The blue road: Provenance study of azurite samples from historical locations through the analysis of minor and trace elements.

The pigments used by artists since ancient times play an important role in historical, artistic, and cultural investigations. They allow the acquisition of useful information for the study of human and technological development. This research aims at differentiating the various sources of azurite exploited in antiquity, based on the study of minor and trace elements. Azurite is one of the most important blue pigments in art history, widely used during the Middle Age and Renaissance. However, very few studies investigated the provenance of the pigment, so today it is still not possible to clearly identify the sources of azurite exploited in the past. This study is based on the analysis of several samples of azurite belonging to the MUST collection (Museum of Earth Sciences, Sapienza University of Rome, Italy) and coming from different historical localities: UK, Italy, Germany, France, Romania and Slovakia (both representative of the resources within the ancient Kingdom of Hungary), Greece and Russia. The samples were analysed by electron microscopy (EMPA and SEM-EDX) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), with the aim of detecting chemical features that are specific to the different azurite ore deposits. Among the trace elements analysed, Zn, As, Sn, Ca and Sr prove the most suitable for discriminating the origin of the samples, as well as rare earth elements. In particular, Ce and Eu anomalies are suggested as markers for the German and Hungarian localities.

Gender-specific effects of capsiate supplementation on body weight and bone mineral density: a randomized, double-blind, placebo-controlled study in slightly overweight women.

INTRODUCTION: Overweight and obesity are highly prevalent conditions associated with premature morbidity and mortality worldwide. Capsiate, a nonpungent analogue of capsaicin, binds to TRP vanilloid 1 (TRPV1) receptor, which is involved in adipogenesis, and could be effective as a weight-lowering agent. METHODS: Eighteen slightly overweight women were enrolled in this randomized, double-blind, placebo-controlled study. Nine patients were included in the capsiate intervention group and received 9 mg/day of capsinoids and 9 patients received placebo for 8 weeks. All patients underwent weight and waist circumference assessment before and after treatment. Body composition and bone mineral density (BMD) were also detected by dual-energy X-ray absorptiometry (DXA). RESULTS: Fourteen patients completed the study. The treatment with capsiate or placebo for 8 weeks was not associated with significant changes in weight or waist circumference. After treatment, there was a significant improvement in BMD values measured at the spine in the capsiate group (1.158 vs 1.106 g/cm2, + 4.7%; p = 0.04), but not in the group treated with placebo. Similarly, the capsiate group showed a 9.1% increase (p = 0.05) in the adipose tissue and an 8.5% decrease in lean mass measured at the supraclavicular level, whereas these changes were not statistically significant in the placebo group. CONCLUSIONS: Treatment with capsiate for 8 weeks led to negligible changes in body weight in a small sample of slightly overweight women, but our findings suggest a potential effect of capsaicin on bone metabolism in humans.

A Machine Learning-Based Approach to Clinopyroxene Thermobarometry: Model Optimization and Distribution for Use in Earth Sciences.

Thermobarometry is a fundamental tool to quantitatively interrogate magma plumbing systems and broaden our appreciation of volcanic processes. Developments in random forest-based machine learning lend themselves to a data-driven approach to clinopyroxene thermobarometry, allowing users to access large experimental data sets that can be tailored to individual applications in Earth Sciences. We present a methodological assessment of random forest thermobarometry using the R freeware package extraTrees. We investigate the model performance, the effect of hyperparameter tuning, and assess different methods for calculating uncertainties. Deviating from the default hyperparameters used in the extraTrees package results in little difference in overall model performance (<0.2 kbar and <3°C difference in standard error estimate, SEE). However, accuracy is greatly affected by how the final value from the distribution of trees in the random forest is selected (mean, median, or mode). Using the mean value leads to higher residuals between experimental and predicted P and T, whereas using median values produces smaller residuals. Additionally, this work provides two scripts for users to apply the methodology to natural data sets. The first script permits modification and filtering of the model calibration data set. The second script contains premade models, where users can rapidly input their data to recover PT estimates (SEE clinopyroxene-only model: 3.2 kbar, 72.5°C and liquid-clinopyroxene model: 2.7 kbar, 44.9°C). Additionally, the scripts allow the user to estimate the uncertainty for each analysis, which in some cases is significantly smaller than the reported SEE. These scripts are open source and can be accessed at https://github.com/corinjorgenson/RandomForest-cpx-thermobarometer.

Technological innovation of Continuous Glucose Monitoring (CGM) as a tool for commercial aviation pilots with insulin-treated diabetes and stakeholders/regulators: A new chance to improve the directives?

Civil aviation pilots who develop insulin-treated diabetes and want to renew a Commercial Pilot License (CPL) represent a medical, social and regulatory problem. This depends on justified concerns about hypoglycemia, the most threatening event for people who carry out jobs requiring a high level of concentration and reliability. This negatively affects social and working aspects of pilots' lives, who have a high profile and a high-cost professional qualification. It could be possible now to revise this attitude thanks to the availability of Continuous Glucose Monitoring (CGM) devices. CGM clearly showed to prevent hypoglycemic events in insulin-treated diabetic patients by allowing strict monitoring and trend prediction of glucose levels. By systematizing available data on such devices and present regulations in CPL issuance worldwide, our review can be used as handy tool for a fruitful discussion among the scientific community, national and international civil aviation regulators, stakeholders and pilots, aimed at evaluating the evidence-based opportunity to revise CPL issuance criteria for insulin-treated diabetic pilots. For the above-mentioned reasons, there are, among the regulatory administrations of Civil Aviation around the globe, several different approaches and limitations set for the subjects with insulin-treated diabetes who want to obtain, or renew, a CPL.

Vitrification treatment of municipal solid waste bottom ash.

This study involves the chemical characterization of municipal solid waste (MSW) bottom ash (BA) produced at a combustor facility in Rimini (Italy), and vitrification experiments, performed at lab scale under atmospheric conditions, maximum temperature of 1100 °C, for different durations (2-16 h). LA-ICP-MS analyses of the glasses obtained revealed that the overall volatility of metal elements increases with the time but it cannot be simply predicted by element boiling point. Elements have been here categorized into three different groups depending on their volatility comparing the glass product with the BA starting sample- high, medium or low, respectively- (1) Cu, W, Cl; (2) Pb, Zn, Sr; (3) Mo, Cr, V, Ni. The behavior of Cs, Rb, Ag, Ba, Ga, Co, U, Zr, Hf and Ta in the glassy slag is not defined because we did not observe statistically significant changes in their volatility behavior. Vitrification allows us to produce chemically stable glassy materials and immobilize potentially harmful elements, thus producing from waste new vitreous materials that are relatively inert and suitable for potential re-utilization in new products and/or applications for building and construction industries. Moreover, the samples show REE chondrite-normalized patterns indicating relative enrichments in Light-Rare Earth Elements (LREE), in particular La and Nd which may be interesting from an economic point of view in terms of waste recovery. Thus, the results obtained show how to treat bottom ashes from incinerator in order to provide more chemically inert and economically useful resources for recycle and reuse of solid waste BA.

Timescales of water accumulation in magmas and implications for short warning times of explosive eruptions.

Water plays a key role in magma genesis, differentiation, ascent and, finally, eruption. Despite the recognized crucial function of water, there are still several issues that continue to blur our view about its role in magmatic systems. What are the timescales of H2O accumulation in crystallizing magmas? What are the ascent rates of water-rich residual melts leading to explosive eruptions? Here, we track the timescale of water accumulation in a residual melt resulting from crystallization of a hydrous CO2-bearing magmatic mass stored at mid- to deep-crustal levels in a subduction-related geodynamic setting. Our results indicate that, after a repose period ranging from few to several thousand years, water-rich melts with water concentrations larger than 6-9 wt.% can migrate towards the Earth surface in very short timescales, on the order of days or even hours, possibly triggering explosive eruptions with short warning times and devoid of long-term geophysical precursors.

High-temperature apparatus for chaotic mixing of natural silicate melts.

A unique high-temperature apparatus was developed to trigger chaotic mixing at high-temperature (up to 1800 °C). This new apparatus, which we term Chaotic Magma Mixing Apparatus (COMMA), is designed to carry out experiments with high-temperature and high-viscosity (up to 10(6) Pa s) natural silicate melts. This instrument allows us to follow in time and space the evolution of the mixing process and the associated modulation of chemical composition. This is essential to understand the dynamics of magma mixing and related chemical exchanges. The COMMA device is tested by mixing natural melts from Aeolian Islands (Italy). The experiment was performed at 1180 °C using shoshonite and rhyolite melts, resulting in a viscosity ratio of more than three orders of magnitude. This viscosity ratio is close to the maximum possible ratio of viscosity between high-temperature natural silicate melts. Results indicate that the generated mixing structures are topologically identical to those observed in natural volcanic rocks highlighting the enormous potential of the COMMA to replicate, as a first approximation, the same mixing patterns observed in the natural environment. COMMA can be used to investigate in detail the space and time development of magma mixing providing information about this fundamental petrological and volcanological process that would be impossible to investigate by direct observations. Among the potentials of this new experimental device is the construction of empirical relationships relating the mixing time, obtained through experimental time series, and chemical exchanges between the melts to constrain the mixing-to-eruption time of volcanic systems, a fundamental topic in volcanic hazard assessment.

Gastric emptying and intragastric balloon in obese patients.

BACKGROUND: Intragastric balloons have been proposed to induce weight loss in obese subjects. The consequences of the balloon on gastric physiology remain poorly studied. We studied the influence of an intragastric balloon on gastric emptying in obese patients. PATIENTS AND METHODS: 12 patients were included in the study, with BMI (mean +/- SD) of 38.51 +/- 4.32 kg/m2. The balloon was inserted under light anaesthesia and endoscopic control, inflated with 700 ml saline, and removed 6 months later. Body weight and gastric emptying (T1/2 and T lag) using 13C-octanoic acid breath test were monitored before balloon placement, during its permanence and 2 months after removal. RESULTS: Mean weight loss was: 6.2 +/- 2.3 kg after one month; 12.4 +/- 5.8 kg after 3 months; 14.4 +/- 6.6 kg after 6 months and 10.1 +/- 4.3 kg two months after BIB removal. Gastric emptying rates were significantly decreased in the first periods with balloon in place, and returned to pre-implantation values after balloon removal. T1/2 was: 87 +/- 32 min before BIB positioning, 181 +/- 91 min after 1 month, 145 +/- 99 min after 3 months, 104 +/- 50 min after 6 months and 90 +/- 43 min 2 months after removal. T lag was 36 +/- 18 min before BIB positioning, 102 +/- 82 min after 1 month, 77 +/- 53 min after 3 months, 59 +/- 28 min after 6 months and 40 +/- 21 min. 2 months after removal. CONCLUSIONS: BIB in obese patients seems to be a good help in following the hypo caloric diet, especially during the first three months when the gastric emptying is slower and the sense of repletion is higher. After this period gastric emptying starts to return to normal and the stomach adapts to BIB loosing efficacy in weight loss.

Severe intrahepatic cholestasis caused by amiodarone toxicity after withdrawal of the drug: a case report and review of the literature.

Cholestasis has been reported as a rare presentation among patients with severe liver injury secondary to amiodarone hepatic toxicity. We report an unusual case of amiodarone-induced cholestatic hepatotoxicity occurring after amiodarone had been discontinued and the initial abnormal liver function findings had improved. The patient, without jaundice at the initial presentation, developed severe jaundice about 4 months after withdrawal of amiodarone. Light and transmission electron microscopic examination of a specimen secured by computed tomographically guided liver biopsy was consistent with amiodarone hepatic toxicity as the cause of intrahepatic cholestasis. An abdominal ultrasound, endoscopic retrograde cholangiography, and dimethyl iminodiacetic acid and computed tomographic scans of the abdomen all failed to demonstrate any other causes for jaundice other than amiodarone toxicity. Thus, amiodarone hepatic toxicity may occur after drug withdrawal even if results of liver function tests improve. Histopathologic examination of a liver biopsy specimen is of value for diagnosis and prognosis. The liver biopsy findings, clinical course, and liver function test results are discussed, and the English-language literature on amiodarone cholestatic hepatotoxicity is reviewed.

Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations.

The exact cause, prevalence, and rate of progression of nonalcoholic fatty liver disease (NAFLD) are unclear because of a lack of agreement on the pathologic features associated with the different types of NAFLD, their clinical syndromes, and because of a lack of accuracy in the interpretation of these pathologic features. Studies of NAFLD would be aided by a consistent and standardized approach to the interpretation of pathologic features. The aim of our study was to assess interobserver and intraobserver variation in the histologic abnormalities associated with NAFLD. We identified histologic features of NAFLD as reported in the literature, and we identified patients with the diagnosis of NAFLD through the databases of two large institutions. Histologic parameters were evaluated for each liver biopsy specimen by four hepatopathologists and twice by two of the four pathologists (blindly). Interobserver and intraobserver concordance among the pathologists was measured by kappa statistics. Nineteen histologic parameters compartmentalized into steatosis, inflammation, liver cell injury, and fibrosis were evaluated on 53 liver biopsy specimens. Significant, substantial, or moderate concordance was present in only six items: the extent of steatosis, sinusoidal location of fibrosis, perivenular fibrosis, grade of fibrosis, ballooning degeneration, and the presence of vacuolated nuclei. Substantial or moderate concordance also was seen for interobserver readings for location of steatosis and periportal injury. Parameters of inflammation were not scored as reliably as parameters of fibrosis and cell injury. We conclude that only some histologic features previously reported in NAFLD (especially those with substantial and moderate concordance for both interobserver and intraobserver interpretation) are interpreted uniformly by experienced pathologists. These histologic features might prove useful for the development of a standardized and reliable pathologic scoring system that includes the full histologic spectrum of NAFLD and its various clinical outcomes.

Intravesicular prostaglandin E2 for the prophylaxis of urinary retention after colpohysterectomy.

The aim of this study was to assess the efficacy of PGE2 in enhancing bladder function after vaginal hysterectomy. A total of 110 women with or without urinary incontinence underwent vaginal hysterectomy and cystourethropexy surgery because of grade II or III genital prolapse. Preoperatively the patients were randomly assigned to two groups: group 1 (n = 50) received on the fourth post-operative day, before removal of the bladder catheter, an intravesicular solution of 1.50 mg PGE2 (2 x 0.75 mg); group 2 (n = 60) did not receive any prophylaxis for urinary retention. In the PGE2-treated group significantly fewer patients had urinary retention for 3 days or more (10%, P < 0.05) than in the control group (27%). The use of intravesicular PGE2 reduced the time taken to restore detrusor function.

ACTH receptor mRNA in human adrenocortical tumors: overexpression in aldosteronomas.

We previously reported that ACTH receptor (ACTH-R) mRNA is expressed in cortisol-secreting adrenal tumors, with significant differences between adenomas and carcinomas. In order to complete the study we have now evaluated 11 aldosteronomas (APA), 14 non-hypersecreting adenomas, 2 androgen-secreting adenomas and 8 normal adrenal glands. The level of ACTH-R mRNA was evaluated by competitive RT-PCR using a non-homologous competitor. ACTH-R gene was expressed in all tissues. All APA showed highest ACTH-R mRNA levels. Despite signs of individual heterogeneity, the level of ACTH-R transcripts was reduced in carcinomas. Furthermore, no significant differences were observed among cortisol-secreting adenomas, non hypersecreting adenomas and controls. The results show that ACTH-R mRNA is expressed in all adrenocortical tumors. The overexpression of ACTH-R in APA supports the role of ACTH on aldosterone secretion in these tumors, as also suggested by the presence of a diurnal rhythm, the lack of response to Angiotensin II, upright posture and captopril administration. The low abundance of ACTH-R in carcinomas might be a useful molecular marker of malignancy even if some overlap between carcinomas and adenomas does exist.

Differential expression of nuclear 11beta-hydroxysteroid dehydrogenase type 2 in mineralocorticoid receptor positive and negative tissues.

Corticosteroid hormone action is controlled at a pre-receptor level by the activity of two isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), catalyzing the interconversion of hormonally active cortisol to inactive cortisone. In particular 11beta-HSD2 protects the mineralocorticoid receptor (MR) from glucocorticoid excess, enabling aldosterone to interact with the MR. We have analyzed the subcellular localization of 11beta-HSD2 in relation to the expression of the MR in human colon and placenta. 3H-aldosterone binding studies confirmed expression of the MR in human colon but not term placental trophoblast. Enzyme activity studies and Western blot analyses carried out on subcellular fractions confirmed the presence of 11beta-HSD2 in microsomes. In colon, but not placenta, 11beta-HSD2 was also localized to the microsome-free, nuclear fraction. Protection upon the MR by 11beta-HSD2 in "classical" mineralocorticoid target tissues such as colon can be subserved at both a nuclear and extra-nuclear level. Tissue specific factors are responsible for the subcellular localization of 11beta-HSD2 and we postulate that one such factor may be the MR itself.

Interleukin-6 production by human monocytes stimulated with Cryptococcus neoformans components.

In order to ascertain if Cryptococcus neoformans components can induce interleukin-6 (IL-6) production, we stimulated human whole blood with purified capsular products. Their potencies in stimulating IL-6 release were mannoproteins > galactoxylomannan = glucuronoxylomannan > alpha(1-3)glucan. IL-6 production was tumor necrosis factor alpha independent and required the presence of monocytes and plasma. Since IL-6 can stimulate replication of the human immunodeficiency virus in monocytic cells, these findings may be clinically relevant.

Immunodetection of 11 beta-hydroxysteroid dehydrogenase type 2 in human mineralocorticoid target tissues: evidence for nuclear localization.

11 beta-Hydroxysteroid dehydrogenase (11 beta HSI) is an enzyme complex responsible for the conversion of hormonally active cortisol to inactive cortisone; two isoforms of the enzyme have been cloned and characterized. Clinical observations from patients with the hypertensive syndrome apparent mineralocorticoid excess, recently explained on the basis of mutations in the human 11 beta HSD2 gene, suggest that it is the 11 beta HSD2 isoform that serves a vital role in dictating specificity upon the mineralocorticoid receptor (MR). We have raised a novel antibody in sheep against human 11 beta HSD2 using synthetic multiantigenic peptides and have examined the localization and subcellular distribution of 11 beta HSD2 in mineralocorticoid target tissues. The immunopurified antibody recognized a single band of approximately 44 kDa in placenta, trophoblast, and distal colon. In kidney tissue, two bands of approximately 44 and 48 kDa were consistently observed. No signal was seen in decidua, adrenal, or liver. Immunoperoxidase studies on the mineralocorticoid target tissues, kidney, colon, and parotid gland indicated positive staining in epithelial cells known to express the MR: respectively, renal collecting ducts, surface and crypt colonic epithelial cells, and parotid duct epithelial cells. No staining was seen in these tissues in other sites. The intracellular localization of 11 beta HSD2 in kidney and colon epithelial cells was addressed using confocal laser microscopy. Parallel measurements of 11 beta HSD2 and nuclear propidium iodide fluorescence on sections scanned through an optical section of approximately 0.1 micron indicated significant 11 beta HSD2 immunofluorescence in the nucleus. In human kidney, colon, and salivary gland, 11 beta HSD2 protects the MR from glucocorticoid excess in an autocrine fashion. Furthermore, within these tissues, 11 beta HSD2, which had been considered to be a microsomal enzyme, is also found in the nucleus, suggesting that the interaction between the MR and aldosterone or cortisol is in part a nuclear event.

TGF-beta 1 immunohistochemistry in goiter: comparison of patients with recurrence or no recurrence.

The aim of this work was to establish whether the immunohistochemical pattern for TGF-beta 1 in goiters that recur after thyroid surgery is different when compared with goiters that do not recur postoperatively. Twelve goiters, surgically removed by partial resection between 1977 and 1982, were studied. Ten years after surgery, 6 patients had recurrence of goiter or thyroid nodules (group 1); the others did not have any recurrence (group 2). The presence and location of TGF-beta 1 were evaluated a posteriori by immunohistochemistry in histological samples of the tissue that was removed. In each goiter specimen, 50 randomly selected subcapsular follicles were studied to evaluate the percentage of follicles negative or positive for TGF-beta 1 and the protein's intrathyrocyte location. In the slides of group 1, the percentage of TGF-beta 1-positive follicles was statistically (p < 0.01) greater (93.1%) than in group 2 (71.4%). No difference in the location of TGF-beta 1 was found. The authors found a greater percentage of positive follicles for the TGF-beta 1 protein in group 1 patients. In conclusion, TGF-beta 1 production in goiter is variable, time dependent, and may be a marker of active cellular proliferation due to chronic exposure to a goitrogen stimulus. Thus, the more TGF-beta 1 found, the more the cell is stimulated and, therefore, the greater the risk of relapse.

First-trimester chromosome diagnosis by lavage of the uterine cavity.

Fetal karyotyping of trophoblast cells obtained by lavage of the uterine cavity was evaluated on 86 first-trimester irrigation fluid samples. Villus fragments were observed in 72 fluid samples indicating an 83.7 per cent sampling success rate. The amount of villi in these samples ranged from 1 to 32 mg. In most cases, villus fragments showed degeneration of the external syncytiotrophoblast layer and absence of blood vessels. In the first phase of this study (15 samples), a high degree of maternal cell contamination was observed after long-term cultures. In the following phase (71 samples), this obstacle was overcome by the application of a semi-direct method. Chromosome preparations were set up after 24 h incubation of villus fragments and QFQ-banded metaphase spreads were scored for chromosome number and sex. Sixty samples showed the presence of villus fragments and the fetal karyotype was established in 40. Male and female chromosome complements were observed in 16 and 24 cases, respectively. In four cases, an abnormal fetal karyotype was diagnosed. These included trisomy of chromosomes 13, 15, and 16, and one mosaic with trisomy 12. Our results indicate that first-trimester fetal karyotyping might be feasible by a semi-direct method using chorionic villus fragments obtained at intrauterine lavage.

TGF beta 1 immunostaining patterns and locations in adenoma which later recurred.

To investigate whether the immunohistochemical pattern of TGF beta 1 may be a marker of relapse for adenomatous pathology, 18 follicular adenomas, surgically removed by hemithyroidectomy between 1977 and 1982, were studied. The adenomas were divided into two groups according to the presence (group 1, N = 9) or absence (group 2, N = 9) of nodules recurring in the residual thyroid tissue. The presence and location of TGF beta 1 were evaluated a posteriori by immunohistochemistry in the removed adenoma. Fifty randomly selected subcapsular follicles were studied in each adenoma in order to evaluate the percentage of positive follicles and TGF beta 1 intra-thyrocyte location. In adenoma of group 1, the percentage of positive follicles for TGF beta 1 was lower (80%) than in adenoma of group 2 (84%); this was, however, not statistically significant. The location of TGF beta 1 was mainly at the cell base of the epithelial cells in the microfollicles of group 1, but was dominant at the cell apex in group 2 (p < 0.01). In conclusion, adenoma recurrence is independent of TGF beta 1 production; it may be due to an abnormal TGF beta 1 regulation in response to hyperplasiogenic stimuli.