Critical Reflection

ERIC Educational Resources Information Center

Bárcena, Elena; Read, Timothy; Underwood, Joshua; Obari, Hiroyuki; Cojocnean, Diana; Koyama, Toshiko; Pareja-Lora, Antonio; Calle, Cristina; Pomposo, Lourdes; Talaván, Noa; Ávila-Cabrera, José; Ibañez, Ana; Vermeulen, Anna; Jordano, María; Arús-Hita, Jorge; Rodríguez, Pilar; Castrillo, María Dolores; Kétyi, Andras; Selwood, Jaime; Gaved, Mark; Kukulska-Hulme, Agnes

2015-01-01

In this paper, experiences from different research groups illustrate the state-of-the-art of Mobile Assisted Language Learning (henceforth, MALL) in formal and non-formal education. These research samples represent recent and on-going progress made in the field of MALL at an international level and offer encouragement for practitioners who are…

A Longitudinal Study in Children with Sequential Bilateral Cochlear Implants: Time Course for the Second Implanted Ear and Bilateral Performance

ERIC Educational Resources Information Center

Reeder, Ruth M.; Firszt, Jill B.; Cadieux, Jamie H.; Strube, Michael J.

2017-01-01

Purpose: Whether, and if so when, a second-ear cochlear implant should be provided to older, unilaterally implanted children is an ongoing clinical question. This study evaluated rate of speech recognition progress for the second implanted ear and with bilateral cochlear implants in older sequentially implanted children and evaluated localization…

Learntime and Learning Place-Focused Forward-Oriented Design for Learning in Technology-Enhanced Classrooms

ERIC Educational Resources Information Center

Sun, Susan Y. H.

2016-01-01

This study reports on a teacher's ongoing design activities in a fully online language course when the class was in progress. The aims were, firstly, to provide first-hand experience and insight into a teacher's design work in a real-life, technology-enhanced learning (TEL) classroom; and secondly, to facilitate reflective analysis of the emerging…

College of DuPage Planning Process: College of DuPage Planning, the Foundation for Decision Making.

ERIC Educational Resources Information Center

College of DuPage, Glen Ellyn, IL. Office of Research and Planning.

At College of DuPage (CD), in Glen Ellyn, Illinois, institutional planning is a multi-level, on-going process involving continuous college-wide input. The nine schematic levels in the CD planning process are interconnected and progress from global and broad-based issues, answering such questions as why the college exists, to concrete levels…

An evaluation of substance misuse treatment providers used by an employee assistance program.

PubMed

Miller, N A

1992-05-01

Structural measures of access, continuity, and quality of substance misuse treatment services were compared in 30 fee-for-service (FFS) facilities and nine health maintenance organizations (HMOs). Probit models related effects of the provider system (FFS or HMO) and the system's structural characteristics to 243 employees' access to and outcomes from treatment. Access was decreased in Independent Practice Association (IPA)/network HMOs and in all facilities which did not employ an addictionologist or provide coordinated treatment services. When bivariate correlations were examined, both use of copayments and imposing limits to the levels of treatment covered were negatively related to access, while a facility's provision of ongoing professional development was positively associated with access. These correlations did not remain significant in the multivariate probits. Receiving treatment in a staff model HMO and facing limits to the levels of treatment covered were negatively associated with attaining sufficient progress, while receiving treatment in a facility which provided ongoing professional development was positively related to progress: these effects did not remain significant in multivariate analyses. Implications for employee assistance program (EAP) staff in their role as case managers and for EAP staff and employers in their shared role as purchasers of treatment are discussed.

Subliminal stimuli modulate somatosensory perception rhythmically and provide evidence for discrete perception.

PubMed

Baumgarten, Thomas J; Königs, Sara; Schnitzler, Alfons; Lange, Joachim

2017-03-09

Despite being experienced as continuous, there is an ongoing debate if perception is an intrinsically discrete process, with incoming sensory information treated as a succession of single perceptual cycles. Here, we provide causal evidence that somatosensory perception is composed of discrete perceptual cycles. We used in humans an electrotactile temporal discrimination task preceded by a subliminal (i.e., below perceptual threshold) stimulus. Although not consciously perceived, subliminal stimuli are known to elicit neuronal activity in early sensory areas and modulate the phase of ongoing neuronal oscillations. We hypothesized that the subliminal stimulus indirectly, but systematically modulates the ongoing oscillatory phase in S1, thereby rhythmically shaping perception. The present results confirm that, without being consciously perceived, the subliminal stimulus critically influenced perception in the discrimination task. Importantly, perception was modulated rhythmically, in cycles corresponding to the beta-band (13-18 Hz). This can be compellingly explained by a model of discrete perceptual cycles.

34 CFR 303.19 - Parent.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH DISABILITIES... in accordance with § 303.406. (b) Foster parent. Unless State law prohibits a foster parent from... extinguished under State law; and (2) The foster parent— (i) Has an ongoing, long-term parental relationship...

An Ongoing Revolution: Resource Sharing and OCLC.

ERIC Educational Resources Information Center

Nevins, Kate

1998-01-01

Discusses early developments in the Online Computer Library Center (OCLC) interlibrary loan, including use of OCLC for verification and request transmittal, improved service to patrons, internal cost control, affect on work flow and borrowing patterns. Describes advances in OCLC, including internationalization, electronic information access,…

Early adolescent deaf boys: a biopsychosocial approach.

PubMed

Feinstein, C B

1983-01-01

In this chapter I have reviewed observations from clinical consultation and group-therapy work with early adolescent deaf boys in a special day school for the deaf. I have stressed how problems in communication exert a profound effect on the lives of these youngsters, both by virtue of their past and present influence on family life and by their ongoing effect on peer-group processes and academic adjustment. Primary consideration was given to certain "here and now" aspects of these boys' lives: ongoing problems in the social fabric of their home and school; narcissistic vulnerabilities and defenses against shame; and language-processing difficulties. The ways in which these problems undermine the supportive effect of the peer group at a time when it plays a particularly important role in development were reviewed. By emphasizing current sources of difficulty, using a biopsychosocial approach, I hope to point out fruitful opportunities for significant psychiatric intervention in a psychiatrically vulnerable population whose needs for professional service have never been met.

Conflict, camps and coercion: the ongoing livelihoods crisis in Darfur.

PubMed

Buchanan-Smith, Margie; Jaspars, Susanne

2007-03-01

This paper presents the findings of a study commissioned by World Food Programme (WFP) in early 2006 to enhance understanding of how the conflict in Darfur has affected livelihoods and markets, and of the effects of food aid. The livelihoods of many in Darfur were devastated early on in the conflict, principally through the widespread looting or destruction of assets and highly restricted population movements, which struck at the heart of pre-conflict livelihoods. Livelihood strategies for most people are now restricted, poorly remunerated and often associated with high risk of attack. Patterns of coercion and exploitation have also become entrenched; and markets and trade, the lifeblood of Da fur's economy pre-conflict, severely disrupted. Against this backdrop the impact of food aid on livelihoods in Darfur has been overwhelmingly positive. The paper proposes a number of preconditions for investment in recovery in Darfur, and recommends ways in which livelihoods can be supported in the current context of ongoing conflict.

Assessing Behavioural Manifestations Prior to Clinical Diagnosis of Huntington Disease: "Anger and Irritability" and "Obsessions and Compulsions"

PubMed Central

Vaccarino, Anthony L; Anonymous; Anderson, Karen E.; Borowsky, Beth; Coccaro, Emil; Craufurd, David; Endicott, Jean; Giuliano, Joseph; Groves, Mark; Guttman, Mark; Ho, Aileen K; Kupchak, Peter; Paulsen, Jane S.; Stanford, Matthew S.; van Kammen, Daniel P; Watson, David; Wu, Kevin D; Evans, Ken

2011-01-01

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess "Anger and Irritability" and "Obsessions and Compulsions" in prHD individuals. PMID:21826116

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

PubMed

Mayo, Ray Cody; Leung, Jessica

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

Survival Outcomes and Effect of Early vs. Deferred cART Among HIV-Infected Patients Diagnosed at the Time of an AIDS-Defining Event: A Cohort Analysis

PubMed Central

Mussini, Cristina; Johnson, Margaret; d'Arminio Monforte, Antonella; Antinori, Andrea; Gill, M. John; Sighinolfi, Laura; Uberti-Foppa, Caterina; Borghi, Vanni; Sabin, Caroline

2011-01-01

Objectives We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997–2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30–270 days after AIDS event) cART. Results The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/µL and 5.2 (4.5, 5.7) log10 copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20). Conclusions Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting. PMID:22043301

Remnants of an ancient forest provide ecological context for Early Miocene fossil apes.

PubMed

Michel, Lauren A; Peppe, Daniel J; Lutz, James A; Driese, Steven G; Dunsworth, Holly M; Harcourt-Smith, William E H; Horner, William H; Lehmann, Thomas; Nightingale, Sheila; McNulty, Kieran P

2014-01-01

The lineage of apes and humans (Hominoidea) evolved and radiated across Afro-Arabia in the early Neogene during a time of global climatic changes and ongoing tectonic processes that formed the East African Rift. These changes probably created highly variable environments and introduced selective pressures influencing the diversification of early apes. However, interpreting the connection between environmental dynamics and adaptive evolution is hampered by difficulties in locating taxa within specific ecological contexts: time-averaged or reworked deposits may not faithfully represent individual palaeohabitats. Here we present multiproxy evidence from Early Miocene deposits on Rusinga Island, Kenya, which directly ties the early ape Proconsul to a widespread, dense, multistoried, closed-canopy tropical seasonal forest set in a warm and relatively wet, local climate. These results underscore the importance of forested environments in the evolution of early apes.

Genetic Insights in Barrett’s Esophagus and Esophageal Adenocarcinoma

PubMed Central

Reid, Brian J.; Paulson, Thomas G.; Li, Xiaohong

2015-01-01

Beginning in the 1980s, an alarming rise in the incidence of esophageal adenocarcinoma (EA) led to screening of patients with reflux to detect Barrett’s esophagus (BE) and surveillance of BE to detect early EA. This strategy, based on linear progression disease models, resulted in selective detection of BE that does not progress to EA over a lifetime (overdiagnosis) and missed BE that rapidly progresses to EA (underdiagnosis). Here we review the historical thought processes that resulted in this undesired outcome and the transformation in our understanding of genetic and evolutionary principles governing neoplastic progression that has come from application of modern genomic technologies to cancers and their precursors. This new synthesis provides improved strategies for prevention and early detection of EA by addressing the environmental and mutational processes that can determine “windows of opportunity” in time to detect rapidly progressing BE and distinguish it from slowly or non-progressing BE. PMID:26208895

Idiopathic Syringomyelia in a Military Helicopter Pilot.

PubMed

Schiemer, Anthony

2017-10-01

A syrinx is a fluid-filled cavity within the spinal cord. They can lead to a variety of symptoms, including limb weakness and back pain. Incidental finding of syringomyelia provides a challenge for clinicians due to the wide variety of possible symptoms. In military aviation, neurological findings in pilots can result in extensive investigation that can lead to potentially invasive management. Conversely, the potential for chronic progression of a spinal syrinx and subsequent neurological deterioration makes early identification critical. Ultimately, the discovery of a lesion may have implications for flying status and operational capability. A 25-yr-old man working as a navy Seahawk helicopter pilot presented with episodes of right arm paraesthesia and pain between the scapulae. On at least one occasion, these symptoms woke him at night. Upon magnetic resonance imaging, dilatation of the central canal in a syrinx-like pattern in the lower cervical region was noted. Neurology review suggested the finding was persistent and unlikely to be responsible for his symptoms. No surgical input was recommended. His symptoms were attributed to mild cervical spondylosis, which resolved with ongoing physiotherapy, and he was returned to flying status. This case highlights several issues involved with the incidental finding of a syringomyelia. Surgical intervention has been known to worsen symptoms. Conversely, studies have identified minimal radiological progression in cases of idiopathic syringomyelia, with fewer individuals displaying neurological deterioration. For aircrew, potentially unnecessary neurosurgical intervention poses risks to a flying career and overall operational capability.Schiemer A. Idiopathic syringomyelia in a military helicopter pilot. Aerosp Med Hum Perform. 2017; 88(10):962-965.

Natural capital and ecosystem services informing decisions: From promise to practice

PubMed Central

Guerry, Anne D.; Polasky, Stephen; Lubchenco, Jane; Chaplin-Kramer, Rebecca; Daily, Gretchen C.; Griffin, Robert; Ruckelshaus, Mary; Bateman, Ian J.; Duraiappah, Anantha; Elmqvist, Thomas; Feldman, Marcus W.; Folke, Carl; Hoekstra, Jon; Kareiva, Peter M.; Keeler, Bonnie L.; Li, Shuzhuo; McKenzie, Emily; Ouyang, Zhiyun; Reyers, Belinda; Ricketts, Taylor H.; Rockström, Johan; Tallis, Heather; Vira, Bhaskar

2015-01-01

The central challenge of the 21st century is to develop economic, social, and governance systems capable of ending poverty and achieving sustainable levels of population and consumption while securing the life-support systems underpinning current and future human well-being. Essential to meeting this challenge is the incorporation of natural capital and the ecosystem services it provides into decision-making. We explore progress and crucial gaps at this frontier, reflecting upon the 10 y since the Millennium Ecosystem Assessment. We focus on three key dimensions of progress and ongoing challenges: raising awareness of the interdependence of ecosystems and human well-being, advancing the fundamental interdisciplinary science of ecosystem services, and implementing this science in decisions to restore natural capital and use it sustainably. Awareness of human dependence on nature is at an all-time high, the science of ecosystem services is rapidly advancing, and talk of natural capital is now common from governments to corporate boardrooms. However, successful implementation is still in early stages. We explore why ecosystem service information has yet to fundamentally change decision-making and suggest a path forward that emphasizes: (i) developing solid evidence linking decisions to impacts on natural capital and ecosystem services, and then to human well-being; (ii) working closely with leaders in government, business, and civil society to develop the knowledge, tools, and practices necessary to integrate natural capital and ecosystem services into everyday decision-making; and (iii) reforming institutions to change policy and practices to better align private short-term goals with societal long-term goals. PMID:26082539

Chemistry, manufacturing and control (CMC) and clinical trial technical support for influenza vaccine manufacturers.

PubMed

Wahid, Rahnuma; Holt, Renee; Hjorth, Richard; Berlanda Scorza, Francesco

2016-10-26

With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization's (WHO's) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic. Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements. Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Epigenetic basis of sensitization to stress, affective episodes, and stimulants: implications for illness progression and prevention.

PubMed

Post, Robert M

2016-06-01

The process of sensitization (increased responsivity) to the recurrence of stressors, affective episodes, and bouts of substance abuse that can drive illness progression in the recurrent affective disorders requires a memory of and increased reactivity to the prior exposures. A wealth of studies now supports the postulate that epigenetic mechanisms underlie both normal and pathological memory processes. We selectively reviewed the literature pertinent to the role of epigenetics in behavioral sensitization phenomena and discuss its clinical implications. Epigenetics means above genetics and refers to environmental effects on the chemistry of DNA, histones (around which DNA is wound), and microRNA that change how easily genes are turned on and off. The evidence supports that sensitization to repeated stressor, affective episodes, and substance is likely based on epigenetic mechanisms and that these environmentally based processes can then become targets for prevention, early intervention, and ongoing treatment. Sensitization processes are remediable or preventable risk factors for a poor illness outcome and deserve increased clinical, public health, and research attention in the hopes of making the recurrent unipolar and bipolar affective disorders less impairing, disabling, and lethal by suicide and increased medical mortality. The findings that epigenetic chemical marks, which change in the most fundamental way how genes are regulated, mediate the long-term increased responsivity to recurrent stressors, mood episodes, and bouts of substance abuse should help change how the affective disorders are conceptualized and move treatment toward earlier, more comprehensive, and sustained pharmacoprophylaxis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Decoupling of Local Metabolic Activity and Functional Connectivity Links to Amyloid in Alzheimer's Disease.

PubMed

Scherr, Martin; Pasquini, Lorenzo; Benson, Gloria; Nuttall, Rachel; Gruber, Martin; Neitzel, Julia; Brandl, Felix; Sorg, Christian

2018-05-19

Both ongoing local metabolic activity (LMA) and corresponding functional connectivity (FC) with remote brain regions are progressively impaired in Alzheimer's disease (AD), particularly in the posterior default mode network (pDMN); however, it is unknown how these impairments interact. It is well known that decreasing mean synaptic activity of a region, i.e., decreasing LMA, reduces the region's sensitivity to afferent input from other regions, i.e., FC. We hypothesized progressive decoupling between LMA and FC in AD, which is linked to amyloid-β pathology (Aβ). Healthy adults (n=20) and Aβ+patients without memory impairment (n=9), early MCI (n=21), late MCI (n=18) and AD (n=22) were assessed by resting-state fMRI, FDG-PET, and AV-45-PET to measure FC, LMA, and Aβ of the pDMN. Coupling between LMA and FC (rLA/FC) was estimated by voxelwise correlation. RLMA/FC decreased with disease severity (F=20.09, p<0.001). This decrease was specifically associated with pDMN Aβ (r=-0.273, p=0.029) but not global Aβ (r=-0.112, p=0.378) and with the impact of Aβ on FC (i.e., rAβ/FC,r=-0.339; p=0.006). In multiple regression models rLMA/FC was also associated with memory impairment, reduced cognitive speed and flexibility, outperforming global Aβ, pDMN Aβ, pDMN LMA, and pDMN FC, respectively. Results demonstrate increasing decoupling of LMA from its FC in AD. Data suggest that decoupling is driven by local Aβ and contributes to memory decline.

Natural capital and ecosystem services informing decisions: From promise to practice.

PubMed

Guerry, Anne D; Polasky, Stephen; Lubchenco, Jane; Chaplin-Kramer, Rebecca; Daily, Gretchen C; Griffin, Robert; Ruckelshaus, Mary; Bateman, Ian J; Duraiappah, Anantha; Elmqvist, Thomas; Feldman, Marcus W; Folke, Carl; Hoekstra, Jon; Kareiva, Peter M; Keeler, Bonnie L; Li, Shuzhuo; McKenzie, Emily; Ouyang, Zhiyun; Reyers, Belinda; Ricketts, Taylor H; Rockström, Johan; Tallis, Heather; Vira, Bhaskar

2015-06-16

The central challenge of the 21st century is to develop economic, social, and governance systems capable of ending poverty and achieving sustainable levels of population and consumption while securing the life-support systems underpinning current and future human well-being. Essential to meeting this challenge is the incorporation of natural capital and the ecosystem services it provides into decision-making. We explore progress and crucial gaps at this frontier, reflecting upon the 10 y since the Millennium Ecosystem Assessment. We focus on three key dimensions of progress and ongoing challenges: raising awareness of the interdependence of ecosystems and human well-being, advancing the fundamental interdisciplinary science of ecosystem services, and implementing this science in decisions to restore natural capital and use it sustainably. Awareness of human dependence on nature is at an all-time high, the science of ecosystem services is rapidly advancing, and talk of natural capital is now common from governments to corporate boardrooms. However, successful implementation is still in early stages. We explore why ecosystem service information has yet to fundamentally change decision-making and suggest a path forward that emphasizes: (i) developing solid evidence linking decisions to impacts on natural capital and ecosystem services, and then to human well-being; (ii) working closely with leaders in government, business, and civil society to develop the knowledge, tools, and practices necessary to integrate natural capital and ecosystem services into everyday decision-making; and (iii) reforming institutions to change policy and practices to better align private short-term goals with societal long-term goals.

Idiopathic Pulmonary Fibrosis: Diagnosis and Clinical Manifestations

PubMed Central

Nakamura, Yutaro; Suda, Takafumi

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a parenchymal lung disease characterized by progressive interstitial fibrosis. The clinical course of IPF can be unpredictable and may be punctuated by acute exacerbations. Although much progress is being made in unraveling the mechanisms underlying IPF, effective therapy for improving survival remains elusive. Longitudinal disease profiling, especially in terms of clinical manifestations in a large cohort of patients, should lead to proper management of the patients and development of new treatments for IPF. Appropriate multidisciplinary assessment in ongoing registries is required to achieve this. This review summarizes the current status of the diagnosis and clinical manifestations of IPF. PMID:27625576

Progress in translational research on intracerebral hemorrhage: Is there an end in sight?

PubMed Central

Xi, Guohua; Strahle, Jennifer; Hua, Ya; Keep, Richard F.

2013-01-01

Intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype for which specific therapies and treatments remain elusive. To address this, many recent experimental and translational studies of ICH have been conducted, and these have led to several ongoing clinical trials. This review focuses on the progress of translational studies of ICH including those of the underlying causes and natural history of ICH, animal models of the condition, and effects of ICH on the immune and cardiac systems, among others. Current and potential clinical trials also are discussed for both ICH alone and with intraventricular extension. PMID:24139872

Persisting eicosanoid pathways in rheumatic diseases.

PubMed

Korotkova, Marina; Jakobsson, Per-Johan

2014-04-01

An unmet clinical need exists for early treatment of rheumatic diseases and improved treatment strategies that can better maintain remission with reduced ongoing subclinical inflammation and bone destruction. Eicosanoids form one of the most complex networks in the body controlling many physiological and pathophysiological processes, including inflammation, autoimmunity and cancer. Persisting eicosanoid pathways are thought to be involved in the development of rheumatic diseases, and targeting this pathway might enable improved treatment strategies. Several enzymes of the arachidonic acid cascade as well as eicosanoid receptors (all part of the eicosanoid pathway) are today well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases. In this Review, we outline the evidence supporting pivotal roles of eicosanoid signalling in the pathogenesis of rheumatic diseases and discuss findings from studies in animals and humans. We focus first on rheumatoid arthritis and discuss the upregulation of the cyclooxygenase and lipoxygenase pathways as most data are available in this condition. Research into the roles of eicosanoids in other rheumatic diseases (osteoarthritis, idiopathic inflammatory myopathies, systemic lupus erythematosus and gout) is also progressing rapidly and is discussed. Finally, we summarize the prospects of targeting eicosanoid pathways as anti-inflammatory treatment strategies for patients with rheumatic diseases.

Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds

PubMed Central

Badosa, Anna; Frisch, Dagmar; Green, Andy J.; Rico, Ciro; Gómez, Africa

2017-01-01

Understanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks. PMID:28276459

[TOPICS-MDS: a versatile resource for generating scientific and social knowledge for elderly care].

PubMed

van den Brink, Danielle; Lutomski, Jennifer E; Qin, Li; den Elzen, Wendy P J; Kempen, Gertrudis I J M; Krabbe, Paul F M; Steyerberg, Ewout W; Muntinga, Maaike; Moll van Charante, Eric P; Bleijenberg, Nienke; Olde Rikkert, Marcel G M; Melis, René J F

2015-04-01

Developed as part of the National Care for the Elderly Programme (NPO), TOPICS-MDS is a uniform, national database on the health and wellbeing of the older persons and caregivers who participated in NPO-funded projects. TOPICS-MDS Consortium has gained extensive experience in constructing a standardized questionnaire to collect relevant health care data on quality of life, health services utilization, and informal care use. A proactive approach has been undertaken not only to ensure the standardization and validation of instruments but also the infrastructure for external data requests. Efforts have been made to promote scientifically and socially responsible use of TOPICS-MDS; data has been available for secondary use since early 2014. Through this data sharing initiative, researchers can explore health issues in a broader framework which may have not been possible within individual NPO projects; this broader framework is highly relevant for influencing health policy. In this article, we provide an overview of the development and on-going progress of TOPICS-MDS. We further describe how information derived from TOPICS-MDS can be applied to facilitate future scientific innovations and public health initiatives to improve care for frail older persons and their caregivers.

Clinical pharmacology of novel anti-Alzheimer disease modifying medications.

PubMed

Caraci, Filippo; Bosco, Paolo; Leggio, Gian Marco; Malaguarnera, Michele; Drago, Filippo; Bucolo, Claudio; Salomone, Salvatore

2013-01-01

In recent years, efforts have been directed to develop "disease-modifying" medications to treat Alzheimer's disease (AD), able to halt or slow the pathological process. Because the earlier the treatment starts, the greater is the possibility of efficacy, it is important to set up biomarkers for early diagnosis of functional brain abnormalities, before the clinical manifestation of the overt disease. Up to now, strategies to develop disease-modifying drugs have mainly targeted β amyloid (Aβ, accumulation, aggregation, clearance) and/or tau protein (phosphorylation and aggregation). Active and passive immunotherapy is the main strategy aimed at increasing Aβ clearance. Unfortunately several candidate diseasemodifying drugs have failed in phase III clinical trials conducted in mild to moderate AD. More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. Several methological problems have been recently pointed out to explain the lack of clinical efficacy of novel disease-modifying drug-treatments; moreover, new insights in pathophysiology of AD give the premise to develop novel drug targeting. Clinical trials recently completed and/or still ongoing are discussed in the present review.

Venetoclax for the treatment of chronic lymphocytic leukemia.

PubMed

Gentile, Massimo; Petrungaro, Annamaria; Uccello, Giuseppina; Vigna, Ernesto; Recchia, Anna Grazia; Caruso, Nadia; Bossio, Sabrina; De Stefano, Laura; Palummo, Angela; Storino, Francesca; Martino, Massimo; Morabito, Fortunato

2017-11-01

Venetoclax, an orally bioavailable inhibitor of BCL-2, was approved in 2016 by the United States Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL) patients with 17p deletion [del(17p)], who have received at least one prior therapy. Areas covered: We focus on the mechanism of action of venetoclax and on the clinical trial data that led to the approval of venetoclax for CLL patients. We also review the studies in which this drug has being explored in combination with other anti-CLL drugs. Expert opinion: Data from early clinical trials have shown that venetoclax, as a single agent, is highly effective for relapsed/refractory CLL patients, including those cases with high-risk features. Furthermore, venetoclax seems to be an appropriate option for patients who progress on B-cell receptor (BCR) pathway kinase inhibitors. Venetoclax is also safe, with the most common serious adverse events being neutropenia. The risk of tumor lysis syndrome (TLS) can be reduced by a slow dose ramp-up, careful monitoring, and adequate prophylaxis. Ongoing trials will further clarify the safety and efficacy of venetoclax in combination with other drugs in both relapsed/refractory and untreated CLL patients.

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

Shiau, Celia E.; Kaufman, Zoe; Meireles, Ana M.

Interferon regulatory factor 8 (Irf8) is critical for mammalian macrophage development and innate immunity, but its role in teleost myelopoiesis remains incompletely understood. Specifically, genetic tools to analyze the role of irf8 in zebrafish macrophage development at larval and adult stages are lacking. In this study, we generated irf8 null mutants in zebrafish using TALEN-mediated targeting. Our analysis defines different requirements for irf8 at different stages. irf8 is required for formation of all macrophages during primitive and transient definitive hematopoiesis, but not during adult-phase definitive hematopoiesis starting at 5-6 days postfertilization. At early stages, irf8 mutants have excess neutrophils andmore » excess cell death in pu.1-expressing myeloid cells. Macrophage fates were recovered in irf8 mutants after wildtype irf8 expression in neutrophil and macrophage lineages, suggesting that irf8 regulates macrophage specification and survival. In juvenile irf8 mutant fish, mature macrophages are present, but at numbers significantly reduced compared to wildtype, indicating an ongoing requirement for irf8 after embryogenesis. As development progresses, tissue macrophages become apparent in zebrafish irf8 mutants, with the possible exception of microglia. Our study defines distinct requirement for irf8 in myelopoiesis before and after transition to the adult hematopoietic system.« less

Fostering learners' interaction with content: A learner-centered mobile device interface

NASA Astrophysics Data System (ADS)

Abdous, M.

2015-12-01

With the ever-increasing omnipresence of mobile devices in student life, leveraging smart devices to foster students' interaction with course content is critical. Following a learner-centered design iterative approach, we designed a mobile interface that may enable learners to access and interact with online course content efficiently and intuitively. Our design process leveraged recent technologies, such as bootstrap, Google's Material Design, HTML5, and JavaScript to design an intuitive, efficient, and portable mobile interface with a variety of built-in features, including context sensitive bookmarking, searching, progress tracking, captioning, and transcript display. The mobile interface also offers students the ability to ask context-related questions and to complete self-checks as they watch audio/video presentations. Our design process involved ongoing iterative feedback from learners, allowing us to refine and tweak the interface to provide learners with a unified experience across platforms and devices. The innovative combination of technologies built around well-structured and well-designed content seems to provide an effective learning experience to mobile learners. Early feedback indicates a high level of satisfaction with the interface's efficiency, intuitiveness, and robustness from both students and faculty.

Fungal keratitis and contact lenses: an old enemy unrecognized or a new nemesis on the block?

PubMed

Tuli, Sonal S; Iyer, Sandhya A; Driebe, William T

2007-11-01

To review studies of fungal keratitis related to contact lenses and determine whether the recent insurgence is a new phenomenon or an exacerbation of an ongoing trend. A review of the recent literature on contact lens-related fungal ulcers and a comparison to older studies. The incidence of fungal keratitis associated with contact lenses increased from 5% in the 1980s to between 10% and 25% in the 1990s and was noted to be 44% in Florida at the turn of the century. The most recent study from Florida showed that the incidence had increased from 29% in the late 1990s to 52% in the early 2000s, even before the Fusarium keratitis epidemic in 2004 and 2005. This increase mainly represented an increase in the number related to nontherapeutic contact lenses. Contact lens-related fungal keratitis was relatively rare 20 years ago. However, the incidence has progressively increased since then. Contact lens-related fungal ulcers had become more common even before the recent Fusarium keratitis epidemic. This change may be related to changing contact lens care habits and younger patients being fitted with contact lenses.

New ground-based lidar enables volcanic CO2 flux measurements.

PubMed

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

2015-09-01

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

Concepts of dental caries and their consequences for understanding the disease.

PubMed

Fejerskov, O

1997-02-01

The way in which we conceptually consider dental caries determines our choice of preventive and treatment strategy. In this paper the definition of dental caries is discussed and the related problems concerning causality are addressed. Dental caries reflects symptoms of ongoing and past disease--not the disease itself. As such, it is important to record early stages of signs of the disease, i.e. non-cavitated stages of lesion development. The dynamic nature of the processes leading to net loss of mineral (hence a lesion) is emphasized, and appreciating that caries is ubiquitous in populations around the world and initiation and progression of lesions continues lifelong leads to the logical conclusion that we can control dental caries through a variety of measures--but not truly prevent the disease. We can prevent cavities by controlling the patho-physiological events which may result in a net loss of mineral. The relative role of dental plaque in caries control is discussed in relation to the role of the many determinants which influence the likelihood for lesion development. It is concluded that several paradigms about the nature of dental caries should be reconsidered to provide the most cost-effective dental services.

[Update on Herpes Simplex Encephalitis].

PubMed

Kuroda, Hiroshi

2015-07-01

Herpes simplex encephalitis (HSE), which is caused by the herpes simplex virus (HSV), is a severe neuro-infectious disease characterized by high mortality and morbidity. We reviewed the pathomechanism, diagnosis, and treatment of HSE based on recent progress in the field. The highlighted mechanism of HSE in this review is immune-mediated tissue damage caused by host immunity. Major symptoms of HSE include psychiatric alteration, Klüver-Bucy syndrome, and amnesia, caused by frequent involvement of the limbic system. An important differential diagnosis of HSE is autoimmune limbic encephalitis, including anti-N-methyl-D-aspartate receptor encephalitis, and anti-voltage-gated K⁺ channel encephalitis. HSE is definitely diagnosed based on the detection of HSV-DNA by polymerase chain reaction and/or the detection of HSV-IgG antibody in the cerebrospinal fluid (CSF). Repeated CSF examinations are required for the accurate diagnosis of HSE. Acyclovir (ACV) plays a central role in the treatment of HSE, and its early initiation is essential for good outcome in patients with HSE. Acute administration of corticosteroids for HSE is controversial; a randomized, double-blind, placebo-controlled trial to investigate the efficacy of add-on corticosteroids to ACV is ongoing.

Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds

NASA Astrophysics Data System (ADS)

Badosa, Anna; Frisch, Dagmar; Green, Andy J.; Rico, Ciro; Gómez, Africa

2017-03-01

Understanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks.

Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

NASA Technical Reports Server (NTRS)

Radhakrishnan, Krisnan; Vyas, Ruchi J.; Murray, Matthew; Predovic, Marina; Lim, Shiyin; Bryant, Douglas; Yaqian, Duan; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

2017-01-01

Purpose: Our hypothesis predicts that blood vessels within the retina increase in density during early-stage nonproliferative diabetic retinopathy (NPDR), based on previous results of a small retrospective study. For the current prospective study, the remodeling of arteries and veins during progression of early NPDR is assessed by a repertoire of parameters that includes the fractal dimension (D(sub f) ). In complex structures such as branching vascular trees, D(sub f) is a sensitive measure of space-filing capacity. The renin-angiotensin system (RAS) is implicated in DR pathogenesis and the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population instrumental in vascular repair. Methods: Arterial and venous branching patterns were extracted from images of 6 normal controls and 3 early NPDR subjects (2 moderate, 1 mild) acquired by Heidelberg Spectralis (Registered Trademark) OCT following fluorescein angiography (FA). The vascular branching patterns were analyzed by NASAs VESsel GENeration Analysis (VESGEN) software, in which skeletonized representations were generated automatically to yield D(sub f) by the box-counting method. For binary 2D images, D(sub f) varies between limiting Euclidean dimensions of 1 and 2. Peripheral blood of diabetics and controls was collected for CD34+ CAC isolation. The gene expression of RAS in CACs was assessed by qPCR for Mas receptor to Ang-(1-7). The vasoreparative function of the CACs was measured by migration ability toward CXCL12 (SDF-1). Results: By D(sub f), venous and arterial densities were 1.370 +/- 0.006 and 1.329 +/- 0.016 for early NPDR, compared to 1.318 +/- 0.012 and 1.320 +/- 0.036 for control. The space filling capacity in early NPDR measured by D(sub f), a sensitive parameter, therefore demonstrated a pronounced increase for veins, but not for arteries. Mas receptor mRNA in CACs was increased in diabetics without DR but reduced with onset of NPDR, indicating possible loss of compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

Assessment of the Continuous Progress Report for the Early Learning Years (An Examination of Scale Construction).

ERIC Educational Resources Information Center

Tuck, Kathy D.

An evaluation was conducted to examine the structure and design of the Continuous Progress Report (CPR), an observation scale used to measure students' early developmental skills in the District of Columbia public schools. Item construction and the relative consistency of measurement constructs in the CPR were the specific focus of the evaluation.…

Realizing a Progressive Pedagogy: A Comparative Case Study of Two Reggio Emilia Preschools in San Francisco

ERIC Educational Resources Information Center

Abdelfattah, Marwa

2015-01-01

This study aims to uncover how a particular imported philosophy of early childhood education, Reggio Emilia, is implemented in the context of one public and one private preschool in San Francisco. The philosophy of Reggio Emilia is believed to be progressive and to be developmentally appropriate for children in early childhood. The study involved…

Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice.

PubMed

Miyazaki, Kazunori; Masamoto, Kazuto; Morimoto, Nobutoshi; Kurata, Tomoko; Mimoto, Takahumi; Obata, Takayuki; Kanno, Iwao; Abe, Koji

2012-03-01

The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow-metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow-metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS.

Direct conversion semiconductor detectors in positron emission tomography

NASA Astrophysics Data System (ADS)

Cates, Joshua W.; Gu, Yi; Levin, Craig S.

2015-05-01

Semiconductor detectors are playing an increasing role in ongoing research to improve image resolution, contrast, and quantitative accuracy in preclinical applications of positron emission tomography (PET). These detectors serve as a medium for direct detection of annihilation photons. Early clinical translation of this technology has shown improvements in image quality and tumor delineation for head and neck cancers, relative to conventional scintillator-based systems. After a brief outline of the basics of PET imaging and the physical detection mechanisms for semiconductor detectors, an overview of ongoing detector development work is presented. The capabilities of semiconductor-based PET systems and the current state of these devices are discussed.

Neogene ongoing tectonics in the Southern Ecuadorian Andes: analysis of the evolution of the stress field

NASA Astrophysics Data System (ADS)

Lavenu, A.; Noblet, C.; Winter, T. H.

1995-01-01

Microtectonic analysis of infilling deposits in South Ecuadorian Neogene basins brings to light a compressive stress field with σ1 along a NNE-SSW to NE-SW direction in the early Miocene, changing to an E-W direction in the Middle and Late Miocene. The syn-sedimentary deformations which affect the deposits of the basins suggest similar stress regimes due to a compressive ongoing tectonic system in the Miocene, for at least 15 Ma. There is a good correlation between rapid convergence in the Neogene and the time period during which the continental South Ecuadorian basins were deformed by compression (Quechua period).

Molecular characterization of turkey enteric coronaviruses circulating in the United States in 2012

USDA-ARS?s Scientific Manuscript database

The use of molecular diagnostic assays has allowed ongoing periodic monitoring of United States turkey flocks for suspected viral enteric pathogens such as reovirus, rotavirus, parvovirus, and astrovirus. Beginning in early 2012, monitoring of commercial turkey flocks in the Southeastern United Stat...

Fluorescence Sensors for Early Detection of Nitrification in Drinking Water Distribution Systems – Interference Corrections (Abstract)

EPA Science Inventory

Nitrification event detection in chloraminated drinking water distribution systems (DWDSs) remains an ongoing challenge for many drinking water utilities, including Dallas Water Utilities (DWU) and the City of Houston (CoH). Each year, these utilities experience nitrification eve...

Fluorescence Sensors for Early Detection of Nitrification in Drinking Water Distribution Systems – Interference Corrections (Poster)

EPA Science Inventory

Nitrification event detection in chloraminated drinking water distribution systems (DWDSs) remains an ongoing challenge for many drinking water utilities, including Dallas Water Utilities (DWU) and the City of Houston (CoH). Each year, these utilities experience nitrification eve...

Reading across Workplace Learning Research to Build Dialogue

ERIC Educational Resources Information Center

Sawchuk, Peter H.

2010-01-01

The field of workplace learning scholarship in Western countries is reviewed. First, the emergence of workplace learning scholarship is discussed historically for its relation to the emergence and ongoing development of capitalism beginning from early thought on markets and productivity, 20th century scientific management, industrialism and…

Sustaining Change in Every Classroom

ERIC Educational Resources Information Center

Heidemann, Sandra; Chang, Claire; Hewitt, Deb; Menninga, Beth

2007-01-01

Words Work! and Community Action Head Start have been working together for seven years to provide training, consultation, mentoring, and resources to teachers in pilot classrooms as they learned to implement effective early literacy strategies. In its work with teachers, Words Work! developed a culture "where ongoing assessment, reflective…

Developing Fluorescence Sensor Systems for Early Detection of Nitrification Events in Chloraminated Drinking Water Distribution Systems

EPA Science Inventory

Detection of nitrification events in chloraminated drinking water distribution systems remains an ongoing challenge for many drinking water utilities, including Dallas Water Utilities (DWU) and the City of Houston (CoH). Each year, these utilities experience nitrification events ...

Cystic fibrosis in young children: A review of disease manifestation, progression, and response to early treatment.

PubMed

VanDevanter, Donald R; Kahle, Jennifer S; O'Sullivan, Amy K; Sikirica, Slaven; Hodgkins, Paul S

2016-03-01

Studies have described illness associated with cystic fibrosis (CF) early in life, but there is no comprehensive accounting of the prevalence and ages of disease manifestation and progression described in individual studies. We searched for peer-reviewed English-language studies of the health of children ≤6years old with CF (published 1990-2014). Structural abnormalities and dysfunction of the digestive and respiratory systems were summarized across relevant studies by system and age group. Primary studies (125 total) from 22 countries described abnormalities, dysfunction, and disease progression in infancy and early childhood. Improved health was consistently observed in association with diagnosis via newborn screening compared with cohorts diagnosed later by symptomatic presentation. The peer-reviewed literature is remarkably consistent: CF-associated growth impairment and airway abnormalities are reported at birth, and disease progression is reported in infancy and throughout childhood. Earlier access to routine CF management is associated with improved subsequent health status. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Integrated versus fragmented implementation of complex innovations in acute health care

PubMed Central

Woiceshyn, Jaana; Blades, Kenneth; Pendharkar, Sachin R.

2017-01-01

Background: Increased demand and escalating costs necessitate innovation in health care. The challenge is to implement complex innovations—those that require coordinated use across the adopting organization to have the intended benefits. Purpose: We wanted to understand why and how two of five similar hospitals associated with the same health care authority made more progress with implementing a complex inpatient discharge innovation whereas the other three experienced more difficulties in doing so. Methodology: We conducted a qualitative comparative case study of the implementation process at five comparable urban hospitals adopting the same inpatient discharge innovation mandated by their health care authority. We analyzed documents and conducted 39 interviews of the health care authority and hospital executives and frontline managers across the five sites over a 1-year period while the implementation was ongoing. Findings: In two and a half years, two of the participating hospitals had made significant progress with implementing the innovation and had begun to realize benefits; they exemplified an integrated implementation mode. Three sites had made minimal progress, following a fragmented implementation mode. In the former mode, a semiautonomous health care organization developed a clear overall purpose and chose one umbrella initiative to implement it. The integrative initiative subsumed the rest and guided resource allocation and the practices of hospital executives, frontline managers, and staff who had bought into it. In contrast, in the fragmented implementation mode, the health care authority had several overlapping, competing innovations that overwhelmed the sites and impeded their implementation. Practice Implications: Implementing a complex innovation across hospital sites required (a) early prioritization of one initiative as integrative, (b) the commitment of additional (traded off or new) human resources, (c) deliberate upfront planning and continual support for and evaluation of implementation, and (d) allowance for local customization within the general principles of standardization. PMID:26469705

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 4 - Diagnostics.

PubMed

Knight-Jones, T J D; Robinson, L; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

2016-06-01

This study assessed knowledge gaps in foot-and-mouth disease (FMD) research in the field of diagnostics. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from around the world. Findings were used to identify priority areas for future FMD research. Molecular and genetic technologies, including sequencing, are developing at an increasing rate both in terms of capability and affordability. These advances potentiate progress in many other fields of research, from vaccine development to epidemiology. The development of RT-LAMP represents an important breakthrough allowing greater use and access to molecular diagnostics. It is now possible to determine virus serotype using PCR, although only for certain virus pools, continued progress is needed to cover the global spectrum of FMD viruses. Progress has also been made in the development of pen-side rapid diagnostics, some with the ability to determine serotype. However, further advances in pen-side serotype or strain determination would benefit both FMD-free countries and endemic countries with limited access to well-resourced laboratories. Novel sampling methods that show promise include air sampling and baited ropes, the latter may aid sampling in wildlife and swine. Studies of infrared thermography for the early detection of FMD have not been encouraging, although investigations are ongoing. Multiplex tests have been developed that are able to simultaneously screen for multiple pathogens with similar clinical signs. Crucial for assessing FMDV freedom, tests exist to detect animals that have been infected with FMDV regardless of vaccination status; however, limitations exist, particularly when testing previously vaccinated animals. Novel vaccines are being developed with complementary DIVA tests for this purpose. Research is also needed to improve the current imprecise approaches to FMD vaccine matching. The development of simple, affordable tests increases access to FMD diagnostics, greatly benefiting regions with limited laboratory capacity. © 2016 Blackwell Verlag GmbH.

How to engage the right brain hemisphere in aphasics without even singing: evidence for two paths of speech recovery

PubMed Central

Stahl, Benjamin; Henseler, Ilona; Turner, Robert; Geyer, Stefan; Kotz, Sonja A.

2012-01-01

There is an ongoing debate as to whether singing helps left-hemispheric stroke patients recover from non-fluent aphasia through stimulation of the right hemisphere. According to recent work, it may not be singing itself that aids speech production in non-fluent aphasic patients, but rhythm and lyric type. However, the long-term effects of melody and rhythm on speech recovery are largely unknown. In the current experiment, we tested 15 patients with chronic non-fluent aphasia who underwent either singing therapy, rhythmic therapy, or standard speech therapy. The experiment controlled for phonatory quality, vocal frequency variability, pitch accuracy, syllable duration, phonetic complexity and other influences, such as the acoustic setting and learning effects induced by the testing itself. The results provide the first evidence that singing and rhythmic speech may be similarly effective in the treatment of non-fluent aphasia. This finding may challenge the view that singing causes a transfer of language function from the left to the right hemisphere. Instead, both singing and rhythmic therapy patients made good progress in the production of common, formulaic phrases—known to be supported by right corticostriatal brain areas. This progress occurred at an early stage of both therapies and was stable over time. Conversely, patients receiving standard therapy made less progress in the production of formulaic phrases. They did, however, improve their production of non-formulaic speech, in contrast to singing and rhythmic therapy patients, who did not. In light of these results, it may be worth considering the combined use of standard therapy and the training of formulaic phrases, whether sung or rhythmically spoken. Standard therapy may engage, in particular, left perilesional brain regions, while training of formulaic phrases may open new ways of tapping into right-hemisphere language resources—even without singing. PMID:23450277

Gene Discovery in Bladder Cancer Progression using cDNA Microarrays

PubMed Central

Sanchez-Carbayo, Marta; Socci, Nicholas D.; Lozano, Juan Jose; Li, Wentian; Charytonowicz, Elizabeth; Belbin, Thomas J.; Prystowsky, Michael B.; Ortiz, Angel R.; Childs, Geoffrey; Cordon-Cardo, Carlos

2003-01-01

To identify gene expression changes along progression of bladder cancer, we compared the expression profiles of early-stage and advanced bladder tumors using cDNA microarrays containing 17,842 known genes and expressed sequence tags. The application of bootstrapping techniques to hierarchical clustering segregated early-stage and invasive transitional carcinomas into two main clusters. Multidimensional analysis confirmed these clusters and more importantly, it separated carcinoma in situ from papillary superficial lesions and subgroups within early-stage and invasive tumors displaying different overall survival. Additionally, it recognized early-stage tumors showing gene profiles similar to invasive disease. Different techniques including standard t-test, single-gene logistic regression, and support vector machine algorithms were applied to identify relevant genes involved in bladder cancer progression. Cytokeratin 20, neuropilin-2, p21, and p33ING1 were selected among the top ranked molecular targets differentially expressed and validated by immunohistochemistry using tissue microarrays (n = 173). Their expression patterns were significantly associated with pathological stage, tumor grade, and altered retinoblastoma (RB) expression. Moreover, p33ING1 expression levels were significantly associated with overall survival. Analysis of the annotation of the most significant genes revealed the relevance of critical genes and pathways during bladder cancer progression, including the overexpression of oncogenic genes such as DEK in superficial tumors or immune response genes such as Cd86 antigen in invasive disease. Gene profiling successfully classified bladder tumors based on their progression and clinical outcome. The present study has identified molecular biomarkers of potential clinical significance and critical molecular targets associated with bladder cancer progression. PMID:12875971

Hepatocellular Carcinoma within Milan Criteria: No-Touch Multibipolar Radiofrequency Ablation for Treatment-Long-term Results.

PubMed

Seror, Olivier; N'Kontchou, Gisèle; Nault, Jean-Charles; Rabahi, Yacine; Nahon, Pierre; Ganne-Carrié, Nathalie; Grando, Véronique; Zentar, Nora; Beaugrand, Michel; Trinchet, Jean-Claude; Diallo, Abou; Sellier, Nicolas

2016-08-01

Purpose To assess the long-term outcome in 108 consecutive patients treated with no-touch multibipolar radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) that met the Milan criteria. Materials and Methods This retrospective study was approved by the ethical review board, and the need to obtain informed consent was waived. Between November 1, 2006, and December 31, 2011, 132 HCC tumors (diameter, 10-45 mm; 39 tumors ≥ 30 mm) in 108 consecutive patients (106 with cirrhosis) that met Milan criteria were treated with no-touch multibipolar RFA, which consisted of activating, in bipolar mode, three or four electrodes inserted just beyond the tumor margins. Follow-up was performed every 3 months for 2 years and every 6 months thereafter with computed tomographic or magnetic resonance imaging. Survival probabilities were computed by using the Kaplan-Meier method. Predictive factors of tumor progression and overall survival were assessed by using the Cox proportional hazard model. Results No technical failure occurred, and complete ablation was achieved for all the nodules. After a median of 40.5 months (range, 2-84 months) of follow-up, 3- and 5-year local and overall tumor progression-free survival were 96%, 94%, 52%, and 32%, respectively. Neither tumor diameter greater than 30 mm nor location abutting a large vessel were associated with local tumor progression. Tumor diameter greater than 30 mm was the only parameter predictive of overall tumor progression (P = .0036). Independent factors associated with shorter overall survival were Child-Pugh class B disease, age greater than 65 years, and platelet count of less than 150 g/L (P < .003). Three major complications occurred (2.7%): hemothorax in one patient and liver failure in two, with major portal-systemic shunts. One patient (0.9%) died, and one underwent transplantation. Conclusion No-touch multibipolar RFA for HCC tumors that meet Milan criteria provides a high local tumor progression-free survival rate. An ongoing randomized trial might help to clarify the role of this new approach for the treatment of early HCC. (©) RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 30, 2016.

Chronic lymphocytic leukemia.

PubMed

Kay, Neil E; Hamblin, Terry J; Jelinek, Diane F; Dewald, Gordon W; Byrd, John C; Farag, Sherif; Lucas, Margaret; Lin, Thomas

2002-01-01

This update of early stage B-cell chronic lymphocytic leukemia (B-CLL) embraces current information on the diagnosis, biology, and intervention required to more fully develop algorithms for management of this disease. Emphasis on early stage is based on the rapid advancement in our understanding of the disease parameters and our increasing ability to predict for a given early stage patient whether there is a need for more aggressive management. In Section I, Dr. Terry Hamblin addresses the nature of the disease, accurate diagnostic procedures, evidence for an early "preclinical" phase, the use of newer prognostic features to distinguish who will be likely to progress or not, and whether it is best to watch or treat early stage disease. In Section II, Dr. Neil Kay and colleagues address the biologic aspects of the disease and how they may relate to disease progression. Review of the newer insights into gene expression, recurring genetic defects, role of cytokines/autocrine pathways, and the interaction of the CLL B cell with the microenvironment are emphasized. The relationship of these events to both trigger disease progression and as opportunities for future therapeutic intervention even in early stage disease is also considered. In Section III, Dr. John Byrd and colleagues review the historical and now current approaches to management of the previously untreated progressive B-CLL patient. They discuss what decision tree could be used in the initial decision to treat a given patient. The use of single agents versus newer combination approaches such as chemoimmunotherapy are discussed here. In addition, the place of marrow transplant and some of the newer antibodies available for treatment of B-CLL are considered. Finally, a challenge to utilize our growing knowledge of the biology of B-CLL in the early stage B-CLL is proffered.

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer.

PubMed

Keating, Gillian M

2009-08-20

Letrozole (Femara) is a third-generation, nonsteroidal aromatase inhibitor. Adjuvant therapy with letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo in this patient population; letrozole is generally well tolerated. Ongoing trials will help answer outstanding questions regarding the optimal duration of letrozole therapy in early breast cancer and its efficacy compared with other third-generation aromatase inhibitors such as anastrozole. In the meantime, letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy.

Imaging outcome measures for progressive multiple sclerosis trials

PubMed Central

Moccia, Marcello; de Stefano, Nicola; Barkhof, Frederik

2017-01-01

Imaging markers that are reliable, reproducible and sensitive to neurodegenerative changes in progressive multiple sclerosis (MS) can enhance the development of new medications with a neuroprotective mode-of-action. Accordingly, in recent years, a considerable number of imaging biomarkers have been included in phase 2 and 3 clinical trials in primary and secondary progressive MS. Brain lesion count and volume are markers of inflammation and demyelination and are important outcomes even in progressive MS trials. Brain and, more recently, spinal cord atrophy are gaining relevance, considering their strong association with disability accrual; ongoing improvements in analysis methods will enhance their applicability in clinical trials, especially for cord atrophy. Advanced magnetic resonance imaging (MRI) techniques (e.g. magnetization transfer ratio (MTR), diffusion tensor imaging (DTI), spectroscopy) have been included in few trials so far and hold promise for the future, as they can reflect specific pathological changes targeted by neuroprotective treatments. Position emission tomography (PET) and optical coherence tomography have yet to be included. Applications, limitations and future perspectives of these techniques in clinical trials in progressive MS are discussed, with emphasis on measurement sensitivity, reliability and sample size calculation. PMID:29041865

Increasing Racial Isolation and Test Score Gaps in Mathematics: A 30-Year Perspective

ERIC Educational Resources Information Center

Berends, Mark; Penaloza, Roberto V.

2010-01-01

Background/Context: Although there has been progress in closing the test score gaps among student groups over past decades, that progress has stalled. Many researchers have speculated why the test score gaps closed between the early 1970s and the early 1990s, but only a few have been able to empirically study how changes in school factors and…

Reasoning with inaccurate spatial knowledge. [for Planetary Rover

NASA Technical Reports Server (NTRS)

Doshi, Rajkumar S.; White, James E.; Lam, Raymond; Atkinson, David J.

1988-01-01

This paper describes work in progress on spatial planning for a semiautonomous mobile robot vehicle. The overall objective is to design a semiautonomous rover to plan routes in unknown, natural terrains. The approach to spatial planning involves deduction of common-sense spatial knowledge using geographical information, natural terrain representations, and assimilation of new and possibly conflicting terrain information. This report describes the ongoing research and implementation.

School District Wellness Policies: Evaluating Progress and Potential for Improving Children's Health Five Years after the Federal Mandate. Brief Report. Volume 3

ERIC Educational Resources Information Center

Chriqui, Jamie; Resnick, Elissa; Schneider, Linda; Schermbeck, Rebecca; Adcock, Tessa; Carrion, Violeta; Chaloupka, Frank

2013-01-01

This brief report updates data published in August 2010 from the most comprehensive, ongoing nationwide analysis of written wellness policies. It includes data from the 2006-07 through the 2010-11 school years, which were the first five years following the required implementation date for wellness policies. The major findings and trends presented…

Structural Integrity of Water Reactor Pressure Boundary Components.

DTIC Science & Technology

1979-12-31

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

Clinical Investigation Program Annual Progress Report

DTIC Science & Technology

1993-09-30

272 93/200A 0 Comparison of Healing Rates of Bones Plated Following Fracture, Among Yucatan Swine Having Open and Closed Physes...Study Objective: Compare two enteral formulas in respect to nutritional aspects. (16) Technical Approach: Protocol will take place in SICU. (17...Protocol #: 93/200A (3) Status: Ongoing (4) Title: Comparison of Healing Rates of Bones Plated Following Fractures, Among Yucatan Swine Having Open and

Professional Development in the United States: Trends and Challenges. Phase II of a Three-Phase Study. Executive Summary

ERIC Educational Resources Information Center

Wei, Ruth Chung; Darling-Hammond, Linda; Adamson, Frank

2010-01-01

A new study that analyzes the status of professional learning in the United States reveals that the nation is making some progress in providing increased support and mentoring for new teachers. But the study also reveals that the United States has moved backward in providing the vast majority of teachers with the kind of ongoing, intensive…

Positions, Dispositions and Practices in Education Policy in Central and South East Europe (Research in Progress)

ERIC Educational Resources Information Center

Kos Kecojevic, Živa; Gaber, Slavko

2012-01-01

In the article, we present the conceptualisation and selected results of ongoing research dealing with the particular area of top decision making in education in Central and South East Europe. Aiming at a Bourdieuian type of objectification of key agents of decision making in education--ministers--a group of researchers from the region is in the…

The Aims and Objectives of the Monitoring the Future Study and Progress toward Fulfilling Them as of 2001. Monitoring the Future Occasional Paper 52.

ERIC Educational Resources Information Center

Johnston, Lloyd D.; O'Malley, Patrick M.; Schulenberg, John E.; Bachman, Jerald G.

Monitoring the Future is an ongoing program of research intended to assess the changing lifestyles, values, and preferences of American youth. This publication, from the occasional paper series, describes a study that monitors drug use and potential explanatory factors among American secondary school students, college students, and young adults.…

Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer

DTIC Science & Technology

2015-09-01

research progress at monthly Patho-epidemiology Group meetings and Prostate Cancer Epidemiology Group meetings throughout the year. She was an active...report on the aspirin component of the ongoing Physicians’ Health Study. Steering Committee of the Physicians’ Health Study Research Group . N Engl J...PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public

From the "Culture Wars" to the Conservative Campaign for Campus Diversity: Or, How Inclusion Became the New Exclusion

ERIC Educational Resources Information Center

Giroux, Susan Searls

2005-01-01

This article explores the new conservative assault on the university and the relative silence on the part of progressives in response to this challenge. In part, this apparent retreat is a consequence of the vulnerabilities and anxieties of workers in the academy that result from the ongoing corporatization of the university as well as the…

Oak Wilt in Minnesota: It's Still Here and We're Doing Something About It!

Treesearch

Jennifer Juzwik; Gary Johnson

1999-01-01

Yes, oak wilt is still around and killing large numbers of oaks annually in Minnesota. Although the progress of oak wilt has been slowed through the concerted efforts of State agencies, private contractors, and determined homeowners, the battle to "control" this infectious disease is ongoing and will continue to be as long as there are oaks in Minnesota....

Recombination of cluster ions

NASA Technical Reports Server (NTRS)

Johnsen, Rainer

1993-01-01

Some of our recent work on molecular band emissions from recombination of molecular dimer ions (N4(+) and CO(+) CO) is discussed. Much of the experimental work was done by Y. S. Cao; the results on N4(+) recombination have been published. A brief progress report is given on our ongoing measurements of neutral products of recombination using the flowing-afterglow Langmuir-probe technique in conjunction with laser-induced fluorescence.

Coding a Weather Model: DOE-FIU Science & Technology Workforce Development Program.

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

Bradley, Jon David

DOE Fellow, Andres Cremisini, completed a 10-week internship with Sandia National Laboratories (SNL) in Albuquerque, New Mexico. Under the management of Kristopher Klingler and the mentorship of Jon Bradley, he was tasked with conceiving and coding a realistic weather model for use in physical security applications. The objective was to make a weather model that could use real data to accurately predict wind and precipitation conditions at any location of interest on the globe at any user-determined time. The intern received guidance on software design, the C++ programming language and clear communication of project goals and ongoing progress. In addition,more » Mr. Cremisini was given license to structure the program however he best saw fit, an experience that will benefit ongoing research endeavors.« less

Immune Checkpoint Inhibition in Hepatocellular Carcinoma: Basics and Ongoing Clinical Trials.

PubMed

Kudo, Masatoshi

2017-01-01

Clinical trials of antibodies targeting the immune checkpoint inhibitors programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for the treatment of advanced hepatocellular carcinoma (HCC) are ongoing. Expansion cohorts of a phase I/II trial of the anti-PD-1 antibody nivolumab in advanced HCC showed favorable results. Two phase III studies are currently ongoing: a comparison of nivolumab and sorafenib in the first-line setting for advanced HCC, and a comparison of the anti-PD-1 antibody pembrolizumab and a placebo in the second-line setting for patients with advanced HCC who progressed on sorafenib therapy. The combination of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies is being evaluated in other phase I/II trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. Immune checkpoint inhibitors may therefore open new doors to the treatment of HCC. © 2017 S. Karger AG, Basel.

Predictors of early neurological deterioration after ischaemic stroke: a case-control study.

PubMed

Barber, Mark; Wright, Fiona; Stott, David J; Langhorne, Peter

2004-01-01

Early neurological deterioration after ischaemic stroke (stroke in progression) is reported to be common and associated with poor outcome or death. The causes of progressing stroke are, however, uncertain. To determine whether prior drug treatment (with anticoagulant or antiplatelet agents) or early adverse physiological features (pyrexia, hypoxia, dehydration or hyperglycaemia) are associated with progressing ischaemic stroke. The study used a case-control design. From a database of 873 consecutive acute stroke admissions, 196 cases of progressing ischaemic stroke (defined by point deterioration in components of the Scandinavian Stroke Scale or death over the first 72 h after hospital admission) were matched to 196 controls on the basis of age and stroke type. Univariate and conditional logistic regression techniques were used to explore predictors of progressing stroke. Cases and controls were well matched for baseline stroke severity. Warfarin use prior to admission was associated with a reduced risk of progressing stroke [odds ratio (OR) 0.10, p = 0.005]. Prior antiplatelet use was not related. A previous history of diabetes (OR 2.11, p = 0.039) and elevated systolic blood pressure on admission (OR 1.01 for each 1 mm Hg rise, p = 0.017) predicted progressing stroke. Although there were no differences in time to presentation or to brain imaging, a visible causative lesion on CT scanning was more common in the progressing stroke group (OR 2.30, p = 0.022). We found no evidence that adverse physiological features were associated with progressing stroke. Outcomes were worse in the progressing stroke group with 70% being dead or dependent by 30 days compared to 55% in the control group (p = 0.002). Prior warfarin use may be protective against progressing ischaemic stroke. A previous history of diabetes along with elevated admission systolic blood pressure predict deterioration. We found no evidence for an association between adverse physiological features and progressing stroke. Copyright 2004 S. Karger AG, Basel

Scanning laser Doppler imaging may predict disease progression of localized scleroderma in children and young adults.

PubMed

Shaw, L J; Shipley, J; Newell, E L; Harris, N; Clinch, J G; Lovell, C R

2013-07-01

Localized scleroderma is a rare but potentially disfiguring and disabling condition. Systemic treatment should be started early in those with active disease in key functional and cosmetic sites, but disease activity is difficult to determine clinically. Superficial blood flow has been shown to correlate with disease activity in localized scleroderma. To examine whether superficial blood flow measured by laser Doppler imaging (LDI) has the potential to predict disease progression and therefore select patients for early systemic treatment. A group of 20 individuals had clinical assessment and scanning LDI blood-flow measurements of 32 affected body sites. After a mean follow-up of 8.7 months their clinical outcome was compared with the results of the initial LDI assessment. Eleven out of 15 patients with an assessment of active LDI had progressed clinically, and 16 out of the 17 scans with inactive LDI assessment had not progressed, giving a positive predictive value of 73% and a negative predictive value of 94%. We believe that LDI can be a useful tool in predicting disease progression in localized scleroderma, and it may help clinicians to decide which patients to treat early. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Comparison of dual RAAS blockade and higher-dose RAAS inhibition on nephropathy progression.

PubMed

Bakris, George L; Weir, Matthew R

2008-04-01

Although the risk of dying from cardiovascular disease (CVD) is greater than for progressing to end-stage renal disease (ESRD), the increasing prevalence of diabetes mellitus and reduced mortality from CVD have contributed to an increased incidence of ESRD. Use of renin-angiotensin-aldosterone system (RAAS) blockers to reduce blood pressure is proven to reduce the rate of nephropathy progression. Theoretically, more complete RAAS inhibition may enhance the ability to slow nephropathy progression. Combining an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB) more completely inhibits the RAAS, potentially providing greater opportunity for renoprotection. Proteinuria is a strong independent predictor of poor renal and cardiovascular outcomes. Therefore, targeting interventions that further reduce proteinuria may yield better outcomes. This review presents evidence supporting the hypothesis that higher doses of RAAS inhibition or dual RAAS blockade are more effective in reducing proteinuria. Clinical data and ongoing trials will be discussed in the context of this hypothesis.

Investigating turkey enteric coronavirus circulating in the southeastern United States and Arkansas during 2012 and 2013

USDA-ARS?s Scientific Manuscript database

The use of molecular diagnostic assays has allowed ongoing periodic monitoring of United States turkey flocks for suspected viral enteric pathogens such as reovirus, rotavirus, parvovirus, and astrovirus. Beginning in early 2012, monitoring of commercial turkey flocks in the Southeastern United Stat...

Fuel Cells Advanced Drivetrain

DTIC Science & Technology

2010-08-09

T800 Silverado Military specific system upscale (4WD) HydroGen3 – CH2 HydroGen3 – LH2 4010 – Early Adopter Engineering Model (GEN Nadeau) Gen4...Timeline Maintenance Infrastructure Fort Belvoir, VA 2003-ongoing Full FCV and Volt Maintenance 350,700bar LH2 (Decommissioned) Volt Charging(pending

Status of Ongoing Work in Software TRAs/TRLs

DTIC Science & Technology

2010-04-29

to changes/updates being driven by corporate market dynamics • Changes not under control or under the influence of the PMO! • On programs with long...observed and reported esearc articles, peer- reviewed white papers, point papers, early conceptual models n a ca em c , experimental as c researc

Emerging Implications of Balancing Disinfection and Primary Treatment as an Element in CSO Control: Model Requirements. A presentation.

EPA Science Inventory

This paper describes early results and directions arising from ongoing research into factors that affect the preferred balance between primary treatment and disinfection in a conventional wastewater treatment plant during periods of wet weather overflow. Despite the fact that na...

The World Fertility Survey: Charting Global Childbearing.

ERIC Educational Resources Information Center

Lightbourne, Robert, Jr.; And Others

1982-01-01

Reported in this bulletin are major results from an ongoing study conducted by the World Fertility Survey (WFS) to examine fertility levels and trends and contraceptive use in developing and developed countries. Major results were available by early 1982 from 29 developing countries and 16 developed countries. These results indicated that while…

Generalizing across Borders: Policy and the Limits of Educational Science

ERIC Educational Resources Information Center

Luke, Allan

2011-01-01

This essay is a critique of the scientific and policy rationales for transnational standardization. It analyzes two examples of policy export: early childhood standards in one of North America's oldest Indigenous communities and the ongoing development of international standards for university teaching. It examines calls for American education to…

Emerging Implications of Balancing Disinfection and Primary Treatment as an Element in CSO Control: Model Requirements

EPA Science Inventory

This paper describes early results and directions arising from ongoing research into factors that affect the preferred balance between primary treatment and disinfection in a conventional wastewater treatment plant during periods of wet weather overflow. Despite the fact that na...

A Strong Start for Families: Voluntary Home Visiting in California

ERIC Educational Resources Information Center

Children Now, 2016

2016-01-01

Home visiting programs are voluntary, family-centered programs that match new and expectant parents with trained professionals who provide ongoing, individualized support during critical points throughout pregnancy and a child's first year(s) of life. By reaching families early in their transition into parenthood, and linking them with needed…

The Factors Influencing Young Children's Social Interaction in Technology Integration

ERIC Educational Resources Information Center

Lim, Eun Mee

2015-01-01

When technology integration is accomplished successfully in early childhood education settings, children tend to interact more with one another and exchange information related to computer tasks as well as the overall classroom on-going curriculum themes. Therefore, to explore how young children are interacting in computer areas when using…

Improving Functional Outcomes in College and University Students with Schizophrenia in the Western World

ERIC Educational Resources Information Center

Christianson, Laura

2018-01-01

Retrospective research from patients with schizophrenia suggests that remission becomes increasingly less likely the longer psychosis goes untreated. Yet symptoms of schizophrenia are insidious and disease evolution varies between patients, requiring an ongoing diagnostic process. One way of justifying early treatment is by focusing on…

WATERSHED CHARACTERISTICS AND PRE-RESTORATION SURFACE-WATER HYDROLOGY OF MINEBANK RUN, BALTIMORE COUNTY, MARYLAND, WATER YEARS 2002-04

EPA Science Inventory

Stream restoration efforts have been ongoing in Maryland since the early 1990s. Physical stream restoration often involves replacement of lost sediments to elevate degraded streambeds, re-establishment of riffle-pool sequences along the channel profile, planting vegetation in rip...

The Effect of Price: Early Observations.

ERIC Educational Resources Information Center

Hunter, Karen

Scientific journal publishers have very little commercial experience with electronic full text distribution and it is difficult to segregate the effect of pricing on user acceptance and behavior. This paper examines some of the known experiences and ongoing and proposed experiments to get a sense of the interaction of pricing and user acceptance…

Neuroscience in Schools

ERIC Educational Resources Information Center

Schachter, Ron

2012-01-01

For generations, teachers in the early elementary years have urged their young pupils to use their brains. They're still offering the same encouragement, but nowadays they can know even more about what they're talking about. Recent advances in neuroscience--from detailed scans of the brain to ongoing research on teaching methods that increase…

Que Es la Mediacion? (What Is Mediation?).

ERIC Educational Resources Information Center

Consortium for Appropriate Dispute Resolution in Special Education (CADRE), Eugene, OR.

This brief paper, in Spanish, discusses the use of mediation as a method for resolving disagreements between schools or early intervention programs and parents of children with disabilities. It identifies benefits of mediation such as maintenance of an ongoing and positive relationship between the school and family, simple resolution of conflicts…

Conversations about Technology

ERIC Educational Resources Information Center

Wagner, Michael Andrew

2012-01-01

Since the early 1980s, exposure to digital technologies/devices has occurred on a wide cultural/societal level. Numerous writers have posited their impressions of these encounters often times suggesting an ease, comfort, and acceptance on the part of the users, especially those born in 1980 or later. This study examined the ongoing relationship…

Functional Analysis and Treatment of Problem Behavior in Early Education Classrooms

ERIC Educational Resources Information Center

Greer, Brian D.; Neidert, Pamela L.; Dozier, Claudia L.; Payne, Steven W.; Zonneveld, Kimberley L. M.; Harper, Amy M.

2013-01-01

We conducted functional analyses (FA) with 4 typically developing preschool children during ongoing classroom activities and evaluated treatments that were based on FA results. Results of each child's FA suggested social-positive reinforcement functions, and differential reinforcement of alternative behavior plus time-out was effective in…

The Occupations of Literacy: Occupational Therapy's Role

ERIC Educational Resources Information Center

Frolek Clark, Gloria

2016-01-01

Nationally, student proficiency in reading and writing is very low and requires ongoing focus from state and local agencies. With almost 25% of occupational therapists working in early intervention and school settings (AOTA, 2015), their role of facilitating literacy (e.g., reading, writing, speaking and listening) is critical. Occupational…

California Colleges and Universities Collaborate to Support Student Mental Health

ERIC Educational Resources Information Center

Woodbridge, Michelle W.; Goldweber, Asha; Yu, Jennifer; Golan, Shari; Stein, Bradley D.

2014-01-01

One key objective of California's Prevention and Early Intervention (PEI) Student Mental Health (SMH) initiative funded under Proposition 63 is to establish a formal process for ongoing collaboration between higher education systems and county mental health, as well as to increase collaboration among higher education campuses to improve student…

Innovations in Detroit Head Start. [Videotape].

ERIC Educational Resources Information Center

Merrill-Palmer Inst., Detroit, MI.

The Reggio Emilia approach to early childhood teaching is based on curriculum and teaching practices developed in the preschools of Reggio Emilia, Italy. This video highlights an ongoing Detroit, Michigan Head Start staff development project, inspired by the Reggio Emilia approach. The staff development program was launched in consultation with…

Business Technology Education in the Early 21st Century: The Ongoing Quest for Relevance

ERIC Educational Resources Information Center

Andriole, Stephen J.

2006-01-01

The field of information technology is changing and those responsible for educating the next generation of technology professionals have responded with a new computing curriculum, which identifies five distinct technology majors: computer engineering, computer science, software engineering, information systems and information technology.…

The Potential Contribution of Intermediary Organizations for Implementation of School Mental Health

ERIC Educational Resources Information Center

Corcoran, Tim; Rowling, Louise; Wise, Marilyn

2015-01-01

Questions persist regarding implementation of mental health promotion, prevention, and early intervention initiatives in schools. To date, attention has targeted the "Whats" and "Hows" in design and implementation. Ongoing clarification of "Who" the key proponents are working in this space receives less consideration.…

A Collaborative Professional Development Initiative Supporting Early Literacy Coaches

ERIC Educational Resources Information Center

Mraz, Maryann; Kissel, Brian; Algozzine, Bob; Babb, Julie; Foxworth, Kimberly

2011-01-01

Many believe that the key to translating research into successful practice lies in providing teachers with continuous professional development and ongoing coaching support. In this article, we provide an overview of the relevant coaching literature and describe 4 critical features of an evidence-based preschool literacy coaching model: the coach…