Establishing riverine nutrient criteria using individual taxa thresholds.

Nutrient enrichment is one of the most pervasive impacts on aquatic ecosystems globally. Approaches to establish nutrient criteria that safeguard aquatic ecosystem health are highly variable and, in many instances, criteria are derived from correlations between in-situ nutrient concentrations and biological indices. Summarising entire assemblages with a single index can result in a substantial loss of information and potentially weaker relationships. In this study, we compared the derivation of nutrient criteria using biological indices and those from individual taxa for rivers and streams in New Zealand. Random forest models, including nutrient concentrations, were built to predict two biological indices and individual taxa across New Zealand's river monitoring network. For all acceptable models, the response of the biological indices and individual taxa to increasing Dissolved Inorganic Nitrogen (DIN) and Dissolved Reactive Phosphorus (DRP) were then predicted for every river reach across the nation, and nutrient concentrations that protected 80% of taxa were then identified. Models for the biological indices were poor but were good for most of the taxa, with nutrient concentrations almost always being the most influential factor. To ensure persistence of at least 80% of the taxa within a river reach, we estimated that DIN (Dissolved Inorganic Nitrogen) concentrations would need to be below 0.57-1.32 mg/L, and DRP (Dissolved Reactive Phosphorus) concentrations below 0.019-0.033 mg/L, depending on the river type. In general, high order, low slope rivers and streams required more stringent nutrient criteria than steep, low order streams. The link between nutrient concentrations and biological indices were weak and likely suffer from the loss of information from summarising an entire assemblage into a single numeric. We consider that the derivation of nutrient criteria for waterways should also examine the individual relationships with the taxa in a river system to establish protection for a desired proportion of taxa.

Changes in mental state associated with prison environments: a systematic review.

OBJECTIVE: To develop an understanding of the stability of mental health during imprisonment through review of existing research evidence relating physical prison environment to mental state changes in prisoners. METHOD: A systematic literature search was conducted looking at changes in mental state and how this related to various aspects of imprisonment and the prison environment. RESULTS: Fifteen longitudinal studies were found, and from these, three broad themes were delineated: being imprisoned and aspects of the prison regime; stage of imprisonment and duration of sentence; and social density. Reception into prison results in higher levels of psychiatric symptoms that seem to improve over time; otherwise, duration of imprisonment appears to have no significant impact on mental health. Regardless of social density, larger prisons are associated with poorer mental state, as are extremes of social density. CONCLUSION: There are large gaps in the literature relating prison environments to changes in mental state; in particular, high-quality longitudinal studies are needed. Existing research suggests that although entry to prison may be associated with deterioration in mental state, it tends to improve with time. Furthermore, overcrowding, ever more likely as prison populations rise, is likely to place a particular burden on mental health services.

Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy.

To define molecular mechanisms of cardiac hypertrophy, genes whose expression was perturbed by any of four different transgenic mouse hypertrophy models [protein kinase C-epsilon activation peptide (PsiepsilonRACK), calsequestrin (CSQ), calcineurin (CN), and Galpha(q)] were compared by DNA microarray analyses using the approximately 8,800 genes present on the Incyte mouse GEM1. The total numbers of regulated genes (tens to hundreds) correlated with phenotypic severity of the model (Galpha(q) > CN > CSQ > PsiepsilonRACK), but demonstrated that no single gene was consistently upregulated. Of the three models exhibiting pathological hypertrophy, only atrial natriuretic peptide was consistently upregulated, suggesting that transcriptional alterations are highly specific to individual genetic causes of hypertrophy. However, hierarchical-tree and K-means clustering analyses revealed that subsets of the upregulated genes did exhibit coordinate regulatory patterns that were unique or overlapping across the different hypertrophy models. One striking set consisted of apoptotic genes uniquely regulated in the apoptosis-prone Galpha(q) model. Thus, rather than identifying a single common hypertrophic cardiomyopathy gene program, these data suggest that extensive groups of genes may be useful for the prediction of specific underlying genetic determinants and condition-specific therapeutic approaches.

Interactions between phospholamban and beta-adrenergic drive may lead to cardiomyopathy and early mortality.

BACKGROUND: Relieving the inhibition of sarcoplasmic reticular function by phospholamban is a major target of beta-adrenergic stimulation. Chronic beta-adrenergic receptor activity has been suggested to be detrimental, on the basis of transgenic overexpression of the receptor or its signaling effectors. However, it is not known whether physiological levels of sympathetic tone, in the absence of preexisting heart failure, are similarly detrimental. METHODS AND RESULTS: Transgenic mice overexpressing phospholamban at 4-fold normal levels were generated, and at 3 months, they exhibited mildly depressed ventricular contractility without heart failure. As expected, transgenic cardiomyocyte mechanics and calcium kinetics were depressed, but isoproterenol reversed the inhibitory effects of phospholamban on these parameters. In vivo cardiac function was substantially depressed by propranolol administration, suggesting enhanced sympathetic tone. Indeed, plasma norepinephrine levels and the phosphorylation status of phospholamban were elevated, reflecting increased adrenergic drive in transgenic hearts. On aging, the chronic enhancement of adrenergic tone was associated with a desensitization of adenylyl cyclase (which intensified the inhibitory effects of phospholamban), the development of overt heart failure, and a premature mortality. CONCLUSIONS: The unique interaction between phospholamban and increased adrenergic drive, elucidated herein, provides the first evidence that compensatory increases in catecholamine stimulation can, even in the absence of preexisting heart failure, be a primary causative factor in the development of cardiomyopathy and early mortality.

Reduction of [Ca(2+)](i) restores uncoupled beta-adrenergic signaling in isolated perfused transgenic mouse hearts.

The effects of alterations in calcium in the perfusion media were studied on ss-adrenergic coupling in isolated hearts from 3 different transgenic mice: cardiac-specific overexpressed alpha(1) subunit of L-type calcium channel, overexpressed Galpha(q), and phospholamban knockout. Isolated hearts from all 3 models, when studied at [Ca(2+)] of 2 mmol/L in the perfusate, showed the usual blunted or no response to ss-adrenergic stimulation. Lowering [Ca(2+)] to 0.75 to 1.5 mmol/L unloaded the hearts of calcium and restored to nearly normal the responsiveness to ss-agonist stimulation.

Structure and energy of the 90 degrees partial dislocation in diamond: a combined Ab initio and elasticity theory analysis.

The core structure and stability of the 90 degrees partial dislocation in diamond is studied within isotropic elasticity theory and ab initio total energy calculations. The double-period reconstruction is found to be more stable than the single-period reconstruction for a broad range of stress states. The analysis of the ab initio results shows further that elasticity theory is valid for dislocation spacings as small as 10-20 A, thus allowing ab initio calculations to provide reliable parameters for continuum theory analysis.

Early and delayed consequences of beta(2)-adrenergic receptor overexpression in mouse hearts: critical role for expression level.

BACKGROUND: Transgenic cardiac beta(2)-adrenergic receptor (AR) overexpression has resulted in enhanced signaling and cardiac function in mice, whereas relatively low levels of transgenically expressed G(alphas) or beta(1)AR have resulted in phenotypes of ventricular failure. Potential relationships between the levels of betaAR overexpression and biochemical, molecular, and physiological consequences have not been reported. METHODS AND RESULTS: We generated transgenic mice expressing beta(2)AR at 3690, 7120, 9670, and 23 300 fmol/mg in the heart, representing 60, 100, 150, and 350 times background betaAR expression. All lines showed enhanced basal adenylyl cyclase activation but a decrease in forskolin- and NaF-stimulated adenylyl cyclase activities. Mice of the highest-expressing line developed a rapidly progressive fibrotic dilated cardiomyopathy and died of heart failure at 25+/-1 weeks of age. The 60-fold line exhibited enhanced basal cardiac function without increased mortality when followed for 1 year, whereas 100-fold overexpressors developed a fibrotic cardiomyopathy and heart failure, with death occurring at 41+/-1 weeks of age. Adenylyl cyclase activation did not correlate with early or delayed decompensation. Propranolol administration reduced baseline +dP/dt(max) to nontransgenic levels in all beta(2)AR transgenics except the 350-fold overexpressors, indicating that spontaneous activation of beta(2)AR was present at this level of expression. CONCLUSIONS: These data demonstrate that the heart tolerates enhanced contractile function via 60-fold beta(2)AR overexpression without detriment for a period of >/=1 year and that higher levels of expression result in either aggressive or delayed cardiomyopathy. The consequences for enhanced betaAR function in the heart appear to be highly dependent on which signaling elements are increased and to what extent.

A randomized controlled trial of an enhanced patient compliance program for Helicobacter pylori therapy.

OBJECTIVES: To determine whether an enhanced compliance program (ECP) improves patient compliance with bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (BMT) triple therapy for the treatment of Helicobacter pylori infection and to identify factors that affect compliance with therapy. DESIGN: A randomized controlled trial conducted in 4 staff-model health centers of a health maintenance organization in Massachusetts. PATIENTS AND METHODS: A total of 125 patients 18 years of age or older with peptic ulcer disease or dyspepsia whose clinicians prescribed BMT triple therapy for 14 days were randomized to a control group or to the ECP group. The ECP group received medication counseling (written and oral) from a pharmacist, along with a medication calendar and a minipillbox, as well as a follow-up telephone call after initiation of therapy. Compliance was assessed by a pill count, and factors affecting adherence to the regimen were identified by patients' reports. RESULTS: There was no statistically significant difference between the 2 groups in the number of patients taking more than 60% of the medications (89% of the control group vs 95% of the ECP group; P>.30). However, there was a statistically significant difference in the number of patients taking more than 90% of the medications (67% of the control group vs 89% of the ECP group; P<.01). An intention-to-treat analysis confirmed these results. The most frequently reported adverse effect was gastrointestinal intolerance. Other factors reported to affect compliance included the frequency of dosing and the number of pills. CONCLUSIONS: These findings suggest that although adverse effects were common, most patients were able to complete 60% or more of the 2-week regimen. An ECP further improved the percentage of medications taken.

Quantitative analysis of chromium(V) by EPR spectroscopy.

A procedure to accurately quantitate chromium(V) in environmental and medicinal chemistry samples was developed using electron paramagnetic resonance spectroscopy (EPRS) as the method of detection. It was found to have an error in the order of +/-10% and a detection limit of 0.010 mM (0.5 mg l(-1)) chromium(V). The method has been used to quantitate the formation of chromium(V) in the interaction of chromium(VI) with fulvic acid and a simple model of this acid, viz, 1.2-dihydroxybenzene. Analysis of solutions obtained from the reaction of 1,2-dihydroxybenzene with chromium(VI) demonstrated that even when the organic substrate was present in a 182-fold excess, the maximum chromium(V) concentration attained represented just 1.44% of the initial chromium(VI). Reactions between chromium(VI) and fulvic acid yielded similar results. It was therefore concluded that at background environmental concentrations of chromium and fulvic acid, the production of chromium(V) is insignificant, however, its possible importance in contaminated systems cannot be disregarded on this basis alone. The method for quantitative analysis reported in this paper should be an invaluable tool for investigations into the significance of chromium(V) in the toxicological mechanism of chromium(VI) and its role as a mutagenic agent.