Glutamate Concentration in the Serum of Patients with Schizophrenia

Glutamate is the major neurotransmitter with multiple functions in the central nervous system. Glutamate-mediated excitotoxicity is involved in the pathophysiological processes in schizophrenia. The purpose of this study was to determine the concentration of glutamate in the serum of patients with paranoid schizophrenia compared with healthy individuals, and depending on the duration of the schizophrenic process and leading clinical symptoms. We investigated the level of glutamate in the serum of 158 patients with paranoid schizophrenia and 94 healthy persons. Higher concentrations of glutamate in schizophrenic patients compared with healthy persons have been found. The maximum concentrations of glutamate were detected in patients with disease duration of more than ten years. Glutamate level in the serum does not depend on the prevailing negative or positive clinical symptoms. The increased concentration of glutamate can hypothetically contribute to dopaminergic and glutamatergic imbalance, leading to the development of psychotic symptoms and cognitive dysfunction

Changes in anticoagulant prescription patterns over time for patients with atrial fibrillation around the world

Background: Prescribing patterns for stroke prevention in atrial fibrillation (AF) patients evolved with approval of non-Vitamin K antagonist oral anticoagulants (NOACs) over time.Objectives: To assess changes in anticoagulant prescription patterns in various geographical regions upon first approval of a NOAC and to analyze the evolution of oral anticoagulants (OACs) use over time in relation to CHA(2)DS(2)-VASc and HAS-BLED risk profiles.Methods: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phases II and III reported data on antithrombotic therapy for patients with newly diagnosed AF and >= 1 stroke risk factor. We focused on sites enrolling patients in both phases and reported treatment patterns for the first 4 years after initial NOAC approval.Results: From GLORIA-AF Phases II and III, 27 432 patients were eligible for this analysis. When contrasting the first year with the fourth year of enrolment, the proportion of NOAC prescriptions increased in Asia from 29.2% to 60.8%, in Europe from 53.4% to 75.8%, in North America from 49.0% to 73.9% and in Latin America from 55.7% to 71.1%. The proportion of Vitamin K antagonists (VKAs) use decreased across all regions over time, in Asia from 26.0% to 9.8%, in Europe from 35.5% to 16.8%, in North America from 28.9% to 12.1%, and in Latin America from 32.4% to 17.8%. In the multivariable analysis, factors associated with NOAC prescription were as follows: enrolment year, type of site, region, stroke and bleeding risk scores, and type and categorization of AF.Conclusions: During 4 years after the approval of the first NOAC, NOAC use increased, while VKA use decreased, across all regions.Thrombosis and Hemostasi

Dynamic redox conditions control late Ediacaran metazoan ecosystems in the Nama Group, Namibia

The first appearance of skeletal metazoans in the late Ediacaran (~550 million years ago; Ma) has been linked to the widespread development of oxygenated oceanic conditions, but a precise spatial and temporal reconstruction of their evolution has not been resolved. Here we consider the evolution of ocean chemistry from ~550 to ~541. Ma across shelf-to-basin transects in the Zaris and Witputs Sub-Basins of the Nama Group, Namibia. New carbon isotope data capture the final stages of the Shuram/Wonoka deep negative C-isotope excursion, and these are complemented with a reconstruction of water column redox dynamics utilising Fe-S-C systematics and the distribution of skeletal and soft-bodied metazoans. Combined, these inter-basinal datasets provide insight into the potential role of ocean redox chemistry during this pivotal interval of major biological innovation.The strongly negative δ13C values in the lower parts of the sections reflect both a secular, global change in the C-isotopic composition of Ediacaran seawater, as well as the influence of 'local' basinal effects as shown by the most negative δ13C values occurring in the transition from distal to proximal ramp settings. Critical, though, is that the transition to positive δ13C values postdates the appearance of calcified metazoans, indicating that the onset of biomineralization did not occur under post-excursion conditions.Significantly, we find that anoxic and ferruginous deeper water column conditions were prevalent during and after the transition to positive δ13C that marks the end of the Shuram/Wonoka excursion. Thus, if the C isotope trend reflects the transition to global-scale oxygenation in the aftermath of the oxidation of a large-scale, isotopically light organic carbon pool, it was not sufficient to fully oxygenate the deep ocean.Both sub-basins reveal highly dynamic redox structures, where shallow, inner ramp settings experienced transient oxygenation. Anoxic conditions were caused either by episodic upwelling of deeper anoxic waters or higher rates of productivity. These settings supported short-lived and monospecific skeletal metazoan communities. By contrast, microbial (thrombolite) reefs, found in deeper inner- and mid-ramp settings, supported more biodiverse communities with complex ecologies and large skeletal metazoans. These long-lived reef communities, as well as Ediacaran soft-bodied biotas, are found particularly within transgressive systems, where oxygenation was persistent. We suggest that a mid-ramp position enabled physical ventilation mechanisms for shallow water column oxygenation to operate during flooding and transgressive sea-level rise. Our data support a prominent role for oxygen, and for stable oxygenated conditions in particular, in controlling both the distribution and ecology of Ediacaran skeletal metazoan communities

Cavity-enhanced direct frequency comb spectroscopy

Cavity-enhanced direct frequency comb spectroscopy combines broad spectral bandwidth, high spectral resolution, precise frequency calibration, and ultrahigh detection sensitivity, all in one experimental platform based on an optical frequency comb interacting with a high-finesse optical cavity. Precise control of the optical frequency comb allows highly efficient, coherent coupling of individual comb components with corresponding resonant modes of the high-finesse cavity. The long cavity lifetime dramatically enhances the effective interaction between the light field and intracavity matter, increasing the sensitivity for measurement of optical losses by a factor that is on the order of the cavity finesse. The use of low-dispersion mirrors permits almost the entire spectral bandwidth of the frequency comb to be employed for detection, covering a range of ~10% of the actual optical frequency. The light transmitted from the cavity is spectrally resolved to provide a multitude of detection channels with spectral resolutions ranging from a several gigahertz to hundreds of kilohertz. In this review we will discuss the principle of cavity-enhanced direct frequency comb spectroscopy and the various implementations of such systems. In particular, we discuss several types of UV, optical, and IR frequency comb sources and optical cavity designs that can be used for specific spectroscopic applications. We present several cavity-comb coupling methods to take advantage of the broad spectral bandwidth and narrow spectral components of a frequency comb. Finally, we present a series of experimental measurements on trace gas detections, human breath analysis, and characterization of cold molecular beams.Comment: 36 pages, 27 figure

Atomic Species Associated with the Portevin–Le Chatelier Effect in Superalloy 718 Studied by Mechanical Spectroscopy

In many Ni-based superalloys, dynamic strain aging (DSA) generates an inhomogeneous plastic deformation resulting in jerky flow known as the Portevin--Le Chatelier (PLC) effect. This phenomenon has a deleterious effect on the mechanical properties and, at high temperature, is related to the diffusion of substitutional solute atoms toward the core of dislocations. However, the question about the nature of the atomic species responsible for the PLC effect at high temperature still remains open. The goal of the present work is to answer this important question; to this purpose, three different 718-type and a 625 superalloy were studied through a nonconventional approach by mechanical spectroscopy. The internal friction (IF) spectra of all the studied alloys show a relaxation peak P718 (at 885 K for 0.1 Hz) in the same temperature range, 700 K to 950 K, as the observed PLC effect. The activation parameters of this relaxation peak have been measured, Ea(P718){\thinspace}={\thinspace}2.68{\thinspace}{\textpm}{\thinspace}0.05 eV, $\tau$0{\thinspace}={\thinspace}2{\textperiodcentered}10-15 {\textpm} 1 s as well as its broadening factor $\beta${\thinspace}={\thinspace}1.1. Experiments on different alloys and the dependence of the relaxation strength on the amount of Mo attribute this relaxation to the stress-induced reorientation of Mo-Mo dipoles due to the short distance diffusion of one Mo atom by exchange with a vacancy. Then, it is concluded that Mo is the atomic species responsible for the high-temperature PLC effect in 718 superallo

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40–31.03, P = 1.36 × 10−54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10−19). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy

Genome-wide association study identifies two susceptibility loci for osteosarcoma

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10⁻⁹) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10⁻⁸ and 2.9 × 10⁻⁷, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma