Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities

Laboratory evaluation of patients with developmental delay/intellectual disability, congenital anomalies, and dysmorphic features has changed significantly in the last several years with the introduction of microarray technologies. Using these techniques, a patient’s genome can be examined for gains or losses of genetic material too small to be detected by standard G-banded chromosome studies. This increased resolution of microarray technology over conventional cytogenetic analysis allows for identification of chromosomal imbalances with greater precision, accuracy, and technical sensitivity. A variety of array-based platforms are now available for use in clinical practice, and utilization strategies are evolving. Thus, a review of the utility and limitations of these techniques and recommendations regarding present and future application in the clinical setting are presented in this study

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Perpetual landfilling through aeration of the waste mass: lessons from test cells in Georgia (USA)

Municipal solid waste (MSW) landfills worldwide are experiencing the consequences of conventional landfilling techniques, whereby anaerobic conditions are created within the landfilled waste. Under anaerobic conditions within a landfill site slow stabilization of the waste mass occurs, producing methane, (an explosive 'green house' gas) and leachate (which can pollute groundwater) over long periods of time. As a potential solution, it was demonstrated that the aerobic degradation of MSW within a landfill can significantly increase the rate of waste decomposition and settlement, decrease the methane production and leachate leaving the system, and potentially increase the operational life of the site. Readily integrated into the existing landfill infrastructure, this approach can safely and cost-effectively convert a MSW landfill from anaerobic to aerobic degradation processes, thereby effectively composting much of the organic portions (one of the potentially polluting elements in a conventional landfill site) of the waste. This paper summarizes the successful results of two separate aerobic landfill projects located in Georgia (USA) and discusses the potential economic and environmental impacts to worldwide solid waste management practices

Aerobic landfill test cells and their implications for sustainable waste disposal

Municipal Solid Waste (MSW) landfills world-wide are experiencing the consequences of conventional landfilling techniques, whereby anaerobic conditions are created within the landfill waste. Under anaerobic conditions, slow stabilisation of the waste mass occurs, producing methane, (an explosive, 'greenhouse' gas) and toxic leachate over long periods of time. As a potential solution, it was demonstrated that the aerobic degradation of MSW within a landfill can significantly increase the rate of waste decomposition and settlement, decrease the production of methane gas, reduce the level of toxic organics in the leachate and decrease quantities of landfill leachate that need treatment. This paper summarises the successful results of two separate aerobic landfill projects located in Georgia (USA) and discusses the potential economic and environmental impacts to world-wide solid waste management

Financial competing interests were associated with favorable conclusions and greater author productivity in nonsystematic reviews of neuraminidase inhibitors

Objective: To characterize the conclusions and production of nonsystematic reviews about neuraminidase inhibitors relative to financial competing interests held by the authors. Study Design and Setting: We searched for articles about neuraminidase inhibitors and influenza (January 2005 to April 2015), identifying nonsystematic reviews and grading them according to the favorable/nonfavorable presentation of evidence on safety and efficacy. We recorded financial competing interests disclosed in the reviews and from other articles written by their authors. We measured associations between competing interests, author productivity, and conclusions. Results: Among 213 nonsystematic reviews, 138 (65%) presented favorable conclusions. Financial competing interests were identified for 26% (137/532) of authors; 51% (108/213) of reviews were associated with a financial competing interest. Reviews produced exclusively by authors with financial competing interests (33%; 71/213) were more likely to present favorable conclusions than reviews with no competing interests (risk ratio 1.27; 95% confidence interval 1.03-1.55). Authors with financial competing interests published more articles about neuraminidase inhibitors than their counterparts. Conclusion: Half of nonsystematic reviews about neuraminidase inhibitors included an author with a financial competing interest. Reviews produced exclusively by these authors were more likely to present favorable conclusions, and authors with financial competing interests published a greater number of reviews

Age- and Tissue-Specific Expression of Senescence Biomarkers in Mice

Cellular senescence is a state of irreversible cellular growth arrest accompanied by distinct changes in gene expression and the acquisition of a complex proinflammatory secretory profile termed the senescence-associated secretory phenotype (SASP). Senescent cells accumulate in aged tissues and contribute to age-related disease in mice. Increasing evidence that selective removal of senescent cells can ameliorate diseases of late life and extend lifespan in mice has given rise to the development of senolytics that target senescent cells as anti-aging therapeutics. To realize the full potential of senolytic medicine, robust biomarkers of senescence must be in place to monitor the in vivo appearance of senescent cells with age, as well as their removal by senolytic treatments. Here we investigate the dynamic changes in expression of the molecular hallmarks of senescence, including p16Ink4a, p21Cip1, and SASP factors in multiple tissues in mice during aging. We show that expression of these markers is highly variable in age- and tissue-specific manners. Nevertheless, Mmp12 represents a robust SASP factor that shows consistent age-dependent increases in expression across all tissues analyzed in this study and p16Ink4a expression is consistently increased with age in most tissues. Likewise, in humans CDKN2A (p16Ink4a) is one of the top genes exhibiting elevated expression in multiple tissues with age as revealed by data analysis of the Genotype-Tissue Expression (GTEx) project. These results support the targeting of p16Ink4a expressing-cells in senolytic treatments, while emphasizing the need to establish a panel of robust biomarkers of senescence in vivo in both mice and humans

A novel approach to surface electromyography: An exploratory study of electrode-pair selection based on signal characteristics

A 3×4 electrode array was placed over each of seven muscles and surface electromyography (sEMG) data were collected during isometric contractions. For each array, nine bipolar electrode pairs were formed off-line and sEMG parameters were calculated and evaluated based on repeatability across trials and comparison to an anatomically placed electrode pair. The use of time-domain parameters for the selection of an electrode pair from within a grid-like array may improve upon existing electrode placement methodologies

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans

Summary: A hallmark of aging is a decline in metabolic homeostasis, which is attenuated by dietary restriction (DR). However, the interaction of aging and DR with the metabolome is not well understood. We report that DR is a stronger modulator of the rat metabolome than age in plasma and tissues. A comparative metabolomic screen in rodents and humans identified circulating sarcosine as being similarly reduced with aging and increased by DR, while sarcosine is also elevated in long-lived Ames dwarf mice. Pathway analysis in aged sarcosine-replete rats identify this biogenic amine as an integral node in the metabolome network. Finally, we show that sarcosine can activate autophagy in cultured cells and enhances autophagic flux in vivo, suggesting a potential role in autophagy induction by DR. Thus, these data identify circulating sarcosine as a biomarker of aging and DR in mammalians and may contribute to age-related alterations in the metabolome and in proteostasis. : In a comparative metabolic screen of rodents and humans, Walters et al. show that circulating sarcosine is similarly reduced with aging and increased by dietary restriction. They demonstrate that sarcosine activates macroautophagy in cultured cells and in vivo, suggesting a role in improved proteostasis via dietary restriction. Keywords: sarcosine, aging, metabolomics, dietary restriction, autophagy, GNMT, glycerophospholipids, amino acids, glycine, methionin