792 research outputs found

    Soule\u27s manual on auditing, suggestions to auditors, receivers and liquidators, and on points on higher and expert accounting; Manual on auditing, suggestions to auditors, receivers and liquidators, and on points on higher and expert accounting

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    The following Manual on Auditing is presented to aid in disseminating, in an economical form, knowledge which is of practical interest to all Book-keepers and to all Business Aspirants. A thorough knowledge of Auditing is a crown of honor, and it should be worn by all who hope to achieve victory in their manifold contests for fortune and fame on the fields of Business. The work here given, though brief, will, it is believed, be of service to thousands of book-keepers and business men, who have not heretofore had an opportunity to study the subject, for want of books treating thereof. The author\u27s large work, the New Science and Practice of Accounts, which combines this subject with Higher and Expert Accounting, Joint Stock Company Book-keeping, and Complex Adjustments in Corporation Accounting, is too expensive to be possessed by many who need this knowledge, and hence these few pages are presented, at a small cost. Indulging the hope that the work may be of some service to the aspiring lover and learner of Auditing and Accounting, the author submits it to the business public with his professional greetings

    A \u3cem\u3eMycobacterium ulcerans\u3c/em\u3e Toxin, Mycolactone, Causes Apoptosis in Guinea Pig Ulcers and Tissue Culture Cells

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    Mycobacterium ulcerans is the causative agent of Buruli ulcer, a tropical ulcerative skin disease. One of the most intriguing aspects of this disease is the presence of extensive tissue damage in the absence of an acute inflammatory response. We recently purified and characterized a macrolide toxin, mycolactone, from M. ulcerans. Injection of this molecule into guinea pig skin reproduced cell death and lack of acute inflammatory response similar to that seen following the injection of viable bacteria. We also showed that mycolactone causes a cytopathic effect on mouse fibroblast L929 cells that is characterized by cytoskeletal rearrangements and growth arrest within 48 h. However, these results could not account for the extensive cell death which occurs in Buruli ulcer. The results presented here demonstrate that L929 and J774 mouse macrophage cells die via apoptosis after 3 to 5 days of exposure to mycolactone. Treatment of cells with a pan-caspase inhibitor can inhibit mycolactone-induced apoptosis. We demonstrate that injection of mycolactone into guinea pig skin results in cell death via apoptosis and that the extent of apoptosis increases as the lesion progresses. These results may help to explain why tissue damage in Buruli ulcer is not accompanied by an acute inflammatory response

    Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting

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    Background: An elevated preoperative white blood cell count has been associated with a worse outcome after coronary artery bypass grafting (CABG). Leukocyte subtypes, and particularly the neutrophil-lymphocyte (N/L) ratio, may however, convey superior prognostic information. We hypothesized that the N/L ratio would predict the outcome of patients undergoing surgical revascularization. Methods: Baseline clinical details were obtained prospectively in 1938 patients undergoing CABG. The differential leukocyte was measured before surgery, and patients were followed-up 3.6 years later. The primary end point was all-cause mortality. Results: The preoperative N/L ratio was a powerful univariable predictor of mortality (hazard ratio [HR] 1.13 per unit, P 3.36). Conclusion: An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.Peer reviewedAuthor versio

    Analysis of innate and acquired resistance to anti-CD20 antibodies in malignant and nonmalignant B cells

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    The anti-CD20 monoclonal antibody, rituximab, provides a significant therapeutic benefit for patients with B-cell disorders. However, response to therapy varies and relapses are common, so an understanding of both inherited and acquired rituximab resistance is needed. In order to identify mechanisms of inherited resistance, sensitive versus resistant individuals were selected from a survey of 92 immortalized lymphoblastoid B-cell lines from normal individuals. Levels of CD20 protein and surface expression were lower in the resistant group. In contrast, CD20 mRNA levels were not correlated with susceptibility, suggesting regulation at a post-transcriptional level. To examine acquired resistance, resistant sublines were selected from both lymphoblastoid as well as lymphoma cell lines. Confirming previous findings, there was significant down-regulation of CD20 protein expression in all the resistant sublines. CD20 mRNA splice variants are reported to be associated with development of resistance. Three splice variants were observed in our cell lines, each lacking the binding epitope for rituximab, but none were associated with rituximab resistance. The second generation anti-CD20 mAb, ofatumumab, was more active compared with rituximab in vitro in the survey of all B-cell lines, mirroring results that have been reported previously with malignant B-cells. These studies show that normal B-lymphoblastoid cell lines can be used to model both innate and acquired mechanisms of resistance. They validate the important role of CD20 expression and enable future genetic studies to identify additional mediators of anti-CD20 mAb resistance

    VH1-44 gene usage defines a subset of canine B-cell lymphomas associated with better patient survival

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    The use of specific immunoglobulin heavy chain variable region (VH) genes has been associated with increased patient survival in human B-cell lymphomas (hBCL). Given the similarity of human and canine BCL (cBCL) in morphology and clinical treatment, we examined the choice of VH in cBCL and determined whether VH gene selection was a distinct feature associated with survival time in dogs. VH gene selection and mutational status in 52 cBCL, including 29 diffuse large B-cell lymphomas (cDLBCL, the most common subtype of cBCL), were analyzed by comparison with the 80 published canine germline VH gene sequences. We further examined the prognostic impact of the subgroups defined by these features on canine survival. We found that VH1-44 was preferentially expressed in the majority of the 52 cBCLs (60%) as well as in the majority of the cDLBCL subset (59%). VH1-44 gene expression was associated with a statistically better overall survival (p=0.039) in cBCL patients, as well as in the cDLBCL subset of patients (p=0.038). These findings suggest that VH gene selection in cBCL is not random and may therefore have functional implications for cBCL lymphomagenesis, in addition to being a useful prognostic biomarker

    Ecological characteristics of core-use areas used by Bering–Chukchi–Beaufort (BCB) bowhead whales, 2006–2012

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    © The Author(s), 2014]. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Progress in Oceanography 136 (2015): 201-222, doi:10.1016/j.pocean.2014.08.012.The Bering–Chukchi–Beaufort (BCB) population of bowhead whales (Balaena mysticetus) ranges across the seasonally ice-covered waters of the Bering, Chukchi, and Beaufort seas. We used locations from 54 bowhead whales, obtained by satellite telemetry between 2006 and 2012, to define areas of concentrated use, termed “core-use areas”. We identified six primary core-use areas and describe the timing of use and physical characteristics (oceanography, sea ice, and winds) associated with these areas. In spring, most whales migrated from wintering grounds in the Bering Sea to the Cape Bathurst polynya, Canada (Area 1), and spent the most time in the vicinity of the halocline at depths <75 m, which are within the euphotic zone, where calanoid copepods ascend following winter diapause. Peak use of the polynya occurred between 7 May and 5 July; whales generally left in July, when copepods are expected to descend to deeper depths. Between 12 July and 25 September, most tagged whales were located in shallow shelf waters adjacent to the Tuktoyaktuk Peninsula, Canada (Area 2), where wind-driven upwelling promotes the concentration of calanoid copepods. Between 22 August and 2 November, whales also congregated near Point Barrow, Alaska (Area 3), where east winds promote upwelling that moves zooplankton onto the Beaufort shelf, and subsequent relaxation of these winds promoted zooplankton aggregations. Between 27 October and 8 January, whales congregated along the northern shore of Chukotka, Russia (Area 4), where zooplankton likely concentrated along a coastal front between the southeastward-flowing Siberian Coastal Current and northward-flowing Bering Sea waters. The two remaining core-use areas occurred in the Bering Sea: Anadyr Strait (Area 5), where peak use occurred between 29 November and 20 April, and the Gulf of Anadyr (Area 6), where peak use occurred between 4 December and 1 April; both areas exhibited highly fractured sea ice. Whales near the Gulf of Anadyr spent almost half of their time at depths between 75 and 100 m, usually near the seafloor, where a subsurface front between cold Anadyr Water and warmer Bering Shelf Water presumably aggregates zooplankton. The amount of time whales spent near the seafloor in the Gulf of Anadyr, where copepods (in diapause) and, possibly, euphausiids are expected to aggregate provides strong evidence that bowhead whales are feeding in winter. The timing of bowhead spring migration corresponds with when zooplankton are expected to begin their spring ascent in April. The core-use areas we identified are also generally known from other studies to have high densities of whales and we are confident these areas represent the majority of important feeding areas during the study (2006–2012). Other feeding areas, that we did not detect, likely existed during the study and we expect core-use area boundaries to shift in response to changing hydrographic conditions.This study is part of the Synthesis of Arctic Research (SOAR) and was funded in part by the U.S. Department of the Interior, Bureau of Ocean Energy Management, Environmental Studies Program through Interagency Agreement No. M11PG00034 with the U.S. Department of Commerce, National Oceanic and Atmospheric Administration (NOAA), Office of Oceanic and Atmospheric Research (OAR), Pacific Marine Environmental Laboratory (PMEL). Funding for this research was mainly provided by U.S. Minerals Management Service (now Bureau of Ocean Energy Management) under contracts M12PC00005, M10PS00192, and 01-05-CT39268, with the support and assistance from Charles Monnett and Jeffery Denton, and under Interagency Agreement No. M08PG20021 with NOAA-NMFS and Contract No. M10PC00085 with ADF&G. Work in Canada was also funded by the Fisheries Joint Management Committee, Ecosystem Research Initiative (DFO), and Panel for Energy Research and Development

    Transitions in microbial communities along a 1600 km freshwater trophic gradient

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    This study examined vertically-resolved patterns in microbial community structure across a freshwater trophic gradient extending 1600 km from the oligotrophic waters of Lake Superior to the eutrophic waters of Lake Erie, the most anthropogenically influenced of the Laurentian Great Lakes system. Planktonic bacterial communities clustered by Principal Coordinates Analysis (PCoA) on UniFrac distance matrices into four groups representing the epilimnion and hypolimnion of the upper Great Lakes (Lakes Superior and Huron), Lake Superior\u27s northern bays (Nipigon and Black bays), and Lake Erie. The microbes within the upper Great Lakes hypolimnion were the most divergent of these groups with elevated abundance of Planctomycetes and Chloroflexi compared to the surface mixed layer. Statistical tests of the correlation between distance matrices identified temperature and sample depth as the most influential community structuring parameters, reflecting the strong UniFrac clustering separating mixed-layer and hypolimnetic samples. Analyzing mixed-layer samples alone showed clustering patterns were correlated with nutrient concentrations. Operational taxonomic units (OTU) which were differentially distributed among these conditions often accounted for a large portion of the reads returned. While limited in coverage of temporal variability, this study contributes a detailed description of community variability that can be related to other large freshwater systems characterized by changing trophic state

    Secondary bacterial infections of buruli ulcer lesions before and after chemotherapy with streptomycin and rifampicin

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    Buruli ulcer (BU), caused by Mycobacterium ulcerans is a chronic necrotizing skin disease. It usually starts with a subcutaneous nodule or plaque containing large clusters of extracellular acid-fast bacilli. Surrounding tissue is destroyed by the cytotoxic macrolide toxin mycolactone produced by microcolonies of M. ulcerans. Skin covering the destroyed subcutaneous fat and soft tissue may eventually break down leading to the formation of large ulcers that progress, if untreated, over months and years. Here we have analyzed the bacterial flora of BU lesions of three different groups of patients before, during and after daily treatment with streptomycin and rifampicin for eight weeks (SR8) and determined drug resistance of the bacteria isolated from the lesions. Before SR8 treatment, more than 60% of the examined BU lesions were infected with other bacteria, with Staphylococcus aureus and Pseudomonas aeruginosa being the most prominent ones. During treatment, 65% of all lesions were still infected, mainly with P. aeruginosa. After completion of SR8 treatment, still more than 75% of lesions clinically suspected to be infected were microbiologically confirmed as infected, mainly with P. aeruginosa or Proteus miriabilis. Drug susceptibility tests revealed especially for S. aureus a high frequency of resistance to the first line drugs used in Ghana. Our results show that secondary infection of BU lesions is common. This could lead to delayed healing and should therefore be further investigated

    Health and environmental consequences of the world trade center disaster.

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    The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperreactivity. Evaluation of 10,116 firefighters showed exposure-related increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on 11 September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster
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