Ethical difficulties in clinical practice : experiences of European doctors

Background: Ethics support services are growing in Europe to help doctors in dealing with ethical difficulties. Currently, insufficient attention has been focused on the experiences of doctors who have faced ethical difficulties in these countries to provide an evidence base for the development of these services. Methods: A survey instrument was adapted to explore the types of ethical dilemma faced by European doctors, how they ranked the difficulty of these dilemmas, their satisfaction with the resolution of a recent ethically difficult case and the types of help they would consider useful. The questionnaire was translated and given to general internists in Norway, Switzerland, Italy and the UK. Results: Survey respondents (n = 656, response rate 43%) ranged in age from 28 to 82 years, and averaged 25 years in practice. Only a minority (17.6%) reported having access to ethics consultation in individual cases. The ethical difficulties most often reported as being encountered were uncertain or impaired decisionmaking capacity (94.8%), disagreement among caregivers (81.2%) and limitation of treatment at the end of life (79.3%). The frequency of most ethical difficulties varied among countries, as did the type of issue considered most difficult. The types of help most often identified as potentially useful were professional reassurance about the decision being correct (47.5%), someone capable of providing specific advice (41.1%), help in weighing outcomes (36%) and clarification of the issues (35.9%). Few of the types of help expected to be useful varied among countries. Conclusion: Cultural differences may indeed influence how doctors perceive ethical difficulties. The type of help needed, however, did not vary markedly. The general structure of ethics support services would not have to be radically altered to suit cultural variations among the surveyed countries

The role of relatives in decisions concerning life-prolonging treatment in patients with end-stage malignant disorders: informants, advocates or surrogate decision-makers?

Background: This study examines the extent to which relatives of severely ill cancer patients are involved in the decision to limit treatment (DLT), their role in communicating patient wishes and the incidence of and reasons for disagreement with relatives. Patients and methods: This cohort study followed 70 patients with terminal cancer, for whom a limitation of life-prolonging treatment was being considered. ‘Embedded researchers' recorded patients' wishes and the relatives' roles and disagreements with DLT. Results: Although 63 out of 70 patients had relatives present during their care, only 32% of relatives were involved in DLT. Physicians were more likely to know the end-of-life (EOL) preferences for those patients who had visiting relatives than those without them (78% versus 29%, P = 0.014). Most relatives supported patients in voicing their preferences (68%), but one-third acted against the known or presumed wishes of patients (32%). Disagreements with patients' relatives occurred in 21% of cases, and predominantly when relatives held views that contradicted known patient preferences (71% versus 7%, P = 0.001). Conclusion: If relatives are to play an important part in EOL decision making, we must devise strategies to recognise their potential as patients' advocates as well as their own need

The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms

The role of the mitochondrial calcium uniporter (MCU) gene (Mcu) in cellular energy homeostasis and generation of electrical brain rhythms is widely unknown. We investigated this issue in mice and rats using Mcu-knockout and -knockdown strategies in vivo and in situ and determined the effects of these genetic manipulations on hippocampal gamma oscillations (30–70 Hz) and sharp wave-ripples. These physiological network states require precise neurotransmission between pyramidal cells and inhibitory interneurons, support spike-timing and synaptic plasticity and are associated with perception, attention and memory. Absence of the MCU resulted in (i) gamma oscillations with decreased power (by >40%) and lower synchrony, including less precise neural action potential generation (‘spiking'), (ii) sharp waves with decreased incidence (by about 22%) and decreased fast ripple frequency (by about 3%) and (iii) lack of activity-dependent pyruvate dehydrogenase dephosphorylation. However, compensatory adaptation in gene expression related to mitochondrial function and glucose metabolism was not detected. These data suggest that the neuronal MCU is crucial for the generation of network rhythms, most likely by influences on oxidative phosphorylation and perhaps by controlling cytoplasmic Ca(2+) homeostasis. This work contributes to an increased understanding of mitochondrial Ca(2+) uptake in cortical information processing underlying cognition and behaviour

Reflecting on the reasons pros and cons coercive measures for patients in psychiatric and somatic care: The role of clinical ethics consultation. A pilot study

Background and aim: Coercive measures in patient care have come under criticism leading to implement guidelines dedicated to the reduction of coercion. This development of bringing to light clinical ethics support is hoped to serve as a means of building up awareness and potentially reducing the use of coercion. This study explores the specific features of ethics consultation (EC) while dealing with coercion. Material and method: Basel EC documentation presents insight to all persons involved with a case. The EC database of two Basel university hospitals was developed on the grounds of systematic screening and categorization by two reviewers. One hundred fully documented EC cases databased from 2013 to 2016 were screened for the discussion of coercive measures (somatic hospital and psychiatry: 50% cases). Results: Twenty-four out of 100 EC cases addressed coercion in relation to a clinically relevant question, such as compulsory treatment (70.8%), involuntary committal (50%), or restricting liberty (16.6%). Only 58.3% of EC requests mentioned coercion as an ethical issue prior to the meeting. In no case was patient decisional capacity given, capacity was impaired (43.5%), not given (33.3%), or unclear (21.7%; one not available). Discussion: As clinical staff appears sensitive to perceiving ethical uncertainty or conflict, but less prepared to articulate ethical concern, EC meetings serve to "diagnose" and "solve" the ethical focus of the problem(s) presented in EC. Patient decisional incapacity proved to be an important part of reasoning, when discussing the principle of harm prevention. While professional judgment of capacity remains unsystematic, rationality or even ethicality of decision making will be hampered. The documented EC cases show a variety of decisions about whether or not coercion was actually applied. Ethical reasoning on the competing options seemed to be instrumental for an unprejudiced decision complying with the normative framework and for building a robust consensus. Conclusions: The recommendation is whether EC should be used as a standard practice whenever coercion is an issue-ideally before coercion is applied, or otherwise. Moreover, more efforts should be made toward early and professional assessment of patient capacity and advance care counseling including the offer of advance directives

Changing Seasonal Rainfall Distribution With Climate Directs Contrasting Impacts at Evapotranspiration and Water Yield in the Western Mediterranean Region

Over the past century, climate change has been reflected in altered precipitation regimes worldwide. Because evapotranspiration is sensitive to both water availability and atmospheric demand for water vapor, it is essential to assess the likely consequences of future changes of these climate variables to evapotranspiration and, thus, runoff. We propose a simplified approach for annual evapotranspiration predictions, based on seasonal evapotranspiration estimates, accounting for the strong seasonality of meteorological conditions typical of Mediterranean climate, still holding the steady state assumption of basin water balance at mean annual scale. Sardinian runoff decreased over the 1975-2010 period by more than 40% compared to the preceding 1922-1974 period. Most of annual runoff in Sardinian basins is produced by winter precipitation, a wet season with relatively high evaporation rates. We derived linear seasonal evapotranspiration responses to seasonal precipitation, and, in turn, a relationship between the parameters of the linear functions and the seasonal vapor pressure deficit (D), accounting for residuals with basin properties. We then used these relationships to predict evapotranspiration and runoff using future Intergovernmental Panel on Climate Change climate scenarios, considering changing precipitation and D seasonality. We show that evapotranspiration is insensitive to D scenario changes. Although both evapotranspiration and runoff are sensitive to precipitation seasonality, future changes in runoff are related only to changes of winter precipitation, while evapotranspiration changes are related to those of spring and summer precipitation. Future scenario predicting further runoff decline is particularly alarming for the Sardinian water resources system, requiring new strategies and designs in water resources planning and management.Peer reviewe

The Clearance of Cyclosporine by Hemodialysis

The pharmacokinetics of cyclosporine were studied in five liver transplant patients when they were on and off hemodialysis. There was no significant difference in the blood clearance of cyclosporine between these two periods. Less than 1 per cent of the dose of cyclosporine was recovered in the dialysate. The mean dialysis clearance was less than 1 ml/min. This represents less than 1 per cent of the total blood clearance of cyclosporine. Dosage alterations of cyclosporine during or after hemodialysis do not appear to be necessary

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Continuum Surface Energy from a Lattice Model

We investigate connections between the continuum and atomistic descriptions of deformable crystals, using certain interesting results from number theory. The energy of a deformed crystal is calculated in the context of a lattice model with general binary interactions in two dimensions. A new bond counting approach is used, which reduces the problem to the lattice point problem of number theory. The main contribution is an explicit formula for the surface energy density as a function of the deformation gradient and boundary normal. The result is valid for a large class of domains, including faceted (polygonal) shapes and regions with piecewise smooth boundaries.Comment: V. 1: 10 pages, no fig's. V 2: 23 pages, no figures. Misprints corrected. Section 3 added, (new results). Intro expanded, refs added.V 3: 26 pages. Abstract changed. Section 2 split into 2. Section (4) added material. V 4, 28 pages, Intro rewritten. Changes in Sec.5 (presentation only). Refs added.V 5,intro changed V.6 address reviewer's comment

A Rejoinder on Energy versus Impact Indicators

Citation distributions are so skewed that using the mean or any other central tendency measure is ill-advised. Unlike G. Prathap's scalar measures (Energy, Exergy, and Entropy or EEE), the Integrated Impact Indicator (I3) is based on non-parametric statistics using the (100) percentiles of the distribution. Observed values can be tested against expected ones; impact can be qualified at the article level and then aggregated.Comment: Scientometrics, in pres

CONSENSUS CONFERENCE REPORT ON LIVER* TRANSPLANTATION.

Liver transplantation has been developed to the point of a service operation, the exploitation of which depends upon the establishment of multiple regional centers. The increased use of this procedure will permit the delivery of optimum health care to victims of end stage liver disease