97 research outputs found

    The “Plumed Knight” At Home: An Intimate Sketch of James G. Blaine

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    This article is a detailed overview of the personal and political lives of Maine\u27s James G. Blaine

    The Blaine House: A Brief History and Guide

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    Few executive mansions in the United States have such rich historical associations as the Blaine House, the official residence of Maine\u27s governors. From 1862 until his death in 1893, it was home to James Gillespie Blaine and his family. Blaine bestrode the political world like a colossus in the post-Civil War Gilded Age. Dazzling, charismatic, worshiped by his friends, loathed by his enemies, ( contemporaries called him variously the \u27\u27Plumed Knight of the Republican Party and the continental liar from the State of Maine ), he dominated the Maine Republican party for a generation, served brilliantly as Speaker of the U.S. House of Representatives; United States Senator; trail-blazing Secretary of State for the two Presidents, and in 1884 came within a whisker of winning the Presidency of the United States himself.https://digitalcommons.usm.maine.edu/mhpc-docs/1004/thumbnail.jp

    Book Reviews

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    Reviews of the following books: Maine: A Bibliography of Its History by John D. Haskell, Jr.; Tombstones and Paving Blocks: The History of the Granite Industry in Maine by Roger E. Grindle; Josiah Volunteered: A Collection of Diaries, Letters and Photographs of Josiah H. Sturtevant, His Wife Helen and His Four Children edited by Arnold H. Sturtevan

    Book Reviews

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    Reviews of the following books: The Kennebec Proprietors, 1749-1775: Gentlemen of Large Property & Judicious Men by Gordon E. Kershaw; Maine Shipbuilding: A Bibliographical Guide compiled by William A. Baker; Maine in the Civil War: A Bibliographical Guide compiled by William B. Jordan, Jr

    Impact on Malaria Parasite Multiplication Rates in Infected Volunteers of the Protein-in-Adjuvant Vaccine AMA1-C1/Alhydrogel+CPG 7909

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    BACKGROUND: Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria. METHODS: In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes. RESULTS: A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9]). CONCLUSIONS: Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers. TRIAL REGISTRATION: ClinicalTrials.gov [NCT00984763]

    Modelling molecular interaction pathways using a two-stage identification algorithm

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    In systems biology, molecular interactions are typically modelled using white-box methods, usually based on mass action kinetics. Unfortunately, problems with dimensionality can arise when the number of molecular species in the system is very large, which makes the system modelling and behavior simulation extremely difficult or computationally too expensive. As an alternative, this paper investigates the identification of two molecular interaction pathways using a black-box approach. This type of method creates a simple linear-in-the-parameters model using regression of data, where the output of the model at any time is a function of previous system states of interest. One of the main objectives in building black-box models is to produce an optimal sparse nonlinear one to effectively represent the system behavior. In this paper, it is achieved by applying an efficient iterative approach, where the terms in the regression model are selected and refined using a forward and backward subset selection algorithm. The method is applied to model identification for the MAPK signal transduction pathway and the Brusselator using noisy data of different sizes. Simulation results confirm the efficacy of the black-box modelling method which offers an alternative to the computationally expensive conventional approach

    A new infrared color criterion for the selection of 0<z<7 AGN: application to deep fields and implications for JWST surveys

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    [Abridged] It is widely accepted that observations at mid-infrared (mid-IR) wavelengths enable the selection of galaxies with nuclear activity, which may not be revealed even in the deepest X-ray surveys. In this work new near- and mid-IR color diagnostics are explored, aiming for improved efficiency - better completeness and less contamination - in selecting AGN out to very high redshifts. We restrict our study to the James Webb Space Telescope wavelength range (0.6-27um). The criteria are created based on the predictions by state-of-the-art galaxy and AGN templates covering a wide variety of galaxy properties, and tested against control samples with deep multi-wavelength coverage (ranging from the X-rays to radio frequencies). We show that the colors Ks-[4.5], [4.5]-[8.0], and [8.0]-[24] are ideal as AGN/non-AGN diagnostics at, respectively, z~2.5-3. However, when the source redshift is unknown, these colors should be combined. We thus develop an improved IR criterion (using Ks and IRAC bands, KI) as a new alternative at z<~2.5. KI does not show improved completeness (50-60% overall) in comparison to commonly used IRAC-based AGN criteria, but is less affected by non-AGN contamination (revealing a >50-90% level of successful AGN selection). We also propose KIM (using Ks, IRAC, and MIPS-24um bands, KIM), which aims to select AGN hosts from local distances to as far back as the end of reionization (0<z<~7) with reduced non-AGN contamination. However, the necessary testing-constraints and the small control-sample sizes prevent the confirmation of its improved efficiency at z<~2.5. Overall, KIM shows a ~30-40% completeness and a >70-90% level of successful AGN selection. KI and KIM are built to be reliable against a ~10-20% error in flux, are based on existing filters, and are suitable for immediate use.Comment: Accepted for publication on the Astrophysical Journa

    Treatment of osteochondral lesions of the talus: a systematic review

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    The aim of this study was to summarize all eligible studies to compare the effectiveness of treatment strategies for osteochondral defects (OCD) of the talus. Electronic databases from January 1966 to December 2006 were systematically screened. The proportion of the patient population treated successfully was noted, and percentages were calculated. For each treatment strategy, study size weighted success rates were calculated. Fifty-two studies described the results of 65 treatment groups of treatment strategies for OCD of the talus. One randomized clinical trial was identified. Seven studies described the results of non-operative treatment, 4 of excision, 13 of excision and curettage, 18 of excision, curettage and bone marrow stimulation (BMS), 4 of an autogenous bone graft, 2 of transmalleolar drilling (TMD), 9 of osteochondral transplantation (OATS), 4 of autologous chondrocyte implantation (ACI), 3 of retrograde drilling and 1 of fixation. OATS, BMS and ACI scored success rates of 87, 85 and 76%, respectively. Retrograde drilling and fixation scored 88 and 89%, respectively. Together with the newer techniques OATS and ACI, BMS was identified as an effective treatment strategy for OCD of the talus. Because of the relatively high cost of ACI and the knee morbidity seen in OATS, we conclude that BMS is the treatment of choice for primary osteochondral talar lesions. However, due to great diversity in the articles and variability in treatment results, no definitive conclusions can be drawn. Further sufficiently powered, randomized clinical trials with uniform methodology and validated outcome measures should be initiated to compare the outcome of surgical strategies for OCD of the talus

    Cognitive Dysfunction Is Sustained after Rescue Therapy in Experimental Cerebral Malaria, and Is Reduced by Additive Antioxidant Therapy

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    Neurological impairments are frequently detected in children surviving cerebral malaria (CM), the most severe neurological complication of infection with Plasmodium falciparum. The pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. In the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatment. Infection of C57BL/6 and Swiss (SW) mice with Plasmodium berghei ANKA (PbA) or a lethal strain of Plasmodium yoelii XL (PyXL), respectively, resulted in documented CM and sustained persistent cognitive damage detected by a battery of behavioral tests after cure of the acute parasitic disease with chloroquine therapy. Strikingly, cognitive impairment was still present 30 days after the initial infection. In contrast, BALB/c mice infected with PbA, C57BL6 infected with Plasmodium chabaudi chabaudi and SW infected with non lethal Plasmodium yoelii NXL (PyNXL) did not develop signs of CM, were cured of the acute parasitic infection by chloroquine, and showed no persistent cognitive impairment. Reactive oxygen species have been reported to mediate neurological injury in CM. Increased production of malondialdehyde (MDA) and conjugated dienes was detected in the brains of PbA-infected C57BL/6 mice with CM, indicating high oxidative stress. Treatment of PbA-infected C57BL/6 mice with additive antioxidants together with chloroquine at the first signs of CM prevented the development of persistent cognitive damage. These studies provide new insights into the natural history of cognitive dysfunction after rescue therapy for CM that may have clinical relevance, and may also be relevant to cerebral sequelae of sepsis and other disorders

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability
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