Bioethics for clinicians: 16. Dealing with demands for inappropriate treatment

Demands by Patients or their Families for treatment thought to be inappropriate by health care providers constitute an important set of moral problems in clinical practice. A variety of approaches to such cases have been described in the literature, including medical futility, standard of care and negotiation. Medical futility fails because it confounds morally distinct cases: demand for an ineffective treatment and demand for an effective treatment that supports a controversial end (e.g., permanent unconsciousness). Medical futility is not necessary in the first case and is harmful in the second. Ineffective treatment falls outside the standard of care, and thus health care workers have no obligation to provide it. Demands for treatment that supports controversial ends are difficult cases best addressed through open communication, negotiation and the use of conflict-resolution techniques. Institutions should ensure that fair and unambiguous procedures for dealing with such cases are laid out in policy statements.     

Early child-care selection: variation by geographic location, maternal characteristics, and family structure

More than half of all U.S. infants and toddlers spend at least 20 hr per week in the care of a nonparent adult. This article uses survival analysis to identify which families are most likely to place their child in care and the ages when these choices are made, using data from a national probability sample of 2,614 households. Median age at first placement is 33 months, but age varies by geographic region, mother's employment status during pregnancy, mother's education level, and family structure (1 vs. 2 parents, mother's age at 1st birth, and number of siblings). Controlling for these effects, differences by race and ethnicity are small. Implications for studies of child-care selection and evaluations of early childhood programs are discussed.     

The Pharmacology and Therapeutic Utility of Sodium Hydroselenide

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe⁻/H₂Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O₂ consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H₂O₂), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.     

(S)-Reutericyclin: Susceptibility Testing and In Vivo Effect on Murine Fecal Microbiome and Volatile Organic Compounds

We aimed to assess the in vitro antimicrobial activity and the in vivo effect on the murine fecal microbiome and volatile organic compound (VOC) profile of (S)-reutericyclin. The antimicrobial activity of (S)-reutericyclin was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Staphylococcus (S.) epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa and Propionibacterium acnes. Reutericyclin or water were gavage fed to male BALBc mice for 7 weeks. Thereafter stool samples underwent 16S based microbiome analysis and VOC analysis by gas chromatography mass spectrometry (GC-MS). (S)-reutericyclin inhibited growth of S. epidermidis only. Oral (S)-reutericyclin treatment caused a trend towards reduced alpha diversity. Beta diversity was significantly influenced by reutericyclin. Linear discriminant analysis Effect Size (LEfSe) analysis showed an increase of Streptococcus and Muribaculum as well as a decrease of butyrate producing Ruminoclostridium, Roseburia and Eubacterium in the reutericyclin group. VOC analysis revealed significant increases of pentane and heptane and decreases of 2,3-butanedione and 2-heptanone in reutericyclin animals. The antimicrobial activity of (S)-reutericyclin differs from reports of (R)-reutericyclin with inhibitory effects on a multitude of Gram-positive bacteria reported in the literature. In vivo (S)-reutericyclin treatment led to a microbiome shift towards dysbiosis and distinct alterations of the fecal VOC profile.     

A variable gap penalty function and feature weights for protein 3-D structure comparisons

We have developed a variable gap penalty function for use inthe comparison program COMPARER which aligns protein sequenceson the basis of their 3-D structures. For deletions and insertions,components are a function of structural features of individualamino acid residues (e.g. secondary structure and accessibility).We have also obtained relative weights for different featuresused in the comparison by examining the equivalent residuesin weight matrices and in alignments for pairs of 3-D structureswhere the equivalences are relatively unambiguous. We have usedthe new parameters and the varible gap penalty function in COMPARERto align protein structures in the Brookhaven Data Bank. Thevariable gap penalty function is useful especially in avoidinggaps in secondary structure elements and the new feature weightsgive improved alignments. The alignments for both azurins andplastocyanins and N- and C-terminal lobes for aspartic proteinasesare discussed     

Using Discriminative Dimensionality Reduction to Visualize Classifiers

Neural Processing Letters - Albeit automated classifiers offer a standard tool in many application areas, there exists hardly a generic possibility to directly inspect their behavior, which goes...     

Workflows for Heliophysics

In this paper we describe how we have introduced workflows into the working practices of a community for whom the concept of workflows is very new, namely the heliophysics community. Heliophysics is a branch of astrophysics which studies the Sun and the interactions between the Sun and the planets, by tracking solar events as they travel throughout the Solar system. Heliophysics produces two major challenges for workflow technology. Firstly it is a systems science where research is currently developed by many different communities who need reliable data models and metadata to be able to work together. Thus it has major challenges in the semantics of workflows. Secondly, the problem of time is critical in heliophysics; the workflows must take account of the propagation of events outwards from the sun. They have to address the four dimensional nature of space and time in terms of the indexing of data. We discuss how we have built an environment for Heliophysics workflows building on and extending the Taverna workflow system and utilising the myExperiment site for sharing workflows. We also describe how we have integrated the workflows into the existing practices of the communities involved in Heliophysics by developing a web portal which can hide the technical details from the users, who can concentrate on the data from their scientific point of view rather than on the methods used to integrate and process the data. This work has been developed in the EU Framework 7 project HELIO, and is being disseminated to the worldwide Heliophysics community, since Heliophysics requires integration of effort on a global scale.     

Dynamic analysis of Java program concepts for visualization and profiling

Concept assignment identifies units of source code that are functionally related, even if this is not apparent from a syntactic point of view. Until now, the results of concept assignment have only been used for static analysis, mostly of program source code. This paper investigates the possibility of using concept information within a framework for dynamic analysis of programs. The paper presents two case studies involving a small Java program used in a previous research exercise, and a large Java virtual machine (the popular Jikes RVM system). These studies investigate two applications of dynamic concept information: visualization and profiling. The paper demonstrates two different styles of concept visualization, which show the proportion of overall time spent in each concept and the sequence of concept execution, respectively. The profiling study concerns the interaction between runtime compilation and garbage collection in Jikes RVM. For some benchmark cases, we are able to obtain a significant reduction in garbage collection time. We discuss how this phenomenon might be harnessed to optimize the scheduling of garbage collection in Jikes RVM.