Echinocandin inhibition of 1,3-β-D-glucan synthase from Candida albicans

AbstractThe cyclic peptide antibiotic echinocandin was found to inhibit 1,3-β-D-glucan synthase activity present in a mixed membrane fraction from Candida albicans. Addition of antibiotic reduced the Vmax of the enzyme, but the Km was unaffected. GTP stimulated enzyme activity ~ 4-fold, but did not affect the percentage inhibition of the enzyme by echinocandin. Treatment of the reaction products with α-amylase and β-glucanase confirmed that the polymer synthesised was 1,3-β-D-glucan, not glycogen

The management of children with Spinal Muscular Atrophy Type 1 in Australia

Aims: To (1) estimate the prevalence of Spinal Muscular Atrophy Type 1 (SMA 1); (2) describe what practices characterise end-of-life care of patients with SMA 1; (3) ascertain whether a consistent approach to the management of these patients exists in Australia. Methods: An audit of the Australasian pathology laboratories offering the diagnostic SMN1 deletion test was conducted for patients diagnosed with SMA in Australia for 2010 and 2011. In addition, a retrospective clinical audit was conducted in eight major Australian paediatric hospitals of the end-of-life care provided to children with confirmed SMA 1 from 2005 to 2010. Results: 35 children were included in the clinical audit, accounting for an estimated 61% of children diagnosed with SMA 1 from 2005-2010. 26% were ventilated invasively, only two of whom were intubated after the diagnosis was confirmed. No children were ventilated long-term (>90 days) or had a tracheostomy performed. Nasogastric tube feeding was a common measure to support adequate nutritional intake. Total parenteral nutrition, gastrostomy and fundoplication were not provided for any children. Conflict over end-of-life care decisions was documented in one instance, without the involvement of a guardianship tribunal. Conclusion: There appears to be a consistent approach in the management of children with SMA 1 in Australia, which can be characterised as ‘actively managed dying.’ This study could contribute to the development of Australian consensus guidelines for the management of these children. These results also highlight a number of ethical issues related to the management of children with SMA 1

Rethinking pediatric ethics consultations

Johnson and colleagues (2015) report a retrospective review of the experience of an ethics consultation service at a single, highly specialized children's hospital over an 11-year period. Despite its methodologic limitations, the results of this study are worthy of note. The St. Jude Children's Research Hospital ethics consultation service consulted on a range of complex cases, including the management of conflict between parents and physicians, futility, parental demands, treatment nonadherence, and, less commonly, end-of-life issues. The number of case consultations was small, fewer than five per year, and did not increase over time. The retrospective nature of the study prevented eliciting how often consultations altered treatment or other decisions. No record was kept of clinical staff, parent, or patient perception of the value of the ethics consultation, nor of the frequency or value of informal (curb side) ethics consultations. The St. Jude ethics consultation process is consistent with “standard” models in the field. An ethics team comprising two to five staff members, including an ethicist, performs the initial ward consultation, which is then discussed with the formal clinical ethics committee of 21 people. Other involved services participate via interdisciplinary meetings. The types of consultation are consistent with many other services, including both formal and informal consultations using a range of methods to assist resolution of cases, including mediation and arbitration. Despite open access to requesting consultations, including anonymous enquiries, almost all requests came from physicians, often the same ones. Only a few came from nurses and none from parents or patients. Importantly, nurses appeared to be subject to repercussions from physicians if they requested consultations, an important issue that requires further attention but goes beyond the scope of our commentary. We suggest that the experience of the St. Jude service illustrates both the limitations of ethics consultation and the need to evaluate the importance and impact of an ethics service using metrics other than simply the number of case consultations

Growing food on the green world: J. H. Prynne’s agro-chemical pastoral in the Vale of Tintern

This article reads the poetry of J. H. Prynne of the early- to mid-1970s through an ecocritical lens, arguing that this work responds to the language of a nascent environmentalism framed by the concerns of political ecology. It does so by drawing on Prynne’s archival correspondence with the American poet Edward Dorn in the mid-1970s, which demonstrates a private concern with agro-chemicals, colour and cultivation that served as an analogue for shifts in the politics of relating to the extra-human world. It argues that Prynne’s High Pink on Chrome (1975) is closely attuned to the suppressed human and extra-human costs of high-yield monocrop cultivation. In turn, the article sets these post-war practices in a longer continuum of pastoral suppression, linking such hidden violence with ecocritical and New Historicist arguments about the ‘green’ politics of William Wordsworth’s ‘Tintern Abbey’, to which Prynne alluded when writing to Dorn in 1975

Pedestrian, Crowd, and Evacuation Dynamics

This contribution describes efforts to model the behavior of individual pedestrians and their interactions in crowds, which generate certain kinds of self-organized patterns of motion. Moreover, this article focusses on the dynamics of crowds in panic or evacuation situations, methods to optimize building designs for egress, and factors potentially causing the breakdown of orderly motion.Comment: This is a review paper. For related work see http://www.soms.ethz.c

Why Do Some Molecules Form Hydrates or Solvates?

The discovery of solvates (crystal structures where the solvent is incorporated into the lattice) dates back to the dawn of chemistry. The phenomenon is ubiquitous, with important applications ranging from the development of pharmaceuticals to the potential capture of CO2 from the atmosphere. Despite this interest, we still do not fully understand why some molecules form solvates. We have employed molecular simulations using simple models of solute and solvent molecules whose interaction parameters could be modulated at will to access a universe of molecules that do and do not form solvates. We investigated the phase behavior of these model solute–solvent systems as a function of solute–solvent affinity, molecule size ratio, and solute concentration. The simulations demonstrate that the primary criterion for solvate formation is that the solute–solvent affinity must be sufficient to overwhelm the solute–solute and solvent–solvent affinities. Strong solute–solvent affinity in itself is not a sufficient condition for solvate formation: in the absence of such strong affinity, a solvate may still form provided that the self-affinities of the solute and the solvent are weaker in relative terms. We show that even solvent-phobic molecules can be induced to form solvates by virtue of a pΔV potential arising either from a more efficient packing or because of high pressure overcoming the energy penalty

What to think of canine obesity? Emerging challenges to our understanding of human-animal health relationships.

The coincident and increasing occurrence of weight-related health problems in humans and canines in Western societies poses a challenge to our understanding of human–animal health relationships. More specifically, the epistemological and normative impetus provided by current approaches to shared health risks and chronic diseases in cohabiting human and animal populations does not account for causal continuities in the way that people and their pets live together. An examination of differences in medical responses to these conditions in human and pet dogs points to the existence of a distinct conceptual and ethical sphere for companion animal veterinary medicine. The disengagement of veterinary medicine for companion animals from human medicine has implications for our understanding what is required for health and disease prevention at the level of populations. This disengagement of companion animal veterinarians from family and preventive medicine, in particular, constrains professional roles, planning processes and, thereby, the potential for better-integrated responses to shared burdens of chronic conditions that increasingly affect the health and welfare of people and companion animals. Keywords: Human–Animal Relationships, Medical Epistemology, Companion Animal Welfare, Veterinary Ethics, Public Health Ethics, One HealthCanadian Institutes of Health Research, Open Operating Gran

Stepping across the line: Information sharing, truth-telling and the role of the personal carer in the Australian Nursing Home

The author draws on an Australian study using multiple qualitative methods to investigate truth telling in aged care. Thematic analysis of data from five nursing homes involving 23 personal care assistants revealed participants’ role understanding as influencing their perceptions about truth telling in practice. Five themes emerged: role as the happy comfort carer, division of labor, division of disclosure, role tension and frustration, and managing the division of disclosure. Role emphasis on comfort and happiness and a dominant perception that telling the truth can cause harm mean that disclosure will be withheld, edited, or partial. Participants’ role understanding divides labor and disclosure responsibility between the personal carer and registered nurse. Personal carers’ strategies for managing the division of disclosure include game playing, obfuscation, lying (denial), and the use of nonverbals. These perceptions about personal carer role, information sharing, and truth telling are paramount for understanding and improving nursing home eldercare