Chronic Mild Stress Assay Leading to Early Onset and Propagation of Alzheimer's Disease Phenotype in Mouse Models.

PubMed

Cuadrado-Tejedor, Mar; García-Osta, Ana

2016-01-01

A comprehensive chronic mild stress (CMS) procedure is presented, which consists in the application of unpredictable mild stressors to animal models in a random order for several weeks. This assay can be applied to Alzheimer's disease (AD) mouse models, leading to accelerated onset and increased severity of AD phenotypes and signs, including memory deficits and the accumulation of amyloid-β and phospho-tau. These assays open the way towards advanced studies on the influence of sustained mild stress, stress responses and pathways on the onset and propagation of Alzheimer's disease.

Mild traumatic brain injury: lessons learned from clinical, sports, and combat concussions.

PubMed

Kelly, Judy C; Amerson, Efland H; Barth, Jeffrey T

2012-01-01

Over the past forty years, a tremendous amount of information has been gained on the mechanisms and consequences of mild traumatic brain injuries. Using sports as a laboratory to study this phenomenon, a natural recovery curve emerged, along with standards for managing concussions and returning athletes back to play. Although advances have been made in this area, investigation into recovery and return to play continues. With the increase in combat-related traumatic brain injuries in the military setting, lessons learned from sports concussion research are being applied by the Department of Defense to the assessment of blast concussions and return to duty decision making. Concussion management and treatment for military personnel can be complicated by additional combat related stressors not present in the civilian environment. Cognitive behavioral therapy is one of the interventions that has been successful in treating symptoms of postconcussion syndrome. While we are beginning to have an understanding of the impact of multiple concussions and subconcussive blows in the sports world, much is still unknown about the impact of multiple blast injuries.

Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease.

PubMed

Loomba, Rohit; Seguritan, Victor; Li, Weizhong; Long, Tao; Klitgord, Niels; Bhatt, Archana; Dulai, Parambir Singh; Caussy, Cyrielle; Bettencourt, Richele; Highlander, Sarah K; Jones, Marcus B; Sirlin, Claude B; Schnabl, Bernd; Brinkac, Lauren; Schork, Nicholas; Chen, Chi-Hua; Brenner, David A; Biggs, William; Yooseph, Shibu; Venter, J Craig; Nelson, Karen E

2017-05-02

The presence of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is the most important predictor of liver mortality. There are limited data on the diagnostic accuracy of gut microbiota-derived signature for predicting the presence of advanced fibrosis. In this prospective study, we characterized the gut microbiome compositions using whole-genome shotgun sequencing of DNA extracted from stool samples. This study included 86 uniquely well-characterized patients with biopsy-proven NAFLD, of which 72 had mild/moderate (stage 0-2 fibrosis) NAFLD, and 14 had advanced fibrosis (stage 3 or 4 fibrosis). We identified a set of 40 features (p < 0.006), which included 37 bacterial species that were used to construct a Random Forest classifier model to distinguish mild/moderate NAFLD from advanced fibrosis. The model had a robust diagnostic accuracy (AUC 0.936) for detecting advanced fibrosis. This study provides preliminary evidence for a fecal-microbiome-derived metagenomic signature to detect advanced fibrosis in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

Mild Oxidation Promotes and Advanced Oxidation Impairs Remodeling of Human High-Density Lipoprotein in vitro

PubMed Central

Gao, Xuan; Jayaraman, Shobini; Gursky, Olga

2008-01-01

SUMMARY High-density lipoproteins (HDL) prevent atherosclerosis by removing cholesterol from macrophages and by exerting anti-oxidant and anti-inflammatory effects. Oxidation is thought to impair HDL functions, yet certain oxidative modifications may be advantageous; thus, mild oxidation reportedly enhances cell cholesterol uptake by HDL whereas extensive oxidation impairs it. To elucidate the underlying energetic and structural basis, we analyzed the effects of copper and hypochlorite (that preferentially oxidize lipids and proteins, respectively) on thermal stability of plasma spherical HDL. Circular dichroism, light scattering, calorimetry, gel electrophoresis and electron microscopy showed that mild oxidation destabilizes HDL and accelerates protein dissociation and lipoprotein fusion, while extensive oxidation inhibits these reactions; this inhibition correlates with massive protein cross-linking and lipolysis. We propose that mild oxidation lowers kinetic barriers for HDL remodeling due to diminished apolipoprotein affinity for lipids resulting from oxidation of methionine and aromatic residues in apolipoproteins A-I and A-II followed by protein cross-linking into dimers and/or trimers. In contrast, advanced oxidation inhibits protein dissociation and HDL fusion due to lipid re-distribution from core to surface upon lipolysis and to massive protein cross-linking. Our results help reconcile the apparent controversy in the studies of oxidized HDL and suggest that mild oxidation may benefit HDL functions. PMID:18190928

[Noninvasive alternatives to CPAP in therapy of obstructive sleep apnea syndrome].

PubMed

Fritsch, K; Bloch, K E

2000-07-01

Non-surgical treatment of the sleep apnea syndrome comprises behavioral modification such as sleep hygiene, weight reduction, and positional training as an adjunct to standard therapy with continuous positive airway pressure (CPAP) applied via a nasal mask. For patients who cannot tolerate or are not willing to use CPAP for psychological or other reasons, removable intraoral appliances that advance the mandible during sleep are a valuable treatment alternative. Randomised controlled trials have confirmed effectiveness of intraoral appliances in relieving symptoms and measured sleep and respiratory disturbances. Side effects including hypersalivation, mucosal dryness, tooth and temporo-mandibular joint discomfort are common but usually mild. To timely detect effects of oral appliances on occlusion and on the temporo-mandibular joint longterm orthodontic monitoring is advisable.

Short-term and long-term outcome of athletic closed head injuries.

PubMed

Webbe, Frank M; Barth, Jeffrey T

2003-07-01

The continued development of the sport environment as a laboratory for clinical investigation of mild head injury has greatly advanced the use of neuropsychological assessment in evaluating brain-injured athletes, and tracking their symptoms and recovery in an objective manner. The use of neurocognitive baseline measures has become critical in determining whether a brain-injured athlete has recovered function sufficiently to return to play. The rapid growth of computerized and web-based neurocognitive assessment measures provides an efficient, valid technology to put such testing within the reach of most institutions and organizations that field sport teams. Moreover, the knowledge of the recovery curve following mild head injury in the sport environment can be generalized to the management of MTBI in general clinical environments where baseline measures are unlikely. What we know today is that sideline assessments of severity are not predictive of which athletes will show the most typical 5- to 10-day recovery period and which will report persistent PCS complaints and exhibit impaired neurocognitive performance for an extended time. The research on mechanisms of brain injury in MTBI suggests that unpredictable, diffuse white-matter damage may control much of the variability in functional impairments and recovery duration.

Development of advanced, continuous mild gasification process for the production of co-products

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

Ness, R.O. Jr.; Aulich, T.R.

1991-05-01

The current objective of the University of North Dakota Energy and Environmental Research Center (EERC) mild gasification project is to optimize reaction char and marketable liquids production on a 100-lb/hr scale using Wyodak subbituminous and Indiana No. 3 bituminous coals. Tests performed using the EERC 100-lb/hr process development unit (PDU) include a refractory-cure (Test P001), a test using petroleum coke (Test P002), and tests using Wyodak and Indiana coals. The reactor system used for the 11 PDU tests conducted to date consists of a spouted, fluid-bed carbonizer equipped with an on-line condensation train that yields three boiling point fractions ofmore » coal liquids ranging in volatility from about (77{degrees}--750{degrees}F) (25{degrees}--400{degrees}C). The September--December 1990 quarterly report described reaction conditions and the bulk of the analytical results for Tests P010 and P011. This report describes further P010 and P011 analytical work, including the generation of simulated distillation curves for liquid samples on the basis of sulfur content, using gas chromatography coupled with atomic emission detection (GC/AED) analysis. 13 figs., 3 tabs.« less

Treatment of obstructive sleep apnea patients using oral appliances--our experiences.

PubMed

Miljus, Dusan; Tihacek-Sojić, Ljiljana; Milić-Lemić, Aleksandra; Andjelković, Marko

2014-07-01

Obstructive sleep apnea (OSA) is one of the most prevalent sleep disorders. It is recognized as a serious risk factor for car and workplace accidents due to daytime sleepiness, and factor for coronary heart diseases and stroke. The aim of this study was to examine the effectiveness of oral appliances for mandibular advance in treating mild to moderate OSA. A total of 15 patients were included in this study, all diagnosed with mild or moderate OSA. Oral appliances were custom made for each patient in protrusive position at 50% of maximum mandibular advancement. The patients were given instructions not to sleep on their backs and avoid alcohol consumption during the study as these are the factors that can contribute to symptoms progression. Complete and partial treatment success was achieve in 14 of the patients. Apnea-hypopnea index values were significantly lower (p < 0.05) at the end of a 6-month observation period compared to those at the treatment beginning. A great improvement in symptoms was observed, with daytime sleepiness index values significantly reduced already within the first month of the treatment. Treatment of obstructive sleep apnea with oral appliances has proven successful. Patients were comfortable using oral appliances and were ready to wear them for prolonged period of time. Use of oral appliances is very common in the world and should not be discarded. They are also very comfortable, practical and affordable comparing to continuous positive airway pressure (CPAP) apparatus, not to mention surgery. Use of oral appliances is safe and very well tolerated, and ought to be offered to patients with OSA.

The effects of mild hypothermia on thiopental-induced electroencephalogram burst suppression.

PubMed

Kim, J H; Kim, S H; Yoo, S K; Kim, J Y; Nam, Y T

1998-07-01

Thiopental intravenous injections before temporary clipping and mild hypothermia have protective effects in the setting of cerebral ischemia, and are used clinically in some centers. However, it is not known whether mild hypothermia affects thiopental-induced electroencephalogram (EEG) burst suppression. In this study, the authors compared the onset and duration of EEG suppression by thiopental in normothermic (n=10) and mildly hypothermic (n=10) patients undergoing cerebral aneurysm surgery. Spectral analysis was used to compare the prethiopentonal continuous EEG patterns in normothermic and mild hypothermic patients. The patients' body temperatures were controlled by a circulating water mattress and intravenous fluids (normothermia = 36.4+/-0.1 degrees C, mild hypothermia = 33.3+/-0.1 degrees C). Immediately before temporary clipping, thiopental sodium (5 mg/kg) was administered intravenously. Onset time (the amount of time from thiopental injection to the first complete EEG suppression), duration of suppression (the amount of time from the first complete EEG suppression to recovery on continuous EEG from burst suppression), and maximum duration of isoelectric EEG (the longest time interval between two bursts during burst suppression) were measured. Onset time was shortened (25.8+/-1.4 versus 43.5+/-5.6 seconds), and duration of suppression (531.0+/-56.6 versus 165.0+/-16.9 seconds) and the maximum duration of isoelectric EEG (47.7+/-5.8 versus 22.8+/-2.0 seconds) were prolonged in the patients with mild hypothermia. In two normothermic patients, the standard dose of thiopental did not produce burst suppression, but only a mild decrease in spectral edge frequency. The authors concluded that the effects of mild hypothermia on thiopental-induced EEG suppression are not simply additive, but synergistic.

SPIRIT advance care planning intervention in early stage dementias: An NIH stage I behavioral intervention development trial.

PubMed

Song, Mi-Kyung; Ward, Sandra E; Hepburn, Kenneth; Paul, Sudeshna; Shah, Raj C; Morhardt, Darby J

2018-06-02

People in the early stages of Alzheimer's disease and related dementias (ADRD) are encouraged to engage in advance care planning (ACP) while they are still competent to appoint a surrogate decision maker and meaningfully participate in ACP discussions with the surrogate. In this NIH Stage I behavioral intervention development trial, we will adapt and test an efficacious ACP intervention, SPIRIT (Sharing Patient's Illness Representation to Increase Trust), with people with mild dementia and their surrogates to promote open, honest discussions while such discussions about end-of-life care are possible. We will first adapt SPIRIT (in person) to target people with mild dementia and their surrogates through a process of modification-pretesting-refinement using stakeholders (persons with mild dementia, family caregivers, and clinicians) and experts, including adapting the delivery mode to interactive web-based videoconference format (SPIRIT-remote). Then in a 3-group RCT with 120 patient-surrogate dyads, we will evaluate the feasibility and acceptability of SPIRIT in-person and SPIRIT remote, and preliminary efficacy of SPIRIT compared to usual care on preparedness outcomes for end-of-life decision making (dyad congruence on goals of care, patient decisional conflict, and surrogate decision-making confidence) shortly after the intervention. This Stage I research of SPIRIT will generate valuable insights regarding how to improve ACP for people with mild dementia who will progress to an advanced stage of the disease in the foreseeable future. ClinicalTrials.gov NCT03311711, Registered 10/12/2017. Copyright © 2018. Published by Elsevier Inc.

Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study.

PubMed

Brown, Jennifer; Plummer, Ruth; Bauer, Todd M; Anthony, Stephen; Sarantopoulos, John; De Vos, Filip; White, Mike; Schupp, Marco; Ou, Ying; Vaishampayan, Ulka

2017-01-01

Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles. The primary objective was to assess the influence of hepatic impairment on carfilzomib PK following 27 and 56 mg/m 2 doses. The majority of patients enrolled in this study had solid tumors (n = 44) vs. MM (n = 2) since patients with multiple myeloma do not tend to have severe hepatic impairment in the same way as patients with solid tumors. A total of 11 normal and 17 mild, 14 moderate, and 4 severe hepatic impairment patients were enrolled. Compared with patients with normal hepatic function, patients with mild and moderate hepatic impairment had 44 and 26% higher carfilzomib AUC 0-last , respectively (27 mg/m 2 dose); increases at the 56 mg/m 2 dose were 45 and 21%, respectively. Considerable PK variability (% coefficient of variation in AUC ≤100%) was discerned and no consistent trend of increasing exposure resulting from increasing hepatic impairment severity (moderate vs. mild) was seen. The observed adverse event (AE) profile in patients of mostly solid tumors was consistent with the known safety profile of carfilzomib, with the exception of an increased frequency of AEs consistent with hepatic function abnormalities. In this population of primarily advanced solid tumor patients, patients with mild and moderate hepatic impairment had approximately 20-50% higher carfilzomib AUC vs. normal hepatic function patients. These increases are unlikely to be clinically significant, in light of the intrinsic PK variability and exposure-response relationship of carfilzomib. Trial registration http://clinicaltrials.gov NCT01949545; date of registration: September 6, 2013.

Optimisation of quantitative lung SPECT applied to mild COPD: a software phantom simulation study.

PubMed

Norberg, Pernilla; Olsson, Anna; Alm Carlsson, Gudrun; Sandborg, Michael; Gustafsson, Agnetha

2015-01-01

The amount of inhomogeneities in a (99m)Tc Technegas single-photon emission computed tomography (SPECT) lung image, caused by reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), is correlated to disease advancement. A quantitative analysis method, the CVT method, measuring these inhomogeneities was proposed in earlier work. To detect mild COPD, which is a difficult task, optimised parameter values are needed. In this work, the CVT method was optimised with respect to the parameter values of acquisition, reconstruction and analysis. The ordered subset expectation maximisation (OSEM) algorithm was used for reconstructing the lung SPECT images. As a first step towards clinical application of the CVT method in detecting mild COPD, this study was based on simulated SPECT images of an advanced anthropomorphic lung software phantom including respiratory and cardiac motion, where the mild COPD lung had an overall ventilation reduction of 5%. The best separation between healthy and mild COPD lung images as determined using the CVT measure of ventilation inhomogeneity and 125 MBq (99m)Tc was obtained using a low-energy high-resolution collimator (LEHR) and a power 6 Butterworth post-filter with a cutoff frequency of 0.6 to 0.7 cm(-1). Sixty-four reconstruction updates and a small kernel size should be used when the whole lung is analysed, and for the reduced lung a greater number of updates and a larger kernel size are needed. A LEHR collimator and 125 (99m)Tc MBq together with an optimal combination of cutoff frequency, number of updates and kernel size, gave the best result. Suboptimal selections of either cutoff frequency, number of updates and kernel size will reduce the imaging system's ability to detect mild COPD in the lung phantom.

Antitrypanosomatid drug discovery: an ongoing challenge and a continuing need

PubMed Central

Field, Mark C.; Horn, David; Fairlamb, Alan H.; Ferguson, Michael A. J.; Gray, David W.; Read, Kevin D.; De Rycker, Manu; Torrie, Leah S.; Wyatt, Paul G.; Wyllie, Susan; Gilbert, Ian H.

2017-01-01

The World Health Organization recognizes human African trypanosomiasis, Chagas’ disease and the leishmaniases as neglected tropical diseases. These diseases are caused by parasitic trypanosomatids and range in severity from mild and self-curing to near invariably fatal. Public health advances have substantially decreased the impact of these diseases in recent decades, but alone will not eliminate these diseases. Here we discuss why new drugs against trypanosomatids are needed, approaches that are under investigation to develop new drugs and why the drug discovery pipeline remains essentially unfilled. Additionally, we consider the important challenges to drug discovery strategies and the new technologies that can address them. The combination of new drugs, new technologies and public health initiatives are essential for the management and hopefully eventual elimination of trypanosomatid diseases from the human population. PMID:28239154

L wave in echo Doppler.

PubMed

Kumar, Vipin; Jose, John; Jose, V Jacob

2014-01-01

62-year-old female presented with progressive dyspnea NYHA class III for six months. Echocardiography showed normal left ventricular (LV) systolic function, mild biatrial enlargement, an L wave in pulse wave Doppler at mitral inflow and in M mode echocardiography across mitral valve. Tissue Doppler imaging at medial mitral annulus showed an L' wave in mid diastole in addition to E' and A' wave. An L wave in pulse wave Doppler and M mode echocardiography represents continued pulmonary vein mid diastolic flow through the left atrium in to LV across mitral valve after early rapid filling. Presence of an L' wave in these patients associated with higher E/E' is indicative of advance diastolic dysfunction with elevated filling pressures. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

PubMed

Gross, H; Kling, A; Henry, G; Herndon, C; Lavretsky, H

1996-01-01

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

Symptoms in patients with skin changes due to chronic venous insufficiency often lead to emergency care service: an Italian observational study.

PubMed

Ruggiero, Michele; Grande, Raffaele; Naso, Agostino; Butrico, Lucia; Rubino, Paolo; Placida, Girolamo Domenico; Cannistrà, Marco; Serra, Raffaele

2016-10-01

Chronic venous insufficiency (CVI) is the most advanced form of chronic venous disease (CVD), and is often associated with skin changes such as hyperpigmentation, eczema, lipodermatosclerosis and venous skin ulceration that cause discomfort, pain, sleep disturbances, absenteeism in the workplace, disability and deteriorated quality of life (QoL). The purpose of this study is to evaluate the prevalence of CVI and skin changes in patients who turn to Continuous Assistance Services due to the presence of disturbing symptoms of their condition. Data were evaluated by consulting the medical records, during a 16-month period, available with three Continuous Assistance Services of the Italian territory. The overall population of the referring centres consisted of 1186 patients [739 females (62·31%) and 447 males (37·69%)]. Seventy-nine patients (6·66%) consulted the emergency unit for venous symptoms related to CVD. Patients with more severe disease (CVI, categories C4-C6) represented the majority accounting for 60·75%, while patients with moderate disease (C3) accounted for 35·44% and patients with mild disease (C1-C2 stages) accounted for 3·79%. The main finding of this study is that despite CVI not being a disease that commonly requires medical emergency/urgency intervention, patients with CVI, especially in advanced stage with skin changes, may turn to Continuous Assistance Service for treating bothersome symptoms related to their condition. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Methodological issues and research recommendations for prognosis after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

PubMed

Kristman, Vicki L; Borg, Jörgen; Godbolt, Alison K; Salmi, L Rachid; Cancelliere, Carol; Carroll, Linda J; Holm, Lena W; Nygren-de Boussard, Catharina; Hartvigsen, Jan; Abara, Uko; Donovan, James; Cassidy, J David

2014-03-01

The International Collaboration on Mild Traumatic Brain Injury (MTBI) Prognosis performed a comprehensive search and critical review of the literature from 2001 to 2012 to update the 2002 best-evidence synthesis conducted by the World Health Organization Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation Task Force on the prognosis of MTBI. Of 299 relevant studies, 101 were accepted as scientifically admissible. The methodological quality of the research literature on MTBI prognosis has not improved since the 2002 Task Force report. There are still many methodological concerns and knowledge gaps in the literature. Here we report and make recommendations on how to avoid methodological flaws found in prognostic studies of MTBI. Additionally, we discuss issues of MTBI definition and identify topic areas in need of further research to advance the understanding of prognosis after MTBI. Priority research areas include but are not limited to the use of confirmatory designs, studies of measurement validity, focus on the elderly, attention to litigation/compensation issues, the development of validated clinical prediction rules, the use of MTBI populations other than hospital admissions, continued research on the effects of repeated concussions, longer follow-up times with more measurement periods in longitudinal studies, an assessment of the differences between adults and children, and an account for reverse causality and differential recall bias. Well-conducted studies in these areas will aid our understanding of MTBI prognosis and assist clinicians in educating and treating their patients with MTBI. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

New vignettes for the experimental manipulation of injury cause in prospective mild traumatic brain injury research.

PubMed

Sullivan, Karen A; Edmed, Shannon L

2016-01-01

This study developed standardized vignettes that depict a mild traumatic brain injury (TBI) from one of several causes and subjected them to formal expert review. A base vignette was developed using the World Health Organization operational criteria for mild TBI. Eight specific causes (e.g. sport vs assault) were examined. A convenience sample of mild TBI experts with a discipline background of Neuropsychology from North America, Australasia and Europe (n = 21) used an online survey to evaluate the vignettes and rated the role of cause on outcome. The vignette suite was rated as fitting the mild TBI WHO operational diagnostic criteria at least moderately well. When compared to other factors, cause was not rated as significantly contributing to outcome. When evaluated in isolation, approximately half of the sample rated cause as important or very important and at least two of three clinical outcomes were associated with a different cause. The vignettes may be useful in experimental mild TBI research. They enable the injury parameters to be controlled so that the effects of cause can be isolated and examined empirically. Such studies should advance understanding of the role of this factor in mild TBI outcome.

Evolution of diagnostic criteria and assessments for Parkinson's disease mild cognitive impairment.

PubMed

Goldman, Jennifer G; Holden, Samantha K; Litvan, Irene; McKeith, Ian; Stebbins, Glenn T; Taylor, John-Paul

2018-04-01

Mild cognitive impairment has gained recognition as a construct and a potential prodromal stage to dementia in both Alzheimer's disease and Parkinson's disease (PD). Although mild cognitive impairment has been recognized in the Alzheimer's disease field, it is a relatively more recent topic of interest in PD. Recent advances include the development of diagnostic criteria for PD mild cognitive impairment to provide more uniform definitions for clinical and research use. Studies reveal that mild cognitive impairment in PD is frequent, but also heterogeneous, with variable clinical presentations, differences in its progression to dementia, and likely differences in underlying pathophysiology. Application of the International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment Task Force diagnostic criteria has provided insights regarding cognitive measures, functional assessments, and other key topics that may require additional refinement. Furthermore, it is important to consider definitions of PD mild cognitive impairment in the landscape of other related Lewy body disorders, such as dementia with Lewy bodies, and in the context of prodromal and early-stage PD. This article examines the evolution of mild cognitive impairment in concept and definition, particularly in PD, but also in related disorders such as Alzheimer's disease and dementia with Lewy bodies; the development and application of International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment diagnostic criteria; and insights and future directions for the field of PD mild cognitive impairment. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

CONTRIBUTIONS OF NEUROPSYCHOLOGY AND NEUROIMAGING TO UNDERSTANDING CLINICAL SUBTYPES OF MILD COGNITIVE IMPAIRMENT

PubMed Central

Jak, Amy J.; Bangen, Katherine J.; Wierenga, Christina E.; Delano-Wood, Lisa; Corey-Bloom, Jody; Bondi, Mark W.

2010-01-01

The original conceptualization of mild cognitive impairment (MCI) was primarily as an amnestic disorder representing an intermediate stage between normal aging and Alzheimer’s dementia (AD). More recently, broader conceptualizations of MCI have emerged that also encompass cognitive domains other than memory. These characterizations delineate clinical subtypes that commonly include amnestic and non-amnestic forms, and that involve single and multiple cognitive domains. With the advent of these broader classifications, more specific information is emerging regarding the neuropsychological presentation of individuals with MCI, risk for dementia associated with different subtypes of MCI, and neuropathologic substrates connected to the clinical subtypes. This review provides an overview of this burgeoning literature specific to clinical subtypes of MCI. Focus is primarily on neuropsychological and structural neuroimaging findings specific to clinical subtypes of MCI as well as the issue of daily functioning. Although investigations of non-amnestic subtypes using advanced neuroimaging techniques and clinical trials are quite limited, we briefly review these topics in MCI because these data provide a framework for future investigations specifically examining additional clinical subtypes of MCI. Finally, the review comments on select methodological issues involved in studying this heterogeneous population, and future directions to continue to improve our understanding of MCI and its clinical subtypes are offered. PMID:19501714

Documenting pain as the fifth vital sign: a feasibility study in an oncology ward in Sarawak, Malaysia.

PubMed

Devi, B C R; Tang, T S

2008-01-01

Monitoring acute postoperative pain as the fifth vital sign is currently practiced in many developed countries. In Sarawak, pain is an important symptom as 70% of cancer patients present with advanced disease. As the existing validated pain assessment tools were found to be difficult to use, we studied the feasibility of modifying the use of a pain assessment tool, consisting of the short form of the Brief Pain Inventory and the Wong-Baker Faces Scale. This tool was used to document pain in all 169 patients who were admitted for pain control to the oncology ward between July 2000 and June 2001. Nurses were trained in the use of the modified scale before the start of the study. The method was easy to use, and the mean number of days to reduce pain was found to be 3.1 days (SD: 2.9; median: 2 days; range: 1-31 days). At discharge, none in the group with initially mild pain had pain, and the severity of pain for 98% of patients with moderate pain and 61% with severe pain was downgraded to mild pain. The staff found that the tool allowed continuous pain assessment in an objective manner. Copyright 2008 S. Karger AG, Basel.

Office management of obstructive sleep apnoea: appliances.

PubMed

Johnson, Matthew D

2015-08-01

Oral appliances are becoming increasingly common in the treatment of obstructive sleep apnoea (OSA). They work by advancing the mandible and opening the pharynx. There are several types of devices available for use. Many patients intolerant to continuous positive airway pressure (CPAP) are using oral appliances for OSA. Oral appliances have been shown to improve polysomnography, quality of life and health measures associated with OSA. There is current work to better identify patients who are ideal candidates. Development of titratable devices and monitoring are optimizing usage. They have been compared with CPAP, with both showing improvement in OSA; however, CPAP remains superior overall. Oral appliances are becoming first-line therapy for mild and moderate OSA. They provide a meaningful alternative in severe OSA for patients unable to use CPAP. Device titration and usage monitoring are beginning to hone oral appliances as a therapeutic option.

A Survey of Past Work on Rates of Advance in Land Combat Operations

DTIC Science & Technology

1990-02-01

Weather: Clear, mild, cold, snow, fog, rain, misty , fair-again objective definitions are not provided. c. Type action: Pursuit, limited objective...90-03 SIMPKIN-1984 J 1. Document: a. Title: Red Armour b. Author: Simpkin, Richard E. c. Date: 1984 d. Organiation: Pergamon Press Ltd, Oxford e...8217Mechanised advances on roads average about 35 miles,’day, advances on the best days achieving 50 miles for typical armoured division wheel/track mixes

Prevalence of Pulmonary Hypertension and its Influence on Survival in Patients With Advanced Chronic Obstructive Pulmonary Disease Prior to Lung Transplantation.

PubMed

Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Mansour, Heidi M; Whitson, Bryan A

2016-01-01

Prevalence of pulmonary hypertension (PH) and its influence on survival in chronic obstructive pulmonary disease (COPD) are not well studied in the lung allocation score (LAS) era. The UNOS database was queried from 2005 to 2013 to identify first-time adult lung transplant candidates with COPD who were tracked from wait list entry date until death or censoring to determine both prevalence and influence of PH. Using right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg and severe ≥ 35 mmHg. Of 1315 COPD candidates not transplanted, 1243 were used for survival analysis using Cox proportional hazards models, and 1010 (mild PH) and 244 (severe PH) were used for propensity score matching, respectively. A total of 52% (652) of subjects had PH mPAP ≥ 25 mmHg. Univariate analysis revealed significant differences in survival for mild PH (HR = 1.769; 95% CI: 1.331, 2.351; p < 0.001) and severe PH (HR = 3.271; 95% CI: 2.311, 4.630; p < 0.001). Kaplan-Meier survival function demonstrated significant disparities for mild PH (Log-rank test: Chi-square1: 15.87, p < 0.0001) and severe PH (Log-rank test: Chi-square1: 50.13, p < 0.0001). Multivariate Cox models identified significant risk for death for mild PH (HR = 1.987; 95% CI: 1.484, 2.662; p < 0.001) and severe PH (HR = 3.432; 95% CI: 2.410, 4.888; p < 0.001). Propensity score matching confirmed increased mortality hazard associated with mild PH (HR = 2.280; 95% CI: 1.425, 3.649; p = 0.001) and severe PH (HR = 7.000; 95% CI: 2.455, 19.957; p < 0.001). PH is highly prevalent in advanced COPD and associated with a significantly higher risk for mortality.

Battery Test Manual For 48 Volt Mild Hybrid Electric Vehicles

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

Walker, Lee Kenneth

2017-03-01

This manual details the U.S. Advanced Battery Consortium and U.S. Department of Energy Vehicle Technologies Program goals, test methods, and analysis techniques for a 48 Volt Mild Hybrid Electric Vehicle system. The test methods are outlined stating with characterization tests, followed by life tests. The final section details standardized analysis techniques for 48 V systems that allow for the comparison of different programs that use this manual. An example test plan is included, along with guidance to filling in gap table numbers.

Evaluation of adverse reactions to contrast media in the hospital

PubMed Central

Ryu, J-H; Kim, E-Y

2013-01-01

Objective: To determine and analyse the characteristics of contrast media adverse reactions (CM-ARs) reported in a hospital. Methods: A retrospective review of CM-ARs from the electronic spontaneous adverse drug reaction (ADR) report system between January 2011 and August 2012 was conducted. CM-ARs were evaluated in terms of causality, severity, preventability and affected organs. Also, agreement and correlation among the tools used to evaluate CM-ARs were analysed. Results: The overall reaction rate was 1.5% (n = 286). In total, 269 CM-ARs were identified. For ADR causality, 96.7% (n = 260) and 98.5% (n = 265) were evaluated as “probable” ADR using the Naranjo probability scale and the World Health Organization–Uppsala Monitoring Centre causality categories, whereas 98.1% (n = 264) were evaluated as “certain” with Korean algorithm v. II. Of these, 91.4% (n = 246) were mild in severity and 96.7% (n = 260) were unpreventable. Most patients (n = 233, 86.7%) could be managed with observation and/or simple treatment. The most frequent reaction (n = 383, 79.5%) was dermatological. Spearman's correlation coefficient was 0.667 (p < 0.01), and the agreement was 98.1% between the Naranjo scale and the World Health Organization–Uppsala Monitoring Centre categories. No relationship was seen between CM-AR severity and gender or between in- and outpatients. Conclusion: In our study, most CM-ARs were mild and managed with simple treatment. However, as the number of patients undergoing CT procedures continues to increase, it is essential to identify and observe patients at risk for CM-ARs to prevent severe ADRs. Advances in knowledge: Continuous careful review of reporting and treatment protocols of CM-ARs is needed to prevent morbidity and mortality. PMID:24191123

[Etiopathogenesis and treatment of breast capsular contracture].

PubMed

Pereira Leite, Luis; Correia Sá, Inês; Marques, Marisa

2013-01-01

Capsular contracture is a chronic and the most frequent complication of augmentation mammoplasty with breast implants and the main cause of patient's and surgeon's dissatisfaction. The mammary capsule consists of a fibrous tissue that surrounds the implant that may contract, changing the shape and consistency of the breast. In its advanced stage is accompanied by pronounced deformity, hardness and pain, being indicated for surgical treatment. All the articles indexed on PubMed through the search 'capsular contracture' (2000 - January 2012) were reviewed and were included the articles of greater interest in terms of etiology, prophylaxis and treatment. Articles referred in relevant publications were also examined. Everything indicates that its etiology is multifactorial; the etiopathology of breast capsular contracture continues being subject of multiple pre-clinical investigations. There are many studies performed in order to prevent the onset of capsular contracture but, although promising results, little is set for its application on clinical practice. The capsulectomy/capsulotomy continues being the gold standard treatment although the future may undergo non invasive techniques, at least in mild stages of disease. Although the surgical techniques and the quality of breast implants have been improving drastically in recent years, capsular contracture remains a real complication with great incidence and that continues affecting thousands of women all over the world.

Inhibiting mild steel corrosion from sulfate-reducing bacteria using antimicrobial-producing biofilms in Three-Mile-Island process water.

PubMed

Zuo, R; Ornek, D; Syrett, B C; Green, R M; Hsu, C-H; Mansfeld, F B; Wood, T K

2004-04-01

Biofilms were used to produce gramicidin S (a cyclic decapeptide) to inhibit corrosion-causing, sulfate-reducing bacteria (SRB). In laboratory studies these biofilms protected mild steel 1010 continuously from corrosion in the aggressive, cooling service water of the AmerGen Three-Mile-Island (TMI) nuclear plant, which was augmented with reference SRB. The growth of both reference SRB (Gram-positive Desulfosporosinus orientis and Gram-negative Desulfovibrio vulgaris) was shown to be inhibited by supernatants of the gramicidin-S-producing bacteria as well as by purified gramicidin S. Electrochemical impedance spectroscopy and mass loss measurements showed that the protective biofilms decreased the corrosion rate of mild steel by 2- to 10-fold when challenged with the natural SRB of the TMI process water supplemented with D. orientis or D. vulgaris. The relative corrosion inhibition efficiency was 50-90% in continuous reactors, compared to a biofilm control which did not produce the antimicrobial gramicidin S. Scanning electron microscope and reactor images also revealed that SRB attack was thwarted by protective biofilms that secrete gramicidin S. A consortium of beneficial bacteria (GGPST consortium, producing gramicidin S and other antimicrobials) also protected the mild steel.

An update on mandibular advancement devices for the treatment of obstructive sleep apnoea hypopnoea syndrome.

PubMed

Basyuni, Shadi; Barabas, Michal; Quinnell, Tim

2018-01-01

Continuous positive airway pressure (CPAP) remains the gold standard treatment for obstructive sleep apnoea hypopnoea syndrome (OSAHS). However, the high efficacy of CPAP is offset by intolerance and poor compliance, which can undermine effectiveness. This means that alternatives to CPAP are also necessary. In recent years, oral appliances have emerged as the leading alternative to CPAP. There is now a strong body of evidence supporting their use in OSAHS and clinical guidelines now recommend their use in mild OSAHS and in more severe cases when CPAP fails. These devices are by no means a homogenous group as they differ greatly in both design and action. The most commonly used appliances are mandibular advancement devices (MAD) that increase airway diameter with soft tissue displacement achieved by mandibular protrusion. Despite the growing evidence, there are still barriers to MAD provision. Their effectiveness can be difficult to predict and there is debate about the required level of design sophistication. These uncertainties prevent more widespread inclusion of MAD within clinical sleep services. This review will focus on the efficacy, effectiveness, design features, side-effects of and patient selection for MAD therapy. Comparison will also be made between MAD and CPAP therapy.

An update on mandibular advancement devices for the treatment of obstructive sleep apnoea hypopnoea syndrome

PubMed Central

Basyuni, Shadi; Barabas, Michal

2018-01-01

Continuous positive airway pressure (CPAP) remains the gold standard treatment for obstructive sleep apnoea hypopnoea syndrome (OSAHS). However, the high efficacy of CPAP is offset by intolerance and poor compliance, which can undermine effectiveness. This means that alternatives to CPAP are also necessary. In recent years, oral appliances have emerged as the leading alternative to CPAP. There is now a strong body of evidence supporting their use in OSAHS and clinical guidelines now recommend their use in mild OSAHS and in more severe cases when CPAP fails. These devices are by no means a homogenous group as they differ greatly in both design and action. The most commonly used appliances are mandibular advancement devices (MAD) that increase airway diameter with soft tissue displacement achieved by mandibular protrusion. Despite the growing evidence, there are still barriers to MAD provision. Their effectiveness can be difficult to predict and there is debate about the required level of design sophistication. These uncertainties prevent more widespread inclusion of MAD within clinical sleep services. This review will focus on the efficacy, effectiveness, design features, side-effects of and patient selection for MAD therapy. Comparison will also be made between MAD and CPAP therapy. PMID:29445528

Neurodiagnostic techniques in neonatal critical care.

PubMed

Chang, Taeun; du Plessis, Adre

2012-04-01

This article reviews recent advances in the neurodiagnostic tools available to clinicians practicing in neonatal critical care. The advent of induced mild hypothermia for acute neonatal hypoxic-ischemic encephalopathy in 2005 has been responsible for renewed urgency in the development of precise and reliable neonatal neurodiagnostic techniques. Traditional evaluations of bedside head ultrasounds, head computed tomography scans, and routine electroencephalograms (EEGs) have been upgraded in most tertiary pediatric centers to incorporate protocols for MRI, continuous EEG monitoring with remote bedside access, amplitude-integrated EEG, and near-infrared spectroscopy. Meanwhile, recent studies supporting the association between placental pathology and neonatal brain injury highlight the need for closer examination of the placenta in the neurodiagnostic evaluation of the acutely ill newborn. As the pursuit of more effective neuroprotection moves into the "hypothermia plus" era, the identification, evaluation, and treatment of the neurologically affected newborn in the neonatal intensive care unit has increasing significance.

Long continuous bridge deck evaluation : John Day River Bridge, Clatsop County, Bridge No. 1827B : final report.

DOT National Transportation Integrated Search

1995-06-01

The John Day River Bridge, near Astoria, Oregon was built with a continuous deck length of 1,105 ft. (340 m). The rationale for designing the John Day River Bridge with an unusually long continuous deck is in part based on the site's very mild climat...

Methylphenidate side effects in advanced cancer: a retrospective analysis.

PubMed

Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Davis, Mellar P; Rivera, Nilo; Khoshknabi, Dilara Seyidova

2010-02-01

Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults. To evaluate MP-associated symptoms or side effects (S/E). Data was collected from 2 published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All 3 reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5, and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. 62 patients were enrolled. Fifty completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most (96%) had improvement in depression and/or fatigue. Among the 62 patients, new symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before MP showed significant improvement during MP therapy. (1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with MP appeared to improve spontaneously despite continued MP therapy. (3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. (4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.

Can gradual dose titration of ketamine for management of neuropathic pain prevent psychotomimetic effects in patients with advanced cancer?

PubMed

Okamoto, Yoshiaki; Tsuneto, Satoru; Tanimukai, Hitoshi; Matsuda, Yoichi; Ohno, Yumiko; Tsugane, Mamiko; Uejima, Etsuko

2013-08-01

Ketamine is often used to manage neuropathic pain in patients with cancer. However, it occasionally causes psychotomimetic effects such as vivid dreams, nightmares, illusions, hallucinations, and altered body image. To examine whether gradual dose titration of ketamine for management of neuropathic pain prevents psychotomimetic effects in patients with advanced cancer. This was a retrospective chart review. We administered ketamine when neuropathic pain in patients with advanced cancer became refractory to opioids and oral adjuvant analgesics. The starting dose of ketamine was 10 mg/d by continuous intravenous infusion. The dose was gradually increased by 10 mg/d every 4 to 6 hours to 50 mg/d or until the pain was relieved. It was subsequently increased by 25 mg/d every 12 to 24 hours until the pain was relieved. For this study, we enrolled 46 patients with advanced cancer. The mean age was 52.2 ± 16.9 years. The mean dose at onset of action and maximum dose of ketamine were 56 ± 58 and 272 ± 214 mg/d, respectively. The mean pain intensity (numerical rating scale) decreased significantly from 7.3 ± 2.0 to 3.5 ± 2.2 after the administration of ketamine (P < .01). The effectiveness was 69.5%. No psychotomimetic effect of less than 300 mg/d was observed during the introduction phase even though psychotropic drugs were not prescribed. Mild sedation was observed in 3 patients (7%) as the only adverse effect during the introduction phase. Gradual dose titration of ketamine for management of neuropathic pain can prevent psychotomimetic effects in patients with advanced cancer.

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

Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients

PubMed Central

Khattab, Mahmoud; Sakr, Mohamed Amin; Fattah, Mohamed Abdel; Mousa, Youssef; Soliman, Elwy; Breedy, Ashraf; Fathi, Mona; Gaber, Salwa; Altaweil, Ahmed; Osman, Ashraf; Hassouna, Ahmed; Motawea, Ibrahim

2016-01-01

AIM To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. METHODS A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR). RESULTS Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage (P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis. CONCLUSION Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy. PMID:27917265

Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients.

PubMed

Khattab, Mahmoud; Sakr, Mohamed Amin; Fattah, Mohamed Abdel; Mousa, Youssef; Soliman, Elwy; Breedy, Ashraf; Fathi, Mona; Gaber, Salwa; Altaweil, Ahmed; Osman, Ashraf; Hassouna, Ahmed; Motawea, Ibrahim

2016-11-18

To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR). Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage ( P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis. Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.

Considerations of physicians about the depth of palliative sedation at the end of life

PubMed Central

Swart, Siebe J.; van der Heide, Agnes; van Zuylen, Lia; Perez, Roberto S.G.M.; Zuurmond, Wouter W.A.; van der Maas, Paul J.; van Delden, Johannes J.M.; Rietjens, Judith A.C.

2012-01-01

Background: Although guidelines advise titration of palliative sedation at the end of life, in practice the depth of sedation can range from mild to deep. We investigated physicians’ considerations about the depth of continuous sedation. Methods: We performed a qualitative study in which 54 physicians underwent semistructured interviewing about the last patient for whom they had been responsible for providing continuous palliative sedation. We also asked about their practices and general attitudes toward sedation. Results: We found two approaches toward the depth of continuous sedation: starting with mild sedation and only increasing the depth if necessary, and deep sedation right from the start. Physicians described similar determinants for both approaches, including titration of sedatives to the relief of refractory symptoms, patient preferences, wishes of relatives, expert advice and esthetic consequences of the sedation. However, physicians who preferred starting with mild sedation emphasized being guided by the patient’s condition and response, and physicians who preferred starting with deep sedation emphasized ensuring that relief of suffering would be maintained. Physicians who preferred each approach also expressed different perspectives about whether patient communication was important and whether waking up after sedation is started was problematic. Interpretation: Physicians who choose either mild or deep sedation appear to be guided by the same objective of delivering sedation in proportion to the relief of refractory symptoms, as well as other needs of patients and their families. This suggests that proportionality should be seen as a multidimensional notion that can result in different approaches toward the depth of sedation. PMID:22331961

Twenty-five-year experience with the Björk-Shiley convexoconcave heart valve: a continuing clinical concern.

PubMed

Blot, William J; Ibrahim, Michel A; Ivey, Tom D; Acheson, Donald E; Brookmeyer, Ron; Weyman, Arthur; Defauw, Joseph; Smith, J Kermit; Harrison, Donald

2005-05-31

The first Björk-Shiley convexoconcave (BSCC) prosthetic heart valves were implanted in 1978. The 25th anniversary provided a stimulus to summarize the research data relevant to BSCC valve fracture, patient management, and current clinical options. Published and unpublished data on the risks of BSCC valve fracture and replacement were compiled, and strategies for identifying candidates for prophylactic valve reoperation were summarized. By December 2003, outlet strut fractures (OSFs), often with fatal outcomes, had been reported in 633 BSCC valves (0.7% of 86,000 valves implanted). Fractures still continue to occur, but average rates of OSFs in 60 degrees valves are now <0.1% per year. OSF risk varies markedly by valve characteristics, especially valve angle and size, with weaker effects associated with other manufacturing variables. OSF risks are mildly lower among women than men but decline sharply with advancing age. The risks of valve replacement typically greatly exceed those of OSF. By comparing individualized estimated risks of OSF versus valve replacement, guidelines have been developed to identify the small percentage of BSCC patients (mostly younger men) who would be expected to have a gain in life expectancy should reoperative surgery be performed. Twenty-five years after the initial BSCC valve implants, fractures continue to occur. Continued monitoring of BSCC patients is needed to track and quantify risks and enable periodic updating of guidelines for patients and their physicians.

A systematic review on the effectiveness of titratable over nontitratable mandibular advancement appliances for sleep apnea.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2017-01-01

Mandibular advancement appliances are being tested for use in patients with obstructive sleep apnea (OSA). However, the effectiveness of titration of these appliances does not have conclusive evidence. Systematic reviews help us to compile all available clinical evidence using statistical principles. Hence, the aim of this systematic review is to identify the effectiveness of titratable over nontitratable mandibular advancement appliances in patients with mild to moderate OSA. This review objective is to identify if titration of these appliances produce significant benefits over fixed appliances. Electronic databases were searched to identify eligible studies based on set inclusion criteria. Data extraction form was created and the data were extracted. The participants were mild to moderate OSA patients who received mandibular advancement appliances. Studies included a comparison between titratable and nontitratable mandibular advancement appliance. Of the five included studies, three were observational and two were a randomized trial. All these studies were conducted in adults. The outcome attributes were polysomnographic readings and apnea-hypopnea index (AHI). A significant heterogeneity was seen between the eligible studies and hence a meta-analysis could not be performed. The results from this systematic review did not show significant advantages of titratable appliances, although titratable appliances performed better from individual studies as regards to reduction in AHI and polysomnography. The reason is the lack of sufficient clinical trials on the same. More high quality randomized controlled trials comparing titratable and fixed appliances have to be initiated to get to conclusive evidence.

Discriminating ability of Cirrus and RTVue optical coherence tomography in different stages of glaucoma

PubMed Central

Mittal, Deepti; Dubey, Suneeta; Gandhi, Monica; Pegu, Julie; Bhoot, Madhu; Gupta, Yadunandan Prasad

2018-01-01

Purpose: The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters. Methods: One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit. Results: Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05). Conclusion: Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma. PMID:29676314

Discriminating ability of Cirrus and RTVue optical coherence tomography in different stages of glaucoma.

PubMed

Mittal, Deepti; Dubey, Suneeta; Gandhi, Monica; Pegu, Julie; Bhoot, Madhu; Gupta, Yadunandan Prasad

2018-05-01

The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters. One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit. Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05). Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma.

Oral appliance therapy in obstructive sleep apnea: Long-term adherence and patients experiences.

PubMed

Saglam-Aydinatay, B; Taner, T

2018-01-01

Despite the advances in the treatment of obstructive sleep apnea (OSA) with mandibular advancement appliances (MAA), their effectiveness is dependent on the patients compliance. Our aims were to evaluate the long-term adherence to MAA therapy and patients experiences of the treatment in OSA. Sixty-nine patients (52 males, 17 females; Mean age: 54.4±10.8 years) were included in the study. The subjects were mild (56%) and moderate (44%) OSA patients who had been treated using MAA at least 4 years prior to the study. A phone survey was used to determine the demographic characteristics of the patients, as well as to assess self-reported adherence to therapy, subjective long-term effectiveness, and patient experiences with the appliance. Descriptive statistics, Pearson Chi-square test, and independent samples t-test were used for data analysis. Only 22 (32%) patients reported using the appliance regularly. Most of the non-adherent patients had stopped using their appliances in the first year (55%). The mean duration of appliance use was 33.5 months (Median: 12 months). No significant differences in appliance type, OSA severity, educational level, gender, marital status, income status, employment status or place of residence existed between adherent and non-adherent subjects. Adherent subjects were significantly younger than non-adherent subjects (Age: 50.6 ± 11.9 versus 56.1 ± 9.9, p < 0.05). The most common reasons reported by patients were inability to adapt to the appliance (62%) and pain in the temporomandibular joint (38%). The most common factors associated with continued usage were effectiveness (100%) and ease of use (64%). The overall long-term nonadherence to MAA therapy in mild-to moderate OSA patients was high suggesting that barriers to MAA therapy adherence should be prevented to increase the efficiency of oral appliance treatment in OSA and achieve better outcomes for this disease.

Targeted-bisulfite sequence analysis of the methylation of CpG islands in genes encoding PNPLA3, SAMM50, and PARVB of patients with non-alcoholic fatty liver disease.

PubMed

Kitamoto, Takuya; Kitamoto, Aya; Ogawa, Yuji; Honda, Yasushi; Imajo, Kento; Saito, Satoru; Yoneda, Masato; Nakamura, Takahiro; Nakajima, Atsushi; Hotta, Kikuko

2015-08-01

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is affected by epigenetic factors as well as by genetic variation. We performed targeted-bisulfite sequencing to determine the levels of DNA methylation of 4 CpG islands (CpG99, CpG71, CpG26, and CpG101) in the regulatory regions of PNPLA3, SAMM50, PARVB variant 1, and PARVB variant 2, respectively. We compared the levels of methylation of DNA in the livers of the first and second sets of patients with mild (fibrosis stages 0 and 1) or advanced (fibrosis stages 2 to 4) NAFLD and in those of patients with mild (F0 to F2) or advanced (F3 and F4) chronic hepatitis C infection. The hepatic mRNA levels of PNPLA3, SAMM50, and PARVB were measured using qPCR. CpG26, which resides in the regulatory region of PARVB variant 1, was markedly hypomethylated in the livers of patients with advanced NAFLD. Conversely, CpG99 in the regulatory region of PNPLA3 was substantially hypermethylated in these patients. These differences in DNA methylation were replicated in a second set of patients with NAFLD or chronic hepatitis C. PNPLA3 mRNA levels in the liver of the same section of a biopsy specimen used for genomic DNA preparation were lower in patients with advanced NAFLD compared with those with mild NAFLD and correlated inversely with CpG99 methylation in liver DNA. Moreover, the levels of CpG99 methylation and PNPLA3 mRNA were affected by the rs738409 genotype. Hypomethylation of CpG26 and hypermethylation of CpG99 may contribute to the severity of fibrosis in patients with NAFLD or chronic hepatitis C infection. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Reasons and evolution of non-thrombolysis in acute ischaemic stroke

PubMed Central

Reiff, T; Michel, P

2017-01-01

Introduction Despite increasing evidence of its efficacy in advanced age or in mild or severe strokes, intravenous thrombolysis remains underused for acute ischaemic stroke (AIS). Our aim was to obtain an updated view of reasons for non-thrombolysis and to identify its changing patterns over time. Methods This is a retrospective study of prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) from the years 2003–2011. Patients admitted with acute stroke in the past 24 hours who had not had thrombolysis were identified; reasons for non-thrombolysis documented in the prospectively entered data were tabulated and analysed for the group as a whole. Data were analysed for the years 2003–2006 and 2007 forward because of changes in contraindications. A subgroup of patients who arrived within the treatment window ≤180 min was separately analysed for reasons for non-thrombolysis. Predictors of non-thrombolysis were investigated via multivariate regression analyses. Results In the 2019 non-thrombolysed patients the most frequent reasons for non-thrombolysis were admission delays (66.3%), stroke severity (mostly mild) (47.9%) and advanced age (14.1%); 55.9% had more than one exclusion criterion. Among patients arriving ≤180 min after onset, the main reasons were stroke severity and advanced age. After 2006, significantly fewer patients were excluded because of age (OR 2.65, p<0.001) or (mostly mild) stroke severity (OR 10.56, p=0.029). Retrospectively, 18.7% of all non-thrombolysed patients could have been treated because they only had relative contraindications. Conclusion Onset-to-admission delays remain the main exclusion criterion for thrombolysis. Among early arrivals, relative contraindications such as minor stroke severity and advanced age were frequent. Thrombolysis rate increased with the reduction of thrombolysis restrictions (eg, age and stroke severity). PMID:27797870

Fractal-Based Oscillation of Macular Arteriogenesis and Dropout During Progressive Diabetic Retinopathy

NASA Technical Reports Server (NTRS)

Radharkrishnan, Krishnan; Kaiser, Peter K.

2011-01-01

By both fractal (D1) and branching (Lv) analysis, macular arterial density oscillated with progression from mild NPDR to PDR. Results are consistent with out study reported recently for the entire arterial and venous branching trees within 50 degree FAs by VESGEN generational branching analysis. Current and previous results are important for advances in early-stage regenerative DR therapies, for which reversal of DR progression to a normal vessel density may be possible. For example, potential use of regenerative angiogenesis stimulators to reverse vascular dropout during mild and severe NPDR is not indicated for treatment of moderate NPDR.

Mild Traumatic Brain Injury and Conduction Aphasia from a Close Proximity Blast Resulting in Arcuate Fasciculus Damage Diagnosed on DTI Tractography

DTIC Science & Technology

2009-11-01

communication which are described below as conduction aphasia and neurogenic stuttering secondary to the aphasia. Also, his family felt that his personality... stuttering , and “mumbling” speech. In continued evaluation, estimated premorbid intellectual ability was at least in the average range. Speech...language production resulted in mild neurogenic stuttering . There was also some evidence of visuoconstructional dysfunction. In addition there was

Eco-Friendly Magnetic Iron Oxide Pillared Montmorillonite for Advanced Catalytic Degradation of Dichlorophenol

EPA Science Inventory

Eco-friendly pillared montmorillonites, in which the pillars consist of iron oxide are expected to have interesting and unusual magnetic properties that are applicable for environmental decontamination. Completely “green” and effective composite was synthesized using mild reactio...

Clinical effectiveness and cost-effectiveness results from the randomised controlled Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and long-term economic analysis of oral devices and continuous positive airway pressure.

PubMed

Sharples, Linda; Glover, Matthew; Clutterbuck-James, Abigail; Bennett, Maxine; Jordan, Jake; Chadwick, Rebecca; Pittman, Marcus; East, Clare; Cameron, Malcolm; Davies, Mike; Oscroft, Nick; Smith, Ian; Morrell, Mary; Fox-Rushby, Julia; Quinnell, Timothy

2014-10-01

Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness (EDS), impairs quality of life (QoL) and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment is clinically effective but undermined by intolerance, and its cost-effectiveness is borderline in milder cases. Mandibular advancement devices (MADs) are another option, but evidence is lacking regarding their clinical effectiveness and cost-effectiveness in milder disease. (1) Conduct a randomised controlled trial (RCT) examining the clinical effectiveness and cost-effectiveness of MADs against no treatment in mild to moderate OSAH. (2) Update systematic reviews and an existing health economic decision model with data from the Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and newly published results to better inform long-term clinical effectiveness and cost-effectiveness of MADs and CPAP in mild to moderate OSAH. A crossover RCT comparing clinical effectiveness and cost-effectiveness of three MADs: self-moulded [SleepPro 1™ (SP1); Meditas Ltd, Winchester, UK]; semibespoke [SleepPro 2™ (SP2); Meditas Ltd, Winchester, UK]; and fully bespoke [bespoke MAD (bMAD); NHS Oral-Maxillofacial Laboratory, Addenbrooke's Hospital, Cambridge, UK] against no treatment, in 90 adults with mild to moderate OSAH. All devices improved primary outcome [apnoea-hypopnoea index (AHI)] compared with no treatment: relative risk 0.74 [95% confidence interval (CI) 0.62 to 0.89] for SP1; relative risk 0.67 (95% CI 0.59 to 0.76) for SP2; and relative risk 0.64 (95% CI 0.55 to 0.76) for bMAD (p < 0.001). Differences between MADs were not significant. Sleepiness [as measured by the Epworth Sleepiness Scale (ESS)] was scored 1.51 [95% CI 0.73 to 2.29 (SP1)] to 2.37 [95% CI 1.53 to 3.22 (bMAD)] lower than no treatment (p < 0.001), with SP2 and bMAD significantly better than SP1. All MADs improved disease-specific QoL. Compliance was lower for SP1, which was unpopular at trial exit. At 4 weeks, all devices were cost-effective at £20,000/quality-adjusted life-year (QALY), with SP2 the best value below £39,800/QALY. A MEDLINE, EMBASE and Science Citation Index search updating two existing systematic reviews (one from November 2006 and the other from June 2008) to August 2013 identified 77 RCTs in adult OSAH patients comparing MAD with conservative management (CM), MADs with CPAP or CPAP with CM. MADs and CPAP significantly improved AHI [MAD -9.3/hour (p < 0.001); CPAP -25.4/hour (p < 0.001)]. Effect difference between CPAP and MADs was 7.0/hour (p < 0.001), favouring CPAP. No trials compared CPAP with MADs in mild OSAH. MAD and CPAP reduced the ESS score similarly [MAD 1.6 (p < 0.001); CPAP 1.6 (p < 0.001)]. An existing model assessed lifetime cost-utility of MAD and CPAP in mild to moderate OSAH, using the revised meta-analysis to update input values. The TOMADO provided utility estimates, mapping ESS score to European Quality of Life-5 Dimensions three-level version for device cost-utility. Using SP2 as the standard device, MADs produced higher mean costs and mean QALYs than CM [incremental cost-effectiveness ratio (ICER) £6687/QALY]. From a willingness to pay (WTP) of £15,367/QALY, CPAP is cost-effective, although the likelihood of MADs (p = 0.48) and CPAP (p = 0.49) being cost-effective is very similar. Both were better than CM, but there was much uncertainty in the choice between CPAP and MAD (at a WTP £20,000/QALY, the probability of being the most cost-effective was 47% for MAD and 52% for CPAP). When SP2 lifespan increased to 18 months, the ICER for CPAP compared with MAD became £44,066. The ICER for SP1 compared with CM was £1552, and for bMAD compared with CM the ICER was £13,836. The ICER for CPAP compared with SP1 was £89,182, but CPAP produced lower mean costs and higher mean QALYs than bMAD. Differential compliance rates for CPAP reduces cost-effectiveness so MADs become less costly and more clinically effective with CPAP compliance 90% of SP2. Mandibular advancement devices are clinically effective and cost-effective in mild to moderate OSAH. A semi-bespoke MAD is the appropriate first choice in most patients in the short term. Future work should explore whether or not adjustable MADs give additional clinical and cost benefits. Further data on longer-term cardiovascular risk and its risk factors would reduce uncertainty in the health economic model and improve precision of effectiveness estimates. This trial is registered as ISRCTN02309506. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 67. See the NIHR Journals Library website for further project information.

Clinical effectiveness and cost-effectiveness results from the randomised controlled Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and long-term economic analysis of oral devices and continuous positive airway pressure.

PubMed Central

Sharples, Linda; Glover, Matthew; Clutterbuck-James, Abigail; Bennett, Maxine; Jordan, Jake; Chadwick, Rebecca; Pittman, Marcus; East, Clare; Cameron, Malcolm; Davies, Mike; Oscroft, Nick; Smith, Ian; Morrell, Mary; Fox-Rushby, Julia; Quinnell, Timothy

2014-01-01

BACKGROUND Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness (EDS), impairs quality of life (QoL) and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment is clinically effective but undermined by intolerance, and its cost-effectiveness is borderline in milder cases. Mandibular advancement devices (MADs) are another option, but evidence is lacking regarding their clinical effectiveness and cost-effectiveness in milder disease. OBJECTIVES (1) Conduct a randomised controlled trial (RCT) examining the clinical effectiveness and cost-effectiveness of MADs against no treatment in mild to moderate OSAH. (2) Update systematic reviews and an existing health economic decision model with data from the Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and newly published results to better inform long-term clinical effectiveness and cost-effectiveness of MADs and CPAP in mild to moderate OSAH. TOMADO A crossover RCT comparing clinical effectiveness and cost-effectiveness of three MADs: self-moulded [SleepPro 1™ (SP1); Meditas Ltd, Winchester, UK]; semibespoke [SleepPro 2™ (SP2); Meditas Ltd, Winchester, UK]; and fully bespoke [bespoke MAD (bMAD); NHS Oral-Maxillofacial Laboratory, Addenbrooke's Hospital, Cambridge, UK] against no treatment, in 90 adults with mild to moderate OSAH. All devices improved primary outcome [apnoea-hypopnoea index (AHI)] compared with no treatment: relative risk 0.74 [95% confidence interval (CI) 0.62 to 0.89] for SP1; relative risk 0.67 (95% CI 0.59 to 0.76) for SP2; and relative risk 0.64 (95% CI 0.55 to 0.76) for bMAD (p < 0.001). Differences between MADs were not significant. Sleepiness [as measured by the Epworth Sleepiness Scale (ESS)] was scored 1.51 [95% CI 0.73 to 2.29 (SP1)] to 2.37 [95% CI 1.53 to 3.22 (bMAD)] lower than no treatment (p < 0.001), with SP2 and bMAD significantly better than SP1. All MADs improved disease-specific QoL. Compliance was lower for SP1, which was unpopular at trial exit. At 4 weeks, all devices were cost-effective at £20,000/quality-adjusted life-year (QALY), with SP2 the best value below £39,800/QALY. META-ANALYSIS A MEDLINE, EMBASE and Science Citation Index search updating two existing systematic reviews (one from November 2006 and the other from June 2008) to August 2013 identified 77 RCTs in adult OSAH patients comparing MAD with conservative management (CM), MADs with CPAP or CPAP with CM. MADs and CPAP significantly improved AHI [MAD -9.3/hour (p < 0.001); CPAP -25.4/hour (p < 0.001)]. Effect difference between CPAP and MADs was 7.0/hour (p < 0.001), favouring CPAP. No trials compared CPAP with MADs in mild OSAH. MAD and CPAP reduced the ESS score similarly [MAD 1.6 (p < 0.001); CPAP 1.6 (p < 0.001)]. LONG-TERM COST-EFFECTIVENESS An existing model assessed lifetime cost-utility of MAD and CPAP in mild to moderate OSAH, using the revised meta-analysis to update input values. The TOMADO provided utility estimates, mapping ESS score to European Quality of Life-5 Dimensions three-level version for device cost-utility. Using SP2 as the standard device, MADs produced higher mean costs and mean QALYs than CM [incremental cost-effectiveness ratio (ICER) £6687/QALY]. From a willingness to pay (WTP) of £15,367/QALY, CPAP is cost-effective, although the likelihood of MADs (p = 0.48) and CPAP (p = 0.49) being cost-effective is very similar. Both were better than CM, but there was much uncertainty in the choice between CPAP and MAD (at a WTP £20,000/QALY, the probability of being the most cost-effective was 47% for MAD and 52% for CPAP). When SP2 lifespan increased to 18 months, the ICER for CPAP compared with MAD became £44,066. The ICER for SP1 compared with CM was £1552, and for bMAD compared with CM the ICER was £13,836. The ICER for CPAP compared with SP1 was £89,182, but CPAP produced lower mean costs and higher mean QALYs than bMAD. Differential compliance rates for CPAP reduces cost-effectiveness so MADs become less costly and more clinically effective with CPAP compliance 90% of SP2. CONCLUSIONS Mandibular advancement devices are clinically effective and cost-effective in mild to moderate OSAH. A semi-bespoke MAD is the appropriate first choice in most patients in the short term. Future work should explore whether or not adjustable MADs give additional clinical and cost benefits. Further data on longer-term cardiovascular risk and its risk factors would reduce uncertainty in the health economic model and improve precision of effectiveness estimates. TRIAL REGISTRATION This trial is registered as ISRCTN02309506. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 67. See the NIHR Journals Library website for further project information. PMID:25359435

Effects of Light and Sound on the Prefrontal Cortex Activation and Emotional Function: A Functional Near-Infrared Spectroscopy Study

PubMed Central

Hori, Shota; Mori, Koichi; Mashimo, Takehisa; Seiyama, Akitoshi

2017-01-01

We constructed a near infrared spectroscopy-based real-time feedback system to estimate the subjects' emotional states using the changes in oxygenated hemoglobin concentration [Δ(oxy-Hb)] in the prefrontal cortex (PFC). Using this system, we investigated the influences of continual mild and equivocal stimuli consisting of lights and a reconstructed waterfall sound on Δ[oxy-Hb] in the PFC. The visual (light) and auditory (sound) stimuli changed randomly and independently, depending on the emotional states of the individual subjects. The emotional states induced by the stimuli were examined via a questionnaire rated on an 11-point scale, from +5 (pleasant) to −5 (unpleasant), through 0 (neutral), after the 5-min experiments. Results from 757 subjects revealed that Δ[oxy-Hb] in the PFC exhibited a weak, but significant, correlation with emotional change, with the given continual and mild stimuli similar to that experienced in response to the intense pleasant/unpleasant stimuli. Based on the results we discuss the generation of pleasant/unpleasant weak emotional change induced by mild and weak stimuli such as light and sound. PMID:28649190

Teacher-Directed and Student-Mediated Textbook Comprehension Strategies.

ERIC Educational Resources Information Center

Reynolds, Catharine J.; Salend, Spencer J.

1990-01-01

The article describes teacher-directed and student-mediated comprehension strategies to improve the text comprehension skills of mainstreamed students with mild disabilities. Techniques include advance organizers, study guides, color coding, oral reading, critical thinking maps, and self-questioning techniques. Guidelines are offered for assessing…

Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnoea syndrome: a randomised, placebo-controlled trial on self-reported symptoms of common sleep disorders and sleep-related problems.

PubMed

Nikolopoulou, M; Byraki, A; Ahlberg, J; Heymans, M W; Hamburger, H L; De Lange, J; Lobbezoo, F; Aarab, G

2017-06-01

Obstructive sleep apnoea syndrome (OSAS) is associated with several sleep disorders and sleep-related problems. Therefore, the aim of this study was to compare the effects of a mandibular advancement device (MAD) with those of nasal continuous positive airway pressure (nCPAP) on self-reported symptoms of common sleep disorders and sleep-related problems in mild and moderate OSAS patients. In this randomised placebo-controlled trial, sixty-four OSAS patients (52·0 ± 9·6 years) were randomly assigned to an MAD, nCPAP or an intra-oral placebo appliance in a parallel design. All participants filled out the validated Dutch Sleep Disorders Questionnaire (SDQ) twice: one before treatment and one after six months of treatment. With 88 questions, thirteen scales were constructed, representing common sleep disorders and sleep-related problems. Linear mixed model analyses were performed to study differences between the groups for the different SDQ scales over time. The MAD group showed significant improvements over time in symptoms corresponding with 'insomnia', 'excessive daytime sleepiness', 'psychiatric sleep disorder', 'periodic limb movements', 'sleep apnoea', 'sleep paralysis', 'daytime dysfunction', 'hypnagogic hallucinations/dreaming', 'restless sleep', 'negative conditioning' and 'automatic behaviour' (range of P values: 0·000-0·014). These improvements in symptoms were, however, not significantly different from the improvements in symptoms observed in the nCPAP and placebo groups (range of P values: 0·090-0·897). It can be concluded that there is no significant difference between MAD and nCPAP in their positive effects on self-reported symptoms of common sleep disorders and sleep-related problems in mild and moderate OSAS patients. These beneficial effects may be a result of placebo effects. © 2017 John Wiley & Sons Ltd.

Does gender matter? Differences in social-emotional behavior among infants and toddlers before and after mild traumatic brain injury: a preliminary study.

PubMed

Kaldoja, Mari-Liis; Kolk, Anneli

2015-06-01

Traumatic brain injury is a common cause of acquired disability in childhood. While much is known about cognitive sequelae of brain trauma, gender-specific social-emotional problems in children with mild traumatic brain injury is far less understood. The aims of the study were to investigate gender differences in social-emotional behavior before and after mild traumatic brain injury. Thirty-five 3- to 65-month-old children with mild traumatic brain injury and 70 controls were assessed with Ages and Stages Questionnaires: Social-Emotional. Nine months later, 27 of 35 patients and 54 of 70 controls were reassessed. We found that before injury, boys had more self-regulation and autonomy difficulties and girls had problems with adaptive functioning. Nine months after injury, boys continued to struggle with self-regulation and autonomy and new difficulties with interaction had emerged, whereas in girls, problems in interaction had evolved. Even mild traumatic brain injury in early childhood disrupts normal social-emotional development having especially devastating influence on interaction skills. © The Author(s) 2014.

Progressive brain atrophy in patients with chronic neuropsychiatric symptoms after mild traumatic brain injury: a preliminary study.

PubMed

Ross, David E; Ochs, Alfred L; Seabaugh, Jan M; Demark, Michael F; Shrader, Carole R; Marwitz, Jennifer H; Havranek, Michael D

2012-01-01

NeuroQuant® is a recently developed, FDA-approved software program for measuring brain MRI volume in clinical settings. The aims of this study were as follows: (1) to examine the test-retest reliability of NeuroQuant®; (2) to test the hypothesis that patients with mild traumatic brain injury (TBI) would have abnormally rapid progressive brain atrophy; and (3) to test the hypothesis that progressive brain atrophy in patients with mild TBI would be associated with vocational outcome. Sixteen patients with mild TBI were compared to 20 normal controls. Vocational outcome was assessed with the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS). NeuroQuant® showed high test-re-test reliability. Patients had abnormally rapid progressive atrophy in several brain regions and the rate of atrophy was associated with inability to return to work. NeuroQuant®, is a reliable and valid method for assessing the anatomic effects of TBI. Progression of atrophy may continue for years after injury, even in patients with mild TBI.

Modeling and Controls Development of 48V Mild Hybrid Electric Vehicles

EPA Science Inventory

The Advanced Light-Duty Powertrain and Hybrid Analysis tool (ALPHA) was created by EPA to evaluate the Greenhouse Gas (GHG) emissions of Light-Duty (LD) vehicles. It is a physics-based, forward-looking, full vehicle computer simulator capable of analyzing various vehicle types c...

A Case of Intestinal Obstruction Caused by Prominent Kyphosis Resulting in Compression of the Intestine by the Costal Arch

PubMed Central

Yoneyama, Satoshi; Kato, Takehito; Yumoto, Tetsuya; Ohwada, Masami; Terashima, Toru; Koizumi, Masanori; Ueki, Hamaichi

2013-01-01

An 85-year-old woman with no history of abdominal surgery complained of abdominal pain and vomiting and was referred to us with a diagnosis of intestinal obstruction a few days later. Upon admission to our facility, she presented with marked abdominal swelling and prominent kyphosis. Because of the kyphosis, most of the dilated bowel was compressing her thoracic cavity. No obvious strangulation or free air was observed via abdominal computed tomography imaging. We attempted decompression using a nasogastric tube, but the symptoms persisted. Surgery was performed 2 days after admission. The origin of the obstruction was a compression of the ileocecal region by the costal arch. The bowel was discolored, and thus surgically excised. There were no major postsurgical complications other than a mild wound infection. Until now, there have been no reports of advanced kyphosis inducing ileus, but there are concerns of an increase in similar cases as society continues to age. PMID:23971780

Recent research about mild cognitive impairment in China

PubMed Central

CHENG, Yan; XIAO, Shifu

2014-01-01

Summary: The rapid aging of the Chinese population has spurred interest in research about the cause and prevention of dementia and its precursor, mild cognitive impairment (MCI). This review summarizes the last decade of research in China about MCI. Extensive research about the epidemiology, neuropsychological characteristics, diagnosis, genetic etiology, neuroimaging and electrophysiological changes, and treatment of MCI has provided some new insights but few breakthroughs. Further advances in the prevention and treatment of MCI will require a greater emphasis on multi-disciplinary prospective studies with large, representative samples that use standardized methods to assess and monitor changes in cognitive functioning over time. PMID:25114476

NASA's future Earth observation plans

NASA Astrophysics Data System (ADS)

Neeck, Steven P.; Paules, Granville E.; McCuistion Ramesh, J. D.

2004-11-01

NASA's Science Mission Directorate, working with its domestic and international partners, provides accurate, objective scientific data and analysis to advance our understanding of Earth system processes. Learning more about these processes will enable improved prediction capability for climate, weather, and natural hazards. Earth interactions occur on a continuum of spatial and temporal scales ranging from short-term weather to long-term climate, and from local and regional to global. Quantitatively describing these changes means precisely measuring from space scores of biological and geophysical parameters globally. New missions that SMD will launch in the coming decade will complement the first series of the Earth Observing System. These next generation systematic measurement missions are being planned to extend or enhance the record of science-quality data necessary for understanding and predicting global change. These missions include the NPOESS Preparatory Project, Ocean Surface Topography Mission, Global Precipitation Measurement, Landsat Data Continuity Mission, and an aerosol polarimetry mission called Glory. New small explorer missions will make first of a kind Earth observations. The Orbiting Carbon Observatory will measure sources and sinks of carbon to help the Nation and the world formulate effective strategies to constrain the amount of this greenhouse gas in the atmosphere. Aquarius will measure ocean surface salinity which is key to ocean circulation in the North Atlantic that produces the current era's mild climate in northern Europe. HYDROS will measure soil moisture globally. Soil moisture is critical to agriculture and to managing fresh water resources. NASA continues to design, develop and launch the Nation's civilian operational environmental satellites, in both polar and geostationary orbits, by agreement with the National Oceanic and Atmospheric Administration (NOAA). NASA plans to develop an advanced atmospheric sounder, GIFTS, for geostationary orbit to facilitate continuous measurements of weather-related phenomena, improve "nowcasting" of extreme weather events, and measure important atmospheric gases. NASA is currently developing with its partners the National Polar-orbiting Operational Environmental Satellite System (NPOESS) and the next-generation geostationary system, GOES-R. Future missions will migrate today's capabilities in low Earth orbit to higher orbits such as L1 and L2 to enable more continuous monitoring of changes in the Earth system with a smaller number of satellites.

The Effect of mandible advancement splints in mild, moderate, and severe obstructive sleep apnea-the need for sleep registrations during follow up.

PubMed

Palotie, Tuula; Riekki, Siru; Mäkitie, Antti; Bachour, Adel; Arte, Sirpa; Bäck, Leif

2017-10-01

Our aim was to evaluate the effect of mandible advancement splint (MAS) in mild, moderate, and severe obstructive sleep apnea (OSA). We also determined, if and in which OSA-groups the adequate forward movement in MAS could be quantified without sleep registration for different OSA levels. A retrospective study. The effect of MAS was measured with clinical methods and by sleep registration. The series consisted of 103 patients, 75 males and 28 females (mean age 52 years) suffering from mild (32 per cent), moderate (32 per cent), or severe (36 per cent) OSA, who were treated with MAS at Helsinki University Hospital, Finland during the years 2011-2012. Seventy per cent of the patients had tried continuous positive airway pressure (CPAP) before MAS. The lower the body mass index (BMI) was the bigger the probability was to get apnea/hypopnea index (AHI) values <5 per hour with MAS (P < 0.01). The total AHI decreased significantly from the baseline with MAS: 23 per hour (range 5-89) to 6 per hour (range 0.3-54), (P < 0.001). The mean oxygen desaturation index (ODI4%) improved significantly from 16 per hour (range 1-76) to 5.3 per hour (range 0.2-49), (P < 0.01), and the minimum oxygen saturation improved significantly from 84 per cent (67-91) to 87 per cent (68-93), (P < 0.01). The reduction of AHI with MAS was significantly bigger in patients with a previous CPAP experience (73 per cent) than those who did not tried CPAP therapy. The positive correlation was found between the decrease in AHI and the increase of the protrusion in MAS. Both sleep recordings and subjective indicators demonstrated that MAS therapy was successful in OSA based on ESS, total AHI, ODI4%, and minimum oxygen saturation values. It seems useful to increase the protrusion at its maximal clinical tolerance. An experienced dentist could make therapeutically decision concerning the follow up of MAS efficacy regardless of the result of sleep study. We suggest that MAS is a valuable treatment alternative for CPAP. However, the previous use of CPAP with MAS as well as lower baseline BMI seem to have a positive correlation with the success of MAS therapy. © The Author 2016. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

Phase I safety, pharmacokinetic, and pharmacodynamic study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced cancer.

PubMed

Hoekstra, Ronald; de Vos, Filip Y F L; Eskens, Ferry A L M; Gietema, Jourik A; van der Gaast, Ate; Groen, Harry J M; Knight, Raymond A; Carr, Robert A; Humerickhouse, Rod A; Verweij, Jaap; de Vries, Elisabeth G E

2005-08-01

ABT-510 is an angiogenesis inhibitor derived from thrombospondin-1, a naturally occurring inhibitor of angiogenesis. We investigated ABT-510, which was administered subcutaneously in patients with advanced solid malignancies, to assess safety, pharmacokinetics, and serum markers of angiogenesis. ABT-510 was administered subcutaneously as a continuous infusion (100 mg/24 h) and bolus injections (100, 200, and 260 mg once daily; 50 and 100 mg twice daily) in 28-day cycles. Thirty-nine patients received a total of 144 treatment cycles. Administration by continuous infusion was hampered by the onset of painful skin infiltrates at the injection site. In the bolus injection regimens, the most common toxicities observed were mild injection-site reactions and fatigue. Maximum-tolerated dose was not defined, but 260 mg was defined as the maximum clinically practical dose. ABT-510 pharmacokinetics were linear across the dosage ranges tested, and the potential therapeutic threshold (plasma concentrations > 100 ng/mL > 3 h/d) was achieved with all dose regimens. Median serum basic fibroblast growth factor (bFGF) levels decreased from 14.1 pg/mL (range, 0.5 to 77.7 pg/mL) at baseline to 3.2 pg/mL (range, 0.2 to 29.4 pg/mL) after 56 days of treatment (P = .003). No correlations with time on study or ABT-510 dose or exposure were observed for individual changes in bFGF. Stable disease lasting for six cycles or more was seen in six patients. ABT-510 demonstrated a favorable toxicity profile and linear and time-independent pharmacokinetics with biologically relevant plasma concentrations. The significant number of patients with prolonged stable disease and the convenient method of dosing merit further studies with this angiogenesis inhibitor.

Automatic voxel-based morphometry of structural MRI by SPM8 plus diffeomorphic anatomic registration through exponentiated lie algebra improves the diagnosis of probable Alzheimer Disease.

PubMed

Matsuda, H; Mizumura, S; Nemoto, K; Yamashita, F; Imabayashi, E; Sato, N; Asada, T

2012-06-01

The necessity for structural MRI is greater than ever to both diagnose AD in its early stage and objectively evaluate its progression. We propose a new VBM-based software program for automatic detection of early specific atrophy in AD. A target VOI was determined by group comparison of 30 patients with very mild AD and 40 age-matched healthy controls by using SPM. Then this target VOI was incorporated into a newly developed automated software program independently running on a Windows PC for VBM by using SPM8 plus DARTEL. ROC analysis was performed for discrimination of 116 other patients with AD with very mild stage (n = 45), mild stage (n = 30) and moderate-to-advanced stages (n = 41) from 40 other age-matched healthy controls by using a z score map in the target VOI. Medial temporal structures involving the entire region of the entorhinal cortex, hippocampus, and amygdala showed significant atrophy in the patients with very mild AD and were determined as a target VOI. When we used the severity score of atrophy in this target VOI, 91.6%, 95.8%, and 98.2% accuracies were obtained in the very mild AD, mild AD, and moderate-to-severe AD groups, respectively. In the very mild AD group, a high specificity of 97.5% with a sensitivity of 86.4% was obtained, and age at onset of AD did not influence this accuracy. This software program with application of SPM8 plus DARTEL to VBM provides a high performance for AD diagnosis by using MRI.

Dual-Retrieval Models and Neurocognitive Impairment

ERIC Educational Resources Information Center

Brainerd, C. J.; Reyna, V. F.; Gomes, C. F. A.; Kenney, A. E.; Gross, C. J.; Taub, E. S.; Spreng, R. N.

2014-01-01

Advances in dual-retrieval models of recall make it possible to use clinical data to test theoretical hypotheses about mild cognitive impairment (MCI) and Alzheimer's dementia (AD), the most common forms of neurocognitive impairment. Hypotheses about the nature of the episodic memory declines in these diseases, about decline versus sparing of…

Regional vascular density-visual field sensitivity relationship in glaucoma according to disease severity.

PubMed

Shin, Joong Won; Lee, Jiyun; Kwon, Junki; Choi, Jaewan; Kook, Michael S

2017-12-01

To study whether there are global and regional relationships between peripapillary vascular density (pVD) assessed by optical coherence tomography angiography (OCT-A) and visual field (VF) mean sensitivity at different glaucoma stages. Microvascular images and peripapillary retinal nerve fibre layer (pRNFL) thicknesses were obtained using a Cirrus OCT-A device in 91 glaucoma subjects. The pVD was measured at various spatial locations according to the Garway-Heath map, using a MATLAB software (The MathWorks, Natick, Massachusetts). VF mean sensitivity (VFMS) was recorded in the 1/L scale. Global and regional vasculature-function (pVD vs VFMS) relationships were assessed in separate patient groups at mild and moderate-to-advanced stages of glaucoma. The pVDs at superotemporal and inferotemporal regions were significantly associated with corresponding VFMS in mild glaucoma (p<0.05). In moderate-to-advanced glaucoma, there were significant associations between pVD and VFMS, regardless of location. The association between global pVD and VFMS was significantly stronger than that between global pRNFL thickness and VFMS in moderate-to-advanced stage glaucoma (p <0.05). Global and regional pVD measured by OCT-A was significantly associated with corresponding VFMS in moderate-to-advanced glaucoma. OCT-A may be useful in monitoring glaucoma at various stages. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Learning and using technology in intertwined processes: a study of people with mild cognitive impairment or Alzheimer's disease.

PubMed

Rosenberg, Lena; Nygård, Louise

2014-09-01

People with mild cognitive impairment and Alzheimer's disease are likely to be challenged by the multitude of everyday technology in today's society. The aim of this study was to explore how they try to prohibit, avoid or solve problems in everyday technology use, maintain skills, and learn to use new technology. To explore how the participants applied and reasoned about using everyday technology in real-life situations interviews were conducted while the participants used their own technology in their homes. Interviews were conducted with 20 participants with mild cognitive impairment (n = 10) or Alzheimer's disease (n = 10). The analyses were inspired from grounded theory and resulted in one core category and three sub-categories that represent sub-processes in the core. The core finding presents a continuous, intertwined process of learning and using everyday technology, highlighting how the context was interwoven in the processes. The participants used a rich variety of management strategies when approaching technology, including communication with the everyday technologies on different levels. The findings underscore that it is important to support continued use of everyday technology as long as it is valued and relevant to the person with mild cognitive impairment or Alzheimer's disease. The intertwined process of learning and using everyday technology suggests how support could target different sub-processes. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

PubMed Central

Poggesi, Anna; Salvadori, Emilia; Pantoni, Leonardo; Pracucci, Giovanni; Cesari, Francesca; Chiti, Alberto; Ciolli, Laura; Cosottini, Mirco; Del Bene, Alessandra; De Stefano, Nicola; Diciotti, Stefano; Dotti, Maria Teresa; Ginestroni, Andrea; Giusti, Betti; Gori, Anna Maria; Nannucci, Serena; Orlandi, Giovanni; Pescini, Francesca; Valenti, Raffaella; Abbate, Rosanna; Federico, Antonio; Mascalchi, Mario; Murri, Luigi; Inzitari, Domenico

2012-01-01

Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD. PMID:22550606

Clinical Course Score (CCS): a new clinical score to evaluate efficacy of neurotrauma treatment in traumatic brain injury and subarachnoid hemorrhage.

PubMed

Brandner, Sebastian; Kellermann, Isabel; Hore, Nirjhar; Bozhkov, Yavor; Buchfelder, Michael

2015-01-01

Neurotrauma continues to represent a challenging public health issue requiring continual improvement in therapeutic approaches. As no such current system exists, we present in this study the Clinical Course Score (CCS) as a new clinical score to evaluate the efficacy of neurotrauma treatment. The CCS was calculated in neurotrauma patients to be the difference between the grade of the Glasgow Outcome Scale 6 months after discharge from our department and the grade of a 1 to 5 point reduced Glasgow Coma Scale on admission. We assessed the CCS in a total of 248 patients (196 traumatic brain injury [TBI] patients and 52 subarachnoid hemorrhage [SAH] patients) who were treated in our Department of Neurosurgery between January 2011 and December 2012. We found negative CCS grades both in mild TBI and in mild SAH patients. In patients with severe TBI or SAH, we found positive CCS grades. In SAH patients, we found higher CCS scores in younger patients compared with elderly subjects in both mild and severe cases. The CCS can be useful in evaluating different therapeutic approaches during neurotrauma therapy. This new score might improve assessment of beneficial effects of therapeutic procedures.

Phase II study of erlotinib in patients with advanced biliary cancer.

PubMed

Philip, Philip A; Mahoney, Michelle R; Allmer, Cristine; Thomas, James; Pitot, Henry C; Kim, George; Donehower, Ross C; Fitch, Tom; Picus, Joel; Erlichman, Charles

2006-07-01

Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months. Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally. Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash. Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.

Reduction of N2 by supported tungsten clusters gives a model of the process by nitrogenase

PubMed Central

Murakami, Junichi; Yamaguchi, Wataru

2012-01-01

Metalloenzymes catalyze difficult chemical reactions under mild conditions. Mimicking their functions is a challenging task and it has been investigated using homogeneous systems containing metal complexes. The nitrogenase that converts N2 to NH3 under mild conditions is one of such enzymes. Efforts to realize the biological function have continued for more than four decades, which has resulted in several reports of reduction of N2, ligated to metal complexes in solutions, to NH3 by protonation under mild conditions. Here, we show that seemingly distinct supported small tungsten clusters in a dry environment reduce N2 under mild conditions like the nitrogenase. N2 is reduced to NH3 via N2H4 by addition of neutral H atoms, which agrees with the mechanism recently proposed for the N2 reduction on the active site of nitrogenase. The process on the supported clusters gives a model of the biological N2 reduction. PMID:22586517

Clinical Interview Assessment of Financial Capacity in Older Adults with Mild Cognitive Impairment and Alzheimer’s Disease

PubMed Central

Marson, Daniel C.; Martin, Roy C.; Wadley, Virginia; Griffith, H. Randall; Snyder, Scott; Goode, Patricia S.; Kinney, F. Cleveland; Nicholas, Anthony P.; Steele, Terri; Anderson, Britt; Zamrini, Edward; Raman, Rema; Bartolucci, Alfred; Harrell, Lindy E.

2009-01-01

Objectives To investigate financial capacity in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) using a clinician interview approach. Design Cross-sectional. Setting Tertiary care medical center. Participants Healthy older adults (N=75), patients with amnestic MCI (N=58), mild AD (N=97), and moderate AD (N=31). Measurements The investigators and five study physicians developed a conceptually based, semi-structured clinical interview for evaluating seven core financial domains and overall financial capacity (Semi-Structured Clinical Interview for Financial Capacity; SCIFC). For each participant, a physician made capacity judgments (capable, marginally capable, or incapable) for each financial domain and for overall capacity. Results Study physicians made a total of over 11,000 capacity judgments across the study sample (N=261). Very good inter-rater agreement was obtained for the SCIFC judgments. Increasing proportions of marginal and incapable judgment ratings were associated with increasing disease severity across the four study groups. For overall financial capacity, 95 percent of physician judgments for older controls were rated as capable, as compared to only 82% for patients with MCI, 26% for patients with mild AD, and 4% for patients with moderate AD. Conclusion Financial capacity in cognitively impaired older adults can be reliably evaluated by physicians using a relatively brief, semi-structured clinical interview. Financial capacity shows mild impairment in MCI, emerging global impairment in mild AD, and advanced global impairment in moderate AD. MCI patients and their families should proactively engage in financial and legal planning given these patients’ risk of developing AD and accelerated loss of financial abilities. PMID:19453308

Critical time window for intra-arrest cooling with cold saline flush in a dog model of cardiopulmonary resuscitation.

PubMed

Nozari, Ala; Safar, Peter; Stezoski, S William; Wu, Xianren; Kostelnik, Scott; Radovsky, Ann; Tisherman, Samuel; Kochanek, Patrick M

2006-06-13

Mild hypothermia improves outcome when induced after cardiac arrest in humans. Recent studies in both dogs and mice suggest that induction of mild hypothermia during cardiopulmonary resuscitation (CPR) greatly enhances its efficacy. In this study, we evaluate the time window for the beneficial effect of intra-arrest cooling in the setting of prolonged CPR in a clinically relevant large-animal model. Seventeen dogs had ventricular fibrillation cardiac arrest no flow of 3 minutes, followed by 7 minutes of CPR basic life support and 50 minutes of advanced life support. In the early hypothermia group (n=9), mild hypothermia (34 degrees C) was induced with an intravenous fluid bolus flush and venovenous blood shunt cooling after 10 minutes of ventricular fibrillation. In the delayed hypothermia group (n=8), hypothermia was induced at ventricular fibrillation 20 minutes. After 60 minutes of ventricular fibrillation, restoration of spontaneous circulation was achieved with cardiopulmonary bypass for 4 hours, and intensive care was given for 96 hours. In the early hypothermia group, 7 of 9 dogs survived to 96 hours, 5 with good neurological outcome. In contrast, 7 of 8 dogs in the delayed hypothermia group died within 37 hours with multiple organ failure (P=0.012). Early application of mild hypothermia with cold saline during prolonged CPR enables intact survival. Delay in the induction of mild hypothermia in this setting markedly reduces its efficacy. Our data suggest that if mild hypothermia is used during CPR, it should be applied as early as possible.

Sepsis and acute respiratory distress syndrome requiring extracorporeal life support in an adolescent with mild cystic fibrosis.

PubMed

Faricy, Lauren Elizabeth; Church, Gwynne

2017-01-01

Outcomes for invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO) to treat acute respiratory failure in patients with mild cystic fibrosis (CF) lung disease are not known. We present a case of the successful use of ECMO to treat acute respiratory failure secondary to staphylococcal sepsis in an adolescent CF patient with previously normal lung function. Her post-ECMO course was notable for severe airflow obstruction, hypoxemia, deconditioning, and growth failure. She had significantly improved at six months follow-up, though she continued to have moderate airflow obstruction on pulmonary function testing. This case illustrates that ECMO and prolonged intubation can prolong life in CF patients with mild lung disease who present with potentially reversible acute respiratory failure, though they are associated with significant morbidity.

Bomb blast, mild traumatic brain injury and psychiatric morbidity: a review.

PubMed

Rosenfeld, Jeffrey V; Ford, Nick L

2010-05-01

Traumatic brain injury (TBI) arising from blast exposure during war is common, and frequently complicated by psychiatric morbidity. There is controversy as to whether mild TBI from blast is different from other causes of mild TBI. Anxiety and affective disorders such as Post-traumatic Stress Disorder (PTSD) and depression are common accompaniments of blast injury with a significant overlap in the diagnostic features of PTSD with post-concussive syndrome (PCS). This review focuses on this overlap and the effects of mild TBI due to bomb blast. Mild TBI may have been over diagnosed by late retrospective review of returned servicemen and women using imprecise criteria. There is therefore a requirement for clear and careful documentation by health professionals of a TBI due to bomb blast shortly after the event so that the diagnosis of TBI can be made with confidence. There is a need for the early recognition of symptoms of PCS, PTSD and depression and early multi-disciplinary interventions focussed on expected return to duties. There also needs to be a continued emphasis on the de-stigmatization of psychological conditions in military personnel returning from deployment. (c) 2009 Elsevier Ltd. All rights reserved.

Structural and Functional Magnetic Resonance Imaging: Mild Cognitive Impairment and Alzheimer Disease.

PubMed

Lockau, Hannah; Jessen, Frank; Fellgiebel, Andreas; Drzezga, Alexander

2013-10-01

Magnetic resonance (MR) imaging is playing an increasingly pivotal role in the clinical management of dementia, including Alzheimer disease (AD). In addition to established MR imaging procedures, the introduction of advanced instrumentation such as 7-T MR imaging, as well as novel MR imaging sequences such as arterial spin labeling, MR spectroscopy, diffusion tensor imaging, and resting-state functional MR imaging, may open new pathways toward improved diagnosis of AD even in early stages of disease such as mild cognitive impairment (MCI). This article describes the typical findings of established and new MR imaging procedures in healthy aging, MCI, and AD. Copyright © 2013 Elsevier Inc. All rights reserved.

Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females

PubMed Central

Treadway, Michael T.; Valeri, Linda; Douglas, Samuel

2017-01-01

The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response (n = 10), moderate-response (n = 21), and mild-response (n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability. SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how individual neuroendocrine stress response patterns are linked to affective responses to stress and structural variability in neuroendocrine regulatory brain regions. By applying latent class linear mixed modeling on individuals' patterns of cortisol responses to a prolonged acute stressor, we identified three distinct trajectories of cortisol response. Relative to the group showing a moderate cortisol response, groups characterized by hyper and mild cortisol response were both associated with more negative affect. Moreover, a continuous measure of cortisol response showed that high and low levels of stress-induced cortisol release correlated with reduced hippocampal gray matter volume. Given that neuroendocrine stress responses are conceptualized as biomarkers of stress susceptibility, these insights may have clinical implications. PMID:28739584

Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.

PubMed

Admon, Roee; Treadway, Michael T; Valeri, Linda; Mehta, Malavika; Douglas, Samuel; Pizzagalli, Diego A

2017-08-16

The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response ( n = 10), moderate-response ( n = 21), and mild-response ( n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability. SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how individual neuroendocrine stress response patterns are linked to affective responses to stress and structural variability in neuroendocrine regulatory brain regions. By applying latent class linear mixed modeling on individuals' patterns of cortisol responses to a prolonged acute stressor, we identified three distinct trajectories of cortisol response. Relative to the group showing a moderate cortisol response, groups characterized by hyper and mild cortisol response were both associated with more negative affect. Moreover, a continuous measure of cortisol response showed that high and low levels of stress-induced cortisol release correlated with reduced hippocampal gray matter volume. Given that neuroendocrine stress responses are conceptualized as biomarkers of stress susceptibility, these insights may have clinical implications. Copyright © 2017 the authors 0270-6474/17/377995-09$15.00/0.

Effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment: the DANTE Study Leiden.

PubMed

Moonen, Justine E F; Foster-Dingley, Jessica C; de Ruijter, Wouter; van der Grond, Jeroen; de Craen, Anton J M; van der Mast, Roos C

2016-03-01

the relationship between antihypertensive medication and orthostatic hypotension in older persons remains ambiguous, due to conflicting observational evidence and lack of data of clinical trials. to assess the effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment. a total of 162 participants with orthostatic hypotension were selected from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study. This randomised clinical trial included community-dwelling participants aged ≥75 years, with mild cognitive impairment, using antihypertensive medication and without serious cardiovascular disease. Participants were randomised to discontinuation or continuation of antihypertensive treatment (ratio 1:1). Orthostatic hypotension was defined as a drop of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure on standing from a seated position. Outcome was the absence of orthostatic hypotension at 4-month follow-up. Relative risks (RR) were calculated by intention-to-treat and per-protocol analyses. at follow-up, according to intention-to-treat analyses, of the 86 persons assigned to discontinuation of antihypertensive medication, 43 (50%) were free from orthostatic hypotension, compared with 29 (38%) of the 76 persons assigned to continuation of medication [RR 1.31 (95% confidence interval (CI) 0.92-1.87); P = 0.13]. Per-protocol analysis showed that recovery from orthostatic hypotension was significantly higher in persons who completely discontinued all antihypertensive medication (61%) compared with the continuation group (38%) [RR 1.60 (95% CI 1.10-2.31); P = 0.01]. in older persons with mild cognitive impairment and orthostatic hypotension receiving antihypertensive medication, discontinuation of antihypertensive medication may increase the probability of recovery from orthostatic hypotension. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Yield potential of spring-harvested sugar beet depends on autumn planting time

USDA-ARS?s Scientific Manuscript database

Sugar crops grown for biofuel production provide a source of simple sugars that can readily be made into advanced biofuels. In the mild climate of the southeastern USA, sugar beet can be grown as a winter crop, providing growers with an alternative crop. Experiments evaluated autumn planting dates...

Inverse association between CSF Aβ 42 levels and years of education in mild form of Alzheimer's disease: the cognitive reserve theory.

PubMed

Dumurgier, Julien; Paquet, Claire; Benisty, Sarah; Kiffel, Claire; Lidy, Claude; Mouton-Liger, François; Chabriat, Hugues; Laplanche, Jean-Louis; Hugon, Jacques

2010-11-01

In Alzheimer's disease (AD), the cognitive reserve theory predicts that at any level of assessed clinical severity, the underlying brain pathology is more advanced in patients with more cognitive reserve. Recent evidences suggest that cerebrospinal fluid (CSF) biomarkers may reflect the brain pathology in AD. We investigated the relationship between education level and CSF concentrations of β-amyloid, total tau and phosphorylated tau (ptau-181) in a cohort of 70 subjects newly diagnosed with AD. We report that CSF concentration of β-amyloid was inversely associated with years of education, after adjustment for age, sex, and severity of the disease. We further demonstrate in stratified analysis that this relation was mainly present in mild form of the disease (CDR1), and was attenuated in more advanced forms of the disease. These results are consistent with the cognitive reserve theory, and suggest that cognitive reserve may be protective against amyloid related cognitive impairment at the onset of the clinical dementia. Copyright © 2010 Elsevier Inc. All rights reserved.

Phase II study of biweekly plitidepsin as second-line therapy for advanced or metastatic transitional cell carcinoma of the urothelium.

PubMed

Dumez, Herlinde; Gallardo, Enrique; Culine, Stephane; Galceran, Joan Carles; Schöffski, Patrick; Droz, Jean P; Extremera, Sonia; Szyldergemajn, Sergio; Fléchon, Aude

2009-09-16

The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m(2)) administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting > or = 6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells

PubMed Central

Pannella, Micaela; Caliceti, Cristiana; Fortini, Francesca; Aquila, Giorgio; Sega, Francesco Vieceli Dalla; Pannuti, Antonio; Fortini, Cinzia; Morelli, Marco Bruno; Fucili, Alessandro; Francolini, Gloria; Voltan, Rebecca; Secchiero, Paola; Dinelli, GiovannI; Leoncini, Emanuela; Ferracin, Manuela; Hrelia, Silvana; Miele, Lucio; Rizzo, Paola

2017-01-01

It is unknown whether components present in heart failure (HF) patients' serum provide an angiogenic stimulus. We sought to determine whether serum from HF patients affects angiogenesis and its major modulator, the Notch pathway, in human umbilical vein endothelial cells (HUVECs). In cells treated with serum from healthy subjects or from patients at different HF stage we determined: (1) Sprouting angiogenesis, by measuring cells network (closed tubes) in collagen gel. (2) Protein levels of Notch receptors 1, 2, 4, and ligands Jagged1, Delta-like4. We found a higher number of closed tubes in HUVECs treated with advanced HF patients serum in comparison with cells treated with serum from mild HF patients or controls. Furthermore, as indicated by the reduction of the active form of Notch4 (N4IC) and of Jagged1, advanced HF patients serum inhibited Notch signalling in HUVECs in comparison with mild HF patients' serum and controls. The circulating levels of NT-proBNP (N-terminal of the pro-hormone brain natriuretic peptide), a marker for the detection and evalutation of HF, were positively correlated with the number of closed tubes (r = 0.485) and negatively with Notch4IC and Jagged1 levels in sera-treated cells (r = −0.526 and r = −0.604, respectively). In conclusion, we found that sera from advanced HF patients promote sprouting angiogenesis and dysregulate Notch signaling in HUVECs. Our study provides in vitro evidence of an angiogenic stimulus arising during HF progression and suggests a role for the Notch pathway in it. PMID:26987674

Report from a quality assurance program on patients undergoing the MILD procedure.

PubMed

Durkin, Brian; Romeiser, Jamie; Shroyer, A Laurie W; Schiller, Robin; Bae, Jin; Davis, Raphael P; Peyster, Robert; Benveniste, Helene

2013-05-01

To characterize trends in pain and functional outcomes and identify risk factors in patients with lumbar spinal stenosis (LSS) and neurogenic claudication undergoing the "Minimally Invasive Lumbar Decompression" (MILD) procedure. Retrospective observational cohort study. Academic multidisciplinary pain center at Stony Brook Medicine. Patients undergoing the MILD procedure from October 2010 to November 2012. De-identified perioperative, pain and function related data for 50 patients undergoing MILD were extracted from the Center for Pain Management's quality assessment database. Data included numerical rating scale (NRS), symptom severity and physical function (Zurich Claudication Questionnaire), functional status (Oswestry Disability Index [ODI]), pain interference scores (National Institutes of Health Patient-Reported Outcomes Measurement Information System [PROMIS]), and patients' self-reported low back and lower extremity pain distribution. No MILD patient incurred procedure-related complications. Average NRS scores decreased postoperatively and 64.3% of patients reported less pain at 3 months. Clinically meaningful functional ODI improvements of at least 20% from baseline were present in 25% of the patients at 6 months. Preliminary analysis of changes in PROMIS scores at 3 months revealed that pre-MILD "severe" lumbar canal stenosis may be associated with high risk of "no improvement." No such impact was observed for NRS or ODI outcomes. Overall, pain is reduced and functional status improved in LSS patients following the MILD procedure at 3 and 6 months. Given the small sample size, it is not yet possible to identify patient subgroups at risk for "no improvement." Continued follow-up of longer-term outcomes appears warranted to develop evidence-based patient selection criteria. Wiley Periodicals, Inc.

Relation Between Open Circuit Potential and Polarization Resistance with Rust and Corrosion Monitoring of Mild Steel

NASA Astrophysics Data System (ADS)

Choudhary, S.; Garg, A.; Mondal, K.

2016-07-01

The present work discusses continuous corrosion assessment from a unique correlation of open circuit potential (OCP) and linear polarization resistance with rust formation on mild steel after prolong exposure in 3.5% NaCl salt fog environment. The OCP measurement and linear polarization tests were carried out of the rusted samples only without the removal of rust. It also discusses the strong influence of the composition, fraction, and morphology of the rust layers with OCP and linear polarization resistance. The rust characterization was done after the measurement of OCP and linear polarization resistance of the rusted steel samples. Therefore, monitoring of both the OCP and linear polarization resistance of the rusted mild steels coupled with rust characterization could be used for easy and dynamic assessment of the nature of corrosion.

Intranasal budesonide treatment for children with mild obstructive sleep apnea syndrome.

PubMed

Kheirandish-Gozal, Leila; Gozal, David

2008-07-01

Intranasal corticosteroids have been advanced as a nonsurgical therapeutic alternative for pediatric obstructive sleep apnea syndrome, particularly for patients with mild disease, and aims at reducing the size of hypertrophic adenotonsillar tissue. Of 71 possible candidates, 62 children with polysomnographically diagnosed mild obstructive sleep apnea syndrome were recruited onto a double-blind, randomized, crossover trial of intranasal budesonide (32 microg per nostril at bedtime) or placebo for 6 weeks followed by an additional 6-week treatment in the alternative treatment arm after allowing for a 2-week washout period. Polysomnographic assessment and radiographs for assessment of adenoid size were performed after completion of each phase. There were significant improvements in both polysomnographic measures (sleep latency, slow-wave sleep, and rapid-eye-movement sleep), in the magnitude of respiratory disturbance (apnea/hypopnea index, nadir pulse oxygen saturation), and in adenoid size among the 48 children who completed the treatment phase compared with 32 children who received placebo in their initial arm, with normalization of sleep measures in 54.1% of the treated children. Furthermore, discontinuation of treatment for 8 weeks for 25 children revealed a sustained duration of the initial treatment effect. A 6-week treatment with intranasal budesonide effectively reduced the severity of mild obstructive sleep apnea syndrome and the magnitude of the underlying adenoidal hypertrophy, and this effect persisted for at least 8 weeks after cessation of therapy. These findings justify the use of topical steroids as the initial therapeutic option in otherwise healthy children with mild obstructive sleep apnea.

Conducting Cognitive Exercises for Early Dementia with the Use of Apps on iPads

ERIC Educational Resources Information Center

Kong, Anthony Pak-Hin

2015-01-01

A list of iTunes apps was compiled for usage with early stage or mild dementia participants. The method in choosing these apps and determining salient features of the most successful apps was reported. The results will advance the knowledge base on innovative use of smart technology in clinical settings.

JB-300: An advanced medium size transport for 2005

NASA Technical Reports Server (NTRS)

Debrouwer, Giles; Graham, Katherine; Ison, Jim; Juarez, Vince; Moskalik, Steve; Pankonin, Jon; Weinstein, Arnold

1993-01-01

In the fall of 1992, the TAC Team was presented with a Request for Proposal (PFP) for a mid-size (250-350 passenger) commercial transport. The aircraft was to be extremely competitive in the areas of passenger comfort, performance, and economic aspects. Through the use of supercritical airfoils, a technologically advanced Very High By-pass Ratio (VHBR) turbofan engine, a low overall drag configuration, a comparable interior layout, and mild use of composites, the JB-300 offers an economically viable choice to the airlines. The cents per passenger mile of the JB-300 is 1.76, which is considerably lower than current aircraft in the same range. Overall, the JB-300 is a technologically advanced aircraft, which will meet the demands of the 21st century.

Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis

PubMed Central

Lessa-Aquino, Carolina; Lindow, Janet C.; Randall, Arlo; Wunder, Elsio; Pablo, Jozelyn; Nakajima, Rie; Jasinskas, Algis; Cruz, Jaqueline S.; Damião, Alcineia O.; Nery, Nívison; Ribeiro, Guilherme S.; Costa, Federico; Hagan, José E.; Reis, Mitermayer Galvão; Ko, Albert I.; Medeiros, Marco Alberto; Felgner, Philip L.

2017-01-01

Background Leptospirosis is an important zoonotic disease worldwide. Humans usually present a mild non-specific febrile illness, but a proportion of them develop more severe outcomes, such as multi-organ failure, lung hemorrhage and death. Such complications are thought to depend on several factors, including the host immunity. Protective immunity is associated with humoral immune response, but little is known about the immune response mounted during naturally-acquired Leptospira infection. Methods and principal findings Here, we used protein microarray chip to profile the antibody responses of patients with severe and mild leptospirosis against the complete Leptospira interrogans serovar Copenhageni predicted ORFeome. We discovered a limited number of immunodominant antigens, with 36 antigens specific to patients, of which 11 were potential serodiagnostic antigens, identified at acute phase, and 33 were potential subunit vaccine targets, detected after recovery. Moreover, we found distinct antibody profiles in patients with different clinical outcomes: in the severe group, overall IgM responses do not change and IgG responses increase over time, while both IgM and IgG responses remain stable in the mild patient group. Analyses of individual patients’ responses showed that >74% of patients in the severe group had significant IgG increases over time compared to 29% of patients in the mild group. Additionally, 90% of IgM responses did not change over time in the mild group, compared to ~51% in the severe group. Conclusions In the present study, we detected antibody profiles associated with disease severity and speculate that patients with mild disease were protected from severe outcomes due to pre-existing antibodies, while patients with severe leptospirosis demonstrated an antibody profile typical of first exposure. Our findings represent a significant advance in the understanding of the humoral immune response to Leptospira infection, and we have identified new targets for the development of subunit vaccines and diagnostic tests. PMID:28141801

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

PubMed

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of beta-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of beta-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction.

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial

PubMed Central

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of β-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of β-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction. PMID:11806769

Risk of Colorectal Neoplasia According to Fatty Liver Severity and Presence of Gall Bladder Polyps.

PubMed

Lee, Taeyoung; Yun, Kyung Eun; Chang, Yoosoo; Ryu, Seungho; Park, Dong Il; Choi, Kyuyong; Jung, Yoon Suk

2016-01-01

Fatty liver is the hepatic manifestation of metabolic syndrome (MetS) and is a known risk factor for colorectal neoplasia (CRN). Gallbladder (GB) polyps share many common risk factors with CRN. However, studies evaluating CRN risk according to fatty liver severity and the presence of GB polyps are rare. To investigate CRN risk according to the fatty liver severity and the presence of GB polyps. A retrospective cross-sectional study was performed on 44,220 participants undergoing colonoscopy and abdominal ultrasonography (US) as part of a health-screening program. Of the participants, fatty liver was diagnosed as mild in 27.7 %, moderate in 5.1 %, and severe in 0.4 % and 13.4 % were diagnosed with GB polyps. Mean age of participants was 42.7 years. In adjusted models, risk of overall CRN and non-advanced CRN increased with worsening fatty liver severity (P for trend = 0.007 and 0.020, respectively). Adjusted odd ratios for overall CRN and non-advanced CRN comparing participants with mild, moderate, and severe fatty liver to participants without fatty liver were 1.13 and 1.12 for mild, 1.12 and 1.10 for moderate, and 1.56 and 1.65 for severe. The presence of GB polyps did not correlate with CRN risk after adjusting for confounders. CRN risk increased with worsening fatty liver severity. However the association between GB polyp and CRN was not significant in the presence of other variables. Considering that many people undergo noninvasive abdominal US as a health screen, our study will contribute to colonoscopy screening strategies in people undergoing abdominal US.

49 CFR 178.338-1 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... contacted with a continuously heated glowing platinum wire. The cargo tank must be marked in accordance with... Gauge Inches Stainless steel 18 0.0428 22 0.0269 Low carbon mild steel 12 0.0946 14 0.0677 Aluminum 0...

Preparation of rotigotine-loaded microspheres and their combination use with L-DOPA to modify dyskinesias in 6-OHDA-lesioned rats.

PubMed

Wang, Aiping; Wang, Lexi; Sun, Kaoxiang; Liu, Wanhui; Sha, Chunjie; Li, Youxin

2012-09-01

To prepare rotigotine loaded microspheres (RoMS) to achieve continuous dopaminergic stimulation (CDS) for the treatment of Parkinson's disease (PD) and investigate both the therapeutic benefit and inducibility of AIMs of administration of RoMS combination with L-DOPA in 6-OHDA-leisioned rats. Rotigotine was encapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres by an oil-in-water emulsion solvent evaporation technique. In vitro characteristics and in vivo pharmacokinetics of RoMS either in rat blood or brain (by microdialysis) were investigated. Contraversive rotations and AIMs were observed to investigate the therapeutic benefit and the propensity to induce dyskinesia of RoMS or RoMS combination with L-DOPA in 6-OHDA-lesioned rats. RoMS displayed continuous-release characteristics of rotigotine in animals and exhibited a steady efficacy lasted for 2 weeks in 6-OHDA-lesioned rats. No significant difference of the therapeutic benefit between the treatment of RoMS and pulsatile L-DOPA combination and mono L-DOPA was found. While the dyskinesia was significantly decreased with the treatment of RoMS and pulsatile L-DOPA combination compared to mono L-DOPA. RoMS could supply an alternative of CDS for the treatment of PD and the study indicates a potential advantage of RoMS for the treatment of mild and advanced PD patient in combination with L-DOPA.

Gemcitabine Chemotherapy and Single-Fraction Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

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

Schellenberg, Devin; Goodman, Karyn A.; Lee, Florence

2008-11-01

Purpose: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. Methods and Materials: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife.more » Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). Conclusion: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant.« less

Prospective clinical study on long-term swallowing function and voice quality in advanced head and neck cancer patients treated with concurrent chemoradiotherapy and preventive swallowing exercises.

PubMed

Kraaijenga, Sophie A C; van der Molen, Lisette; Jacobi, Irene; Hamming-Vrieze, Olga; Hilgers, Frans J M; van den Brekel, Michiel W M

2015-11-01

Concurrent chemoradiotherapy (CCRT) for advanced head and neck cancer (HNC) is associated with substantial early and late side effects, most notably regarding swallowing function, but also regarding voice quality and quality of life (QoL). Despite increased awareness/knowledge on acute dysphagia in HNC survivors, long-term (i.e., beyond 5 years) prospectively collected data on objective and subjective treatment-induced functional outcomes (and their impact on QoL) still are scarce. The objective of this study was the assessment of long-term CCRT-induced results on swallowing function and voice quality in advanced HNC patients. The study was conducted as a randomized controlled trial on preventive swallowing rehabilitation (2006-2008) in a tertiary comprehensive HNC center with twenty-two disease-free and evaluable HNC patients as participants. Multidimensional assessment of functional sequels was performed with videofluoroscopy, mouth opening measurements, Functional Oral Intake Scale, acoustic voice parameters, and (study specific, SWAL-QoL, and VHI) questionnaires. Outcome measures at 6 years post-treatment were compared with results at baseline and at 2 years post-treatment. At a mean follow-up of 6.1 years most initial tumor-, and treatment-related problems remained similarly low to those observed after 2 years follow-up, except increased xerostomia (68%) and increased (mild) pain (32%). Acoustic voice analysis showed less voicedness, increased fundamental frequency, and more vocal effort for the tumors located below the hyoid bone (n = 12), without recovery to baseline values. Patients' subjective vocal function (VHI score) was good. Functional swallowing and voice problems at 6 years post-treatment are minimal in this patient cohort, originating from preventive and continued post-treatment rehabilitation programs.

Peptide protected gold clusters: chemical synthesis and biomedical applications

NASA Astrophysics Data System (ADS)

Yuan, Qing; Wang, Yaling; Zhao, Lina; Liu, Ru; Gao, Fuping; Gao, Liang; Gao, Xueyun

2016-06-01

Bridging the gap between atoms and nanoparticles, noble metal clusters with atomic precision continue to attract considerable attention due to their important applications in catalysis, energy transformation, biosensing and biomedicine. Greatly different to common chemical synthesis, a one-step biomimetic synthesis of peptide-conjugated metal clusters has been developed to meet the demand of emerging bioapplications. Under mild conditions, multifunctional peptides containing metal capturing, reactive and targeting groups are rationally designed and elaborately synthesized to fabricate atomically precise peptide protected metal clusters. Among them, peptide-protected Au Cs (peptide-Au Cs) possess a great deal of exceptional advantages such as nanometer dimensions, high photostability, good biocompatibility, accurate chemical formula and specific protein targeting capacity. In this review article, we focus on the recent advances in potential theranostic fields by introducing the rising progress of peptide-Au Cs for biological imaging, biological analysis and therapeutic applications. The interactions between Au Cs and biological systems as well as potential mechanisms are also our concerned theme. We expect that the rapidly growing interest in Au Cs-based theranostic applications will attract broader concerns across various disciplines.

Biodegradable Materials for Bone Repair and Tissue Engineering Applications

PubMed Central

Sheikh, Zeeshan; Najeeb, Shariq; Khurshid, Zohaib; Verma, Vivek; Rashid, Haroon; Glogauer, Michael

2015-01-01

This review discusses and summarizes the recent developments and advances in the use of biodegradable materials for bone repair purposes. The choice between using degradable and non-degradable devices for orthopedic and maxillofacial applications must be carefully weighed. Traditional biodegradable devices for osteosynthesis have been successful in low or mild load bearing applications. However, continuing research and recent developments in the field of material science has resulted in development of biomaterials with improved strength and mechanical properties. For this purpose, biodegradable materials, including polymers, ceramics and magnesium alloys have attracted much attention for osteologic repair and applications. The next generation of biodegradable materials would benefit from recent knowledge gained regarding cell material interactions, with better control of interfacing between the material and the surrounding bone tissue. The next generations of biodegradable materials for bone repair and regeneration applications require better control of interfacing between the material and the surrounding bone tissue. Also, the mechanical properties and degradation/resorption profiles of these materials require further improvement to broaden their use and achieve better clinical results. PMID:28793533

Isolated limb perfusion electrochemotherapy for the treatment of an advanced squamous cell carcinoma of the hoof in a mare.

PubMed

Spugnini, Enrico Pierluigi; Bolaffio, Carlo; Scacco, Licia; Baldi, Alfonso

2017-01-01

A twenty-year-old female saddle horse was referred for evaluation of a seven month, non-healing erosive lesion of the right hind hoof with proliferation and bleeding of the underlying soft tissues. This lesion had been twice surgically treated as a canker but rapidly recurred. Histological examination of the second excision revealed a well-differentiated squamous cell carcinoma. At presentation, the horse was mildly depressed, lame and partially non-weight-bearing on the right hind leg, which exhibited a 10 x 10 cm erosive and proliferative lesion remodeling the hoof. After completing staging procedures, the lesion was approached with surgery and intraoperative electrochemotherapy (ECT) administration of bleomycin in isolated limb perfusion. A second session of surgery and ECT was performed one month later, followed by three additional monthly sessions of ECT. During periodic recheck, the mare showed continuous improvement. One year after presentation, the mare was in complete remission and her gait markedly improved. ECT was well-tolerated and resulted in improved local control of a tumor in a challenging anatomical district.

Accelerated Changes in Cortical Thickness Measurements with Age in Military Service Members with Traumatic Brain Injury.

PubMed

Savjani, Ricky R; Taylor, Brian A; Acion, Laura; Wilde, Elisabeth A; Jorge, Ricardo E

2017-11-15

Finding objective and quantifiable imaging markers of mild traumatic brain injury (TBI) has proven challenging, especially in the military population. Changes in cortical thickness after injury have been reported in animals and in humans, but it is unclear how these alterations manifest in the chronic phase, and it is difficult to characterize accurately with imaging. We used cortical thickness measures derived from Advanced Normalization Tools (ANTs) to predict a continuous demographic variable: age. We trained four different regression models (linear regression, support vector regression, Gaussian process regression, and random forests) to predict age from healthy control brains from publicly available datasets (n = 762). We then used these models to predict brain age in military Service Members with TBI (n = 92) and military Service Members without TBI (n = 34). Our results show that all four models overpredicted age in Service Members with TBI, and the predicted age difference was significantly greater compared with military controls. These data extend previous civilian findings and show that cortical thickness measures may reveal an association of accelerated changes over time with military TBI.

Association between macular degeneration and mild to moderate chronic kidney disease: A nationwide population-based study.

PubMed

Chen, Chun-Yu; Dai, Ciou-Sia; Lee, Chin-Chan; Shyu, Yu-Chiau; Huang, Ting-Shuo; Yeung, Ling; Sun, Chi-Chin; Yang, Huang-Yu; Wu, I-Wen

2017-03-01

Chronic kidney disease (CKD) and macular degeneration (MD) are 2 grave diseases leading to significant disability secondary to renal failure and blindness. The 2 diseases share not only common risk factors but also similar pathogenic mechanisms to renal and retinal injuries. Previous epidemiological studies indicated association between these 2 diseases. However, this concept is challenged by recent investigations. Patients with mild to moderate CKD (n = 30,696) between January 1, 1995 and December 31, 2005 were selected from the Taiwan National Health Insurance Database. Controls (n = 122,784) were matched by age, gender, diabetes mellitus type 2, and hypertension status (1:4 ratios). The risk of MD was compared between the 2 groups. The mean age of patients was 54.9 ± 15.7 years. The proportion of MD was 2.7% in mild to moderate CKD patients and 1.9% in normal controls (P < 0.001); and, 0.39% and 0.26% (P < 0.001) in advanced MD. Mild to moderate CKD patients had higher risk for MD [adjusted odds ratio (OR), 1.301; 95% confidence interval (CI), 1.200-1.411; P < 0.001] than normal renal function subjects. The association was more pronounced for advanced MD. From all age strata (10 years increase), the presence of CKD in those patients aged less than 40 years had highest OR for all MD (OR = 2.125, 95% CI: 1.417-3.186, P < 0.001). The results were consistent in interaction terms, highlighting the importance of CKD in young age patient for risk of MD. The high risk for MD in mild to moderate CKD patients remains significant after adjustment for personal habits (alcohol drinking and smoking, model 1; OR: 1.371; 95% CI: 1.265-1.486; P < 0.001), comorbidities (dyslipidemia, cerebrovascular disease, and peripheral vascular disease, model 2; OR: 1.369; 95% CI: 1.264-1.484; P < 0.001) and all these factors (model 3; OR: 1.320, 95% CI: 1.218-1.431, P < 0.001). This association was consistent in the subanalysis, excluding those patients with diabetic retinopathy. Proper diagnosis and timely intervention should be warranted to retard visual loss of these patients.

An interview study of young adults born to mothers with mild intellectual disability.

PubMed

Lindblad, Ida; Billstedt, Eva; Gillberg, Christopher; Fernell, Elisabeth

2013-12-01

A group of 10 young adults from a population-based series in Sweden, of originally 42 individuals, born to mothers with mild intellectual disability (ID), were interviewed with regard to their experiences during childhood, adolescence, and their current situation. The interview revealed that 6 of the 10 individuals had been removed from their biological parents during childhood, 6 reported clear child abuse and/or neglect, and 6 individuals had mild ID. The majority of the individuals reported difficulties in their relations with family and in school. The small number of participants (n = 10) who could be personally interviewed reflected the major problems that were encountered in the process of making contact with this group of young individuals. In conclusion, this study adds to other reports that children of mothers with ID constitute an extremely vulnerable group. Therefore, these families need full and continuous attention from the supportive systems in society.

Differential effects of severe vs mild GBA mutations on Parkinson disease.

PubMed

Gan-Or, Ziv; Amshalom, Idan; Kilarski, Laura L; Bar-Shira, Anat; Gana-Weisz, Mali; Mirelman, Anat; Marder, Karen; Bressman, Susan; Giladi, Nir; Orr-Urtreger, Avi

2015-03-03

To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD). We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results. Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p < 0.0001, Fisher exact test). In the different models of the meta-analysis, the odds ratios for PD ranged between 2.84 and 4.94 for mild GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers (p < 1 × 10(-6) for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively (p = 4.3 × 10(-5)). These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up. © 2015 American Academy of Neurology.

Acylation, Diastereoselective Alkylation, and Cleavage of an Oxazolidinone Chiral Auxiliary: A Multistep Asymmetric Synthesis Experiment for Advanced Undergraduates

ERIC Educational Resources Information Center

Smith, Thomas E.; Richardson, David P.; Truran, George A.; Belecki, Katherine; Onishi, Megumi

2008-01-01

An introduction to the concepts and experimental techniques of diastereoselective synthesis using a chiral auxiliary is described. The 4-benzyl-2-oxazolidinone chiral auxiliary developed by Evans is acylated with propionic anhydride under mild conditions using DMAP as an acyl transfer catalyst. Deprotonation with NaN(TMS)[subscript 2] at -78…

Corneal Biomechanics in Ectatic Diseases: Refractive Surgery Implications

PubMed Central

Ambrósio, Jr, Renato; Correia, Fernando Faria; Lopes, Bernardo; Salomão, Marcella Q.; Luz, Allan; Dawson, Daniel G.; Elsheikh, Ahmed; Vinciguerra, Riccardo; Vinciguerra, Paolo; Roberts, Cynthia J.

2017-01-01

Background: Ectasia development occurs due to a chronic corneal biomechanical decompensation or weakness, resulting in stromal thinning and corneal protrusion. This leads to corneal steepening, increase in astigmatism, and irregularity. In corneal refractive surgery, the detection of mild forms of ectasia pre-operatively is essential to avoid post-operative progressive ectasia, which also depends on the impact of the procedure on the cornea. Method: The advent of 3D tomography is proven as a significant advancement to further characterize corneal shape beyond front surface topography, which is still relevant. While screening tests for ectasia had been limited to corneal shape (geometry) assessment, clinical biomechanical assessment has been possible since the introduction of the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, USA) in 2005 and the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) in 2010. Direct clinical biomechanical evaluation is recognized as paramount, especially in detection of mild ectatic cases and characterization of the susceptibility for ectasia progression for any cornea. Conclusions: The purpose of this review is to describe the current state of clinical evaluation of corneal biomechanics, focusing on the most recent advances of commercially available instruments and also on future developments, such as Brillouin microscopy. PMID:28932334

Fatigue Performance of Advanced High-Strength Steels (AHSS) GMAW Joints

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

Feng, Zhili; Sang, Yan; Jiang, Cindy

2009-01-01

The fatigue performance of gas metal arc welding (GMAW) joints of advanced high strength steels (AHSS) are compared and analyzed. The steel studied included a number of different grades of AHSS and baseline mild steels: DP600, DP780, DP980, M130, M220, solution annealed boron steel, fully hardened boron steels, HSLA690 and DR210 (a mild steel). Fatigue testing was conducted under a number of nominal stress ranges to obtain the S/N curves of the weld joints. A two-phase analytical model is developed to predict the fatigue performance of AHSS welds. It was found that there are appreciable differences in the fatigue S/Nmore » curves among different AHSS joints made using the same welding practices, suggesting that the local microstructure in the weld toe and root region plays non-negligible role in the fatigue performance of AHSS welds. Changes in weld parameters can influence the joint characteristics which in turn influence fatigue life of the weld joints, particularly of those of higher strength AHSS. The analytical model is capable of reasonably predicting the fatigue performance of welds made with various steel grades in this study.« less

Sleep, sleep disorders, and circadian health following mild traumatic brain injury: Review and research agenda.

PubMed

Wickwire, Emerson; Schnyer, David M; Germain, Anne; Williams, Scott; Lettieri, Christopher; McKeon, Ashlee; Scharf, Steven; Stocker, Ryan; Albrecht, Jennifer S; Badjatia, Neeraj; Markowitz, Amy; Manley, Geoffrey

2018-06-07

A rapidly expanding scientific literature supports the frequent co-occurrence of sleep and circadian disturbances following mild traumatic brain injury (mTBI). Although many questions remain unanswered, the preponderance of evidence suggests that sleep and circadian disorders can result from mTBI. Among those with mTBI, sleep disturbances and clinical sleep and circadian disorders contribute to the morbidity and long-term sequelae across domains of functional outcomes and quality of life. Specifically, along with deterioration of neurocognitive performance, insufficient and disturbed sleep can precede, exacerbate, or perpetuate many of the other common sequelae of mTBI, including depression, post-traumatic stress disorder, and chronic pain. Further, sleep and mTBI share neurophysiologic and neuroanatomic mechanisms that likely bear directly on success of rehabilitation following mTBI. For these reasons, focus on disturbed sleep as a modifiable treatment target has high likelihood of improving outcomes in mTBI. Here, we review relevant literature and present a research agenda to 1) advance understanding of the reciprocal relationships between sleep and circadian factors and mTBI sequelae and 2) advance rapidly the development of sleep-related treatments in this population.

Traumatic brain injury: next steps, research needed, and priority focus areas.

PubMed

Helmick, Kathy; Baugh, Laura; Lattimore, Tracie; Goldman, Sarah

2012-08-01

Traumatic brain injury (TBI) has been not only a major focus of concern during the recent conflicts in Afghanistan and Iraq, but also among our garrison service members. The prevalence of these injuries has compelled the nation and Congress to invest in the development of policies and programs that support evidence-based care for the full continuum of TBI, from mild (otherwise known as concussion) to severe and penetrating brain injuries. Although, the Department of Defense has made great strides in the areas of TBI clinical care, education, and research, there remains a great need to leverage scientific, policy, and clinical advancement to maximize care of the service member. The purpose of this article is to outline the 7 major areas of work currently being undertaken to help advance the field of TBI. The 7 areas include: (1) eliminating undetected mild traumatic brain injury through prompt early diagnosis, (2) ensuring force readiness and addressing cultural barriers, (3) improving collaborations with the Department of Veterans Affairs, other federal agencies, and academic and civilian organizations, (4) improving deployment-related assessments, (5) deploying effective treatments, (6) conducting military-relevant and targeted research, and (7) enhancing information technology systems.

Cethromycin: A-195773, A-195773-0, A-1957730, Abbott-195773, ABT 773.

PubMed

2007-01-01

Cethromycin [ABT 773, A-195773, Abbott-195773, A-1957730, A-195773-0] is a once-daily ketolide antibiotic that originated from Abbott Laboratories' research into next-generation compounds to the macrolide antibacterial, clarithromycin. The aim of the research programme was to maintain the positive attributes of clarithromycin and to add the property of efficacy against macrolide-resistant organisms. Cethromycin acts by binding to the 23S molecule of the 50S ribosomal subunit. Advanced Life Sciences is conducting multinational, pivotal phase III trials of cethromycin for the treatment of mild-to-moderate community-acquired pneumonia, phase II/III trials for treatment of acute bacterial sinusitis, as well as preclinical trials for the treatment of anthrax. Advanced Life Sciences plans to advance discussions with prospective commercialisation partners for cethromycin during 2006. Abbott Laboratories and Taisho Pharmaceutical entered a collaboration to develop and commercialise new macrolide antibacterials in October 1997. Each company brought its existing macrolides into the collaboration and both companies were to jointly develop novel new macrolides. Abbott was to have exclusive marketing, manfacturing and supply rights worldwide (except in Japan) to any compounds resulting from this collaboration. Taisho was to receive royalties on Abbott's sales in consideration of granted rights. In Japan, the two companies were to co-market any resulting macrolide antibacterials. This agreement extended to the development of cethromycin; however, the agreement was suspended in April 2004 and appears to have been terminated. Abbott exclusively licensed cethromycin to Advanced Life Sciences worldwide excluding Japan in December 2004. Advanced Life Sciences initiated commercial manufacturing agreements for cethromycin with DSM and Cardinal Health in May 2006. In March 2006, Advanced Life Sciences completed private placement of $US36 million from which the net proceeds will be used to advance development of cethromycin. The company plans to submit an NDA for cethromycin in 2007. In Japan, phase II trials were being conducted with Abbott's partner, Taisho Pharmaceutical. Although development in the US had been put on hold, Abbott was to continue to support product development in Japan by Taisho. However, in April 2004, Taisho and Abbott Japan decided to suspend co-development activities for cethromycin. A patent has been granted for cethromycin (US patent number 5 866 549) that expires in September 2016.

Evaluation of autonomic functions of patients with multiple system atrophy and Parkinson's disease by head-up tilt test.

PubMed

Watano, Chikako; Shiota, Yuri; Onoda, Keiichi; Sheikh, Abdullah Md; Mishima, Seiji; Nitta, Eri; Yano, Shozo; Yamaguchi, Shuhei; Nagai, Atsushi

2018-02-01

The aim of this study was to evaluate the autonomic neural function in Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test and spectral analysis of cardiovascular parameters. This study included 15 patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects. High frequency power of the RR interval (RR-HF), the ratio of low frequency power of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively. Both patients with PD and MSA showed orthostatic hypotension and lower parasympathetic function (RR-HF) at tilt position as compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was significantly high in patients with PD than MSA at supine position. RR-LF/HF tended to increase in MSA and HC, but decreased in PD by tilting. Consequently, the change of the ratio due to tilting (ΔRR-LF/HF) was significantly lower in patients with PD than in HC subjects. Further analysis showed that compared to mild stage of PD, RR-LF/HF at the supine position was significantly higher in advanced stage. By tilting, it was increased in mild stage and decreased in the advanced stage of PD, causing ΔRR-LF/HF to decrease significantly in the advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular parameters is useful to identify sympathetic and parasympathetic disorders in MSA and PD. High cardiac sympathetic function at the supine position, and its reduction by tilting might be a characteristic feature of PD, especially in the advanced stage.

[Chronic pancreatitis: which is the role of 320-row CT for the staging?].

PubMed

Stabile Ianora, Amato Antonio; Rubini, Giuseppe; Lorusso, Filomenamila; Ambriola, Angela; Rella, Leonarda; Di Crescenzo, Vincenzo; Moschetta, Marco

2013-01-01

The purpose of this study was to evaluate the diagnostic potential of multi-planar and volumetric reconstructions obtained from isotropic data by using 16-slice computed tomography (CT) in the diagnosis and staging of chronic pancreatitis. In a group of 42 patients CT images were evaluated searching for alterations in morphology and structure of the pancreas, alterations of the Wirsung duct, dilatation of the bile ducts, fluid collections, and vascular involvement of the digestive tract. The disease was then staged in mild, moderate and severe and correlated with the clinical staging. CT allowed the recognition of chronic pancreatitis in all cases. The staging was correct in 25/42 patients, with an accuracy rate of 59.5%. In the staging of moderate and severe forms, CT correlation with clinical and laboratory data was valid, but in mild forms it appeared less significant. Multi-detector CT is accurate in the recognition of moderate, advanced forms of chronic pancreatitis and in the identification of its complications, while it is poorly correlated with the clinical staging in mild forms of the disease.

Predictors of patient dependence in mild-to-moderate Alzheimer's disease.

PubMed

Benke, Thomas; Sanin, Günter; Lechner, Anita; Dal-Bianco, Peter; Ransmayr, Gerhard; Uranüs, Margarete; Marksteiner, Josef; Gaudig, Maren; Schmidt, Reinhold

2015-01-01

Patient dependence has rarely been studied in mild-to-moderate Alzheimer's disease (AD). To identify factors which predict patient dependence in mild-to-moderate AD. We studied 398 non-institutionalized AD patients (234 females) of the ongoing Prospective Registry on Dementia (PRODEM) in Austria. The Dependence Scale (DS) was used to assess patient dependence. Patient assessment comprised functional abilities, neuropsychiatric symptoms and cognitive functions. A multiple linear regression analysis was performed to identify predictors of patient dependence. AD patients were mildly-to-moderately impaired (mean scores and SDs were: CDR 0.84 ± 0.43; DAD 74.4 ± 23.3, MMSE = 22.5 ± 3.6). Psychopathology and caregiver burden were in the low range (mean NPI score 13.2, range 0 to 98; mean ZBI score 18, range 0-64). Seventy five percent of patients were classified as having a mild level of patient dependence (DS sum score 0 to 6). Patient dependence correlated significantly and positively with age, functional measures, psychopathology and depression, disease duration, and caregiver burden. Significant negative, but low correlations were found between patient dependence, cognitive variables, and global cognition. Activities of daily living, patient age, and disease severity accounted for 63% of variance in patient dependence, whereas cognitive variables accounted for only 11%. Dependence in this cohort was mainly related to age and functional impairment, and less so to cognitive and neuropsychiatric variables. This differs from studies investigating patients in more advanced disease stages which found abnormal behavior and impairments of cognition as main predictors of patient dependence.

Religious Life-Styles and Mental Health: An Exploratory Study.

ERIC Educational Resources Information Center

Bergin, Allen E.; And Others

1988-01-01

Assessed lifestyles of religious college students. Subjects with continuous religious development and mild religious experiences were healthier than those with discontinuous development and intense religious experiences; however, intense religious experiences enhanced adjustment. Religiousness and mental health did not correlate significantly, but…

Early supported discharge following mild stroke: a qualitative study of patients' and their partners' experiences of rehabilitation at home.

PubMed

Lou, Stina; Carstensen, Kathrine; Møldrup, Marie; Shahla, Seham; Zakharia, Elias; Nielsen, Camilla Palmhøj

2017-06-01

Early supported discharge (ESD) allows mild-to-moderate stroke patients to return home as soon as possible and continue rehabilitation at their own pace in familiar surroundings. Thus, the main responsibility for continued rehabilitation is in the hands of patients and their partners, who must collaborate to adjust to poststroke everyday life. However, couples' joint experiences of stroke, early discharge and rehabilitation at home remain minimally investigated. To investigate how mild stroke patients' and their partners' experience and manage everyday life in a context of ESD. We conducted qualitative interviews with a purposive sample of 22 ESD patients and 18 partners. Interviews were conducted 3-6 weeks after stroke, and we used thematic analysis to analyse the data. The analysis identified three themes. First, 'Home as a healing place' involved the couples' experiences of a well-informed discharge from hospital. They trusted the health professionals' assessment that the patient was ready to go home. They described home as a comforting and calm place, where recovery could meaningfully take place. The second theme, 'Flow of everyday life', comprised the experiences of adapting to and continuing everyday life. Most of the interviewees had relatively minor physical and cognitive impairments, and the patients and their partners were hopeful for a full recovery in the foreseeable future. Finally, 'Professional safety net' involved the much appreciated stroke team. Although most of the participants only had one visit from the team, knowing that they were an accessible resource was very important to the couples. ESD was experienced as a meaningful and adequate rehabilitation service that allowed patients and partners to collaboratively reinvent and rebuild their flow of everyday life by jointly adjusting routines, activities and their relationship. © 2016 Nordic College of Caring Science.

Switch maintenance chemotherapy using S-1 with or without bevacizumab in patients with advanced non-small cell lung cancer: a phase II study.

PubMed

Niho, Seiji; Ohe, Yuichiro; Ohmatsu, Hironobu; Umemura, Shigeki; Matsumoto, Shingo; Yoh, Kiyotaka; Goto, Koichi

2017-06-01

We conducted this single-institute; prospective, non-randomized parallel two-arm phase II study to evaluate the efficacy and safety of switch maintenance chemotherapy with S-1 after induction therapy with a platinum-based regimen in patients with advanced non-small cell lung cancer (NSCLC). Patients not showing disease progression after induction platinum-based chemotherapy received S-1 at the dose of 40mg/m 2 twice daily for 14 consecutive days, every three weeks, with or without bevacizumab (Bev) at the dose of 15mg/kg. In cases where the induction chemotherapy regimen contained Bev, Bev was used as continuation maintenance chemotherapy where appropriate. The efficacy/toxicity of switch maintenance chemotherapy with S-1 and S-1+Bev was evaluated separately. The primary end point of this study was the treatment success rate at three months after the start of S-1 treatment. Between July 2010 and January 2014, 79 patients were enrolled, of which 78 were found to be eligible for inclusion in this study. The treatment success rate at three months was 28.2% (90% confidence interval (CI), 7.1-17.1%) in the S-1 group and 64.1% (90% CI, 50.0-76.8%) in the S-1+Bev group. The primary endpoint was met in the S-1+Bev group. The median PFS and OS were 2.6 months and 11.0 months in the S-1 group, and 4.6 months and 19.9 months in the S-1+Bev group, respectively. The most common grade three toxicity was neutropenia (10% incidence in the S-1+Bev group). There were no cases of febrile neutropenia. Switch maintenance chemotherapy with S-1 in combination with continuation maintenance chemotherapy with bevacizumab yielded modest efficacy with mild and acceptable toxicities. Copyright © 2017. Published by Elsevier B.V.

Revised Criteria for Mild Cognitive Impairment May Compromise the Diagnosis of Alzheimer Disease Dementia

PubMed Central

Morris, John C.

2012-01-01

Objective To evaluate the potential impact of revised criteria for mild cognitive impairment (MCI), developed by a Workgroup sponsored by the National Institute on Aging and the Alzheimer’s Association, on the diagnosis of very mild and mild Alzheimer disease (AD) dementia. Design Retrospective review of ratings of functional impairment across diagnostic categories. Participants: The functional ratings of individuals (N = 17,535) with normal cognition, MCI, or AD dementia who were evaluated at Alzheimer’s Disease Centers and submitted to the National Alzheimer’s Coordinating Center were assessed in accordance with the definition of “functional independence” allowed by the revised criteria. Methods Pairwise demographic differences between the 3 diagnostic groups were tested using t-tests for continuous variables and chi-square for categorical variables. Results Almost all (99.8%) of individuals currently diagnosed with very mild AD dementia and the large majority (92.7%) of those diagnosed with mild AD dementia could be reclassified as MCI with the revised criteria, based on their level of impairment in the Clinical Dementia Rating domains for performance of instrumental activities of daily living in the community and at home. Large percentages of these AD dementia individuals also meet the revised “functional independence” criterion for MCI as measured by the Functional Assessment Questionnaire. Conclusions The categorical distinction between MCI and milder stages of Alzheimer dementia has been compromised by the revised criteria. The resulting diagnostic overlap supports the premise that “MCI due to AD” represents the earliest symptomatic stage of AD. PMID:22312163

Revised criteria for mild cognitive impairment may compromise the diagnosis of Alzheimer disease dementia.

PubMed

Morris, John C

2012-06-01

To evaluate the potential impact of revised criteria for mild cognitive impairment (MCI), developed by a work group sponsored by the National Institute on Aging and the Alzheimer's Association, on the diagnosis of very mild and mild Alzheimer disease (AD)dementia. Retrospective review of ratings of functional impairment across diagnostic categories. Alzheimer's Disease Centers and the National Alzheimer's Coordinating Center. Individuals (N=17 535) with normal cognition,MCI, or AD dementia. The functional ratings of individuals with normal cognition, MCI, or AD dementia who were evaluated at Alzheimer's Disease Centers and submitted to the National Alzheimer's Coordinating Center were assessed in accordance with the definition of "functional independence" allowed by the revised criteria. Pairwise demographic differences between the 3 diagnostic groups were tested using t tests for continuous variables and 2 for categorical variables. Almost all (99.8%) individuals currently diagnosed with very mild AD dementia and the large majority(92.7%) of those diagnosed with mild AD dementia could be reclassified as having MCI with the revised criteria,based on their level of impairment in the Clinical Dementia Rating domains for performance of instrumental activities of daily living in the community and at home.Large percentages of these individuals with AD dementia also meet the revised "functional independence" criterion for MCI as measured by the Functional Assessment Questionnaire. The categorical distinction between MCI and milder stages of AD dementia has been compromised by the revised criteria. The resulting diagnostic overlap supports the premise that "MCI due to AD" represents the earliest symptomatic stage of AD.

Diagnosis and Management of Acute Concussion.

PubMed

McCrea, Michael A; Nelson, Lindsay D; Guskiewicz, Kevin

2017-05-01

Over the past 2 decades, there have been major advances in the basic and clinical science of concussion and mild traumatic brain injury. These advances now provide a more evidence-informed approach to the definition, diagnosis, assessment, and management of acute concussion. Standardized clinical tools have been developed and validated for assessment of acute concussion across injury settings (eg, civilian, sport, military). Consensus guidelines now provide guidance regarding injury management and approaches to ensure safe return to activity after acute concussion. This article provides a brief, high-level overview of approaches to best practice in diagnosis, assessment, and management of acute concussion. Copyright © 2017 Elsevier Inc. All rights reserved.

Dementia and legal determination of capacity.

PubMed

Delineau, Valeska Maria Eboli Bello; Schultz, Rodrigo Rizek

2017-06-01

To assess the legal capacity and guardianship proceedings in patients diagnosed with dementia. Ninety-seven patients diagnosed with dementia and seen at a tertiary hospital were evaluated. Of these 97 patients, 60 (62%) were female. The mean age of the patients was 77.9 years; average schooling was 5.5 years. The main diagnosis was Alzheimer's disease (73%): 16 patients were at a mild stage, eight at a moderate stage and 73 at an advanced stage of dementia. Only 28 patients had been legally declared incapable. The large numbers of patients at an advanced stage of dementia, and the relatively few patients legally declared incapable show that legal issues in dementia are problematic.

Association of the DD genotype and development of Japanese type 2 diabetic nephropathy.

PubMed

Gohda, T; Makita, Y; Shike, T; Kobayashi, M; Funabiki, K; Haneda, M; Kikkawa, R; Watanabe, T; Baba, T; Yoshida, H; Tomino, Y

2001-12-01

We determined the insertion/deletion (I/D) polymorphism of the angiotensin-coverting enzyme (ACE) gene in a multicenter trial of ethnically homogeneous Japanese type 2 diabetes mellitus (DM) patients. All patients (n = 748) were divided into 5 groups as follows: group I (normoalbuminuric patients), group II (microalbuminuric patients), group III (overt albuminuric patients with serum creatinine (s-Cr) levels of less than 1.2 mg/dl), group IV (overt albuminuric patients with s-Cr levels of more than 1.3 mg/dl but excluding hemodialysis patients), and group V (hemodialysis patients). We selected patients with a diabetic duration of more than 15 years in the mild stage (groups I and II), but placed no limits on those in the advanced and end-stages (groups III, IV and V). The frequency of the DD genotype was slightly higher in the advanced and end stages. The frequency of the DD genotype in the mild stage differed from that in the end stage (II/ID/DD 47.8%/41.0%/11.2% vs. 37.0 %/43.3%/19.7% p = 0.07, II + ID/DD 88.8%/11.2% vs. 80.3%/19.7%, p < 0.05). D allele frequency in the mild stage also differed from that in the end stage (I/D 68.3%/31.7% vs. 58.7%/41.3%, p < 0.02). The presence of the DD genotype increased the risk of end-stage renal disease (ESRD) more than that of the other genotypes (odds ratio ID/II = 1.37, 95% CI 0.82-2.27; DD/II = 2.27, 95% CI 1.12-4.61). It appears that the DD genotype is associated with progression of Japanese type 2 diabetic nephropathy.

Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation.

PubMed

Leoutsakos, Jeannie-Marie S; Yan, Haijuan; Anderson, William S; Asaad, Wael F; Baltuch, Gordon; Burke, Anna; Chakravarty, M Mallar; Drake, Kristen E; Foote, Kelly D; Fosdick, Lisa; Giacobbe, Peter; Mari, Zoltan; McAndrews, Mary Pat; Munro, Cynthia A; Oh, Esther S; Okun, Michael S; Pendergrass, Jo Cara; Ponce, Francisco A; Rosenberg, Paul B; Sabbagh, Marwan N; Salloway, Stephen; Tang-Wai, David F; Targum, Steven D; Wolk, David; Lozano, Andres M; Smith, Gwenn S; Lyketsos, Constantine G

2018-06-09

Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years. To examine the long-term safety and clinical effects of sustained and delayed-on DBS-f treatment of mild AD after two years. 42 participants underwent implantation of DBS-f electrodes, with half randomized to active DBS-f stimulation (early on) for two years and half to delayed-on (sham) stimulation after 1 year to provide 1 year of active DBS-f stimulation (delayed on). We evaluated safety and clinical outcomes over the two years of the trial. DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms. There were no differences between treatment arms on any primary clinical outcomes. However, post-hoc age group analyses suggested a possible benefit among older (>65) participants. DBS-f was safe. Additional study of mechanisms of action and methods for titrating stimulation parameters will be needed to determine if DBS has potential as an AD treatment. Future efficacy studies should focus on patients over age 65.

Promoting Sleep Oscillations and Their Functional Coupling by Transcranial Stimulation Enhances Memory Consolidation in Mild Cognitive Impairment.

PubMed

Ladenbauer, Julia; Ladenbauer, Josef; Külzow, Nadine; de Boor, Rebecca; Avramova, Elena; Grittner, Ulrike; Flöel, Agnes

2017-07-26

Alzheimer's disease (AD) not only involves loss of memory functions, but also prominent deterioration of sleep physiology, which is already evident at the stage of mild cognitive impairment (MCI). Cortical slow oscillations (SO; 0.5-1 Hz) and thalamocortical spindle activity (12-15 Hz) during sleep, and their temporal coordination, are considered critical for memory formation. We investigated the potential of slow oscillatory transcranial direct current stimulation (so-tDCS), applied during a daytime nap in a sleep-state-dependent manner, to modulate these activity patterns and sleep-related memory consolidation in nine male and seven female human patients with MCI. Stimulation significantly increased overall SO and spindle power, amplified spindle power during SO up-phases, and led to stronger synchronization between SO and spindle power fluctuations in EEG recordings. Moreover, visual declarative memory was improved by so-tDCS compared with sham stimulation and was associated with stronger synchronization. These findings indicate a well-tolerated therapeutic approach for disordered sleep physiology and memory deficits in MCI patients and advance our understanding of offline memory consolidation. SIGNIFICANCE STATEMENT In the light of increasing evidence that sleep disruption is crucially involved in the progression of Alzheimer's disease (AD), sleep appears as a promising treatment target in this pathology, particularly to counteract memory decline. This study demonstrates the potential of a noninvasive brain stimulation method during sleep in patients with mild cognitive impairment (MCI), a precursor of AD, and advances our understanding of its mechanism. We provide first time evidence that slow oscillatory transcranial stimulation amplifies the functional cross-frequency coupling between memory-relevant brain oscillations and improves visual memory consolidation in patients with MCI. Copyright © 2017 the authors 0270-6474/17/377111-14$15.00/0.

[Study of the beneficial effects of triptorelin on lower urinary tract symptoms in Algeria in patients with non-localized prostate cancer].

PubMed

Hachi, K; Boualga, K; Chettibi, K; Harouni, M; Ounnoughene, M; Bekkat-Berkani, N; Maisonobe, P; Yousfi, M J

2018-05-20

This study aims to assess the effectiveness of triptorelin on lower urinary tract symptoms (LUTS) in Algerian patients with non-localized prostate cancer in routine practice. This prospective, observational, non-interventional, multicentre study was conducted in Algeria. Included patients who had locally advanced or metastatic prostate cancer and were treated with triptorelin 11.25mg given every 12 weeks. LUTS were evaluated with the International Prostate Symptom Score (IPSS) until week 48 after treatment initiation. An IPSS>7 indicated moderate to severe LUTS. The primary objective of the study was to determine the distribution of IPSS at week 48. This study enrolled 193 patients at 21 centres. A total of 144 participants had IPSS available at baseline and after baseline (136 patients had moderate to severe LUTS and eight had mild LUTS at baseline). At week 48, amongst the 116 patients with IPSS available and moderate to severe LUTS at baseline, 94 (81.0%) had moderate to severe LUTS and 22 (19.0%) had mild LUTS. At week 48, the eight patients with mild symptoms at baseline remained in this category. The proportion of patient with severe LUTS decreased from 53.7% at baseline to 12.1% at week 48. Adverse events were reported in 22.9% of participants. A reduction of LUTS is observed in patients with locally advanced or metastatic prostate cancer treated with triptorelin in routine practice. This is in agreement with similar observational studies of triptorelin conducted in other countries. 4. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Cost-benefit analysis of cranial computed tomography in mild traumatic brain injury--appropriate depiction within the G-DRG system?].

PubMed

Garving, C; Weber, C D; Poßelt, S; Pishnamaz, M; Pape, H C; Dienstknecht, T

2014-06-01

The treatment of patients with mild head injury is related to a continuous lack of finances. The current investigation summarises radiological costs of patients from a level I trauma centre and discusses the indication for CT scanning within the G-DRG system. The study includes all patients who underwent a CCT scan in 2011. Diagnosis, length of stay and cost data were recorded for every patient. Finally, frequent diagnosis groups were summarised to clusters (Basis-DRG/MDC 21A). A total of 380 patients was treated. Within the largest group (G-DRG B80Z) the costs for a CCT already took up one quarter of the total proceedings. In combination with the high cost for monitoring patients with mild head injuries this causes an ongoing lack of finances. In spite of the often necessary CCT investigation in mild head injuries, the earnings do not cover the costs of the patients. To improve the situation clear guidelines for CCT scanning should be provided and the reimbursement in particular in the diagnosis group of the G-DRG B80Z has to be improved. Georg Thieme Verlag KG Stuttgart · New York.

Effects of multisensory stimulation on cognition, depression and anxiety levels of mildly-affected Alzheimer's patients.

PubMed

Ozdemir, Leyla; Akdemir, Nuran

2009-08-15

The purpose of this study was to investigate and assess the effects of musical therapy, painting inanimate-animate object pictures, and orientation to time-place-person interventions on the cognitive state, depression, and anxiety levels of mildly-affected Alzheimer's patients. The study using a quasi-experimental design was conducted with 27 mildly-affected Alzheimer's patients. The effects of the multisensory stimulation were evaluated with the "Mini Mental State Examination," the "Geriatric Depression Scale," and the "Beck Anxiety Scale." All of these were administered one day prior to beginning the study, immediately after its completion, and three weeks thereafter. A significant negative correlation was determined to exist between the MMSE-depression scores and MMSE-anxiety scores; the correlation between the depression-anxiety scores, on the other hand, had a positive significance. The shifts over time in the MMSE, depression and anxiety scores were significant. The primary conclusion of the study is that the multisensory stimulation method applied to mildly-affected Alzheimer's patients had a positive effect on their cognitive state, depression, and anxiety, and that this effect continued for three weeks following completion of the study intervention, with a tendency to decline progressively.

Magnetic resonance imaging for white matter degradation in fornix following mild traumatic brain injury

NASA Astrophysics Data System (ADS)

Zhan, Wang; Boreta, Lauren; Gauger, Grant

2010-03-01

The alterations of the fornix in mild traumatic brain injury (mTBI) were investigated using diffusion tensor imaging (DTI) and T1-weighetd anatomical imaging. The primary goal of this study was to test that hypothesis that the fornix might play a major role in the memory and learning dysfunctions in the post-concussion syndrome, which may related to the white matter (WM) degradations following mild traumatic brain injury. N=24 mTBI patients were longitudinally studied in two time points with 6-month intervals using a 4-Tesla MRI scanner to measure the WM integrity of fornix and the fornix-to-brain ratio (FBR), and compared with matched healthy controls. Our data show that the WM degradation in fornix onset in the acute stage after mild TBI when the post-injury time was less than 6 weeks, and that this WM degradation continued during the following 6-month period of recovery. In summary, using DTI and structural MRI together can effectively detect the fornix changes in both cross-sectional and longitudinal investigations. Further studies are warranted to exam the association between the fornix alterations and neurocognitive performance of TBI patients.

First Aid: Dehydration

MedlinePlus

... rapid or weakened pulse What to Do Mild dehydration often can be treated at home. If your child has diarrhea but no vomiting, continue feeding a ... 20 minutes. Seek Emergency Medical Care If Your Child: shows any sign of severe dehydration is unable to keep clear fluids down Think ...

Hepatotoxicity associated with choline magnesium trisalicylate: case report and review of salicylate-induced hepatotoxicity.

PubMed

Cersosimo, R J; Matthews, S J

1987-01-01

A case of a 21-year-old woman who had developed mild hepatotoxicity while receiving choline magnesium trisalicylate therapy is described. She presented with fever and mild hepatic enzyme elevations before salicylate therapy was instituted. Liver function tests (LFT) returned to normal within five days of hospitalization but she continued to develop daily fevers. Blood, urine, and throat cultures were negative. An acute viral illness or reactivation of systemic lupus erythematosus were the suspected diagnoses. Choline magnesium trisalicylate was then administered in an effort to control her fever, and was successful. After three days of salicylate therapy her LFT values began to rise. They continued to rise for five more days before salicylate hepatotoxicity was suspected. Choline magnesium trisalicylate was discontinued after eight days and the patient's LFT quickly returned to normal. The source of fever was never identified, although infection with cytomegalovirus was considered the most likely cause. Salicylate-induced hepatotoxicity is reviewed.

Recent advances in biotechnological applications of alcohol dehydrogenases.

PubMed

Zheng, Yu-Guo; Yin, Huan-Huan; Yu, Dao-Fu; Chen, Xiang; Tang, Xiao-Ling; Zhang, Xiao-Jian; Xue, Ya-Ping; Wang, Ya-Jun; Liu, Zhi-Qiang

2017-02-01

Alcohol dehydrogenases (ADHs), which belong to the oxidoreductase superfamily, catalyze the interconversion between alcohols and aldehydes or ketones with high stereoselectivity under mild conditions. ADHs are widely employed as biocatalysts for the dynamic kinetic resolution of racemic substrates and for the preparation of enantiomerically pure chemicals. This review provides an overview of biotechnological applications for ADHs in the production of chiral pharmaceuticals and fine chemicals.

Manifestation Pattern of Early-Late Vaginal Morbidity After Definitive Radiation (Chemo)Therapy and Image-Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: An Analysis From the EMBRACE Study

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

Kirchheiner, Kathrin, E-mail: kathrin.kirchheiner@meduniwien.ac.at; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna; Nout, Remi A.

2014-05-01

Background and Purpose: Brachytherapy in the treatment of locally advanced cervical cancer has changed substantially because of the introduction of combined intracavitary/interstitial applicators and an adaptive target concept, which is the focus of the prospective, multi-institutional EMBRACE study ( (www.embracestudy.dk)) on image-guided adaptive brachytherapy (IGABT). So far, little has been reported about the development of early to late vaginal morbidity in the frame of IGABT. Therefore, the aim of the present EMBRACE analysis was to evaluate the manifestation pattern of vaginal morbidity during the first 2 years of follow-up. Methods and Materials: In total, 588 patients with a median follow-up timemore » of 15 months and information on vaginal morbidity were included. Morbidity was prospectively assessed at baseline, every 3 months during the first year, and every 6 months in the second year according to the Common Terminology Criteria for Adverse Events, version 3, regarding vaginal stenosis, dryness, mucositis, bleeding, fistula, and other symptoms. Crude incidence rates, actuarial probabilities, and prevalence rates were analyzed. Results: At 2 years, the actuarial probability of severe vaginal morbidity (grade ≥3) was 3.6%. However, mild and moderate vaginal symptoms were still pronounced (grade ≥1, 89%; grade ≥2, 29%), of which the majority developed within 6 months. Stenosis was most frequently observed, followed by vaginal dryness. Vaginal bleeding and mucositis were mainly mild and infrequently reported. Conclusion: Severe vaginal morbidity within the first 2 years after definitive radiation (chemo)therapy including IGABT with intracavitary/interstitial techniques for locally advanced cervical cancer is limited and is significantly less than has been reported from earlier studies. Thus, the new adaptive target concept seems to be a safe treatment with regard to the vagina being an organ at risk. However, mild to moderate vaginal morbidity is still pronounced with currently applied IGABT, and it needs further attention.« less

Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial.

PubMed

Ponce, Francisco A; Asaad, Wael F; Foote, Kelly D; Anderson, William S; Rees Cosgrove, G; Baltuch, Gordon H; Beasley, Kara; Reymers, Donald E; Oh, Esther S; Targum, Steven D; Smith, Gwenn S; Lyketsos, Constantine G; Lozano, Andres M

2016-07-01

OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. Clinical trial registration no.: NCT01608061 ( clinicaltrials.gov ).

Bilateral deep brain stimulation of the fornix for Alzheimer’s disease: surgical safety in the ADvance trial

PubMed Central

Ponce, Francisco A.; Asaad, Wael F.; Foote, Kelly D.; Anderson, William S.; Cosgrove, G. Rees; Baltuch, Gordon H.; Beasley, Kara; Reymers, Donald E.; Oh, Esther S.; Targum, Steven D.; Smith, Gwenn S.; Lyketsos, Constantine G.; Lozano, Andres M.

2016-01-01

OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer’s disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intra-operative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0–79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0–7.9 mm), y = 9.6 ± 0.9 mm (range 8.0–11.6 mm), z = −7.5 ± 1.2 mm (range −5.4 to −10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2–4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. PMID:26684775

Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation.

PubMed

Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Kirkby, Stephen; Mansour, Heidi M; Whitson, Bryan A

2016-01-01

The influence of varying levels of pulmonary hypertension (PH) on survival in idiopathic pulmonary fibrosis is not well defined. The United Network for Organ Sharing database was queried from 2005 to 2013 to identify first-time lung transplant candidates listed for lung transplantation who were tracked from waitlist entry date until death or censoring to determine the influence of PH on patients with advanced lung disease. Using data for right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure of 25 mm Hg or more, and severe as 35 mm Hg or more. Of 6,657 idiopathic pulmonary fibrosis patients, 6,651 were used for univariate analysis, 6,126 for Kaplan-Meier survival function, 6,013 for multivariate Cox models, and 5,186 (mild PH) and 2,014 (severe PH) for propensity score matching, respectively. Univariate Cox proportional hazards analysis found significant differences in survival for mild PH (hazard ratio [HR] 1.689, 95% confidence interval [CI]: 1.434 to 1.988, p < 0.001) and severe PH (HR 2.068, 95% CI: 1.715 to 2.493, p < 0.001). Further assessment by multivariate Cox models identified significant risk for death for mild PH (HR 1.433, 95% CI: 1.203 to 1.706, p < 0.001) and severe PH (HR 1.597, 95% CI: 1.308 to 1.949, p < 0.001). Propensity score matching confirmed the risk for death for mild PH (HR 1.530, 95% CI: 1.189 to 1.969, p = 0.001) and severe PH (HR 2.103, 95% CI: 1.436 to 3.078, p < 0.001). The manifestation of PH, even with mild severity, is associated with significantly increased risk for death among patients with idiopathic pulmonary fibrosis awaiting lung transplantation, so referral should be considered early in the disease course. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

MiDAS I (mild Decompression Alternative to Open Surgery): a preliminary report of a prospective, multi-center clinical study.

PubMed

Chopko, Bohdan; Caraway, David L

2010-01-01

Neurogenic claudication due to lumbar spinal stenosis is a common problem that can be caused by many factors including hypertrophic ligamentum flavum, facet hypertrophy, and disc protrusion. When standard medical therapies such as pain medication, epidural steroid injections, and physical therapy fail, or when the patient is unwilling, unable, or not severe enough to advance to more invasive surgical procedures, both physicians and patients are often left with a treatment dilemma. Patients in this study were treated with mild, an ultra-minimally invasive lumbar decompression procedure using a dorsal approach. The mild procedure is performed under fluoroscopic imaging to resect bone adjacent to, and achieve partial resection of, the hypertrophic ligamentum flavum with minimal disruption of surrounding muscular and skeletal structure. To assess the clinical application and patient safety and functional outcomes of the mild lumbar decompression procedure in the treatment of symptomatic central canal spinal stenosis. Multi-center, non-blinded, prospective clinical study. Fourteen US spine specialist practices. Between July 2008 and January 2010, 78 patients were enrolled in the MiDAS I Study and treated with the mild procedure for lumbar decompression. Of these patients, 6-week follow-up was available for 75 patients. Visual Analog Score (VAS), Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and SF-12v2 Health Survey. Outcomes were assessed at baseline and 6 weeks post-treatment. There were no major device or procedure-related complications reported in this patient cohort. At 6 weeks, the MiDAS I Study showed statistically and clinically significant reduction of pain as measured by VAS, ZCQ, and SF-12v2. In addition, improvement in physical function and mobility as measured by ODI, ZCQ, and SF-12v2 was statistically and clinically significant in this study. This is a preliminary report encompassing 6-week follow-up. There was no control group. In this 75-patient series, and in keeping with a previously published 90-patient safety cohort, the mild procedure proved to be safe. Further, based on near-term follow-up, the mild procedure demonstrated efficacy in improving mobility and reducing pain associated with lumbar spinal canal stenosis.

Catalytic intermolecular carbon electrophile induced semipinacol rearrangement.

PubMed

Zhang, Qing-Wei; Zhang, Xiao-Bo; Li, Bao-Sheng; Xiang, Kai; Zhang, Fu-Min; Wang, Shao-Hua; Tu, Yong-Qiang

2013-02-25

A catalytic intermolecular carbon electrophile induced semipinacol rearrangement was realized and the asymmetric version was also preliminarily accomplished with 92% and 82% ee. The complex tricyclic system architecture with four continuous stereogenic centers could be achieved from simple starting materials in a single step under mild conditions.

The Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Umbreit, John; Ostrow, Lisa S.

1980-01-01

Fetal alcohol syndrome is a pattern of altered growth and morphogenesis found in about half the offspring of severely and chronically alcoholic women who continue drinking throughout their pregnancy. Of children studied, mild to moderate mental retardation was the most common disorder, occurring in 44 percent of the cases. (PHR)

The Role of Colleges of Advanced Education in the Education of Adults. A Report to the Australian Commission on Advanced Education.

ERIC Educational Resources Information Center

Nelson, A. J. A.

This report to the Australian Commission on Advanced Education is intended as a basis for discussion by those who have the responsibility for making program and policy decisions in continuing education in Australia's colleges of advanced education. Though the idea that education is continuous with life is coming to be widely accepted…

Pharmacists' Interest in and Commitment to Obtaining an Advanced Pharmacy Degree through Continuing Education.

ERIC Educational Resources Information Center

Riley, David A.

1986-01-01

Describes results of a survey of all West Virginia pharmacists concerning their views on continuing education and advanced pharmacy degrees. Conclusions indicate a small percentage of pharmacists are interested in a higher degree via continuing education. (Author/CT)

42 CFR § 414.1410 - Advanced APM determination.

Code of Federal Regulations, 2010 CFR

2017-10-01

... SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Merit-Based Incentive Payment System and Alternative Payment Model Incentive § 414.1410 Advanced APM determination. (a) General. An APM is an Advanced APM for a payment year if CMS determines that it meets the...

Free and Cued Recall Memory in Parkinson’s Disease Associated with Amnestic Mild Cognitive Impairment

PubMed Central

Costa, Alberto; Monaco, Marco; Zabberoni, Silvia; Peppe, Antonella; Perri, Roberta; Fadda, Lucia; Iannarelli, Francesca; Caltagirone, Carlo; Carlesimo, Giovanni A.

2014-01-01

The hypothesis has been advanced that memory disorders in individuals with Parkinson’s disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients’ performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning. PMID:24465977

A hybrid feature selection approach for the early diagnosis of Alzheimer’s disease

NASA Astrophysics Data System (ADS)

Gallego-Jutglà, Esteve; Solé-Casals, Jordi; Vialatte, François-Benoît; Elgendi, Mohamed; Cichocki, Andrzej; Dauwels, Justin

2015-02-01

Objective. Recently, significant advances have been made in the early diagnosis of Alzheimer’s disease (AD) from electroencephalography (EEG). However, choosing suitable measures is a challenging task. Among other measures, frequency relative power (RP) and loss of complexity have been used with promising results. In the present study we investigate the early diagnosis of AD using synchrony measures and frequency RP on EEG signals, examining the changes found in different frequency ranges. Approach. We first explore the use of a single feature for computing the classification rate (CR), looking for the best frequency range. Then, we present a multiple feature classification system that outperforms all previous results using a feature selection strategy. These two approaches are tested in two different databases, one containing mild cognitive impairment (MCI) and healthy subjects (patients age: 71.9 ± 10.2, healthy subjects age: 71.7 ± 8.3), and the other containing Mild AD and healthy subjects (patients age: 77.6 ± 10.0 healthy subjects age: 69.4 ± 11.5). Main results. Using a single feature to compute CRs we achieve a performance of 78.33% for the MCI data set and of 97.56% for Mild AD. Results are clearly improved using the multiple feature classification, where a CR of 95% is found for the MCI data set using 11 features, and 100% for the Mild AD data set using four features. Significance. The new features selection method described in this work may be a reliable tool that could help to design a realistic system that does not require prior knowledge of a patient's status. With that aim, we explore the standardization of features for MCI and Mild AD data sets with promising results.

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life.

PubMed

Gupta, Kamlesh Kumar; Roy, Bidyut; Chaudhary, Shyam Chand; Mishra, Arvind; Patel, M L; Singh, Jitendra; Kumar, Vivek

2018-01-01

Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis. The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life. It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires. Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH. The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH.

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life

PubMed Central

Gupta, Kamlesh Kumar; Roy, Bidyut; Chaudhary, Shyam Chand; Mishra, Arvind; Patel, M. L.; Singh, Jitendra; Kumar, Vivek

2018-01-01

Background: Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis. Aims and Objective: The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life. Materials and Methods: It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires. Results: Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH. Conclusion: The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH. PMID:29915733

Free and cued recall memory in Parkinson's disease associated with amnestic mild cognitive impairment.

PubMed

Costa, Alberto; Monaco, Marco; Zabberoni, Silvia; Peppe, Antonella; Perri, Roberta; Fadda, Lucia; Iannarelli, Francesca; Caltagirone, Carlo; Carlesimo, Giovanni A

2014-01-01

The hypothesis has been advanced that memory disorders in individuals with Parkinson's disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients' performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning.

Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.

PubMed

Bratton, Daniel J; Gaisl, Thomas; Schlatzer, Christian; Kohler, Malcolm

2015-11-01

Excessive daytime sleepiness is the most important symptom of obstructive sleep apnoea and can affect work productivity, quality of life, and the risk of road traffic accidents. We aimed to quantify the effects of the two main treatments for obstructive sleep apnoea (continuous positive airway pressure and mandibular advancement devices) on daytime sleepiness and to establish predictors of response to continuous positive airway pressure. We searched MEDLINE and the Cochrane Library from inception to May 31, 2015, to identify randomised controlled trials comparing the effects of continuous positive airway pressure, mandibular advancement devices or an inactive control (eg, placebo or no treatment) on the Epworth Sleepiness Scale (ESS, range 0-24 points) in patients with obstructive sleep apnoea. We did a network meta-analysis using multivariate random-effects meta-regression to assess the effect of each treatment on ESS. We used meta-regression to assess the association of the reported effects of continuous positive airway pressure versus inactive controls with the characteristics of trials and their risk of bias. We included 67 studies comprising 6873 patients in the meta-analysis. Compared with an inactive control, continuous positive airway pressure was associated with a reduction in ESS score of 2·5 points (95% CI 2·0-2·9) and mandibular advancement devices of 1·7 points (1·1-2·3). We estimated that, on average, continuous positive airway pressure reduced the ESS score by a further 0·8 points compared with mandibular advancement devices (95% CI 0·1-1·4; p=0·015). However, there was a possibility of publication bias in favour of continuous positive airway pressure that might have resulted in this difference. We noted no evidence that studies reporting higher continuous positive airway pressure adherence also reported larger treatment effects (p=0·70). Continuous positive airway pressure and mandibular advancement devices are effective treatments for reducing daytime sleepiness in patients with obstructive sleep apnoea. Continuous positive airway pressure seemed to be a more effective treatment than mandibular advancement devices, and had an increasingly larger effect in more severe or sleepier obstructive sleep apnoea patients when compared with inactive controls. However, mandibular advancement devices are an effective alternative treatment should continuous positive airway pressure not be tolerated. Swiss National Science Foundation and the University of Zurich Clinical Research Priority Program Sleep and Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lasers in tattoo and pigmentation control: role of the PicoSure(®) laser system.

PubMed

Torbeck, Richard; Bankowski, Richard; Henize, Sarah; Saedi, Nazanin

2016-01-01

The use of picosecond lasers to remove tattoos has greatly improved due to the long-standing outcomes of nanosecond lasers, both clinically and histologically. The first aesthetic picosecond laser available for this use was the PicoSure(®) laser system (755/532 nm). Now that a vast amount of research on its use has been conducted, we performed a comprehensive review of the literature to validate the continued application of the PicoSure(®) laser system for tattoo removal. A PubMed search was conducted using the term "picosecond" combined with "laser", "dermatology", and "laser tattoo removal". A total of 13 articles were identified, and ten of these met the inclusion criteria for this review. The majority of studies showed that picosecond lasers are an effective and safe treatment mode for the removal of tattoo pigments. Several studies also indicated potential novel applications of picosecond lasers in the removal of various tattoo pigments (eg, black, red, and yellow). Adverse effects were generally mild, such as transient hypopigmentation or blister formation, and were rarely more serious, such as scarring and/or textural change. Advancements in laser technologies and their application in cutaneous medicine have revolutionized the field of laser surgery. Computational modeling provides evidence that the optimal pulse durations for tattoo ink removal are in the picosecond domain. It is recommended that the PicoSure(®) laser system continue to be used for safe and effective tattoo removal, including for red and yellow pigments.

Mild traumatic brain injury literature review and proposed changes to classification.

PubMed

Krainin, Benjamin M; Forsten, Robert D; Kotwal, Russ S; Lutz, Robert H; Guskiewicz, Kevin M

2011-01-01

Mild traumatic brain injury (mTBI) reportedly occurs in 8-22% of U.S. servicemembers who conduct combat operations in Afghanistan and Iraq. The current definition for mTBI found in the medical literature, to include the Department of Defense (DoD) and Veterans Administration (VA) clinical practice guidelines is limited by the parameters of loss of consciousness, altered consciousness, or post-traumatic amnesia, and does not account for other constellations of potential symptoms. Although mTBI symptoms typically resolve within seven days, some servicemembers experience symptoms that continue for weeks, months, or years following an injury. Mild TBI is one of few disorders in medicine where a benign and misleading diagnostic classification is bestowed on patients at the time of injury, yet still can be associated with lifelong complications. This article comprehensively reviews the clinical literature over the past 20 years and proposes a new classification for TBI that addresses acute, sub-acute, and chronic phases, and includes neurocognitive, somatic, and psychological symptom presentation. 2011.

Possibility of High Phosphorus Pig Iron as Sacrificial Anode

NASA Astrophysics Data System (ADS)

Prasad, Nisheeth Kr.; Pathak, A. S.; Kundu, S.; Mondal, K.

2018-05-01

Cathodic protection is an effective method to control the corrosion of underground pipelines and submerged structures. In the present work, high phosphorus containing pig iron was utilized as sacrificial anode for cathodic protection of underground mild steel plates and the results were compared with that of a commercially pure magnesium sacrificial anode. Driving potential and current between the galvanically coupled sacrificial anodes and mild steel plates were continuously monitored in real time for one month. Microstructure and morphology of the corrosion products formed on the surface of pig iron, magnesium sacrificial anodes and mild steel plates were observed with the help of optical microscope and scanning electron microscopy, and phase identification were performed using x-ray diffraction, Raman spectroscopy and Fourier transform infrared spectroscopy. The distribution of phosphorus in the pig iron matrix and soluble rust formation on the surface of pig iron under buried condition were critical from the point of sacrificial effect, indicating the possible scientific reasons for high phosphorous pig iron to be used as sacrificial anode.

Cognitive Training Using a Novel Memory Game on an iPad in Patients with Amnestic Mild Cognitive Impairment (aMCI)

PubMed Central

Savulich, George; Piercy, Thomas; Fox, Chris; Suckling, John; Rowe, James B; O’Brien, John T

2017-01-01

Abstract Background Cognitive training is effective in patients with mild cognitive impairment but does not typically address the motivational deficits associated with older populations with memory difficulties. Methods We conducted a randomized controlled trial of cognitive training using a novel memory game on an iPad in 42 patients with a diagnosis of amnestic mild cognitive impairment assigned to either the cognitive training (n=21; 8 hours of gameplay over 4 weeks) or control (n=21; clinic visits as usual) groups. Results Significant time-by-pattern-by-group interactions were found for cognitive performance in terms of the number of errors made and trials needed on the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning task (P=.044; P=.027). Significant time-by-group interactions were also found for the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning first trial memory score (P=.002), Mini-Mental State Examination (P=.036), the Brief Visuospatial Memory Test (P=.032), and the Apathy Evaluation Scale (P=.026). Within-group comparisons revealed highly specific effects of cognitive training on episodic memory. The cognitive training group maintained high levels of enjoyment and motivation to continue after each hour of gameplay, with self-confidence and self-rated memory ability improving over time. Conclusions Episodic memory robustly improved in the cognitive training group. “Gamified” cognitive training may also enhance visuospatial abilities in patients with amnestic mild cognitive impairment. Gamification maximizes engagement with cognitive training by increasing motivation and could complement pharmacological treatments for amnestic mild cognitive impairment and mild Alzheimer’s disease. Larger, more controlled trials are needed to replicate and extend these findings. PMID:28898959

Cognitive Training Using a Novel Memory Game on an iPad in Patients with Amnestic Mild Cognitive Impairment (aMCI).

PubMed

Savulich, George; Piercy, Thomas; Fox, Chris; Suckling, John; Rowe, James B; O'Brien, John T; Sahakian, Barbara J

2017-08-01

Cognitive training is effective in patients with mild cognitive impairment but does not typically address the motivational deficits associated with older populations with memory difficulties. We conducted a randomized controlled trial of cognitive training using a novel memory game on an iPad in 42 patients with a diagnosis of amnestic mild cognitive impairment assigned to either the cognitive training (n=21; 8 hours of gameplay over 4 weeks) or control (n=21; clinic visits as usual) groups. Significant time-by-pattern-by-group interactions were found for cognitive performance in terms of the number of errors made and trials needed on the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning task (P=.044; P=.027). Significant time-by-group interactions were also found for the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning first trial memory score (P=.002), Mini-Mental State Examination (P=.036), the Brief Visuospatial Memory Test (P=.032), and the Apathy Evaluation Scale (P=.026). Within-group comparisons revealed highly specific effects of cognitive training on episodic memory. The cognitive training group maintained high levels of enjoyment and motivation to continue after each hour of gameplay, with self-confidence and self-rated memory ability improving over time. Episodic memory robustly improved in the cognitive training group. "Gamified" cognitive training may also enhance visuospatial abilities in patients with amnestic mild cognitive impairment. Gamification maximizes engagement with cognitive training by increasing motivation and could complement pharmacological treatments for amnestic mild cognitive impairment and mild Alzheimer's disease. Larger, more controlled trials are needed to replicate and extend these findings. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin.

PubMed

Li, Quan; Cohn, David; Waller, Allyson; Backes, Floor; Copeland, Larry; Fowler, Jeffrey; Salani, Ritu; O'Malley, David

2014-10-01

The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. From January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. The outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin. Copyright © 2014 Elsevier Inc. All rights reserved.

Identifying acceptable components for home-based health promotion services for older people with mild frailty: A qualitative study.

PubMed

Frost, Rachael; Kharicha, Kalpa; Jovicic, Ana; Liljas, Ann E M; Iliffe, Steve; Manthorpe, Jill; Gardner, Benjamin; Avgerinou, Christina; Goodman, Claire; Drennan, Vari M; Walters, Kate

2018-05-01

Mild frailty is common in later life, increasing the risk of hospitalisation, loss of independence and premature death. Targeted health promotion services may reduce adverse outcomes and increase quality of life; however, effective, well-developed theory-based interventions are lacking. We aimed to explore perceptions of health promotion behaviours undertaken by older people with mild frailty, barriers and facilitators to engagement, and identify potential components for new home-based health promotion services. We carried out 17 semi-structured qualitative interviews and six focus groups with 53 stakeholders, including 14 mildly frail older people, 12 family carers, 19 community health and social care professionals, and 8 homecare workers, in one urban and one semi-rural area of England. Transcripts were thematically analysed. Older people with mild frailty reported engaging in a variety of lifestyle behaviours to promote health and well-being. Key barriers or facilitators to engaging in these included transport, knowledge of local services, social support and acceptance of personal limitations. Older people, carers and professionals agreed that any new service should address social networks and mobility and tailor other content to each individual. Services should aim to increase motivation through focussing on independence and facilitate older people to continue carrying out behaviours that improve their well-being, as well as provide information, motivation, psychological support and practical support. Stakeholders agreed services should be delivered over a sustained period by trained non-specialist workers. New services including these components are likely to be acceptable to older people with mild frailty. © 2017 The Authors. Health and Social Care in the Community Published by John Wiley & Sons Ltd.

Advanced MRI in Acute Military TBI

DTIC Science & Technology

2014-09-01

symptoms onmental health and service discharge outcomes. J Neurotrauma. 2013; 30(16):1391-1397. 16. GalarneauMR,Woodruff SI, Dye JL, Mohrle CR, Wade...related mild traumatic brain injury acute symptoms on mental health and service discharge outcomes. J. Neurotrauma 30, 1391–1397. 22. Casscells, S. (2007...radiation (include optic radiation) left 37 Anterior corona radiata right 102 Anterior corona radiata left 38 Superior corona radiata right 103 Superior

Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

PubMed

Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

2007-07-01

Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

Analysis of risk factors for mild cognitive impairment based on word list memory test results and questionnaire responses in healthy Japanese individuals registered in an online database.

PubMed

Ogawa, Masayo; Sone, Daichi; Maruo, Kazushi; Shimada, Hiroyuki; Suzuki, Keisuke; Watanabe, Hiroshi; Matsuda, Hiroshi; Mizusawa, Hidehiro

2018-01-01

Although the development of effective therapeutic drugs and radical treatment options for dementia and Alzheimer's disease (AD) remains urgent, progress in recent clinical trials of AD drugs has been less than adequate. In order to advance the progress of clinical trials, it is necessary to establish more efficient methods of recruitment. In Japan, there are registration systems stratified by mild cognitive impairment and preclinical and clinical stages of early and advanced stage dementia, but there is no registration system for healthy individuals yet. Therefore, in the present study, we developed a large-scale, internet-based health registry to investigate factors associated with cognitive function among registered participants. A total of 1038 participants completed the initial questionnaire and word list memory test. Among these participants, 353 individuals completed a second questionnaire and memory test. Stepwise multiple regression analysis was performed using IBM SPSS version 23.0 for Windows at a statistical significance level of p<0.05. We found that mood, motivation, and a decreased ability to perform activities of daily living were significantly associated with cognitive function. The results of the present study suggest that maintaining social involvement is important to prevent decreases in physical activity, daily function, mood, and motivation.

Clinical trials in mild traumatic brain injury.

PubMed

Hoffer, Michael E; Szczupak, Mikhaylo; Balaban, Carey

2016-10-15

Traumatic brain injury is an increasingly prevalent injury seen in both civilian and military populations. Regardless of the mechanisms of injury, the most common sub-type of injury continues to be mild traumatic brain injury. Within the last decade, there has been tremendous growth in the literature regarding this disease entity. To describe the obstacles necessary to overcome in performing a rigorous and sound clinical research study investigating mild traumatic brain injury. This examination begins by a consideration of changing standards for good faith open and total reporting of any and all conflicts of interest or commitment. This issue is particularly critical in mTBI research. We next examine obstacles that include but are not limited to diagnostic criteria, inclusion/exclusion criteria, source of injury, previous history of injury, presence of comorbid conditions and proper informed consent of participants. Frequently, multi-center studies are necessary for adequate subject accrual with the added challenges of site coordination, data core management and site specific study conduct. We propose a total reversal to the traditional translational research approach where clinical studies drive new concepts for future basic science studies. There have been few mild traumatic brain injury clinical trials in the literature with treatments/interventions that have been able to overcome many of these described obstacles. We look forward to the results of current and ongoing clinical mild traumatic brain injury studies providing the tools necessary for the next generation of basic science projects. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion caused by methicillin-sensitive Staphylococcus aureus bacteremia with toxic shock syndrome: a case report.

PubMed

Kosami, Koki; Kenzaka, Tsuneaki; Sagara, Yuka; Minami, Kensuke; Matsumura, Masami

2016-04-18

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a mild encephalopathy caused by various pathological processes, but encephalopathy due to bacteria is rare. We report the case of a 45-year-old Japanese woman who on receiving chemotherapy for advanced breast cancer developed an altered mental status and dysarthria soon after fever from infection of a subcutaneous implantable port. Staphylococcus aureus was detected in her blood cultures. Magnetic resonance imaging (MRI) revealed an ovoid lesion in the central portion of the splenium of the corpus callosum (SCC). Although hypotension was not observed, we diagnosed probable toxic shock syndrome (TSS) based on fever (temperature: >38.9 °C), altered mental status, erythema, desquamation, thrombocytopenia, liver dysfunction, and creatine phosphokinase elevation. We administered antimicrobial therapy and her neurological symptoms improved gradually. The lesion in the SCC completely disappeared on MRI 7 days after disease onset. We diagnosed this case as MERS caused by S. aureus bacteremia with TSS. This is the first report of such a case, and we suggest that when a TSS patient presents with neurological symptoms, the possibility of MERS should be considered.

Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999-2013).

PubMed

McQuown, B; Keyerleber, M A; Rosen, K; McEntee, M C; Burgess, K E

2017-09-01

Currently no standard of care exists for advanced, inoperable or metastatic anal sac adenocarcinoma (ASAC). The objective of this retrospective study was to assess the role of hypofractionated radiation therapy (RT) in 77 dogs with measurable ASAC. A total of 38% of dogs experienced a partial response to RT. For dogs presenting with clinical signs related to the tumour, improvement or resolution of signs was noted in 63%. For dogs presenting with hypercalcemia of malignancy, resolution was noted in 31% with RT alone and an additional 46% with radiation, prednisone, and/or bisphosphonates. Median overall survival was 329 days (range: 252-448 days). Median progression free survival was 289 days (range: 224-469). There was no difference in survival based on radiation protocol, use of chemotherapy, previous surgery or advanced stage. Radiation toxicities were mild and infrequent. Hypofractionated RT is well tolerated and is applicable in the treatment of advanced primary, locoregional or metastatic ASAC. © 2016 John Wiley & Sons Ltd.

Sono-bromination of aromatic compounds based on the ultrasonic advanced oxidation processes.

PubMed

Fujita, Mitsue; Lévêque, Jean-Marc; Komatsu, Naoki; Kimura, Takahide

2015-11-01

A novel, mild "sono-halogenation" of various aromatic compounds with potassium halide was investigated under ultrasound in a biphasic carbon tetrachloride/water medium. The feasibility study was first undertaken with the potassium bromide and then extended to chloride and iodide analogues. This methodology could be considered as a new expansion of the ultrasonic advanced oxidation processes (UAOPs) into a synthetic aspect as the developed methodology is linked to the sonolytic disappearance of carbon tetrachloride. Advantages of the present method are not only that the manipulation of the bromination is simple and green, but also that the halogenating agents used are readily available, inexpensive, and easy-handling. Copyright © 2015 Elsevier B.V. All rights reserved.

Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions.

PubMed

Cole, Kevin P; Groh, Jennifer McClary; Johnson, Martin D; Burcham, Christopher L; Campbell, Bradley M; Diseroad, William D; Heller, Michael R; Howell, John R; Kallman, Neil J; Koenig, Thomas M; May, Scott A; Miller, Richard D; Mitchell, David; Myers, David P; Myers, Steven S; Phillips, Joseph L; Polster, Christopher S; White, Timothy D; Cashman, Jim; Hurley, Declan; Moylan, Robert; Sheehan, Paul; Spencer, Richard D; Desmond, Kenneth; Desmond, Paul; Gowran, Olivia

2017-06-16

Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods. Success was enabled by advances in chemistry, engineering, analytical science, process modeling, and equipment design. Substantial technical and business drivers were identified, which merited the continuous process. The continuous process afforded improved performance and safety relative to batch processes and also improved containment of a highly potent compound. Copyright © 2017, American Association for the Advancement of Science.

Clostridium difficile infection: epidemiology, diagnosis and understanding transmission.

PubMed

Martin, Jessica S H; Monaghan, Tanya M; Wilcox, Mark H

2016-04-01

Clostridium difficile infection (CDI) continues to affect patients in hospitals and communities worldwide. The spectrum of clinical disease ranges from mild diarrhoea to toxic megacolon, colonic perforation and death. However, this bacterium might also be carried asymptomatically in the gut, potentially leading to 'silent' onward transmission. Modern technologies, such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis, are helping to track C. difficile transmission across health-care facilities, countries and continents, offering the potential to illuminate previously under-recognized sources of infection. These typing strategies have also demonstrated heterogeneity in terms of CDI incidence and strain types reflecting different stages of epidemic spread. However, comparison of CDI epidemiology, particularly between countries, is challenging due to wide-ranging approaches to sampling and testing. Diagnostic strategies for C. difficile are complicated both by the wide range of bacterial targets and tests available and the need to differentiate between toxin-producing and non-toxigenic strains. Multistep diagnostic algorithms have been recommended to improve sensitivity and specificity. In this Review, we describe the latest advances in the understanding of C. difficile epidemiology, transmission and diagnosis, and discuss the effect of these developments on the clinical management of CDI.

Novel Positional Devices for the Treatment of Positional Obstructive Sleep Apnea, and How This Relates to Sleep Surgery.

PubMed

Ravesloot, Madeline J L; Benoist, Linda; van Maanen, Peter; de Vries, Nico

2017-01-01

If untreated, obstructive sleep apnea (OSA) develops as a gradual progressive disease. In the early stage of the disease most patients with OSA are positional. The archetypical patient might progress from simple positional snoring via positional early-stage mild disease to less positional moderate and finally nonpositional severe OSA. At first, the apnea-hypopnea index (AHI) is high only in the supine position, and later is high in all sleeping positions. The phenomenon is reversible. After partial effective treatment, patients with severe OSA can reverse to less severe positional OSA or, in other words, the AHI drops more in the lateral position than in supine position. This has been shown for palatal surgery, multilevel surgery, bimaxillary osteotomies, and bariatric surgery. The absence or presence of positional dependency has a great influence on sleep surgery. First, the results of sleep surgery might be worse in positional patients. Second, the addition of positional therapy to sleep surgery might improve the overall outcome and, as such, enhance the indication of sleep surgery as an alternative to continuous positive airway pressure and mandibular advancement device treatment. © 2017 S. Karger AG, Basel.

26 CFR 1.612-3 - Depletion; treatment of bonus and advanced royalty.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Depletion; treatment of bonus and advanced... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.612-3 Depletion; treatment... the payee as a cost depletion deduction in respect of the bonus an amount equal to that proportion of...

26 CFR 1.612-3 - Depletion; treatment of bonus and advanced royalty.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Depletion; treatment of bonus and advanced royalty. 1.612-3 Section 1.612-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.612-3 Depletion; treatment...

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

PubMed

Tew, Garry A; Carpenter, Roger; Seed, Michael; Anderson, Simon; Langmead, Louise; Fairhurst, Caroline; Bottoms, Lindsay

2017-01-01

Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire. This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

Biographical disruption, adjustment and reconstruction of everyday occupations and work participation after mild traumatic brain injury. A focus group study.

PubMed

Sveen, Unni; Søberg, Helene Lundgaard; Østensjø, Sigrid

2016-11-01

To explore traumatic brain injury (TBI) as a biographical disruption and to study the reconstruction of everyday occupations and work participation among individuals with mild TBI. Seven focus groups were conducted with 12 women and 8 men (22-60 years) who had sustained mild TBI and participated in a return-to-work program. Interviews were analyzed using qualitative content analysis. Four interrelated themes emerged: disruption of occupational capacity and balance; changes in self-perceptions; experience of time; and occupational adjustment and reconstruction. The meaning of the impairments lies in their impact on the individual's everyday occupations. The abandonment of meaningful daily occupations and the feeling of not recognizing oneself were experienced as threats to the sense of self. Successful integration of the past, present and future was paramount to continuing life activities. The unpredictability of the future seemed to permeate the entire process of adjustment and reconstruction of daily life. Our findings show that the concept of time is important in understanding and supporting the reconstruction of daily life after TBI. The fundamental work of rehabilitation is to ameliorate the disruptions caused by the injury, restoring a sense of personal narrative and supporting the ability to move forward with life. Implications for Rehabilitation Individuals with a protracted recovery after a mild traumatic brain injury must reconstruct a new way of being and acting in the world to achieve biographical continuity. The perceived anxiety regarding changes in self and occupational identity, as well as loss of control over the future, can be attenuated through informational sessions during the hospital stay and at follow-up visits. The significant personal costs of returning to full-time employment too early indicate the need for early and ongoing vocational support in achieving a successful return to work.

A clinical ladder for occupational health nurses.

PubMed

Lang, Yolanda C

2010-06-01

Occupational health nurses must have a growing, expanding knowledge base to remain current in practice. The American Board for Occupational Health Nurses, Inc. encourages advancement with the availability of certification examinations. Health care centers support clinical advancement programs for bedside nurses. Nurses who continue their education either through a degree program or via continuing education or certification advance up the clinical ladder, receiving a higher salary, recognition from their peers, and perhaps even financial assistance to continue climbing, yet occupational health nurses do not have their own clinical advancement ladder. This article examines the steps necessary to develop a clinical ladder and presents a clinical ladder specific to occupational health nursing developed by the author. Copyright 2010, SLACK Incorporated.

A Phase II Study of Docetaxel and Epirubicin in Advanced Adult Soft Tissue Sarcomas (STS).

PubMed

Kalofonos, Haralabos P; Kourousis, Charalabos; Karamouzis, Michalis V; Iconomou, Gregoris; Tsiata, Ekaterini; Tzorzidis, Fotis; Megas, Panagiotis; Lambiris, Elias; Georgoulias, Vasilios

2004-01-01

The aim of this study was to determine the efficacy and safety of docetaxel plus epirubicin combination as first-line chemotherapy in patients with locally advanced and/or metastatic adult STS. Eighteen patients were treated with epirubicin 30 mg/m(2) on days 1 to 3 and docetaxel 100 mg/m(2) on day 1 every 3 weeks. Fifteen out of 18 patients (83.4%) were assessable for response. No complete response was recorded. Three (20%) patients achieved PR, 3 had SD and 9 PD. The overall median survival was 14 months (range, 3-48 months) and the median time to disease progression was 4 months (range, 2-45 months). Grade >/= 3 neutropenia occurred in 88% and neutropenic fever in 27.8% of patients. Other toxicities were mild. No treatment related deaths occurred. Docetaxel plus epirubicin combination achieved low response rate with severe myelotoxicity in patients with advanced STS.

Magnetic and thermal behavior of a family of compositionally related zero-dimensional fluorides

NASA Astrophysics Data System (ADS)

Felder, Justin B.; Smith, Mark D.; Sefat, Athena; zur Loye, Hans-Conrad

2018-07-01

The mild hydrothermal crystal growth technique has been leveraged to synthesize four new zero-dimensional transition metal fluorides. Their structures were determined by single crystal X-ray diffraction and confirmed by powder X-ray diffraction. The thermal, optical, and magnetic properties were investigated and the presence of thermal polymorphism and antiferromagnetism were observed. In addition, the potential application of these materials as precursors for advanced functional materials was explored.

[Accidental hypothermia].

PubMed

Soteras Martínez, Iñigo; Subirats Bayego, Enric; Reisten, Oliver

2011-07-09

Accidental hypothermia is an infrequent and under-diagnosed pathology, which causes fatalities every year. Its management requires thermometers to measure core temperature. An esophageal probe may be used in a hospital situation, although in moderate hypothermia victims epitympanic measurement is sufficient. Initial management involves advance life support and body rewarming. Vigorous movements can trigger arrhythmia which does not use to respond to medication or defibrillation until the body reaches 30°C. External, passive rewarming is the method of choice for mild hypothermia and a supplementary method for moderate or severe hypothermia. Active external rewarming is indicated for moderate or severe hypothermia or mild hypothermia that has not responded to passive rewarming. Active internal rewarming is indicated for hemodynamically stable patients suffering moderate or severe hypothermia. Patients with severe hypothermia, cardiac arrest or with a potassium level below 12 mmol/l may require cardiopulmonary bypass treatment. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Perspectives on Creating Clinically Relevant Blast Models for Mild Traumatic Brain Injury and Post Traumatic Stress Disorder Symptoms

PubMed Central

Brenner, Lisa A.; Bahraini, Nazanin; Hernández, Theresa D.

2012-01-01

Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic), behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI) and/or post traumatic stress disorder (PTSD). Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast) traumatic brain injury can be used to facilitate the development of clinically relevant blast models. PMID:22408635

Dysphagia in Parkinson's disease.

PubMed

Hisashi, Shinobu; Fukumitsu, Ryoko; Ishida, Mitsuyo; Nodera, Atsuko; Otani, Takahiro; Maruoka, Takahiro; Nakamura, Kazumi; Izumi, Yuishin; Kaji, Ryuji; Nishida, Yoshihiko

2016-08-31

Although dysphagia is an important symptom associated with prognosis in patients with Parkinson's disease (PD), dysphagia tends to be overlooked until swallowing difficulties reach an advanced phase. We assessed dysphagia with videofluoroscopic examination of swallowing in 31 patients with mainly mild or moderate PD. Swallowing problems were observed in the pharyngeal phase in 28 patients, oral phase in 19 patients, esophageal phase in 15 patients, and oral preparatory phase in 1 patient. Therefore, dysphagia in the pharyngeal phase was observed in almost all patients with mild or moderate PD. In contrast, no dysfunction was detected in most patients when screening was conducted via questionnaire or other methods. Assessment of clinical parameters in the present study suggests that latent swallowing dysfunction may be present even in the early disease stage in PD. A future prospective study to follow swallowing functions in a pre-symptomatic phase in PD would be fruitful to find whether swallowing dysfunction is one of the prodromal symptoms.

Apathy associated with neurocognitive disorders: Recent progress and future directions.

PubMed

Lanctôt, Krista L; Agüera-Ortiz, Luis; Brodaty, Henry; Francis, Paul T; Geda, Yonas E; Ismail, Zahinoor; Marshall, Gad A; Mortby, Moyra E; Onyike, Chiadi U; Padala, Prasad R; Politis, Antonios M; Rosenberg, Paul B; Siegel, Emma; Sultzer, David L; Abraham, Eleenor H

2017-01-01

Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs. Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches. Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Problems in Classifying Mild Cognitive Impairment (MCI): One or Multiple Syndromes?

PubMed Central

Díaz-Mardomingo, María del Carmen; García-Herranz, Sara; Rodríguez-Fernández, Raquel; Venero, César; Peraita, Herminia

2017-01-01

As the conceptual, methodological, and technological advances applied to dementias have evolved the construct of mild cognitive impairment (MCI), one problem encountered has been its classification into subtypes. Here, we aim to revise the concept of MCI and its subtypes, addressing the problems of classification not only from the psychometric point of view or by using alternative methods, such as latent class analysis, but also considering the absence of normative data. In addition to the well-known influence of certain factors on cognitive function, such as educational level and cultural traits, recent studies highlight the relevance of other factors that may significantly affect the genesis and evolution of MCI: subjective memory complaints, loneliness, social isolation, etc. The present work will contemplate the most relevant attempts to clarify the issue of MCI categorization and classification, combining our own data with that from recent studies which suggest the role of relevant psychosocial factors in MCI. PMID:28862676

Long-term follow-up of the AdVance®/AdVanceXP® sling. What are the surgeons' impressions? What are the patients'?

PubMed

Romero Hoyuela, A; Reina Alcaina, L; Izquierdo Morejon, E; Rosino Sanchez, A; Carrillo George, C; Rivero Guerra, A; Barcelo Bayonas, I; Pardo Martinez, A; Muñoz Guillermo, V; Pietricica, B; Fernandez Aparicio, T; Hita Villaplana, G; Miñana Lopez, B

2018-04-01

To analyse the safety, efficacy and quality of life of patients with male stress urinary incontinence after radical prostatectomy treated with the AdVance ® and AdvanceXP ® slings. The study included 92 patients with stress urinary incontinence after radical prostatectomy treated with the AdVance ® and AdVanceXP ® sling between May 2008 and December 2015. A perineal repositioning test was performed in all cases with sphincter coaptation of≥1.5cm. Mild stress urinary incontinence was defined as the use of 1-2 absorbers/24h; moderate was defined as 3-5 absorbers/24h; and severe was defined as more than 5 absorbers/24h. Healing was defined as the total absence of using pads; improvement was defined as a reduction>50% in the number of pads; and failure was defined as a reduction<50, no improvement or worsened incontinence. Check-ups were conducted at 3, 12 and 36 months after the surgery. We employed the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) for the quality of life index. The complications are listed according to the Clavien-Dindo classification. The degree of preoperative incontinence was mild in 23.9%, moderate in 67.4% and severe in 8.7% of the patients. The mean use of preoperative pads was 3.1 (range 1-6, 95% CI). The mean preoperative ICIQ-SF score was 16.5 (15-20). Sphincter coaptation≥1.5cm using the perineal repositioning test was present in 87 patients (94.6%). The mean follow-up from insertion of the sling was 42.1 months. Some 89.1% of the patients were healed at 3 months, 70.7% were healed at 12 months, and 70.4% were healed at 36 months. The ICIQ-SF score at 3, 12 and 36 months showed significant improvement (P<.001) compared with the preoperative score. The Advance ® and AdvanceXP ® system are effective over time in terms of urinary continence and patient satisfaction. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Great Expectations in the Joint Advanced Manufacturing Region

DTIC Science & Technology

2016-12-01

would be continuous experimentation and risk reduction prototyping. The entire manufacturing life cycle— design , testing, product development...on the back of a napkin, they decided to call their effort the Joint Advanced Manufacturing Region (JAMR) and manage it as an Integrated Product ... designed to support the continuous experimentation of advanced manufacturing tactics, tech- niques and procedures under actual operational or combat

Handbook of Institutional Advancement. A Practical Guide to College and University Relations, Fund Raising, Alumni Relations, Government Relations, Publications, and Executive Management for Continued Advancement.

ERIC Educational Resources Information Center

Rowland, A. Westley, Ed.

The guide's purpose is to provide administrators with essential information that will maintain public confidence in higher education and ensure continued financial support. Six major aspects of institutional advancement are considered: (1) institutional relation (programs to improve communication and understanding among students, administrators,…

The Antivascular Actions of Mild Intensity Ultrasound on a Murine Neoplasm

NASA Astrophysics Data System (ADS)

Wood, Andrew K. W.; Bunte, Ralph M.; Ansaloni, Sara; Lee, William M.-F.; Sehgal, Chandra M.

2006-05-01

This study was aimed at determining whether mild intensity ultrasound affected the fragile and leaky angiogenic blood vessels in a tumor. In 27 mice (C3HV/HeN strain) a subcutaneous melanoma (K173522) was insonated with continuous physiotherapy ultrasound (1 MHz; spatial-average-temporal-average = 2.3 W cm-2). Analyses of contrast enhanced power Doppler observations showed that insonation significantly increased the avascular area in the neoplasm. A linear regression analysis demonstrated that each min of insonation lead to a 25% reduction in tumor vascularity. The predominant acute effect of insonation was an apparently irreparable dilation of the tumor capillaries; liquefactive necrosis of neoplastic cells, related to a secondary ischemia, was a delayed effect.

A selenium species in cerebrospinal fluid predicts conversion to Alzheimer's dementia in persons with mild cognitive impairment.

PubMed

Vinceti, Marco; Chiari, Annalisa; Eichmüller, Marcel; Rothman, Kenneth J; Filippini, Tommaso; Malagoli, Carlotta; Weuve, Jennifer; Tondelli, Manuela; Zamboni, Giovanna; Nichelli, Paolo F; Michalke, Bernhard

2017-12-19

Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form. We determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin. We then investigated the relation of these concentrations to subsequent conversion from mild cognitive impairment to Alzheimer's dementia. Twenty-one out of the 56 subjects developed Alzheimer's dementia during a median follow-up of 42 months; four subjects developed frontotemporal dementia and two patients Lewy body dementia. In a Cox proportional hazards model adjusting for age, sex, duration of sample storage, and education, an inorganic selenium form, selenate, showed a strong association with Alzheimer's dementia risk, with an adjusted hazard ratio of 3.1 (95% confidence interval 1.0-9.5) in subjects having a cerebrospinal fluid content above the median level, compared with those with lower concentration. The hazard ratio of Alzheimer's dementia showed little departure from unity for all other inorganic and organic selenium species. These associations were similar in analyses that measured exposure on a continuous scale, and also after excluding individuals who converted to Alzheimer's dementia at the beginning of the follow-up. These results indicate that higher amounts of a potentially toxic inorganic selenium form in cerebrospinal fluid may predict conversion from mild cognitive impairment to Alzheimer's dementia.

29 CFR 1990.141 - Advance notice of proposed rulemaking.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 1990.141 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.141 Advance notice of proposed rulemaking...

29 CFR 1990.141 - Advance notice of proposed rulemaking.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 1990.141 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.141 Advance notice of proposed rulemaking...

Continuous flow room temperature reductive aqueous homo-coupling of aryl halides using supported Pd catalysts

PubMed Central

Feiz, Afsaneh; Bazgir, Ayoob; Balu, Alina M.; Luque, Rafael

2016-01-01

A convenient and environmentally friendly protocol for the preparation of biaryls at room temperature under continuous flow conditions is reported. A simple reductive homo-coupling Ullmann-type reaction was performed in an H-Cube mini using commercially available supported Pd catalysts under mild reaction conditions, with quantitative conversion to target products. Commercial Pd catalysts were found to be highly stable under the investigated reaction conditions, with a minimum Pd leaching into solution after several reaction runs (ca. 20 h on stream). PMID:27600989

Tolerability of ketorolac administered via continuous subcutaneous infusion for cancer pain: a preliminary report.

PubMed

De Conno, F; Zecca, E; Martini, C; Ripamonti, C; Caraceni, A; Saita, L

1994-02-01

We evaluated the local and systemic tolerability of ketorolac administered through continuous subcutaneous infusion in ten cancer patients. The patients were monitored daily for the severity and duration of pain, and the development of other symptoms. The duration of injection site varied from 1 to more than 7 days. No patients complained of local discomfort or pain. Mild local bleeding at the site of drug injection was observed in seven cases. No increase in the intensity of symptoms was observed during the infusion of ketorolac.

Investigation of test methods, material properties, and processes for solar cell encapsulants

NASA Technical Reports Server (NTRS)

Willis, P. B.

1983-01-01

A study of potentially useful low cost encapsulation materials for the Flat-Plate Solar Array project is discussed. The goal is to identify, evaluate, test and recommend encapsulant materials and processes for the production of cost-effective, long life solar cell modules. Technical investigations included studies of aging and degradation of candidate encapsulation materials, continued identification of primers for durable bonding of module interfaces, continued evaluation of soil resistant treatments for the sunlit surface of the module and testing of corrosion protective coatings for use low cost mild steel substrates.

Fully integrated biochip platforms for advanced healthcare.

PubMed

Carrara, Sandro; Ghoreishizadeh, Sara; Olivo, Jacopo; Taurino, Irene; Baj-Rossi, Camilla; Cavallini, Andrea; de Beeck, Maaike Op; Dehollain, Catherine; Burleson, Wayne; Moussy, Francis Gabriel; Guiseppi-Elie, Anthony; De Micheli, Giovanni

2012-01-01

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications.

Fully Integrated Biochip Platforms for Advanced Healthcare

PubMed Central

Carrara, Sandro; Ghoreishizadeh, Sara; Olivo, Jacopo; Taurino, Irene; Baj-Rossi, Camilla; Cavallini, Andrea; de Beeck, Maaike Op; Dehollain, Catherine; Burleson, Wayne; Moussy, Francis Gabriel; Guiseppi-Elie, Anthony; De Micheli, Giovanni

2012-01-01

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications. PMID:23112644

Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

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

Xiang, Li; Zhang, Jian-wen; Lin, Sheng

2015-08-01

Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planningmore » target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.« less

Nurses' Internet self-efficacy and attitudes toward web-based continuing learning.

PubMed

Liang, Jyh-Chong; Wu, Szu-Hsien; Tsai, Chin-Chung

2011-11-01

There are increasing opportunities for nurses to engage in continuing learning via the Internet; hence, it is important to explore nurses' attitudes toward web-based continuing learning. This paper explores 267 Taiwanese clinical nurses' attitudes toward web-based continuing learning. In addition, the role of the nurses' Internet self-efficacy in their attitudes is investigated. This study utilizes two questionnaires to respectively survey the nurses' Internet self-efficacy and their attitudes toward web-based continuing learning. In particular, the Internet Self-efficacy Survey includes two scales: 'Basic self-efficacy' (the perceived confidence of using basic Internet functions, such as the confidence in using a web browser or searching for online information) and 'Advanced self-efficacy' (the perceived confidence of using advanced Internet functions, such as the confidence in online discussion or making online payments). Exploratory factor analyses indicated adequate reliability and validity of the two questionnaires. The regression analyses revealed that both nurses' basic and advanced Internet self-efficacy can positively explain the perceived usefulness, ease of use and friendly feeling when using web-based continuing learning environments, whereas nurses' advanced Internet self-efficacy was the only predictor to explain how they intend to use web-based continuing learning environments more. Copyright © 2010 Elsevier Ltd. All rights reserved.

Development of the Write Process for Pipeline-Ready Heavy Oil

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

Lee Brecher; Charles Mones; Frank Guffey

Work completed under this program advances the goal of demonstrating Western Research Institute's (WRI's) WRITE{trademark} process for upgrading heavy oil at field scale. MEG Energy Corporation (MEG) located in Calgary, Alberta, Canada supported efforts at WRI to develop the WRITE{trademark} process as an oil sands, field-upgrading technology through this Task 51 Jointly Sponsored Research project. The project consisted of 6 tasks: (1) optimization of the distillate recovery unit (DRU), (2) demonstration and design of a continuous coker, (3) conceptual design and cost estimate for a commercial facility, (4) design of a WRITE{trademark} pilot plant, (5) hydrotreating studies, and (6) establishmore » a petroleum analysis laboratory. WRITE{trademark} is a heavy oil and bitumen upgrading process that produces residuum-free, pipeline ready oil from heavy material with undiluted density and viscosity that exceed prevailing pipeline specifications. WRITE{trademark} uses two processing stages to achieve low and high temperature conversion of heavy oil or bitumen. The first stage DRU operates at mild thermal cracking conditions, yielding a light overhead product and a heavy residuum or bottoms material. These bottoms flow to the second stage continuous coker that operates at severe pyrolysis conditions, yielding light pyrolyzate and coke. The combined pyrolyzate and mildly cracked overhead streams form WRITE{trademark}'s synthetic crude oil (SCO) production. The main objectives of this project were to (1) complete testing and analysis at bench scale with the DRU and continuous coker reactors and provide results to MEG for process evaluation and scale-up determinations and (2) complete a technical and economic assessment of WRITE{trademark} technology to determine its viability. The DRU test program was completed and a processing envelope developed. These results were used for process assessment and for scaleup. Tests in the continuous coker were intended to determine the throughput capability of the coker so a scaled design could be developed that maximized feed rate for a given size of reactor. These tests were only partially successful because of equipment problems. A redesigned coker, which addressed the problems, has been build but not operated. A preliminary economic analysis conducted by MEG and an their engineering consultant concluded that the WRITE{trademark} process is a technically feasible method for upgrading bitumen and that it produces SCO that meets pipeline specifications for density. When compared to delayed coking, the industry benchmark for thermal upgrading of bitumen, WRITE{trademark} produced more SCO, less coke, less CO{sub 2} per barrel of bitumen fed, and had lower capital and operating costs. On the other hand, WRITE{trademark}'s lower processing severity yielded crude with higher density and a different product distribution for naphtha, light gas oil and vacuum oil that, taken together, might reduce the value of the SCO. These issues plus the completion of more detailed process evaluation and economics need to be resolved before WRITE{trademark} is deployed as a field-scale pilot.« less

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

PubMed Central

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Elucidating the Role of Compression Waves and Impact Duration for Generating mild Traumatic Brain Injury in Rats

PubMed Central

Lucke-Wold, Brandon P.; Phillips, Michael; Turner, Ryan C.; Logsdon, Aric F.; Smith, Kelly E.; Huber, Jason D.; Rosen, Charles L.; Regele, Jonathan D.

2016-01-01

3 million concussions occur each year in the United States. The mechanisms linking acute injury to chronic deficits are poorly understood. Mild traumatic brain injury has been described clinically in terms of acute functional deficits, but the underlying histopathologic changes that occur are relatively unknown due to limited high-function imaging modalities. In order to improve our understanding of acute injury mechanisms, appropriately designed preclinical models must be utilized. The clinical relevance of compression wave injury models revolves around the ability to produce consistent histopathologic deficits. Repetitive mild traumatic brain injuries activate similar neuroinflammatory cascades, cell death markers, and increases in amyloid precursor protein in both humans and rodents. Humans however infrequently succumb to mild traumatic brain injuries and therefore the intensity and magnitude of impacts must be inferred. Understanding compression wave properties and mechanical loading could help link the histopathologic deficits seen in rodents to what might be happening in human brains following repetitive concussions. Advances in mathematical and computer modeling can help characterize the wave properties generated by the compression wave model. While this concept of linking duration and intensity of impact to subsequent histopathologic deficits makes sense, numerical modeling of compression waves has not been performed in this context. In this collaborative interdisciplinary work, numerical simulations were performed to study the creation of compression waves in our experimental model. This work was conducted in conjunction with a repetitive compression wave injury paradigm in rats in order to better understand how the wave generation correlates with validated histopathologic deficits. PMID:27880054

Advanced Airframe Structural Materials: A Primer and Cost Estimating Methodology

DTIC Science & Technology

1991-01-01

laying machines for larger, mildly con- toured parts such as wing and stabilizer skins. For such parts, automated tape laying machines can operate many...heat guns (90-130°F). However, thermoplastics require as much as 650°F for forming. Automated tape laying machines for these materials use warm...cycles to properly seat the plies onto the tool. This time-consuming process can sometimes be eliminated or reduced by the use of automated tape laying procedures

Developing a Novel Eye Tracking Paradigm to Assess Mild Traumatic Brain Injury: A Feasibility Study of the Bethesda Eye and Attention Measure (BEAM)

DTIC Science & Technology

2012-10-01

system, which includes the retina, lateral geniculate nucleus, striate cortex, superior colliculus, parietal cortex, frontal eye fields... body penetrating the brain, forces generated from events such as a blast or explosion, or other forces yet to be defined. Consistent with the...and loss of productivity (47-57%; Tanielian & Jaycox, 2008). With advances in modern medicine and neuroimaging, more Service Members and civilians

Cone opsins, colour blindness and cone dystrophy: Genotype-phenotype correlations.

PubMed

Gardner, J C; Michaelides, M; Hardcastle, A J

2016-05-25

X-linked cone photoreceptor disorders caused by mutations in the OPN1LW (L) and OPN1MW (M) cone opsin genes on chromosome Xq28 include a range of conditions from mild stable red-green colour vision deficiencies to severe cone dystrophies causing progressive loss of vision and blindness. Advances in molecular genotyping and functional analyses of causative variants, combined with deep retinal phenotyping, are unravelling genetic mechanisms underlying the variability of cone opsin disorders.

Improving quality and patient satisfaction in a pediatric resident continuity clinic through advanced access scheduling.

PubMed

Tuli, Sanjeev Y; Thompson, Lindsay A; Ryan, Kathleen A; Srinivas, Ganga L; Fillipps, Donald J; Young, Christopher M; Tuli, Sonal S

2010-06-01

To evaluate the impact of advanced access scheduling in a pediatric residency clinic on resident and patient satisfaction, medical education, practice quality, and efficiency. Residents were assigned to either the advanced access template (10 appointments available to patients and 2 physician overbooks) or the prior template (5 available and 8 overbooks). Outcomes included resident and patient satisfaction, appointment availability, and continuity of care and clinic costs. Patient satisfaction improved in 7 areas (P < .001). Residents in either template did not report an impact on medical education experiences. Significant increases were realized with appointment availability and the number of patients seen. Continuity also increased as the overflow/acute visits decreased (P < .001). Overall costs per visit decreased 22%. Because of the significant improvements in access, continuity, and efficiency, all residents were switched to the advanced access template after completion of the study. Improvement in access to the primary physician has a significant impact on patient satisfaction with health care delivery. This model optimizes the limited time that residents have in continuity clinic, and it has implications for health care delivery quality improvement.

A novel cosmetic antifungal/anti-inflammatory topical gel for the treatment of mild to moderate seborrheic dermatitis of the face: an open-label trial utilizing clinical evaluation and erythema-directed digital photography.

PubMed

Dall' Oglio, Federica; Tedeschi, Aurora; Fusto, Carmelinda M; Lacarrubba, Francesco; Dinotta, Franco; Micali, Giuseppe

2017-10-01

Topical cosmetic agents may play a role in the management of facial seborrheic dermatitis by reducing inflammation and scale production. Advanced digital photography, equipped with technology able to provide a detailed evaluation of red skin components corresponding to vascular flare (erythema-directed digital photography), is a useful tool for evaluation of erythema in patients affected by inflammatory dermatoses. The aim of this study was to assess the efficacy and safety of a new cosmetic topical gel containing piroctone olamine, lactoferrin, glycero-phospho-inositol, and Aloe vera for the treatment of facial seborrheic dermatitis by clinical and advanced digital photography evaluation. An open-label, prospective, clinical trial was conducted on 25 patients with mild to moderate facial seborrheic dermatitis. Subjects were instructed to apply the gel twice daily for 45 days. The clinical efficacy was evaluated by measuring at baseline, at day 15 and 45 the degree of desquamation (by clinical examination) and erythema (by digital photography technology via VISIA-CR™ system equipped with RBX™), using a 5-point severity scale, and pruritus (by subject-completed Visual Analogue Scale; scale from 0 to 100 mm). Finally, at baseline and at the end of the study, IGA (Investigator Global Assessment) was performed using a 5-point severity scale (from 0 = worsening to 4 = excellent response). At the end of treatment, a significant reduction (P<0.001) of all considered parameters was observed. Moreover, an excellent response (>80% improvement) was recorded in 47.9% of patients, with no case of worsening. No signs of local intolerance were documented. The tested cosmetic topical gel was effective in treating mild to moderate seborrheic dermatitis of the face. Erythema-directed digital photography may represent a noteworthy tool for the therapeutic monitoring of facial seborrheic dermatitis and an important adjunct aid in the dermatologic clinical practice.

Temperature Management After Cardiac Arrest: An Advisory Statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation.

PubMed

Donnino, Michael W; Andersen, Lars W; Berg, Katherine M; Reynolds, Joshua C; Nolan, Jerry P; Morley, Peter T; Lang, Eddy; Cocchi, Michael N; Xanthos, Theodoros; Callaway, Clifton W; Soar, Jasmeet

2016-01-01

For more than a decade, mild induced hypothermia (32 °C-34 °C) has been standard of care for patients remaining comatose after resuscitation from out-of-hospital cardiac arrest with an initial shockable rhythm, and this has been extrapolated to survivors of cardiac arrest with initially nonshockable rhythms and to patients with in-hospital cardiac arrest. Two randomized trials published in 2002 reported a survival and neurological benefit with mild induced hypothermia. One recent randomized trial reported similar outcomes in patients treated with targeted temperature management at either 33 °C or 36 °C. In response to these new data, the International Liaison Committee on Resuscitation Advanced Life Support Task Force performed a systematic review to evaluate 3 key questions: (1) Should mild induced hypothermia (or some form of targeted temperature management) be used in comatose post-cardiac arrest patients? (2) If used, what is the ideal timing of the intervention? (3) If used, what is the ideal duration of the intervention? The task force used Grading of Recommendations Assessment, Development and Evaluation methodology to assess and summarize the evidence and to provide a consensus on science statement and treatment recommendations. The task force recommends targeted temperature management for adults with out-of-hospital cardiac arrest with an initial shockable rhythm at a constant temperature between 32 °C and 36 °C for at least 24 hours. Similar suggestions are made for out-of-hospital cardiac arrest with a nonshockable rhythm and in-hospital cardiac arrest. The task force recommends against prehospital cooling with rapid infusion of large volumes of cold intravenous fluid. Additional and specific recommendations are provided in the document. Copyright © 2015. Published by Elsevier Ireland Ltd.

Temperature Management After Cardiac Arrest: An Advisory Statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation.

PubMed

Donnino, Michael W; Andersen, Lars W; Berg, Katherine M; Reynolds, Joshua C; Nolan, Jerry P; Morley, Peter T; Lang, Eddy; Cocchi, Michael N; Xanthos, Theodoros; Callaway, Clifton W; Soar, Jasmeet

2015-12-22

For more than a decade, mild induced hypothermia (32 °C-34 °C) has been standard of care for patients remaining comatose after resuscitation from out-of-hospital cardiac arrest with an initial shockable rhythm, and this has been extrapolated to survivors of cardiac arrest with initially nonshockable rhythms and to patients with in-hospital cardiac arrest. Two randomized trials published in 2002 reported a survival and neurological benefit with mild induced hypothermia. One recent randomized trial reported similar outcomes in patients treated with targeted temperature management at either 33 °C or 36 °C. In response to these new data, the International Liaison Committee on Resuscitation Advanced Life Support Task Force performed a systematic review to evaluate 3 key questions: (1) Should mild induced hypothermia (or some form of targeted temperature management) be used in comatose post-cardiac arrest patients? (2) If used, what is the ideal timing of the intervention? (3) If used, what is the ideal duration of the intervention? The task force used Grading of Recommendations Assessment, Development and Evaluation methodology to assess and summarize the evidence and to provide a consensus on science statement and treatment recommendations. The task force recommends targeted temperature management for adults with out-of-hospital cardiac arrest with an initial shockable rhythm at a constant temperature between 32 °C and 36 °C for at least 24 hours. Similar suggestions are made for out-of-hospital cardiac arrest with a nonshockable rhythm and in-hospital cardiac arrest. The task force recommends against prehospital cooling with rapid infusion of large volumes of cold intravenous fluid. Additional and specific recommendations are provided in the document. © 2015 by the American Heart Association, Inc., and the European Resuscitation Council.

Utilization of free dental health care services provided to the perinatally infected human immunodeficiency virus children in Bangalore: longitudinal study.

PubMed

Parvathy, Beena Javaregowda

2014-01-01

Use of Highly active anti-retroviral therapy have increased the life expectancy of human immunodeficiency virus (HIV) infected patients and hence it is imperative that all efforts have to be made by Pediatric dentists to provide a better oral health for these children. The aim of this study was to evaluate the rate of utilization of free dental treatment provided to these perinatally infected HIV positive children who were previously screened as a part of oral health survey. Purposive sampling was used. Perinatally infected HIV children screened for oral health status. Patients not screened during the oral health survey. Attendance records of 319 perinatally HIV infected children consisting of 178 males and 141 females attending a specialized pediatric outpatient clinic at Indira Gandhi Institute of Child Health were examined to compare treatment compliance rates. The number of patients in the severe category who completed treatment was significantly less compared with mild and advanced categories (P < 0.001). The difference in the proportion of patients who completed treatment between mild and advanced group was not statistically significant (P > 0.05). The results show that children with HIV have significantly lower compliance. Even though all dental treatment provided to them was free of the cost it still had no impetus to encourage them to go through with the treatment.

Integration of advanced oxidation processes at mild conditions in wet scrubbers for odourous sulphur compounds treatment.

PubMed

Vega, Esther; Martin, Maria J; Gonzalez-Olmos, Rafael

2014-08-01

The effectiveness of different advanced oxidation processes on the treatment of a multicomponent aqueous solution containing ethyl mercaptan, dimethyl sulphide and dimethyl disulphide (0.5 mg L(-1) of each sulphur compound) was investigated with the objective to assess which one is the most suitable treatment to be coupled in wet scrubbers used in odour treatment facilities. UV/H2O2, Fenton, photo-Fenton and ozone treatments were tested at mild conditions and the oxidation efficiency obtained was compared. The oxidation tests were carried out in magnetically stirred cylindrical quartz reactors using the same molar concentration of oxidants (hydrogen peroxide or ozone). The results show that ozone and photo-Fenton are the most efficient treatments, achieving up to 95% of sulphur compounds oxidation and a mineralisation degree around 70% in 10 min. Furthermore, the total costs of the treatments taking into account the capital and operational costs were also estimated for a comparative purpose. The economic analysis revealed that the Fenton treatment is the most economical option to be integrated in a wet scrubber to remove volatile organic sulphur compounds, as long as there are no space constraints to install the required reactor volume. In the case of reactor volume limitation or retrofitting complexities, the ozone and photo-Fenton treatments should be considered as viable alternatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pulmonary hypertension in chronic obstructive pulmonary disease and interstitial lung diseases.

PubMed

Weitzenblum, Emmanuel; Chaouat, Ari; Canuet, Matthieu; Kessler, Romain

2009-08-01

Pulmonary hypertension (PH) is a common complication of chronic respiratory diseases and particularly of chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD). Owing to its frequency COPD is by far the most common cause of PH. It is generally a mild to moderate PH, pulmonary artery mean pressure (PAP) usually ranging between 20 and 25 mm Hg, but PH may worsen during exercise, sleep, and particularly during exacerbations of the disease. These acute increases in PAP may lead to the development of right heart failure. A small proportion of COPD patients may present "disproportionate" PH defined by a resting PAP >35 to 40 mm Hg. The prognosis is particularly poor in these patients. PH is relatively frequent in advanced ILD and particularly in idiopathic pulmonary fibrosis. As in COPD the diagnosis is suggested by Doppler echocardiography, but the confirmation still requires right heart catheterization. As in COPD, functional (alveolar hypoxia) and morphological factors (vascular remodeling, destruction of the pulmonary parenchyma) explain the elevation of pulmonary vascular resistance that leads to PH. Also as in COPD PH is most often mild to moderate. In ILD the presence of PH predicts a poor prognosis. The treatment of PH relies on long-term oxygen therapy. "New" vasodilator drugs have rarely been used in COPD and ILD patients exhibiting severe PH. In advanced ILD the presence of PH is a supplemental argument for considering lung transplantation.

Anticipatory grief in new family caregivers of persons with mild cognitive impairment and dementia.

PubMed

Garand, Linda; Lingler, Jennifer H; Deardorf, Kaitlyn E; DeKosky, Steven T; Schulz, Richard; Reynolds, Charles F; Dew, Mary Amanda

2012-01-01

Anticipatory grief is the process of experiencing normal phases of bereavement in advance of the loss of a significant person. To date, anticipatory grief has been examined in family caregivers to individuals who have had Alzheimer disease (AD) an average of 3 to 6 years. Whether such grief is manifested early in the disease trajectory (at diagnosis) is unknown. Using a cross-sectional design, we examined differences in the nature and extent of anticipatory grief between family caregivers of persons with a new diagnosis of mild cognitive impairment (MCI, n=43) or AD (n=30). We also determined whether anticipatory grief levels were associated with caregiver demographics, caregiving burden, depressive symptoms, and marital quality. The mean anticipatory grief levels were high in the total sample, with AD caregivers endorsing significantly more anticipatory grief than MCI caregivers. In general, AD caregivers endorsed difficulty in functioning, whereas MCI caregivers focused on themes of "missing the person" they once knew. Being a female caregiver, reporting higher levels of objective caregiving burden, and higher depression levels each had independent, statistically significant relationships with anticipatory grief. Given these findings, family caregivers of individuals with mild cognitive deficits or a new AD diagnosis may benefit from interventions specifically addressing anticipatory grief.

Con: Higher serum bicarbonate in dialysis patients is protective.

PubMed

Chauveau, Philippe; Rigothier, Claire; Combe, Christian

2016-08-01

Metabolic acidosis is often observed in advanced chronic kidney disease, with deleterious consequences on the nutritional status, bone and mineral status, inflammation and mortality. Through clearance of the daily acid load and a net gain in alkaline buffers, dialysis therapy is aimed at correcting metabolic acidosis. A normal bicarbonate serum concentration is the recommended target in dialysis patients. However, several studies have shown that a mild degree of metabolic acidosis in patients treated with dialysis is associated with better nutritional status, higher protein intake and improved survival. Conversely, a high bicarbonate serum concentration is associated with poor nutritional status and lower survival. It is likely that mild acidosis results from a dietary acid load linked to animal protein intake. In contrast, a high bicarbonate concentration in patients treated with dialysis could result mainly from an insufficient dietary acid load, i.e. low protein intake. Therefore, a high pre-dialysis serum bicarbonate concentration should prompt nephrologists to carry out nutritional investigations to detect insufficient dietary protein intake. In any case, a high bicarbonate concentration should be neither a goal of dialysis therapy nor an index of adequate dialysis, whereas mild acidosis could be considered as an indicator of appropriate protein intake. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Anticipatory Grief in New Family Caregivers of Persons with Mild Cognitive Impairment and Dementia

PubMed Central

Garand, Linda; Lingler, Jennifer H.; Deardorf, Kaitlyn E.; DeKosky, Steven T.; Schulz, Richard; Reynolds, Charles F.; Dew, Mary Amanda

2011-01-01

Anticipatory grief is the process of experiencing normal phases of bereavement in advance of the loss of a significant person. To date, anticipatory grief has been examined in family caregivers to individuals who have had Alzheimer’s Disease (AD) an average of 3 to 6 years. Whether such grief is manifested early in the disease trajectory (at diagnosis) is unknown. Using a cross-sectional design, we examined differences in the nature and extent of anticipatory grief between family caregivers of persons with a new diagnosis of mild cognitive impairment (MCI, n=43) or AD (n=30). We also determined whether anticipatory grief levels were associated with caregiver demographics, caregiving burden, depressive symptoms and marital quality. Mean anticipatory grief levels were high in the total sample, with AD caregivers endorsing significantly more anticipatory grief than MCI caregivers. In general, AD caregivers endorsed difficulty functioning whereas MCI caregivers focused on themes of “missing the person” they once knew. Being a female caregiver, reporting higher levels of objective caregiving burden and higher depression levels each bore independent, statistically significant relationships with anticipatory grief. Given these findings, family caregivers of individuals with mild cognitive deficits or a new AD diagnosis may benefit from interventions specifically addressing anticipatory grief. PMID:21946013

Cross-stress resistance in Saccharomyces cerevisiae yeast--new insight into an old phenomenon.

PubMed

Święciło, Agata

2016-03-01

Acquired stress resistance is the result of mild stress causing the acquisition of resistance to severe stress of the same or a different type. The mechanism of "same-stress" resistance (resistance to a second, strong stress after mild primary stress of the same type) probably depends on the activation of defense and repair mechanisms specific for a particular type of stress, while cross-stress resistance (i.e., resistance to a second, strong stress after a different type of mild primary stress) is the effect of activation of both a specific and general stress response program, which in Saccharomyces cerevisiae yeast is known as the environmental stress response (ESR). Advancements in research techniques have made it possible to study the mechanism of cross-stress resistance at various levels of cellular organization: stress signal transduction pathways, regulation of gene expression, and transcription or translation processes. As a result of this type of research, views on the cross-stress protection mechanism have been reconsidered. It was originally thought that cross-stress resistance, irrespective of the nature of the two stresses, was determined by universal mechanisms, i.e., the same mechanisms within the general stress response. They are now believed to be more specific and strictly dependent on the features of the first stress.

Histopathological analysis for osteomalacia and tubulopathy in itai-itai disease.

PubMed

Baba, Hayato; Tsuneyama, Koichi; Kumada, Tokimasa; Aoshima, Keiko; Imura, Johji

2014-02-01

Cadmium (Cd) is a widespread environmental contaminant that causes both renal tubulopathy and osteomalacia. Osteomalacia is thought to be a result of renal tubulopathy, but there are few studies about the histopathological relationship between the two pathoses. Therefore, in the present study, we examined specimens from cases of itai-itai disease (IID), the most severe form of chronic cadmium poisoning, to evaluate the relationship between them. We analyzed kidney and bone specimens of 61 IID cases and the data regarding Cd concentration in kidney and bone. Tubulopathy was graded on the basis of a three-step scale (mild, moderate, and severe) using the following three items: the degree of proximal tubular defluxion, thickness of renal cortex, and weight of the kidney. Osteomalacia was evaluated using the relative osteoid volume (ROV). There were 15 cases of mild, 19 cases of moderate, and 27 cases of severe tubulopathy. The average ROV was 24.9 ± 2.0%. ROV tended to increase as tubulopathy advanced in severity, and ROV was significantly higher in cases with severe tubulopathy than those with mild or moderate tubulopathy. ROV had a negative correlation with Cd concentration in the kidney but no correlation with that in the bone. Our results suggest that the development of osteomalacia was related to the development of tubulopathy.

Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer's Disease

PubMed Central

Solfrizzi, Vincenzo; Imbimbo, Bruno P.; Lozupone, Madia; Santamato, Andrea; Zecca, Chiara; Barulli, Maria Rosaria; Bellomo, Antonello; Pilotto, Alberto; Daniele, Antonio; Greco, Antonio

2016-01-01

The failure of several Phase II/III clinical trials in Alzheimer's disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT+). MT chloride (methylene blue) was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks) and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid. PMID:27429978

Assessment of factors possibly contributing to the susceptibility of sickle trait erythrocytes to mild hypoxia. I., Design considerations and research protocol.

DOT National Transportation Integrated Search

1978-08-01

This report continues a review (see FAA-AM-76-15) of the evidence for mixed dominance of the Hbs beta gene in people with the sickle cell trait. These individuals, whose erythrocytes contain a mixture of hemoglobins (HbA/HbS), are healthy and have a ...

A Family History Study of Asperger Syndrome

ERIC Educational Resources Information Center

Ghaziuddin, Mohammad

2005-01-01

Asperger syndrome (AS) is a childhood-onset disorder often described as a mild variant of autism. Although classified as a distinct disorder in the DSM-IV, its overlap with autism continues to be a matter of ongoing debate. While the family genetic origins of autism are well established, few studies have investigated this topic in AS using current…

The Role of Research in the Future of Special Education.

ERIC Educational Resources Information Center

Gallagher, James J.

The role of research in the future of special education is discussed. The impact of research on practice is exemplified in the rise of the mainstreaming movement from research findings unable to find benefits in special class instruction for the mildly handicapped. The continuing ambivalence of the practitioner toward research is noted. The past…

Mild Airflow Limitation during N2 Sleep Increases K-complex Frequency and Slows Electroencephalographic Activity

PubMed Central

Nguyen, Chinh D.; Wellman, Andrew; Jordan, Amy S.; Eckert, Danny J.

2016-01-01

Study Objectives: To determine the effects of mild airflow limitation on K-complex frequency and morphology and electroencephalogram (EEG) spectral power. Methods: Transient reductions in continuous positive airway pressure (CPAP) during stable N2 sleep were performed to induce mild airflow limitation in 20 patients with obstructive sleep apnea (OSA) and 10 healthy controls aged 44 ± 13 y. EEG at C3 and airflow were measured in 1-min windows to quantify K-complex properties and EEG spectral power immediately before and during transient reductions in CPAP. The frequency and morphology (amplitude and latency of P200, N550 and N900 components) of K-complexes and EEG spectral power were compared between conditions. Results: During mild airflow limitation (18% reduction in peak inspiratory airflow from baseline, 0.38 ± 0.11 versus 0.31 ± 0.1 L/sec) insufficient to cause American Academy of Sleep Medicine-defined cortical arousal, K-complex frequency (9.5 ± 4.5 versus 13.7 ± 6.4 per min, P < 0.01), N550 amplitude (25 ± 3 versus 27 ± 3 μV, P < 0.01) and EEG spectral power (delta: 147 ± 48 versus 230 ± 99 μV2, P < 0.01 and theta bands: 31 ± 14 versus 34 ± 13 μV2, P < 0.01) significantly increased whereas beta band power decreased (14 ± 5 versus 11 ± 4 μV2, P < 0.01) compared to the preceding non flow-limited period on CPAP. K-complex frequency, morphology, and timing did not differ between patients and controls. Conclusion: Mild airflow limitation increases K-complex frequency, N550 amplitude, and spectral power of delta and theta bands. In addition to providing mechanistic insight into the role of mild airflow limitation on K-complex characteristics and EEG activity, these findings may have important implications for respiratory conditions in which airflow limitation during sleep is common (e.g., snoring and OSA). Citation: Nguyen CD, Wellman A, Jordan AS, Eckert DJ. Mild airflow limitation during N2 sleep increases k-complex frequency and slows electroencephalographic activity. SLEEP 2016;39(3):541–550. PMID:26612389

5 CFR 892.211 - What options are available to me if I go on a period of leave without pay (LWOP) or other types...

Code of Federal Regulations, 2010 CFR

2010-01-01

... will continue FEHB coverage while on LWOP; your employer will advance your share of your FEHB premium during your LWOP period; and you will repay the advanced amounts when you return from LWOP. (Described in... you now waive). (b)(1) You may continue your FEHB coverage by agreeing in advance of LWOP to one of...

7 CFR 1980.472 - Protective advances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED... liquidation is contemplated or in process. A precise rule of when a protective advance should be made is...

Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe in 2015: magnitude, temporal trends and projections

PubMed Central

Cicinelli, Maria Vittoria; Das, Aditi; Flaxman, Seth R; Friedman, David S; Keeffe, Jill E; Kempen, John H; Limburg, Hans; Naidoo, Kovin; Pesudovs, Konrad; Peto, Tunde; Saadine, Jinan; Silvester, Alexander J; Tahhan, Nina; Taylor, Hugh R; Varma, Rohit; Wong, Tien Y

2018-01-01

Background Within a surveillance of the prevalence and causes of vision impairment in high-income regions and Central/Eastern Europe, we update figures through 2015 and forecast expected values in 2020. Methods Based on a systematic review of medical literature, prevalence of blindness, moderate and severe vision impairment (MSVI), mild vision impairment and presbyopia was estimated for 1990, 2010, 2015, and 2020. Results Age-standardised prevalence of blindness and MSVI for all ages decreased from 1990 to 2015 from 0.26% (0.10–0.46) to 0.15% (0.06–0.26) and from 1.74% (0.76–2.94) to 1.27% (0.55–2.17), respectively. In 2015, the number of individuals affected by blindness, MSVI and mild vision impairment ranged from 70 000, 630 000 and 610 000, respectively, in Australasia to 980 000, 7.46 million and 7.25 million, respectively, in North America and 1.16 million, 9.61 million and 9.47 million, respectively, in Western Europe. In 2015, cataract was the most common cause for blindness, followed by age-related macular degeneration (AMD), glaucoma, uncorrected refractive error, diabetic retinopathy and cornea-related disorders, with declining burden from cataract and AMD over time. Uncorrected refractive error was the leading cause of MSVI. Conclusions While continuing to advance control of cataract and AMD as the leading causes of blindness remains a high priority, overcoming barriers to uptake of refractive error services would address approximately half of the MSVI burden. New data on burden of presbyopia identify this entity as an important public health problem in this population. Additional research on better treatments, better implementation with existing tools and ongoing surveillance of the problem is needed. PMID:29545417

[Mild therapeutic hypothermia in cardiogenic shock : Retrospective analysis of 80 patients with preclinical cardiac arrest due to cardiac causes].

PubMed

Adler, C; Pfister, R; Baldus, S; Reuter, H

2017-02-01

The mortality in patients with cardiogenic shock after out-of-hospital cardiac arrest (OHCA) remains high despite advances in resuscitation and early revascularization strategies. The use of mild therapeutic hypothermia (MTH) for improvement of survival and neurological outcome in patients with cardiogenic shock is currently subject to renewed discussion. The aim of this study was the detection of risk factors for mortality and morbidity in patients under MTH in cardiogenic shock following preclinical resuscitation for OHCA. A total of 80 consecutive patients in cardiogenic shock after successful resuscitation (mean age 60 ± 3.2 years) treated with MTH were retrospectively analyzed. Patients were cooled to 33 °C for 24 h using an endovascular cooling device. Neurological outcome was assessed after 2 months based on the Glasgow-Pittsburgh cerebral performance category (CPC) and correlated with various blood parameter values. After 2 months 31 patients (39 %) showed a good neurological recovery with CPC scores of 1-2, 20 patients (25 %) had a poor neurological outcome with CPC scores of 3-4 and 29 (36 %) patients enrolled in the trial died (CPC 5). Patients with a poor outcome showed significantly higher mean serum levels for lactate, creatinine and urea. In addition, these patients showed a continuous increase of serum neuron-specific enolase (NSE) values in contrast to patients with a good outcome (∆ NSE from admission to day 1, CPC 1 and 2: - 10.6 ± 3 µg/l and CPC 3-5: 33 ± 12 µg/l, p = 0.02). Changes in the course of serum creatinine, urea and NSE levels within the first 72 h after OHCA could provide valuable additional information for the early assessment of the neurological prognosis in patients treated with MTH.

Effect of Bauxite addition on Adhesion Strength and Surface Roughness of Fly ash based Plasma Sprayed Coatings

NASA Astrophysics Data System (ADS)

Bhuyan, S. K.; Samal, S.; Pattnaik, D.; Sahu, A.; Swain, B.; Thiyagarajan, T. K.; Mishra, S. C.

2018-03-01

The environment is being contaminated with advancement of new technology, day by day. One of the primary sources for this contamination is the industrial waste. Industrialization is the prime reason behind the prosperity of any country to meet the materialistic demand. To run the industries, a huge amount of (electric) power is needed and hence need for thermal power plants to serve the purpose. In present scenario, coal fired thermal power plants are set up which generates a huge quantity of Fly ash. Consumption of industrial waste (Fly ash), continually a major concern for human race. In recent years, fly ash is being utilized for various purposes i.e. making bricks, mine reclamation, production of cements etc. The presence of Silica and Alumina in fly ash makes it useful for thermal barrier applications also. The plasma spray technology has the advantage of being able to process any types of metal/ceramic mineral, low-grade-ore minerals etc. to make value-added products and also to deposit ceramics, metals and a combination of these to deposit composite coatings with desired microstructure and required properties on a range of substrate materials. The present work focuses on utilization of fly ash mixing with bauxite (ore mineral) for a high valued application. Fly ash with 10 and 20% bauxite addition is used to deposit plasma spray overlay coatings at different power levels (10-20kW) on aluminum and mild steel substrates. Adhesion strength and surface roughness of the coatings are evaluated. Phase composition analysis of the coatings were done using X-ray diffraction analysis. Surface morphology of the coatings was studied using a scanning electron microscope (SEM). Maximum adhesion strength of 4.924 MPa is obtained for the composition fly ash and bauxite (10%), coated on mild steel at 16kW torch power level. The surface roughness (Ra) of the coatings is found to vary between 10.0102 to 17.2341 micron.

The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

PubMed

de Waal, Hanneke; Stam, Cornelis J; Lansbergen, Marieke M; Wieggers, Rico L; Kamphuis, Patrick J G H; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C W

2014-01-01

Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. 179 drug-naïve mild AD patients who participated in the Souvenir II study. Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Dutch Trial Register NTR1975.

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

PubMed Central

de Waal, Hanneke; Stam, Cornelis J.; Lansbergen, Marieke M.; Wieggers, Rico L.; Kamphuis, Patrick J. G. H.; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C. W.

2014-01-01

Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Trial registration Dutch Trial Register NTR1975. PMID:24475144

Impact of Reduced Renal Function on the Glucose-Lowering Effects of Luseogliflozin, a Selective SGLT2 Inhibitor, Assessed by Continuous Glucose Monitoring in Japanese Patients with Type 2 Diabetes Mellitus.

PubMed

Jinnouchi, Hideaki; Nozaki, Kazunari; Watase, Hirotaka; Omiya, Hirohisa; Sakai, Soichi; Samukawa, Yoshishige

2016-03-01

We investigated the impact of reduced renal function on 24-h glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM) treated with luseogliflozin. In this double-blind, placebo-controlled, crossover study, 37 Japanese patients with T2DM [glycated hemoglobin (HbA1c) 7.0-10.0%] and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m(2) were randomized into two groups in which patients first received luseogliflozin then placebo, or vice versa, for 7 days each. Twenty-four-hour glucose variability was measured on day 7 in each period and was compared among patients divided into three groups according to their baseline eGFR (mL/min/1.73 m(2)): normal (≥90; n = 13; normal group), normal-to-mildly reduced renal function (≥75 to <90; n = 12; normal-mild group), and mild-to-moderately reduced renal function (<75; n = 9; mild-moderate group). The mean [95% confidence interval (CI)] placebo-subtracted 24-h cumulative urinary glucose excretion (g) was 82.1 (72.7, 91.5), 82.5 (73.4, 91.5), and 62.2 (51.2, 73.3); the placebo-subtracted 24-h mean glucose concentration (mg/dL) was -24.39 (-32.53, -16.26), -28.28 (-39.35, -17.22), and -11.53 (-23.93, 0.86); and the placebo-subtracted peak postprandial glucose (mg/dL) was -26.9 (-46.9, -6.9), -38.1 (-59.6, -16.6), and 1.5 (-25.5, 28.4) in the normal, normal-mild, and mild-moderate groups, respectively. The mean lowest glucose concentrations (placebo vs. luseogliflozin, mg/dL) decreased to similar levels in the normal (115.4 vs. 93.4), normal-mild (121.0 vs. 97.9), and mild-moderate (104.0 vs. 91.1) groups. This post hoc subanalysis revealed that although mild-to-moderately reduced renal function attenuated the glucose-lowering effects of luseogliflozin on peak postprandial glucose, it did not attenuate the effects of luseogliflozin on fasting glucose. These findings may explain the smaller increase in urinary glucose excretion in these patients relative to patients with normal renal function or normal-to-moderately reduced renal function. Further studies may be needed to examine these findings in large populations of patients with T2DM and reduced renal function. JapicCTI-142548. Taisho Pharmaceutical Co., Ltd.

Mild Airflow Limitation during N2 Sleep Increases K-complex Frequency and Slows Electroencephalographic Activity.

PubMed

Nguyen, Chinh D; Wellman, Andrew; Jordan, Amy S; Eckert, Danny J

2016-03-01

To determine the effects of mild airflow limitation on K-complex frequency and morphology and electroencephalogram (EEG) spectral power. Transient reductions in continuous positive airway pressure (CPAP) during stable N2 sleep were performed to induce mild airflow limitation in 20 patients with obstructive sleep apnea (OSA) and 10 healthy controls aged 44 ± 13 y. EEG at C3 and airflow were measured in 1-min windows to quantify K-complex properties and EEG spectral power immediately before and during transient reductions in CPAP. The frequency and morphology (amplitude and latency of P200, N550 and N900 components) of K-complexes and EEG spectral power were compared between conditions. During mild airflow limitation (18% reduction in peak inspiratory airflow from baseline, 0.38 ± 0.11 versus 0.31 ± 0.1 L/sec) insufficient to cause American Academy of Sleep Medicine-defined cortical arousal, K-complex frequency (9.5 ± 4.5 versus 13.7 ± 6.4 per min, P < 0.01), N550 amplitude (25 ± 3 versus 27 ± 3 μV, P < 0.01) and EEG spectral power (delta: 147 ± 48 versus 230 ± 99 μV(2), P < 0.01 and theta bands: 31 ± 14 versus 34 ± 13 μV(2), P < 0.01) significantly increased whereas beta band power decreased (14 ± 5 versus 11 ± 4 μV(2), P < 0.01) compared to the preceding non flow-limited period on CPAP. K-complex frequency, morphology, and timing did not differ between patients and controls. Mild airflow limitation increases K-complex frequency, N550 amplitude, and spectral power of delta and theta bands. In addition to providing mechanistic insight into the role of mild airflow limitation on K-complex characteristics and EEG activity, these findings may have important implications for respiratory conditions in which airflow limitation during sleep is common (e.g., snoring and OSA). © 2016 Associated Professional Sleep Societies, LLC.

Tolerance to extended galvanic vestibular stimulation: optimal exposure for astronaut training.

PubMed

Dilda, Valentina; MacDougall, Hamish G; Moore, Steven T

2011-08-01

We have developed an analogue of postflight sensorimotor dysfunction in astronauts using pseudorandom galvanic vestibular stimulation (GVS). To date there has been no study of the effects of extended GVS on human subjects and our aim was to determine optimal exposure for astronaut training based on tolerance to intermittent and continuous galvanic stimulation. There were 60 subjects who were exposed to a total of 10.5 min of intermittent GVS at a peak current of 3.5 mA or 5 mA. A subset of 24 subjects who tolerated the intermittent stimulus were subsequently exposed to 20-min continuous stimulation at 3.5 mA or 5 mA. During intermittent GVS the large majority of subjects (78.3%) reported no or at most mild motion sickness symptoms, 13.3% reported moderate symptoms, and 8.3% experienced severe nausea and requested termination of the stimulus. During 20-min continuous exposure, 83.3% of subjects reported no or at most mild motion sickness symptoms and 16.7% (all in the 5-mA group) experienced severe nausea. Based on these results, we propose two basic modes of GVS application to minimize the incidence of motion sickness: intermittent high (5 mA) amplitude, suited to simulation of intensive operator tasks requiring a high-fidelity analogue of postflight sensorimotor dysfunction such as landing or docking maneuvers; and continuous low (3.5 mA) amplitude stimulation, for longer simulation scenarios such as extra vehicular activity. Our results suggest that neither mode of stimulation would induce motion sickness in the large majority of subjects for up to 20 min exposure.

Recent advances in acetylcholinesterase Inhibitors and Reactivators: an update on the patent literature (2012-2015).

PubMed

McHardy, Stanton F; Wang, Hua-Yu Leo; McCowen, Shelby V; Valdez, Matthew C

2017-04-01

Acetylcholinesterase (AChE) is the major enzyme that hydrolyzes acetylcholine, a key neurotransmitter for synaptic transmission, into acetic acid and choline. Mild inhibition of AChE has been shown to have therapeutic relevance in Alzheimer's disease (AD), myasthenia gravis, and glaucoma among others. In contrast, strong inhibition of AChE can lead to cholinergic poisoning. To combat this, AChE reactivators have to be developed to remove the offending AChE inhibitor, restoring acetylcholine levels to normal. Areas covered: This article covers recent advances in the development of acetylcholinesterase modulators, including both inhibitors of acetylcholinesterase for the efforts in development of new chemical entities for treatment of AD, as well as re-activators for resurrection of organophosphate bound acetylcholinesterase. Expert opinion: Over the past three years, research efforts have continued to identify novel small molecules as AChE inhibitors for both CNS and peripheral diseases. The more recent patent activity has focused on three AChE ligand design areas: derivatives of known AChE ligands, natural product based scaffolds and multifunctional ligands, all of which have produced some unique chemical matter with AChE inhibition activities in the mid picomolar to low micromolar ranges. New AChE inhibitors with polypharmacology or dual inhibitory activity have also emerged as highlighted by new AChE inhibitors with dual activity at L-type calcium channels, GSK-3, BACE1 and H3, although most only show low micromolar activity, thus further research is warranted. New small molecule reactivators of organophosphate-inhibited AChE have also been disclosed, which focused on the design of neutral ligands with improved pharmaceutical properties and blood-brain barrier (BBB) penetration. Gratifyingly, some research in this area is moving away from the traditional quaternary pyridinium oximes AChE reactivators, while still employing the necessary reactivation group (oximes). However, selectivity over inhibition of native AChE enzyme, effectiveness of reactivation, broad-spectrum reactivation against multiple organophosphates and reactivation of aged-enzyme continue to be hurdles for this area of research.

Role of mouthguards in reducing mild traumatic brain injury/concussion incidence in high school football athletes.

PubMed

Winters, Jackson; DeMont, Richard

2014-01-01

There is continued speculation on the value of mouthguards (MGs) in preventing mild traumatic brain injury (MTBI)/concussion injuries. The purpose of this randomized prospective study was to compare the impact of pressure-laminated (LM), custom-made, properly fitted MGs to over-the-counter (OTC) MGs on the MTBI/concussion incidence in high school football athletes over a season of play. Four hundred twelve players from 6 high school football teams were included in the study. Twenty-four MTBI/concussion injuries (5.8%) were recorded. When examining the MTBI/concussion injury rate by MG type, there was a significant difference (P = 0.0423) with incidence rates of 3.6% and 8.3% in the LM MG and OTC MG groups, respectively.

Tribological Behavior of Mg97Zn1Y2 Alloy at Elevated Temperatures of 50-200 °C

NASA Astrophysics Data System (ADS)

An, J.; Feng, J. H.; Yan, X. H.; Li, R. G.

2017-10-01

The tribological behavior of Mg97Zn1Y2 alloy was investigated using a pin-on-disk wear machine at wear temperatures of 50-200 °C. Morphologies and chemical compositions of worn surfaces were analyzed using scanning electron microscope and energy-dispersive x-ray spectrometer. The microstructural evolution and hardness change in subsurfaces were examined by optical microscopy and hardness tester. The results showed that the wear temperature had significant influence on the coefficient of friction and wear rate. At wear temperatures of 50-200 °C, with increasing applied load, the coefficient of friction went down rapidly then turned to decrease slowly in the mild wear regime, and continuously decreased modestly until the largest applied load in the severe wear regime. Increasing wear temperature from 50 to 200 °C decreased the mild to severe wear transition load linearly from 120 to 60 N. In the mild wear regime, the main wear mechanisms were identified as abrasion + oxidation and delamination + surface oxidation at 50-150 °C, and delamination at 200 °C, while in the severe wear regime, the main wear mechanisms were identified as severe plastic deformation + spallation of oxide layer and surface melting at 50-150 °C, and severe plastic deformation and surface melting at 200 °C. The microstructural transformation from the deformed to the dynamically recrystallized (DRX), and hardness change from the strain hardening to softening were found in the subsurfaces before and after mild to severe transition. The DRX softening mechanism was determined for mild to severe wear transition at 50-200 °C. A wear transition map was constructed for Mg97Zn1Y2 alloy on applied load versus wear temperature.

Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

PubMed

Olde Rikkert, Marcel G M; Verhey, Frans R; Blesa, Rafael; von Arnim, Christine A F; Bongers, Anke; Harrison, John; Sijben, John; Scarpini, Elio; Vandewoude, Maurits F J; Vellas, Bruno; Witkamp, Renger; Kamphuis, Patrick J G H; Scheltens, Philip

2015-01-01

The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

Mild heat stress enhances differentiation and proliferation of Japanese quail myoblasts and enhances slow muscle fiber characteristics.

PubMed

Choi, Y M; Chen, P R; Shin, S; Zhang, J; Hwang, S; Lee, K

2016-08-01

The objective of this study was to investigate the effect of mild heat stress on muscle fiber hyperplastic and hypertrophic growth in quail primary myogenic cells to better understand the mechanisms leading to increased skeletal muscle development in avian embryos incubated at a higher temperature. Compared to control cultures maintained at 37°C, incubation at 39°C enhanced myotube length (P < 0.01) and diameter (P < 0.001) at 3 days after differentiation (D3). This enlargement of the myotubes incubated at 39°C can be explained by differences in the fusion index (56.7 vs. 46.2%, P < 0.05) and nuclei number per myotube (18.1 vs. 10.8, P < 0.001) compared to the control cells at D3. Additionally, a higher density of myotubes at D3 in cultures exposed to a higher temperature were related to higher levels of Pax-7 (P < 0.05) compared to the control cells incubated continuously at 37°C. These results indicated a higher proliferative capacity in cells exposed to mild heat stress compared to the control cells. On the other hand, mild heat stress enhanced protein levels of slow myosin heavy chain isoform (P < 0.01) and cytochrome c oxidase subunit IV (P < 0.01) compared to the control cells at D3. These discrepancies in protein expression indicated maintenance of slow muscle fiber type characteristics in myotubes incubated at 39°C. Our results suggest that mild heat stress plays a significant role in myogenic mechanisms related to muscle mass and development. © 2016 Poultry Science Association Inc.

7 CFR 1779.84 - Additional loans or advances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Additional loans or advances. 1779.84 Section 1779.84 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.84 Additional loans or...

Continued advancement of the programming language HAL to an operational status

NASA Technical Reports Server (NTRS)

1971-01-01

The continued advancement of the programming language HAL to operational status is reported. It is demonstrated that the compiler itself can be written in HAL. A HAL-in-HAL experiment proves conclusively that HAL can be used successfully as a compiler implementation tool.

42 CFR § 414.1415 - Advanced APM criteria.

Code of Federal Regulations, 2010 CFR

2017-10-01

... (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Merit-Based Incentive Payment System and Alternative Payment Model Incentive § 414.1415 Advanced APM criteria. (a) Use... is responsible under an APM. For episode payment models, expected expenditures mean the episode...

New and developing therapies for atopic dermatitis*

PubMed Central

Hajar, Tamar; Gontijo, João Renato Vianna; Hanifin, Jon M

2018-01-01

Atopic dermatitis is a common inflammatory skin disease. New understanding in disease pathogenesis has led to a considerable number of promising new drugs in development. New topical agents can be especially helpful for children, providing an alternative to the need for chronic topical corticosteroid use. While many patients with mild or moderate disease can be managed with topical treatments, there are unmet needs for recalcitrant and severe cases. New and developing therapies hold promise for real advances in management of this complex disease. PMID:29641707

Curative effect of photodynamic therapy for 42 cases of moderate or late stage in esophagus cancer

NASA Astrophysics Data System (ADS)

Bai, Xiao-Min; Shen, Guang-Rong; Chen, Weng-Ge; Guo, Tao

1998-11-01

34 patients with advanced esophagus cancer and 8 cases of cancer of gastric cardia were treated by photodynamic therapy. The therapeutic effectiveness of the treatment was evaluated according the criteria used in China. CR 63.2 percent SR 11.3 percent, MR 2 percent. The total effective rate was 76.5 percent. There was no significant side effect in this group except mild skin photosensitization and pigmentation and exacerbation of pain in a few cases.

Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT

PubMed Central

Yang, James Chin-Hsin; Ahn, Myung-Ju; Nakagawa, Kazuhiko; Tamura, Tomohide; Barraclough, Helen; Enatsu, Sotaro; Cheng, Rebecca; Orlando, Mauro

2015-01-01

Purpose A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. Materials and Methods Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaïve, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, post-marketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. Results In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT’s safety profile. Conclusion The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC. PMID:25410761

Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT.

PubMed

Yang, James Chin-Hsin; Ahn, Myung-Ju; Nakagawa, Kazuhiko; Tamura, Tomohide; Barraclough, Helen; Enatsu, Sotaro; Cheng, Rebecca; Orlando, Mauro

2015-07-01

A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaïve, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, post-marketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT's safety profile. The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC.

The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease.

PubMed

Houston, Mark

2018-03-01

Numerous clinical trials suggest that we have reached a limit in our ability to decrease the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) utilizing the traditional diagnostic evaluation, prevention and treatment strategies for the top five cardiovascular risk factors of hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. About 80% of heart disease (heart attacks, angina, coronary heart disease and congestive heart failure) can be prevented by optimal nutrition, optimal exercise, optimal weight and body composition, mild alcohol intake and avoiding smoking. Statistics show that approximately 50% of patients continue to have CHD or myocardial infarction (MI) despite presently defined 'normal' levels of the five risk factors listed above. This is often referred to as the 'CHD gap'. Novel and more accurate definitions and evaluations of these top five risk factors are required, such as 24 h ambulatory blood pressure (ABM) results, advanced lipid profiles, redefined fasting and 2 h dysglycemia parameters, a focus on visceral obesity and body composition and the effects of adipokines on cardiovascular risk. There are numerous traumatic insults from the environment that damage the cardiovascular system but there are only three finite vascular endothelial responses, which are inflammation, oxidative stress and immune vascular dysfunction. In addition, the concept of translational cardiovascular medicine is mandatory in order to correlate the myriad of CHD risk factors to the presence or absence of functional or structural damage to the vascular system, preclinical and clinical CHD. This can be accomplished by utilizing advanced and updated CV risk scoring systems, new and redefined CV risk factors and biomarkers, micronutrient testing, cardiovascular genetics, nutrigenomics, metabolomics, genetic expression testing and noninvasive cardiovascular testing.

The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease

PubMed Central

Houston, Mark

2018-01-01

Numerous clinical trials suggest that we have reached a limit in our ability to decrease the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) utilizing the traditional diagnostic evaluation, prevention and treatment strategies for the top five cardiovascular risk factors of hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. About 80% of heart disease (heart attacks, angina, coronary heart disease and congestive heart failure) can be prevented by optimal nutrition, optimal exercise, optimal weight and body composition, mild alcohol intake and avoiding smoking. Statistics show that approximately 50% of patients continue to have CHD or myocardial infarction (MI) despite presently defined ‘normal’ levels of the five risk factors listed above. This is often referred to as the ‘CHD gap’. Novel and more accurate definitions and evaluations of these top five risk factors are required, such as 24 h ambulatory blood pressure (ABM) results, advanced lipid profiles, redefined fasting and 2 h dysglycemia parameters, a focus on visceral obesity and body composition and the effects of adipokines on cardiovascular risk. There are numerous traumatic insults from the environment that damage the cardiovascular system but there are only three finite vascular endothelial responses, which are inflammation, oxidative stress and immune vascular dysfunction. In addition, the concept of translational cardiovascular medicine is mandatory in order to correlate the myriad of CHD risk factors to the presence or absence of functional or structural damage to the vascular system, preclinical and clinical CHD. This can be accomplished by utilizing advanced and updated CV risk scoring systems, new and redefined CV risk factors and biomarkers, micronutrient testing, cardiovascular genetics, nutrigenomics, metabolomics, genetic expression testing and noninvasive cardiovascular testing. PMID:29316855

Use of varenicline for more than 12 months for smoking cessation in heavy chronic obstructive pulmonary disease smokers unmotivated to quit: a pilot study

PubMed Central

Sansores, Raúl H.; Ramírez-Venegas, Alejandra; Arellano-Rocha, Rosario; Noé-Díaz, Valeri; García-Gómez, Leonor; Pérez Bautista, Oliver; Velázquez Uncal, Mónica

2016-01-01

Introduction: Use of varenicline for as long as necessary to achieve abstinence has not been studied. The aim of this study was to test whether smokers with mild-to-moderate chronic obstructive pulmonary disease (COPD) are able to quit if they use varenicline for a sufficient length of time. Methods: A total of 30 heavy smokers with COPD took varenicline for sufficiently long enough for smoking cessation. Smokers were allowed to smoke without a fixed quit date. The main endpoints were the time of voluntary abstinence (VA) and the continuous abstinence rate (CAR) at 12 and 18 months. Results: Of 28 subjects, eight subjects continued to smoke and 20 subjects stopped smoking, demonstrating a CAR up to 18 months (71%). Median time of treatment was 6 (range 3–24) and 2 (range 1–8) months for abstainers and non-abstainers, respectively, and the median time of VA for abstainers was 4 (range 1–21) months. Conclusions: Use of varenicline for more than the traditional 12 recommended weeks may be a good strategy to increase the cessation rate in heavy smokers with mild COPD. PMID:27352612

Use of varenicline for more than 12 months for smoking cessation in heavy chronic obstructive pulmonary disease smokers unmotivated to quit: a pilot study.

PubMed

Sansores, Raúl H; Ramírez-Venegas, Alejandra; Arellano-Rocha, Rosario; Noé-Díaz, Valeri; García-Gómez, Leonor; Pérez Bautista, Oliver; Velázquez Uncal, Mónica

2016-10-01

Use of varenicline for as long as necessary to achieve abstinence has not been studied. The aim of this study was to test whether smokers with mild-to-moderate chronic obstructive pulmonary disease (COPD) are able to quit if they use varenicline for a sufficient length of time. A total of 30 heavy smokers with COPD took varenicline for sufficiently long enough for smoking cessation. Smokers were allowed to smoke without a fixed quit date. The main endpoints were the time of voluntary abstinence (VA) and the continuous abstinence rate (CAR) at 12 and 18 months. Of 28 subjects, eight subjects continued to smoke and 20 subjects stopped smoking, demonstrating a CAR up to 18 months (71%). Median time of treatment was 6 (range 3-24) and 2 (range 1-8) months for abstainers and non-abstainers, respectively, and the median time of VA for abstainers was 4 (range 1-21) months. Use of varenicline for more than the traditional 12 recommended weeks may be a good strategy to increase the cessation rate in heavy smokers with mild COPD. © The Author(s), 2016.

Assessing female sexual arousal with the labial thermistor: response specificity and construct validity.

PubMed

Prause, N; Heiman, J R

2009-05-01

The labial thermistor offers several potential psychometric advantages over existing measures of female sexual response; however, the thermistor lacked data to support these presumed advantages, especially with respect to its discriminant validity. In this study, both the labial thermistor was worn simultaneously with the vaginal photoplethysmograph as women viewed films. They also indicated their level of subjective sexual arousal using a lever. The labial thermistor discriminated sexual from nonsexual arousing stimuli and was sensitive to different levels of sexual arousal. The correspondence of the instrument with subjective sexual arousal, measured using a continuous lever, was lower during the mildly arousing sexual film and higher during the maximally sexual arousing film. One woman reported that the labial thermistor was very uncomfortable, while others indicated no or mild discomfort from each instrument. The vaginal photoplethysmograph largely replicated the effects documented by the labial thermistor, although it did not discriminate sexual stimuli of different intensity nor correspond with women's continuous lever responses as closely during the more arousing stimulus. Difficulties recording simultaneously with these instruments are noted. The labial thermistor adequately discriminates between generally arousing and sexually arousing stimuli, increasing its utility as a measure for between-subject study designs.

New developments in psychosocial interventions for adults with unipolar depression.

PubMed

Lau, Mark A

2008-01-01

Depression treatment guidelines typically recommend cognitive behavioral therapy and/or interpersonal therapy for the acute treatment of mild-moderate depression. However, several new developments support an expanded role for psychotherapy in depression treatment. This article summarizes recent psychotherapy efficacy studies across the depression treatment continuum and the effectiveness of psychosocial interventions in community settings. New psychotherapies in the acute treatment of mild-moderate depression include emotion-focused therapy, self-system therapy, cognitive control training and positive psychotherapy. Furthermore, emerging evidence supports the use of psychotherapy for moderate-severe and treatment-resistant depression and for recurrent depression with a seasonal pattern. An important area of growth is the development and evaluation of continuation/maintenance treatments based on cognitive behavioral therapy and interpersonal therapy to reduce depressive relapse risk in recurrent and chronic depression. Finally, there is evidence supporting the effectiveness of stepped care, chronic disease management and collaborative care models in community settings. Emerging evidence supports an expanded role for the use of psychosocial interventions as acute and continuation/maintenance treatments for unipolar depression. Although further research is required to replicate these findings, a remaining challenge is to increase the availability of these treatments to the mental health consumer.

Brain tissue partial pressure of oxygen predicts the outcome of severe traumatic brain injury under mild hypothermia treatment.

PubMed

Sun, Hongtao; Zheng, Maohua; Wang, Yanmin; Diao, Yunfeng; Zhao, Wanyong; Wei, Zhengjun

2016-01-01

The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2) in the course of mild hypothermia treatment (MHT) for treating severe traumatic brain injury (sTBI). There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), and cerebral perfusion pressure (CPP) were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome.

Nonparametric methods for doubly robust estimation of continuous treatment effects.

PubMed

Kennedy, Edward H; Ma, Zongming; McHugh, Matthew D; Small, Dylan S

2017-09-01

Continuous treatments (e.g., doses) arise often in practice, but many available causal effect estimators are limited by either requiring parametric models for the effect curve, or by not allowing doubly robust covariate adjustment. We develop a novel kernel smoothing approach that requires only mild smoothness assumptions on the effect curve, and still allows for misspecification of either the treatment density or outcome regression. We derive asymptotic properties and give a procedure for data-driven bandwidth selection. The methods are illustrated via simulation and in a study of the effect of nurse staffing on hospital readmissions penalties.

Influence of the pressure dependent coefficient of friction on deep drawing springback predictions

NASA Astrophysics Data System (ADS)

Gil, Imanol; Galdos, Lander; Mendiguren, Joseba; Mugarra, Endika; Sáenz de Argandoña, Eneko

2016-10-01

This research studies the effect of considering an advanced variable friction coefficient on the springback prediction of stamping processes. Traditional constant coefficient of friction considerations are being replaced by more advanced friction coefficient definitions. The aim of this work is to show the influence of defining a pressure dependent friction coefficient on numerical springback predictions of a DX54D mild steel, a HSLA380 and a DP780 high strength steel. The pressure dependent friction model of each material was fitted to the experimental data obtained by Strip Drawing tests. Then, these friction models were implemented in a numerical simulation of a drawing process of an industrial automotive part. The results showed important differences between defining a pressure dependent friction coefficient or a constant friction coefficient.

Advances in protease engineering for laundry detergents.

PubMed

Vojcic, Ljubica; Pitzler, Christian; Körfer, Georgette; Jakob, Felix; Ronny Martinez; Maurer, Karl-Heinz; Schwaneberg, Ulrich

2015-12-25

Proteases are essential ingredients in modern laundry detergents. Over the past 30 years, subtilisin proteases employed in the laundry detergent industry have been engineered by directed evolution and rational design to tailor their properties towards industrial demands. This comprehensive review discusses recent success stories in subtilisin protease engineering. Advances in protease engineering for laundry detergents comprise simultaneous improvement of thermal resistance and activity at low temperatures, a rational strategy to modulate pH profiles, and a general hypothesis for how to increase promiscuous activity towards the production of peroxycarboxylic acids as mild bleaching agents. The three protease engineering campaigns presented provide in-depth analysis of protease properties and have identified principles that can be applied to improve or generate enzyme variants for industrial applications beyond laundry detergents. Copyright © 2015 Elsevier B.V. All rights reserved.

A study of an advanced confined linear energy source

NASA Technical Reports Server (NTRS)

Anderson, M. C.; Heidemann, W. B.

1971-01-01

A literature survey and a test program to develop and evaluate an advanced confined linear energy source were conducted. The advanced confined linear energy source is an explosive or pyrotechnic X-Cord (mild detonating fuse) supported inside a confining tube capable of being hermetically sealed and retaining all products of combustion. The energy released by initiation of the X-Cord is transmitted through the support material to the walls of the confining tube causing an appreciable change in cross sectional configuration and expansion of the tube. When located in an assembly that can accept and use the energy of the tube expansion, useful work is accomplished through fracture of a structure, movement of a load, reposition of a pin, release of a restraint, or similar action. The tube assembly imparts that energy without release of debris or gases from the device itself. This facet of the function is important to the protection of men or equipment located in close proximity to the system during the time of function.

A Phase II Study of Docetaxel and Epirubicin in Advanced Adult Soft Tissue Sarcomas (STS)

PubMed Central

Kourousis, Charalabos; Karamouzis, Michalis V.; Iconomou, Gregoris; Tsiata, Ekaterini; Tzorzidis, Fotis; Megas, Panagiotis; Lambiris, Elias; Georgoulias, Vasilios

2004-01-01

Purpose: The aim of this study was to determine the efficacy and safety of docetaxel plus epirubicin combination as first-line chemotherapy in patients with locally advanced and/or metastatic adult STS. Patients and Methods: Eighteen patients were treated with epirubicin 30 mg/m2 on days 1 to 3 and docetaxel 100 mg/m2 on day 1 every 3 weeks. Results: Fifteen out of 18 patients (83.4%) were assessable for response. No complete response was recorded. Three (20%) patients achieved PR, 3 had SD and 9 PD. The overall median survival was 14 months (range, 3–48 months) and the median time to disease progression was 4 months (range, 2–45 months). Grade ≥ 3 neutropenia occurred in 88% and neutropenic fever in 27.8% of patients. Other toxicities were mild. No treatment related deaths occurred. Discussion: Docetaxel plus epirubicin combination achieved low response rate with severe myelotoxicity in patients with advanced STS. PMID:18521407

Advances in Scanning Reflectarray Antennas Based on Ferroelectric Thin Film Phase Shifters for Deep Space Communications

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R.

2007-01-01

Though there are a few examples of scanning phased array antennas that have flown successfully in space, the quest for low-cost, high-efficiency, large aperture microwave phased arrays continues. Fixed and mobile applications that may be part of a heterogeneous exploration communication architecture will benefit from the agile (rapid) beam steering and graceful degradation afforded by phased array antennas. The reflectarray promises greater efficiency and economy compared to directly-radiating varieties. Implementing a practical scanning version has proven elusive. The ferroelectric reflectarray, under development and described herein, involves phase shifters based on coupled microstrip patterned on Ba(x)Sr(1-x)TiO3 films, that were laser ablated onto LaAlO3 substrates. These devices outperform their semiconductor counterparts from X- through and K-band frequencies. There are special issues associated with the implementation of a scanning reflectarray antenna, especially one realized with thin film ferroelectric phase shifters. This paper will discuss these issues which include: relevance of phase shifter loss; modulo 2(pi) effects and phase shifter transient effects on bit error rate; scattering from the ground plane; presentation of a novel hybrid ferroelectric-semiconductor phase shifter; and the effect of mild radiation exposure on phase shifter performance.

Non-surgical treatment of obstructive sleep apnea syndrome.

PubMed

Tingting, Xu; Danming, You; Xin, Chen

2018-02-01

Obstructive sleep apnea syndrome (OSAS), a pervasive disease, is closely associated with complications such as cardiovascular diseases, neurocognitive diseases, and metabolic syndromes. Continuous positive airway pressure (CPAP) is the standard treatment for OSAS, with low compliance due to multifarious factors. The two other modes of ventilation, bi-level positive airway pressure (BPAP) and autotitrating positive airway pressure (APAP), which were developed from CPAP, are slightly different from CPAP in specific groups, as well as the corresponding treatment effect and compliance. The compliance of traditional positional therapy is not high, but with the emergence of the neck-based position treatment device, its compliance and indications have changed. Although CPAP is superior to mandibular advancement device (MAD) in improving AHI, MAD seems to be comparable to CPAP in improving other indicators. Corticosteroids and leukotriene receptor antagonists are effective treatments for mild OSAS children. Whether corticosteroids can be used in other OSAS groups and their adjunctive functions to CPAP remains unclear. The combination of these two kinds of drugs appears to be more effective than single drug. Researches on transcutaneous electrical stimulation are still not enough. Its effectiveness and stimulation settings still need further study. This review summarized the various OSAS non-surgical treatments from indications, treatment outcomes, compliance, adverse reactions, and recent progress.

Cross-linked carbon networks constructed from N-doped nanosheets with enhanced performance for supercapacitors

NASA Astrophysics Data System (ADS)

Liu, Qingqing; Zhong, Jialiang; Sun, Zhipeng; Mi, Hongyu

2017-02-01

Hierarchically porous carbons offer great benefits for constructing advanced electrodes for energy-related applications. Herein, we reported facile synthesis of cross-linked carbon networks (HPCNs) made from N-doped nanosheets. By using MgO as self-sacrificial templates, the polyethylene glycol and melamine precursors were first uniformly coated on the template, and then annealed at the elevated temperature in inert atmosphere before removing the templates by mild acid etching. Interestingly, the capacitance performance of HPCNs could be easily modulated by adjusting the mass ratio of the precursors and templates, as well as the carbonization temperature. The optimized HPCNs showed specific capacitances of 192.6 F g-1 at 1.0 A g-1 and 156.2 F g-1 even at 20 A g-1 in 6.0 M KOH solution, and long-term cyclability with 85.5% capacitance retention at high current load of 10 A g-1 after 8000 successive cycles, which were attributed to structural merits of these continuous networks including high surface area of 370.8 m2 g-1, high pore volume of 1.65 cm3 g-1, as well as high nitrogen content of 9.920 wt.%. Owing to simplicity of the synthesis method and superior performance, such HPCNs may promise great potential in energy storage fields.

Intellectual developmental disorders: towards a new name, definition and framework for "mental retardation/intellectual disability" in ICD-11.

PubMed

Salvador-Carulla, Luis; Reed, Geoffrey M; Vaez-Azizi, Leila M; Cooper, Sally-Ann; Martinez-Leal, Rafael; Bertelli, Marco; Adnams, Colleen; Cooray, Sherva; Deb, Shoumitro; Akoury-Dirani, Leyla; Girimaji, Satish Chandra; Katz, Gregorio; Kwok, Henry; Luckasson, Ruth; Simeonsson, Rune; Walsh, Carolyn; Munir, Kemir; Saxena, Shekhar

2011-10-01

Although "intellectual disability" has widely replaced the term "mental retardation", the debate as to whether this entity should be conceptualized as a health condition or as a disability has intensified as the revision of the World Health Organization (WHO)'s International Classification of Diseases (ICD) advances. Defining intellectual disability as a health condition is central to retaining it in ICD, with significant implications for health policy and access to health services. This paper presents the consensus reached to date by the WHO ICD Working Group on the Classification of Intellectual Disabilities. Literature reviews were conducted and a mixed qualitative approach was followed in a series of meetings to produce consensus-based recommendations combining prior expert knowledge and available evidence. The Working Group proposes replacing mental retardation with intellectual developmental disorders, defined as "a group of developmental conditions characterized by significant impairment of cognitive functions, which are associated with limitations of learning, adaptive behaviour and skills". The Working Group further advises that intellectual developmental disorders be incorporated in the larger grouping (parent category) of neurodevelopmental disorders, that current subcategories based on clinical severity (i.e., mild, moderate, severe, profound) be continued, and that problem behaviours be removed from the core classification structure of intellectual developmental disorders and instead described as associated features.

Management of Clostridium difficile Infection

PubMed Central

Al-Jashaami, Layth S.

2016-01-01

Since the discovery of Clostridium difficile infection (CDI) in the 1970s, there has been an increase in the incidence, severity, and recurrence rate of the disease. We reviewed the recent CDI literature in PubMed published before February 28, 2016 that focused on advances in therapy. Despite a large number of studies describing methods for diagnosing the disease, there is currently no definitive test that identifies this infection with certainty, which complicates therapy. Recommended therapy for CDI includes oral metronidazole for mild cases and oral vancomycin or fidaxomicin for moderate to severe cases, each given for 10 to 14 days. For infection with spore-forming C difficile, this length of treatment may be insufficient to lead to cure; however, continuing antibiotics for longer periods of time may unfavorably alter the microbiome, preventing recovery. Treatment with metronidazole has been associated with an increasing failure rate, and the only clear recommended form of metronidazole for treatment of CDI is the intravenous formulation for patients unable to take oral medications. For vancomycin or fidaxomicin treatment of first CDI recurrences, the drug used in the initial bout can be repeated. For second or future recurrences, vancomycin can be given in pulsed or tapered doses. New modalities of treatment, such as bacteriotherapy and immunotherapy, show promise for the treatment of recurrent CDI. PMID:27917075

Habit Doesn’t Make the Predictions Stronger: Implicit Alcohol Associations and Habitualness Predict Drinking Uniquely

PubMed Central

Lindgren, Kristen P.; Neighbors, Clayton; Teachman, Bethany A.; Gasser, Melissa L.; Kaysen, Debra; Norris, Jeanette; Wiers, Reinout W.

2015-01-01

Introduction As research on implicit (in the sense of fast/reflexive/impulsive) alcohol associations and alcohol advances, there is increasing emphasis on understanding the circumstances under which implicit alcohol associations predict drinking. In this study, we investigated habitualness of drinking (i.e., the extent to which drinking is automatic or occurs without thinking) as a moderator of the relations between several measures of implicit alcohol associations and key drinking outcomes. Method A sample of 506 participants (57% female) completed web-based measures of implicit alcohol associations (drinking identity, alcohol approach, and alcohol excitement), along with indicators of habitualness, and typical alcohol consumption, alcohol problems, and risk of alcohol use disorders. Results As expected, implicit alcohol associations, especially drinking identity, were positively associated with, and predicted unique variance in, drinking outcomes. Further, habitualness emerged as a consistent, positive predictor of drinking outcomes. Contrary to expectations, habitualness rarely moderated the relation between implicit alcohol associations and drinking outcomes. Conclusions Although moderation was rarely observed, findings indicated that even mild levels of habitualness are risky. Findings also continue to support implicit alcohol associations, particularly drinking identity, as a risk factor for hazardous drinking. Collectively, this suggests the importance of targeting both in prevention and intervention efforts. PMID:25665917

An ultra-sensitive biophysical risk assessment of light effect on skin cells.

PubMed

Bennet, Devasier; Viswanath, Buddolla; Kim, Sanghyo; An, Jeong Ho

2017-07-18

The aim of this study was to analyze photo-dynamic and photo-pathology changes of different color light radiations on human adult skin cells. We used a real-time biophysical and biomechanics monitoring system for light-induced cellular changes in an in vitro model to find mechanisms of the initial and continuous degenerative process. Cells were exposed to intermittent, mild and intense (1-180 min) light with On/Off cycles, using blue, green, red and white light. Cellular ultra-structural changes, damages, and ECM impair function were evaluated by up/down-regulation of biophysical, biomechanical and biochemical properties. All cells exposed to different color light radiation showed significant changes in a time-dependent manner. Particularly, cell growth, stiffness, roughness, cytoskeletal integrity and ECM proteins of the human dermal fibroblasts-adult (HDF-a) cells showed highest alteration, followed by human epidermal keratinocytes-adult (HEK-a) cells and human epidermal melanocytes-adult (HEM-a) cells. Such changes might impede the normal cellular functions. Overall, the obtained results identify a new insight that may contribute to premature aging, and causes it to look aged in younger people. Moreover, these results advance our understanding of the different color light-induced degenerative process and help the development of new therapeutic strategies.

The Persistence of the Self over Time in Mild Cognitive Impairment and Alzheimer's Disease

PubMed Central

Tippett, Lynette J.; Prebble, Sally C.; Addis, Donna Rose

2018-01-01

Diachronic unity is the belief that, despite changes, we are the same person across the lifespan. We propose that diachronic unity is supported by the experience of remembering the self over time during episodic recall (i.e., phenomenological continuity). However, we also predict that diachronic unity is also possible when episodic memory is impaired, as long as the ability to construct life narratives from semantic memory (i.e., semantic continuity) is intact. To examine this prediction, we investigated diachronic unity in Alzheimer's Disease (AD) and amnestic mild cognitive impairment (aMCI), two conditions characterised by disrupted phenomenological continuity. If semantic continuity is also altered in these conditions, there should be an associated deterioration in diachronic unity. Participants with AD, aMCI, and healthy controls (HC) completed a self-persistence interview measuring diachronic unity (beliefs about self-persistence, explanations for stability/change). Semantic continuity was assessed with a life-story interview measuring autobiographical reasoning (self-event connections), and coherence (temporal/thematic/causal) of narratives. Our results highlight a complex relationship between semantic continuity and diachronic unity and revealed a divergence between two aspects of diachronic unity: AD/aMCI groups did not differ from HC in continuity beliefs, but AD explanations for self-persistence were less sophisticated. Semantic continuity was most impaired in AD: their narratives had fewer self-event connections (vs. HCs) and lower temporal/thematic coherence (vs. HC/aMCI), while both AD/aMCI groups had lower causal coherence. Paradoxically AD participants who scored higher on measures of beliefs in the persistence of the core self, provided less sophisticated explanations for their self-persistence and were less able to explore persistence in their life narratives. These findings support the importance of semantic continuity to diachronic unity, but suggest a more nuanced and multifaceted relationship than originally proposed in our model. In AD, diminished life narratives that retain features of cultural life scripts are sufficient for strong subjective beliefs of self-persistence, but not for sophisticated explanations about persistence. Better semantic continuity, with the ability to weave high-quality life narratives, may scaffold the capacity to understand and explain one's diachronic unity, but this produces less surety about self-persistence. PMID:29515473

Rivastigmine transdermal patch and capsule in Alzheimer's disease: influence of disease stage on response to therapy.

PubMed

Farlow, Martin R; Grossberg, George T; Meng, Xiangyi; Olin, Jason; Somogyi, Monique

2011-12-01

The cholinesterase inhibitor rivastigmine is approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). This exploratory, hypothesis-forming analysis assessed response to rivastigmine according to severity of dementia at baseline. This was a retrospective analysis of a large randomized, placebo-controlled trial (ENA713D2320). AD patients treated with 9.5 mg/24 h rivastigmine patch, 17.4 mg/24 h rivastigmine patch, rivastigmine capsule (12 mg/day), or placebo were stratified according to baseline Mini-Mental State Examination (MMSE) scores: ≥7 to ≤12 (severe disease), ≥13 to ≤15 (moderately severe), ≥16 to ≤18 (moderate), or ≥19 to ≤25 (mild to moderate). Changes from baseline at Week 24 on Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) were assessed. Based on baseline MMSE scores, 141, 228, 333, and 348 patients had severe, moderately severe, moderate, and mild to moderate dementia. Worsening of ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients receiving placebo were greater in patients with more severe dementia. Significant improvements versus placebo were seen with rivastigmine patch and/or capsule on ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients with severe, moderately severe, and moderate AD (all p < 0.05). However, no significant improvements were seen in rivastigmine-treated patients with mild to moderate AD. Rivastigmine benefits AD patients across dementia stages. Similar to previous cholinesterase inhibitor studies, greatest treatment effects with rivastigmine patch and capsule were seen in patients with more advanced dementia, most likely driven by greater placebo decline in this population. Copyright © 2010 John Wiley & Sons, Ltd.

The relationship between 3D morphology of optic disc and spatial patterns of visual field loss in glaucoma

NASA Astrophysics Data System (ADS)

Wang, Mengyu; Wang, Hui; Baniasadi, Neda; Elze, Tobias

2017-02-01

Purpose: Optic disc tilt defined over 3D optic disc morphology has been shown to be associated with the location of initial glaucomatous damages. In this work, we study the impact of optic cup depth (OCD) on spatial patterns of visual field loss in glaucoma. Methods: Pairs of reliable Cirrus OCT scans around optic disc and Humphrey visual fields of glaucoma patients without visually significant cataract and age-related macular degeneration were selected. The most recent visit of a randomly selected eye of each patient was chosen. The OCD was automatically calculated on the superior-inferior cross sectional image passing through the optic disc center. The correlations between the mean pattern deviation (PD) of each sector in glaucoma hemifield test (GHT) and Garway-Heath scheme and OCD were evaluated for all severities glaucoma and mild glaucoma (mean deviation >= -5 dB), respectively. Results: 424 eyes of 424 patients passed the data reliability criteria with 346 mild glaucoma patients. For all severities glaucoma, there was no significant correlation between the mean sector PD and OCD. For mild glaucoma, OCD was uniquely correlated to the mean PD of the inferior pericentral sector (r=-0.18, p=0.01) in GHT, which was independent of mean deviation and retinal nerve fiber layer thickness (p<0.001 for both). Conclusion: OCD was uniquely correlated to the vision loss of the inferior pericentral sector in GHT and Garway- Health scheme for mild glaucoma. Future advancement of OCT imaging techniques may provide better clinical diagnosis for early glaucoma by focusing on 3D morphological variation of the optic disc.

Efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% formulation for the treatment of acne vulgaris: pooled analysis of data from three randomised, double-blind, parallel-group, phase III studies.

PubMed

Dréno, Brigitte; Bettoli, Vincenzo; Ochsendorf, Falk; Layton, Alison M; Perez, Montserrat; Dakovic, Rada; Gollnick, Harald

2014-01-01

The efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% (Clin-RA) were evaluated in three 12-week randomised studies. To perform a pooled analysis of data from these studies to evaluate Clin-RA's efficacy and safety in a larger overall population, in subgroups of adolescents and according to acne severity. 4550 patients were randomised to Clin-RA, clindamycin, tretinoin and vehicle. Evaluations included percentage change in lesions, treatment success rate, proportions of patients with ≥50% or ≥80% continuous reduction in lesions, adverse events and cutaneous tolerability. In the overall population, the percentage reduction in inflammatory, non-inflammatory and total lesions and the treatment success rate were significantly greater with Clin-RA compared with clindamycin, tretinoin and vehicle alone (all p<0.01). The percentage reduction in all types of lesions was also significantly greater with Clin-RA in the adolescent subgroup (2915 patients, p<0.002) and in patients with mild/moderate acne (3662 patients, p<0.02) versus comparators. In patients with severe acne (n = 880), the percentage reduction in all lesion types was significantly greater with Clin-RA versus vehicle (p<0.0001). A greater proportion of Clin-RA treated patients had a ≥50% or ≥80% continuous reduction in all types of lesions at week 12 compared with clindamycin, tretinoin and vehicle. Adverse event frequencies in the active and vehicle groups were similar. Baseline-adjusted mean tolerability scores over time were <1 (mild) and similar in all groups. Clin-RA is safe, has superior efficacy to its component monotherapies and should be considered as one of the first-line therapies for mild-to-moderate facial acne.

A sigh of relief or a sigh of expected relief: Sigh rate in response to dyspnea relief.

PubMed

Vlemincx, Elke; Meulders, Michel; Luminet, Olivier

2018-02-01

Research has suggested that sighs may serve a regulatory function during stress and emotions by facilitating relief. Evidence supports the hypotheses that sighs both express and induce relief from stress. To explore the potential role of sighs in the regulation of symptoms, the present study aimed to investigate the relationship between sighs and relief of symptoms, and relief of dyspnea, specifically. Healthy volunteers participated in two studies (N = 44, N = 47) in which dyspnea was induced by mild (10 cmH 2 O/l/s) or high (20 cmH 2 0/l/s) inspiratory resistances. Dyspnea relief was induced by the offset of the inspiratory resistances (transitions from high and mild inspiratory resistance to no resistance). Control comparisons included dyspnea increases (transitions from no or mild inspiratory resistance to high inspiratory resistance) and dyspnea continuations (continuations of either no resistance or a high resistance). In Experiment 1, dyspnea levels were cued. In Experiment 2, no cues were provided. Sigh rate during dyspnea relief was significantly higher compared to control conditions, and sigh rate increased as self-reported dyspnea decreased. Additionally, sigh rate was higher during cued dyspnea relief compared to noncued dyspnea relief. These results suggest that sighs are important markers of dyspnea relief. Moreover, sighs may importantly express dyspnea relief, as they are related to experiential dyspnea decreases and occur more frequently during expected dyspnea relief. These findings suggest that sighs may not only be important in the regulation of stress and emotions, but also may be functional in the regulation of dyspnea. © 2017 Society for Psychophysiological Research.

Medical-School Partnership in Guiding Return to School Following Mild Traumatic Brain Injury in Youth

PubMed Central

Gioia, Gerard A.

2015-01-01

Mild traumatic brain injury (mTBI) is recognized as a prevalent and significant risk concern for youth. Appropriate school return is particularly challenging. The medical and school systems must be prepared partners to support the school return of the student with mTBI. Medical providers must be trained in assessment and management skills with a focused understanding of school demands. Schools must develop policies and procedures to prepare staff to support a gradual return process with the necessary academic accommodations. Ongoing communication between the family, student, school, and medical provider is essential to supporting recovery. A systematic gradual return to school process is proposed including levels of recommended activity and criteria for advancement. Targets for intervention are described with associated strategies for supporting recovery. A ten element PACE model for activity-exertion management is introduced to manage symptom exacerbation. A strong medical-school partnership will maximize outcomes for students with mTBI. PMID:25535055

[Mental disorders due to brain lesions in the DSM-5 in the light of the previous versions].

PubMed

Derouesné, Christian

2013-12-01

The DSM-5 introduces major modifications in the category of mental disorders due to brain lesions compared to the previous DSM versions, which are reviewed in this paper. The description of the category Major neurocognitive disorder, as a substitute for dementia, seems to fit better for patients and families, and more adapted to many neurodegenerative cognitive disorders for which memory impairment is not predominant. Similarly, the introduction of the category of Mild neurocognitive disorder appears to be an improvement although some difficulty still remains for distinguishing mild cognitive disorder from normal aging. The addition of new etiological categories such as fronto-temporal NCD or NCD with Lewy bodies should also to be considered as a significant improvement. Despite these advances, to circumscribe the mental disorders due to brain lesions to cognitive deficits and biological mechanisms remains highly questionable, and does not provide an adequate care for the patients and families if not complemented by a psychological and environmental approach.

Emerging MRI and metabolic neuroimaging techniques in mild traumatic brain injury.

PubMed

Lu, Liyan; Wei, Xiaoer; Li, Minghua; Li, Yuehua; Li, Wenbin

2014-01-01

Traumatic brain injury (TBI) is one of the leading causes of death worldwide, and mild traumatic brain injury (mTBI) is the most common traumatic injury. It is difficult to detect mTBI using a routine neuroimaging. Advanced techniques with greater sensitivity and specificity for the diagnosis and treatment of mTBI are required. The aim of this review is to offer an overview of various emerging neuroimaging methodologies that can solve the clinical health problems associated with mTBI. Important findings and improvements in neuroimaging that hold value for better detection, characterization and monitoring of objective brain injuries in patients with mTBI are presented. Conventional computed tomography (CT) and magnetic resonance imaging (MRI) are not very efficient for visualizing mTBI. Moreover, techniques such as diffusion tensor imaging, magnetization transfer imaging, susceptibility-weighted imaging, functional MRI, single photon emission computed tomography, positron emission tomography and magnetic resonance spectroscopy imaging were found to be useful for mTBI imaging.

CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society

PubMed Central

Austin, John H. M.; Hogg, James C.; Grenier, Philippe A.; Kauczor, Hans-Ulrich; Bankier, Alexander A.; Barr, R. Graham; Colby, Thomas V.; Galvin, Jeffrey R.; Gevenois, Pierre Alain; Coxson, Harvey O.; Hoffman, Eric A.; Newell, John D.; Pistolesi, Massimo; Silverman, Edwin K.; Crapo, James D.

2015-01-01

The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis. © RSNA, 2015 PMID:25961632

New PbSnTe heterojunction laser diode structures with improved performance

NASA Technical Reports Server (NTRS)

Fonstad, C. G.; Kasemset, D.; Hsieh, H. H.; Rotter, S.

1980-01-01

Several recent advances in the state-of-the-art of lead tin telluride double heterojunction laser diodes are summarized. Continuous Wave operation to 120 K and pulsed operation to 166 K with single, lowest order transverse mode emission to in excess of four times threshold at 80 K were achieved in buried stripe lasers fabricated by liquid phase epitaxy in the lattice-matched system, lead-tin telluride-lead telluride selenide. At the same time, liquid phase epitaxy was used to produce PbSnTe distributed feedback lasers with much broader continuous single mode tuning ranges than are available from Fabry-Perot lasers. The physics and philosophy behind these advances is as important as the structures and performance of the specific devices embodying the advances, particularly since structures are continually being evolved and the performance continues to be improved.

Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics.

PubMed

Vezir, Emine; Dibek Misirlioglu, Emine; Civelek, Ersoy; Capanoglu, Murat; Guvenir, Hakan; Ginis, Tayfur; Toyran, Muge; Kocabas, Can N

2016-02-01

Skin testing has a limited role in the diagnosis of non-immediate beta-lactam hypersensitivity in children. The aim of this study was to report the results of oral provocation tests performed without skin tests in children with non-immediate mild cutaneous reactions without systemic symptoms caused by beta-lactam antibiotics. Oral provocation tests with suspected antibiotics were performed to patients with non-immediate mild cutaneous reactions without systemic symptoms caused by beta-lactam antibiotics. Skin tests were not performed before provocation tests. A total of five doses were administered with half-an-hour intervals in increasing doses. Provocation was continued for 5 days. A total of 119 patients with a median age of 4.3 (IQR: 2-7.5) years, of whom 58% were males, were included in the study. Amoxicillin-clavulanic acid was the most frequently responsible agent in 87 (73.1%) patients, and most common type of rash was maculopapular in 74 (62.2%) patients. Four patients (3.4%) had an urticarial reaction during the provocation test. We did not experience any severe reactions during oral provocation test without previous skin tests performed to children with non-immediate mild cutaneous reactions without systemic symptoms. Omitting skin tests before oral provocation test in this group of children can help decreasing the burden of allergy clinics and alleviating the discomfort of children. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis.

PubMed

Eichenfield, Lawrence F; Call, Robert S; Forsha, Douglass W; Fowler, Joseph; Hebert, Adelaide A; Spellman, Mary; Stein Gold, Linda F; Van Syoc, Merrie; Zane, Lee T; Tschen, Eduardo

2017-10-01

Long-term topical treatment is often required for atopic dermatitis (AD), a chronic inflammatory skin disease. To assess the long-term safety results from a multicenter, open-label, 48-week safety study (AD-303) of patients (N = 517) ≥2 years of age with mild to moderate AD who continued crisaborole treatment, a topical phosphodiesterase-4 inhibitor, after completing a 28-day phase 3 pivotal study (AD-301, AD-302). Global disease severity was assessed in patients every 4 weeks, and if assessed as mild or greater, a 28-day treatment period with crisaborole applied twice daily was initiated. Adverse events (AEs), including treatment-emergent AEs (TEAEs), and serious AEs were analyzed. During the pivotal studies and AD-303, 65% of patients reported ≥1 TEAE, most of which were mild (51.2%) or moderate (44.6%) and considered unrelated to treatment (93.1%). The frequency and severity of TEAEs were consistent. The most frequently reported treatment-related AEs (overall, 10.2%) were dermatitis atopic (3.1%), application-site pain (2.3%), and application-site infection (1.2%). Nine patients (1.7%) discontinued the long-term study because of TEAEs. Long-term efficacy was not analyzed. Crisaborole ointment had a low frequency of treatment-related AEs over 48 weeks of treatment of patients with AD. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Long-term effect of budesonide on hypothalamic-pituitary-adrenal axis function in children with mild to moderate asthma.

PubMed

Bacharier, Leonard B; Raissy, Hengameh H; Wilson, Laura; McWilliams, Bennie; Strunk, Robert C; Kelly, H William

2004-06-01

To determine the safety of long-term (36 months) administration of an inhaled corticosteroid (budesonide) on hypothalamic-pituitary-adrenal (HPA) axis function in children with mild to moderate asthma. This was an ancillary study of the Childhood Asthma Management Program (CAMP). Sixty-three children who had mild to moderate asthma and were enrolled in CAMP underwent evaluation of HPA axis function before and 12 and 36 months after receiving continuous therapy with either an inhaled anti-inflammatory agent (budesonide 400 microg/day or nedocromil 16 mg/day) or placebo. HPA axis function was assessed by serum cortisol levels 30 and 60 minutes after 0.25 mg of adrenocorticotrophic hormone (ACTH) and 24-hour urinary free cortisol excretion. There were no differences in serum cortisol levels after ACTH stimulation between treatment groups, regardless of time after ACTH administration or months of follow-up. Urinary cortisol excretion per body surface area was similar in both treatment groups at 36 months, after adjusting for age at randomization, race, gender, and clinic. Cumulative inhaled corticosteroid exposure did not influence serum cortisol response to ACTH or urinary free cortisol excretion at 36 months. We found no effects of chronic budesonide treatment at a dose of 400 micro g/day on HPA axis function in children with mild to moderate asthma and demonstrated the absence of a cumulative effect on HPA axis function over a 3-year period.

Bacterial Stressors in Minimally Processed Food

PubMed Central

Capozzi, Vittorio; Fiocco, Daniela; Amodio, Maria Luisa; Gallone, Anna; Spano, Giuseppe

2009-01-01

Stress responses are of particular importance to microorganisms, because their habitats are subjected to continual changes in temperature, osmotic pressure, and nutrients availability. Stressors (and stress factors), may be of chemical, physical, or biological nature. While stress to microorganisms is frequently caused by the surrounding environment, the growth of microbial cells on its own may also result in induction of some kinds of stress such as starvation and acidity. During production of fresh-cut produce, cumulative mild processing steps are employed, to control the growth of microorganisms. Pathogens on plant surfaces are already stressed and stress may be increased during the multiple mild processing steps, potentially leading to very hardy bacteria geared towards enhanced survival. Cross-protection can occur because the overlapping stress responses enable bacteria exposed to one stress to become resistant to another stress. A number of stresses have been shown to induce cross protection, including heat, cold, acid and osmotic stress. Among other factors, adaptation to heat stress appears to provide bacterial cells with more pronounced cross protection against several other stresses. Understanding how pathogens sense and respond to mild stresses is essential in order to design safe and effective minimal processing regimes. PMID:19742126

Low-heat, mild alkaline pretreatment of switchgrass for anaerobic digestion.

PubMed

Jin, Guang; Bierma, Tom; Walker, Paul M

2014-01-01

This study examines the effectiveness of alkaline pretreatment under mild heat conditions (100°C or 212°F) on the anaerobic co-digestion of switchgrass. The effects of alkaline concentration, types of alkaline, heating time and rinsing were evaluated. In addition to batch studies, continuous-feed studies were performed in triplicate to identify potential digester operational problems caused by switchgrass co-digestion while accounting for uncertainty due to digester variability. Few studies have examined anaerobic digestion of switchgrass or the effects of mild heating to enhance alkaline pretreatment prior to biomass digestion. Results indicate that pretreatment can significantly enhance digestion of coarse-ground (≤ 0.78 cm particle size) switchgrass. Energy conversion efficiency as high as 63% was observed, and was comparable or superior to fine-grinding as a pretreatment method. The optimal NaOH concentration was found to be 5.5% (wt/wt alkaline/biomass) with a 91.7% moisture level. No evidence of operational problems such as solids build-up, poor mixing, or floating materials were observed. These results suggest the use of waste heat from a generator could reduce the concentration of alkaline required to adequately pretreat lignocellulosic feedstock prior to anaerobic digestion.

Conceptualizing a Framework for Advanced Placement Statistics Teaching Knowledge

ERIC Educational Resources Information Center

Haines, Brenna

2015-01-01

The purpose of this article is to sketch a conceptualization of a framework for Advanced Placement (AP) Statistics Teaching Knowledge. Recent research continues to problematize the lack of knowledge and preparation among secondary level statistics teachers. The College Board's AP Statistics course continues to grow and gain popularity, but is a…

Road map to esophagectomy for nurses.

PubMed

Logue, Barbara; Griffin, Scott

2011-08-01

Esophageal cancer, although considered uncommon in the United States, continues to exhibit increased incidence. Esophageal cancer now ranks seventh among cancers in mortality for men in the United States. Even as treatment continues to advance, the mortality rate remains high, with a 5-year survival rate less than 35%. Esophageal cancer typically is discovered in advanced stages, which reduces the treatment options. When disease is locally advanced, esophagectomy remains the standard for treatment. Surgery remains challenging and complicated. Multiple surgical approaches are available, with the choice determined by tumor location and stage of disease. Recovery is often fraught with complications-both physical and emotional. Nursing care revolves around complex care managing multiple body systems and providing effective education and emotional support for both patients and patients' families. Even after recovery, local recurrence and distant metastases are common. Early diagnosis, surgical advancement, and improvements in postoperative care continue to improve outcomes.

Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

PubMed

Leone, B; Vallejo, C; Perez, J; Cuevas, M A; Machiavelli, M; Lacava, J; Focaccia, G; Ferreyra, R; Suttora, G; Romero, A; Castaldi, J; Arroyo, A; Rabinovich, M

1996-04-01

A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

The Characterization of Biological Rhythms in Mild Cognitive Impairment

PubMed Central

Díaz-Mardomingo, Carmen; García-Herranz, Sara; Pereda-Pérez, Inmaculada; Peraita, Herminia; Venero, César; Madrid, Juan Antonio; Rol, Maria Angeles

2014-01-01

Introduction. Patients with dementia, especially Alzheimer's disease, present several circadian impairments related to an accelerated perturbation of their biological clock that is caused by the illness itself and not merely age-related. Thus, the objective of this work was to elucidate whether these circadian system alterations were already present in patients with mild cognitive impairment (MCI), as compared to healthy age-matched subjects. Methods. 40 subjects (21 patients diagnosed with MCI, 74.1 ± 1.5 y.o., and 19 healthy subjects, 71.7 ± 1.4 y.o.) were subjected to ambulatory monitoring, recording wrist skin temperature, motor activity, body position, and the integrated variable TAP (including temperature, activity, and position) for one week. Nonparametrical analyses were then applied. Results. MCI patients exhibited a significant phase advance with respect to the healthy group for the following phase markers: temperature M5 (mean ± SEM: 04:20 ± 00:21 versus 02:52 ± 00:21) and L10 (14:35 ± 00:27 versus 13:24 ± 00:16) and TAP L5 (04:18 ± 00:14 versus 02:55 ± 00:30) and M10 (14:30 ± 00:18 versus 13:28 ± 00:23). Conclusions. These results suggest that significant advances in the biological clock begin to occur in MCI patients, evidenced by an accelerated aging of the circadian clock, as compared to a healthy population of the same age. PMID:25157363

Barriers to mental health treatment: results from the WHO World Mental Health surveys.

PubMed

Andrade, L H; Alonso, J; Mneimneh, Z; Wells, J E; Al-Hamzawi, A; Borges, G; Bromet, E; Bruffaerts, R; de Girolamo, G; de Graaf, R; Florescu, S; Gureje, O; Hinkov, H R; Hu, C; Huang, Y; Hwang, I; Jin, R; Karam, E G; Kovess-Masfety, V; Levinson, D; Matschinger, H; O'Neill, S; Posada-Villa, J; Sagar, R; Sampson, N A; Sasu, C; Stein, D J; Takeshima, T; Viana, M C; Xavier, M; Kessler, R C

2014-04-01

To examine barriers to initiation and continuation of mental health treatment among individuals with common mental disorders. Data were from the World Health Organization (WHO) World Mental Health (WMH) surveys. Representative household samples were interviewed face to face in 24 countries. Reasons to initiate and continue treatment were examined in a subsample (n = 63,678) and analyzed at different levels of clinical severity. Among those with a DSM-IV disorder in the past 12 months, low perceived need was the most common reason for not initiating treatment and more common among moderate and mild than severe cases. Women and younger people with disorders were more likely to recognize a need for treatment. A desire to handle the problem on one's own was the most common barrier among respondents with a disorder who perceived a need for treatment (63.8%). Attitudinal barriers were much more important than structural barriers to both initiating and continuing treatment. However, attitudinal barriers dominated for mild-moderate cases and structural barriers for severe cases. Perceived ineffectiveness of treatment was the most commonly reported reason for treatment drop-out (39.3%), followed by negative experiences with treatment providers (26.9% of respondents with severe disorders). Low perceived need and attitudinal barriers are the major barriers to seeking and staying in treatment among individuals with common mental disorders worldwide. Apart from targeting structural barriers, mainly in countries with poor resources, increasing population mental health literacy is an important endeavor worldwide.

Barriers to Mental Health Treatment: Results from the WHO World Mental Health (WMH) Surveys

PubMed Central

Andrade, L. H.; Alonso, J.; Mneimneh, Z.; Wells, J. E.; Al-Hamzawi, A.; Borges, G.; Bromet, E.; Bruffaerts, R.; de Girolamo, G.; de Graaf, R.; Florescu, S.; Gureje, O.; Hinkov, H. R.; Hu, C.; Huang, Y.; Hwang, I.; Jin, R.; Karam, E. G.; Kovess-Masfety, V.; Levinson, D.; Matschinger, H.; O’Neill, S.; Posada-Villa, J.; Sagar, R.; Sampson, N. A.; Sasu, C.; Stein, D.; Takeshima, T.; Viana, M. C.; Xavier, M.; Kessler, R. C.

2014-01-01

Background To examine barriers to initiation and continuation of mental health treatment among individuals with common mental disorders. Methods Data are from the WHO World Mental Health (WMH) Surveys. Representative household samples were interviewed face-to-face in 24 countries. Reasons to initiate and continue treatment were examined in a subsample (n= 63,678) and analyzed at different levels of clinical severity. Results Among those with a DSM-IV disorder in the past twelve months, low perceived need was the most common reason for not initiating treatment and more common among moderate and mild than severe cases. Women and younger people with disorders were more likely to recognize a need for treatment. Desire to handle the problem on one’s own was the most common barrier among respondents with a disorder who perceived a need for treatment (63.8%). Attitudinal barriers were much more important than structural barriers both to initiating and continuing treatment. However, attitudinal barriers dominated for mild-moderate cases and structural barriers for severe cases. Perceived ineffectiveness of treatment was the most commonly reported reason for treatment dropout (39.3%) followed by negative experiences with treatment providers (26.9% of respondents with severe disorders). Conclusions Low perceived need and attitudinal barriers are the major barriers to seeking and staying in treatment among individuals with common mental disorders worldwide. Apart from targeting structural barriers, mainly in countries with poor resources, increasing population mental health literacy is an important endeavor worldwide. PMID:23931656

Neuromuscular rate of force development deficit in Parkinson disease.

PubMed

Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

2017-06-01

Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

Characteristic MR image finding of squatting exercise-induced rhabdomyolysis of the thigh muscles.

PubMed

Yeon, Eung K; Ryu, Kyung N; Kang, Hye J; Yoon, So H; Park, So Y; Park, Ji S; Jin, Wook

2017-04-01

To describe the characteristic MRI appearance of squatting-induced rhabdomyolysis involving the thigh muscles. This study consisted of 10 cases obtained at 3 institutions from 2005 to 2015. A retrospective review was performed to obtain clinical information and MR scans for rhabdomyolysis of the thigh muscles. MRI was analyzed according to the distribution and degree of muscle involvement; the degree was assessed and graded as normal, mild or prominent. The mean patient age was 20.2 years (range, 15-24 years), and 7 of the 10 patients were male. All patients had history of excessive squatting action, suffered clinically from bilateral thigh pain and were confirmed to have rhabdomyolysis through analysis of serum creatine kinase (CK) levels. All of the patients (10/10) exhibited diffuse mild to prominent degree involvement of the anterior thigh muscles according to fluid-sensitive MR sequences. Among the anterior thigh muscles, the rectus femoris was spared in 8 patients (8/10) and mild degree involved in 2 patients (2/10). Thus, no cases exhibited prominent degree involvement of the rectus femoris muscle. Preservation of the rectus femoris muscle on MRI in squatting-induced rhabdomyolysis may be useful for differentiating rhabdomyolysis from other aetiologies. Advances in knowledge: Preservation of rectus femoris on MRI is distinguishable finding in squatting-induced rhabdomyolysis and reflects the functional anatomy of anterior thigh muscles.

Characteristic MR image finding of squatting exercise-induced rhabdomyolysis of the thigh muscles

PubMed Central

Yeon, Eung K; Kang, Hye J; Yoon, So H; Park, So Y; Park, Ji S; Jin, Wook

2017-01-01

Objective: To describe the characteristic MRI appearance of squatting-induced rhabdomyolysis involving the thigh muscles. Methods: This study consisted of 10 cases obtained at 3 institutions from 2005 to 2015. A retrospective review was performed to obtain clinical information and MR scans for rhabdomyolysis of the thigh muscles. MRI was analyzed according to the distribution and degree of muscle involvement; the degree was assessed and graded as normal, mild or prominent. Results: The mean patient age was 20.2 years (range, 15–24 years), and 7 of the 10 patients were male. All patients had history of excessive squatting action, suffered clinically from bilateral thigh pain and were confirmed to have rhabdomyolysis through analysis of serum creatine kinase (CK) levels. All of the patients (10/10) exhibited diffuse mild to prominent degree involvement of the anterior thigh muscles according to fluid-sensitive MR sequences. Among the anterior thigh muscles, the rectus femoris was spared in 8 patients (8/10) and mild degree involved in 2 patients (2/10). Thus, no cases exhibited prominent degree involvement of the rectus femoris muscle. Conclusion: Preservation of the rectus femoris muscle on MRI in squatting-induced rhabdomyolysis may be useful for differentiating rhabdomyolysis from other aetiologies. Advances in knowledge: Preservation of rectus femoris on MRI is distinguishable finding in squatting-induced rhabdomyolysis and reflects the functional anatomy of anterior thigh muscles. PMID:28181821

Efficacy and safety of faldaprevir, deleobuvir, and ribavirin in treatment-naive patients with chronic hepatitis C virus infection and advanced liver fibrosis or cirrhosis.

PubMed

Zeuzem, Stefan; Soriano, Vicente; Asselah, Tarik; Gane, Edward J; Bronowicki, Jean-Pierre; Angus, Peter; Lohse, Ansgar W; Stickel, Felix; Müllhaupt, Beat; Roberts, Stuart; Schuchmann, Marcus; Manns, Michael; Bourlière, Marc; Buti, Maria; Stern, Jerry O; Gallivan, John-Paul; Voss, Florian; Sabo, John P; Böcher, Wulf; Mensa, Federico J

2015-02-01

Patients with advanced hepatic fibrosis or cirrhosis with chronic hepatitis C virus (HCV) infection represent an unmet need. The HCV NS3/4A inhibitor, faldaprevir, was evaluated in combination with the nonnucleoside NS5B inhibitor, deleobuvir, with or without ribavirin in treatment-naive patients with HCV genotype 1 infection in the SOUND-C2 study. Here, the efficacy and safety of this interferon-free regimen in a subset of patients with advanced liver fibrosis, including those with compensated cirrhosis, were assessed. Patients (n=362) were randomized to once-daily faldaprevir with either twice-daily (BID) or three-times-daily (TID) deleobuvir for 16 (TID16W), 28 (TID28W and BID28W), or 40 (TID40W) weeks with or without ribavirin (TID28W-NR). Patients were classified according to fibrosis stage (F0 to F2 versus F3 to F4) and the presence of cirrhosis (yes/no). In total, 85 (24%) patients had advanced fibrosis/cirrhosis (F3 to F4) and 33 (9%) had cirrhosis. Within each treatment arm, differences in rates of sustained virologic response 12 weeks after completion of treatment (SVR12) between patients with mild to moderate fibrosis (F0 to F2) versus F3 to F4 did not show a consistent pattern and were not statistically significant (63% versus 47% for TID16W, 53% versus 76% for TID28W, 48% versus 67% for TID40W, 70% versus 67% for BID28W, and 40% versus 36% for TID28W-NR, respectively; P > 0.05 for each arm). The most frequent adverse events in patients with/without cirrhosis were gastrointestinal and skin events, which were mostly mild or moderate in intensity. The degree of liver fibrosis did not appear to affect the probability of achieving SVR12 following treatment with the interferon-free regimen of faldaprevir, deleobuvir, and ribavirin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01132313.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Efficacy and Safety of Faldaprevir, Deleobuvir, and Ribavirin in Treatment-Naive Patients with Chronic Hepatitis C Virus Infection and Advanced Liver Fibrosis or Cirrhosis

PubMed Central

Soriano, Vicente; Asselah, Tarik; Gane, Edward J.; Bronowicki, Jean-Pierre; Angus, Peter; Lohse, Ansgar W.; Stickel, Felix; Müllhaupt, Beat; Roberts, Stuart; Schuchmann, Marcus; Manns, Michael; Bourlière, Marc; Buti, Maria; Stern, Jerry O.; Gallivan, John-Paul; Voss, Florian; Sabo, John P.; Böcher, Wulf; Mensa, Federico J.

2014-01-01

Patients with advanced hepatic fibrosis or cirrhosis with chronic hepatitis C virus (HCV) infection represent an unmet need. The HCV NS3/4A inhibitor, faldaprevir, was evaluated in combination with the nonnucleoside NS5B inhibitor, deleobuvir, with or without ribavirin in treatment-naive patients with HCV genotype 1 infection in the SOUND-C2 study. Here, the efficacy and safety of this interferon-free regimen in a subset of patients with advanced liver fibrosis, including those with compensated cirrhosis, were assessed. Patients (n = 362) were randomized to once-daily faldaprevir with either twice-daily (BID) or three-times-daily (TID) deleobuvir for 16 (TID16W), 28 (TID28W and BID28W), or 40 (TID40W) weeks with or without ribavirin (TID28W-NR). Patients were classified according to fibrosis stage (F0 to F2 versus F3 to F4) and the presence of cirrhosis (yes/no). In total, 85 (24%) patients had advanced fibrosis/cirrhosis (F3 to F4) and 33 (9%) had cirrhosis. Within each treatment arm, differences in rates of sustained virologic response 12 weeks after completion of treatment (SVR12) between patients with mild to moderate fibrosis (F0 to F2) versus F3 to F4 did not show a consistent pattern and were not statistically significant (63% versus 47% for TID16W, 53% versus 76% for TID28W, 48% versus 67% for TID40W, 70% versus 67% for BID28W, and 40% versus 36% for TID28W-NR, respectively; P > 0.05 for each arm). The most frequent adverse events in patients with/without cirrhosis were gastrointestinal and skin events, which were mostly mild or moderate in intensity. The degree of liver fibrosis did not appear to affect the probability of achieving SVR12 following treatment with the interferon-free regimen of faldaprevir, deleobuvir, and ribavirin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01132313.) PMID:25512403

19 CFR 181.94 - Nonconforming requests for advance rulings.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Nonconforming requests for advance rulings. 181.94...; DEPARTMENT OF THE TREASURY (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Advance Ruling Procedures § 181.94 Nonconforming requests for advance rulings. A person submitting a request for an advance ruling that does not...

19 CFR 181.97 - Withdrawal of NAFTA advance ruling requests.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal of NAFTA advance ruling requests. 181...; DEPARTMENT OF THE TREASURY (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Advance Ruling Procedures § 181.97 Withdrawal of NAFTA advance ruling requests. Any request for an advance ruling may be withdrawn by the person...

Cross-reacting Material-positive Hemophilia A Diagnosed in a Patient with a Spontaneous Thigh Hemorrhage

PubMed Central

Saito, Tatsuya; Mukae, Jyunichi; Nakamura, Yosuke; Inaba, Hiroshi; Nogami, Keiji; Koyama, Takatoshi; Fukutake, Katsuyuki; Yamamoto, Koh

2017-01-01

A 53-year-old man, who had been diagnosed with mild hemophilia A (HA) at 35 years of age, was hospitalized with a thigh hematoma. His bleeding continued despite the administration of recombinant factor VIII (FVIII). The results of an FVIII/von Willebrand factor binding assay were normal. The patient's FVIII coagulant activity (FVIII:C) was low, but his FVIII antigen levels were within the normal limits, suggesting FVIII protein dysfunction. The FVIII:C measurements obtained by one-stage clotting and chromogenic assays were different. An FVIII gene analysis revealed a missense mutation p.Ser308Leu, which is rare in Japan. This case highlights that gene analyses and chromogenic assays are necessary to interpret the discrepancies between FVIII:C and the bleeding phenotype of patients with mild HA. PMID:28674365

Nonsurgical Treatment of Hemifacial Microsomia: A Case Report.

PubMed

Nouri, Mahtab; Farzan, Arash

2015-11-01

Hemifacial microsomia (HFM) is a birth defect involving craniofacial structures derived from the first and second branchial arches. Although it is a relatively uncommon malformation, it is the second most common craniofacial birth defect after cleft lip and palate (CL/P). This is a case report about the successful orthodontic treatment of a patient with mild hemifacial microsomia (HFM), using a non-surgical orthopedic and orthodontic treatment approach. The aim of this approach was to make the best noninvasive modality to treat HFM. A 7-year-old boy with a mild HFM presented with a convex profile and slight chin deviation. Orthopedic treatment performed using a hybrid functional and high pulls headgear. Treatment continued by fixed orthodontic straight wire appliance to achieve perfect occlusion. Excellent esthetic and functional results achieved; total treatment duration was about 72 months.

Cross-reacting Material-positive Hemophilia A Diagnosed in a Patient with a Spontaneous Thigh Hemorrhage.

PubMed

Saito, Tatsuya; Mukae, Jyunichi; Nakamura, Yosuke; Inaba, Hiroshi; Nogami, Keiji; Koyama, Takatoshi; Fukutake, Katsuyuki; Yamamoto, Koh

2017-01-01

A 53-year-old man, who had been diagnosed with mild hemophilia A (HA) at 35 years of age, was hospitalized with a thigh hematoma. His bleeding continued despite the administration of recombinant factor VIII (FVIII). The results of an FVIII/von Willebrand factor binding assay were normal. The patient's FVIII coagulant activity (FVIII:C) was low, but his FVIII antigen levels were within the normal limits, suggesting FVIII protein dysfunction. The FVIII:C measurements obtained by one-stage clotting and chromogenic assays were different. An FVIII gene analysis revealed a missense mutation p.Ser308Leu, which is rare in Japan. This case highlights that gene analyses and chromogenic assays are necessary to interpret the discrepancies between FVIII:C and the bleeding phenotype of patients with mild HA.

A qualitative study protocol of ageing carers' caregiving experiences and their planning for continuation of care for their immediate family members with intellectual disability.

PubMed

Low, Lisa Pau Le; Chien, Wai Tong; Lam, Lai Wah; Wong, Kayla Ka Yin

2017-04-07

Understanding the difficulties and needs of the family carers in taking care of a person with ID can facilitate the development of appropriate intervention programmes and services to strengthen their caring capacity and empower them to continue with their caring roles. This study aims to explore ageing family carers' caregiving experiences and the plans they have to provide care for themselves and their ageing children with mild or moderate intellectual disability (ID). A constructivist grounded theory will be used to interview around 60 carers who have a family member with mild or moderate ID and attending sheltered workshops in Hong Kong. Constant comparative analysis methods will be used for data analysis. The theory will capture family caregiving experiences and the processes of carers in addressing caregiving needs, support received and plans to continue to provide care for themselves and their relatives with ID in their later life. New insights into the emerging issues, needs and plights of family caregivers will be provided to inform the policies and practices of improving the preparation for the ageing process of the persons with ID, and to better support the ageing carers. The theoretical framework that will be generated will be highly practical and useful in generating knowledge about factors that influence the caregiving processes; and, tracking the caregiving journey at different time-points to clearly delineate areas to implement practice changes. In this way, the theoretical framework will be highly useful in guiding timely and appropriate interventions to target at the actual needs of family carers as they themselves are ageing and will need to continue to take care of their family members with ID in the community.

Practical management of everolimus-related toxicities in patients with advanced solid tumors.

PubMed

Grünwald, Viktor; Weikert, Steffen; Pavel, Marianne E; Hörsch, Dieter; Lüftner, Diana; Janni, Wolfgang; Geberth, Matthias; Weber, Matthias M

2013-01-01

Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), an intracellular protein kinase downstream of the phosphatidylinositol 3-kinase/AKT pathway involved in key components of tumorigenesis, including cell growth, proliferation, and angiogenesis. In the advanced cancer setting, based on favorable results from phase III trials, everolimus is indicated for the treatment of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, and advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Additional oncology indications for everolimus include renal angiomyolipoma with tuberous sclerosis complex and subependymal giant-cell astrocytoma. Although it is generally well tolerated, with most adverse events of mild to moderate severity and manageable, everolimus exhibits a distinct adverse event profile that warrants guidance for proper diagnostic and medical management. This guidance is particularly important given the potential for widespread long-term use of everolimus. This review will focus on the most relevant toxicities associated with mTOR inhibitors and on their management. Practical treatment recommendations are presented for stomatitis, noninfectious pneumonitis, rash, selected metabolic abnormalities, and infections. Provided these events are rapidly identified and treated, the vast majority should resolve with minimal effect on treatment outcomes and patients' quality of life. Copyright © 2013 S. Karger AG, Basel.

Postoperative airway findings after maxillomandibular advancement for obstructive sleep apnea syndrome.

PubMed

Li, K K; Riley, R W; Powell, N B; Zonato, A; Troell, R; Guilleminault, C

2000-02-01

To evaluate the upper airway characteristics in the early postoperative period after maxilomandibular advancement for obstructive sleep apnea syndrome. Nasopharyngolaryngoscopy was performed before and 48 hours after surgery on 70 consecutive patients who underwent maxillomandibular advancement for obstructive sleep apnea syndrome. The preoperative and the postoperative evaluations were performed by the same examiner for consistency. Mild to moderate lateral pharyngeal wall edema was identified in 70 consecutive patients. Fourteen patients (20%) had edema as well as ecchymosis involving the pyriform sinus and aryepiglottic fold. Four of these patients (6%) were also noted to have hypopharyngeal hematoma involving the pyriform sinus, aryepiglottic fold, arytenoid, and false vocal cord that partially obstructed the airway. These four patients were closely monitored for 1 to 2 additional days for possible expanding hematoma leading to airway compromise. None of these patients were found to have airway difficulty, and the minimum oxygen saturation was more than 90% throughout the hospitalization. All four patients were discharged uneventfully, and the hematoma resolved completely within 10 days. Although postoperative edema was expected after maxillomandibular advancement, hypopharyngeal hematoma was unexpected. Although none of our patients had evidence of airway difficulty, the possibility of an expanding hypopharyngeal hematoma should be considered in patients complaining of breathing difficulty after maxillomandibular advancement surgery.

7 CFR 1980.372 - Protective advances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... or protect the physical security. Attorney fees are not a protective advance. The Lender will not... 7 Agriculture 14 2010-01-01 2009-01-01 true Protective advances. 1980.372 Section 1980.372...) PROGRAM REGULATIONS (CONTINUED) GENERAL Rural Housing Loans § 1980.372 Protective advances. Protective...

Efficacy and safety of mini-dose glucagon for treatment of nonsevere hypoglycemia in adults with type 1 diabetes

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to evaluate low-dose glucagon to treat mild hypoglycemia in ambulatory adults with type 1 diabetes (T1D). This was a randomized crossover trial (two 3-week periods) conducted at five U.S. diabetes clinics. Twenty adults with T1D using an insulin pump and continuous gluc...

Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity.

PubMed

van Leijsen, Esther M C; Bergkamp, Mayra I; van Uden, Ingeborg W M; Ghafoorian, Mohsen; van der Holst, Helena M; Norris, David G; Platel, Bram; Tuladhar, Anil M; de Leeuw, Frank-Erik

2018-05-03

White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normal-appearing white matter (NAWM) into WMH remains unknown. We examined whether and when progression of WMH was preceded by changes in fluid-attenuated inversion recovery and diffusion tensor imaging values, thereby taking into account differences between participants with mild versus severe baseline WMH. From 266 participants of the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort), we semiautomatically segmented WMH at 3 time points for 9 years. Images were registered to standard space through a subject template. We analyzed differences in baseline fluid-attenuated inversion recovery, fractional anisotropy, and mean diffusivity (MD) values and changes in MD values over time between 4 regions: (1) remaining NAWM, (2) NAWM converting into WMH in the second follow-up period, (3) NAWM converting into WMH in the first follow-up period, and (4) WMH. NAWM converting into WMH in the first or second time interval showed higher fluid-attenuated inversion recovery and MD values than remaining NAWM. MD values in NAWM converting into WMH in the first time interval were similar to MD values in WMH. When stratified by baseline WMH severity, participants with severe WMH had higher fluid-attenuated inversion recovery and MD and lower fractional anisotropy values than participants with mild WMH, in all areas including the NAWM. MD values in WMH and in NAWM that converted into WMH continuously increased over time. Impaired microstructural integrity preceded conversion into WMH and continuously declined over time, suggesting a continuous disease process of white matter integrity loss that can be detected using diffusion tensor imaging even years before WMH become visible on conventional neuroimaging. Differences in microstructural integrity between participants with mild versus severe WMH suggest heterogeneity of both NAWM and WMH, which might explain the clinical variability observed in patients with similar small vessel disease severity. © 2018 American Heart Association, Inc.

10 CFR 611.3 - Advanced technology vehicle.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Advanced technology vehicle. 611.3 Section 611.3 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM General § 611.3 Advanced technology vehicle. In order to demonstrate that a vehicle is an...

10 CFR 611.3 - Advanced technology vehicle.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Advanced technology vehicle. 611.3 Section 611.3 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM General § 611.3 Advanced technology vehicle. In order to demonstrate that a vehicle is an...

10 CFR 611.3 - Advanced technology vehicle.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Advanced technology vehicle. 611.3 Section 611.3 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM General § 611.3 Advanced technology vehicle. In order to demonstrate that a vehicle is an...

10 CFR 611.3 - Advanced technology vehicle.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Advanced technology vehicle. 611.3 Section 611.3 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM General § 611.3 Advanced technology vehicle. In order to demonstrate that a vehicle is an...

10 CFR 611.3 - Advanced technology vehicle.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Advanced technology vehicle. 611.3 Section 611.3 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM General § 611.3 Advanced technology vehicle. In order to demonstrate that a vehicle is an...

"Hope for the best, prepare for the worst": A qualitative interview study on parents' needs and fears in pediatric advance care planning.

PubMed

Lotz, Julia Desiree; Daxer, Marion; Jox, Ralf J; Borasio, Gian Domenico; Führer, Monika

2017-09-01

Pediatric advance care planning is advocated by healthcare providers because it may increase the chance that patient and/or parent wishes are respected and thus improve end-of-life care. However, since end-of-life decisions for children are particularly difficult and charged with emotions, physicians are often afraid of addressing pediatric advance care planning. We aimed to investigate parents' views and needs regarding pediatric advance care planning. We performed a qualitative interview study with parents of children who had died from a severe illness. The interviews were analyzed by descriptive and evaluation coding according to Saldaña. We conducted semi-structured interviews with 11 parents of 9 children. Maximum variation was sought regarding the child's illness, age at death, care setting, and parent gender. Parents find it difficult to engage in pediatric advance care planning but consider it important. They argue for a sensitive, individualized, and gradual approach. Hope and quality of life issues are primary. Parents have many non-medical concerns that they want to discuss. Written advance directives are considered less important, but medical emergency plans are viewed as necessary in particular cases. Continuity of care and information should be improved through regular pediatric advance care planning meetings with the various care providers. Parents emphasize the importance of a continuous contact person to facilitate pediatric advance care planning. Despite a need for pediatric advance care planning, it is perceived as challenging. Needs-adjusted content and process and continuity of communication should be a main focus in pediatric advance care planning. Future research should focus on strategies that facilitate parent engagement in pediatric advance care planning to increase the benefit for the families.

The pharmacotherapy of the HeartMate II, a continuous flow left ventricular assist device, in patients with advanced heart failure: integration of disease, device, and drug.

PubMed

Jennings, Douglas L; Chambers, Rachel M; Schillig, Jessica M

2010-10-01

Advanced heart failure continues to be a significant cause of morbidity and mortality in the US. Patients with advanced heart failure have a poor prognosis without cardiac transplantation. The use of left ventricular assist devices (LVADs) as destination therapy for these patients is therefore expected to increase in the coming years as technology advances. The HeartMate II, a continuous flow implantable device, is currently the only LVAD that has been approved by the Food and Drug Administration for destination therapy in patients with advanced heart failure. The pharmacotherapy associated with this device is very complex and, therefore, the need for expertly trained clinical pharmacists to care for this expanding patient population will also likely increase. Unfortunately, most pharmacists are unfamiliar with the effect of LVADs on the physiology and pharmacotherapy of a patient's heart failure. The purpose of this article is to give clinical pharmacists an introduction to the most common pharmacotherapeutic issues for patients with LVADs and present practical solutions for managing common drug therapy problems.

Advances in Technology in Continuing Education: Who Should Foot the Bill?

ERIC Educational Resources Information Center

Hanson, Matthew

2013-01-01

Every continuing education unit must be at the forefront of the technology boom in order to remain attractive to students and best prepare them for the work force. Unfortunately, there is a significant cost associated with technological advancement sparking the debate over who should foot the bill for innovations. This article applies the Higher…

The geology of the terrestrial planets.

USGS Publications Warehouse

Carr, M.H.

1983-01-01

During the last four years our knowledge of the geology of the terrestrial planets has advanced rapidly. The advances are particularly noticeable for Venus and Mars. Improved understanding of Venus has come largely from the Pioneer Venus mission. The period was also one of almost continuous data gathering for Mars as the Viking orbiters and landers, emplaced at the planet in 1976, continued to function. The last orbiter ran out of attitude- control gas in August of 1980 by which time about 55 000 pictures and vast amounts of infrared data had been collected. One lander continues to function and is expected to do so for several years. Only modest advances were made in the cases of Moon and Mercury, however, for little new data was acquired. -from Author

Outcome of primary trabeculotomy ab interno (Trabectome) surgery in patients with steroid-induced glaucoma

PubMed Central

Ngai, Philip; Kim, Grace; Chak, Garrick; Lin, Ken; Maeda, Masahiro; Mosaed, Sameh

2016-01-01

Abstract To determine the efficacy and safety of Trabectome surgery on patients with steroid response, ranging from ocular hypertension refractory to maximal medical therapy to the development of steroid-induced glaucoma. A nonrandomized, nonblinded, retrospective study of 20 subjects with steroid response was conducted. All 20 eyes underwent Trabectome surgery alone. Nine subjects had steroid response with unremarkable visual field, 3 had mild steroid-induced glaucoma, and 8 had advanced steroid-induced glaucoma. Outcome measures included intraocular pressure (IOP), number of glaucoma medications, need for secondary glaucoma surgery, and steroid regimen. Mann–Whitney U test was used to compare postoperative IOP and number of medications to preoperative IOP and number of medications. Kaplan–Meier was used for survival analysis, and success was defined as: IOP reduced by 20% or more on any 2 consecutive visits after 3 months; IOP ≤21 mm Hg on any 2 consecutive visits after 3 months; and no secondary glaucoma surgery. The average preoperative IOP was 33.8 ± 6.9 mm Hg and average preoperative glaucoma medication usage was 3.85 ± 0.75 medications. At 12 months, the IOP was reduced to 15.00 ± 3.46 mm Hg (P = 0.03) and glaucoma medication was reduced to 2.3 ± 1.4 (P < 0.01). The survival rate at 12 months was 93%. At 12 months, 10 patients were continued on their preoperative steroid treatments, 5 were on tapered steroid treatments, and 5 had ceased steroid treatments entirely. One patient required secondary glaucoma surgery (glaucoma drainage device). No other complications were noted. The Trabectome procedure is safe and highly effective for steroid-response glaucoma, even in the context of continued steroid treatment. PMID:27977576

THE INCIDENCE OF HYPERGLYCAEMIA IN VERY LOW BIRTH WEIGHT PRETERM NEWBORNS. RESULTS OF A CONTINUOUS GLUCOSE MONITORING STUDY--PRELIMINARY REPORT.

PubMed

Szymońska, Izabela; Jagła, Mateusz; Starzec, Katarzyna; Hrnciar, Katarzyna; Kwinta, Przemko

2015-01-01

To determine the incidence of hyperglycaemia in very low birth weight preterm newborns. To assess risk factors in hyperglycemia and outcome in groups of children with and without clinically significant hyperglycaemia. The prospective study included newborns with very low birth weight in whom the continuous glucose monitoring system was used for glucose measurements. A standardized hyperglycaemia treatment schedule was implemented and a uniform nutrition strategy introduced. The patients were divided into groups: group A--patients with under 5% of the readings over 150 mg/dL of glucose (control group), group B--patients with more than 5% of the readings over 150 mg/dL of glucose and under 5% of the readings over 180 mg/dL of glucose (mild hyperglycaemia), and group C--patients with over 5% of the readings > 180 mg/dL or on insulin treatment (moderate or severe hyperglycaemia). 63 patients were included in the study. Their mean gestational age was 27.7 weeks (SD:2.4), the mean birth weight was 1059g (SD: 262 g). Hyperglycaemia was detected in 27 (42.9%), including mild hyperglycaemia in 19 (30.2%), and moderate or severe hyperglycaemia in 8 (12.7%) neonates. Lower gestational age (p = 0.02) and higher CRIB IIscore (p < 0.01) were positively associated with hyperglycaemia. Early-onset sepsis (p < 0.01) was associated with higher glucose levels as well. A significantly higher mortality rate on the 28th day of life (p = 0.02), depending on the severity of hyperglycemia, was noted. No adverse effects related to the continuous glucose monitoring system were observed. The study confirmed the usefulness and safety of the continuous glucose monitoring system in VLBW neonates. A continuous glucose monitoring system should be used in neonatal intensive care units as a standard method.

A multidisciplinary approach for the treatment of GIST liver metastasis

PubMed Central

Radkani, Pejman; Ghersi, Marcelo M; Paramo, Juan C; Mesko, Thomas W

2008-01-01

Background Advanced gastrointestinal stromal tumors (GISTs) can metastasize and recur after a long remission period, resulting in serious morbidity, mortality, and complex management issues. Case presentation A 67-year-old woman presented with epigastric fullness, mild jaundice and weight loss with a history of a bowel resection 7 years prior for a primary GIST of the small bowel. The finding of a heterogeneous mass 15.5 cm in diameter replacing most of the left lobe of the liver by ultrasonography and CT, followed by positive cytological studies revealed a metastatic GIST. Perioperative optimization of the patient's nutritional status along with biliary drainage, and portal vein embolization were performed. Imatinib was successful in reducing the tumor size and facilitating surgical resection. Conclusion A well-planned multidisciplinary approach should be part of the standard management of advanced or metastatic GIST. PMID:18471285

Dementia resulting from traumatic brain injury

PubMed Central

Ramalho, Joana; Castillo, Mauricio

2015-01-01

Traumatic brain injury (TBI) represents a significant public health problem in modern societies. It is primarily a consequence of traffic-related accidents and falls. Other recently recognized causes include sports injuries and indirect forces such as shock waves from battlefield explosions. TBI is an important cause of death and lifelong disability and represents the most well-established environmental risk factor for dementia. With the growing recognition that even mild head injury can lead to neurocognitive deficits, imaging of brain injury has assumed greater importance. However, there is no single imaging modality capable of characterizing TBI. Current advances, particularly in MR imaging, enable visualization and quantification of structural and functional brain changes not hitherto possible. In this review, we summarize data linking TBI with dementia, emphasizing the imaging techniques currently available in clinical practice along with some advances in medical knowledge. PMID:29213985

Natural history of echocardiographic abnormalities in mucopolysaccharidosis III.

PubMed

Wilhelm, Carolyn M; Truxal, Kristen V; McBride, Kim L; Kovalchin, John P; Flanigan, Kevin M

2018-06-01

Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials. A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3). Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range. Copyright © 2018 Elsevier Inc. All rights reserved.

Mild-moderate congenital hearing loss: secular trends in outcomes across four systems of detection.

PubMed

Carew, P; Mensah, F K; Rance, G; Flynn, T; Poulakis, Z; Wake, M

2018-01-01

Universal newborn hearing screening (UNHS) targets moderate or greater hearing loss. However, UNHS also frequently detects children with mild loss that results in many receiving early treatment. The benefits of this approach are not yet established. We aimed to (i) compare language and psychosocial outcomes between four hearing loss detection systems for children aged 5-8 years with congenital mild-moderate hearing loss; (ii) determine whether age of detection predicts outcomes; and (iii) compare outcomes between children identified via well-established UNHS and the general population. Linear regression adjusted for potential confounding factors was used throughout. Via a quasi-experimental design, language and psychosocial outcomes were compared across four population-based Australian systems of hearing loss detection: opportunistic detection, born 1991-1993, n = 50; universal risk factor referral, born 2003-2005, n = 34; newly established UNHS, born 2003-2005, n = 41; and well-established UNHS, born 2007-2010, n = 21. In pooled analyses, we examined whether age of detection predicted outcomes. Outcomes were similarly compared between the current well-established UNHS system and typically developing children in the Early Language in Victoria Study, born 2003, n = 1217. Age at diagnosis and hearing aid fitting fell steadily across the four systems. For moderate losses, mean expressive language (P for trend .05) and receptive vocabulary (P for trend .06) improved across the four systems, but benefit was not obvious for mild losses. In pooled analyses, diagnosis before age six months predicted better language outcomes for moderate losses. Children with mild-moderate losses exposed to well-established UNHS continue to experience expressive language scores well below children in the general population (adjusted mean difference -8.9 points, 95% CI -14.7 to -3.1). Treatment arising from UNHS appears to be clearly benefitting children with moderate hearing losses. However, rigorous trials are needed to quantify benefits, versus costs and potential harms, of early aiding of children with mild losses. © 2017 John Wiley & Sons Ltd.

Balance and gait of adults with very mild Alzheimer disease.

PubMed

Gras, Laura Z; Kanaan, Saddam F; McDowd, Joan M; Colgrove, Yvonne M; Burns, Jeffrey; Pohl, Patricia S

2015-01-01

Studies have shown that adults with Alzheimer disease (AD) have gait and balance deficits; however, the focus has been on those with mild to severe disease. The purpose of this study was to determine whether balance and gait deficits are present in those with very mild AD. Thirteen adults (72.9±4.7 years old) with very mild AD and 13 age-matched (72.6±4.6 years old) and sex-matched (10 males and 3 females) participants in a control group without AD performed balance and gait tests. All participants were living in the community and independent in community ambulation. Participants with very mild AD had shorter times in tandem stance with eyes open (P<0.001) and with eyes closed (P=0.007) compared with participants in the control group. Those with AD also took longer to complete the Timed "Up & Go" Test (P<0.001). Gait deficits were found for those with AD as demonstrated by slower velocities in the 10-m walk at a comfortable pace (P=0.029) and on an instrumented walkway (P<0.001). Stance times were longer for those with AD (P<0.001) and step length was shorter (P=0.001). There were no group differences in the 10-m walk at a fast pace. The gait velocity of participants in the control group was faster on the instrumented walkway than in the 10-m walk at a comfortable pace (P=0.031). In contrast, the gait velocity of those with AD was significantly slower on the instrumented walkway than in the 10-m walk at a comfortable pace (P=0.024). Balance and gait deficits may be present in those in the very early stages of AD. Novel surfaces may affect gait speed in those with very mild AD. Identifying mobility deficits early in the progression of AD may provide an opportunity for early physical therapy intervention, thus promoting continued functional independence. Adults in the very early stages of AD may show signs of balance and gait deficits. Recognition of these problems early with subsequent physical therapy may slow the progression of further balance and gait dysfunction.

Diagnostic protocol for gestational diabetes mellitus (GDM) (IADPSG/ADA, 2011): influence on the occurrence of GDM and mild gestational hyperglycemia (MGH) and on the perinatal outcomes.

PubMed

Sirimarco, Mariana Pinto; Guerra, Helena Maciel; Lisboa, Eduardo Guimarães; Vernini, Joice Monalisa; Cassetari, Bianca Nicolosi; de Araujo Costa, Roberto Antonio; Rudge, Marilza Vieira Cunha; de Mattos Paranhos Calderon, Iracema

2017-01-01

In August 2011, the Specialized Center for Diabetes and Pregnancy of the Botucatu Medical School/Unesp adopted a new diagnostic protocol for gestational diabetes mellitus, recommended by the American Diabetes Association and the International Association of the Diabetes and Pregnancy Study Group. The glycemic profile was evaluated using the 75-g oral glucose tolerance test (OGTT) used to diagnose mild gestational hyperglycemia, recognized and treated in our department as gestational diabetes mellitus. The cost-effectiveness of the new guidelines and the continued need for the evaluation of the glycemic profile, as part of our Service protocol, are controversial and require further investigation. We aimed to assess the impact of the new guidelines on the evaluation of mild gestational hyperglycemia and gestational diabetes mellitus, the incidence of adverse perinatal outcomes, and the association between the 75-g OGTT and the glycemic profile for the diagnosis of mild gestational hyperglycemia. This cross-sectional study was performed identifying a convenience sample of pregnant women and their newborns. The women used our Service for diagnostic procedures, prenatal care and delivery, both before (January 2008 to August 14, 2011) and after (August 15, 2011 to December 2014) the protocol modification. The following variables were compared, following stratification according to diagnostic protocol: prevalence of gestational diabetes mellitus and mild gestational hyperglycemia, newborns large for gestational age, macrosomia, first cesarean delivery, and newborn hospital stay. Statistical analysis was performed using Poisson regression, the Student's t test, the Chi square or Fisher's exact test and risk estimate. The statistical significance threshold was set at 95% (p < 0.05). The new protocol resulted in an 85% increase in the number of women with GDM, but failed to identify 17.3% of pregnant women classified as having mild gestational hyperglycemia, despite a normal 75-g OGTT. The new guidelines did not affect perinatal outcome. These results support the validity of maintaining the glycemic profile as part of the diagnostic protocol at our hospital. Large multicenter studies with an adequate sample size are required for conclusive evidence on the cost-effectiveness of the new protocol.

10 CFR 75.44 - Timing of advance notification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Timing of advance notification. 75.44 Section 75.44 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT Advanced Notification and Expenses § 75.44 Timing of advance notification. (a) Except as provided...

10 CFR 75.44 - Timing of advance notification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Timing of advance notification. 75.44 Section 75.44 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT Advanced Notification and Expenses § 75.44 Timing of advance notification. (a) Except as provided...

Continuous but diverse advancement of spring-summer phenology in response to climate warming across the Qinghai-Tibetan Plateau

DOE PAGES

Zheng, Zhoutao; Zhu, Wenquan; Chen, Guangsheng; ...

2016-04-25

The Qinghai-Tibetan Plateau (QTP) is more vulnerable and sensitive to climate change than many other regions worldwide because of its high altitude, permafrost geography, and harsh physical environment. As a sensitive bio-indicator of climate change, plant phenology shift in this region has been intensively studied during the recent decades, primarily based on satellite-retrieved data. However, great controversy still exists regarding the change in direction and magnitudes of spring-summer phenology. Based on a large number (11,000+ records) of long-term and continuous ground observational data for various plant species, our study intended to more comprehensively assess the changing trends of spring-summer phenologymore » and their relationships with climatic change across the QTP. The results indicated a continuous advancement (–2.69 days decade –1) in spring-summer phenology from 1981 to 2011, with an even more rapid advancement during 2000–2011 (–3.13 days decade –1), which provided new field evidence for continuous advancement in spring-summer phenology across the QTP. However, diverse advancing rates in spring-summer phenology were observed for different vegetation types, thermal conditions, and seasons. The advancing trends matched well with the difference in sensitivity of spring-summer phenology to increasing temperature, implying that the sensitivity of phenology to temperature was one of the major factors influencing spring-summer phenology shifts. Besides, increased precipitation could advance the spring-summer phenology. As a result, the response of spring-summer phenology to temperature tended to be stronger from east to west across all species, while the response to precipitation showed no consistent spatial pattern.« less

Continuous but diverse advancement of spring-summer phenology in response to climate warming across the Qinghai-Tibetan Plateau

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

Zheng, Zhoutao; Zhu, Wenquan; Chen, Guangsheng

The Qinghai-Tibetan Plateau (QTP) is more vulnerable and sensitive to climate change than many other regions worldwide because of its high altitude, permafrost geography, and harsh physical environment. As a sensitive bio-indicator of climate change, plant phenology shift in this region has been intensively studied during the recent decades, primarily based on satellite-retrieved data. However, great controversy still exists regarding the change in direction and magnitudes of spring-summer phenology. Based on a large number (11,000+ records) of long-term and continuous ground observational data for various plant species, our study intended to more comprehensively assess the changing trends of spring-summer phenologymore » and their relationships with climatic change across the QTP. The results indicated a continuous advancement (–2.69 days decade –1) in spring-summer phenology from 1981 to 2011, with an even more rapid advancement during 2000–2011 (–3.13 days decade –1), which provided new field evidence for continuous advancement in spring-summer phenology across the QTP. However, diverse advancing rates in spring-summer phenology were observed for different vegetation types, thermal conditions, and seasons. The advancing trends matched well with the difference in sensitivity of spring-summer phenology to increasing temperature, implying that the sensitivity of phenology to temperature was one of the major factors influencing spring-summer phenology shifts. Besides, increased precipitation could advance the spring-summer phenology. As a result, the response of spring-summer phenology to temperature tended to be stronger from east to west across all species, while the response to precipitation showed no consistent spatial pattern.« less

Tracking Pulse Oximeter Findings Before, During and After Titration of Mandibular Advancement Devices (MAD) for Patients With Mild to Moderate Obstructive Sleep Apnea (OSA)

DTIC Science & Technology

2015-06-01

CP AP because of claustrophobia, noise, nose bleeds, dermatitis and nasal bridge sores. In many cases, these effects are due to incorrect pressure...checked for contact data in case a subject must be contacted due to scheduling problems, or some new information is learned that a subject needs to know...Subject initiated contacts via phone or email to the PI with respect to adverse events, side effects or questions will be recorded on an electronic log

Dry eye after laser in-situ keratomileusis.

PubMed

Raoof, Duna; Pineda, Roberto

2014-01-01

Laser-assisted in-situ keratomileusis (LASIK) is one of the most commonly performed refractive procedures with excellent visual outcomes. Dry eye syndrome is one of the most frequently seen complications after LASIK, with most patients developing at least some mild dry eye symptoms postoperatively. To achieve improved visual outcomes and greater patient satisfaction, it is essential to identify patients prone to dry eyes preoperatively, and initiate treatment early in the course. Enhanced understanding of the pathophysiology of post-LASIK dry eye will help advance our approach to its management.

Designing new functional cosmetic ingredients from polyglycerol, a versatile bio-based platform for improved sustainability.

PubMed

Fevola, Michael J; Sun, Frank C; York, Stacey E

Polyglycerol (PG) is a well-known cosmetic ingredient and important precursor for the synthesis of a variety of cosmetic ingredients, such as surfactants, emulsifiers, and conditioning agents for hair and skin. When derived from renewable resources, PG can provide a more sustainable platform for the development of new ingredients with improved performance in cosmetic applications. This paper will discuss recent advances in the utilization of bio-based PG ingredients as alternatives to traditional ethoxylate chemistries for mild nonionic surfactants, substantive humectants, and micellar thickeners.

Mild versus moderate stages of Alzheimer's disease: three-year outcomes in a routine clinical setting of cholinesterase inhibitor therapy.

PubMed

Wattmo, Carina; Minthon, Lennart; Wallin, Åsa K

2016-02-17

There is an increasing interest in cognitive and functional outcomes in the respective stages of Alzheimer's disease (AD) and in novel therapies particularly for the milder phases of AD. Our aim was to describe and compare various aspects of disease progression in patients with mild versus moderate AD in routine clinical practice of cholinesterase inhibitor (ChEI) therapy. This 3-year, prospective, observational, multicentre study included 1021 participants. Of these, 734 had mild AD (Mini-Mental State Examination (MMSE) score, 20-26) and 287 had moderate AD (MMSE score, 10-19) at the start of ChEI treatment. At baseline and every 6 months, patients were assessed using cognitive, global, instrumental and basic activities of daily living (ADL) scales. Potential predictors of deterioration in moderate AD were analysed using mixed-effects models. The change from baseline between participants with mild and moderate stages of AD after 3 years of ChEI therapy differed significantly on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and basic ADL, but not using the MMSE and instrumental ADL scales. Protective independent factors for better cognitive long-term outcome in the group with moderate AD were older age, higher instrumental ADL ability, no antipsychotics, usage of non-steroidal anti-inflammatory drugs/acetylsalicylic acid, living with family member, lower education and a higher mean dose of ChEI. Apolipoprotein E genotype did not influence the rates of disease progression or the longitudinal outcomes. Prediction models were provided for moderate AD. More sensitive cognitive measures, such as the ADAS-cog scale, are required to detect a possibly faster deterioration among the participants with moderate AD. This study highlighted the clinical importance of instrumental ADL evaluations in patients at a mild stage of AD, and the importance of optimizing the ChEI dose even for individuals with moderate AD. Solitary living was a risk factor for faster cognitive decline, and probably expanded the need for formal care in the group with moderate AD. The patients with more advanced AD and presumably more pronounced neuroinflammation might have additional cognitive benefits from longer-term treatment with anti-inflammatory drugs.

Advanced Traveler Information Systems (ATIS) 2.0 Precursor System: Final Report

DOT National Transportation Integrated Search

2018-03-01

Advanced Traveler Information Systems (ATIS) have experienced significant growth since their initial inception in the 1990s. Technologies have continued to evolve at a rapid pace, enabling the integration of advanced solutions for traveler informatio...

Teaching neuroimages: infant with glutaric aciduria type 1 presenting with infantile spasms and hypsarrhythmia.

PubMed

Young-Lin, Nichole; Shalev, Sarah; Glenn, Orit A; Gardner, Marisa; Lee, Chung; Wynshaw-Boris, Anthony; Gelfand, Amy A

2013-12-10

A 7-month-old boy with glutaric aciduria type 1 (GA1) presented with 1 week of clustered flexor spasms. Examination revealed mild axial hypotonia without encephalopathy. Video-EEG monitoring revealed hypsarrhythmia and infantile spasms (figure, A). MRI showed acute basal ganglia injury (figure, B). After 3 weeks of prednisolone treatment, 5-month follow-up showed continued resolution of hypsarrhythmia and spasms.

U.S. Air Force Research Technology Area Plan, FY 1989

DTIC Science & Technology

1988-09-01

Continue on reverse if necessaty and identify by block number) FIELD GROUP SUB-GROUP 19. ABSTRACT (Continue on reverse if necessary and identify by...Armstrong Aerospace Medical Research Laboratory (AAMRL) USAF School of Aerospace Medical Research Laboratory (USAFSAM) Rome Air Development Center...development of advanced weapon concepts and advance the state of the art in systems development, electromagnetic countermeasures, nuclear weapons

Determinants of parental decision to abort or continue after non-aneuploid ultrasound-detected fetal abnormalities.

PubMed

Pryde, P G; Isada, N B; Hallak, M; Johnson, M P; Odgers, A E; Evans, M I

1992-07-01

This study evaluated factors influencing the decision to abort after abnormalities in the karyotypically normal fetus were found through ultrasonography. We reviewed all pregnancies complicated by ultrasound-detected abnormalities managed on our service from April 1990 through August 1991 (N = 262). Cases with associated karyotypic abnormalities were excluded (N = 35), as were cases diagnosed after the legal gestational age limit for abortion (N = 68). The remaining 159 cases were stratified into prognosis groups of "severe," "uncertain," and "mild." The prognostic severity of the ultrasound abnormality strongly correlated with the decision to abort (P less than .0001). Rates of termination were 0, 12, and 66% in the "mild," "uncertain," and "severe" groups, respectively. The patients' age, gravidity, and parity, and the fetal gestational age at diagnosis did not differ significantly between the groups. 1) In non-aneuploid pregnancies with an ultrasound diagnosis of fetal abnormality, the major predictor of the decision to abort was the severity of fetal prognosis. 2) The gestational age at diagnosis was not an important variable in the decision to abort for fetal structural abnormalities. 3) Parents who had fetuses with abnormalities associated with uncertain prognoses usually opted to continue the pregnancy. This appeared to be particularly true for defects that were potentially correctable in utero or by neonatal intervention (even if investigational).

A behavioral rehabilitation intervention for amnestic Mild Cognitive Impairment

PubMed Central

Greenaway, Melanie C.; Hanna, Sherrie M.; Lepore, Susan W.; Smith, Glenn E.

2010-01-01

Individuals with amnestic Mild Cognitive Impairment (MCI) currently have few treatment options for combating their memory loss. The Memory Support System (MSS) is a calendar and organization system with accompanying 6-week curriculum designed for individuals with progressive memory impairment. Ability to learn the MSS and its utility were assessed in 20 participants. Participants were significantly more likely to successfully use the calendar system after training. Ninety-five percent were compliant with the MSS at training completion, and 89% continued to be compliant at follow-up. Outcome measures revealed a medium effect size for improvement in functional ability. Subjects further reported improved independence, self-confidence, and mood. This initial examination of the MSS suggests that with appropriate training, individuals with amnestic MCI can and will use a memory notebook system to help compensate for memory loss. These results are encouraging that the MSS may help with the symptoms of memory decline in MCI. PMID:18955724

Waning of maternal immunity and the impact of diseases: the example of myxomatosis in natural rabbit populations.

PubMed

Fouchet, D; Marchandeau, S; Langlais, M; Pontier, D

2006-09-07

Myxomatosis is a leporipoxvirus that infects the european rabbit, inducing a high mortality rate. Observations lead us to hypothesize that a rabbit carrying maternal antibodies (or having recovered) can be infected (or re-infected) upon being exposed (or re-exposed) to the virus. Infection will lead to mild disease, boosting host immune protection. Using a modelling approach we show that this phenomenon may lead to a difference of impact of myxomatosis according to its transmission rate. Young are exposed when they still carry maternal antibodies and develop a mild disease in high transmission populations. Our results show that the impact of myxomatosis is generally higher in epidemic situations compared to populations where the virus circulates all the year. As a consequence, waning of acquired immunity and the continuous supply of newborn along the year may reduce the impact of the disease.

Pool Boiling Heat Transfer on structured Surfaces

NASA Astrophysics Data System (ADS)

Addy, J.; Olbricht, M.; Müller, B.; Luke, A.

2016-09-01

The development in the process and energy sector shows the importance of efficient utilization of available resources to improve thermal devices. To achieve this goal, all thermal components have to be optimized continuously. Various applications of multi-phase heat and mass transfer have to be improved. Therefore, the heat transfer and the influence of surface roughness in nucleate boiling with the working fluid propane is experimentally investigated on structured mild steel tubes, because only few data are available in the literature. The mild steel tube is sandblasted to obtain different surface roughness. The measurements are carried out over wide ranges of heat flux and pressure. The experimental results are compared with correlations from literature and the effect of surface roughness on the heat transfer is discussed. It is shown that the heat transfer coefficient increases with increasing surface roughness, heat flux and reduced pressure at nucleate pool boiling.

Arthroscopic debridement of the ankle for mild to moderate osteoarthritis: a midterm follow-up study in former professional soccer players.

PubMed

Osti, Leonardo; Del Buono, Angelo; Maffulli, Nicola

2016-03-30

The aim of this study is to report the clinical and functional outcomes following arthroscopic management of anterior impingement, grade III-IV cartilage lesions, and mild to moderate osteoarthritis of the ankle in former soccer players. The study included 15 former male professional soccer players with mild to moderate degenerative changes of the ankle who had undergone arthroscopic debridement and management of secondary injuries of the ankle. Preoperatively and at the last follow-up, at an average of 7.4 years, the American Orthopaedic Foot and Ankle Society (AOFAS) and the Kaikkonen scales and visual analogue scale (VAS) assessment were administered to all patients. Ankle osteoarthritis was assessed from weightbearing anteroposterior and lateral radiographs of both ankles. At the last follow-up, the average AOFAS score had increased significantly from 48 (range, 29-69) to 86 (range, 63-94) (P < 0.0001), with good to excellent scores in 11 patients (74 %). The average Kaikkonen preoperative score of 43 (range, 28-70) had significantly improved to 85 (range, 61-95) (P < 0.0001), with good excellent scores in 11 patients (74 %). VAS values were also improved at the last follow-up. At the last appointment, only one (7 %) patient had abandoned altogether any sport, as he did not feel safe with his ankle and he felt too old to continue. Anterior ankle arthroscopy for management of mild to moderate ankle arthritis is safe, effective, and low cost and allows former athletes to safely return to ordinary daily activities and recreational sport activities.

Slight hypercalcemia is not associated with positive responses in the Comet Assay in male rat liver.

PubMed

Thiel, Anette; Hamel, Annie; Schaefer, Katrien; Cardoso, Renato; Beilstein, Paul

2017-08-01

Maintenance of physiological levels of intracellular and extracellular calcium is essential for life. Increased intracellular calcium levels are involved in cell death (apoptosis and necrosis) and are associated with positive responses in the Comet assay in vitro. In addition, high calcium and vitamin D intakes were reported to induce apoptosis in adipose tissue in obese mice and to increase DNA-migration in the Comet assay. To investigate increased serum concentration of calcium as a potential confounding factor in the regulatory Comet assay in vivo, we induced mild hypercalcemia in male Wistar rats by 3-day continuous intravenous infusion of calcium gluconate and performed the Comet assay in the liver in line with regulatory guidelines. The results of the study showed that mild increases in serum calcium concentration (up to 1.4 times above the concurrent control) and increased urinary calcium concentration (up to 27.8 times above the concurrent control) results in clinical signs like mild tremor, faster respiration rate and decreased activity in a few animals. However, under the conditions of the study, no increase in the %Tail DNA in the Comet assay and no indication of liver damage as determined by histopathological means were observed. Thus, mild increases in plasma calcium did not lead to positive results in a genotoxicity assessment by the Comet assay in the rat liver. This result is important as it confirms the reliability of this assay for regulatory evaluation of safety. Copyright © 2017 DSM Nutritional Products AG. Published by Elsevier B.V. All rights reserved.

Unobtrusive measurement of daily computer use to detect mild cognitive impairment

PubMed Central

Kaye, Jeffrey; Mattek, Nora; Dodge, Hiroko H; Campbell, Ian; Hayes, Tamara; Austin, Daniel; Hatt, William; Wild, Katherine; Jimison, Holly; Pavel, Michael

2013-01-01

Background Mild disturbances of higher order activities of daily living are present in people diagnosed with mild cognitive impairment (MCI). These deficits may be difficult to detect among those still living independently. Unobtrusive continuous assessment of a complex activity such as home computer use may detect mild functional changes and identify MCI. We sought to determine whether long-term changes in remotely monitored computer use differ in persons with MCI in comparison to cognitively intact volunteers. Methods Participants enrolled in a longitudinal cohort study of unobtrusive in-home technologies to detect cognitive and motor decline in independently living seniors were assessed for computer usage (number of days with use, mean daily usage and coefficient of variation of use) measured by remotely monitoring computer session start and end times. Results Over 230,000 computer sessions from 113 computer users (mean age, 85; 38 with MCI) were acquired during a mean of 36 months. In mixed effects models there was no difference in computer usage at baseline between MCI and intact participants controlling for age, sex, education, race and computer experience. However, over time, between MCI and intact participants, there was a significant decrease in number of days with use (p=0.01), mean daily usage (~1% greater decrease/month; p=0.009) and an increase in day-to-day use variability (p=0.002). Conclusions Computer use change can be unobtrusively monitored and indicate individuals with MCI. With 79% of those 55–64 years old now online, this may be an ecologically valid and efficient approach to track subtle clinically meaningful change with aging. PMID:23688576

Patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma.

PubMed

Mizuno, Ryuichi; Asano, Koichiro; Mikami, Shuji; Nagata, Hirohiko; Kaneko, Gou; Oya, Mototsugu

2012-05-01

To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.

Alternative oil extraction methods from Echium plantagineum L. seeds using advanced techniques and green solvents.

PubMed

Castejón, Natalia; Luna, Pilar; Señoráns, Francisco J

2018-04-01

The edible oil processing industry involves large losses of organic solvent into the atmosphere and long extraction times. In this work, fast and environmentally friendly alternatives for the production of echium oil using green solvents are proposed. Advanced extraction techniques such as Pressurized Liquid Extraction (PLE), Microwave Assisted Extraction (MAE) and Ultrasound Assisted Extraction (UAE) were evaluated to efficiently extract omega-3 rich oil from Echium plantagineum seeds. Extractions were performed with ethyl acetate, ethanol, water and ethanol:water to develop a hexane-free processing method. Optimal PLE conditions with ethanol at 150 °C during 10 min produced a very similar oil yield (31.2%) to Soxhlet using hexane for 8 h (31.3%). UAE optimized method with ethanol at mild conditions (55 °C) produced a high oil yield (29.1%). Consequently, advanced extraction techniques showed good lipid yields and furthermore, the produced echium oil had the same omega-3 fatty acid composition than traditionally extracted oil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Induced Resistance to Meloidogyne hapla by other Meloidogyne species on Tomato and Pyrethrum Plants

PubMed Central

Ogallo, J. L.; McClure, M. A.

1995-01-01

Advance inoculation of the tomato cv. Celebrity or the pyrethrum clone 223 with host-incompatible Meloidogyne incognita or M. javanica elicited induced resistance to host-compatible M. hapla in pot and field experiments. Induced resistance increased with the length of the time between inoculations and with the population density of the induction inoculum. Optimum interval before challenge inoculation, or population density of inoculum for inducing resistance, was 10 days, or 5,000 infective nematodes per 500-cm³ pot. The induced resistance suppressed population increase of M. hapla by 84% on potted tomato, 72% on potted pyrethrum, and 55% on field-grown pyrethrum seedlings, relative to unprotected treatments. Pyrethrum seedlings inoculated with M. javanica 10 days before infection with M. hapla were not stunted, whereas those that did not receive the advance inoculum were stunted 33% in pots and 36% in field plots. The results indicated that advance infection of plants with incompatible or mildly virulent nematode species induced resistance to normally compatible nematodes and that the induced resistance response may have potential as a biological control method for plant nematodes. PMID:19277310

Oral Appliances for Obstructive Sleep Apnea

PubMed Central

2009-01-01

Executive Summary Objective The objective of this review was to determine the clinical effectiveness of oral appliances compared to ‘no treatment’, continuous positive airway pressure (CPAP), or surgery for the management of obstructive sleep apnea (OSA). Clinical Need: Condition and Target Population OSA is characterized by repeated occurrences of upper airway collapse and obstruction during sleep. The condition leads to excessive daytime sleepiness, diminished quality of life, and increased risks of accidents, cardiovascular disease and death. In the general population, the prevalence of OSA is estimated to be 4% in men and 2% in women. Risk factors for OSA include obesity, male gender, increasing age, alcohol use, sedative use, and a family history of OSA. Description of Oral Appliances Oral appliances for OSA fall into two broad categories: mandibular advancement splints (MAS), also known as mandibular repositioning devices, and tongue repositioning or retaining devices. The aim of MAS devices is to advance the mandible forward slightly to enlarge the upper airway and prevent it from collapsing. Similarly, tongue repositioning devices suction the tongue forward to prevent it from falling back and obstructing the airway during sleep. The alternatives to oral appliances include continuous positive airway pressure (CPAP) devices, surgery, drug therapy, positional devices, and lifestyle modification. CPAP is the gold standard of treatment, but despite its effectiveness, compliance rates for CPAP have declined because required systems are noisy and because wearing the mask can be uncomfortable, causing claustrophobia in some users. Evidence-Based Analysis Methods Research Questions Are oral appliances effective in improving sleep-disordered breathing in patients with OSA compared to alternative treatments? Are there safety concerns with oral appliances? What is the evidence regarding patient preference, quality of life, and compliance for oral appliances? If effective, are oral appliances cost effective? Literature Search A literature search was conducted up to February 2009. Systematic reviews, meta-analyses and randomized controlled trials (RCTs) with more than 20 adults with OSA were eligible for inclusion. The primary outcomes of interest were the Apnea Hypopnea Index (AHI), measures of daytime sleepiness, patient preference, compliance, and adverse events. Summary of Findings Five systematic reviews and 16 RCTs that met the inclusion criteria were identified. The systematic reviews consistently concluded that CPAP was more effective than oral appliances at improving sleep disordered breathing, although there may be a niche area for the latter, especially among those with mild OSA as CPAP is difficult to tolerate by some users. Based on the results of the RCTs analyzed for this review, MAS devices are less effective than CPAP when AHI is used as the outcome of interest. MAS devices were shown to decrease AHI levels, but whether this reduction is clinically meaningful is uncertain. The Epworth Sleepiness Scale (ESS) was not able to achieve statistical significance in comparisons of MAS versus CPAP and MAS versus placebo. Nonetheless, after treatment with either MAS or CPAP, patients seem to be able to achieve normal ESS levels. The ESS has substantial limitations including its subjective nature and low construct validity (i.e. it is unclear if the scale is an accurate measure of sleepiness). Adverse events among patients with MAS devices in the RCTs were common, but mostly mild and transient. Jaw discomfort was the most commonly reported adverse event. Based on the results of the RCTs, compliance does not seem to be better or worse with MAS or CPAP. Similarly, there is no clear patient preference for MAS or CPAP among the studies reporting preference and satisfaction. Keywords Obstructive sleep apnea, oral appliances, mandibular advancement splints, tongue repositioning devices PMID:23074535

Growth, fire history, and browsing recorded in wood rings of shrubs in a mild temperate climate.

PubMed

Coale, Tyler H; Deveny, Adrian J; Fox, Laurel R

2011-05-01

Separate effects of abiotic and biotic factors on the structure and dynamics of ecological communities may be recorded in growth rings of woody plants. We used Ceanothus cuneatus rigidus and Arctostaphylos pumila to tease apart the roles of fire, rain, and herbivores on the histories and community structure of four areas in a coastal mediterranean-type climate in central California with mild winters and mild summers. Ring widths of both species were related to rainfall in two of the areas; heavy deer browsing on Ceanothus overwhelmed the climate signal in the others. Ceanothus germination was more closely related to heavy rainfall, especially during ENSO years, than to fire events. In a related greenhouse experiment that evaluated these observations, the same proportions of new Ceanothus seeds germinated after burning and after receiving regular water for several months, but germination of old seeds responded primarily to the fire treatment. In areas where heavy browsing by mammals reduces recruitment and growth of Ceanothus and increases mortality, the continuance of the Ceanothus population must rely heavily on germination from the persistent seed bank during unusually wet years or after occasional fires. Because Arctostaphylos can produce new stems from underground roots, individual plants may survive and produce seeds until another fire.

A mild traumatic brain injury in mice produces lasting deficits in brain metabolism.

PubMed

Lyons, Danielle N; Vekaria, Hemendra; Macheda, Teresa; Bakshi, Vikas; Powell, David K; Gold, Brian T; Lin, Ai-Ling; Sulllivan, Pat; Bachstetter, Adam D

2018-05-29

Metabolic uncoupling has been well-characterized during the first minutes-to-days after a traumatic brain injury (TBI), yet mitochondrial bioenergetics during the weeks-to-months after a brain injury is poorly defined, particularly after a mild TBI. We hypothesized that a closed head injury (CHI) would be associated with deficits in mitochondrial bioenergetics at one month after the injury. A significant decrease in state-III (ATP production) and state-V (complex-I) driven mitochondrial respiration was found at 1-month post-injury in adult C57Bl/6J mice. Isolation of synaptic mitochondria demonstrated that the deficit in state-III and state-V was primarily neuronal. Injured mice had a temporally consistent deficit in memory recall at 1-month post injury. Using proton magnetic resonance spectroscopy (1H MRS) at 7-Tesla, we found significant decreases in phosphocreatine, N-Acetylaspartic acid (NAA), and total choline. We also found regional variations in cerebral blood flow, including both hypo- and hyper- perfusion, as measured by a pseudo-continuous arterial spin labeling MR sequence. Our results highlight a chronic deficit in mitochondrial bioenergetics associated with a CHI that may lead toward a novel approach for neurorestoration following a mild TBI. Magnetic resonance spectroscopy provides a potential biomarker for assessing the efficacy of candidate treatments targeted at improving mitochondrial bioenergetics.

Long-term mortality risks associated with mild anaemia in older persons: the Busselton Health Study.

PubMed

Chalmers, Kerry A; Knuiman, Matthew W; Divitini, Mark L; Bruce, David G; Olynyk, John K; Milward, Elizabeth A

2012-11-01

up to 25% of older people in the USA and other Western countries are anaemic by World Health Organization (WHO) criteria. The objective of this study was to examine the long-term relationships of haemoglobin concentration with all-cause and cause-specific mortality in a community-based sample of Australian adults surveyed in 1978. a community survey of 2,194 adults aged 40+ years in Busselton, Western Australia in 1978 with mortality follow-up to 2001. Cox regression models were used to investigate the relationships of haemoglobin as a continuous measure and anaemia by WHO criteria (women <12 g/dl (7.5 mmol/l); men <13 g/dl (8.1 mmol/l)) with all-cause, cardiovascular and cancer mortality. anaemia was predominantly mild (>10 g/dl) and normocytic. There was an increased risk of death from all causes and from cancer for men with low haemoglobin. Cancers were predominantly of the prostate and genito-urinary organs, and to a lesser extent the gastrointestinal tract. There was no increased risk of all cause or cancer death in women. mild, normocytic anaemia is associated with survival reductions in middle-aged and older men, where it often occurs with prostate, gastrointestinal and other cancers, and should be investigated to exclude treatable causes.

Uncaging the Dragon: Vietnam and the Middle-Income Trap

DTIC Science & Technology

2013-11-01

compete with high- income advanced economies because it lacks the institutions necessary to continue economic growth . The author suggests that...but then cannot compete with high- income advanced economies because it lacks the institutions necessary to continue economic growth . The author...Vietnam modifies its current economic strategy, the factors that limit economic growth will leave it mired in the middle- income trap. The Communist

Microgravity Manufacturing: Extending Rapid Prototyping Past the Horizon

NASA Technical Reports Server (NTRS)

Cooper, Ken

2003-01-01

Over the last decade, rapid prototyping (RP) technologies have continued to advance in all aspects of operation and application. From continuously advanced materials and processes development to more hard-core manufacturing uses, the RP realm has stretched considerably past its original expectations as a prototyping capability. This paper discusses the unique applications for which NASA has chosen these manufacturing techniques to be utilized in outer space.

Microvascular endothelial function and severity of primary open angle glaucoma.

PubMed

Bukhari, S M I; Kiu, K Y; Thambiraja, R; Sulong, S; Rasool, A H G; Liza-Sharmini, A T

2016-12-01

PurposeThe role of microvascular endothelial dysfunction on severity of primary open angle glaucoma (POAG) was investigated in this study.Patients and methodsA prospective cohort study was conducted. One hundred and fourteen ethnically Malay patients (114 eyes) with POAG treated at the eye clinic of Hospital University Sains Malaysia between April 2012 and December 2014 were recruited. Patients aged between 40 and 80 years with two consecutive reliable and reproducible Humphrey visual field 24-2 analyses were selected. Patients who were diagnosed with any other type of glaucoma, previous glaucoma-filtering surgery, or other surgeries except uncomplicated cataract and pterygium surgery were excluded. Humphrey visual field analysis 24-2 was used to stratify the severity of glaucoma using Advanced Glaucoma Intervention Study (AGIS) score at the time of recruitment. Microvascular endothelial function was assessed using Laser Doppler fluximetry and iontophoresis. Iontophoresis process with acetylcholine (ACh) and sodium nitroprusside (SNP) was used to measure microvascular endothelium-dependent and -independent vasodilatation, respectively.ResultsBased on the AGIS score, 55 patients showed mild glaucoma, with 29 moderate and 30 severe. There was statistically significant difference in microvascular endothelial function (ACh% and ACh max ) between mild and moderate POAG cases (P=0.023) and between mild and severe POAG cases (P<0.001). There was negative correlation between microvascular endothelial function and severity of POAG (r=-0.457, P<0.001).ConclusionMicrovascular endothelial dysfunction may have a role in influencing the severity of POAG in Malay patients.

Characterization of abdominal pain during methylnaltrexone treatment of opioid-induced constipation in advanced illness: a post hoc analysis of two clinical trials.

PubMed

Slatkin, Neal E; Lynn, Richard; Su, Chinyu; Wang, Wenjin; Israel, Robert J

2011-11-01

Methylnaltrexone is a selective peripherally acting mu-opioid receptor antagonist that decreases the constipating effects of opioids without affecting centrally mediated analgesia. In two double-blind, placebo-controlled, Phase III studies of methylnaltrexone for opioid-induced constipation in patients with advanced illness, abdominal pain was the most common adverse event (AE) reported. This analysis sought to further characterize the Medical Dictionary for Regulatory Activities-defined abdominal pain AEs experienced in these studies. A post hoc analysis of verbatim descriptions was used to further assess AEs characterized as abdominal pain in both trials. Descriptive summary statistics were used to assess severity of abdominal pain, effect of abdominal pain on global pain scores, and other characteristics. Logistic regression analysis was used to determine the association of baseline characteristics with abdominal pain. Most verbatim descriptions of abdominal pain referred to "abdominal cramps" or "cramping." Abdominal pain AEs were mostly mild to moderate in severity and did not affect patients' global evaluation of pain. The incidence of abdominal pain AEs in methylnaltrexone-treated patients was greatest after the first dose and decreased with subsequent doses. No association between abdominal pain AEs and most baseline patient characteristics was noted. Abdominal pain AEs in methylnaltrexone-treated patients in clinical trials are usually described as "cramps" or "cramping," are mostly mild to moderate in severity, and decrease in incidence with subsequent dosing. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Comparison between mono-bloc and bi-bloc mandibular advancement devices for obstructive sleep apnea.

PubMed

Lee, Woo Hyun; Wee, Jee Hye; Lee, Chul Hee; Kim, Min-Su; Rhee, Chae-Seo; Yun, Pil-Young; Yoon, In-Young; Kim, Jeong-Whun

2013-11-01

Although mandibular advancement device (MAD) is widely used, there are a few papers comparing the efficacy and compliance at the same time according to the type of MAD. The aim of this study is to compare the efficacy and compliance between mono-bloc and bi-bloc MAD in the treatment of obstructive sleep apnea (OSA). Ninety-three patients who treated with mono-bloc MAD and 60 patients with bi-bloc MAD from January 2007 through September 2011 were retrospectively enrolled. All the patients underwent full-night polysomnography(PSG) before and 3 months after MAD was applied. The response rate was significantly higher in the patients using mono-bloc than those using bi-bloc MAD (77.4 vs. 58.3 %; P = 0.012). In contrast, the compliance rate of MAD use was significantly higher in the patients using bi-bloc than those using mono-bloc MAD (68.8 vs. 83.3 %; P = 0.044) at 1 year. According to the severity of OSA, the response rate was significantly higher in severe OSA than in mild to moderate OSA (P = 0.033 for mono-bloc MAD and P = 0.048 for bi-bloc MAD). However, there was no difference in the compliance between mild to moderate OSA and severe OSA. Our study showed that mono-bloc MAD was superior to bi-bloc MAD in efficacy while bi-bloc MAD is superior to mono-bloc MAD in compliance. We propose that both the efficacy and compliance should be considered in using MAD for treatment of OSA.

Rates of decline in Alzheimer disease decrease with age.

PubMed

Holland, Dominic; Desikan, Rahul S; Dale, Anders M; McEvoy, Linda K

2012-01-01

Age is the strongest risk factor for sporadic Alzheimer disease (AD), yet the effects of age on rates of clinical decline and brain atrophy in AD have been largely unexplored. Here, we examined longitudinal rates of change as a function of baseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI), and cognitively healthy (HC) individuals aged 65 to 90 years (total n = 723). The effect of age was modeled using mixed effects linear regression. There was pronounced reduction in rates of clinical decline and atrophy with age for AD and MCI individuals, whereas HCs showed increased rates of clinical decline and atrophy with age. This resulted in convergence in rates of change for HCs and patients with advancing age for several measures. Baseline cerebrospinal fluid densities of AD-relevant proteins, Aβ(1-42), tau, and phospho-tau(181p) (ptau), showed a similar pattern of convergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicating uniformity of clinical severity at baseline. These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, and this may affect the ability to distinguish AD from normal aging in the very old. Our findings show that inclusion of older individuals in clinical trials will substantially reduce the power to detect disease-modifying therapeutic effects, leading to dramatic increases in required clinical trial sample sizes with age of study sample.

Prevalence and Indicators of Portal Hypertension in Patients with Nonalcoholic Fatty Liver Disease

PubMed Central

Mendes, Flavia D.; Suzuki, Ayako; Sanderson, Schuyler O.; Lindor, Keith D.; Angulo, Paul

2012-01-01

Background & Aims Little is known about the prevalence and severity of portal hypertension in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the prevalence and non-invasive predictors of portal hypertension in patients with NAFLD. Methods Signs of portal hypertension, including esophageal varices, splenomegaly, portosystemic encephalopathy, and ascites where investigated in 354 patients with NAFLD. Results One-hundred patients had portal hypertension at the time of NAFLD diagnosis (28.2%), 88 of these with septal fibrosis or cirrhosis (88%). Fibrosis stage correlated with presence (r=0.41, P<.0001) and number of findings (r=0.48, P=.006) of portal hypertension. Of the 204 patients with no or mild fibrosis (stages 0–2), 12 had portal hypertension (6%); they had a significantly higher grade of steatosis, based on biopsy analysis, compared to the 192 patients without portal hypertension (94%). Thrombocytopenia, hyperbilirubinemia, cirrhosis, and obesity were independently associated with portal hypertension. Esophageal varices were found in 57 of the 128 patients undergoing endoscopic screening (44.5%) and independently associated with thrombocytopenia, type 2 diabetes, and splenomegaly. Conclusions Signs of portal hypertension are present in 25% of patients at the time of diagnosis of NAFLD; most had advanced fibrosis or cirrhosis. Portal hypertension can occur in a small proportion of patients with mild or no fibrosis and is associated with the extent of steatosis. Features of advanced liver disease and insulin resistance might identify patients with NAFLD and portal hypertension, and those expected to derive the most benefit from endoscopic screening for esophageal varices. PMID:22610002

A next generation advanced traveler information precursor system (ATIS 2.0 precursor system) concept of operations.

DOT National Transportation Integrated Search

2016-10-27

Advanced Traveler Information Systems (ATIS) have experienced significant growth since its initial inception in the 1990s. Technologies have continued to evolve at a rapid pace, enabling the integration of advanced solutions for traveler information ...

7 CFR 56.58 - Advance information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Advance information. 56.58 Section 56.58 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... EGGS Grading of Shell Eggs Grading Certificates § 56.58 Advance information. Upon request of an...

49 CFR 585.15 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.15 Reporting requirements. (a) Advanced credit phase-in reporting... any of those production years as complying with phase one of the advanced air bag requirements of...

49 CFR 585.15 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.15 Reporting requirements. (a) Advanced credit phase-in reporting... any of those production years as complying with phase one of the advanced air bag requirements of...

7 CFR 1006.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1006.50 Section 1006.50 Agriculture Regulations of the Department of Agriculture (Continued..., and advanced pricing factors. See § 1000.50. ...

7 CFR 1007.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1007.50 Section 1007.50 Agriculture Regulations of the Department of Agriculture (Continued..., and advanced pricing factors. See § 1000.50. ...

7 CFR 1126.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1126.50 Section 1126.50 Agriculture Regulations of the Department of Agriculture (Continued..., and advanced pricing factors. See § 1000.50. ...

7 CFR 1131.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1131.50 Section 1131.50 Agriculture Regulations of the Department of Agriculture (Continued..., and advanced pricing factors. See § 1000.50. ...

7 CFR 1005.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1005.50 Section 1005.50 Agriculture Regulations of the Department of Agriculture (Continued..., and advanced pricing factors. See § 1000.50. ...

7 CFR 1032.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1032.50 Section 1032.50 Agriculture Regulations of the Department of Agriculture (Continued..., and advanced pricing factors. See § 1000.50. ...

7 CFR 1001.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1001.50 Section 1001.50 Agriculture Regulations of the Department of Agriculture (Continued..., and advanced pricing factors. See § 1000.50. ...

7 CFR 1033.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1033.50 Section 1033.50 Agriculture Regulations of the Department of Agriculture (Continued..., and advanced pricing factors. See § 1000.50. ...

A next generation advanced traveler information precursor system (ATIS 2.0 precursor system) system requirements.

DOT National Transportation Integrated Search

2016-12-01

Advanced Traveler Information Systems (ATIS) have experienced significant growth since their initial inception in the 1990s. Technologies have continued to evolve at a rapid pace, enabling the integration of advanced solutions for traveler informatio...

Advances in induction-heated plasma torch technology

NASA Technical Reports Server (NTRS)

Poole, J. W.; Vogel, C. E.

1972-01-01

Continuing research has resulted in significant advances in induction-heated plasma torch technology which extend and enhance its potential for broad range of uses in chemical processing, materials development and testing, and development of large illumination sources. Summaries of these advances are briefly described.

A next generation advanced traveler information precursor system (ATIS 2.0 precursor system) use cases report.

DOT National Transportation Integrated Search

2017-05-01

Advanced Traveler Information Systems (ATIS) have experienced significant growth since their initial inception in the 1990s. Technologies have continued to evolve at a rapid pace, enabling the integration of advanced solutions for traveler informatio...

Endoscopic Skull Base Surgery

PubMed Central

Senior, Brent A

2008-01-01

Endoscopic skull base surgery has undergone rapid advancement in the past decade moving from pituitary surgery to suprasellar lesions and now to a myriad of lesions extending from the cribriform plate to C2 and laterally out to the infratemporal fossa and petrous apex. Evolution of several technological advances as well as advances in understanding of endoscopic anatomy and the development of surgical techniques both in resection and reconstruction have fostered this capability. Management of benign disease via endoscopic methods is largely accepted now but more data is needed before the controversy on the role of endoscopic management of malignant disease is decided. Continued advances in surgical technique, navigation systems, endoscopic imaging technology, and robotics assure continued brisk evolution in this expanding field. PMID:19434274

Characterization of the Intrinsic Water Wettability of Graphite Using Contact Angle Measurements: Effect of Defects on Static and Dynamic Contact Angles.

PubMed

Kozbial, Andrew; Trouba, Charlie; Liu, Haitao; Li, Lei

2017-01-31

Elucidating the intrinsic water wettability of the graphitic surface has increasingly attracted research interests, triggered by the recent finding that the well-established hydrophobicity of graphitic surfaces actually results from airborne hydrocarbon contamination. Currently, static water contact angle (WCA) is often used to characterize the intrinsic water wettability of graphitic surfaces. In the current paper, we show that because of the existence of defects, static WCA does not necessarily characterize the intrinsic water wettability. Freshly exfoliated graphite of varying qualities, characterized using atomic force microscopy and Raman spectroscopy, was studied using static, advancing, and receding WCA measurements. The results showed that graphite of different qualities (i.e., defect density) always has a similar advancing WCA, but it could have very different static and receding WCAs. This finding indicates that defects play an important role in contact angle measurements, and the static contact angle does not always represent the intrinsic water wettability of pristine graphite. On the basis of the experimental results, a qualitative model is proposed to explain the effect of defects on static, advancing, and receding contact angles. The model suggests that the advancing WCA reflects the intrinsic water wettability of pristine (defect-free) graphite. Our results showed that the advancing WCA for pristine graphite is 68.6°, which indicates that graphitic carbon is intrinsically mildly hydrophilic.

[Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified].

PubMed

Li, Xi; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Xinyong; Lv, Jialin; Wu, Yuhua; Zhang, Hui; Nong, Jingying; Zhang, Quan; Zhang, Shucai

2015-12-01

Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation and wild-type. Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type) with advanced NSCLC were enrolled in this study. The patients' overall objective response rate (ORR) was 51.6 % and the disease control rate (DCR) was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6%) and diarrhea (16.1%). Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.


NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

PubMed

Nickolas, Thomas L; Forster, Catherine S; Sise, Meghan E; Barasch, Nicholas; Solá-Del Valle, David; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

2012-09-01

The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 μg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 μg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.

Sublimation-assisted graphene transfer technique based on small polyaromatic hydrocarbons

NASA Astrophysics Data System (ADS)

Chen, Mingguang; Stekovic, Dejan; Li, Wangxiang; Arkook, Bassim; Haddon, Robert C.; Bekyarova, Elena

2017-06-01

Advances in the chemical vapor deposition (CVD) growth of graphene have made this material a very attractive candidate for a number of applications including transparent conductors, electronics, optoeletronics, biomedical devices and energy storage. The CVD method requires transfer of graphene on a desired substrate and this is most commonly accomplished with polymers. The removal of polymer carriers is achieved with organic solvents or thermal treatment which makes this approach inappropriate for application to plastic thin films such as polyethylene terephthalate substrates. An ultraclean graphene transfer method under mild conditions is highly desired. In this article, we report a naphthalene-assisted graphene transfer technique which provides a reliable route to residue-free transfer of graphene to both hard and flexible substrates. The quality of the transferred graphene was characterized with atomic force microscopy, scanning electron microscopy, and Raman spectroscopy. Field effect transistors, based on the naphthalene-transfered graphene, were fabricated and characterized. This work has the potential to broaden the applications of CVD graphene in fields where ultraclean graphene and mild graphene transfer conditions are required.

Recent clinical advances in diabetic polyneuropathy.

PubMed

Horowitz, Steven H

2006-10-01

Recent dramatic increases in the incidence and prevalence of diabetes make an understanding of chronic symmetric sensorimotor diabetic polyneuropathy, the most common and problematic of chronic diabetic complications, essential for a wide range of medical practitioners. The demonstration of neuropathic dysfunction in patients with prediabetes or impaired glucose tolerance emphasizes the susceptibility of peripheral nerve fibers, especially small A delta fibers and C fibers, to relatively mild, short-duration hyperglycemia. New testing can reveal peripheral nerve dysfunction prior to clinical neuropathic symptoms and signs. In the absence of effective medications to halt or reverse nerve damage or promote nerve regeneration, early diagnosis of diabetic polyneuropathy, followed by tight glycemic control with diet and exercise, offers the best opportunity to prevent progressive symptoms of sensory loss, pain, autonomic dysfunction, ulcerations, and amputations. Some patients with impaired glucose tolerance have a reversal of neuropathic features with tight glycemic control. Nonpharmacologic therapies for neuropathic pain in diabetic polyneuropathy appear promising. Tight glycemic control, especially early in diabetes, is the best approach to minimizing the prevalence and severity of diabetic polyneuropathy and makes research into the deleterious effects of even mild hyperglycemia imperative.

Regional cyst concentration as a prognostic biomarker for polycystic kidney disease

NASA Astrophysics Data System (ADS)

Warner, Joshua D.; Irazabal, Maria V.; Torres, Vicente E.; King, Bernard F.; Erickson, Bradley J.

2014-03-01

Polycystic kidney disease (PKD) is a major cause of renal failure. Despite recent advances in understanding the biochemistry and genetics of PKD, the functional mechanisms underpinning the declines in renal function observed in the disorder are not well established. No studies investigating the distribution of cysts within polycystic kidneys exist. This work introduces regional cyst concentration as a new biomarker for evaluation of patients suffering from PKD. We derive a method to define central and peripheral regions of the kidney, approximating the anatomical division between cortex and medulla, and apply it to two cohorts of ten patients with early/mild or late/severe disease. Our results from the late/severe cohort show peripheral cyst concentration correlates with the current standard PKD biomarker, total kidney volume (TKV), signi cantly better than central cyst concentration (p < 0.05). We also find that cyst concentration was globally increased in the late/severe cohort (p << 0.01) compared to the early/mild cohort, for both central and peripheral regions. These findings show cysts in PKD are not distributed homogeneously throughout the renal tissues.

Room temperature synthesis of pH-switchable polyaniline quantum dots as a turn-on fluorescent probe for acidic biotarget labeling.

PubMed

Liu, Yanfeng; Ding, Yin; Gou, Huilin; Huang, Xin; Zhang, Guiyang; Zhang, Qi; Liu, Yunzhong; Meng, Zhen; Xi, Kai; Jia, Xudong

2018-04-05

The synthesis of well-defined light-element-derived quantum dots (LEQDs) with advanced optical properties under mild conditions is highly desirable yet challenging. Here, a polyaniline (PANI) structure is introduced into carbon-rich LEQDs to yield well-defined, fluorescent polyaniline quantum dots (PAQDs), PAQD24, through a one-pot room temperature reaction. The mild synthetic conditions effectively minimize the defects introduced during the conventional synthesis and endow PAQD24 with desirable optical properties, including a narrow emission band (full width at half maximum = 55 nm), an optimal quantum yield of 32.5% and two-photon fluorescence. Furthermore, the bandgap of PAQD24 is highly sensitive toward pH variations in the near-neutral region, due to the proton doping and dedoping of the PANI structure. Such unique properties together with its fine bio-compatibility enable the application of this material as a turn-on fluorescent probe for the labeling of acidic biotargets from sub-cellular to organ levels, providing potential applications in diagnosis and surgery guidance for certain diseases.

Balance and mobility dysfunction and falls risk in older people with mild to moderate Alzheimer disease.

PubMed

Suttanon, Plaiwan; Hill, Keith D; Said, Catherine M; Logiudice, Dina; Lautenschlager, Nicola T; Dodd, Karen J

2012-01-01

This study aimed to identify the magnitude and type of balance and mobility impairments in people with Alzheimer disease by comparing their performance with that of older people without cognitive impairment. Twenty-five community-dwelling people with mild to moderate Alzheimer disease and a comparison group of 25 cognitively intact age- and sex-matched people completed a comprehensive balance and mobility assessment. This included computerized posturography measures of static and dynamic balance under various conditions, clinical balance, and mobility measures, and measures of falls and falls risk. The level of falls risk was higher in people with Alzheimer disease. Standing balance in people with Alzheimer disease was significantly impaired across a range of static and dynamic balance conditions. Activity level, gait, and mobility measures were also impaired, particularly turning and dual tasks. The findings of the study highlight the value of including balance screening as a routine component of early dementia assessment. This would allow for the early detection of balance dysfunction and the introduction of balance retraining before impairments progress to more advanced levels.

Cool Decision-Making in Adolescents with Behavior Disorder and/or Mild-to-Borderline Intellectual Disability.

PubMed

Bexkens, Anika; Jansen, Brenda R J; Van der Molen, Maurits W; Huizenga, Hilde M

2016-02-01

Adolescents with Behavior Disorders (BD), Mild-to-Borderline Intellectual Disability (MBID), and with both BD and MBID (BD + MBID) are known to take more risks than normal controls. To examine the processes underlying this increased risk-taking, the present study investigated cool decision-making strategies in 479 adolescents (12-18 years, 55.9 % male) from these four groups. Cool decision-making was assessed with the paper-and-pencil Gambling Machine Task. This task, in combination with advanced latent group analysis, allows for an assessment of decision strategies. Results indicated that adolescents with BD and controls were almost equivalent in their decision-making strategies, whereas adolescents with MBID and adolescents with BD + MBID were characterized by suboptimal decision-making strategies, with only minor differences between these two clinical groups. These findings may have important clinical implications, as they suggest that risk taking in adolescents with MBID and in adolescents with BD + MBID can be (partly) attributed to the strategies that these adolescents use to make their decisions. Interventions may therefore focus on an improvement of these strategies.

Antimicrobial potential of selected brown seaweeds from Vedalai coastal waters, Gulf of Mannar

PubMed Central

Manivannan, K; Karthikai devi, G; Anantharaman, P; Balasubramanian, T

2011-01-01

Objective To evaluate the antimicrobial activity of Turbinaria conoides (T. conoides), Padina gymnospora (P. gymnospora) and Sargassum tenerrimum against human bacterial and fungal pathogens. Methods The antimicrobial activities of the extracts against various organisms were tested by using disc diffusion method. Results The methanol extract showed the better result than the other extracts. Whereas, the strong antibacterial inhibition was noted in methanol extracts of P. gymnospora against Bacillus subtilus (26.33±1.86) and the mild inhibition of ethanol extracts from T. conoides against Klebsiella pneumoniae (2.33±0.51). Acetone extraction of P. gymnospora had strong antifungal inhibition against Cryptococcus neoformans (23.00±1.78), and acetone extract of T. conoides had mild inhibition against Aspergillus niger (3.00±0.89). Conclusions The seven different solvent extracts of seaweeds used in the present study have shown significant bacterial action. Further, a detailed study on the principle compound in the seaweeds which is responsible for antimicrobial activity is still needed and it can be achieved by using advanced separation techniques. PMID:23569739

Epidemiological Study of Mild Tramautic Brain Injury Sequelae Cause by Blast Exposure During Operations Iraqi Freedom and Enduring Freedom

DTIC Science & Technology

2012-10-01

Principal Investigator September, 2008 20 (see: VCU sub- award) David X. Cifu, MD Co-Investigator September, 2008 5 (VCU sub-award) Jessica...proven reliability: Wechsler Test of Adult Reading (WTAR, pre- morbid IQ estimate),(Mathias, Bowden, Bigler, & Rosenfeld, 2007) Conners Continuous...II (CVLT-II) (learning and working memory),(Vanderploeg et al., 2005) Wechsler Adult Intelligence Scale III (WAIS-III) items: Digit Symbol Coding

Laparoscopic extended cardiomyotomy in children: an effective procedure for the treatment of esophageal achalasia.

PubMed

Tannuri, Ana Cristina Aoun; Tannuri, Uenis; Velhote, Manoel Carlos Prieto; Romão, Rodrigo Luiz Pinto

2010-07-01

Achalasia of the esophagus is characterized by aperistalsis and incomplete relaxation of the lower esophageal sphincter in response to swallowing. The objective of the present study is to present the experience of a modified Heller myotomy via a laparoscopic approach for the treatment of children who had this condition. A retrospective review of medical records of all patients who underwent this procedure from 2000 to 2009 was performed. The procedure consisted of an extended esophagomyotomy beginning on the lower part of the lower esophageal sphincter and continuing 5 to 6 cm above on the lower third of the esophagus, and then extended 3 to 4 cm below to the stomach, associated with an anterior 180-degree hemi-fundoplication according to Dor's technique. Fifteen patients were included in the study. There were 8 female and 7 male patients. Mean operating time was 190 minutes with no intraoperative complications and 1 conversion to open surgery because of difficulty in dissecting an inflamed distal esophagus. In a mean follow-up period of 32.3 months, 2 patients had recurrence of mild dysphagia that disappeared spontaneously, and 1 required a single botulinum toxin injection with complete resolution of symptoms. We conclude that the laparoscopic extended Heller myotomy with Dor fundoplication is a safe and effective method for the treatment for achalasia in the pediatric population even in advanced cases. Copyright 2010 Elsevier Inc. All rights reserved.

Management of adverse events related to new cancer immunotherapy (immune checkpoint inhibitors).

PubMed

Bourke, Jack M; O'Sullivan, Michael; Khattak, Muhammad A

2016-11-07

New immunotherapies have significantly improved survival in certain advanced cancers in recent years, particularly metastatic melanoma and lung cancer. The most effective of these therapies are the immune checkpoint inhibitors (ICIs) such as ipilimumab, nivolumab and pembrolizumab. The use of ICIs will continue to increase in the coming years as evidence of their benefit in a range of other cancers builds. ICIs are associated with novel immune-related adverse events (irAEs), which can involve a wide range of organs. The most common irAEs involve the skin (rash, pruritus), gastrointestinal tract (diarrhoea, colitis) and endocrine system (thyroid, pituitary). While severity is generally mild, life-threatening complications can occur if not recognised and treated promptly. Due to the diverse manifestations of irAEs, patients may present to doctors who are not familiar with these drugs, which creates the potential for delays in management. Management of irAEs depends on severity and the organ affected. Systemic steroids are often required and ICI therapy may be withheld or discontinued. Additional immunosuppressive medications may be necessary in steroid-refractory cases. This review provides an overview of the potential toxicities and their management for general clinicians. Broader awareness of these issues among medical professionals will hopefully reduce unnecessary delays in diagnosis and treatment. Patient and carer education regarding irAEs is extremely important; patients and carers should be advised to seek urgent medical attention if required.

Evolution and mechanisms of plant tolerance to flooding stress

PubMed Central

Jackson, Michael B.; Ishizawa, Kimiharu; Ito, Osamu

2009-01-01

Background In recognition of the 200th anniversary of Charles Darwin's birth, this short article on flooding stress acknowledges not only Darwin's great contribution to the concept of evolution but also to the study of plant physiology. In modern biology, Darwin-inspired reductionist physiology continues to shed light on mechanisms that confer competitive advantage in many varied and challenging environments, including those where flooding is prevalent. Scope Mild flooding is experienced by most land plants but as its severity increases, fewer species are able to grow and survive. At the extreme, a highly exclusive aquatic lifestyle appears to have evolved numerous times over the past 120 million years. Although only 1–2% of angiosperms are aquatics, some of their adaptive characteristics are also seen in those adopting an amphibious lifestyle where flooding is less frequent. Lowland rice, the staple cereal for much of tropical Asia falls into this category. But, even amongst dry-land dwellers, or certain of their sub-populations, modest tolerance to occasional flooding is to be found, for example in wheat. The collection of papers summarized in this article describes advances to the understanding of mechanisms that explain flooding tolerance in aquatic, amphibious and dry-land plants. Work to develop more tolerant crops or manage flood-prone environments more effectively is also included. The experimental approaches range from molecular analyses, through biochemistry and metabolomics to whole-plant physiology, plant breeding and ecology. PMID:19145714

With-in host dynamics of L. monocytogenes and thresholds for distinct infection scenarios.

PubMed

Rahman, Ashrafur; Munther, Daniel; Fazil, Aamir; Smith, Ben; Wu, Jianhong

2018-05-26

The case fatality and illness rates associated with L. monocytogenes continue to pose a serious public health burden despite the significant efforts and control protocol administered by private and public sectors. Due to the advance in surveillance and improvement in detection methodology, the knowledge of sources, transmission routes, growth potential in food process units and storage, effect of pH and temperature are well understood. However, the with-in host growth and transmission mechanisms of L. monocytogenes, particularly within the human host, remain unclear, largely due to the limited access to scientific experimentation on the human population. In order to provide insight towards the human immune response to the infection caused by L. monocytogenes, we develop a with-in host mathematical model. The model explains, in terms of biological parameters, the states of asymptomatic infection, mild infection and systemic infection leading to listeriosis. The activation and proliferation of T-cells are found to be critical for the susceptibility of the infection. Utilizing stability analysis and numerical simulation, the ranges of the critical parameters relative to infection states are established. Bifurcation analysis shows the impact of the differences of these parameters on the dynamics of the model. Finally, we present model applications in regards to predicting the risk potential of listeriosis relative to the susceptible human population. Copyright © 2018. Published by Elsevier Ltd.

Morbidity and mortality in stranded Cook Inlet beluga whales Delphinapterus leucas.

PubMed

Burek-Huntington, Kathleen A; Dushane, Jennifer L; Goertz, Caroline E C; Measures, Lena N; Romero, Carlos H; Raverty, Stephen A

2015-05-11

The endangered Cook Inlet (Alaska, USA) stock of beluga whales Delphinapterus leucas declined 47% between 1994 and 1998, from an estimated 653 whales to 347 whales, with a continued decline to approximately 312 in 2012. Between 1998 and 2013, 164 known dead strandings were reported by the National Marine Fisheries Service. Only 38 of these animals, or 23% of the known stranded carcasses, were necropsied. Carcasses were found between April and October. The majority of animals necropsied were adults (n=25), followed by juveniles (n=6), calves (n=3), and aborted fetuses (n=4). Eight of the 11 mature females were pregnant, post-partum, or lactating. Many (82%) of these belugas were in moderate to advanced autolysis, which hampered determination of a cause of death (COD). Each animal had a single primary COD assigned within a broad set of categories. The CODs were unknown (29%), trauma (18%), perinatal mortality (13%), mass stranding (13%), single stranding (11%), malnutrition (8%), or disease (8%). Other disease processes were coded as contributory or incidental to COD. Multiple animals had mild to moderate verminous pneumonia due to Stenurus arctomarinus, renal granulomas due to Crassicauda giliakiana, and ulcerative gastritis due to Anisakis sp. Each stranding affords a unique opportunity to obtain natural history data and evidence of human interactions, and, by long-term monitoring, to characterize pathologies of importance to individual and population health.

Intellectual developmental disorders: towards a new name, definition and framework for “mental retardation/intellectual disability” in ICD-11

PubMed Central

CARULLA, LUIS SALVADOR; REED, GEOFFREY M.; VAEZ-AZIZI, LEILA M.; COOPER, SALLY-ANN; LEAL, RAFAEL MARTINEZ; BERTELLI, MARCO; ADNAMS, COLLEEN; COORAY, SHERVA; DEB, SHOUMITRO; DIRANI, LEYLA AKOURY; GIRIMAJI, SATISH CHANDRA; KATZ, GREGORIO; KWOK, HENRY; LUCKASSON, RUTH; SIMEONSSON, RUNE; WALSH, CAROLYN; MUNIR, KEMIR; SAXENA, SHEKHAR

2011-01-01

Although “intellectual disability” has widely replaced the term “mental retardation”, the debate as to whether this entity should be conceptualized as a health condition or as a disability has intensified as the revision of the World Health Organization (WHO)’s International Classification of Diseases (ICD) advances. Defining intellectual disability as a health condition is central to retaining it in ICD, with significant implications for health policy and access to health services. This paper presents the consensus reached to date by the WHO ICD Working Group on the Classification of Intellectual Disabilities. Literature reviews were conducted and a mixed qualitative approach was followed in a series of meetings to produce consensus-based recommendations combining prior expert knowledge and available evidence. The Working Group proposes replacing mental retardation with intellectual developmental disorders, defined as “a group of developmental conditions characterized by significant impairment of cognitive functions, which are associated with limitations of learning, adaptive behaviour and skills”. The Working Group further advises that intellectual developmental disorders be incorporated in the larger grouping (parent category) of neurodevelopmental disorders, that current subcategories based on clinical severity (i.e., mild, moderate, severe, profound) be continued, and that problem behaviours be removed from the core classification structure of intellectual developmental disorders and instead described as associated features. PMID:21991267

7 CFR 70.93 - Advance information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Advance information. 70.93 Section 70.93 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Advance information. Upon request of an applicant, all or part of the contents of any grading certificate...

14 CFR 151.119 - Advance planning proposals: Procedures; funding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Advance planning proposals: Procedures; funding. 151.119 Section 151.119 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Rules and Procedures for Advance Planning and...

14 CFR 151.117 - Advance planning proposals: Procedures; application.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Advance planning proposals: Procedures; application. 151.117 Section 151.117 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Rules and Procedures for Advance Planning and...

14 CFR 151.117 - Advance planning proposals: Procedures; application.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Advance planning proposals: Procedures; application. 151.117 Section 151.117 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Rules and Procedures for Advance Planning and...

14 CFR 151.117 - Advance planning proposals: Procedures; application.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Advance planning proposals: Procedures; application. 151.117 Section 151.117 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Rules and Procedures for Advance Planning and...

7 CFR 1030.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1030.50 Section 1030.50 Agriculture Regulations of the Department of Agriculture (Continued... prices, and advanced pricing factors. See § 1000.50. ...

7 CFR 1124.50 - Class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class prices, component prices, and advanced pricing factors. 1124.50 Section 1124.50 Agriculture Regulations of the Department of Agriculture (Continued... prices, and advanced pricing factors. See § 1000.50. ...

49 CFR 585.15 - Reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase... any of those production years as complying with phase one of the advanced air bag requirements of... manufactured during that production year as complying with phase two of the advanced air bag requirements of...

49 CFR 585.15 - Reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase... any of those production years as complying with phase one of the advanced air bag requirements of... manufactured during that production year as complying with phase two of the advanced air bag requirements of...

49 CFR 585.15 - Reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase... any of those production years as complying with phase one of the advanced air bag requirements of... manufactured during that production year as complying with phase two of the advanced air bag requirements of...

Additive manufacturing technology in reconstructive surgery.

PubMed

Fuller, Scott C; Moore, Michael G

2016-10-01

Technological advances have been part and parcel of modern reconstructive surgery, in that practitioners of this discipline are continually looking for innovative ways to perfect their craft and improve patient outcomes. We are currently in a technological climate wherein advances in computers, imaging, and science have coalesced with resulting innovative breakthroughs that are not merely limited to improved outcomes and enhanced patient care, but may provide novel approaches to training the next generation of reconstructive surgeons. New developments in software and modeling platforms, imaging modalities, tissue engineering, additive manufacturing, and customization of implants are poised to revolutionize the field of reconstructive surgery. The interface between technological advances and reconstructive surgery continues to expand. Additive manufacturing techniques continue to evolve in an effort to improve patient outcomes, decrease operative time, and serve as instructional tools for the training of reconstructive surgeons.

49 CFR 585.12 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting... Traffic Safety Administration in determining whether a manufacturer has complied with the advanced air bag...

49 CFR 585.12 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting... Traffic Safety Administration in determining whether a manufacturer has complied with the advanced air bag...

49 CFR 585.12 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting... Traffic Safety Administration in determining whether a manufacturer has complied with the advanced air bag...

49 CFR 585.12 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting... Traffic Safety Administration in determining whether a manufacturer has complied with the advanced air bag...

49 CFR 585.12 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting... Traffic Safety Administration in determining whether a manufacturer has complied with the advanced air bag...

Continuously variable transmission: Assessment of applicability to advance electric vehicles

NASA Technical Reports Server (NTRS)

Loewenthal, S. H.; Parker, R. J.

1981-01-01

A brief historical account of the evolution of continuously variable transmissions (CVT) for automotive use is given. The CVT concepts which are potentially suitable for application with electric and hybrid vehicles are discussed. The arrangement and function of several CVT concepts are cited along with their current developmental status. The results of preliminary design studies conducted on four CVT concepts for use in advanced electric vehicles are discussed.

7 CFR 70.93 - Advance information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF POULTRY...

7 CFR 58.21 - Advance information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) GRADING AND INSPECTION...

7 CFR 70.93 - Advance information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF POULTRY...

7 CFR 56.58 - Advance information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF SHELL...

7 CFR 70.93 - Advance information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF POULTRY...

7 CFR 56.58 - Advance information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF SHELL...

7 CFR 56.58 - Advance information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF SHELL...

7 CFR 58.21 - Advance information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) GRADING AND INSPECTION...

7 CFR 58.21 - Advance information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) GRADING AND INSPECTION...

7 CFR 56.58 - Advance information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF SHELL...

7 CFR 70.93 - Advance information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF POULTRY...

7 CFR 58.21 - Advance information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) GRADING AND INSPECTION...

Docetaxel and gemcitabine combination therapy in advanced transitional cell carcinoma of the urothelium: results of a phase II and pharmacologic study.

PubMed

Dumez, Herlinde; Martens, Marc; Selleslach, Johan; Guetens, Gunter; De Boeck, Gert; Aerts, Rita; De Bruijn, Ernst A; Maes, Robert A; van Oosterom, Allan T

2007-02-01

Our objective was to determine the response to gemcitabine plus docetaxel in advanced urothelial transitional cell carcinoma in a phase II trial, and gemcitabine distribution between plasma and erythrocytes, following docetaxel administration. Patients with locally advanced or metastatic transitional cell carcinoma, following a maximum of one prior chemotherapy regimen, were given gemcitabine 800 mg/m on days 1 and 8 plus docetaxel 85 mg/m on day 8, every 21 days. Gemcitabine was measured in the plasma and erythrocytes of nine patients before and after docetaxel administration. Thirty-four patients (median 63 years; range 49-79 years), of whom seven had prior chemotherapy and 27 were chemotherapy-naive, received a median of six cycles (range 1-6). Complete and partial remissions were observed in two and 16 (including three pretreated) patients, respectively, for an overall response rate of 53%. Median response duration was 5 months (range 1-39+). Haematoxicity was manageable, despite grade 3 infections in 24% of patients, but other toxicities were mostly mild. An apparent shift of gemcitabine from plasma to erythrocytes occurred after docetaxel in five of six patients evaluable for this analysis. We conclude gemcitabine plus docetaxel is tolerable and highly active in treated and untreated patients with advanced transitional cell carcinoma.

Safinamide as Add-On Therapy to Levodopa in Mid- to Late-Stage Parkinson's Disease Fluctuating Patients: Post hoc Analyses of Studies 016 and SETTLE.

PubMed

Cattaneo, Carlo; Sardina, Marco; Bonizzoni, Ermino

2016-01-01

Studies 016 and SETTLE showed that safinamide was safe and effective as adjunct therapy in patients with advanced Parkinson's disease (PD) and motor fluctuations. The addition of safinamide to a stable dose of levodopa alone or with other antiparkinsonian medications significantly increased ON time with no/non-troublesome dyskinesia, decreased OFF time and improved Parkinson's symptoms. To evaluate the clinical effects of safinamide 100 mg/day on motor fluctuations and cardinal Parkinson's symptoms in specific patient subgroups using pooled data from Studies 016 and SETTLE. Both studies were double blind, placebo-controlled, randomized, phase 3 trials which enrolled patients with mid- to late-stage PD experiencing motor fluctuations while receiving optimized and stable doses of levodopa, alone or with other dopaminergic treatments. The present post-hoc analyses assessed the change from baseline in ON time (with no or non-troublesome dyskinesia) and OFF time in subgroups of patients who were receiving only levodopa at baseline, who were classified as "mild fluctuators" (daily OFF time ≤4 h), and who were receiving concomitant dopaminergic therapy, with or without amantadine, and the effects of safinamide versus placebo on individual cardinal PD symptoms during ON time. Safinamide significantly increased mean ON time (with no or non-troublesome dyskinesia) and reduced mean OFF time when used as first adjunct therapy in levodopa-treated patients and patients with mild motor fluctuations. Mean daily ON time (with no or non-troublesome dyskinesia) and OFF time were favorably changed, compared with placebo, to similar extents regardless of whether patients were receiving concomitant dopamine agonists, catechol-O-methyltransferase inhibitors and amantadine. Additionally, safinamide improved bradykinesia, rigidity, tremor and gait. Safinamide was a safe and effective first adjunct therapy in levodopa-treated patients and improved 4/5 cardinal symptoms of PD while providing benefits to mild and non-mild fluctuators and patients receiving other concomitant dopaminergic therapies.

Effect of the menstrual cycle on the optic nerve head in diabetes: analysis by confocal scanning laser ophthalmoscopy.

PubMed

Akar, Munire Erman; Yucel, Iclal; Erdem, Uzeyir; Taskin, Omur; Ozel, Alper; Akar, Yusuf

2005-04-01

The purpose of this study was to examine and compare menstrual-cycle-dependent topographic changes in the optic nerve head of normally menstruating women with different grades of type 2 diabetes mellitus. We studied the right eyes of 123 normally menstruating women (36 with severe nonproliferative diabetic retinopathy [NPDR], 42 with mild NPDR and 45 healthy subjects). All subjects underwent a complete ocular examination at baseline. At 4 hormonally distinct phases of the menstrual cycle (early follicular, late follicular, mid-luteal and late luteal), we analysed the topography of the optic nerve head, using a confocal scanning laser ophthalmoscope, and measured the serum levels of estradiol, progesterone and luteinizing hormone. We excluded from analysis the data for 8 patients with severe NPDR, 10 patients with mild NPDR and 15 control subjects who were lost to follow-up examinations during the menstrual cycle. The mean age and optic disc area did not differ significantly among the 3 groups. The duration of diabetes was significantly longer in the patients with severe NPDR than in those with mild NPDR (p < 0.05). The women with severe NPDR had a significantly increased neuroretinal rim area and a significantly decreased cup-shape measure, linear cup/disc ratio, cup/disc area ratio and cup area in the late luteal phase compared with the other phases of the menstrual cycle (p < 0.05). Those with mild NPDR or a normal retina had no significant topographic changes in the optic nerve head during the menstrual cycle. Severe NPDR is associated with significant topographic changes in the rim and cup of the optic nerve head during the menstrual cycle. This must be considered in the evaluation of women with both diabetes and glaucoma. The normal fluctuations in serum sex hormone levels during the menstrual cycle of diabetic women seem to affect the optic nerve head more when the disease is advanced.

7 CFR 58.21 - Advance information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Advance information. 58.21 Section 58.21 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Grading Service § 58.21 Advance information. Upon request of an applicant, all or part of the contents of...

40 CFR 1037.615 - Hybrid vehicles and other advanced technologies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... technologies. 1037.615 Section 1037.615 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Provisions § 1037.615 Hybrid vehicles and other advanced technologies. (a) This section applies for hybrid... credits under 40 CFR part 1036. (b) Generate advanced technology emission credits for hybrid vehicles that...

A stepwise algorithm using an at-a-glance first-line test for the non-invasive diagnosis of advanced liver fibrosis and cirrhosis.

PubMed

Boursier, Jérôme; de Ledinghen, Victor; Leroy, Vincent; Anty, Rodolphe; Francque, Sven; Salmon, Dominique; Lannes, Adrien; Bertrais, Sandrine; Oberti, Frederic; Fouchard-Hubert, Isabelle; Calès, Paul

2017-06-01

Chronic liver diseases (CLD) are common, and are therefore mainly managed by non-hepatologists. These physicians lack access to the best non-invasive tests of liver fibrosis, and consequently cannot accurately determine the disease severity. Referral to a hepatologist is then needed. We aimed to implement an algorithm, comprising a new first-line test usable by all physicians, for the detection of advanced liver fibrosis in all CLD patients. Diagnostic study: 3754 CLD patients with liver biopsy were 2:1 randomized into derivation and validation sets. Prognostic study: longitudinal follow-up of 1275 CLD patients with baseline fibrosis tests. Diagnostic study: the easy liver fibrosis test (eLIFT), an "at-a-glance" sum of points attributed to age, gender, gamma-glutamyl transferase, aspartate aminotransferase (AST), platelets and prothrombin time, was developed for the diagnosis of advanced fibrosis. In the validation set, eLIFT and fibrosis-4 (FIB4) had the same sensitivity (78.0% vs. 76.6%, p=0.470) but eLIFT gave fewer false positive results, especially in patients ≥60years old (53.8% vs. 82.0%, p<0.001), and was thus more suitable as screening test. FibroMeter with vibration controlled transient elastography (VCTE) was the most accurate among the eight fibrosis tests evaluated. The sensitivity of the eLIFT-FM VCTE algorithm (first-line eLIFT, second-line FibroMeter VCTE ) was 76.1% for advanced fibrosis and 92.1% for cirrhosis. Prognostic study: patients diagnosed as having "no/mild fibrosis" by the algorithm had excellent liver-related prognosis with thus no need for referral to a hepatologist. The eLIFT-FM VCTE algorithm extends the detection of advanced liver fibrosis to all CLD patients and reduces unnecessary referrals of patients without significant CLD to hepatologists. Blood fibrosis tests and transient elastography accurately diagnose advanced liver fibrosis in the large population of patients having chronic liver disease, but these non-invasive tests are only currently available in specialized centers. We have developed an algorithm including the easy liver fibrosis test (eLIFT), a new simple and widely available blood test. It is used as a first-line procedure that selects at-risk patients who need further evaluation with the FibroMeter VCTE , an accurate fibrosis test combining blood markers and transient elastography result. This new algorithm, called the eLIFT-FM VCTE , accurately identifies the patients with advanced chronic liver disease who need referral to a specialist, and those with no or mild liver lesions who can remain under the care of their usual physician. No registration (analysis of pooled data from previously published diagnostic studies). Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A method to switch from oral dopamine agonists to rotigotine in patients with restless legs syndrome and mild augmentation.

PubMed

Winkelman, John W; Mackie, Susan E; Mei, Leslie A; Platt, Samuel; Schoerning, Laura

2016-08-01

We examined the short- and long-term efficacy and tolerability of a cross-titration algorithm from oral dopamine agonists to the rotigotine transdermal patch in patients dissatisfied with their restless legs syndrome (RLS) treatment, predominantly with mild augmentation. Patients with RLS (n = 20) were recruited at a single site. The cross-titration consisted of decreasing oral dopaminergic agents (ropinirole by 1 mg or pramipexole by 0.25 mg) and increasing rotigotine by 1 mg every two days. Efficacy and adverse events (AEs) were assessed at one, three, six and 12 months after the switch. Patients had moderate-severe RLS symptoms at the baseline (mean international restless legs syndrome (IRLS) score 19.4 ± 5.5); 85% had augmentation and 45% reported afternoon RLS symptoms. The baseline mean pramipexole equivalent dose was 0.6 ± 0.3 mg. At Week 5, 85% (17/20) had successfully switched from their oral dopamine agonist to rotigotine (mean dose 2.5 ± 0.6 mg; change in IRLS score: -6.7 ± 8.4, p = 0.002); 14 patients were CGI-I responders (much or very much improved). Three patients withdrew due to lack of efficacy. Twelve months after cross-titration, 10 patients continued on rotigotine, of whom four required either higher doses of rotigotine or supplemental RLS medication compared with their optimal Week 5 dose; five patients withdrew due to AEs and two due to lack of efficacy. A cross-titration to rotigotine was efficacious after five weeks in 70% of patients dissatisfied with RLS treatment, most of whom had mild augmentation. At one year following the medication switch, 50% had discontinued rotigotine due to lack of continued efficacy or side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of direction of rotation in continuous and discontinuous 8 hour shift systems

PubMed Central

Tucker, P.; Smith, L.; Macdonald, I.; Folkard, S.

2000-01-01

OBJECTIVES—Previous research has produced conflicting evidence on the relative merits of advancing and delaying shift systems. The current study assessed the effects of the direction of shift rotation within 8 hour systems, upon a range of measures including sleep, on shift alertness, physical health, and psychological wellbeing.
METHODS—An abridged version of the standard shiftwork index which included retrospective alertness ratings was completed by four groups of industrial shiftworkers on relatively rapidly rotating 8 hour systems (n=611). Two groups worked continuous systems that were either advancing or delaying; the other two groups worked discontinuous systems that were either advancing or delaying.
RESULTS—Few effects were found of direction of rotation on chronic measures of health and wellbeing, even when the systems incorporated "quick returns" (a break of only 8 hours when changing from one shift to another). This was despite the use of measures previously shown to be sensitive to the effects of a broad range of features of shift systems. However, advancing continuous systems seemed to be associated with marginally steeper declines in alertness across the shift (F (3,1080)=2.87, p<0.05). They were also associated with shorter sleeps between morning shifts (F (1,404)=4.01, p<0.05), but longer sleeps between afternoons (F (1,424)=4.16, p<0.05).
CONCLUSIONS—The absence of negative effects of advancing shifts upon the chronic outcome measures accorded with previous evidence that advancing shifts may not be as harmful as early research indicated. However, this interpretation is tempered by the possibility that difficult shift systems self select those workers most able to cope with their deleterious effects. The presence of quick returns in advancing continuous systems seemed to impact upon some of the acute measures such as duration of sleep, although the associated effects on alertness seemed to be marginal.


Keywords: shift rotation; health; alertness PMID:10984340

Discovery of an α-Amino C–H Arylation Reaction Using the Strategy of Accelerated Serendipity

PubMed Central

McNally, Andrew; Prier, Christopher K.; MacMillan, David W. C.

2012-01-01

Serendipity has long been a welcome yet elusive phenomenon in the advancement of chemistry. We sought to exploit serendipity as a means of rapidly identifying unanticipated chemical transformations. By using a high-throughput, automated workflow and evaluating a large number of random reactions, we have discovered a photoredox-catalyzed C–H arylation reaction for the construction of benzylic amines, an important structural motif within pharmaceutical compounds that is not readily accessed via simple substrates. The mechanism directly couples tertiary amines with cyanoaromatics by using mild and operationally trivial conditions. PMID:22116882

Final Technical Report for grant entitled "New Horizons in C-F Activation by Main Group Electrophiles"

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

Ozerov, Oleg V; Ozerov, Oleg V.

2014-01-16

We became interested in developing new methods for hydrodefluorination (HDF) and other types of C-F bond conversion in polyfluoroalkanes under mild conditions. We were attracted to an approach to C-F activation, where the key C-F cleavage proceeds by a Lewis acid abstraction of fluoride rather than a redox event. The efforts during the previous period were aimed at a) advancing the HDF reactivity with improvement in scope and catalyst longevity; b) extending C-F activation beyond HDF; c) generating insight about the elementary steps of the reaction and potential intermediates.

Mid-maxillary distraction osteogenesis of cleft patients using a special custom-made tooth-borne device.

PubMed

Dias, D K; De Silva, H L; Senadeera, W M

2011-09-01

A relatively new approach to maxillary advancement by maxillary distraction using a combined surgical and modified orthodontic technique is described. This protocol and the technique have been used for the past 3 years (2006 to 2009) on more than 60 patients, aged between 14-29 years. Distraction of between 7 and 18 mm has been achieved, creating class 1 or mild class 2 arch relationships in cleft lip and cleft palate patients who had class 3 arch relationship compounded by significant maxillary retrusion. The technique is simple, inexpensive and less time consuming.

Hyperthermia Using Nanoparticles – Promises and Pitfalls

PubMed Central

Kaur, Punit; Aliru, Maureen L.; Chadha, Awalpreet S.; Asea, Alexzander; Krishnan, Sunil

2016-01-01

An ever-increasing body of literature affirms the physical and biological basis for sensitization of tumors to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fueled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalizes on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia. PMID:26757879

Hyperthermia using nanoparticles--Promises and pitfalls.

PubMed

Kaur, Punit; Aliru, Maureen L; Chadha, Awalpreet S; Asea, Alexzander; Krishnan, Sunil

2016-01-01

An ever-increasing body of literature affirms the physical and biological basis for sensitisation of tumours to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fuelled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalises on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia.

Maximal Aortic Valve Cusp Separation and Severity of Aortic Stenosis

PubMed Central

Dilu, VP; George, Raju

2017-01-01

Introduction An integrated approach that incorporates two dimensional, M mode and Doppler echocardiographic evaluation has become the standard means for accurate quantification of severity of valvular aortic stenosis. Maximal separation of the aortic valve cusps during systole has been shown to correlate well with the severity of aortic stenosis measured by other echocardiographic parameters. Aim To study the correlation between Maximal Aortic valve Cusp Separation (MACS) and severity of aortic valve stenosis and to find cut-off values of MACS for detecting severe and mild aortic stenosis. Materials and Methods In the present prospective observational study, we have compared the accuracy of MACS distance and the aortic valve area calculated by continuity equation in 59 patients with varying degrees of aortic valve stenosis. Aortic leaflet separation in M mode was identified as the distance between the inner edges of the tips of these structures at mid systole in the parasternal long axis view. Cuspal separation was also measured in 2D echocardiography from the parasternal long axis view and the average of the two values was taken as the MACS. Patients were grouped into mild, moderate and severe aortic stenosis based on the aortic valve area calculated by continuity equation. The resultant data regarding maximal leaflet separation on cross-sectional echocardiogram was then subjected to linear regression analysis in regard to correlation with the peak transvalvular aortic gradient as well as the calculated aortic valve area. A cut-off value for each group was derived using ROC curve. Results There was a strong correlation between MACS and aortic valve area measured by continuity equation and the peak and mean transvalvular aortic gradients. Mean MACS was 6.89 mm in severe aortic stenosis, 9.97 mm in moderate aortic stenosis and 12.36 mm in mild aortic stenosis. MACS below 8.25 mm reliably predicted severe aortic stenosis, with high sensitivity, specificity and positive predictive value. MACS above 11.25 mm practically ruled out significant aortic stenosis. Conclusion Measurement of MACS is a simple echocardio-graphic method to assess the severity of valvular aortic stenosis, with high sensitivity and specificity. MACS can be extremely useful in two clinical situations as a simple screening tool for assessment of stenosis severity and also helps in decision making non invasively when there is discordance between the other echocardiographic parameters of severity of aortic stenosis. PMID:28764221

eHealth: individualization of mesalazine treatment through a self-managed web-based solution in mild-to-moderate ulcerative colitis.

PubMed

Pedersen, Natalia; Thielsen, Peter; Martinsen, Lars; Bennedsen, Mette; Haaber, Anne; Langholz, Ebbe; Végh, Zsuzsanna; Duricova, Dana; Jess, Tine; Bell, Sally; Burisch, Johan; Munkholm, Pia

2014-12-01

To individualize treatment with mesalazine for ulcerative colitis relapses through a self-managed, web-based solution to optimize the short-term disease course. Prospective, open-label, web-guided study with 3 months mesalazine therapy among patients with mild-to-moderate ulcerative colitis. Once a week, patients completed the simple clinical colitis activity index (SCCAI) and registered fecal calprotectin (FC) on the web application: www.meza.constant-care.dk. SCCAI and FC were summed and resulted in a total inflammatory burden score (TIBS). Deep remission was defined as SCCAI ≤1; FC = 0, and TIBS ≤1. A total of 95 patients (62% females; median age 45 yr) were included in the study and allocated 4.8 g mesalazine per day. Of these, 82 (86%) patients were adherent to web therapy, completing 3 months of web-guided mesalazine therapy. Of the 82 adherent patients, 72 (88%) continued mesalazine and 10 (12%) needed rescue therapy. From weeks 0 to 12, patients had experienced a significant reduction in mean SCCAI (4.6 versus 1.6, P < 0.001), mean FC (437 versus 195, P < 0.001), and mean TIBS (6.7 versus 2.4, P < 0.001). Based on TIBS values (≤1), the dose of mesalazine was reduced to 2.4 g in 25% of patients at week 3 in 50% of subjects at week 5 and in 88% of patients at week 12. Web-guided therapy with mesalazine in mild-to-moderate ulcerative colitis helps to individualize the dose and improve adherence to therapy. The study confirms mesalazine efficacy in mild-to-moderate UC, significantly improving TIBS values in majority of the patients.

Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: A pilot double-blind randomized trial [ISRCTN45683816

PubMed Central

Akhondzadeh, Shahin; Fallah-Pour, Hasan; Afkham, Khosro; Jamshidi, Amir-Hossein; Khalighi-Cigaroudi, Farahnaz

2004-01-01

Background The morbidity and mortality associated with depression are considerable and continue to increase. Depression currently ranks fourth among the major causes of disability worldwide, after lower respiratory infections, prenatal conditions, and HIV/AIDS. Crocus sativus L. is used to treat depression. Many medicinal plants textbooks refer to this indication whereas there is no evidence-based document. Our objective was to compare the efficacy of stigmas of Crocus sativus (saffron) with imipramine in the treatment of mild to moderate depression in a 6-week pilot double-blind randomized trial. Methods Thirty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, single-center trial, patients were randomly assigned to receive capsule of saffron 30 mg/day (TDS) (Group 1) and capsule of imipramine 100 mg/day (TDS) (Group 2) for a 6-week study. Results Saffron at this dose was found to be effective similar to imipramine in the treatment of mild to moderate depression (F = 2.91, d.f. = 1, P = 0.09). In the imipramine group anticholinergic effects such as dry mouth and also sedation were observed more often that was predictable. Conclusion The main overall finding from this study is that saffron may be of therapeutic benefit in the treatment of mild to moderate depression. To the best of our knowledge this is the first clinical trial that supports this indication for saffron. A large-scale trial with placebo control is warranted. PMID:15341662

Complete mucosal healing of distal lesions induced by twice-daily budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative colitis with distal active inflammation: double-blind, randomized study.

PubMed

Naganuma, Makoto; Aoyama, Nobuo; Tada, Tomohiro; Kobayashi, Kiyonori; Hirai, Fumihito; Watanabe, Kenji; Watanabe, Mamoru; Hibi, Toshifumi

2018-04-01

Budesonide foam is used for the topical treatment of distal ulcerative colitis. This phase III study was performed to confirm mucosal healing and other therapeutic effects of twice-daily budesonide 2-mg foam in patients with mild-to-moderate ulcerative colitis including left-sided colitis and pancolitis. This was a multicenter, randomized, placebo-controlled, double-blind trial. A total of 126 patients with mild-to-moderate ulcerative colitis with active inflammation in the distal colon were randomized to two groups receiving twice-daily budesonide 2 mg/25 ml foam or placebo foam. The primary endpoint was the percentage of complete mucosal healing of distal lesions (endoscopic subscore of 0) at week 6. Some patients continued the treatment through week 12. Drug efficacy and safety were evaluated. The percentages of both complete mucosal healing of distal lesions and clinical remission were significantly improved in the budesonide as compared with the placebo group (p = 0.0003 and p = 0.0035). Subgroup analysis showed similar efficacy of budesonide foam for complete mucosal healing of distal lesions and clinical remission regardless of disease type. The clinical remission percentage tended to be higher in patients achieving complete mucosal healing of distal lesions than in other patients. There were no safety concerns with budesonide foam. This study confirmed for the first time complete mucosal healing with twice-daily budesonide 2-mg foam in mild-to-moderate ulcerative colitis with distal active inflammation. The results also indicated that complete mucosal healing of distal lesions by budesonide foam promotes clinical remission of ulcerative colitis. Clinical trial registration no.: Japic CTI-142704.

Cognitive and Affective Changes in Mild to Moderate Alzheimer’s Disease Patients Undergoing Switch of Cholinesterase Inhibitors: A 6-Month Observational Study

PubMed Central

Spalletta, Gianfranco; Caltagirone, Carlo; Padovani, Alessandro; Sorbi, Sandro; Attar, Mahmood; Colombo, Delia; Cravello, Luca

2014-01-01

Patients with Alzheimer’s disease after an initial response to cholinesterase inhibitors may complain a later lack of efficacy. This, in association with incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the switch to another cholinesterase inhibitor could represent a valid therapeutic strategy. The aim of this study was to investigate the effectiveness of the switch from one to another cholinesterase inhibitor on cognitive and affective symptoms in mild to moderate Alzheimer disease patients. Four hundred twenty-three subjects were included from the EVOLUTION study, an observational, longitudinal, multicentre study conducted on Alzheimer disease patients who switched to different cholinesterase inhibitor due either to lack/loss of efficacy or response, reduced tolerability or poor compliance. All patients underwent cognitive and neuropsychiatric assessments, carried out before the switch (baseline), and at 3 and 6-month follow-up. A significant effect of the different switch types was found on Mini-Mental State Examination score during time, with best effectiveness on mild Alzheimer’s disease patients switching from oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when measured using continuous Neuropsychiatric Inventory values, decreased significantly, while apathy symptoms remained stable over the 6 months after the switch. However, frequency of both depression and apathy, when measured categorically using Neuropsychiatric Inventory cut-off scores, did not change significantly during time. In mild to moderate Alzheimer disease patients with loss of efficacy and tolerability during cholinesterase inhibitor treatment, the switch to another cholinesterase inhibitor may represent an important option for slowing cognitive deterioration. The evidence of apathy stabilization and the positive tendency of depressive symptom improvement should definitively be confirmed in double-blind controlled studies. PMID:24586603

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

PubMed

Vellinga, Namkje A R; Boerma, E Christiaan; Koopmans, Matty; Donati, Abele; Dubin, Arnaldo; Shapiro, Nathan I; Pearse, Rupert M; van der Voort, Peter H J; Dondorp, Arjen M; Bafi, Tony; Fries, Michael; Akarsu-Ayazoglu, Tulin; Pranskunas, Andrius; Hollenberg, Steven; Balestra, Gianmarco; van Iterson, Mat; Sadaka, Farid; Minto, Gary; Aypar, Ulku; Hurtado, F Javier; Martinelli, Giampaolo; Payen, Didier; van Haren, Frank; Holley, Anthony; Gomez, Hernando; Mehta, Ravindra L; Rodriguez, Alejandro H; Ruiz, Carolina; Canales, Héctor S; Duranteau, Jacques; Spronk, Peter E; Jhanji, Shaman; Hubble, Sheena; Chierego, Marialuisa; Jung, Christian; Martin, Daniel; Sorbara, Carlo; Bakker, Jan; Ince, Can

2017-10-18

Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

Anxiety levels and related symptoms in emergency nursing personnel in Greece.

PubMed

Stathopoulou, Hariklia; Karanikola, Maria N K; Panagiotopoulou, Fotini; Papathanassoglou, Elizabeth D E

2011-07-01

Several studies provide evidence for the association between work stress and mild psychiatric morbidity among emergency nurses. These symptoms have not been explored in Greek nursing personnel employed in emergency departments. The aim of this descriptive correlational study was to investigate the presence of anxiety and stress symptoms among emergency nursing personnel in Greece. The sample was composed of nursing personnel employed in emergency departments of 8 adult General hospitals in Greece (N = 213). The Hamilton Anxiety Scale was applied for the quantitative assessment of anxiety symptoms, along with demographic, vocational, and educational data. Descriptive statistics were explored, and nonparametric comparisons, as well as correlational tests, were performed. Anxiety levels were found to be mild (1.102 ± 0.53), with women (P = .021, Mann-Whitney U test) and nursing personnel employed in public sector hospitals (P = .029, Mann-Whitney U test) having higher anxiety level scores. In addition, a statistically significant mild correlation was observed between work experience in the emergency department and anxiety states (τ = 0.178, P = .011). The most commonly reported manifestations of mild psychiatric symptomatology were sleep disturbances (2.32 ± 1.2), anxious mood (1.57 ± 1.1), and depressed mood (2.38 ± 1.2), with 24.8% of the participants reporting very severe sleep disturbance, 23.9% reporting very severe depressive mood, and 10.7% reporting very severe anxious mood. Hospital administrators need to be aware of the extent of workplace stress and subsequent anxiety symptoms that exist in emergency nurses. Staff counseling, continuing professional education, and empowerment strategies may need to be implemented to prevent psychiatric morbidity, as well as job dissatisfaction and resignations. Copyright © 2011 Emergency Nurses Association. Published by Mosby, Inc. All rights reserved.

Unobtrusive measurement of daily computer use to detect mild cognitive impairment.

PubMed

Kaye, Jeffrey; Mattek, Nora; Dodge, Hiroko H; Campbell, Ian; Hayes, Tamara; Austin, Daniel; Hatt, William; Wild, Katherine; Jimison, Holly; Pavel, Michael

2014-01-01

Mild disturbances of higher order activities of daily living are present in people diagnosed with mild cognitive impairment (MCI). These deficits may be difficult to detect among those still living independently. Unobtrusive continuous assessment of a complex activity such as home computer use may detect mild functional changes and identify MCI. We sought to determine whether long-term changes in remotely monitored computer use differ in persons with MCI in comparison with cognitively intact volunteers. Participants enrolled in a longitudinal cohort study of unobtrusive in-home technologies to detect cognitive and motor decline in independently living seniors were assessed for computer use (number of days with use, mean daily use, and coefficient of variation of use) measured by remotely monitoring computer session start and end times. More than 230,000 computer sessions from 113 computer users (mean age, 85 years; 38 with MCI) were acquired during a mean of 36 months. In mixed-effects models, there was no difference in computer use at baseline between MCI and intact participants controlling for age, sex, education, race, and computer experience. However, over time, between MCI and intact participants, there was a significant decrease in number of days with use (P = .01), mean daily use (∼1% greater decrease/month; P = .009), and an increase in day-to-day use variability (P = .002). Computer use change can be monitored unobtrusively and indicates individuals with MCI. With 79% of those 55 to 64 years old now online, this may be an ecologically valid and efficient approach to track subtle, clinically meaningful change with aging. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Severity of Visual Field Loss and Health Related Quality of Life

PubMed Central

McKean-Cowdin, Roberta; Varma, Rohit; Wu, Joanne; Hays, Ron D.; Azen, Stanley P.

2009-01-01

Purpose To examine the association between severity of visual field loss (VFL) and self-reported health-related quality of life (HRQOL) in a population-based sample. Design Population-based cross-sectional study. Methods Participants in the Los Angeles Latino Eye Study underwent a comprehensive ophthalmic examination including visual field testing using the Humphrey Automated Field Analyzer II (SITA Standard 24-2). Mean Deviation (MD) scores were used to determine severity of VFL both as a continuous variable and stratified by severity: no VFL (MD≥ − 2 decibels [dB]), mild VFL (6dB

Supplementary feeding with locally-produced Ready-to-Use Food (RUF) for mildly wasted children on Nias Island, Indonesia: comparison of daily and weekly program outcomes.

PubMed

Purwestri, Ratna C; Scherbaum, Veronika; Inayati, Dyah A; Wirawan, Nia N; Suryantan, Julia; Bloem, Maurice A; Pangaribuan, Rosnani V; Stuetz, Wolfgang; Hoffmann, Volker; Qaim, Matin; Biesalski, Hans K; Bellows, Anne C

2012-01-01

Ready-to-Use Foods (RUFs) in the form of fortified cereal/nut/legume-based biscuits (±500 kcal and 8-10% protein per 100 g) were tested among mildly wasted children from October 2007 to June 2008, and were labelled as RUF-Nias biscuits. This study reports on a comparison of supplementary feeding program outcomes of mildly wasted children with weight-for-height z-score (WHZ) >=-2 to <-1.5 SD aged >=6 to <60 months old given locally produced RUF-Nias biscuits within daily (in semi-urban areas) and weekly (in rural remote regions) distribution and supervision program settings. In the Church World Service project area, all eligible children were recruited continuously from monthly community-based screening programs and admitted into existing nutrition centers managed by the community on Nias Island, Indonesia. Individual discharge criterion of the programs was WHZ >=-1.5 SD. Of the index children admitted in daily programs (n=51), 80.4% reached target WHZ, which was higher than in weekly programs (72.9%; n=48) by a similar length of stay of about 6 weeks. Weight gain of the children in daily programs was higher (3.1±3.6 g/kg body weight/day) than in weekly programs (2.0±2.1 g/kg body weight/day), and they achieved significantly higher WHZ at discharge. However, the majority of caretakers preferred weekly programs due to lower time constraints. Locally produced RUF in the form of biscuits for treatment of mild wasting among children demonstrated promising results both in daily and weekly community-based intervention programs.

Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist.

PubMed

Fosgerau, Keld; Weber, Uno J; Gotfredsen, Jacob W; Jayatissa, Magdalena; Buus, Carsten; Kristensen, Niels B; Vestergaard, Mogens; Teschendorf, Peter; Schneider, Andreas; Hansen, Philip; Raunsø, Jakob; Køber, Lars; Torp-Pedersen, Christian; Videbaek, Charlotte

2010-10-09

The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion. Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.

Continuing Efforts to Upgrade the Aeronautics Curriculum at Jacksonville University

ERIC Educational Resources Information Center

Terrell, Jerry L.; Merkt, Juan; Harrison, Jeffrey; Yates, Rhett

2012-01-01

The aviation industry is exceptionally dynamic. Advances in technology have enabled the industry to change drastically in a short period of time. The transition to jet propulsion advances in aerodynamics, avionics improvements, and introduction of revolutionary navigation systems have all occurred within the past 60 years. These advances have…

38 CFR 36.4511 - Advances after loan closing.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Advances after loan closing. 36.4511 Section 36.4511 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) LOAN GUARANTY Direct Loans § 36.4511 Advances after loan closing. (a) The Department of Veterans...

49 CFR 585.14 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.14 Definitions. For the purposes of this subpart, (a) Phase one of the advanced air bag....208. (b) Phase two of the advanced air bag reporting requirements of Standard No. 208 refers to the...

49 CFR 585.14 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.14 Definitions. For the purposes of this subpart, (a) Phase one of the advanced air bag....208. (b) Phase two of the advanced air bag reporting requirements of Standard No. 208 refers to the...

49 CFR 585.14 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.14 Definitions. For the purposes of this subpart, (a) Phase one of the advanced air bag....208. (b) Phase two of the advanced air bag reporting requirements of Standard No. 208 refers to the...

49 CFR 585.14 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.14 Definitions. For the purposes of this subpart, (a) Phase one of the advanced air bag....208. (b) Phase two of the advanced air bag reporting requirements of Standard No. 208 refers to the...

49 CFR 585.14 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.14 Definitions. For the purposes of this subpart, (a) Phase one of the advanced air bag....208. (b) Phase two of the advanced air bag reporting requirements of Standard No. 208 refers to the...

Balance and gait of adults with very mild Alzheimer’s disease

PubMed Central

Gras, LZ; Kanaan, SF; McDowd, JM; Colgrove, YM; Burns, J; Pohl, PS

2015-01-01

Background and Purpose Studies have shown that adults with Alzheimer’s disease (AD) have gait and balance deficits, however the focus has been on those with mild to severe disease. The purpose of this study was to determine if balance and gait deficits are present in those with very mild AD. Methods Thirteen adults (72.9 ± 4.7 years old) with very mild AD and thirteen age (72.6 ± 4.6 years old) and gender-matched (10 males, 3 females) participants in a control group without AD performed balance and gait tests. All participants were living in the community and independent in community ambulation. Results Participants with very mild AD had shorter times in the sharpened Romberg tests with eyes open (p<0.001) and with eyes closed (p=0.007) compared to participants in the control group. Those with AD also took longer to complete the Timed “Up & Go” Test (TUG), (p< 0.001). Gait deficits were found for those with AD as demonstrated by slower velocities in the 10-meter walk at a comfortable pace (p=0.029) and on an instrumented walkway (p<0.001). Stance times were longer for those with AD (p<0.001) and step length was shorter (p=0.001). There were no group differences in the 10-meter walk at a fast pace. The gait velocity of participants in the control group was faster on the instrumented walkway than in the 10-meter walk at a comfortable pace (p=0.031). In contrast, the gait velocity of those with AD was significantly slower on the instrumented walkway than in the 10-meter walk at a comfortable pace, (p=0.024). Discussion Balance and gait deficits may be present in those in the very early stages of AD. Novel surfaces may affect gait speed in those with very mild AD. Identifying mobility deficits early in the progression of AD may provide an opportunity for early physical therapy intervention, thus promoting continued functional independence. Conclusions Adults in the very early stages of AD may show signs of balance and gait deficits. Recognition of these problems early with subsequent physical therapy may slow the progression of further balance and gait dysfunction. PMID:24755691

Effects of Souvenaid on plasma micronutrient levels and fatty acid profiles in mild and mild-to-moderate Alzheimer's disease.

PubMed

Rijpma, Anne; Meulenbroek, Olga; van Hees, Anneke M J; Sijben, John W C; Vellas, Bruno; Shah, Raj C; Bennett, David A; Scheltens, Philip; Olde Rikkert, Marcel G M

2015-01-01

Circulating levels of uridine, selenium, vitamins B12, E and C, folate, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been shown to be lower in patients with Alzheimer's disease (AD) than in healthy individuals. These low levels may affect disease pathways involved in synapse formation and neural functioning. Here, we investigated whether, and to what extent, circulating levels of micronutrients and fatty acids can be affected by oral supplementation with Souvenaid (containing a specific nutrient combination), using data derived from three randomized clinical trials (RCT) and an open-label extension (OLE) study with follow-up data from 12 to 48 weeks. Subjects with mild (RCT1, RCT2) or mild-to-moderate AD (RCT3) received active or control product once daily for 12-24 weeks or active product during the 24-week OLE following RCT2 (n = 212-527). Measurements included plasma levels of B vitamins, choline, vitamin E, selenium, uridine and homocysteine and proportions of DHA, EPA and total n-3 long-chain polyunsaturated fatty acids in plasma and erythrocytes. Between-group comparisons were made using t tests or non-parametric alternatives. We found that 12-24-week active product intake increased plasma and/or erythrocyte micronutrients: uridine; choline; selenium; folate; vitamins B6, B12 and E; and fatty acid levels of DHA and EPA (all p < 0.001). In the OLE study, similar levels were reached in former control product/initial active product users, whereas 24-week continued active product intake showed no suggestion of a further increase in nutrient levels. These data show that circulating levels of nutrients known to be decreased in the AD population can be increased in patients with mild and mild-tomoderate AD by 24-48-week oral supplementation with Souvenaid. In addition, to our knowledge, this is the first report of the effects of sustained dietary intake of uridine monophosphate on plasma uridine levels in humans. Uptake of nutrients is observed within 6 weeks, and a plateau phase is reached for most nutrients during prolonged intake, thus increasing the availability of precursors and cofactors in the circulation that may be used for the formation and function of neuronal membranes and synapses in the brain.

Recent advances in microparticle continuous separation.

PubMed

Kersaudy-Kerhoas, M; Dhariwal, R; Desmulliez, M P Y

2008-03-01

Recent advances in microparticle separation in continuous flow are presented. It is intended for scientists in the field of separation science in biology, chemistry and microsystems engineering. Recent techniques of micron-sized particle separation within microsystems are described with emphasis on five different categories: optical, magnetic, fluidic-only, electrical and minor separation methods. Examples from the growing literature are explained with insights on separation efficiency and microengineering challenges. Current applications of the techniques are discussed.

Securing the High Ground: Dominant Combat Air Force for America. 2008 Combat Air Force Strategic Plan

DTIC Science & Technology

2008-07-28

continue to be beyond our technical ability to realize aggresively pursue advanced technical solutions to stay at the leading edge of technological...inherent to each caf Way and to seek continual improvement through exploration of innovative concepts, advanced capabilities, game -changing...available online at the air force portal: https://wwwd.my.af.mil/afknprod/strat_plan COMBAT AIR FORCE STRATEGIC PLAN Points of Contact securing the high

Effects of UAV Supervisory Control on F-18 Formation Flight Performance in a Simulator Environment

DTIC Science & Technology

2013-03-01

words) Continual advances in technology, along with increased cockpit workload— particularly the shift from two- seat to single- seat fighters to save...INTENTIONALLY LEFT BLANK v ABSTRACT Continual advances in technology, along with increased cockpit workload— particularly the shift from two- seat to...single- seat fighters to save money and reduce risk to life—push the limits of human mental capacity. Additionally, there is interest within the

Advanced electromagnetic methods for aerospace vehicles

NASA Technical Reports Server (NTRS)

Balanis, Constantine A.; Sun, Weimin; El-Sharawy, El-Budawy; Aberle, James T.; Birtcher, Craig R.; Peng, Jian; Tirkas, Panayiotis A.

1992-01-01

The Advanced Helicopter Electromagnetics (AHE) Industrial Associates Program continues its research on variety of main topics identified and recommended by the Advisory Task Force of the program. The research activities center on issues that advance technology related to helicopter electromagnetics. While most of the topics are a continuation of previous works, special effort has been focused on some of the areas due to recommendations from the last annual conference. The main topics addressed in this report are: composite materials, and antenna technology. The area of composite materials continues getting special attention in this period. The research has focused on: (1) measurements of the electrical properties of low-conductivity materials; (2) modeling of material discontinuity and their effects on the scattering patterns; (3) preliminary analysis on interaction of electromagnetic fields with multi-layered graphite fiberglass plates; and (4) finite difference time domain (FDTD) modeling of fields penetration through composite panels of a helicopter.

Advances in aortic disease management: a year in review.

PubMed

Garg, Vinay; Ouzounian, Maral; Peterson, Mark D

2016-03-01

The medical and surgical management of aortic disease is continually changing in search for improved outcomes. Our objective is to highlight recent advances in a few select areas pertaining to aortic disease and aortic surgery: the genetics of aortopathy, medical therapy of aortic aneurysms, advances in cardiac imaging, and operative strategies for the aortic arch. As our understanding of the genetic basis for aortopathy continues to improve, routine genetic testing may be of value in assessing patients with genetically triggered forms of aortic disease. With regard to medical advances, treating patients with Marfan syndrome with either losartan or atenolol at an earlier stage in their disease course improves outcomes. In addition, novel imaging indices such as wall shear stress and aortic stiffness assessed by MRI may become useful markers of aortopathy and warrant further study. With regard to the optimal technique for cerebral perfusion in aortic arch surgery, high-quality data are still lacking. Finally, in patients with complex, multilevel aortic disease, the frozen elephant trunk is a viable single-stage option compared with the conventional elephant trunk, although with an increased risk for spinal cord injury. Based on recent advances, continued studies in genetics, cardiac imaging, and surgical trials will further elucidate the etiology of aortopathy and ultimately guide management, both medically and surgically.

Inverse effects of Polyacrylamide (PAM) usage in furrow irrigation on advance time and deep percolation.

PubMed

Meral, Ramazan; Cemek, Bilal; Apan, Mehmet; Merdun, Hasan

2006-10-01

The positive effects of Polyacrylamide (PAM), which is used as a soil conditioner in furrow irrigation, on sediment transport, erosion, and infiltration have been investigated intensively in recent years. However, the effects of PAM have not been considered enough in irrigation system planning and design. As a result of increased infiltration because of PAM, advance time may be inversely affected and deep percolation increases. However, advance time in furrow irrigation is a crucial parameter in order to get high application efficiency. In this study, inverse effects of PAM were discussed, and as an alternative solution, the applicability of surge flow was investigated. PAM application significantly increased the advance time at the rates of 41.3-56.3% in the first irrigation. The application of surge flow with PAM removed this negative effect on advance time, where there was no statistically significant difference according to normal continuous flow (without PAM). PAM applications significantly increased the deep percolation, 80.3-117.1%. Surge flow with PAM had significantly positive effect on the deep percolation compared to continuous flow with PAM but not compared to normal continuous flow. These results suggested that irrigation planning should me made based on the new soil and flow conditions because of PAM usage, and surge flow can be a solution to these problems.

Effect of core body temperature, time of day, and climate conditions on behavioral patterns of lactating dairy cows experiencing mild to moderate heat stress.

PubMed

Allen, J D; Hall, L W; Collier, R J; Smith, J F

2015-01-01

Cattle show several responses to heat load, including spending more time standing. Little is known about what benefit this may provide for the animals. Data from 3 separate cooling management trials were analyzed to investigate the relationship between behavioral patterns in lactating dairy cows experiencing mild to moderate heat stress and their body temperature. Cows (n=157) were each fitted with a leg data logger that measured position and an intravaginal data logger that measures core body temperature (CBT). Ambient conditions were also collected. All data were standardized to 5-min intervals, and information was divided into several categories: when standing and lying bouts were initiated and the continuance of each bout (7,963 lying and 6,276 standing bouts). In one location, cows were continuously subjected to heat-stress levels according to temperature-humidity index (THI) range (THI≥72). The THI range for the other 2 locations was below and above a heat-stress threshold of 72 THI. Overall and regardless of period of day, cows stood up at greater CBT compared with continuing to stand or switching to a lying position. In contrast, cows lay down at lower CBT compared with continuing to lie or switching to a standing position, and lying bouts lasted longer when cows had lower CBT. Standing bouts also lasted longer when cattle had greater CBT, and they were less likely to lie down (less than 50% of lying bouts initiated) when their body temperature was over 38.8°C. Also, cow standing behavior was affected once THI reached 68. Increasing CBT decreased lying duration and increased standing duration. A CBT of 38.93°C marked a 50% likelihood a cow would be standing. This is the first physiological evidence that standing may help cool cows and provides insight into a communally observed behavioral response to heat. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Combat-Related Posttraumatic Headache: Diagnosis, Mechanisms of Injury, and Challenges to Treatment

DTIC Science & Technology

2010-09-01

514 • JAOA • Vol 110 • No 9 • September 2010 Kozminski • Original Contribution Context: Studies have revealed the rates of posttraumatic stress ...Although studies1-4 have reported rates of post- traumatic stress disorder (PTSD) and concussion or mild TBI for US soldiers returning from combat... stressful response that the details of the head injury also completed the required half day per week of continuity clinic. During this time frame, I

Forging Oxide-Dispersion-Strengthened Superalloys

NASA Technical Reports Server (NTRS)

Harf, F. H.; Glasgow, T. K.; Moracz, D. J.; Austin, C. M.

1986-01-01

Cladding of mild steel prevents surface cracking when alloy contacts die. Continual need for improvements in properties of alloys capable of withstanding elevated temperatures. Accomplished by using oxide-dispersion-strengthed superalloys such as Inconel Alloy MA 6000. Elevated tensile properties of forged alloy equal those of hot-rolled MA 6000 bar. Stress-rupture properties somewhat lower than those of bar stock but, at 1,100 degrees C, exceed those of strongest commercial single crystal, directionally solidified and conventionally cast superalloys.

Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain.

PubMed

Ahern, Terence L; Herring, Andrew A; Miller, Steve; Frazee, Bradley W

2015-07-01

Use of low-dose ketamine infusions in the emergency department (ED) has not previously been described, despite routine use in perioperative and other settings. Our hypothesis was that a low-dose ketamine bolus followed by continuous infusion would 1) provide clinically significant and sustained pain relief; 2) be well tolerated; and 3) be feasible in the ED. We prospectively administered 15 mg intravenous ketamine followed immediately by continuous ketamine infusion at 20 mg/h for 1 hour. Optional morphine (4 mg) was offered at 20, 40, and 60 minutes. Pain intensity, vitals signs, level of sedation, and adverse reactions were assessed for 120 minutes. A total of 38 patients were included with a median initial numerical rating scale (NRS) pain score of 9. At 10 minutes, the median reduction in pain score was 4, with 7 patients reporting a score of 0. At 60 and 120 minutes, 25 and 26 patients, respectively, reported clinically significant pain reduction (decrease NRS score > 3). Heart rate, blood pressure, respiratory rate, and oxygen saturation remained stable. Mild or moderate side effects including dizziness, fatigue, and headache were common. Patient satisfaction was high; 85% reported they would have this medication again for similar pain. A low-dose ketamine infusion protocol provided significant pain relief with mostly mild side effects and no severe adverse events. Wiley Periodicals, Inc.

Cot-side electroencephalography monitoring is not clinically useful in the detection of mild neonatal hypoglycemia.

PubMed

Harris, Deborah L; Weston, Philip J; Williams, Christopher E; Pleasants, Anthony B; Battin, Malcolm R; Spooner, Claire G; Harding, Jane E

2011-11-01

To determine whether there is a relationship between electroencephalography patterns and hypoglycemia, by using simultaneous cot-side amplitude integrated electroencephalography (aEEG) and continuous interstitial glucose monitoring, and whether non-glucose cerebral fuels modified these patterns. Eligible babies were ≥ 32 weeks gestation, at risk for hypoglycemia, and admitted to the neonatal intensive care unit. Electrodes were placed in C3-P3, C4-P4 O1-O2 montages. A continuous interstitial glucose sensor was placed subcutaneously, and blood glucose was measured by using the glucose oxidase method. Non-glucose cerebral fuels were measured at study entry, exit, and during recognized hypoglycemia. A total of 101 babies were enrolled, with a median weight of 2179 g and gestation of 35 weeks. Twenty-four of the babies had aEEG recordings, and glucose concentrations were low (< 2.6 mM). There were 103 episodes of low glucose concentrations lasting 5 to 475 minutes, but no observable changes in aEEG variables. Plasma concentrations of lactate, beta-hydroxybutyrate, and glycerol were low and did not alter during hypoglycemia. Cot-side aEEG was not useful for the detection of neurological changes during mild hypoglycemia. Plasma concentrations of non-glucose cerebral fuels were low and unlikely to provide substantial neuroprotection. Copyright © 2011 Mosby, Inc. All rights reserved.

Impact of the removal of light and mild descriptors from cigarette packages in Ontario, Canada: switching to "light replacement" brand variants.

PubMed

Cohen, Joanna E; Yang, Jingyan; Donaldson, Elisabeth A

2014-12-01

This study assessed cessation and brand switching among smokers in Ontario, Canada after tobacco companies' voluntary removal of 'light' and 'mild' descriptors from cigarette packages. We analyzed longitudinal data on brand preference and cessation from a cohort of smokers (n=632) in the Ontario Tobacco Survey in Canada from 2006 to 2008 with a longitudinal regression model. While cessation differed by brand variant prior to the ban (7% light vs. 3% regular; P<0.05), it did not differ by brand variant after the ban was implemented. In 2008, when light cigarette brand variants were no longer available, 33% of the sample still reported smoking lights and 31% smoked light replacement brand variants. During each subsequent follow-up, light brand smokers had 2 times the odds of smoking regular brand variants (Adjusted OR: 2.03, 95% CI 1.80,2.29), and almost 5 times the odds of using light replacement brand variants (Adjusted OR: 4.87, 95% CI 4.07,5.84), respectively, compared to continuing to smoke lights. Even after removing misleading descriptors from cigarette packs, smokers continued to report using light brand variants, and many switched to newly introduced light replacement brand variants. After full implementation of the ban, cessation did not vary by brand variant. Copyright © 2014. Published by Elsevier Inc.

Five-months-postoperative neuropsychological outcome from a pilot prospective randomized clinical trial of thalamic deep brain stimulation for Tourette syndrome.

PubMed

Schoenberg, Mike R; Maddux, Brian N; Riley, David E; Whitney, Christina M; Ogrocki, Paula K; Gould, Deborah; Maciunas, Robert J

2015-02-01

Tourette syndrome (TS) is a neuropsychiatric disorder presenting with motor and/or sonic tics associated with frontostriatal dysfunction. This study provided pilot data of the neuropsychological safety of bilateral thalamic deep brain stimulation (DBS) to treat medication-refractory TS in adults. This study used a repeated-measures design with pretest and 3-month follow-up from start of continuous bilateral DBS. Five male patients underwent DBS surgery for medically refractory TS. Repeated-measures ANOVA was used to evaluate for any change in neuropsychological test scores, employing a false discovery rate. Outcome measures included 14 neuropsychological tests assessing psychomotor speed, attention, memory, language, visuoconstructional, and executive functions, as well as subjective mood ratings of depression and anxiety. Average age was 28.2 years (SD = 7.5) with 12-17 years of education. Participants were disabled by tics, with a tic frequency of 50-80 per minute before surgery. At baseline, subjects' cognitive function was generally average, although mild deficits in sequencing and verbal fluency were present, as were clinically mild obsessive-compulsive symptoms. At 3 months of continuous DBS (5 months after implantation), 3 of 5 participants had clinical reductions in motor and sonic tics. Cognitive scores generally remained stable, but declines of moderate to large effect size (Cohen's d > 0.6) in verbal fluency, visual immediate memory, and reaction time were observed. Fewer symptoms of depression and anxiety, as well as fewer obsessions and compulsions, were reported after 3 months of continuous high-frequency DBS. Bilateral centromedian-parafascicular thalamic DBS for medically refractory TS shows promise for treatment of medically refractory TS without marked neuropsychological morbidity. Symptoms of depression and anxiety improved. © 2014 International Neuromodulation Society.

Maxillomandibular advancement as the initial treatment of obstructive sleep apnoea: Is the mandibular occlusal plane the key?

PubMed

Rubio-Bueno, P; Landete, P; Ardanza, B; Vázquez, L; Soriano, J B; Wix, R; Capote, A; Zamora, E; Ancochea, J; Naval-Gías, L

2017-11-01

Maxillomandibular advancement (MMA) can be effective for managing obstructive sleep apnoea (OSA); however, limited information is available on the predictor surgical variables. This study investigated whether normalization of the mandibular occlusal plane (MOP) was a determinant factor in curing OSA. Patients with moderate or severe OSA who underwent MMA were evaluated by preoperative and postoperative three-dimensional (3D) scans and polysomnograms. The postoperative value of MOP and the magnitude of skeletal advancement were the predictor variables; change in the apnoea-hypopnoea index (AHI) was the main outcome variable. Thirty-four subjects with a mean age of 41±14years and 58,8% female were analysed. The Epworth Sleepiness Scale (ESS) was 17.4±5.4 and AHI was 38.3±10.7 per hour before surgery. Postoperative AHI was 6.5±4.3 per hour (P<0.001) with 52.94% of the patients considered as cured, and 47.06% suffering from a mild residual OSA with ESS 0.8±1.4 (P<0.001). 3D changes revealed a volume increase of 106.3±38.8%. The mandible was advanced 10.4±3.9mm and maxilla 4.9±3.2mm. MOP postoperative value was concluded to be the best predictor variable. Treatment planning should include MOP normalization and a mandibular advancement between 6 and 10mm. The maxillary advancement would depend on the desired aesthetic changes and final occlusion. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Incidence and Predictors of Advance Care Planning Among Persons with Cognitive Impairment

PubMed Central

Garand, Linda; Dew, Mary Amanda; Lingler, Jennifer H.; DeKosky, Steven T.

2010-01-01

Objective Persons with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) are at heightened risk for future decisional incapacity. We sought to characterize advance care planning (ACP) rates over time in individuals who had no advance directives (living will or durable power of attorney) in place when they initially presented for a cognitive evaluation. Design Retrospective analysis of data that had been prospectively collected. Setting Alzheimer’s Disease Research Center memory disorders clinic. Participants Persons (N=127) with a diagnosis of MCI or early AD (n = 72) or moderate to severe AD (n = 55) and no advance directives upon initial presentation for a cognitive evaluation. Measurements Extraction of responses to items pertaining to advance care planning assessed during annual semi-structured interviews. Results By 5 years of follow-up, 39% of the sample had initiated ACP, with little difference by baseline diagnosis. Younger subjects (under 65 years old) were significantly more likely to initiate advance directives (43%) than were older subjects (37%). This age effect was more pronounced in men than women as well as in married subjects, those with a family history of dementia, no depressive disorder, and subjects with moderate to severe AD (versus those with MCI or early AD) at baseline. Conclusion Only a minority of subjects initiated ACPs. The findings suggest the need for interventions aimed at enhancing ACP completion rates, particularly among older adults with cognitive impairment since these individuals may have a timed-limited opportunity to plan for future medical, financial, and other major life decisions. PMID:21785291

Advance directives as a tool to respect patients' values and preferences: discussion on the case of Alzheimer's disease.

PubMed

Porteri, Corinna

2018-02-20

The proposal of the new criteria for the diagnosis of Alzheimer's disease (AD) based on biomarker data is making possible a diagnosis of AD at the mild cognitive impairment (MCI) or predementia/prodromal- stage. Given the present lack of effective treatments for AD, the opportunity for the individuals to personally take relevant decisions and plan for their future before and if cognitive deterioration occurs is one the main advantages of an early diagnosis. Advance directives are largely seen as an effective tool for planning medical care in the event the subject becomes incompetent. Nevertheless, their value has been questioned with regard to people with dementia by scholars who refer to the arguments of personal identity and of patient's changing interests before and after the onset of dementia. In this paper, I discuss the value of advance directives in Alzheimer's disease and other kind of dementia. Despite critics, I argue that advance directives are especially advisable in dementia and provide reasons in favor of their promotion at an early stage of the disease as a valuable tool to respect patients' values and preferences on medical treatment, including participation in research and end of life decisions. I mainly support advance directives that include both decisions regarding health care and the appointment of an attorney in fact. I conclude that patients with AD at a prodromal or early stage should be offered the opportunity to execute an advance directive, and that not to honor a demented individual's directive would be an unacceptable form of discrimination towards those patients.

Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi's sarcoma.

PubMed

Gill, P S; Tulpule, A; Espina, B M; Cabriales, S; Bresnahan, J; Ilaw, M; Louie, S; Gustafson, N F; Brown, M A; Orcutt, C; Winograd, B; Scadden, D T

1999-06-01

Liposomal anthracyclines are the present standard treatment for advanced AIDS-related Kaposi's sarcoma (KS). No effective therapies have been defined for use after treatment failure of these agents. A phase II trial was thus conducted with paclitaxel in patients with advanced KS to assess safety and antitumor activity. A regimen of paclitaxel at a dose of 100 mg/m(2) was given every 2 weeks to patients with advanced AIDS-related KS. Patients were treated until complete remission, disease progression, or unacceptable toxicity occurred. Fifty-six patients with advanced AIDS-related KS were accrued. Tumor-associated edema was present in 70% of patients and visceral involvement in 45%. Forty patients (71%) had received prior systemic therapy; 31 of these were resistant to an anthracycline. The median entry CD4(+) lymphocyte count was 20 cells/mm(3) (range, 0 to 358). A median of 10 cycles (range, 1 to 54+) of paclitaxel was administered. Fifty-nine percent of patients showed complete (n = 1) or partial response (n = 32) to paclitaxel. The median duration of response was 10.4 months (range, 2.8 to 26.7+ months) and the median survival was 15.4 months. The main side effects of therapy were grade 3 or 4 neutropenia in 61% of patients and mild-to-moderate alopecia in 87%. Paclitaxel at 100 mg/m(2) given every 2 weeks is active and well tolerated in the treatment of advanced and previously treated AIDS-related KS. The median duration of response is among the longest observed for any regimen or single agent reported for AIDS-related KS. Paclitaxel at this dosage and schedule is a treatment option for patients with advanced AIDS-related KS, including those who have experienced treatment failure of prior systemic therapy.

The Attitudes of Indian Palliative-care Nurses and Physicians to Pain Control and Palliative Sedation.

PubMed

Gielen, Joris; Gupta, Harmala; Rajvanshi, Ambika; Bhatnagar, Sushma; Mishra, Seema; Chaturvedi, Arvind K; den Branden, Stef Van; Broeckaert, Bert

2011-01-01

We wanted to assess Indian palliative-care nurses and physicians' attitudes toward pain control and palliative sedation. From May to September 2008, we interviewed 14 physicians and 13 nurses working in different palliative-care programs in New Delhi, using a semi-structured questionnaire, and following grounded-theory methodology (Glaser and Strauss). The interviewees did not consider administration of painkillers in large doses an ethical problem, provided the pain killers are properly titrated. Mild palliative sedation was considered acceptable. The interviewees disagreed whether palliative sedation can also be deep and continuous. Arguments mentioned against deep continuous palliative sedation were the conviction that it may cause unacceptable side effects, and impedes basic daily activities and social contacts. A few interviewees said that palliative sedation may hasten death. Due to fears and doubts regarding deep continuous palliative sedation, it may sometimes be too easily discarded as a treatment option for refractory symptoms.

Organization and Management of Continuing Education in German and Finnish Universities

ERIC Educational Resources Information Center

Zawacki-Richter, Olaf; Knust, Michaela; Hanft, Anke

2009-01-01

In 2006, an international comparison study investigated the organization and management of university continuing education (UCE). The Finnish continuing education system proved to be especially advanced in this study. On the other hand, it became clear that Germany was still lagging behind in continuing education. In this article, German and…

Evaluation Models for Continuing Education Program Efficacy: How Does Athletic Training Continuing Education Measure up?

ERIC Educational Resources Information Center

Doherty-Restrepo, Jennifer L.; Hughes, Brian J.; Del Rossi, Gianluca; Pitney, William A.

2009-01-01

Objective: Although continuing education is required for athletic trainers (AT) to maintain their Board of Certification credential, little is known regarding its efficacy for advancing knowledge and improving patient care. Continuing professional education (CPE) is designed to provide professionals with important practical learning opportunities.…

Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries

PubMed Central

2013-01-01

Background Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common. Methods Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12–24 months after delivery (n = 1070). Women with a CD4 count of 200-500cells/mm3 and gestational age 28–36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: <200 cells/mm3 initiated antiretroviral therapy, and >500 cells/mm3 received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin < 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models. Results At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥6 months) and shorter ARV exposure. Severe anaemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1–2 months of ARV’s, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort. Conclusions Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring. Trial registration number ISRCTN71468401 PMID:24192332

Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries.

PubMed

Sartorius, Benn K D; Chersich, Matthew F; Mwaura, Mary; Meda, Nicolas; Temmerman, Marleen; Newell, Marie Louise; Farley, Timothy M M; Luchters, Stanley

2013-11-06

Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common. Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12-24 months after delivery (n = 1070). Women with a CD4 count of 200-500 cells/mm(3) and gestational age 28-36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: <200 cells/mm(3) initiated antiretroviral therapy, and >500 cells/mm(3) received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin < 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models. At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥ 6 months) and shorter ARV exposure. Severe anaemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1-2 months of ARV's, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort. Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring. ISRCTN71468401.

Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer

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

Maurel, Joan; Martin-Richard, Marta; Conill, Carlos

Purpose: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor is overexpressed in pancreatic cancer, and in vitro studies have shown that epidermal growth factor receptor inhibitors can overcome radio- and chemoresistance. The aim of the study was to determine whether the addition of gefitinib to RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe. Methods and Materials: Eighteen patients with pathologically proven LAPC, based on major vascular invasion based on helical computed tomography (CT) and endoscopic ultrasound, were entered into the study. The targeted irradiated volume includedmore » the tumor and 2-cm margin. Prophylactic irradiation of regional nodes was not allowed. Patients with >500 cm{sup 3} of planning tumor volume were excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150, and 200 mg/m{sup 2}/day of gemcitabine in a 2-h infusion over Weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers was also performed to evaluate a possible antiangiogenic effect. Results: There were no dose-limiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95% confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5) months, and the median overall survival was 7.5 (95% CI 5.2-9.9) months. No significant reduction of vascular endothelial growth factor and interleukin-8 was observed after treatment. Conclusion: Our results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC.« less

A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

PubMed

Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

2017-01-01

In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild ovarian stimulation versus 13.6% (27/199) for conventional ovarian stimulation leading to a risk ratio of 0.95 (95% CI: 0.57-1.57), representing an absolute difference of -0.7% (95% CI: -7.4 to 5.9). This 95% CI does not extend below the predefined threshold of 10% for inferiority. The duration of ovarian stimulation was significantly lower in the mild ovarian stimulation strategy than in the conventional ovarian stimulation strategy (mean difference -1.2 days, 95% CI: -1.88 to -0.62). Also, a significantly lower amount of gonadotropins was used in the mild simulation strategy, with a mean difference of 3135 IU (95% CI: -3331 to -2940). A limitation of our study was the lack of data concerning the cryopreservation of surplus embryos, so we are not informed on cumulative pregnancy rates. Another limitation is that we were not able to follow up on the ongoing pregnancies in all centers, so we are not informed on live birth rates. The results are directly applicable in daily clinical practice and may lead to considerable cost savings as high dosages of gonadotropins are not necessary in women with poor ovarian reserve undergoing IVF. A health economic analysis of our data planned to test the hypothesis that mild ovarian stimulation strategy is more cost-effective than the conventional ovarian stimulation strategy is underway. This study was supported by NUFFIC scholarship (the Netherlands) and STDF short-term fellowship (Egypt). NTR2788 (Trialregister.nl). 01 March 2011. May 2011. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Proposal for Using a Studio Format to Enhance Institutional Advancement

ERIC Educational Resources Information Center

Chance, Shannon

2008-01-01

Universities today need to become quicker on their toes. They must continually scan the environment and seize emerging opportunities--and institutional advancement must lead this effort. An unfortunate number of institutional advancement operations are ill equipped for the task at hand. Many suffer from high staff turnover and overly hierarchical…

A Continuation Study Using Sunitinib Malate For Patients Leaving Treatment On A Previous Sunitinib Study.

ClinicalTrials.gov

2015-10-07

Metastatic Breast Cancer [F]; Advanced Breast Cancer; Metastatic Castration Resistant Prostate Cancer; Metastatic Renal Cell Cancer; Non-Small Cell Lung Cancer; Thyroid Cancer; Advanced/Metastatic Non-Small Cell Lung Cancer; Advanced Gastric Cancer; Gastrointestinal Stromal Tumor; Hepatocellular Carcinoma; Pancreatic Islet Cell Carcinoma; Pancreatic Neuroendocrine Tumor

45 CFR 1355.54 - Submittal of advance planning documents.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Submittal of advance planning documents. 1355.54 Section 1355.54 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN... § 1355.54 Submittal of advance planning documents. The State title IV-E agency must submit an APD for a...

Patterns of False Memory in Patients with Huntington's Disease.

PubMed

Chen, I-Wen; Chen, Chiung-Mei; Wu, Yih-Ru; Hua, Mau-Sun

2017-06-01

Increased false memory recognition in patients with Huntington's disease (HD) has been widely reported; however, the underlying memory constructive processes remain unclear. The present study explored gist memory, item-specific memory, and monitoring ability in patients with HD. Twenty-five patients (including 13 patients with mild HD and 12 patients with moderate-to-severe HD) and 30 healthy comparison participants (HC) were recruited. We used the Deese-Roediger-McDermott (DRM) paradigm to investigate participants' false recognition patterns, along with neuropsychological tests to assess general cognitive function. Both mild and moderate-to-severe patients with HD showed significant executive functioning and episodic memory impairment. On the DRM tasks, both HD patient groups showed significantly impaired performance in tasks assessing unrelated false recognition and item-specific memory as compared to the HC group; moderate-to-severe patients performed more poorly than mild patients did. Only moderate-severe patients exhibited significantly poorer related false recognition index scores than HCs in the verbal DRM task; performance of HD patient groups was comparable to the HC group on the pictorial DRM task. It appears that diminished verbatim memory and monitoring ability are early signs of cognitive decline during the HD course. Conversely, gist memory is relatively robust, with only partial decline during advanced-stage HD. Our findings suggest that medial temporal lobe function is relatively preserved compared to that of frontal-related structures in early HD. Thus, gist-based memory rehabilitation programs might be beneficial for patients with HD. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

FDG-PET imaging in mild traumatic brain injury: a critical review

PubMed Central

Byrnes, Kimberly R.; Wilson, Colin M.; Brabazon, Fiona; von Leden, Ramona; Jurgens, Jennifer S.; Oakes, Terrence R.; Selwyn, Reed G.

2013-01-01

Traumatic brain injury (TBI) affects an estimated 1.7 million people in the United States and is a contributing factor to one third of all injury related deaths annually. According to the CDC, approximately 75% of all reported TBIs are concussions or considered mild in form, although the number of unreported mild TBIs (mTBI) and patients not seeking medical attention is unknown. Currently, classification of mTBI or concussion is a clinical assessment since diagnostic imaging is typically inconclusive due to subtle, obscure, or absent changes in anatomical or physiological parameters measured using standard magnetic resonance (MR) or computed tomography (CT) imaging protocols. Molecular imaging techniques that examine functional processes within the brain, such as measurement of glucose uptake and metabolism using [18F]fluorodeoxyglucose and positron emission tomography (FDG-PET), have the ability to detect changes after mTBI. Recent technological improvements in the resolution of PET systems, the integration of PET with magnetic resonance imaging (MRI), and the availability of normal healthy human databases and commercial image analysis software contribute to the growing use of molecular imaging in basic science research and advances in clinical imaging. This review will discuss the technological considerations and limitations of FDG-PET, including differentiation between glucose uptake and glucose metabolism and the significance of these measurements. In addition, the current state of FDG-PET imaging in assessing mTBI in clinical and preclinical research will be considered. Finally, this review will provide insight into potential critical data elements and recommended standardization to improve the application of FDG-PET to mTBI research and clinical practice. PMID:24409143

Identifying Specific Combinations of Multimorbidity that Contribute to Health Care Resource Utilization: An Analytic Approach.

PubMed

Schiltz, Nicholas K; Warner, David F; Sun, Jiayang; Bakaki, Paul M; Dor, Avi; Given, Charles W; Stange, Kurt C; Koroukian, Siran M

2017-03-01

Multimorbidity affects the majority of elderly adults and is associated with higher health costs and utilization, but how specific patterns of morbidity influence resource use is less understood. The objective was to identify specific combinations of chronic conditions, functional limitations, and geriatric syndromes associated with direct medical costs and inpatient utilization. Retrospective cohort study using the Health and Retirement Study (2008-2010) linked to Medicare claims. Analysis used machine-learning techniques: classification and regression trees and random forest. A population-based sample of 5771 Medicare-enrolled adults aged 65 and older in the United States. Main covariates: self-reported chronic conditions (measured as none, mild, or severe), geriatric syndromes, and functional limitations. Secondary covariates: demographic, social, economic, behavioral, and health status measures. Medicare expenditures in the top quartile and inpatient utilization. Median annual expenditures were $4354, and 41% were hospitalized within 2 years. The tree model shows some notable combinations: 64% of those with self-rated poor health plus activities of daily living and instrumental activities of daily living disabilities had expenditures in the top quartile. Inpatient utilization was highest (70%) in those aged 77-83 with mild to severe heart disease plus mild to severe diabetes. Functional limitations were more important than many chronic diseases in explaining resource use. The multimorbid population is heterogeneous and there is considerable variation in how specific combinations of morbidity influence resource use. Modeling the conjoint effects of chronic conditions, functional limitations, and geriatric syndromes can advance understanding of groups at greatest risk and inform targeted tailored interventions aimed at cost containment.

Kidney function and cognitive decline in frail elderly: two faces of the same coin?

PubMed

Coppolino, Giuseppe; Bolignano, Davide; Gareri, Pietro; Ruberto, Carmen; Andreucci, Michele; Ruotolo, Giovanni; Rocca, Maurizio; Castagna, Alberto

2018-06-04

Cognitive and renal impairment are pervasive among elderly frails, a high-risk, geriatric sub-population with peculiar clinical characteristics. In a series of frail individuals with non-advanced chronic kidney disease (CKD), we aimed at assessing the entity of functional, general health and cognitive impairment and the possible relationship between these types of dysfunction and the severity of renal impairment. 2229 geriatric subjects were screened for frailty and CKD. Severity of CKD was assessed by eGFR (CKD-EPI formula). Frailty was established by the Fried Index. Functional, general health and cognitive status were assessed by validated score measures. Final analysis included 271 frail CKD subjects (162 women, 109 men). Mean eGFR was 64.25 ± 25.04 mL/min/1.73 m 2 . Prevalence of mild-to-moderate CKD (stage 3-4) was 44%. Twenty-six percent of patients had severe cognitive impairment, while mild and moderate impairment was found in 7 and 67% of individuals, respectively. All subjects had poor functional and general health status. Cognitive capacities significantly decreased across CKD stages (p for trend < 0.0001). In fully adjusted multivariate analyses, cognitive status remained an independent predictor of eGFR (β = 0.465; p < 0.0001). Mild-to-moderate CKD is highly pervasive among frail elderly individuals and the severity of renal dysfunction is independently correlated with that of cognitive impairment. Future studies are advocated to clarify whether the combination of kidney and mental dysfunction may portend a higher risk of worsen outcomes in this high-risk population.

Pulsed dye laser treatment of rosacea using a novel 15 mm diameter treatment beam.

PubMed

Bernstein, Eric F; Schomacker, Kevin; Paranjape, Amit; Jones, Christopher J

2018-04-10

The pulsed-dye laser has been used to treat facial redness and rosacea for decades. Recent advances in dye laser technology enable 50% higher output energies supporting 50% larger treatment areas, and beam-diameters up to 15 mm with clinically-relevant fluences. In this study, we investigate this novel pulsed-dye laser using a 15 mm diameter beam for treatment of rosacea. Twenty subjects with erythemato-telangiectatic rosacea were enrolled in the study. A total of 4 monthly treatments were administered, first treating linear vessels with a 3 × 10 mm elliptical beam, then diffuse redness with a 15-mm diameter circular beam. Blinded assessment of digital, cross-polarized photographs taken 2 months following the last treatment was performed using an 11-point clearance scale. Nineteen subjects completed the study. Blinded reviewers correctly identified baseline photos in 55 out of the total of 57 images (96.5%). The blinded reviewers scored 17 of the 19 subjects with an improvement greater than 40%, and 11 of the 19 subjects greater than 50%. The average improvement was 53.9%. Side effects were limited to mild edema, mild to moderate erythema, and mild to moderate bruising. This study demonstrates that a newly designed pulsed-dye laser having a novel 15-mm diameter treatment beam improves the appearance of rosacea with a favorable safety profile. Lasers Surg. Med. 9999:1-5, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Education of advanced practice nurses in Canada.

PubMed

Martin-Misener, Ruth; Bryant-Lukosius, Denise; Harbman, Patricia; Donald, Faith; Kaasalainen, Sharon; Carter, Nancy; Kilpatrick, Kelley; DiCenso, Alba

2010-12-01

In Canada, education programs for the clinical nurse specialist (CNS) and nurse practitioner (NP) roles began 40 years ago. NP programs are offered in almost all provinces. Education for the CNS role has occurred through graduate nursing programs generically defined as providing preparation for advanced nursing practice. For this paper, we drew on pertinent sections of a scoping review of the literature and key informant interviews conducted for a decision support synthesis on advanced practice nursing to describe the following: (1) history of advanced practice nursing education in Canada, (2) current status of advanced practice nursing education in Canada, (3) curriculum issues, (4) interprofessional education, (5) resources for education and (6) continuing education. Although national frameworks defining advanced nursing practice and NP competencies provide some direction for education programs, Canada does not have countrywide standards of education for either the NP or CNS role. Inconsistency in the educational requirements for primary healthcare NPs continues to cause significant problems and interferes with inter-jurisdictional licensing portability. For both CNSs and NPs, there can be a mismatch between a generalized education and specialized practice. The value of interprofessional education in facilitating effective teamwork is emphasized. Recommendations for future directions for advanced practice nursing education are offered.

Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

PubMed

Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

2013-11-15

Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

Thyroid hormones and thermogenesis: the metabolic cost of food and exercise.

PubMed

Acheson, K; Jéquier, E; Burger, A; Danforth, E

1984-03-01

To mimic plasma T3 levels observed in a previous overfeeding study, six lean healthy men received replacement amounts of L-thyroxine (200 micrograms/d) to block endogenous thyroid hormone production while consuming their habitual diet. After 4 weeks equilibration on T4, L-triiodothyronine (T3) was given (45 micrograms/d) in addition to T4, to produce mild T3-thyrotoxicosis, for another 2 weeks. At the end of this period T3 was discontinued but the subjects continued to receive T4 for another 2 weeks. Resting metabolic rate, exercise efficiency, and the thermic effect of food were measured using a ventilated hood, open circuit indirect calorimeter at the end of each phase of the experiment. There was a significant increase in the resting metabolic rate of 6% (P less than 0.01) while the subjects were mildly T3-thyrotoxic. The increase in energy expenditure however, during exercise on a bicycle ergometer or following a 500 kcal liquid-formula meal remained unaltered in the same situation. Thus, mild T3-toxicosis does not alter the efficiency of exercise or the thermic effect of food. These results suggest that the increased plasma T3 levels, observed in overfeeding, could explain corresponding increases in resting metabolic rate but not changes in the efficiency of exercise or the utilization of food.

Patiromer: A Review in Hyperkalaemia.

PubMed

Kim, E S; Deeks, Emma D

2016-08-01

Patiromer (Veltassa(™)) for oral suspension is a sodium-free potassium binder that is approved in the USA for the treatment of hyperkalaemia. In clinical trials, patiromer significantly reduced serum potassium levels from baseline to week 4 in patients with chronic kidney disease (CKD) and mild to severe hyperkalaemia (OPAL-HK), or CKD, mild to moderate hyperkalaemia and type 2 diabetes mellitus (AMETHYST-DN), who were receiving renin-angiotensin-aldosterone system inhibitors (RAASis; drugs that inhibit the renal excretion of potassium). Among patients in OPAL-HK who had moderate to severe hyperkalaemia at baseline and normokalaemia on patiromer and RAASis at week 4, continuing patiromer for a further 8 weeks maintained reductions in potassium levels more effectively than switching to placebo (i.e. withdrawing patiromer); consequently, fewer patiromer than placebo recipients experienced recurrent hyperkalaemia during this period. Furthermore, almost all patiromer (vs. less than half of placebo) recipients were still receiving RAASi therapy at the end of this trial. In AMETHYST-DN, the significant reduction from baseline in serum potassium levels seen at week 4 was sustained for up to 52 weeks. Patiromer was generally well tolerated in these trials, with no treatment-related serious adverse events or deaths. Commonly occurring treatment-related adverse events include mild to moderate constipation and hypomagnesaemia, and there is a low risk of hypokalaemia. In conclusion, oral patiromer is a useful new option for patients with hyperkalaemia.

Angiotensin-converting enzyme gene polymorphism (insertion/deletion) and liver fibrosis in Turkish patients from the western Black Sea region, Turkey.

PubMed

Turhan, N K; Ilikhan, S Uygun; Hamamcioglu, A C; Ustundag, Y; Dursun, A; Kokturk, F

2015-12-16

Chronic viral hepatitis B, chronic viral hepatitis C, non-alcoholic steatohepatitis, alcoholic liver disease, autoimmune hepatitis, primary biliary cirrhosis, and secondary biliary cirrhosis are important health issues worldwide. While an association between angiotensin-converting enzyme gene insertion/deletion (ACE gene I/D) polymorphism and liver fibrosis has been demonstrated in rat studies, the results of clinical studies area have been contradictory. The aim of this study was to assess the possible association between ACE gene I/D polymorphism and liver fibrosis in a large group of Turkish patients from the western Black Sea region. In 418 patients with different etiologies, ACE gene I/D polymorphism and serum ACE levels were investigated. The distribution of the "DD", "ID", "II" genotypes of the ACE gene were 32.5, 48.8, and 18.7% in the mild to moderate fibrosis group (N = 246, F:1-3 according to Ishak's score) and 39.0, 44.2, and 16.9% in the advanced fibrosis group (N = 172, F:4-6 according to Ishak's score). A significant correlation between serum ACE levels and ACE gene alleles was identified (P < 0.001): serum ACE levels of patients with D alleles were higher than those of patients with I alleles [44 (min 7-max 101) versus 29 (min 7-max 96)]. Patients with advanced fibrosis were also found to be older than those with mild to moderate fibrosis (P < 0.001). No significant association was noted between the patient gender and fibrosis severity. We conclude that ACE I/D polymorphism is not associated with the degree of liver fibrosis.

Efficacy of the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program among patients with mild cognitive impairment: a randomized controlled crossover trial.

PubMed

Han, Ji Won; Son, Kyung Lak; Byun, Hye Jin; Ko, Ji Won; Kim, Kayoung; Hong, Jong Woo; Kim, Tae Hyun; Kim, Ki Woong

2017-06-06

Spaced retrieval training (SRT) is a nonpharmacological intervention for mild cognitive impairment (MCI) and dementia that trains the learning and retention of target information by recalling it over increasingly long intervals. We recently developed the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program as a convenient, self-administered tablet-based SRT program. We also demonstrated the utility of USMART for improving memory in individuals with MCI through an open-label uncontrolled trial. This study had an open-label, single-blind, randomized, controlled, two-period crossover design. Fifty patients with MCI were randomized into USMART-usual care and usual care-USMART treatment sequences. USMART was completed or usual care was provided biweekly over a 4-week treatment period with a 2-week washout period between treatment periods. Primary outcome measures included the Word List Memory Test, Word List Recall Test (WLRT), and Word List Recognition Test. Outcomes were measured at baseline, week 5, and week 11 by raters who were blinded to intervention type. An intention-to-treat analysis and linear mixed modeling were used. Of 50 randomized participants, 41 completed the study (18% dropout rate). The USMART group had larger improvements in WLRT score (effect size = 0.49, p = 0.031) than the usual care group. There were no significant differences in other primary or secondary measures between the USMART and usual care groups. Moreover, no USMART-related adverse events were reported. The 4-week USMART modestly improved information retrieval in older people with MCI, and was well accepted with minimal technical support. ClinicalTrials.gov NCT01688128 . Registered 12 September 2012.

Biomarkers of Rheumatoid Arthritis–Associated Interstitial Lung Disease

PubMed Central

Chen, Juan; Doyle, Tracy J.; Liu, Yongliang; Aggarwal, Rohit; Wang, Xiaoping; Shi, Yonghong; Ge, Sheng Xiang; Huang, Heqing; Lin, Qingyan; Liu, Wen; Cai, Yongjin; Koontz, Diane; Fuhrman, Carl R.; Golzarri, Maria F.; Liu, Yushi; Hatabu, Hiroto; Nishino, Mizuki; Araki, Tetsuro; Dellaripa, Paul F.; Oddis, Chester V.; Rosas, Ivan O.; Ascherman, Dana P.

2015-01-01

Objective Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication. Methods Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA–no ILD, RA–mild ILD, or RA–advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest. Results MMP-7 and interferon-γ–inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA–no ILD, 41 RA-ILD, 42 RA–indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA–no ILD, 49 RA-ILD, 15 RA–indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses. Conclusion Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication. PMID:25302945

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

PubMed Central

Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

2015-01-01

Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

Application of advanced machine learning methods on resting-state fMRI network for identification of mild cognitive impairment and Alzheimer's disease.

PubMed

Khazaee, Ali; Ebrahimzadeh, Ata; Babajani-Feremi, Abbas

2016-09-01

The study of brain networks by resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for identifying patients with dementia from healthy controls (HC). Using graph theory, different aspects of the brain network can be efficiently characterized by calculating measures of integration and segregation. In this study, we combined a graph theoretical approach with advanced machine learning methods to study the brain network in 89 patients with mild cognitive impairment (MCI), 34 patients with Alzheimer's disease (AD), and 45 age-matched HC. The rs-fMRI connectivity matrix was constructed using a brain parcellation based on a 264 putative functional areas. Using the optimal features extracted from the graph measures, we were able to accurately classify three groups (i.e., HC, MCI, and AD) with accuracy of 88.4 %. We also investigated performance of our proposed method for a binary classification of a group (e.g., MCI) from two other groups (e.g., HC and AD). The classification accuracies for identifying HC from AD and MCI, AD from HC and MCI, and MCI from HC and AD, were 87.3, 97.5, and 72.0 %, respectively. In addition, results based on the parcellation of 264 regions were compared to that of the automated anatomical labeling atlas (AAL), consisted of 90 regions. The accuracy of classification of three groups using AAL was degraded to 83.2 %. Our results show that combining the graph measures with the machine learning approach, on the basis of the rs-fMRI connectivity analysis, may assist in diagnosis of AD and MCI.

Oxidative stress and APO E polymorphisms in Alzheimer's disease and in mild cognitive impairment.

PubMed

Chico, L; Simoncini, C; Lo Gerfo, A; Rocchi, A; Petrozzi, L; Carlesi, C; Volpi, L; Tognoni, G; Siciliano, G; Bonuccelli, U

2013-08-01

A number of evidences indicates oxidative stress as a relevant pathogenic factor in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Considering its recognized major genetic risk factors in AD, apolipoprotein (APO E) has been investigated in several experimental settings regarding its role in the process of reactive oxygen species (ROS) generation. The aim of this work has been to evaluate possible relationships between APO E genotype and plasma levels of selected oxidative stress markers in both AD and MCI patients. APO E genotypes were determined using restriction enzyme analysis. Plasma levels of oxidative markers, advanced oxidation protein products, iron-reducing ability of plasma and, in MCI, activity of superoxide dismutases were evaluated using spectrophotometric analysis. We found, compared to controls, increased levels of oxidized proteins and decreased values of plasma-reducing capacity in both AD patients (p < 0.0001) and MCI patients (p < 0.001); the difference between AD and MCI patients was significant only for plasma-reducing capacity (p < 0.0001), the former showing the lowest values. Superoxide dismutase activity was reduced, although not at statistical level, in MCI compared with that in controls. E4 allele was statistically associated (p < 0.05) with AD patients. When comparing different APO E genotype subgroups, no difference was present, as far as advanced oxidation protein products and iron-reducing ability of plasma levels were concerned, between E4 and non-E4 carriers, in both AD and MCI; on the contrary, E4 carriers MCI patients showed significantly decreased (p < 0.05) superoxide dismutase activity with respect to non-E4 carriers. This study, in confirming the occurrence of oxidative stress in AD and MCI patients, shows how it can be related, at least for superoxide dismutase activity in MCI, to APO E4 allele risk factor.

Differentiated Responses of Apple Tree Floral Phenology to Global Warming in Contrasting Climatic Regions.

PubMed

Legave, Jean-Michel; Guédon, Yann; Malagi, Gustavo; El Yaacoubi, Adnane; Bonhomme, Marc

2015-01-01

The responses of flowering phenology to temperature increases in temperate fruit trees have rarely been investigated in contrasting climatic regions. This is an appropriate framework for highlighting varying responses to diverse warming contexts, which would potentially combine chill accumulation (CA) declines and heat accumulation (HA) increases. To examine this issue, a data set was constituted in apple tree from flowering dates collected for two phenological stages of three cultivars in seven climate-contrasting temperate regions of Western Europe and in three mild regions, one in Northern Morocco and two in Southern Brazil. Multiple change-point models were applied to flowering date series, as well as to corresponding series of mean temperature during two successive periods, respectively determining for the fulfillment of chill and heat requirements. A new overview in space and time of flowering date changes was provided in apple tree highlighting not only flowering date advances as in previous studies but also stationary flowering date series. At global scale, differentiated flowering time patterns result from varying interactions between contrasting thermal determinisms of flowering dates and contrasting warming contexts. This may explain flowering date advances in most of European regions and in Morocco vs. stationary flowering date series in the Brazilian regions. A notable exception in Europe was found in the French Mediterranean region where the flowering date series was stationary. While the flowering duration series were stationary whatever the region, the flowering durations were far longer in mild regions compared to temperate regions. Our findings suggest a new warming vulnerability in temperate Mediterranean regions, which could shift toward responding more to chill decline and consequently experience late and extended flowering under future warming scenarios.

A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium.

PubMed

Xu, Nong; Zhang, Xiao Chen; Xiong, Jian Ping; Fang, Wei Jia; Yu, Lan Fang; Qian, Jiong; Zhang, Ling

2007-06-09

Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC) of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium. Patients with advanced TCC were treated with gemcitabine 1200 mg/m2 on days 1 and 8 and carboplatin area under the concentration-time curve(AUC) 5 on day 1 every 21 days. Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1-6) was administered. Overall response rate was 46.2% (95% confidence interval: 32-65%) including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6-8.4 months) and 13.6 months (95% confidence interval: 10.2-17.0 months), respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4%) patients. The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens. ISRCTN88259320.

Hybrid Cubature Kalman filtering for identifying nonlinear models from sampled recording: Estimation of neuronal dynamics.

PubMed

Madi, Mahmoud K; Karameh, Fadi N

2017-01-01

Kalman filtering methods have long been regarded as efficient adaptive Bayesian techniques for estimating hidden states in models of linear dynamical systems under Gaussian uncertainty. Recent advents of the Cubature Kalman filter (CKF) have extended this efficient estimation property to nonlinear systems, and also to hybrid nonlinear problems where by the processes are continuous and the observations are discrete (continuous-discrete CD-CKF). Employing CKF techniques, therefore, carries high promise for modeling many biological phenomena where the underlying processes exhibit inherently nonlinear, continuous, and noisy dynamics and the associated measurements are uncertain and time-sampled. This paper investigates the performance of cubature filtering (CKF and CD-CKF) in two flagship problems arising in the field of neuroscience upon relating brain functionality to aggregate neurophysiological recordings: (i) estimation of the firing dynamics and the neural circuit model parameters from electric potentials (EP) observations, and (ii) estimation of the hemodynamic model parameters and the underlying neural drive from BOLD (fMRI) signals. First, in simulated neural circuit models, estimation accuracy was investigated under varying levels of observation noise (SNR), process noise structures, and observation sampling intervals (dt). When compared to the CKF, the CD-CKF consistently exhibited better accuracy for a given SNR, sharp accuracy increase with higher SNR, and persistent error reduction with smaller dt. Remarkably, CD-CKF accuracy shows only a mild deterioration for non-Gaussian process noise, specifically with Poisson noise, a commonly assumed form of background fluctuations in neuronal systems. Second, in simulated hemodynamic models, parametric estimates were consistently improved under CD-CKF. Critically, time-localization of the underlying neural drive, a determinant factor in fMRI-based functional connectivity studies, was significantly more accurate under CD-CKF. In conclusion, and with the CKF recently benchmarked against other advanced Bayesian techniques, the CD-CKF framework could provide significant gains in robustness and accuracy when estimating a variety of biological phenomena models where the underlying process dynamics unfold at time scales faster than those seen in collected measurements.

Hybrid Cubature Kalman filtering for identifying nonlinear models from sampled recording: Estimation of neuronal dynamics

PubMed Central

2017-01-01

Kalman filtering methods have long been regarded as efficient adaptive Bayesian techniques for estimating hidden states in models of linear dynamical systems under Gaussian uncertainty. Recent advents of the Cubature Kalman filter (CKF) have extended this efficient estimation property to nonlinear systems, and also to hybrid nonlinear problems where by the processes are continuous and the observations are discrete (continuous-discrete CD-CKF). Employing CKF techniques, therefore, carries high promise for modeling many biological phenomena where the underlying processes exhibit inherently nonlinear, continuous, and noisy dynamics and the associated measurements are uncertain and time-sampled. This paper investigates the performance of cubature filtering (CKF and CD-CKF) in two flagship problems arising in the field of neuroscience upon relating brain functionality to aggregate neurophysiological recordings: (i) estimation of the firing dynamics and the neural circuit model parameters from electric potentials (EP) observations, and (ii) estimation of the hemodynamic model parameters and the underlying neural drive from BOLD (fMRI) signals. First, in simulated neural circuit models, estimation accuracy was investigated under varying levels of observation noise (SNR), process noise structures, and observation sampling intervals (dt). When compared to the CKF, the CD-CKF consistently exhibited better accuracy for a given SNR, sharp accuracy increase with higher SNR, and persistent error reduction with smaller dt. Remarkably, CD-CKF accuracy shows only a mild deterioration for non-Gaussian process noise, specifically with Poisson noise, a commonly assumed form of background fluctuations in neuronal systems. Second, in simulated hemodynamic models, parametric estimates were consistently improved under CD-CKF. Critically, time-localization of the underlying neural drive, a determinant factor in fMRI-based functional connectivity studies, was significantly more accurate under CD-CKF. In conclusion, and with the CKF recently benchmarked against other advanced Bayesian techniques, the CD-CKF framework could provide significant gains in robustness and accuracy when estimating a variety of biological phenomena models where the underlying process dynamics unfold at time scales faster than those seen in collected measurements. PMID:28727850

The picture of happiness in Alzheimer's disease: living a life congruent with personal values.

PubMed

Shell, Lynn

2015-01-01

It is generally understood that happiness is an important goal of dementia care, though evaluation has been challenging. Concerns about cognitive and communicative limitations have led to the use of proxy reports to assess positive affect. However, proxy reports have been shown to differ from appraisals obtained by the person with Alzheimer's disease (AD). This article reports on a qualitative study of happiness in a sample of 12 persons with mild to moderate AD using photo-elicitation and individual interviews for data collection. Results demonstrate people with mild to moderate AD can provide meaningful evaluations of happiness, and that lifelong values continue to be important in the presence of AD. This study suggests photographs may offer a novel approach to obtain a contextualized understanding of happiness and other values in this population which may lead to the development of person centered interventions aimed to improve the individual's quality of life. Copyright © 2015 Elsevier Inc. All rights reserved.

Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

PubMed

de la Monte, Suzanne M

Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

Azelaic acid 15% gel in the treatment of rosacea.

PubMed

Gollnick, Harald; Layton, Alison

2008-10-01

Rosacea represents a chronic inflammatory dermatosis of uncertain pathophysiology. There are several associated risk factors and the need for long-term treatment is well recognized. This diverse disease is frequently difficult to manage and has a significant impact on quality of life. There are several topical and oral treatments available, of which azelaic acid 15% gel (Finacea) is the first new treatment for rosacea in more than a decade. Azelaic acid per se has multiple modes of action in rosacea, but an anti-inflammatory effect achieved by reducing reactive oxygen species appears to be the main pharmacological action. Clinical studies have shown that azelaic acid 15% gel is an effective and safe first-line topical therapeutic option in patients with mild-to-moderate papulopustular rosacea. Significant continuous improvement in the number of inflammatory lesions and in erythema has been shown over a period of 15 weeks. Adverse effects associated with azelaic acid 15% gel are mostly mild or transient and do not usually necessitate discontinuation of therapy.