Non-invasive prenatal diagnosis of multiple endocrine neoplasia type 2A using COLD-PCR combined with HRM genotyping analysis from maternal serum.

The multiple endocrine neoplasia type 2A (MEN2A) is a monogenic disorder characterized by an autosomal dominant pattern of inheritance which is characterized by high risk of medullary thyroid carcinoma in all mutation carriers. Although this disorder is classified as a rare disease, the patients affected have a low life quality and a very expensive and continuous treatment. At present, MEN2A is diagnosed by gene sequencing after birth, thus trying to start an early treatment and by reduction of morbidity and mortality. We first evaluated the presence of MEN2A mutation (C634Y) in serum of 25 patients, previously diagnosed by sequencing in peripheral blood leucocytes, using HRM genotyping analysis. In a second step, we used a COLD-PCR approach followed by HRM genotyping analysis for non-invasive prenatal diagnosis of a pregnant woman carrying a fetus with a C634Y mutation. HRM analysis revealed differences in melting curve shapes that correlated with patients diagnosed for MEN2A by gene sequencing analysis with 100% accuracy. Moreover, the pregnant woman carrying the fetus with the C634Y mutation revealed a melting curve shape in agreement with the positive controls in the COLD-PCR study. The mutation was confirmed by sequencing of the COLD-PCR amplification product. In conclusion, we have established a HRM analysis in serum samples as a new primary diagnosis method suitable for the detection of C634Y mutations in MEN2A patients. Simultaneously, we have applied the increase of sensitivity of COLD-PCR assay approach combined with HRM analysis for the non-invasive prenatal diagnosis of C634Y fetal mutations using pregnant women serum.

Sevelamer hydrochloride: A novel treatment of hyperphosphatemia associated with tumor lysis syndrome in children

Background. Sevelamer is a phosphate-binder used effectively for the treatment of hyperphosphatemia in patients treated with dialysis. Objectives. To describe the safety of sevelamer in children with hyperphosphatemia secondary to tumor lysis syndrome and the serum phosphate concentrations observed following its administration. Procedure. A retrospective chart review of all children with leukemia/lymphoma diagnosed between November 2002 and April 2004 who received sevelamer during their initial admission was conducted. We monitored the effects of sevelamer on serum phosphate concentration, calcium/phosphate product and renal function at hours 24, 48, and 72 from sevelamer initiation. Results. Thirteen patients received sevelamer during the Study period. Their median age was 13 years (range 2.7-17.9) and eight were boys. Nine children had acute lymphoblastic leukemia, one had acute myeloid leukemia and 3 had non-Hodgkin's lymphoma. The most frequently used dose of sevelamer was 400 mg orally twice daily. The median duration of sevelamer therapy was 2 days (range 1 -7). Two children were excluded from the efficacy analysis due to concurrent use of dialysis. Mean serum phosphate levels decreased after sevelamer administration, in eleven patients, from a baseline 2.2 mmol/L +/- 0.4 (95% Cl, 1.7-3.1) to 1.1 mmol/L +/- 0.2 at hour 72 (95%Cl, 0.6-1.5). The only toxicity attributed to sevelamer was mild vomiting in three patients. Conclusions. Sevelamer appears to be effective and tolerable for the treatment of hyperphosphatemia associated with tumor lysis syndrome.

La cascarilla cerámica y su uso innovador

The ceramic shell is a material mainly used for making foundry molds. This research demonstrates that ceramic shell can be used for making sculptures with exceptional definition in its finish. The research has identified a number of advantages of the material to meet the challenges of an artist during the making of a sculpture. The research has been developed in six stages: In the first stage data were collected from the chaff as the process material. This was the starting point for research. In the second stage, we have set the appropriate composition of the slurry, both in percentage and type of binder, and firing curve. To this end, we evaluated the application characteristics, thickness, drying, mechanical strength, the reduction coefficient and porosity. In the third stage it was observed that the husk is suitable for all types of materials acting as support. It was also found that the slurry can be used with various sculptural processes: modeling, molding using silicone or plaster mold, shuttering, with internal metal frame, and so on. In addition, we have established methods to repair and modify the husk by hand and power tools. In the fourth stage we have found ways to modify the surface of the husk with other minerals that affect the structure: introduction of filing of copper, bronze and iron in the slurry ceramics, different staining procedure in hot or cold, by enamel slip, and so on. In the fifth stage sculptures were made using the methods established in the previous stages, to verify this hypothesis. The sixth stage, which is annexed, contains a new method to process the ceramic shell as a mold in casting that emerged from the proven methods in the investigation.

Leucine supplementation protects from insulin resistance by regulating adiposity levels.

BACKGROUND Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed. METHODOLOGY/PRINCIPAL FINDINGS Male C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed. CONCLUSIONS/SIGNIFICANCE These findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation is lacking in already obese animals, a phenomenon possibly related to the extent of the obesity before starting the supplementation.

Post-collisional Neogene magmatism of the Mediterranean Maghreb margin: a consequence of slab breakoff

A 1 200 km-long linear magmatic belt extends along the Mediterranean coast the Maghreb from Eastern Tunisia to Morocco. This belt is mainly composed of Langan calc-alkaline metaluminous to peraluminous granitoids and associated andesites/cites Central and Eastern Algeria. In Tunisia and Oranie/Western Morocco, calc alkaline activity started later (during the Serravallian) and was followed by the placement of alkali basalts and basanites since the Tortonian to the Pliocene and, in me places, the Pleistocene. Available data on the tectonic setting, petrology, age and biochemistry of this belt show that most of its striking features, e.g. (1) very low magma production rate, subduction-related geochemical imprint, extensive crustal contamination the calc-alkaline magmatism and (2) progressive magmatic change from calc-alkaline alkaline, are consistent with magma generation during a slab breakoff process as proposed Carminati et al, in 1998. The magmatism associated with this breakoff started in Central Eastern Algeria at 16 Ma, then propagated eastwards and westwards, The upward of asthenospheric enriched plume-type mantle through the tear in the downgoing first triggered melting of the overlying lithospheric mantle which had been metasomatised during a previous subduction period. Heat supply from this uprising asthenosphere may have warmed up the continental crust and made its involvement in assimilation processes easier. As the asthenosphere ascended through the `window' in the slab, partial melting occurred at the uprising boundary between asthenosphere and lithosphere, generating basalts with transitional characteristics between those of calc-alkaline and alkaline basalts. As the asthhenospheric upwelling proceeded partial:melting then occurred in the sole asthenospheric mantle, producing alkali basalts. (C) 2000 Academie des sciences Editions scientifiques et medicales Elsevier SAS.

Investigating the genetic variation underlying episodicity in major depressive disorder: Suggestive evidence for a bipolar contribution.

BACKGROUND: Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. METHODS: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. RESULTS: Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. LIMITATIONS: Episode count was self-reported and, therefore, subject to recall bias. CONCLUSIONS: Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts.

The suitability of steam exploded vitis vinifera and alkaline lignin for the manufacture of fiberboard

The main objective of this study was to explore the suitability of Vitis vinifera as a raw material and alkaline lignin as a natural binder for fiberboard manufacturing. In the first step, Vitis vinifera was steam- exploded through a thermo-mechanical vapor process in a batch reactor, and the obtained pulp was dried, ground, and pressed to produce the boards. The effects of pretreatment factors and pressing conditions on the chemical composition of the fibers and the physico-mechanical properties of binderless fiberboards were evaluated, and the conditions that optimize these properties were found. A response surface method based on a central composite design and multiple-response optimization was used. The variables studied and their respective variation ranges were: pretreatment temperature (Tr: 190-210ºC), pretreatment time (tr: 5-10 min), pressing temperature (Tp: 190-210ºC), pressing pressure (Pp: 8-16MPa), and pressing time (tp: 3-7min). The results of the optimization step show that binderless fiberboards have good water resistance and weaker mechanical properties. In the second step, fiberboards based on alkaline lignin and Vitis vinifera pulp produced at the optimal conditions determined for binderless fiberboards were prepared and their physico-mechanical properties were tested. Our results show that the addition of about 15% alkaline lignin leads to the production of fiberboards that fully meet the requirements of the relevant standard specifications

Late Labradorian metamorphism and anorthosite-granitoid intrusion, Cape-Caribou River allochthon, Grenville Province, Labrador - Evidence from U-Pb geochronology

In the Cape Caribou River allochthon (CCRA), metaigneous and gneissic units occur as a shallowly plunging synform in the hanging wall of the Grand Lake thrust system (GLTS), a Grenvillian structure that forms the boundary between the Mealy Mountains and Groswater Bay terranes. The layered rocks of the CCRA are cut by a stockwork of monzonite dykes related to the Dome Mountain suite and by metadiabase-amphibolite dykes that probably form part of the ca. 1380 Ma Mealy swarm. The mafic dykes appear to postdate much of the development of subhorizontal metamorphic layering within the lower parts of the CCRA. The uppermost (least metamorphosed) units of the CCRA, the North West River anorthosite-metagabbro and the Dome Mountain monzonite suite, have been dated at 1625 +/- 6 and 1626 +/- 2 Ma, respectively. An amphibolite unit that concordantly underlies the anorthosite-metagabbro and is intruded discordantly by monzonite dykes has given metamorphic ages of 1660 +/- 3 and 1631 +/- 2 Ma. Granitoid gneisses that form the lowest level of the CCRA have given a migmatization age of 1622 +/- 6 Ma. The effects of Grenvillian metamorphism become apparent in the lower levels of the allochthon where gneisses, amphibolite, and mafic dykes have given new generation zircon ages of 1008 +/- 2, 1012 +/- 3, and 1011 +/- 3 Ma, respectively. A posttectonic pegmatite has also given zircon and monazite ages of 1016(-3)(+7) and 1013 +/- 3 Ma, respectively. Although these results indicate new growth of Grenvillian zircon, this process was generally not accompanied by penetrative deformation or melting. Thus, the formation of gneissic fabrics and the overall layered nature of the lower CCRA are a result primarily of Labradorian (1660-1620 Ma) tectonism and intrusion, and probably reflect early movement on an ancestral GLTS. Grenvillian heating and metamorphism (up to granulite facies) was strongly concentrated towards the base of the CCRA and probably occurred during northwestward thrusting of the allochthon over the Groswater Bay terrane.

Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study.

Epidemiological studies have recognized a genetic diathesis for suicidal behavior, which is independent of other psychiatric disorders. Genome-wide association studies (GWAS) on suicide attempt (SA) and ideation have failed to identify specific genetic variants. Here, we conduct further GWAS and for the first time, use polygenic score analysis in cohorts of patients with mood disorders, to test for common genetic variants for mood disorders and suicide phenotypes. Genome-wide studies for SA were conducted in the RADIANT and GSK-Munich recurrent depression samples and London Bipolar Affective Disorder Case-Control Study (BACCs) then meta-analysis was performed. A GWAS on suicidal ideation during antidepressant treatment had previously been conducted in the Genome Based Therapeutic Drugs for Depression (GENDEP) study. We derived polygenic scores from each sample and tested their ability to predict SA in the mood disorder cohorts or ideation status in the GENDEP study. Polygenic scores for major depressive disorder, bipolar disorder and schizophrenia from the Psychiatric Genomics Consortium were used to investigate pleiotropy between psychiatric disorders and suicide phenotypes. No significant evidence for association was detected at any SNP in GWAS or meta-analysis. Polygenic scores for major depressive disorder significantly predicted suicidal ideation in the GENDEP pharmacogenetics study and also predicted SA in a combined validation dataset. Polygenic scores for SA showed no predictive ability for suicidal ideation. Polygenic score analysis suggests pleiotropy between psychiatric disorders and suicidal ideation whereas the tendency to act on such thoughts may have a partially independent genetic diathesis. © 2014 Wiley Periodicals, Inc.

Lektüren im intermedialen Dialog

Die Studie geht davon aus, dass das Zusammenspiel von Text und Bild auf dem Prinzip der Dialogizität und Komplementarität zwischen zwei einander fremden Systemen gründet. Texte generieren Bilder, Bilder evozieren Narrationen. Im Zusammentreffen zwischen den beiden Medien werden Energien freigesetzt und ein Mehr an Bedeutung entsteht. Sprache und Bild können rivalisieren oder sich gegenseitig inspirieren, einander ergänzen oder ersetzen, ineinandergreifen oder kontrastieren. Abhängig von der jeweiligen Inszenierung, von der visuellen Anordnung, von inhaltlichen llbereinstimmungen oder formalen Annäherungen setzen die Medien divergierende oder kongruierende Systeme in Szene. Aus dem weiten Feld der intermedialen Verknüpfungen von Text und Bild wählt die Studie eine Reihe von Text-Bild-Kombinationen, in denen skripturale und piktoriale Elemente nebeneinander inszeniert werden und in ihrem prozesshaften Zusammenwirken den Rezipienten zur Lekture von unterschiedlichen narrativen Möglichkeiten herausfordern: Max Ernsts Collageroman Rêve d'une petite fille qui voulut entrer au CarmeI ; Peter Weiss' Text- Bild-Ensemble Der Schatten des Kòrpers des Kutschers, Le rêve de Paul Delvaux, ein Text- Bild-Projekt, für das der Nouveau Romancier Michel Butor eine Erzählung zu einer Reihe von Bildern des Surrealisten Paul Delvaux verfasst ; die Ballade Minotaurus von Friedrich Dürrenmatt , sowie Der Schachspieler, eine Reaktion des Illustrators Hannes Binder auf einen posthum erschienenen Text Durrenmatts . In fünf Einzellektüren und fünf Kapiteln wird der Frage nachgegangen wie sich Narration im Text-Bild-Spiegel generiert und welche Rolle der Lektüreakt dabei spielt. Dabei interessieren die Werke als vergleichbare, aber heterogene Kombinationsformen von Text und Bild. Im Zentrum der Analysen stehen die Darstellung von Raum- und Zeitelementen, die sprachlichen Erzählinstanzen, die das Zusammenspiel von Stimme und Körper konstituieren, sowie der Informationstrager Buch als medialer wie auch materieller Gegenstand.

Delirium auf der Intensivstation [Delirium in the intensive care unit.]

The prevalence of delirium in the Intensive Care Unit (ICU) is reported to vary from 20 to 80 %. Delirium in the ICU is not only a frightening experience for the patient and his or her family, it is also a challenge for the nurses and physicians taking care of the patient. Furthermore, it is also associated with worse outcome, prolonged hospitalisation, increased costs, long-term cognitive impairment and higher mortality rates. Thus, strategies to prevent ICU-delirium in addition to the early diagnosis and treatment of delirium are important. The pathophysiology of delirium is still incompletely understood, but numerous risk factors for the development of delirium have been identified in ICU-patients, among which are potentially modifiable factors such as metabolic disturbances, hypotension, anaemia, fever and infection. Key factors are the prevention and management of common risk factors, including avoiding overzealous sedation and analgesia and creating an environment that enhances reintegration. Once delirium is diagnosed, treatment consists of the use of typical and atypical antipsychotics. Haloperidol is still the drug of choice for the treatment of delirium and can be given intravenously in incremental doses of 1 to 2 to 5 (to 10) mg every 15 - 20 minutes.

Entrained macrocryst minerals as a key to the source region of olivine nephelinites: Humberg, Kaiserstuhl, Germany

Olivine nephelinites commonly contain macrocrysts of olivine and clinopyroxene. Some of these macrocrysts might represent fragments of the source region of the host magma transported to the Earth surface. If this hypothesis is correct these fragments can be used to characterize the composition of the source region and to put constraints on the magma generation process. In this study, we investigate the origin of macrocrysts and mineral aggregates from an olivine nephelinite from the Kaiserstuhl, Germany. We focus on clinopyroxenes (Cpx), which can be divided into three groups. Cpx I is relict Cpx from aggregates with deformed olivine that is depleted in Ca and characterized by strong light rare earth element (LREE) fractionation, low Ti/Eu and negative high field strength element (HFSE) anomalies. Its geochemical signature is consistent with formation by carbonatite metasomatism and with equilibration in the Presence of orthopyroxene. Cpx II is Ca-rich Cpx, forming both aggregates with deformed olivine and individual macrocrysts. The LREE, as for Cpx I, are strongly fractionated. Convex REE patterns may be present. The depletion in HFSE is less pronounced. Cpx III is oscillatory zoned Cpx phenociysis showing enrichment in Ca, convex REE patterns and no HFSE anomalies. The transition in the trace element abundances between the Cpx of the three groups is gradual. However, Cpx I and H did not crystallize from the host magma, as demonstrated by the presence of kink-bands and undulose extinction in the associated olivine and by the composition of alkali aluminosilicate glass inclusions in Cpx H. Based on the Cpx relationships, we interpret the studied suite of macrocrysts and mineral aggregates as a mixture of disintegrated fragments of the source region of the host olivine nephelinite. The process of melt generation was multi-stage. A primary carbonatite melt ascending from deeper levels in the mantle, probably from the dolomite-garnet peridotite stability field, reacted with mantle peridotite along the solidus ledge in the system lherzolite-CO2 (< 20-22 kbar) and started to crystallize carbonate minerals. Because of its low solidus temperature, the resulting carbonate-wehrlite assemblage melted incongruently with the formation of additional clinopyroxene. The carbonatite melt evolved during crystallization of carbonate minerals and concomitant incongruent melting of the carbonate-wehrlite, accompanied by the segregation of incipient alkali aluminosilicate melts. As a consequence of fast reaction rates in the presence of a carbonatite melt, this process probably took place under disequilibrium conditions. Further melting of the assemblage wehrlite + alkali aluminosilicate melt led to the generation of the olivine nephelinite magma. It entrained fragments of the wehrlite and brought them to the surface.

Pre-Treatment for Reduction of Asphalt Absorption in Porous Aggregate, April 2005

The objective of this research was to evaluate the performance of the product Ultracote® (a polymer based additive produced by Ultrapave, a division of Goodyear) as an aggregate pre-treatment for the reduction of asphalt binder absorption in hot mix asphalt (HMA). The product was tested with a paving project in Louisa county, Iowa with aggregate that had historically shown very high asphalt binder absorption. Results of the testing did not provide any evidence of reduction in binder absorption.

Sustainable Development and Concrete Technology, May 2004

For a variety of reasons, the concrete construction industry is not sustainable. First, it consumes huge quantities of virgin materials. Second, the principal binder in concrete is portland cement, the production of which is a major contributor to greenhouse gas emissions that are implicated in global warming and climate change. Third, many concrete structures suffer from lack of durability which has an adverse effect on the resource productivity of the industry. Because the high-volume fly ash concrete system addresses all three sustainability issues, its adoption will enable the concrete construction industry to become more sustainable. In this paper, a brief review is presented of the theory and construction practice with concrete mixtures containing more than 50% fly ash by mass of the cementitious material. Mechanisms are discussed by which the incorporation of high volume of fly ash in concrete reduces the water demand, improves the workability, minimizes cracking due to thermal and drying shrinkage, and enhances durability to reinforcement corrosion, sulfate attack, and alkali-silica expansion. For countries like China and India, this technology can play an important role in meeting the huge demand for infrastructure in a sustainable manner.

The Carboniferous Baralacha La basaltic dykes (Upper Lahul, Ladakh): remnants of an early rifting event along the Indian northern plate

The Lower Carboniferous Baralacha La basaltic dykes were emplaced along transtensional faults. The basalts exhibit tholeiitic and alkaline affinities. The tholeiites are TiO2-poor, moderately enriched in light rare earth (LREE), and display Nb and Ta negative and Th positive anomalies. The alkali basalts, compared to the tholeiites, have higher TiO2, rare earth and highly incompatible trace element contents and greater LREE enrichments. The Nd and Pb isotope compositions of the Baralacha La basalts suggest that they derive from the partial melting of an enriched OIB mantle source. characterized by a HIMU component, and contaminated by the lower continental crust. The Baralacha La dyke swarm represent the remnants of an early rifting event on the northern Indian passive margin.