DNA testing and domestic dogs

There are currently about 80 different DNA tests available for mutations that are associated with inherited disease in the domestic dog, and as the tools available with which to dissect the canine genome become increasingly sophisticated, this number can be expected to rise dramatically over the next few years. With unrelenting media pressure focused firmly on the health of the purebred domestic dog, veterinarians and dog breeders are turning increasingly to DNA tests to ensure the health of their dogs. It is ultimately the responsibility of the scientists who identify disease-associated genetic variants to make sensible choices about which discoveries are appropriate to develop into commercially available DNA tests for the lay dog breeder, who needs to balance the need to improve the genetic health of their breed with the need to maintain genetic diversity. This review discusses some of the factors that should be considered along the route from mutation discovery to DNA test and some representative examples of DNA tests currently available

Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study

Background: There is evidence that cancer survivors are at increased risk of second primary cancers. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks.<p></p> Methods: We examined the incidence of second primary cancer among adults in the West of Scotland, UK, diagnosed with cancer between 2000 and 2004 (n = 57,393). We used National Cancer Institute Surveillance Epidemiology and End Results and International Agency for Research on Cancer definitions of multiple primary cancers and estimated indirectly standardised incidence ratios (SIR) with 95% confidence intervals (CI).<p></p> Results: There was a high incidence of cancer during the first 60 days following diagnosis (SIR = 2.36, 95% CI = 2.12 to 2.63). When this period was excluded the risk was not raised, but it was high for some patient groups; in particular women aged <50 years with breast cancer (SIR = 2.13, 95% CI = 1.58 to 2.78), patients with bladder (SIR = 1.41, 95% CI = 1.19 to 1.67) and head & neck (SIR = 1.93, 95% CI = 1.67 to 2.21) cancer. Head & neck cancer patients had increased risks of lung cancer (SIR = 3.75, 95% CI = 3.01 to 4.62), oesophageal (SIR = 4.62, 95% CI = 2.73 to 7.29) and other head & neck tumours (SIR = 6.10, 95% CI = 4.17 to 8.61). Patients with bladder cancer had raised risks of lung (SIR = 2.18, 95% CI = 1.62 to 2.88) and prostate (SIR = 2.41, 95% CI = 1.72 to 3.30) cancer.<p></p> Conclusions: Relative risks of second primary cancers may be smaller than previously reported. Premenopausal women with breast cancer and patients with malignant melanomas, bladder and head & neck cancers may benefit from increased surveillance and advice to avoid known risk factors

Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration

Investigating the impact of poverty on colonization and infection with drug-resistant organisms in humans: a systematic review

Background Poverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions. Methods A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool. Results Nineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings. Conclusions Despite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance

Risk factors for pressure sores in adult patients with myelomeningocele – a questionnaire-based study

BACKGROUND: Myelomeningocele (MMC) is a part of a complex neural tube defect and a disorder of the cerebrospinal fluid system. Pressure sores are a frequent complication for patients with MMC. Little is known about the risk factors for pressure sores in adults with MMC. The aim of this study was to investigate an association between the presence of pressure sores and other patient characteristics, in order to develop an improved strategy for the management of sores. METHODS: A structured questionnaire regarding sores, medical condition, function and living factors was designed and sent to the 193 patients with MMC registered in the year 2003 at TRS, a National Centre for Rare Disorders in Norway. RESULTS: Out of 193 total, 87 patients participated and 71 patients (82%) reported sores; 26 (30%) at the time of the interview and 45 (52%) during the last 5 years. Sores were mostly localized on toes and feet and occurred exclusively in regions with reduced or missing sensibility. A significant association was found between sores and memory deficit (p = 0.02), Arnold Chiari malformation (p = 0.02) and a record of previous sores (p = 0.004). Sores were not significantly associated with hydrocephalus, syringomyelia, nutrition, body mass index, smoking, physical activity, employment or living together with other persons. Some patients (18, 21%) reported skin inspection by others and the remainder relied on self-inspection. CONCLUSION: Patients with sensory deficit, memory problems, and Arnold Chiari malformation had a higher risk of having pressure sores. This patient group needs improved skin inspection routines and sore treatment

Detection of Gene Expression in an Individual Cell Type within a Cell Mixture Using Microarray Analysis

BACKGROUND: A central issue in the design of microarray-based analysis of global gene expression is the choice between using cells of single type and a mixture of cells. This study quantified the proportion of lipopolysaccharide (LPS) induced differentially expressed monocyte genes that could be measured in peripheral blood mononuclear cells (PBMC), and determined the extent to which gene expression in the non-monocyte cell fraction diluted or obscured fold changes that could be detected in the cell mixture. METHODOLOGY/PRINCIPAL FINDINGS: Human PBMC were stimulated with LPS, and monocytes were then isolated by positive (Mono+) or negative (Mono-) selection. The non-monocyte cell fraction (MonoD) remaining after positive selection of monocytes was used to determine the effect of non-monocyte cells on overall expression. RNA from LPS-stimulated PBMC, Mono+, Mono- and MonoD samples was co-hybridised with unstimulated RNA for each cell type on oligonucleotide microarrays. There was a positive correlation in gene expression between PBMC and both Mono+ (0.77) and Mono- (0.61-0.67) samples. Analysis of individual genes that were differentially expressed in Mono+ and Mono- samples showed that the ability to detect expression of some genes was similar when analysing PBMC, but for others, differential expression was either not detected or changed in the opposite direction. As a result of the dilutional or obscuring effect of gene expression in non-monocyte cells, overall about half of the statistically significant LPS-induced changes in gene expression in monocytes were not detected in PBMC. However, 97% of genes with a four fold or greater change in expression in monocytes after LPS stimulation, and almost all (96-100%) of the top 100 most differentially expressed monocyte genes were detected in PBMC. CONCLUSIONS/SIGNIFICANCE: The effect of non-responding cells in a mixture dilutes or obscures the detection of subtle changes in gene expression in an individual cell type. However, for studies in which only the most highly differentially expressed genes are of interest, separating and analysing individual cell types may be unnecessary

Prospective study of the primary evaluation of 1016 horses with clinical signs of abdominal pain by veterinary practitioners, and the differentiation of critical and non‑critical cases

Background: The majority of research on the evaluation of horses with colic is focused on referral hospital populations. Early identification of critical cases is important to optimise outcome and welfare. The aim of this prospective study was to survey the primary evaluation of horses with clinical signs of abdominal pain by veterinary practitioners, and compare the initial presentation of critical and non-critical cases. Results: Data from 1016 primary evaluations of horses presenting with clinical signs of colic were submitted by 167 veterinary practitioners across the United Kingdom over a 13 month period. The mean age of the study population was 13.5 years (median 12.0, range 0–42). Mean heart rate on primary presentation was 47 beats/min (median 44, range 18–125), mean respiratory rate was 20 breaths/min (median 16, range 6–100), and median gastrointestinal auscultation score (0–12, minimum–maximum) was 5 (range 0–12). Clinical signs assessed using a behavioural severity score (0–17, minimum–maximum), were between 0 and 6 in 70.4 % of cases, and 7 12 for 29.6 % of cases. Rectal examination was performed in 73.8 % of cases. Cases that responded positively to simple medical treatment were categorised retrospectively as ‘non-critical’; cases that required intensive medical treatment, surgical intervention, died or were euthanased were categorised as ‘critical’. Eight-hundred-and-twenty- two cases met these criteria; 76.4 % were ‘non-critical’ and 23.6 % were ‘critical’. Multivariable logistic regression was used to identify features of the clinical presentation associated with critical cases. Five variables were retained in the final multivariable model: combined pain score: (OR 1.19, P 2.5 s (OR 3.21, P = 0.046, 95 % CI 1.023–10.09), weak pulse character (OR 2.90, P = 0.004, 95 % CI 1.39–5.99) and absence of gut sounds in ≥1 quadrant (OR 3.65, P < 0.001, 95 % CI 2.08–6.41). Conclusions: This is the first study comparing the primary presentation of critical and non-critical cases of abdominal pain. Pain, heart rate, gastrointestinal borborygmi and simple indicators of hypovolaemia were significant indicators of critical cases, even at the primary veterinary examination, and should be considered essential components of the initial assessment and triage of horses presenting with colic

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Complex Fluids and Hydraulic Fracturing

Nearly 70 years old, hydraulic fracturing is a core technique for stimulating hydrocarbon production in a majority of oil and gas reservoirs. Complex fluids are implemented in nearly every step of the fracturing process, most significantly to generate and sustain fractures and transport and distribute proppant particles during and following fluid injection. An extremely wide range of complex fluids are used: naturally occurring polysaccharide and synthetic polymer solutions, aqueous physical and chemical gels, organic gels, micellar surfactant solutions, emulsions, and foams. These fluids are loaded over a wide range of concentrations with particles of varying sizes and aspect ratios and are subjected to extreme mechanical and environmental conditions. We describe the settings of hydraulic fracturing (framed by geology), fracturing mechanics and physics, and the critical role that non-Newtonian fluid dynamics and complex fluids play in the hydraulic fracturing process