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Objectives: Oral anticoagulants are the cornerstone of stroke prevention in high-risk patients with atrial fibrillation (AF). Geriatric elements, such as cognitive impairment and frailty, commonly occur in these patients and are often cited as reasons for not prescribing oral anticoagulants. We sought to systematically assess geriatric impairments in patients with AF and determine whether they were associated with oral anticoagulant prescribing., Design: Cross-sectional analysis of baseline data from the ongoing Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF) prospective cohort study., Setting: Multicenter study with site locations in Massachusetts and Georgia that recruited participants from cardiology, electrophysiology, and primary care clinics from 2016 to 2018., Participants: Participants with AF age 65 years or older, CHA 2 DS 2 -VASc (congestive heart failure; hypertension; aged ≥75 y [doubled]; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism [doubled]; vascular disease; age 65-74; female sex) score of 2 or higher, and no oral anticoagulant contraindications (n = 1244)., Measurements: A six-component geriatric assessment included validated measures of frailty, cognitive function, social support, depressive symptoms, vision, and hearing. Oral anticoagulant use was abstracted from the medical record., Results: A total of 1244 participants (mean age = 76 y; 49% female; 85% white) were enrolled; 42% were cognitively impaired, 14% frail, 53% pre-frail, 12% socially isolated, and 29% had depressive symptoms. Oral anticoagulants were prescribed to 86% of the cohort. Oral anticoagulant prescribing did not vary according to any of the geriatric elements (adjusted odds ratios [ORs] for oral anticoagulant prescribing and cognitive impairment: OR = .75; 95% confidence interval [CI] = .51-1.09; frail OR = .69; 95% CI = .35-1.36; social isolation OR = .90; 95% CI = .52-1.54; depression OR = .79; 95% CI = .49-1.27; visual impairment OR = .98; 95% CI = .65-1.48; and hearing impairment OR = 1.05; 95% CI = .71-1.54)., Conclusion: Geriatric impairments, particularly cognitive impairment and frailty, were common in our cohort, but treatment with oral anticoagulants did not differ by impairment status. These geriatric impairments are commonly cited as reasons for not prescribing oral anticoagulants, suggesting that prescribers may either be unaware or deliberately ignoring the presence of these factors in clinical settings. J Am Geriatr Soc 68:147-154, 2019., (© 2019 The American Geriatrics Society.)

Background: Successful anticoagulation is critical for stroke prevention in adults with atrial fibrillation (AF). Anticoagulation satisfaction is a key indicator of treatment success. While physical, cognitive, and psychosocial limitations are common in elderly AF patients, their associations with anticoagulation satisfaction are unknown., Objective: Examine whether anticoagulation satisfaction differs among AF patients with and without physical, cognitive, and psychosocial conditions., Methods: The study comprised AF patients greater than or equal to 65 years old who were prescribed an oral anticoagulant (warfarin 57%; direct oral anticoagulant [DOAC] 43%). Frailty, cognitive function, social support, depressive symptoms, vision, hearing, and anxiety were assessed using validated measures. Anticoagulation satisfaction was measured using the anticlot treatment scale., Results: Participants (n = 1037, 50% female) were on average 76 years old. The following conditions were prevalent: frailty (14%), cognitive impairment (42%), social isolation (13%), vision impairment (35%), hearing impairment (36%), depression (29%), and anxiety (24%). Average anticlot treatment burden scale was 55 out of 60 (lower burden scales indicating higher perceived burden). Patients with high perceived burden were older, more likely to be female, and receive warfarin. After adjusting for confounders, visual impairment (adjusted odds ratio [95% confidence interval]: 1.7 [1.2-2.4]), depressive symptoms (2.4 [1.6-3.7]), and anxiety (1.8 [1.2-2.7]) were significantly associated with high perceived burden. Different conditions were associated with high perceived burden in warfarin vs DOAC users., Conclusion: Physical, cognitive, and psychosocial limitations are prevalent and associated with high perceived anticoagulation burden among elderly AF adults. These conditions merit consideration in anticoagulation prescribing., (© 2019 Wiley Periodicals, Inc.)

Background: Geriatric conditions are common among patients with atrial fibrillation (AF) and relate to complications of oral anticoagulation (OAC). Objective: To examine the prevalence of geriatric conditions among older patients with AF on OAC and relate type of OAC to geriatric conditions. Methods: Participants had a diagnosis of AF, were aged ≥65 years, CHA 2 DS 2 VASC ≥ 2, and had no OAC contraindications. Participants completed a 6-component geriatric assessment that included validated measures of frailty (CHS Frailty Scale), cognitive function (MoCA), social support (MOS), depressive symptoms (PHQ9), vision, and hearing. Type of OAC prescribed was documented in medical records. Results: 86% of participants were prescribed an OAC. These participants were on average aged 75.7 ( SD : 7.1) years, 49% were women, two thirds were frail or pre-frail, and 44% received a DOAC. DOAC users were younger, had lower CHA 2 DS 2 VASC and HAS-BLED scores, and were less likely to be frail. In Massachusetts, pre-frailty was associated with a significantly lower odds of DOAC vs. VKA use ( OR = 0.64, 95%CI 0.45, 0.91). Pre-frailty ( OR = 0.33, 95%CI 0.18-0.59) and social isolation ( OR = 0.38, 95%CI 0.14-0.99) were associated with lower odds of DOAC receipt in patients aged 75 years or older. Social isolation was associated with higher odds of DOAC use ( OR = 2.13, 95%CI 1.05-4.29) in patients aged 65-74 years. Conclusions: Geriatric conditions were common and related to type of OAC prescribed, differentially by age group. Research is needed to evaluate whether a geriatric examination can be used clinically to better inform OAC decision-making in older patients with AF., (Copyright © 2019 McManus, Kiefe, Lessard, Waring, Parish, Awad, Marino, Helm, Sogade, Goldberg, Hayward, Gurwitz, Wang, Mailhot, Barton and Saczynski.)

Context: In the aging brain, reduction in the pulsation of cerebral vasculature and fluid circulation causes impairment in the fluid exchange between different compartments and lays a foundation for the neuroinflammation that results in Alzheimer disease (AD). The knowledge that lymphatic vessels in the central nervous system play a role in the clearance of brain-derived metabolic waste products opens an unprecedented capability to increase the clearance of macromolecules such as amyloid β proteins. However, currently there is no pharmacologic mechanism available to increase fluid circulation in the aging brain., Objective: To demonstrate the influence of an osteopathic cranial manipulative medicine (OCMM) technique, specifically, compression of the fourth ventricle, on spatial memory and changes in substrates associated with mechanisms of metabolic waste clearance in the central nervous system using the naturally aged rat model of AD., Results: Significant improvement was found in spatial memory in 6 rats after 7 days of OCMM sessions. Live animal positron emission tomographic imaging and immunoassays revealed that OCMM reduced amyloid β levels, activated astrocytes, and improved neurotransmission in the aged rat brains., Conclusion: These findings demonstrate the molecular mechanism of OCMM in aged rats. This study and further investigations will help physicians promote OCMM as an evidence-based adjunctive treatment for patients with AD.

Positron annihilation lifetime spectroscopy (PALS) provides a powerful technique for non-destructive microstructure investigations in a broad field of material classes such as metals, semiconductors, polymers or porous glasses. Even though this method is well established for more than five decades, no proper standardization for the used setup configuration and subsequent data processing exists. Eventually, this could lead to an insufficiency of data reproducibility and avoidable deviations. Here we present experimentally obtained and simulated data of positron lifetime spectra at various statistics measured on pure tin (4N-Sn) by using a semi-analog/digital setup, where the digital section consists of the DRS4 evaluation board, "Design and performance of the 6 GHz waveform digitizing chip DRS4" [1]. The analog section consists of nuclear instrument modules (NIM), which externally trigger the DRS4 evaluation board to reduce the digitization and, thus, increase the acquisition efficiency. For the experimentally obtained lifetime spectra, 22 Na sealed in Kapton foil served as a positron source, whereas 60 Co was used for the acquisition of the prompt spectrum, i.e. the quasi instrument response function. Both types of measurements were carried out under the same conditions. All necessary data and information regarding the data acquisition and data reduction are provided to allow reproducibility by other research groups.

The originally published version of this Article contained an error in Fig. 3, whereby an additional unrelated graph was overlaid on top of the magnetic susceptibility plot. Furthermore, the Article title contained an error in the capitalisation of 'Stone Age'. Both of these errors have now been corrected in both the PDF and HTML versions of the Article.

The Middle to Later Stone Age transition in Africa has been debated as a significant shift in human technological, cultural, and cognitive evolution. However, the majority of research on this transition is currently focused on southern Africa due to a lack of long-term, stratified sites across much of the African continent. Here, we report a 78,000-year-long archeological record from Panga ya Saidi, a cave in the humid coastal forest of Kenya. Following a shift in toolkits ~67,000 years ago, novel symbolic and technological behaviors assemble in a non-unilinear manner. Against a backdrop of a persistent tropical forest-grassland ecotone, localized innovations better characterize the Late Pleistocene of this part of East Africa than alternative emphases on dramatic revolutions or migrations.

We assembled genome-wide data from 16 prehistoric Africans. We show that the anciently divergent lineage that comprises the primary ancestry of the southern African San had a wider distribution in the past, contributing approximately two-thirds of the ancestry of Malawi hunter-gatherers ∼8,100-2,500 years ago and approximately one-third of the ancestry of Tanzanian hunter-gatherers ∼1,400 years ago. We document how the spread of farmers from western Africa involved complete replacement of local hunter-gatherers in some regions, and we track the spread of herders by showing that the population of a ∼3,100-year-old pastoralist from Tanzania contributed ancestry to people from northeastern to southern Africa, including a ∼1,200-year-old southern African pastoralist. The deepest diversifications of African lineages were complex, involving either repeated gene flow among geographically disparate groups or a lineage more deeply diverging than that of the San contributing more to some western African populations than to others. We finally leverage ancient genomes to document episodes of natural selection in southern African populations. PAPERCLIP., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This article outlines the steps to success in quality improvement and explains how quality improvement can help you, your patients and your institution. Although many tactics can be used to drive quality improvement, some tactics deliver results that are short term and unsustainable and that fail to embed a culture of quality improvement within organizations. Consensus is emerging that a bottom-up approach may be better - where the intrinsic motivations of clinical staff are harnessed to drive quality improvement. This is an ideal opportunity for clinical staff at all levels to join in. The steps involved in quality improvement include choosing a topic, choosing tools to measure the problem, using plan, do, study, act cycles to drive improvement, and then writing up and sharing the project. Quality improvement projects can achieve multiple outcomes including improved patient experience and saved costs.

The Austronesian settlement of the remote island of Madagascar remains one of the great puzzles of Indo-Pacific prehistory. Although linguistic, ethnographic, and genetic evidence points clearly to a colonization of Madagascar by Austronesian language-speaking people from Island Southeast Asia, decades of archaeological research have failed to locate evidence for a Southeast Asian signature in the island's early material record. Here, we present new archaeobotanical data that show that Southeast Asian settlers brought Asian crops with them when they settled in Africa. These crops provide the first, to our knowledge, reliable archaeological window into the Southeast Asian colonization of Madagascar. They additionally suggest that initial Southeast Asian settlement in Africa was not limited to Madagascar, but also extended to the Comoros. Archaeobotanical data may support a model of indirect Austronesian colonization of Madagascar from the Comoros and/or elsewhere in eastern Africa.

The hypothalamus integrates energy balance information from the periphery using different neuronal subtypes within each of the hypothalamic areas. However, the effects of prandial state on global mRNA, microRNA and long noncoding (lnc) RNA expression within the whole hypothalamus are largely unknown. In this study, mice were given either a 24-h fast, or ad libitum access to food. RNA samples were analyzed by microarray, and then a subset was confirmed using quantitative real-time PCR (QPCR). A total of 540 mRNAs were either up- or down-regulated with food deprivation. Since gene ontology enrichment analyses identified several categories of mRNAs related to cell cycle processes, ten cell-cycle-related genes were further analyzed using QPCR with six confirmed to be significantly up-regulated and one down-regulated in response to 24-h fasting. While 22 independent microRNAs were differentially expressed by microarray, secondary analysis by QPCR failed to confirm significant changes with fasting. There were 622 lncRNAs identified as differentially expressed, and of three tested by QPCR, two were confirmed. Overall, this is the first time that expression of hypothalamic lncRNAs has been shown to be responsive to food deprivation. In addition, this study is the first to identify a list of lncRNAs with high expression in RNA extracted from hypothalamus. Individual contributions from specific miRNA, lncRNA and mRNAs to the food deprivation response can now be further studied at the physiological and biochemical levels.

Damage by late spring frost is a risk deciduous trees have to cope with in order to optimize the length of their growing season. The timing of spring phenological development plays a crucial role, not only at the species level, but also at the population and individual level, since fresh new leaves are especially vulnerable. For the pronounced late spring frost in May 2011 in Germany, we studied the individual leaf development of 35 deciduous trees (mainly European beech Fagus sylvatica L.) at a mountainous forest site in the Bayerischer Wald National Park using repeated digital photographs. Analyses of the time series of greenness by a novel Bayesian multiple change point approach mostly revealed five change points which almost perfectly matched the expected break points in leaf development: (i) start of the first greening between day of the year (DOY) 108-119 (mean 113), (ii) end of greening, and (iii) visible frost damage after the frost on the night of May 3rd/4th (DOY 123/124), (iv) re-sprouting 19-38 days after the frost, and (v) full maturity around DOY 178 (166-184) when all beech crowns had fully recovered. Since frost damage was nearly 100%, individual susceptibility did not depend on the timing of first spring leaf unfolding. However, we could identify significant patterns in fitness linked to an earlier start of leaf unfolding. Those individuals that had an earlier start of greening during the first flushing period had a shorter period of recovery and started the second greening earlier. Thus, phenological timing triggered the speed of recovery from such an extreme event. The maximum greenness achieved, however, did not vary with leaf unfolding dates. Two mountain ashes (Sorbus aucuparia L.) were not affected by the low temperatures of -5°C. Time series analysis of webcam pictures can thus improve process-based knowledge and provide valuable insights into the link between phenological variation, late spring frost damage, and recovery within one stand.

With widespread detection of endocrine disrupting compounds including hormones in wastewater, there is a need to develop cost-effective remediation technologies for their removal from wastewater. Previous research has shown that Fe(3+)-saturated montmorillonite is effective in quickly transforming phenolic organic compounds such as pentachlorophenol, phenolic acids, and triclosan via surface-catalyzed oligomerization. However, little is known about its effectiveness and reaction mechanisms when reacting with hormones. In this study, the reaction kinetics of Fe(3+)-saturated montmorillonite catalyzed 17β-estradiol (βE2) transformation was investigated. The transformation products were identified using liquid chromatography coupled with mass spectrometry, and their structures were further confirmed using computational approach. Rapid βE2 transformation in the presence of Fe(3+)-saturated montmorillonite in an aqueous system was detected. The disappearance of βE2 follows first-order kinetics, while the overall catalytic reaction follows the second-order kinetics with an estimated reaction rate constant of 200 ± 24 (mmol βE2/g mineral)(−1) h(–1). The half-life of βE2 in this system was estimated to be 0.50 ± 0.06 h. βE2 oligomers were found to be the major products of βE2 transformation when exposed to Fe(3+)-saturated montmorillonite. About 98% of βE2 were transformed into βE2 oligomers which are >10(7) times less water-soluble than βE2 and, therefore, are much less bioavailable and mobile then βE2. The formed oligomers quickly settled from the aqueous phase and were not accumulated on the reaction sites of the interlayer surfaces of Fe(3+)-saturated montmorillonite, the major reason for the observed >84% βE2 removal efficiency even after five consecutive usages of the same of Fe(3+)-saturated montmorillonite. The results from this study clearly demonstrated that Fe(3+)-saturated montmorillonite has a great potential to be used as a cost-effective material for efficient removal of phenolic organic compounds from wastewater.

Objective: A number of established regional quality improvement collaboratives have partnered to assess and improve care across their regions under the umbrella of the Cardiac Surgery Quality Improvement (IMPROVE) Network. The first effort of the IMPROVE Network has been to assess regional differences in potentially discretionary transfusions (<3 units red blood cells [RBCs])., Methods: We examined 11,200 patients undergoing isolated nonemergent coronary artery bypass graft surgery across 56 medical centers in 4 IMPROVE Network regions between January 2008 and June 2012. Each center submitted the most recent 200 patients who received 0, 1, or 2 units of RBC transfusion during the index admission. Patient and disease characteristics, intraoperative practices, and percentage of patients receiving RBC transfusions were collected. Region-specific transfusion rates were calculated after adjusting for pre- and intraoperative factors among region-specific centers., Results: There were small but significant differences in patient case mix across regions. RBC transfusions of 1 or 2 units occurred among 25.2% of coronary artery bypass graft procedures (2826 out of 11,200). Significant variation in the number of RBC units used existed across regions (no units, 74.8% [min-max, 70.0%-84.1%], 1 unit, 9.7% [min-max, 5.1%-11.8%], 2 units, 15.5% [min-max, 9.1%-18.2%]; P < .001). Variation in overall transfusion rates remained after adjustment (9.1%-31.7%; P < .001)., Conclusions: Delivery of small volumes of RBC transfusions was common, yet varied across geographic regions. These data suggest that differences in regional practice environments, including transfusion triggers and anemia management, may contribute to variability in RBC transfusion rates., (Copyright © 2014 The American Association for Thoracic Surgery. All rights reserved.)

Background: Carpal tunnel syndrome is traditionally treated with open release through a long palmar incision, which leaves some patients with pillar pain and scar tenderness. The Knifelight (Stryker, Kalamazoo, MI) is an exciting new instrument that allows minimally invasive release of the transcarpal ligament without subjecting the patient to the traditional problematic open palmar incision. However, no long-term data has been published in the literature so far., Material and Methods: A modified QuickDASH score questionnaire was used to assess long-term results and patient satisfaction 10 years following our department's original randomized control trial comparing open carpal tunnel release (43 patients) to carpal tunnel release using the Knifelight method (39 patients)., Results: The mean modified QuickDASH score was 33.71 (SD 23.27) for the open group and 13.22 (SD 13.62) for the Knifelight group (P-value=0.0024). Patients from the open group complained of pillar pain (30%), scar tenderness (25%) and recurrence of carpal tunnel symptoms (18%). Three patients had symptoms so severe that they could not perform their jobs. In the Knifelight group there were no reports of any pain, recurrence or scar-related problems and a high level of general satisfaction was observed with this group of patients., Conclusions: Our study results show that the minimally invasive Knifelight carpal tunnel release was associated with better clinical outcomes, less complications and overall better quality of life when compared to the conventional open carpal tunnel release.

This is the first of seven papers resulting from a Society of Environmental Toxicology and Chemistry (SETAC) international workshop titled "The Influence of Global Climate Change on the Scientific Foundations and Applications of Environmental Toxicology and Chemistry." The workshop involved 36 scientists from 11 countries and was designed to answer the following question: How will global climate change influence the environmental impacts of chemicals and other stressors and the way we assess and manage them in the environment? While more detail is found in the complete series of articles, some key consensus points are as follows: (1) human actions (including mitigation of and adaptation to impacts of global climate change [GCC]) may have as much influence on the fate and distribution of chemical contaminants as does GCC, and modeled predictions should be interpreted cautiously; (2) climate change can affect the toxicity of chemicals, but chemicals can also affect how organisms acclimate to climate change; (3) effects of GCC may be slow, variable, and difficult to detect, though some populations and communities of high vulnerability may exhibit responses sooner and more dramatically than others; (4) future approaches to human and ecological risk assessments will need to incorporate multiple stressors and cumulative risks considering the wide spectrum of potential impacts stemming from GCC; and (5) baseline/reference conditions for estimating resource injury and restoration/rehabilitation will continually shift due to GCC and represent significant challenges to practitioners., (Copyright © 2013 SETAC.)

Background: There are now a multitude of articles published in a diversity of journals providing information about genes, proteins, pathways, and diseases. Each article investigates subsets of a biological process, but to gain insight into the functioning of a system as a whole, we must integrate information from multiple publications. Particularly, unraveling relationships between extra-cellular inputs and downstream molecular response mechanisms requires integrating conclusions from diverse publications., Methodology: We present an automated approach to biological knowledge discovery from PubMed abstracts, suitable for "connecting the dots" across the literature. We describe a storytelling algorithm that, given a start and end publication, typically with little or no overlap in content, identifies a chain of intermediate publications from one to the other, such that neighboring publications have significant content similarity. The quality of discovered stories is measured using local criteria such as the size of supporting neighborhoods for each link and the strength of individual links connecting publications, as well as global metrics of dispersion. To ensure that the story stays coherent as it meanders from one publication to another, we demonstrate the design of novel coherence and overlap filters for use as post-processing steps., Conclusions: WE DEMONSTRATE THE APPLICATION OF OUR STORYTELLING ALGORITHM TO THREE CASE STUDIES: i) a many-one study exploring relationships between multiple cellular inputs and a molecule responsible for cell-fate decisions, ii) a many-many study exploring the relationships between multiple cytokines and multiple downstream transcription factors, and iii) a one-to-one study to showcase the ability to recover a cancer related association, viz. the Warburg effect, from past literature. The storytelling pipeline helps narrow down a scientist's focus from several hundreds of thousands of relevant documents to only around a hundred stories. We argue that our approach can serve as a valuable discovery aid for hypothesis generation and connection exploration in large unstructured biological knowledge bases.

Peanut (Arachis hypogaea, Leguminosae) allergy is a major cause of food-induced anaphylaxis. The potential use of activated charcoal (AC) to adsorb and reduce the bioavailability of peanut protein allergens for use in the moderation of hypersensitivity reactions was investigated. The rate and extent of protein release from peanut and the adsorption of the solubilized protein by AC was determined under physiological pH values and confirmed in vivo using a porcine animal model system. Peanut proteins were adsorbed with equal efficiency at pH 2 and 7 and are completely removed from solution by an AC/protein ratio of approximately 80:1. This suggests that AC can bind protein under gastric (pH 2) or intestinal (pH 7) conditions. The rapid adsorption of soluble peanut allergens and the continuous binding of allergens released from peanut particulate material suggest the potential efficacy of using AC for gastric decontamination and possible elimination of a biphasic allergic reaction.

Objectives: We sought to investigate the impact of left ventricular (LV) pacing site on mechanical response to cardiac resynchronization therapy (CRT) in patients with ischemic cardiomyopathy (ICM)., Background: CRT reduces morbidity and mortality in patients with dyssynchronous LV failure; however, variability in response, particularly in ICM patients, poses ongoing challenges. Endocardial biventricular (BiV) stimulation may provide more flexibility in LV site selection and yield more natural transmural activation patterns. Whether this applies to ICM and whether optimal LV endocardial pacing locations vary among ICM patients remain unknown., Methods: Peak rate of LV pressure increase (dP/dt(max)) was measured at baseline, during VDD pacing at the right ventricular apex, and during BiV pacing from the right ventricular apex and 51 +/- 14 different LV endocardial sites in patients with ICM (n = 11). Seven patients already had an epicardial LV lead (CRT) in place, allowing comparison of epicardial BiV stimulation with that using an endocardial site directly transmural to the CRT-coronary sinus lead tip. Electroanatomic 3-dimensional maps with color-coded dP/dt(max) response defined optimal pacing regions delivering >or=85% of maximal increase in dP/dt(max)., Results: Endocardial BiV pacing improved dP/dt(max) over right ventricular apex pacing in all patients (mean increase 241 +/- 38 mm Hg/s; p < 0.0001). In patients with pre-existing CRT leads, LV endocardial versus epicardial pacing at transmural sites yielded equivalent dP/dt(max) values. However, dP/dt(max) at the best endocardial site exceeded that achieved with the pre-implanted CRT device (mean increase 111 +/- 25 mm Hg/s; p = 0.004). An average of approximately 2 optimal endocardial sites were identified for each patient, located at the extreme basal lateral wall (8 of 11 patients) and other regions (9 of 11). Standard mid-LV free wall pacing yielded suboptimal LV function in 73% of patients. Optimal pacing sites were typically located in LV territories remote (9.3 +/- 3.6 cm) from the infarct zone., Conclusions: CRT delivered at best LV endocardial sites is more effective than via pre-implanted coronary sinus lead pacing. The location of optimal LV endocardial pacing varies among patients with ICM, and individual tailoring may improve CRT efficacy in such patients., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A SETAC Technical Workshop titled "The Nexus Between Ecological Risk Assessment and Natural Resource Damage Assessment Under CERCLA: Understanding and Improving the Common Scientific Underpinnings," was held 18-22 August 2008 in Gregson, Montana, USA, to examine the linkage, nexus, and overlap between ecological risk assessment (ERA) and natural resource damage assessment (NRDA) under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Experts from a broad range of relevant scientific, legal, and policy disciplines convened to 1) ascertain the potential for improved scientific harmonization of the processes of ERA and NRDA; 2) identify where statutory, regulatory, or scientific constraints might exist that would constrain or preclude the harmonization of the 2 processes; 3) determine approaches that might overcome these constraints; and 4) recommend research or potential changes in regulatory policies that might serve to improve both processes. This is the introduction to a series of 3 papers that describe the findings and conclusions of this workshop. Although unanimity was not achieved on all technical, legal, or policy questions posed to the participants, some consensus areas did arise. First, there appear to be few if any legal constraints to using the environmental data collected for ERA or NRDA for both processes. Second, although it is important to recognize and preserve the distinctions between ERA and NRDA, opportunities for data sharing exist, particularly for the characterization of environmental exposures and derivation of ecotoxicological information. Thus, effective coordination is not precluded by the underlying science. Where a cooperative, interactive process is involved among the response agencies, the natural resource trustees, and the responsible party(s), technical, legal or regulatory constraints can be minimized. Finally, one approach that might enhance the potential applicability of data collected for the ERA is to consider ecosystem services in the development of assessment endpoints. These points are explained in greater detail in the series of papers published herein.

Querying patient electronic medical records to improve patient care and process outcomes can seem overwhelming. Our quality improvement model is a simple, user-friendly approach to make quality improvement tasks less daunting. We have successfully used the quality improvement model, written meaningful reports, and given provider feedback that has led to measurable improvements in our clinical and operational performance.

Objectives: The purpose of this study was to test the hypothesis, with noninvasive multimodality imaging, that allogeneic mesenchymal stem cells (MSCs) produce and/or stimulate active cardiac regeneration in vivo after myocardial infarction (MI)., Background: Although intramyocardial injection of allogeneic MSCs improves global cardiac function after MI, the mechanism(s) underlying this phenomenon are incompletely understood., Methods: We employed magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) imaging in MSC-treated pigs (n = 10) and control subjects (n = 12) serially for a 2-month period after anterior MI. A sub-endocardial rim of tissue, demonstrated with MDCT, was assessed for regional contraction with MRI tagging. Rim thickness was also measured on gross pathological specimens, to confirm the findings of the MDCT imaging, and the size of cardiomyocytes was measured in the sub-endocardial rim and the non-infarct zone., Results: Multi-detector computed tomography demonstrated increasing thickness of sub-endocardial viable myocardium in the infarct zone in MSC-treated animals (1.0 +/- 0.2 mm to 2.0 +/- 0.3 mm, 1 and 8 weeks after MI, respectively, p = 0.028, n = 4) and a corresponding reduction in infarct scar (5.1 +/- 0.5 mm to 3.6 +/- 0.2 mm, p = 0.044). No changes occurred in control subjects (n = 4). Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance. This rim was composed of morphologically normal cardiomyocytes, which were smaller in MSC-treated versus control subjects (11.6 +/- 0.2 mum vs. 12.6 +/- 0.2 mum, p < 0.05)., Conclusions: With serially obtained MRI and MDCT, we demonstrate in vivo reappearance of myocardial tissue in the MI zone accompanied by time-dependent restoration of contractile function. These data are consistent with a regenerative process, highlight the value of noninvasive multimodality imaging to assess the structural and functional basis for myocardial regenerative strategies, and have potential clinical applications.

It is not uncommon for patients to have adverse reactions during or after blood transfusions, as they occur in 1%-6% of all blood transfusions. Although many of the reactions are clinically insignificant, a small subset of adverse reactions can lead to serious illness and even death. The authors describe a healthy young man who exhibited an acute pulmonary injury reaction to a blood product transfusion. However, he also suffered significant myocardial insult, as documented by decreased left ventricular ejection fraction and a significant rise in cardiac biomarkers. Based on current understanding of the pathophysiologic mechanisms in transfusion-related acute lung injury, the authors hypothesized that coronary endothelial injury may have caused microvascular ischemia or have induced acute myocarditis. Empiric treatment with steroids and a beta blocker resulted in improved left ventricular function in our patient.

The Medical College of Wisconsin (MCW) and the Wisconsin Geriatric Education Center (WGEC) are committed to developing educational materials for primary care physicians in training. In response to the opportunity created by the Accreditation Council for Graduate Medical Education (ACGME) competency mandate, an MCW-led interdisciplinary working group has developed competency-linked video-based assessment tools for use in primary care residency training programs. Modeled after the Objective Structured Clinical Examinations (OSCE), used as part of the medical licensing examination process, we created geriatric-focused Objective Structured Video Examinations (OSVEs) as a strategy to infuse geriatrics into residency training. Each OSVE tool contains a 1-3 minute video trigger that is associated with a series of multiple choice and/or constructed response questions (e.g., fill in the blank). These questions assess residents' understanding of video-demonstrated ACGME competencies including professionalism, systems-based practice, communication, and practice-based learning. An instructor's guide and scoring key are provided for each tool. Response to the OSVEs has been overwhelmingly enthusiastic including greater than 90% commitment by statewide faculty to use the tools in residency training.

Attempts to treat peanut allergy using traditional methods of allergen desensitization are accompanied by a high risk of anaphylaxis. The aim of this study was to determine if modifications to the IgE-binding epitopes of a major peanut allergen would result in a safer immunotherapeutic agent for the treatment of peanut-allergic patients. IgE-binding epitopes on the Ara h 2 allergen were modified, and modified Ara h 2 (mAra h 2) protein was produced. Wild-type (wAra h 2) and mAra h 2 proteins were analyzed for their ability to interact with T-cells, their ability to bind IgE, and their ability to release mediators from a passively sensitized RBL-2H3 cell line. Multiple T-cell epitopes were identified on the major peanut allergen, Ara h 2. Ara h 2 amino acid regions 11-35, 86-125, and 121-155 contained the majority of peptides that interact with T-cells from most patients. The wAra h 2 and mAra h 2 proteins stimulated proliferation of T-cells from peanut-allergic patients to similar levels. In contrast, the mAra h 2 protein exhibited greatly reduced IgE-binding capacity compared to the wild-type allergen. In addition, the modified allergen released significantly lower amounts of beta-hexosaminidase, a marker for IgE-mediated RBL-2H3 degranulation, compared to the wild-type allergen.

Mass spectrometry data is inherently uncertain. Rather than compare peak heights across samples, a comparison can be made of the relative ordering of the peak height across samples. Order statistics are used to provide a distance metric between each ordered list of peak heights from the samples. A principal component analysis is performed on the set of distance vectors to highlight to important components.

When soluble extracts of the extreme acidothermophilic archaeon Sulfolobus solfataricus were incubated with [gamma-(32)P]ATP, several proteins were radiolabeled. One of the more prominent of these, which migrated with a mass of approximately 46 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was purified by column chromatography and SDS-PAGE and subjected to amino acid sequence analysis via both the Edman technique and mass spectroscopy. The best match to the partial sequence obtained was the potential polypeptide product of open reading frame sso0417, whose DNA-derived amino acid sequence displayed many features reminiscent of the 2,3-diphosphoglycerate-independent phosphoglycerate (PGA) mutases [iPGMs]. Open reading frame sso0417 was therefore cloned, and its protein product was expressed in Escherichia coli. Assays of its catalytic capabilities revealed that the protein was a moderately effective PGA mutase that also exhibited low levels of phosphohydrolase activity. PGA mutase activity was dependent upon the presence of divalent metal ions such as Co(2+) or Mn(2+). The recombinant protein underwent autophosphorylation when incubated with either [gamma-(32)P]ATP or [gamma-(32)P]GTP. The site of phosphorylation was identified as Ser(59), which corresponds to the catalytically essential serine residue in bacterial and eucaryal iPGMs. The phosphoenzyme intermediate behaved in a chemically and kinetically competent manner. Incubation of the (32)P-labeled phosphoenzyme with 3-PGA resulted in the disappearance of radioactive phosphate and the concomitant appearance of (32)P-labeled PGA at rates comparable to those measured in steady-state assays of PGA mutase activity.

In the therapy process, the process of disclosing about stressful or traumatic events is often considered essential. One such manner is through focused expressive writing (FEW) about stressful or traumatic experiences. FEW is related to improvements in health and well-being, across a wide array of outcomes and participant characteristics. As FEW requires limited involvement of other individuals, is relatively low cost, and portable, it has tremendous potential as self-help. In particular, FEW may be an effective means to reach populations unwilling or unable to engage in psychotherapy. A case illustration of FEW is presented. Evidence and future directions for FEW as self-help are reviewed., (Copyright 2003 Wiley Periodicals, Inc.)

There have been many refinements in cardiopulmonary bypass (CPB) techniques over the past few decades specific to design, materials and function. Despite these improvements, use of the standard length circuit tubing and pump oxygenator alter cellular, biochemical and rheological properties by inducing a systemic inflammatory response, persisting well into the early postoperative phase. We have designed a new condensed CPB circuit, the MAST system, where the oxygenator and the pumps are brought closer to the operating table (within 30 inches) with the help of a series of telescopic swivel steel poles to which they are attached. The control console is retained at the usual remote location of 2ft behind the MAST system. This configuration accomplishes a decrease in tubing length, priming volume and blood circulatory time within the extracorporeal circuit. Early experience of a hundred consecutive cases utilizing the MAST CPB system is presented along with a comparative analysis of prime volume, hemodilution and transfusion parameters of MAST system vs the low prime system, which is another newly developed CPB circuit utilizing a pediatric oxygenator to reduce prime volume and hemodilution.

A number of advances in the scientific knowledge concerning adverse food reactions have been made in the past few years. Understanding about the nature of the food allergen itself, the molecular characterization of the epitopes on these allergens, the pathophysiology of the clinical reaction, and the diagnostic methods have all been significantly enhanced.

Background: Numerous strategies have been proposed for the treatment of peanut allergies, but despite the steady advancement in our understanding of atopic immune responses and the increasing number of deaths each year from peanut anaphylaxis, there is still no safe, effective, specific therapy for the peanut-sensitive individual. Immunotherapy would be safer and more effective if the allergens could be altered to reduce their ability to initiate an allergic reaction without altering their ability to desensitize the allergic patient., Methods: The cDNA clones for three major peanut allergens, Ara h 1, Ara h 2, and Ara h 3, have been cloned and characterized. The IgE-binding epitopes of each of these allergens have been determined and amino acids critical to each epitope identified. Site-directed mutagenesis of the allergen cDNA clones, followed by recombinant production of the modified allergen, provided the reagents necessary to test our hypothesis that hypoallergenic proteins are effective immunotherapeutic reagents for treating peanut-sensitive patients. Modified peanut allergens were subjected to immunoblot analysis using peanut-positive patient sera IgE, T cell proliferation assays, and tested in a murine model of peanut anaphylaxis., Results: In general, the modified allergens were poor competitors for binding of peanut-specific IgE when compared to their wild-type counterpart. The modified allergens demonstrated a greatly reduced IgE-binding capacity when individual patient serum IgE was compared to the binding capacity of the wild-type allergens. In addition, while there was considerable variability between patients, the modified allergens retained the ability to stimulate T cell proliferation., Conclusions: These modified allergen genes and proteins should provide a safe immunotherapeutic agent for the treatment of peanut allergy., (Copyright 2001 S. Karger AG, Basel)

Soybean proteins share a large number of cross-reacting allergens with other members of the legume family; however, soy-allergic patients rarely react clinically to other members of the legume family. Gly m Bd 30K, an IgE-binding protein with a molecular weight of 30 kD, was identified in soybean extracts by Western IgE-immunoblot analysis. This monomeric allergen was shown to have an N-terminal amino acid sequence and amino acid composition identical to that of the seed 34-kD protein, P34, a thiol protease of the papain family. Electron-microscopic immunolocalization of P34 monoclonal antibodies and IgE binding to sections of soybean seeds showed dense staining throughout the vacuolar bodies, localizing the allergens in protein storage vacuoles of seed cotyledons. We used pooled serum from soybean-sensitive patients to determine the linear IgE-specific epitopes in the 34-kD allergen amino acid sequence. B-cell epitope mapping revealed 10 regions of IgE-binding activity using an overlapping peptide strategy of 15-mers offset by 8 amino acids throughout the P34 sequence. Smaller overlapping peptides, 10-mers offset by 2 amino acids, revealed 16 distinct linear epitopes, 9 of which were mapped to the mature protein. No obvious amino acid sequence motifs could be identified by the smaller IgE-binding epitopes. Using individual patient serum, 5 immunodominant epitopes were identified in this allergen.

Objectives: The obligatory hemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusion in cardiac operations. We therefore examined whether retrograde autologous priming of the bypass circuit would result in decreased hemodilution and red cell transfusion., Methods: Sixty patients having first-time coronary bypass were prospectively randomized to cardiopulmonary bypass with or without retrograde autologous priming. Retrograde autologous priming was performed at the start of bypass by draining crystalloid prime from the arterial and venous lines into a recirculation bag (mean volume withdrawal: 880 +/- 150 ml). Perfusion and anesthetic techniques were otherwise identical for the two groups. The hematocrit value was maintained at a minimum of 16% and 23% during and after cardiopulmonary bypass, respectively, in all patients. Patients were well matched for all preoperative variables, including established transfusion risk factors. Subsequent hemodynamic parameters, pressor requirements, and fluid requirements were equivalent in the two groups., Results: The lowest hematocrit value during cardiopulmonary bypass was 22% +/- 3% versus 20% +/- 3% in patients subjected to retrograde autologous priming and in control patients, respectively (p = 0.002). One (3%) of 30 patients subjected to retrograde autologous priming had intraoperative transfusion, and seven (23%) of 30 control patients required transfusion during the operation (p = 0.03). The number of patients receiving any homologous red cell transfusions in the two groups during the entire hospitalization was eight of 30 (27%; retrograde autologous priming) versus 16 of 30 (53%; control) (p = 0.03)., Conclusions: These data suggest that retrograde autologous priming is a safe and effective means of significantly decreasing hemodilution and the number of patients requiring red cell transfusion during cardiac operations.

Previous studies have established that atopic individuals living in cockroach-infested housing become sensitized to cockroach aeroallergens and produce IgE antibodies to a variety of proteins. We describe the isolation of a complementary DNA clone from an expression library, constructed with messenger RNA from German (Blattella germanica) cockroaches, which encodes a major allergen involved in mediating cockroach hypersensitivity. Approximately 0.2% of the clones from a lambda ZAP XR cDNA library bound IgE from a patient with cockroach sensitivity. A randomly selected subset of these clones revealed that they were either different isolates of the same gene or members of a closely related gene family. One of the largest clones (a 4 kb insert) from this subset, Bla g Bd90K hybridized to a single mRNA of approximately the same size. DNA sequence analysis showed that this gene consisted of seven 576 bp tandem repeats with a short unique region at either end. No significant sequence homologies were found between the cockroach clone and any other gene reported in the GenBank database. Serum from 17 of 22 (77%) patients with cockroach hypersensitivity identified IgE-binding recombinant protein expressed from clone Bla g Bd90K in Escherichia coli XL-Blue cells as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis/immunoblot analysis. This recombinant protein migrates with a molecular weight (90 kd) apparently similar to one identified in whole body extracts. We have identified and isolated a cDNA that encodes a major cockroach allergen (Bla g Bd90K) present in German cockroaches.

IgE-antibody reactivity to boiled Atlantic shrimp (Pandalus borealis) and German cockroach (Blattella germanica) of sera from 89 patients, sensitive to one or the other, was investigated with an enzymatic immunoassay for specific IgE detection (CAP-FEIA System, Pharmacia, Sweden). IgE serum levels to both antishrimp and anticockroach allergens were found to be positive in 76 of the 89 (85.4%) tested sera. A positive anticockroach IgE was very rare in the absence of detectable antishrimp IgE (five of 89 sera). Linear regression analysis on antishrimp and anti-German cockroach IgE levels-log plot revealed a correlation coefficient (r) of 0.73. Inhibition experiments showed that boiled Atlantic shrimp extract inhibited CAP with German cockroach, and vice versa. Immunoblotting showed the strongest IgE binding for both allergenic extracts between 30 and 43 kDa. By blot inhibition, the binding capacity of German cockroach was totally abolished by Atlantic shrimp extract, while German cockroach extract only partially IgE binding to Atlantic shrimp. Cross-reactivity exists between shrimp, an important food allergen, and German cockroach, which has an increasing role in allergic asthma. It could be important to determine the clinical significance of cross-allergy to both allergens, in which exposures occur in different ways.

The translation of mRNA within total RNA of German (Blattella germanica) cockroaches was performed using a rabbit reticulocyte lysate system. Analysis of the translation products by SDS-PAGE and combined autoradiography revealed several synthesized proteins with apparent molecular weights ranging from 20 kD to 110 kD. SDS-PAGE/Western blotting of non-radiolabeled translation products and incubation with human serum with IgE to cockroach allergens showed the presence of a 36 kD and 50 kD allergen. The confirmation of the translation of the cockroach allergens from total RNA is an important first step in the cloning of cockroach allergens.

Biochemical and immunological data suggest that a relatively limited number of polypeptide antigens of viable Onchocerca volvulus-infective larvae are available to be recognized by the host's immune system. A partial cDNA clone encoding one such antigen, designated lambda RAL-2, was isolated by screening an expression cDNA library with antisera raised against viable O. volvulus L3. The antigen encoded by this clone was subsequently found to be immunogenic in the majority of individuals exposed to O. volvulus. In the present study, the native antigen corresponding to lambda RAL-2 (Ov17) has been characterized. Immunolocalization and in situ hybridization techniques have been used to localize Ov17 in adult and larval stages of the parasite. In adult females, Ov17 was localized primarily in the hypodermis. Ov17 was accessible to surface labeling reagents in viable adult parasites. Full-length cDNA clones encoding Ov17 suggested that the nascent protein contains a putative leader sequence, which is almost immediately followed by a polyglutamine tract. Analysis of antibody reactivity to recombinant proteins containing and lacking the polyglutamine tract demonstrated that this structure was not a significant B cell epitope in individuals exposed to O. volvulus.

In 37 patients with chronic hepatitis B in the stage of active viral replication the authors tried to assess the time of seroconversion of HBeAg to anti-HBe and HBsAg to anti-HBs (21 men, 13 women and 3 boys, mean age of adults 44 years). During the 8-years investigation period seroconversion of HBeAg occurred in 19 of 37 patients (51.3%) which is an annual rate of seroconversion 6.4%. HBeAg disappeared from serum after a mean period of 82 months (range 29-228 months). After seroconversion of HBeAg the ALT and AST activity declined significantly. Acute exacerbation of hepatitis before seroconversion of HBeAg was recorded in 13 of 37 patients (35%). The mean ALT activity at the peak of exacerbation was 7.93 mu kat/l, the average duration of exacerbation was 9.8 months. Seroconversion of HBsAg occurred in 7 of 37 patients (19%). The mean annual rate of seroconversion of HBsAg was 2.4% after an average period of 98 months. During the investigation period 7 patients died (19%), four of them had a constantly positive HBeAg. The authors conclude that very low annual average seroconversion of HBeAg (6.4%) and HBsAg (2.4%) in patients with chronic hepatitis B is probably caused by previous glucocorticoid treatment.

We report here a panel of cDNA clones from Onchocerca volvulus which were isolated on the basis of being uniquely recognised by onchocerciasis sera and not by sera from patients infected with the major lymphatic filarial nematode parasite Wuchereria bancrofti. Over 90% of O. volvulus recombinants from a primary screen were found to cross-react with lymphatic filariasis sera and were discarded. The subset of specific clones, selected with pooled sera, was then screened with panels of individual patient sera. Individual onchocerciasis cases showed a highly heterogeneous pattern of recognition of recombinant peptides, but several clones were identified which could be combined in a cocktail of antigenic epitopes to successfully detect all infected cases in the study. All these clones encode low molecular weight proteins of the parasite, confirming earlier reports that antigens of this size class show greater species specificity. Several clones encode proteins of 20-23 kDa, the same molecular weight range as the major surface protein of adult worms. The two most commonly recognised clones, Ov22/31M and Ov20/36M were subcloned into the vector pNGS 8 which produces fusion proteins attached to a polyasparagine leader. The fusion peptides of both Ov22/31M and Ov20/36M were soluble and easily purified by gel filtration. Purified fusion protein was used in ELISA to assess reactivity of infected patients giving 90% sensitivity with 100% specificity.

Ten adults were studied two to seven years after resection of a fibula for use as a free vascularised bone graft. Six had no symptoms in the donor leg, four had some aching, weakness or paraesthesia and three had definite weakness of the long toe flexors and extensors. All knees and ankles were clinically and radiologically stable, but the distal fibular remnant was osteoporotic in nine patients. Gait analysis of the donor leg and the contralateral normal leg showed definite differences, which could be attributed to weakness of the deep muscles caused by loss of their normal origin and to the change in load transmission through the fibula.

The results are presented of 47 compression arthrodeses of the ankle performed for osteoarthritis in 44 patients. In 26 cases the transverse anterior incision of Charnley had been used and in 21 cases medial and lateral incisions with division of the malleoli. Complications included infection (19%), non-union (14.9%) and malposition requiring a further procedure (8.5%). Three patients (6.4%) eventually had an amputation. Clinical assessment using a standard grading method showed that the functional result was not related to the angle of plantar flexion of the ankle, but was related to the varus/valgus position of the heel, the neutral position being associated with the best results. The anterior approach was more reliable in avoiding varus or valgus of the heel.