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.     

Toughening epoxy resins with polyepichlorohydrin

Polyepichlorohydrin (PECH) rubbers were found to toughen epoxy resins based on the diglycidyl ether of bisphenol A (DGEBA) and cured with piperidine. The degree of toughening depends on the molecular weight of the PECH and on the curing temperature. Best toughening was achieved with PECH of the highest nominal molecular weight of 3400 (Hydrin 10 × 2). Hydrin 10 × 1 (nominal molecular weight 1700) did not toughen the epoxy resin unless bisphenol A was also added, whereas Hydrin 10 × 2 toughened it in the absence of bisphenol A. Curing resins containing bisphenol A and Hydrin 10 × 1 at 160°C resulted in a slightly more brittle resin than when cured at 120°C. The effect of PECH rubbers on the T_g, modulus, and hot/wet properties is similar to that of carboxy-terminated butadiene-acrylonitrile rubbers (CTBN). Dynamic mechanical thermal analysis (DMTA) and scanning electron micrographs (SEM) of fractured surfaces show that the PECH separates as a discrete phase during curing. © 1993 John Wiley & Sons, Inc.     

Bench-scale continuous hydrogenation of Australian coals — study of iron catalysts and recycle solvent composition

The inter-relations between iron catalysts, recycle solvent composition and product yield and composition have been investigated in bench-scale (1–2 kg h^?1) continuous hydrogenation of Australian coals at process severity of 21–22 MPa at 400–430°C. Products and recycle solvent are recovered in batch distillation (atmospheric and vacuum) and the distillate solvent is returned to slurry feed without further treatment. Successive samples of recycle solvent are analysed by g.c.-m.s., i.r. and titrimetry. The effect of adding iron catalysts in the form of red mud - sulphur mixtures or compounds after a short period of continuous operation without catalyst is demonstrated. Distillate yields from black coals increase from 24–34 wt% daf under non-catalytic conditions to 35–53 wt% daf by adding iron catalysts. The composition of the almost equilibrated recycle solvent also changes and a new equilibrium is approached after the iron catalyst is added. The effect of solvent composition on distillate yield can not be determined from these data. The ratio of hydroaromatic components to hydroaromatic plus aromatic components in the solvent increases from ≈0.2 at non-catalytic equilibrium to ≈0.5–0.6 at catalysed equilibrium after adding iron. Other compositional parameters in the recycle solvent do not show any clear responses to the addition of iron. Equilibrium solvent composition under constant operating conditions is attained at ≈10 passes at 1 kg ^h?1 throughput with total system holdup of ≈20 kg. Paraffins for the Queensland subbituminous coal equilibrated at 18–24% in the solvent, phenolics at 16–21%, basic nitrogen at ≈0.4% (as N), and the balance a mixture of aromatics and hydroaromatics. The total aromatics neglecting phenolics in the equilibrium recycle solvent consists of ≈40–50% each of two-and three-ring and 5–10% four-ring members.     

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.