Diazepam and its metabolites in the mothers' and newborns' hair as a biomarker of prenatal exposure

Pregnant women are exposed to benzodiazepines for therapeutic purposes during gestation. The goal of this study was to evaluate prenatal exposure to benzodiazepines. Time of exposure during course of pregnancy is a significant aspect of fetal exposure to drugs. Benzodiazepine concentration assay in hair of mothers and newborns exposed prenatally to these drugs was performed in the studies. Development, validation and evaluation of benzodiazepine determination method in mothers and their newborns enables assessment of health risks for the child and implementation of adequate therapeutic procedures. We used A LC-ESI-MS/MS method that allowed determination of diazepam (the main benzodiazepine used by pregnant women was diazepam) and its metabolites (nordazepam, oxazepam) in hair of mothers and newborns. LOQ 10 pg/mg of hair was used in the study. Results: concentration of nordazepam was higher than parent drug (diazepam) and higher in newborns’ hair when compared to mothers’. The mean concentrations of diazepam in mothers’ hair were 31.6±36.0 and 34.1±42.4 pg/mg in the second and third trimester of pregnancy respectively. The mean concentration of diazepam in newborns’ hair was higher and reached levels of 53.3±36.5 pg/mg. The mean concentration of nordazepam in the mothers’ hair corresponding to the second and third trimester was 52.9±48.1 and 89.9±122.8 pg/mg, respectively. Nordazepam in the newborns’ hair was detected at the mean level of 108.1±144.2 pg/mg. It was concluded that diazepam and nordazepam are permanently incorporated into the hair structure. Presence of diazepam and its metabolites in newborn’s hair confirms that these benzodiazepines permeate placental barrier. Segmental analysis of mothers’ hair enabled the assessment of drug administration time. Diazepam and its metabolites determined in hair of newborns may serve as biomarkers of prenatal exposure to these drugs. The performed LC-MS/MS analysis was accurate enough to determine even low concentrations of benzodiazepines, at the level of few pg/mg of hair. Levels of diazepam detected in hair of newborns were higher than levels determined in mothers. This may confirm the fact, that fetus’s ability to metabolize diazepam is scarce. Nordazepam was found in higher concentrations in hair of newborns than in hair of mothers, which may suggest that it is cumulated in child’s organism. Other metabolites of diazepam - oxazepam and temazepam - were detected in very few cases, in low concentrations

Mechanisms of the Vertical Secular Heating of a Stellar Disk

We investigate the nonlinear growth stages of bending instability in stellar disks with exponential radial density profiles.We found that the unstable modes are global (the wavelengths are larger than the disk scale lengths) and that the instability saturation level is much higher than that following from a linear criterion. The instability saturation time scales are of the order of one billion years or more. For this reason, the bending instability can play an important role in the secular heating of a stellar disk in the $z$ direction. In an extensive series of numerical $N$-body simulations with a high spatial resolution, we were able to scan in detail the space of key parameters (the initial disk thickness $z_0$, the Toomre parameter $Q$, and the ratio of dark halo mass to disk mass $M_{\rm h} / M_{\rm d}$). We revealed three distinct mechanisms of disk heating in the $z$ direction: bending instability of the entire disk, bending instability of the bar, and heating on vertical inhomogeneities in the distribution of stellar matter.Comment: 22 pages including 8 figures. To be published in Astronomy Letters (v.29, 2003

Dark matter and Colliders searches in the MSSM

We study the complementarity between dark matter experiments (direct detection and indirect detections) and accelerator facilities (the CERN LHC and a $\sqrt{s}= 1$ TeV $e^+e^-$ Linear Collider) in the framework of the constrained Minimal Supersymmetric Standard Model (MSSM). We show how non--universality in the scalar and gaugino sectors can affect the experimental prospects to discover the supersymmetric particles. The future experiments will cover a large part of the parameter space of the MSSM favored by WMAP constraint on the relic density, but there still exist some regions beyond reach for some extreme (fine tuned) values of the supersymmetric parameters. Whereas the Focus Point region characterized by heavy scalars will be easily probed by experiments searching for dark matter, the regions with heavy gauginos and light sfermions will be accessible more easily by collider experiments. More informations on both supersymmetry and astrophysics parameters can be thus obtained by correlating the different signals.Comment: 25 pages, 10 figures, corrected typos and reference adde

Theoretical Directional and Modulated Rates for Direct SUSY Dark Matter Detection

Exotic dark matter together with the vacuum energy (cosmological constant) seem to dominate in the flat Universe. Thus direct dark matter detection is central to particle physics and cosmology. Supersymmetry provides a natural dark matter candidate, the lightest supersymmetric particle (LSP). Furthermore from the knowledge of the density and velocity distribution of the LSP, the quark substructure of the nucleon and the nuclear structure (form factor and/or spin response function), one is able to evaluate the event rate for LSP-nucleus elastic scattering. The thus obtained event rates are, however, very low. So it is imperative to exploit the two signatures of the reaction, namely the modulation effect, i.e. the dependence of the event rate on the Earth's motion, and the directional asymmetry, i.e. the dependence of the rate on the the relative angle between the direction of the recoiling nucleus and the sun's velocity. These two signatures are studied in this paper employing various velocity distributions and a supersymmetric model with universal boundary conditions at large tan(beta).Comment: 11 LATEX pages, 1 table and 4 ps figures included. Paper presented in DARK2002, Fourth Heidelberg International Conference on Dark Matter in Astro- and Particle Physics, Cape Town, South Africa, 4-9 February, 2002, to appear in the proceedings (to be published by Springer Verlag

Effects of Temperature, Salinity and Fish in Structuring the Macroinvertebrate Community in Shallow Lakes: Implications for Effects of Climate Change

Climate warming may lead to changes in the trophic structure and diversity of shallow lakes as a combined effect of increased temperature and salinity and likely increased strength of trophic interactions. We investigated the potential effects of temperature, salinity and fish on the plant-associated macroinvertebrate community by introducing artificial plants in eight comparable shallow brackish lakes located in two climatic regions of contrasting temperature: cold-temperate and Mediterranean. In both regions, lakes covered a salinity gradient from freshwater to oligohaline waters. We undertook day and night-time sampling of macroinvertebrates associated with the artificial plants and fish and free-swimming macroinvertebrate predators within artificial plants and in pelagic areas. Our results showed marked differences in the trophic structure between cold and warm shallow lakes. Plant-associated macroinvertebrates and free-swimming macroinvertebrate predators were more abundant and the communities richer in species in the cold compared to the warm climate, most probably as a result of differences in fish predation pressure. Submerged plants in warm brackish lakes did not seem to counteract the effect of fish predation on macroinvertebrates to the same extent as in temperate freshwater lakes, since small fish were abundant and tended to aggregate within the macrophytes. The richness and abundance of most plant-associated macroinvertebrate taxa decreased with salinity. Despite the lower densities of plant-associated macroinvertebrates in the Mediterranean lakes, periphyton biomass was lower than in cold temperate systems, a fact that was mainly attributed to grazing and disturbance by fish. Our results suggest that, if the current process of warming entails higher chances of shallow lakes becoming warmer and more saline, climatic change may result in a decrease in macroinvertebrate species richness and abundance in shallow lakes

Analyzing the Impacts of Dams on Riparian Ecosystems: A Review of Research Strategies and Their Relevance to the Snake River Through Hells Canyon

River damming provides a dominant human impact on river environments worldwide, and while local impacts of reservoir flooding are immediate, subsequent ecological impacts downstream can be extensive. In this article, we assess seven research strategies for analyzing the impacts of dams and river flow regulation on riparian ecosystems. These include spatial comparisons of (1) upstream versus downstream reaches, (2) progressive downstream patterns, or (3) the dammed river versus an adjacent free-flowing or differently regulated river(s). Temporal comparisons consider (4) pre- versus post-dam, or (5) sequential post-dam conditions. However, spatial comparisons are complicated by the fact that dams are not randomly located, and temporal comparisons are commonly limited by sparse historic information. As a result, comparative approaches are often correlative and vulnerable to confounding factors. To complement these analyses, (6) flow or sediment modifications can be implemented to test causal associations. Finally, (7) process-based modeling represents a predictive approach incorporating hydrogeomorphic processes and their biological consequences. In a case study of Hells Canyon, the upstream versus downstream comparison is confounded by a dramatic geomorphic transition. Comparison of the multiple reaches below the dams should be useful, and the comparison of Snake River with the adjacent free-flowing Salmon River may provide the strongest spatial comparison. A pre- versus post-dam comparison would provide the most direct study approach, but pre-dam information is limited to historic reports and archival photographs. We conclude that multiple study approaches are essential to provide confident interpretations of ecological impacts downstream from dams, and propose a comprehensive study for Hells Canyon that integrates multiple research strategies

Combined searches for the production of supersymmetric top quark partners in proton–proton collisions at √s=13Te

A combination of searches for top squark pair production using proton–proton collision data at a center-of-mass energy of 13TeV at the CERN LHC, corresponding to an integrated luminosity of 137fb$^{-1}$ collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325GeV for a massless neutralino, and a neutralino mass up to 700GeV for a top squark mass of 1150GeV. Top squarks with masses from 145 to 295GeV, for neutralino masses from 0 to 100GeV, with a mass difference between the top squark and the neutralino in a window of 30GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420GeV

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%