Biophotonic Tools in Cell and Tissue Diagnostics.

In order to maintain the rapid advance of biophotonics in the U.S. and enhance our competitiveness worldwide, key measurement tools must be in place. As part of a wide-reaching effort to improve the U.S. technology base, the National Institute of Standards and Technology sponsored a workshop titled "Biophotonic tools for cell and tissue diagnostics." The workshop focused on diagnostic techniques involving the interaction between biological systems and photons. Through invited presentations by industry representatives and panel discussion, near- and far-term measurement needs were evaluated. As a result of this workshop, this document has been prepared on the measurement tools needed for biophotonic cell and tissue diagnostics. This will become a part of the larger measurement road-mapping effort to be presented to the Nation as an assessment of the U.S. Measurement System. The information will be used to highlight measurement needs to the community and to facilitate solutions

Glioblastoma multiforme: a rare manifestation of extensive liver and bone metastases

Glioblastoma multiforme (GBM) is the most aggressive form of primary brain tumours known collectively as gliomas. Gliomas are graded by their microscopic appearance. As a rule, their behaviour can be predicted from histology: Grade I (pilocytic astrocytomas) and Grade II (benign astrocytomas) tumours are of low grade and grow slowly over many years. Grade IV tumours (GBM) are the most aggressive and, unfortunately, also the most common in humans, growing rapidly, invading and altering brain function. These tumours arise from the supporting glial cells of the brain during childhood and in adulthood

Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique

Introduction: Leptospirosis is a neglected zoonotic disease caused by a bacteria of the genus Leptospira. In Africa, it is frequently mistaken for frequently occurring conditions such as malaria. The aim of this study was to identify rodent species involved in the transmission of the disease, the prevalence of pathogenic Leptospira spp. in selected rodent species and risk factors for human leptospirosis. Material and Methods: We conducted a descriptive and exploratory epidemiological and molecular study in Mozambique Island city in 2015. Six neighborhoods, comprising 30 households each were randomly selected. People from the selected 180 households were interviewed regarding their awareness of the disease, the presence of rodents in their houses, chemicals used to eliminate them, sewage disposal, water supply system, and other key issues related to the disease. In each neighborhood, we trapped 10 rodents for a morphometric study to identify their species and for molecular isolation of Leptospira DNA. We extracted kidneys from 57/60 of rodents trapped and performed nested polymerase chain reaction targeting rrs 16S ribosomal RNA and lipL32 genes for identification of Leptospira genus and pathogenic Leptospira spp. respectively. Results: Of the 180 participants 92 (51%) reported having heard of leptospirosis;107 (59%) have had the disease; 151 (83%) reported the existence of rats in their house; 100 (56%) had latrines; 118 (66%) used chemicals to kill the rats; 102 (57%) used well water and 114 (63%) used trash containers. The most prevalent rodent species captured was Rattus norvegicus 36/60 (60%), followed by Rattus rattus 19/60 (31.67%) and Mus musculus 3/60 (5%). Sequences of rrs 16S rRNA gene were identified rrs 16S ribosomal DNA RNA was identified in 20/57 (35.%) rodents. Out these two were positive for lipL32 gene, giving an overall pathogenic Leptospira infection of 3.5% (2/57). The rodent species identified as carriers of pathogenic Leptospira were Rattus norvegicus (1) and R. rattus (1). Conclusion: This is the first study in Mozambique to identify the presence of pathogenic species of Leptospira using molecular tools. Leptospirosis risk factors in Mozambique Island city are rodent’s infestation, limited disease awareness, lack of access to clean water, insufficient resources for waste collection, greater clustering of households, poor sanitation environment and degradation of living conditions. Pathogenic Leptospira spp. are present in the area studied and at least two species of rodents, the R. rattus and R. norvegicus are potentially involved in the transmission of the causal agents of the disease.publishersversionpublishe

Promoter optimisation of lentiviral vectors for efficient insulin gene expression in canine mesenchymal stromal cells: potential surrogate beta cells.

BACKGROUND: The lack of an ideal cell type that can be easily acquired, modified to produce insulin, and re-implanted has been a limitation for ex vivo insulin gene therapy. Canine diabetes is currently treated with human insulin and is a good model for human diabetes. Mesenchymal stromal cells (MSCs) are a promising candidate cell type for gene therapy. In the present study, we optimised insulin production using lentiviral transduced canine MSCs (cMSCs), aiming to evaluate their ability for use as surrogate beta cells. METHODS: Canine MSCs were derived from bone marrow and validated by measuring the expression of MSC lineage specific markers. Lentivirus vectors encoding the proinsulin gene (with or without a Kozak sequence) under the control of spleen focus forming virus, cytomegalovirus, elongation factor 1α and simian virus 40 promotors were generated and used to transduce primary cMSCs and a hepatocyte cell line. The insulin-producing capacity of transduced primary cMSCs was assessed by measuring the concentration of C-peptide produced. RESULTS: Primary cMSC could be readily expanded in culture and efficiently transduced using lentiviral vectors encoding proinsulin. Increasing the multiplicity of infection from 3 to 20 led to an increase in C-peptide secretion (from 1700 to 4000 pmol/l). The spleen focus forming virus promoter conferred the strongest transcriptional ability. CONCLUSIONS: The results of the present study suggest that optimised lentiviral transduction of the insulin gene into primary cMSCs renders these cells capable of secreting insulin over both the short- and long-term, in sufficient quantities in vitro to support their potential use in insulin gene therapy.The study was funded by the Lollipop Trust. Work in the laboratory is supported by the Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/jgm.290

Coherent Signal Amplification in Bistable Nanomechanical Oscillators by Stochastic Resonance

Stochastic resonance is a counter-intuitive concept[1,2], ; the addition of noise to a noisy system induces coherent amplification of its response. First suggested as a mechanism for the cyclic recurrence of ice ages, stochastic resonance has been seen in a wide variety of macroscopic physical systems: bistable ring lasers[3], SQUIDs[4,5], magnetoelastic ribbons[6], and neurophysiological systems such as the receptors in crickets[7] and crayfish[8]. Although it is fundamentally important as a mechanism of coherent signal amplification, stochastic resonance is yet to be observed in nanoscale systems. Here we report the observation of stochastic resonance in bistable nanomechanical silicon oscillators, which can play an important role in the realization of controllable high-speed nanomechanical memory cells. Our nanomechanical systems were excited into a dynamic bistable state and modulated in order to induce controllable switching; the addition of white noise showed a marked amplification of the signal strength. Stochastic resonance in nanomechanical systems paves the way for exploring macroscopic quantum coherence and tunneling, and controlling nanoscale quantum systems for their eventual use as robust quantum logic devices.Comment: 18 pages, 4 figure

A fast Metropolis-Hastings method for generating random correlation matrices

We propose a novel Metropolis-Hastings algorithm to sample uniformly from the space of correlation matrices. Existing methods in the literature are based on elaborated representations of a correlation matrix, or on complex parametrizations of it. By contrast, our method is intuitive and simple, based the classical Cholesky factorization of a positive definite matrix and Markov chain Monte Carlo theory. We perform a detailed convergence analysis of the resulting Markov chain, and show how it benefits from fast convergence, both theoretically and empirically. Furthermore, in numerical experiments our algorithm is shown to be significantly faster than the current alternative approaches, thanks to its simple yet principled approach.Comment: 8 pages, 3 figures, 2018 conferenc

Divergent mathematical treatments in utility theory

In this paper I study how divergent mathematical treatments affect mathematical modelling, with a special focus on utility theory. In particular I examine recent work on the ranking of information states and the discounting of future utilities, in order to show how, by replacing the standard analytical treatment of the models involved with one based on the framework of Nonstandard Analysis, diametrically opposite results are obtained. In both cases, the choice between the standard and nonstandard treatment amounts to a selection of set-theoretical parameters that cannot be made on purely empirical grounds. The analysis of this phenomenon gives rise to a simple logical account of the relativity of impossibility theorems in economic theory, which concludes the paper

Associations between insulin and glucose concentrations and anthropometric measures of fat mass in Australian adolescents

<p>Abstract</p> <p>Background</p> <p>One of the most serious, yet common co-morbidities of obesity is insulin resistance, which if untreated may progress to type 2 diabetes. This paper describes the insulin and glucose concentration distributions, the prevalence of elevated insulin, the associations between insulin and body mass index (BMI), waist circumference, waist-to-height ratio (WHtR) and fat mass index in a representative sample of Australian adolescents.</p> <p>Methods</p> <p>Cross-sectional population-based study of adolescent boys and girls (N = 496, mean age 15.3 years) attending schools in metropolitan Sydney, Australia. Fasting venous blood collected and analysed for insulin and glucose concentrations. Height, weight, waist circumference measured, BMI and waist-to-height ratio calculated. Pubertal status self-reported.</p> <p>Results</p> <p>Glucose concentrations were normally distributed and were not associated with adiposity. Insulin concentrations were distributed logarithmically, were higher among girls than boys overall and within the same ranges of BMI and waist circumference, but were lower among girls than boys within the same ranges of fat mass adjusted for height. The prevalence of elevated insulin concentration (defined as > 100 pmol/L) was 15.9% and 17.1% among boys and girls, respectively. Correlations between insulin concentration and BMI, waist circumference, WHtR and fat mass adjusted for height were 0.53, 0.49, 0.51 and 0.55, among boys, respectively, and 0.35, 0.40, 0.42 and 0.34, among girls, respectively.</p> <p>Conclusions</p> <p>Elevated insulin is highly correlated with adiposity in adolescents. BMI and WHtR are simple measures that can be used to identify young people who should be screened for insulin resistance and other co-morbidities.</p

8th International Conference: Primary Therapy of Early Breast Cancer, St Gallen, Switzerland, March 12–15 2003

The International St Gallen Breast Cancer Conference concentrates almost exclusively on adjuvant, multimodal primary therapy for early breast cancer. Begun 25 years ago, this meeting was initially held every 4 years, but therapeutic progress, new strategies and provocative trials data have accelerated to the extent that conferences are now held biennially. The meeting this year was attended by almost 3000 delegates. Major topics included new prognostic and predictive markers in early breast cancer, the best use of adjuvant chemotherapy and endocrine therapy, and innovations in local surgery and radiation therapy