The antimicrobial resistance crisis: Management through gene monitoring

© 2016 The Authors. Antimicrobial resistance (AMR) is an acknowledged crisis for humanity. Its genetic origins and dire potential outcomes are increasingly well understood. However, diagnostic techniques for monitoring the crisis are currently largely limited to enumerating the increasing incidence of resistant pathogens. Being the end-stage of the evolutionary process that produces antimicrobial resistant pathogens, these measurements, while diagnostic, are not prognostic, and so are not optimal in managing this crisis. A better test is required. Here, using insights from an understanding of evolutionary processes ruling the changing abundance of genes under selective pressure, we suggest a predictive framework for the AMR crisis. We then discuss the likely progression of resistance for both existing and prospective antimicrobial therapies. Finally, we suggest that by the environmental monitoring of resistance gene frequency, resistance may be detected and tracked presumptively, and how this tool may be used to guide decision-making in the local and global use of antimicrobials

Laguerre-Gaussian Modes and the Wigner Transform

Recent developments in laser physics have called renewed attention to Laguerre-Gaussian (LG) beams of paraxial light. In this paper we consider the corresponding LG modes for the two-dimensional harmonic oscillator, which appear in the transversal plane at the laser beam's waist. We see how they arise as Wigner transforms of Hermite-Gaussian modes, and we proceed to find a closed form for their own Wigner transforms, providing an alternative to the methods of Simon and Agarwal. Our main observation is that the Wigner transform intertwines the creation and annihilation operators for the two classes of modes.Comment: 12 pages, minor corrections; submitted, Journal of Modern Optic

Evaluating and monitoring analgesia and sedation in the intensive care unit

Management of analgesia and sedation in the intensive care unit requires evaluation and monitoring of key parameters in order to detect and quantify pain and agitation, and to quantify sedation. The routine use of subjective scales for pain, agitation, and sedation promotes more effective management, including patient-focused titration of medications to specific end-points. The need for frequent measurement reflects the dynamic nature of pain, agitation, and sedation, which change constantly in critically ill patients. Further, close monitoring promotes repeated evaluation of response to therapy, thus helping to avoid over-sedation and to eliminate pain and agitation. Pain assessment tools include self-report (often using a numeric pain scale) for communicative patients and pain scales that incorporate observed behaviors and physiologic measures for noncommunicative patients. Some of these tools have undergone validity testing but more work is needed. Sedation-agitation scales can be used to identify and quantify agitation, and to grade the depth of sedation. Some scales incorporate a step-wise assessment of response to increasingly noxious stimuli and a brief assessment of cognition to define levels of consciousness; these tools can often be quickly performed and easily recalled. Many of the sedation-agitation scales have been extensively tested for inter-rater reliability and validated against a variety of parameters. Objective measurement of indicators of consciousness and brain function, such as with processed electroencephalography signals, holds considerable promise, but has not achieved widespread implementation. Further clarification of the roles of these tools, particularly within the context of patient safety, is needed, as is further technology development to eliminate artifacts and investigation to demonstrate added value

Influence of anatomical site and topical formulation on skin penetration of sunscreens

Sunscreen products are widely used to protect the skin from sun-related damage. Previous studies have shown that some sunscreen chemicals are absorbed across the skin to the systemic circulation. The current study shows that absorption into the skin of sunscreen chemicals applied to the face is up to four times greater than that of the same product applied to the back. This has implications for the way sunscreen products are formulated and may allow the use of less potent products on the face compared with the rest of the body. The effect of formulation vehicles on the release and skin penetration of the common sunscreen agent benzophenone-3 (common name oxybenzone) was also assessed. Penetration of benzophenone-3 across excised human epidermis and high-density polyethylene (HDPE) membrane was measured using in vitro Franz-type diffusion cells. Penetration and epidermal retention was measured following application of infinite and finite (epidermis only) doses of benzophenone-3 in five vehicles: liquid paraffin, coconut oil, 50:50 ethanol:coconut oil, aqueous cream BP, and oily cream BP. Highest benzophenone-3 skin retention was observed for the ethanol:coconut oil combination. Maximal and minimal benzophenone-3 fluxes were observed from liquid paraffin and coconut oil, respectively. The alcohol-based vehicle exhibited low benzophenone-3 release from the vehicle but high skin penetration and retention

Alterations in the lipid profile and liver enzymes of rats treated with monosodium glutamate

This study was carried out to evaluate the effects of monosodium glutamate on the liver and lipid profile of eighteen adult male Wistar rats as measured by biochemical parameters. The rats received monosodium glutamate at dose rate of 0, 0.5 and 1.0g per day for 28 days. There was significant increase (P<0.05) in aminotransferases i.e. alanine and aspartate aminotransferases as well as increase in total plasma cholesterol and low density lipoprotein cholesterol most obvious at higher dose of 1.0g of monosodium glutamate. Though there was decrease in plasma protein concentration, triglyceride and high density lipoprotein cholesterol which was not statistically significant, therefore monosodium glutamate has both hepatotoxic and dyslipidaemia effects due to its alterations in both aminotransferase activities and lipid profile, hence monosodium glutamate though a flavor enhancer food additive but it must be carefully used in food preparation due to it alterations in both the liver enzymes and the lipid profile.Keywords: Adult rats, dyslipidaemia, flavor enhancer, hepatotoxic, monosodium glutamat

Does implementation matter if comprehension is lacking? A qualitative investigation into perceptions of advance care planning in people with cancer

Purpose: While advance care planning holds promise, uptake is variable and it is unclear how well people engage with or comprehend advance care planning. The objective of this study was to explore how people with cancer comprehended Advance Care Plans and examine how accurately advance care planning documentation represented patient wishes. Methods: This study used a qualitative descriptive design. Data collection comprised interviews and an examination of participants’ existing advance care planning documentation. Participants included those who had any diagnosis of cancer with an advance care plan recorded: Refusal of Treatment Certificate; Statement of Choices; and/or Enduring Power of Attorney (Medical Treatment) at one cancer treatment centre. Results: Fourteen participants were involved in the study. Twelve participants were female (86%). The mean age was 77 (range: 61-91) and participants had completed their advance care planning documentation between 8 and 72 weeks prior to the interview (mean 33 weeks). Three themes were evident from the data: Incomplete advance care planning understanding and confidence; Limited congruence for attitude and documentation; Advance care planning can enable peace of mind. Complete advance care planning understanding was unusual; most participants demonstrated partial comprehension of their own advance care plan, and some indicated very limited understanding. Participants’ attitudes and their written document congruence was limited, but advance care planning was seen as helpful. Conclusions: This study highlighted advance care planning was not a completely accurate representation of patient wishes. There is opportunity to improve how patients comprehend their own advance care planning documentation

Heterochromatin is refractory to γ-H2AX modification in yeast and mammals

Double-strand break (DSB) damage in yeast and mammalian cells induces the rapid ATM (ataxia telangiectasia mutated)/ATR (ataxia telangiectasia and Rad3 related)-dependent phosphorylation of histone H2AX (γ-H2AX). In budding yeast, a single endonuclease-induced DSB triggers γ-H2AX modification of 50 kb on either side of the DSB. The extent of γ-H2AX spreading does not depend on the chromosomal sequences. DNA resection after DSB formation causes the slow, progressive loss of γ-H2AX from single-stranded DNA and, after several hours, the Mec1 (ATR)-dependent spreading of γ-H2AX to more distant regions. Heterochromatic sequences are only weakly modified upon insertion of a 3-kb silent HMR locus into a γ-H2AX–covered region. The presence of heterochromatin does not stop the phosphorylation of chromatin more distant from the DSB. In mouse embryo fibroblasts, γ-H2AX distribution shows that γ-H2AX foci increase in size as chromatin becomes more accessible. In yeast, we see a high level of constitutive γ-H2AX in telomere regions in the absence of any exogenous DNA damage, suggesting that yeast chromosome ends are transiently detected as DSBs

A Bound on the Superpotential

We prove a general bound on the superpotential in theories with broken supersymmetry and broken R-symmetry, 2|W|< f_a F, where f_a and F are the R-axion and Goldstino decay constants, respectively. The bound holds for weakly coupled as well as strongly coupled theories, thereby providing an exact result in theories with broken supersymmetry. We briefly discuss several possible applications.Comment: 20 page

Women’s experiences of wearing therapeutic footwear in three European countries

Background: Therapeutic footwear is recommended for those people with severe foot problems associated with rheumatoid arthritis (RA). However, it is known that many do not wear them. Although previous European studies have recommended service and footwear design improvements, it is not known if services have improved or if this footwear meets the personal needs of people with RA. As an earlier study found that this footwear has more impact on women than males, this study explores women’s experiences of the process of being provided with it and wearing it. No previous work has compared women’s experiences of this footwear in different countries, therefore this study aimed to explore the potential differences between the UK, the Netherlands and Spain. Method: Women with RA and experience of wearing therapeutic footwear were purposively recruited. Ten women with RA were interviewed in each of the three countries. An interpretive phenomenological approach (IPA) was adopted during data collection and analysis. Conversational style interviews were used to collect the data. Results: Six themes were identified: feet being visibly different because of RA; the referring practitioners’ approach to the patient; the dispensing practitioners’ approach to the patient; the footwear being visible as different to others; footwear influencing social participation; and the women’s wishes for improved footwear services. Despite their nationality, these women revealed that therapeutic footwear invokes emotions of sadness, shame and anger and that it is often the final and symbolic marker of the effects of RA on self perception and their changed lives. This results in severe restriction of important activities, particularly those involving social participation. However, where a patient focussed approach was used, particularly by the practitioners in Spain and the Netherlands, the acceptance of this footwear was much more evident and there was less wastage as a result of the footwear being prescribed and then not worn. In the UK, the women were more likely to passively accept the footwear with the only choice being to reject it once it had been provided. All the women were vocal about what would improve their experiences and this centred on the consultation with both the referring practitioner and the practitioner that provides the footwear. Conclusion: This unique study, carried out in three countries has revealed emotive and personal accounts of what it is like to have an item of clothing replaced with an ‘intervention’. The participant’s experience of their consultations with practitioners has revealed the tension between the practitioners’ requirements and the women’s ‘social’ needs. Practitioners need greater understanding of the social and emotional consequences of using therapeutic footwear as an intervention