Ethics roundtable debate: should a sedated dying patient be wakened to say goodbye to family?

Intensivists have the potential to maintain vital signs almost indefinitely, but not necessarily the potential to make moribund patients whole. Current ethical and legal mandates push patient autonomy to the forefront of care plans. When patients are incapable of expressing their preferences, surrogates are given proxy. It is unclear how these preferences extend to the very brink of inevitable death. Some say that patients should have the opportunity and authority to direct their death spiral. Others say it would be impossible for them to do so because an inevitable death spiral cannot be effectively palliated. Humane principles dictate they be spared the unrelenting discomfort surrounding death. The present case examines such a patient and the issues surrounding a unique end-of-life decision

Vortex rings impinging on permeable boundaries

Experiments with vortex rings impinging permeable and solid boundaries are presented in order to investigate the influence of permeability. Utilizing Particle Image Velocimetry, we compared the behaviour of a vortex ring impinging four different reticulated foams (with permeability k ∼ 26 − 85 × 10−8 m2) and a solid boundary. Results show how permeability affects the stretching phenomena of the vortex ring and the formation and evolution of the secondary vortex ring with opposite sign. Moreover, permeability also affects the macroscopic no-slip boundary condition found on the solid boundary, turning it into an apparent slip boundary condition for the most permeable boundary. The apparent slip-boundary condition and the flux exchange between the ambient fluid and the foam are jointly responsible for both the modified formation of the secondary vortex and changes on the vortex ring diameter increase.The experimental work presented herein was conducted during a four-months-long visit of A.M.C. to the Department of Applied Mathematics and Theoretical Physics at Cambridge University, UK. The financial support of the Ministerio de Educacion y Ciencia de España through Grant No. CGL 2009-13039 is gratefully acknowledged. The support of the UPC-Barcelona Tech University is also acknowledged.This is the accepted manuscript. Copyright (2015) American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Physics of Fluids 27, 015106 (2015) and may be found at (http://scitation.aip.org/content/aip/journal/pof2/27/1/10.1063/1.4906504)

Strong Universality in Forced and Decaying Turbulence

The weak version of universality in turbulence refers to the independence of the scaling exponents of the $n$th order strcuture functions from the statistics of the forcing. The strong version includes universality of the coefficients of the structure functions in the isotropic sector, once normalized by the mean energy flux. We demonstrate that shell models of turbulence exhibit strong universality for both forced and decaying turbulence. The exponents {\em and} the normalized coefficients are time independent in decaying turbulence, forcing independent in forced turbulence, and equal for decaying and forced turbulence. We conjecture that this is also the case for Navier-Stokes turbulence.Comment: RevTex 4, 10 pages, 5 Figures (included), 1 Table; PRE, submitte

By the Black Ditch: archaeological discoveries at Rustington, Littlehampton,West Sussex

A series of archaeological investigations were undertaken on land south of the A259 New Road, Littlehampton, in advance of commercial redevelopment. The earliest activity comprised a Middle Bronze Age enclosure, field boundary ditch and burnt mound. The burnt mound included an associated hearth, trough and waterhole. Later activity included a prehistoric droveway and Late Iron Age/Roman field boundary ditches

Drugs for neglected tropical diseases : availability of age-appropriate oral formulations for young children

It is recognised that paediatric indications and age-appropriate formulations are required to ensure that paediatric populations receive appropriate pharmacotherapeutic treatment. The lack of information on dosing, efficacy and safety data (labelling) is a well-recognised problem for all diseases affecting children. For neglected tropical diseases, the fact that they affect to a large extent poor and marginalised populations in low- and middle-income countries means that there is a low economic return on investment into paediatric development activities compared to other diseases [e.g. human immunodeficiency virus (HIV)]. This review provides an introduction to issues affecting the availability and development of paediatric population-relevant data and appropriate formulations of drugs for NTDs. We are summarising why age-appropriate formulations are important to ensure treatment efficacy, safety and effectiveness, outline initiatives to increase the number of paediatric indications/labelling and age-appropriate formulations, provide an overview of publicly available information on the formulations of oral drugs for NTDs relative to age appropriateness and give an introduction to options for age-appropriate formulations. The review completes with ‘case studies’ of recently developed paediatric formulations for NTDs, complemented by case studies for fixed-dose combinations for HIV infection in children since such formulations have not been developed for NTDs. Graphical Abstract: [Figure not available: see fulltext.]

The pipeline for drugs for control and elimination of neglected tropical diseases : 2. Oral anti-infective drugs and drug combinations for off-label use

In its ‘Road map for neglected tropical diseases 2021–2030’, the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed. WHO guidelines and country policies show that drugs may be recommended for control and elimination for NTDs for which they are not SRA approved (i.e. for ‘off-label’ use) if efficacy and safety data for the relevant NTD are considered sufficient by WHO and country authorities. Here, we are providing an overview of clinical research in the past 10 years evaluating the anti-infective efficacy of oral small-molecule drugs for NTD(s) for which they are neither SRA approved, nor included in current WHO strategies nor, considering the research sponsors, likely to be registered with a SRA for that NTD, if found to be effective and safe. No such research has been done for yaws, guinea worm, Trypanosoma brucei gambiense human African trypanosomiasis (HAT), rabies, trachoma, visceral leishmaniasis, mycetoma, T. b. rhodesiense HAT, echinococcosis, taeniasis/cysticercosis or scabies. Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising path is exploitation of the worldwide experience with ‘off-label’ treatment of diseases with insufficient treatment options as pursued by the ‘CURE ID’ initiative. Graphical abstract: [Figure not available: see fulltext.]

Variability in COVID-19 in-hospital mortality rates between national health service trusts and regions in England: A national observational study for the Getting It Right First Time Programme

Background A key first step in optimising COVID-19 patient outcomes during future case-surges is to learn from the experience within individual hospitals during the early stages of the pandemic. The aim of this study was to investigate the extent of variation in COVID-19 outcomes between National Health Service (NHS) hospital trusts and regions in England using data from March–July 2020. Methods This was a retrospective observational study using the Hospital Episode Statistics administrative dataset. Patients aged ≥ 18 years who had a diagnosis of COVID-19 during a hospital stay in England that was completed between March 1st and July 31st, 2020 were included. In-hospital mortality was the primary outcome of interest. In secondary analysis, critical care admission, length of stay and mortality within 30 days of discharge were also investigated. Multilevel logistic regression was used to adjust for covariates. Findings There were 86,356 patients with a confirmed diagnosis of COVID-19 included in the study, of whom 22,944 (26.6%) died in hospital with COVID-19 as the primary cause of death. After adjusting for covariates, the extent of the variation in-hospital mortality rates between hospital trusts and regions was relatively modest. Trusts with the largest baseline number of beds and a greater proportion of patients admitted to critical care had the lowest in-hospital mortality rates. Interpretation There is little evidence of clustering of deaths within hospital trusts. There may be opportunities to learn from the experience of individual trusts to help prepare hospitals for future case-surges

Variational finite element methods for waves in a Hele–Shaw tank

The damped motion of driven water waves in a Hele-Shaw tank is investigated variationally and numerically. The equations governing the hydrodynamics of the problem are derived from a variational principle for shallow water. The variational principle includes the effects of surface tension, linear momentum damping due to the proximity of the tank walls and incoming volume flux through one of the boundaries representing the generation of waves by a wave pump. The model equations are solved numerically using (dis)continuous Galerkin finite element methods and are compared to exact linear wave sloshing and driven wave sloshing results. Numerical solutions of the nonlinear shallow water-wave equations are also validated against laboratory experiments of artificially driven waves in the Hele-Shaw tank