An experimental study of carbonated eclogite at 3.5-5.5 GPa – Implications for silicate and carbonate metasomatism in the cratonic mantle

We have experimentally investigated a K-bearing altered mid-ocean ridge basalt (MORB) composition to which 10% CaCO3 was added (GA1+10%cc), at temperatures of 1050-1400oC and pressures of 3•5-5•5 GPa. Experiments were conducted in piston-cylinder apparatus in Pt-Gr (Pt with inner graphite) and Au-Pd capsules. Sub-solidus assemblages for both sets of experiments contain clinopyroxene, garnet, carbonate, rutile, coesite and K-feldspar. Apatite was observed only in the Pt-Gr experiments. Melting behaviour in experiments using different capsule materials contrasted markedly. Experiments in Pt-Gr capsules showed the silicate solidus to be at temperatures less than 1100oC at 3•5GPa and less than 1050oC at 4•5-5•0 GPa.These are similar (3•5GPa) or lower (4•5-5•0 GPa) temperatures compared with the carbonate solidus (1075-1125oC at 3•5-5•0 GPa). Melts in the Pt-Gr runs evolve with increasing degree of melting from K-rich silicate melts at the lowest degree of melting to carbonate-silicate immiscible liquids and silicate-carbonate melts at intermediate degrees of melting, and finally to silicate melts at the highest degrees of melting. Experiments in Au-Pd capsules were performed only at 5•0GPa. The carbonate solidus is between 1200 and 1225oC (at least 100oC higher than in the experiments in Pt-Gr capsules at the same pressure-temperature conditions).The first melts to be produced are carbonatitic and exhibit increasing SiO2 content with increasing temperature.This contrast in melting behaviour is explained by the relatively rapid diffusion of H through the Pt-Gr capsules, resulting in formation of H2O, and thus dramatically depressing both the silicate and the carbonate solidi in the Pt-Gr experiments compared with those in the Au-Pd experiments. This presumably reflects the lower permeability of Au-Pd to H, resulting in a much lower H2O/CO2 ratio in the Au-Pd encapsulated experiments. The presence of water in the melt was demonstrated by Fourier transform infrared (FTIR) spectroscopic analysis of one Pt-Gr experiment, indicating ~0•5wt % H2O in the bulk composition. Further confirmation that H2O plays such a role in the Pt-Gr experiments was provided by an additional experiment performed in a Au-Pd capsule with ~10 wt % H2Ospecifically added. In this experiment immiscible carbonate and silicate melts were observed. Carbonate- silicate liquid immiscibility is considered to occur as a result of the H2O present in the system. These results can be applied to natural systems in several ways. First, the presence of a small amount of either silicate melt or H2O-fluid in the system will act as a ‘flux’, depressing the carbonate solidus to much lower temperatures than inanhydrous systems. Second, the full trend in melt evolution from silicate-rich to carbonate-rich melts, which is also observed in inclusions in diamonds, can be explained by melting of K- and CO2-bearing, water-undersaturated MORB compositions. In cratonic environments low-degree silicate and immiscible silicate and carbonate melts will metasomatize the overlying mantle in different ways, producing, in the first instance, Si enrichment and crystallization of additional orthopyroxene, phlogopite, pyrope-rich garnet and consuming olivine, and, in the second case, carbonate metasomatism, with additional magnesite-dolomite, clinopyroxene and apatite. Both metasomatic styles have been described in natural peridotite xenoliths from the cratonic lithosphere

The crossroads of evidence-based medicine and health policy: implications for urology

As healthcare spending in the United States continues to rise at an unsustainable rate, recent policy decisions introduced at the national level will rely on precepts of evidence-based medicine to promote the determination, dissemination, and delivery of “best practices” or quality care while simultaneously reducing cost. We discuss the influence of evidence-based medicine on policy and, in turn, the impact of policy on the developing clinical evidence base with an eye to the potential effects of these relationships on the practice and provision of urologic care

Imaging glial activation in patients with post-treatment Lyme disease symptoms: A pilot study using [ ¹¹ C]DPA-713 PET

The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity of the brain's resident immune cells, microglia. Here we used [ 11 C]DPA-713 and positron emission tomography to quantify the 18 kDa translocator protein, a marker of activated microglia or reactive astrocytes, in the brains of patients with post-treatment Lyme disease symptoms of any duration compared to healthy controls. Genotyping for the TSPO rs6971 polymorphism was completed, and individuals with the rare, low affinity binding genotype were excluded. Data from eight brain regions demonstrated higher [ 11 C]DPA-713 binding in 12 patients relative to 19 controls. [ 11 C]DPA-713 PET is a promising tool to study cerebral glial activation in PTLDS and its link to cognitive symptoms

Professionalism and Evolving Concepts of Quality

For much of the twentieth century, quality of care was defined specifically in terms of physician characteristics and behaviors. High-quality physicians were well trained, knowledgeable, skillful, and compassionate. More recently, quality of care has been defined in terms of systems of care. High-quality organizations develop and adopt practices to reduce adverse events and optimize outcomes. This essay discusses this transformation from physician-based to organization-based concepts of quality and the consequences for patient care and medical professionalism

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Body Size Measurements as Predictors of Type 2 Diabetes in Aboriginal People

OBJECTIVE: To investigate waist circumference, waist-to-hip ratio, body mass index (BMI), weight and hip circumference as risk factors for type 2 diabetes in Aboriginal Australians. DESIGN: Community-based cross-sectional study. SUBJECTS: In total, 915 Australian Aboriginal adults (age: 18-74 y) from a remote Aboriginal community in the Northern Territory of Australia. MEASUREMENTS: Body size measurements included waist circumference, waist-to-hip ratio, BMI, weight and hip circumference. Diabetes status was determined according to medical history and fasting and 2-h postload plasma glucose values. Logistic regression was used to calculate odds ratio for diabetes associated with 1 standard deviation (s.d.) increase in a body size measurement. The areas under the ROC curves of five body size measurements were calculated and compared. RESULTS: Risk of diabetes increased with increasing levels of body size. ORs (95% CI) for diabetes with adjustment for age and sex were 2.16 (1.75, 2.66), 1.80 (1.49, 2.17), 1.41 (1.17, 1.71), 1.81 (1.51, 2.19) and 1.84 (1.50, 2.24) associated with 1 s.d. increase in waist circumference, BMI, weight, waist-to-hip ratio, and hip circumference, respectively. The area under the ROC curve for waist circumference was significantly higher than those for other measurements. CONCLUSION: Waist circumference is the best body size measurement in predicting diabetes in Aboriginal people

Biochemical Properties of a Novel Cysteine Protease of Plasmodium vivax, Vivapain-4

Plasmodium vivax affects hundreds of millions each year and results in severe morbidity and mortality. Plasmodial cysteine proteases (CPs) play crucial roles during the progression of malaria since inhibition of these molecules impairs parasite growth. These CPs might be targeted for new antimalarial drugs. We characterized a novel P. vivax CP, vivapain-4 (VX-4), which appeared to evolve differentially among primate Plasmodium species. VX-4 showed highly unique substrate preference depending on surrounding micro-environmental pH. It effectively hydrolyzed benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA) and Z-Phe-Arg-MCA at acidic pH and Z-Arg-Arg-MCA at neutral pH. Three amino acids (Ala90, Gly157 and Glu180) that delineate the S2 pocket were found to be substituted in VX-4. Alteration of Glu180 abolished hydrolytic activity against Z-Arg-Arg-MCA at neutral pH, indicating Glu180 is intimately involved in the pH-dependent substrate preference. VX-4 hydrolyzed actin at neutral pH and hemoglobin at acidic pH, and participated in plasmepsin 4 activation at neutral/acidic pH. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of P. vivax. The differential substrate preferences depending on pH suggested a highly efficient mechanism to enlarge biological implications of VX-4, including hemoglobin degradation, maturation of plasmepsin, and remodeling of the parasite architecture during growth and development of P. vivax

The health disparities cancer collaborative: a case study of practice registry measurement in a quality improvement collaborative

<p>Abstract</p> <p>Background</p> <p>Practice registry measurement provides a foundation for quality improvement, but experiences in practice are not widely reported. One setting where practice registry measurement has been implemented is the Health Resources and Services Administration's Health Disparities Cancer Collaborative (HDCC).</p> <p>Methods</p> <p>Using practice registry data from 16 community health centers participating in the HDCC, we determined the completeness of data for screening, follow-up, and treatment measures. We determined the size of the change in cancer care processes that an aggregation of practices has adequate power to detect. We modeled different ways of presenting before/after changes in cancer screening, including count and proportion data at both the individual health center and aggregate collaborative level.</p> <p>Results</p> <p>All participating health centers reported data for cancer screening, but less than a third reported data regarding timely follow-up. For individual cancers, the aggregate HDCC had adequate power to detect a 2 to 3% change in cancer screening, but only had the power to detect a change of 40% or more in the initiation of treatment. Almost every health center (98%) improved cancer screening based upon count data, while fewer (77%) improved cancer screening based upon proportion data. The aggregate collaborative appeared to increase breast, cervical, and colorectal cancer screening rates by 12%, 15%, and 4%, respectively (p < 0.001 for all before/after comparisons). In subgroup analyses, significant changes were detectable among individual health centers less than one-half of the time because of small numbers of events.</p> <p>Conclusions</p> <p>The aggregate HDCC registries had both adequate reporting rates and power to detect significant changes in cancer screening, but not follow-up care. Different measures provided different answers about improvements in cancer screening; more definitive evaluation would require validation of the registries. Limits to the implementation and interpretation of practice registry measurement in the HDCC highlight challenges and opportunities for local and aggregate quality improvement activities.</p

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0–2. The first cohort received SPI-77 at 100 mg m−2, the second 200 mg m−2 and the final cohort 260 mg m−2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m−2 dose level for an overall response rate of 4.5% (7.1% at ⩾200 mg m−2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC