Islet Assessment for Transplantation

Author 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

Using GIS to integrate old and new archaeological data from Stone Age deposits in Karonga, Malawi

The Karonga District of northern Malawi has an extensive Stone Age archaeological record, primarily represented by stone artefacts that occur in both superficial and buried contexts. Work conducted in the 1960s provided initial documentation of this record. Some of this was presented in summary form in a small number of publications. However, most data were restricted to unpublished field notes, maps, and other static or largely inaccessible formats. GIS has been an essential tool for bringing together these diverse datasets in a digital format to facilitate integration of new research and promote reinvestigation of old sites. Examples from both the regional and site scale demonstrate how old data have been combined with recent survey and excavation data to document, analyse, interpret, and archive current knowledge about the rich Stone Age record of northern Malawi. A significant result from this approach has been the suggested reinterpretation of the Mwanganda’s Village Site

Determination of the optimal sample size for a clinical trial accounting for the population size

The problem of choosing a sample size for a clinical trial is a very common one. In some settings, such as rare diseases or other small populations, the large sample sizes usually associated with the standard frequentist approach may be infeasible, suggesting that the sample size chosen should reflect the size of the population under consideration. Incorporation of the population size is possible in a decision-theoretic approach either explicitly by assuming that the population size is fixed and known, or implicitly through geometric discounting of the gain from future patients reflecting the expected population size. This paper develops such approaches. Building on previous work, an asymptotic expression is derived for the sample size for single and two-arm clinical trials in the general case of a clinical trial with a primary endpoint with a distribution of one parameter exponential family form that optimizes a utility function that quantifies the cost and gain per patient as a continuous function of this parameter. It is shown that as the size of the population, N, or expected size, inline image in the case of geometric discounting, becomes large, the optimal trial size is inline image or inline image. The sample size obtained from the asymptotic expression is also compared with the exact optimal sample size in examples with responses with Bernoulli and Poisson distributions, showing that the asymptotic approximations can also be reasonable in relatively small sample sizes

Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply

Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO to a supraphysiological level that maintains all islets viable and functional. These levels were determined from measurements of pO profiles in islet-alginate slabs. Encapsulated islets implanted with surface density as high as 4,800 islet equivalents/cm in diabetic rats maintained normoglycemia for more than 7 months and provided near-normal intravenous glucose tolerance tests. Nearly 90% of the original viable tissue was recovered after device explantation. Damaged islets failed after progressively shorter times. The required values of gas chamber pO were predictable from a mathematical model of oxygen consumption and diffusion in the device. These results demonstrate feasibility of developing retrievable macroencapsulated devices small enough for clinical use and provide a firm basis for design of devices for testing in large animals and humans

Baseline Methods for Automated Fictional Ideation

The invention of fictional ideas (ideation) is often a central process in the creative production of artefacts such as poems, music and paintings, but has barely been studied in the Computational Creativity community. We present here three baseline approaches for automated fictional ideation, using methods which invert and alter facts from the ConceptNet and ReVerb databases, and perform bisociative discovery. For each method, we present a curation analysis, by calculating the proportion of ideas which pass a typicality evaluation. We further evaluate one ideation approach through a crowd- sourcing experiment in which participants were asked to rank ideas. The results from this study, and the baseline methods and methodologies presented here, constitute a firm basis on which to build more sophisticated models for automated ideation with evaluative capacity

Observations of Binary Stars with the Differential Speckle Survey Instrument. IX. Observations of Known and Suspected Binaries, and a Partial Survey of Be Stars

We report 370 measures of 170 components of binary and multiple star systems, obtained from speckle imaging observations made with the Differential Speckle Survey Instrument at Lowell Observatory's Discovery Channel Telescope in 2015 through 2017. Of the systems studied, 147 are binary stars, 10 are seen as triple systems, and 1 quadruple system is measured. Seventy-six high-quality non-detections and fifteen newly resolved components are presented in our observations. The uncertainty in relative astrometry appears to be similar to our previous work at Lowell, namely linear measurement uncertainties of approximately 2 mas, and the relative photometry appears to be uncertain at the 0.1 to 0.15 magnitude level. Using these measures and those in the literature, we calculate six new visual orbits, including one for the Be star 66 Oph, and two combined spectroscopic-visual orbits. The latter two orbits, which are for HD 22451 (YSC 127) and HD 185501 (YSC 135), yield individual masses of the components at the level of 2 percent or better, and independent distance measures that in one case agrees with the value found in the Gaia DR2, and in the other disagrees at the 2-$\sigma$ level. We find that HD 22451 consists of an F6V+F7V pair with orbital period of $2401.1 \pm 3.2$ days and masses of $1.342 \pm 0.029$ and $1.236 \pm 0.026$ $M_{\odot}$. For HD 185501, both stars are G5 dwarfs that orbit one another with a period of $433.94 \pm 0.15$ days, and the masses are $0.898 \pm 0.012$ and $0.876 \pm 0.012$ $M_{\odot}$. We discuss the details of both the new discoveries and the orbit objects

Geophysical monitoring of simulated clandestine graves using electrical and ground-penetrating radar methods: 0-3 years after burial.

This study provides forensic search teams with systematic geophysical monitoring data over simulated clandestine graves for comparison to active cases. Simulated "wrapped" and "naked" burials were created. Multigeophysical surveys were collected over a 3-year monitoring period. Bulk ground resistivity, electrical resistivity imaging, multifrequency ground-penetrating radar (GPR), and grave and background "soil-water" conductivity data were collected. Resistivity surveys revealed the naked burial had consistently low-resistivity anomalies, whereas the wrapped burial had small, varying high-resistivity anomalies. GPR 110- to 900-MHz frequency surveys showed the wrapped burial could be detected throughout, with the "naked" burial mostly resolved. Two hundred and twenty-five megahertz frequency GPR data were optimal. "Soil-water" analyses showed rapidly increasing (year 1), slowly increasing (year 2), and decreasing (year 3) conductivity values. Results suggest resistivity and GPR surveys should be collected if target "wrapping" is unknown, with winter to spring surveys optimal. Resistivity surveys should be collected in clay-rich soils

Spin dynamics in semiconductors

This article reviews the current status of spin dynamics in semiconductors which has achieved a lot of progress in the past years due to the fast growing field of semiconductor spintronics. The primary focus is the theoretical and experimental developments of spin relaxation and dephasing in both spin precession in time domain and spin diffusion and transport in spacial domain. A fully microscopic many-body investigation on spin dynamics based on the kinetic spin Bloch equation approach is reviewed comprehensively.Comment: a review article with 193 pages and 1103 references. To be published in Physics Reports

Quantitative analysis of cell composition and purity of human pancreatic islet preparations

Author 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

Resilient Pedagogy: Practical Teaching Strategies to Overcome Distance, Disruption, and Distraction

Resilient Pedagogy offers a comprehensive collection on the topics and issues surrounding resilient pedagogy framed in the context of the COVID-19 pandemic and the social justice movements that have swept the globe. As a collection, Resilient Pedagogy is a multi-disciplinary and multi-perspective response to actions taken in different classrooms, across different institution types, and from individuals in different institutional roles with the purpose of allowing readers to explore the topics to improve their own teaching practice and support their own students through distance, disruption, and distraction