548 research outputs found
Michigan, Wisconsin and Minnesota 1836
No full textRelief shown by hachures. "Engraved by Rawdon Clark & Co., Albany, N.Y." "Entered according to act of Congress... by J.H. Colton & Co. on the 9th Nov. 1835." Oriented with north toward the upper left. Prime meridians: Greenwich and Washington. Includes inset: Map of part of Ste. Marie River from actual survey. Indexed in:Karpinski 130E3 Moore 1-0809. This map has been conserved through the generosity of Dr. Donn K. Haglund, 2012.Color1:1,900,8
Islet Assessment for Transplantation
No full textAuthor Manuscript: 2010 December 1.Purpose of review:
There is a critical need for meaningful viability and potency assays that characterize islet preparations for release prior to clinical islet cell transplantation (ICT). Development, testing, and validation of such assays have been the subject of intense investigation for the past decade. These efforts are reviewed, highlighting the most recent results while focusing on the most promising assays.
Recent Findings:
Assays based on membrane integrity do not reflect true viability when applied to either intact islets or dispersed islet cells. Assays requiring disaggregation of intact islets into individual cells for assessment introduce additional problems of cell damage and loss. Assays evaluating mitochondrial function, specifically mitochondrial membrane potential, bioenergetic status, and cellular oxygen consumption rate (OCR), especially when conducted with intact islets, appear most promising in evaluating their quality prior to ICT. Prospective, quantitative assays based on measurements of OCR with intact islets have been developed, validated and their results correlated with transplant outcomes in the diabetic nude mouse bioassay.
Conclusion:
More sensitive and reliable islet viability and potency tests have been recently developed and tested. Those evaluating mitochondrial function are most promising, correlate with transplant outcomes in mice, and are currently being evaluated in the clinical setting.National Center for Research Resources (U.S.) (Grant)National Institutes of Health (U.S.) (Grant U42 RR 016598–01)National Institutes of Health (U.S.) (Grant RO1-DK063108–01A1)Iacocca FoundationSchott FoundationCarol Olson Memorial Diabetes Research Fun
Quantitative analysis of cell composition and purity of human pancreatic islet preparations
No full textAuthor Manuscript 2011 May 1.Despite improvements in outcomes for human islet transplantation, characterization of islet preparations remains poorly defined. This study used both light microscopy (LM) and electron microscopy (EM) to characterize 33 islet preparations used for clinical transplants. EM allowed an accurate identification and quantification of cell types with measured cell number fractions (mean±s.e.m.) of 35.6±2.1% β-cells, 12.6±1.0% non-β-islet cells (48.3±2.6% total islet cells), 22.7±1.5% duct cells, and 25.3±1.8% acinar cells. Of the islet cells, 73.6±1.7% were β-cells. For comparison with the literature, estimates of cell number fraction, cell volume, and extracellular volume were combined to convert number fraction data to volume fractions applicable to cells, islets, and the entire preparation. The mathematical framework for this conversion was developed. By volume, β-cells were 86.5±1.1% of the total islet cell volume and 61.2±0.8% of intact islets (including the extracellular volume), which is similar to that of islets in the pancreas. Our estimates produced 1560±20 cells in an islet equivalent (volume of 150-μm diameter sphere), of which 1140±15 were β-cells. To test whether LM analysis of the same tissue samples could provide reasonable estimates of purity of the islet preparations, volume fraction of the islet tissue was measured on thin sections available from 27 of the clinical preparations by point counting morphometrics. Islet purity (islet volume fraction) of individual preparations determined by LM and EM analyses correlated linearly with excellent agreement (R[superscript 2]=0.95). However, islet purity by conventional dithizone staining was substantially higher with a 20–30% overestimation. Thus, both EM and LM provide accurate methods to determine the cell composition of human islet preparations and can help us understand many of the discrepancies of islet composition in the literature.National Institutes of Health (U.S.) (Grant RO1-DK063108)National Institutes of Health (U.S.) (Grant NCRR ICR U4Z RR 16606)Joslin Diabetes and Endocrinology Research Center (Grant DK36836)Diabetes Research & Wellness FoundationJuvenile Diabetes Research Foundation International (Islet Transplantation, Harvard Medical School
MANOVA modelling of a chiropractic longitudinal study using multiple imputation
No full textThe purpose of this report is to present the detailed statistical analysis of a randomised, placebo-controlled trial comparing two different treatment modalities to an intervention of no known benefit for people with acute or subacute thoracic spine pain.
The therapy arms consist of Spinal Manipulative Therapy (SMT) and Graston Technique (GT) and the placebo is a non-functional ultrasound. A placebo group was utilised because at present there are no proven treatments for non-specific thoracic pain. This trial is registered with the Australia and New Zealand Clinical Trials Registry. Ethics approval has been granted by Murdoch University Human Research and Ethics Committee, number 2007/274.
The aim of this three arm trial was to test the efficacy of SMT and GT as independent modalities compared to detuned ultrasound for the outcomes of pain and disability. The latter were measured using the Visual Analogue Scale (VAS) and a modified Oswestry Back Pain Disability Index. The study was conducted at the Murdoch University Chiropractic student clinic in Perth, Australia, and the protocol published in Crothers et al (2008).
In this report, Section 2 provides an initial exploratory analysis of the data, Section 3 outlines the statistical models used in the final analysis, Section 4 defines these models in mathematical terms, Section 5 discusses the management of missing values via multiple imputation and Section 6 presents the results of the statistical modelling and hypothesis tests. The clinical study will be published in full elsewhere
Enumeration of islets by nuclei counting and light microscopic analysis
No full textAuthor Manuscript 2011 May 1.Islet enumeration in impure preparations by conventional dithizone staining and visual counting is inaccurate and operator dependent. We examined nuclei counting for measuring the total number of cells in islet preparations, and we combined it with morphological analysis by light microscopy (LM) for estimating the volume fraction of islets in impure preparations. Cells and islets were disrupted with lysis solution and shear, and accuracy of counting successively diluted nuclei suspensions was verified with (1) visual counting in a hemocytometer after staining with crystal violet, and automatic counting by (2) aperture electrical resistance measurement and (3) flow cytometer measurement after staining with 7-aminoactinomycin-D. DNA content averaged 6.5 and 6.9 pg of DNA per cell for rat and human islets, respectively, in agreement with literature estimates. With pure rat islet preparations, precision improved with increasing counts, and samples with about greater than or equal to 160 islets provided a coefficient of variation of about 6%. Aliquots of human islet preparations were processed for LM analysis by stereological point counting. Total nuclei counts and islet volume fraction from LM analysis were combined to obtain the number of islet equivalents (IEs). Total number of IE by the standard method of dithizone staining/manual counting was overestimated by about 90% compared with LM/nuclei counting for 12 freshly isolated human islet research preparations. Nuclei counting combined with islet volume fraction measurements from LM is a novel method for achieving accurate islet enumeration.National Institutes of Health (U.S.) (Grant NCRR ICR U4Z 16606)National Institutes of Health (U.S.) (Grant R01-DK063108-01A1)National Institutes of Health (U.S.) (Grant NCRR ICR U42 RR0023244-01)Joslin Diabetes and Endocrinology Research Center (Grant DK36836)Diabetes Research & Wellness FoundationJuvenile Diabetes Research Foundation International (Islet Transplantation, Harvard Medical School
Transplantation of human islets without immunosuppression
No full textTransplantation of pancreatic islets is emerging as a successful treatment for type-1 diabetes. Its current stringent restriction to patients with critical metabolic lability is justified by the long-term need for immunosuppression and a persistent shortage of donor organs. We developed an oxygenated chamber system composed of immune-isolating alginate and polymembrane covers that allows for survival and function of islets without immunosuppression. A patient with type-1 diabetes received a transplanted chamber and was followed for 10 mo. Persistent graft function in this chamber system was demonstrated, with regulated insulin secretion and preservation of islet morphology and function without any immunosuppressive therapy. This approach may allow for future widespread application of cell-based therapies
13 Environmental Chemical Engineering
No full textAs environmental regulations have expanded and the technology being controlled has become more advanced, the associated chemical engineering problems have grown more complex. Chemical engineers have had prominent roles in the development of stack gas scrubbing technologies, in understanding the mechanisms of particle and NO_x, formation in coal combustion, and in developing mathematical models of air pollution. Research that can be classified as environmental engineering occurs in academic departments of civil engineering, mechanical engineering, and chemical engineering, and environmental engineering. In terms of numbers of faculty members, the majority is carried out in departments of civil and environmental engineering. There are certain problems and opportunities for chemical engineers in environmental research. This chapter discusses some important problems in environmental chemical engineering to convey their flavor and challenges. There exist significant environmental research opportunities for chemical engineers, for example, in incineration of hazardous wastes, environmental behavior of toxic substances, synthesis and design of nonpolluting plants, regional and global air pollution, and water chemistry. Most environmental problems are highly complex and often ill defined. At a minimum, they usually require a synthesis of virtually all elements of the chemical engineer's arsenal-thermodynamics, chemical kinetics, and transport phenomena; at the most, an interdisciplinary team
Remote administration and user experience evaluation of the iLab Heat Transfer Project site
No full textThesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2006.Includes bibliographical references.The iLab Heat Transfer Project provides a means for students to remotely execute, via a web interface, experiments related to the topic of heat transfer. The website associated with this project provides instructors with the ability to remotely manage the performance of experiments by their students. This thesis describes improvements made to this website that are intended to grant more control to instructors. Specifically, the website has been augmented to provide remote instructors with complete control over experiment scheduling, user registration, document uploading, and other relevant administrative tasks. The interfaces by which users perform experiments have been modified to incorporate an audio and video feed of the laboratory equipment used in these experiments. In addition, the website has been extended with a feature that facilitates the viewing and analysis of questionnaire responses collected from students. The questionnaire responses provided by students have been examined to gain more knowledge about the effectiveness of various aspects of the website and experiment interfaces.by Rodney K. Graham.M.Eng
Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation
No full textBackground
Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity.
Methods
Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis.
Results
Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6–12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72).
Conclusions
Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.National Institutes of Health (U.S.) (Clinical Islet Transplantation Consortium Grant)Iscel Cell Resources (Grant)Carol Olson Memorial Diabetes Research FundSchott FoundationIacocca FoundationNational Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (K23 DK084315
Quantitative Assessment of Islets of Langerhans Encapsulated in Alginate
No full textImproved methods have recently been developed for assessing islet viability and quantity in human islet
preparations for transplantation, and these measurements have proven useful for predicting transplantation
outcome. The objectives of this study were to adapt these methods for use with microencapsulated islets, to
verify that they provide meaningful quantitative measurements, and to test them with two model systems: (1)
barium alginate and (2) barium alginate containing a 70% (w/v) perfluorocarbon (PFC) emulsion, which
presents challenges to use of these assays and is of interest in its own right as a means for reducing oxygen
supply limitations to encapsulated tissue. Mitochondrial function was assessed by oxygen consumption rate
measurements, and the analysis of data was modified to account for the increased solubility of oxygen in the
PFC-alginate capsules. Capsules were dissolved and tissue recovered for nuclei counting to measure the number
of cells. Capsule volume was determined from alginate or PFC content and used to normalize measurements.
After low oxygen culture for 2 days, islets in normal alginate lost substantial viable tissue and displayed necrotic
cores, whereas most of the original oxygen consumption rate was recovered with PFC alginate, and little necrosis
was observed. All nuclei were recovered with normal alginate, but some nuclei from nonrespiring cells were lost
with PFC alginate. Biocompatibility tests revealed toxicity at the islet periphery associated with the lipid
emulsion used to provide surfactants during the emulsification process. We conclude that these new assay
methods can be applied to islets encapsulated in materials as complex as PFC-alginate. Measurements made
with these materials revealed that enhancement of oxygen permeability of the encapsulating material with a
concentrated PFC emulsion improves survival of encapsulated islets under hypoxic conditions, but reformulation
of the PFC emulsion is needed to reduce toxicity.National Institutes of Health (U.S.) (Grant R01DK50657)National Institutes of Health (U.S.) (Grant R01-DK063108-01A1)National Institutes of Health (U.S.) (Grant NCRR ICR U42 16606)Juvenile Diabetes Research Foundation Internationa
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