Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

BackgroundCompounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products.Hypothesis/objectivesThe initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies.AnimalsThirty-seven dogs treated with FDA-approved or compounded lomustine.MethodsDogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection.ResultsTwenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration.Conclusions and clinical importanceThese data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products

Fundamental Aspects of the ISM Fractality

The ubiquitous clumpy state of the ISM raises a fundamental and open problem of physics, which is the correct statistical treatment of systems dominated by long range interactions. A simple solvable hierarchical model is presented which explains why systems dominated by gravity prefer to adopt a fractal dimension around 2 or less, like the cold ISM and large scale structures. This has direct relation with the general transparency, or blackness, of the Universe.Comment: 6 pages, LaTeX2e, crckapb macro, no figure, uuencoded compressed tar file. To be published in the proceeedings of the "Dust-Morphology" conference, Johannesburg, 22-26 January, 1996, D. Block (ed.), (Kluwer Dordrecht

Kanamycin resistance during in vitro development of pollen from transgenic tomato plants

Effects of kanamycin on pollen germination and tube growth of pollen from non-transformed plants and from transgenic tomato plants containing a chimaeric kanamycin resistance gene were determined. Germination of pollen was not affected by the addition of kanamycin to the medium in both genotypes. Kanamycin, however, severely affected tube growth of pollen from non-transformed plants, while pollen from plants containing the chimaeric gene were less sensitive and produced significantly longer tubes at kanamycin concentrations between 200-400 mg l-1. Apparently, this resistance for kanamycin correlates with the expression of the chimaeric gene during male gametophytic development.

Tissue multifractality and Born approximation in analysis of light scattering: a novel approach for precancers detection

Multifractal, a special class of complex self-affine processes, are under recent intensive investigations because of their fundamental nature and potential applications in diverse physical systems. Here, we report on a novel light scattering-based inverse method for extraction/quantification of multifractality in the spatial distribution of refractive index of biological tissues. The method is based on Fourier domain pre-processing via the Born approximation, followed by the Multifractal Detrended Fluctuation Analysis. The approach is experimentally validated in synthetic multifractal scattering phantoms, and tested on biopsy tissue slices. The derived multifractal properties appear sensitive in detecting cervical precancerous alterations through an increase of multifractality with pathology progression, demonstrating the potential of the developed methodology for novel precancer biomarker identification and tissue diagnostic tool. The novel ability to delineate the multifractal optical properties from light scattering signals may also prove useful for characterizing a wide variety of complex scattering media of non-biological origin

Inner wellbeing: concept and validation of a new approach to subjective perceptions of wellbeing-India

© The Author(s) 2013. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This paper describes the conceptual development of a multi-domain, psychosocial model of 'Inner Wellbeing' (IWB) and assesses the construct validity of the scale designed to measure it. IWB expresses what people think and feel they are able to be and do. Drawing together scholarship in wellbeing and international development it is grounded in field research in marginalised, rural communities in the global South. Results from research in India at two points in time (2011 and 2013) are reported. At Time 1 (n = 287), we were unable to confirm an eight-factor, correlated model as distinct yet interrelated domains. However, at Time 2 (n = 335), we were able to confirm a revised, seven-factor correlated model with economic confidence, agency and participation, social connections, close relationships, physical and mental health, competence and self-worth, and values and meaning (five items per domain) as distinct yet interrelated domains. In particular, at Time 2, a seven-factor, correlated model provided a significantly better fit to the data than did a one-factor model.This work is supported by the Economic and Social Research Council/Department for International Development Joint Scheme for Research on International Development (Poverty Alleviation) grant number RES-167-25-0507 ES/H033769/1. Special thanks are due to Chaupal and Gangaram Paikra, Pritam Das, Usha Kujur, Kanti Minjh, Susanna Siddiqui, and Dinesh Tirkey

Sustained CD28 Expression Delays Multiple Features of Replicative Senescence in Human CD8 T Lymphocytes

CD28 costimulatory signal transduction in T lymphocytes is essential for optimal telomerase activity, stabilization of cytokine mRNAs, and glucose metabolism. During aging and chronic infection with HIV-1, there are increased proportions of CD8 T lymphocytes that lack CD28 expression and show additional features of replicative senescence. Moreover, the abundance of these cells correlates with decreased vaccine responsiveness, early mortality in the very old, and accelerated HIV disease progression. Here, we show that sustained expression of CD28, via gene transduction, retards the process of replicative senescence, as evidenced by enhanced telomerase activity, increased overall proliferative potential, and reduced secretion of pro-inflammatory cytokines. Nevertheless, the transduced cultures eventually do reach senescence, which is associated with increased CTLA-4 gene expression and a loss of CD28 cell surface expression. These findings further elucidate the central role of CD28 in the replicative senescence program, and may ultimately lead to novel therapies for diseases associated with replicative senescence

Climate Change and invasibility of the Antarctic benthos

Benthic communities living in shallow-shelf habitats in Antarctica (<100-m depth) are archaic in their structure and function. Modern predators, including fast-moving, durophagous (skeleton-crushing) bony fish, sharks, and crabs, are rare or absent; slow-moving invertebrates are the top predators; and epifaunal suspension feeders dominate many soft substratum communities. Cooling temperatures beginning in the late Eocene excluded durophagous predators, ultimately resulting in the endemic living fauna and its unique food-web structure. Although the Southern Ocean is oceanographically isolated, the barriers to biological invasion are primarily physiological rather than geographic. Cold temperatures impose limits to performance that exclude modern predators. Global warming is now removing those physiological barriers, and crabs are reinvading Antarctica. As sea temperatures continue to rise, the invasion of durophagous predators will modernize the shelf benthos and erode the indigenous character of marine life in Antarctica

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

Top-down social modulation of interpersonal observation-execution.

Cyclical upper limb movement can involuntarily deviate from its primary movement axis when the performer concurrently observes incongruent biological motion (i.e. interpersonal observation-execution). The current study examined the social modulation of such involuntary motor interference using a protocol that reflected everyday social interactions encountered in a naturalistic social setting. Eighteen participants executed cyclical horizontal arm movements during the observation of horizontal (congruent) or curvilinear (incongruent) biological motion. Both prior to, and during the interpersonal observation-execution task, participants also received a series of social words designed to prime a pro-social or anti-social attitude. The results showed greater orthogonal movement deviation, and thus interference, for the curvilinear compared to horizontal stimuli. Importantly, and opposite to most of the previous findings from work on automatic imitation and mimicry, there was a greater interference effect for the anti-social compared to pro-social prime condition. These findings demonstrate the importance of interpreting the context of social primes, and strongly support predictions of a comparison between the prime construct and the self-concept/-schema and the top-down response modulation of social incentives

A philosophical analysis of the evidence-based medicine debate

BACKGROUND: The term "evidence-based medicine" (or EBM) was introduced about ten years ago, and there has been considerable debate about the value of EBM. However, this debate has sometimes been obscured by a lack of conceptual clarity concerning the nature and status of EBM. DISCUSSION: First, we note that EBM proponents have obscured the current debate by defining EBM in an overly broad, indeed almost vacuous, manner; we offer a clearer account of EBM and its relation to the alternative approaches to medicine. Second, while EBM proponents commonly cite the philosophical work of Thomas Kuhn and claim that EBM is a Kuhnian 'paradigm shift,' we argue that such claims are seriously mistaken and unduly polarize the EBM debate. Third, we suggest that it is much more fruitful to understand the relationship between EBM and its alternatives in light of a different philosophical metaphor: W.V. Quine's metaphor of the web of belief. Seen in this way, we argue that EBM is an approach to medical practice that is indeed importantly different from the alternatives. SUMMARY: We can have a more productive debate about the value of EBM by being clearer about the nature of EBM and its relationship to alternative approaches to medicine