Comparative Developmental Neurotoxicity of Organophosphate Insecticides: Effects on Brain Development Are Separable from Systemic Toxicity

A comparative approach to the differences between systemic toxicity and developmental neurotoxicity of organophosphates is critical to determine the degree to which multiple mechanisms of toxicity carry across different members of this class of insecticides. We contrasted neuritic outgrowth and cholinergic synaptic development in neonatal rats given different organophosphates (chlorpyrifos, diazinon, parathion) at doses spanning the threshold for impaired growth and viability. Animals were treated daily on postnatal days 1–4 by subcutaneous injection so as to bypass differences in first-pass activation to the oxon or catabolism to inactive products. Evaluations occurred on day 5. Parathion (maximum tolerated dose, 0.1 mg/kg) was far more systemically toxic than was chlorpyrifos or diazinon (maximum tolerated dose, 1–5 mg/kg). Below the maximum tolerated dose, diazinon impaired neuritic outgrowth in the forebrain and brainstem, evidenced by a deficit in the ratio of membrane protein to total protein. Diazinon also decreased choline acetyltransferase activity, a cholinergic neuronal marker, whereas it did not affect hemicholinium-3 binding to the presynaptic choline transporter, an index of cholinergic neuronal activity. There was no m(2)-muscarinic acetylcholine receptor down-regulation, as would have occurred with chronic cholinergic hyper-stimulation. The same pattern was found previously for chlorpyrifos. In contrast, parathion did not elicit any of these changes at its maximum tolerated dose. These results indicate a complete dichotomy between the systemic toxicity of organophosphates and their propensity to elicit developmental neurotoxicity. For parathion, the threshold for lethality lies below that necessary for adverse effects on brain development, whereas the opposite is true for chlorpyrifos and diazinon

Scope for Credit Risk Diversification

This paper considers a simple model of credit risk and derives the limit distribution of losses under different assumptions regarding the structure of systematic risk and the nature of exposure or firm heterogeneity. We derive fat-tailed correlated loss distributions arising from Gaussian risk factors and explore the potential for risk diversification. Where possible the results are generalised to non-Gaussian distributions. The theoretical results indicate that if the firm parameters are heterogeneous but come from a common distribution, for sufficiently large portfolios there is no scope for further risk reduction through active portfolio management. However, if the firm parameters come from different distributions, then further risk reduction is possible by changing the portfolio weights. In either case, neglecting parameter heterogeneity can lead to underestimation of expected losses. But, once expected losses are controlled for, neglecting parameter heterogeneity can lead to overestimation of risk, whether measured by unexpected loss or value-at-risk

BLAST: the Redshift Survey

The Balloon-borne Large Aperture Submillimeter Telescope (BLAST) has recently surveyed ~8.7 deg^2 centered on GOODS-South at 250, 350, and 500 microns. In Dye et al. (2009) we presented the catalogue of sources detected at 5-sigma in at least one band in this field and the probable counterparts to these sources in other wavebands. In this paper, we present the results of a redshift survey in which we succeeded in measuring redshifts for 82 of these counterparts. The spectra show that the BLAST counterparts are mostly star-forming galaxies but not extreme ones when compared to those found in the Sloan Digital Sky Survey. Roughly one quarter of the BLAST counterparts contain an active nucleus. We have used the spectroscopic redshifts to carry out a test of the ability of photometric redshift methods to estimate the redshifts of dusty galaxies, showing that the standard methods work well even when a galaxy contains a large amount of dust. We have also investigated the cases where there are two possible counterparts to the BLAST source, finding that in at least half of these there is evidence that the two galaxies are physically associated, either because they are interacting or because they are in the same large-scale structure. Finally, we have made the first direct measurements of the luminosity function in the three BLAST bands. We find strong evolution out to z=1, in the sense that there is a large increase in the space-density of the most luminous galaxies. We have also investigated the evolution of the dust-mass function, finding similar strong evolution in the space-density of the galaxies with the largest dust masses, showing that the luminosity evolution seen in many wavebands is associated with an increase in the reservoir of interstellar matter in galaxies.Comment: Accepted for publication in the Astrophysical Journal. Maps and associated results are available at http://blastexperiment.info

Reconstructing the Inflaton Potential---in Principle and in Practice

Generalizing the original work by Hodges and Blumenthal, we outline a formalism which allows one, in principle, to reconstruct the potential of the inflaton field from knowledge of the tensor gravitational wave spectrum or the scalar density fluctuation spectrum, with special emphasis on the importance of the tensor spectrum. We provide some illustrative examples of such reconstruction. We then discuss in some detail the question of whether one can use real observations to carry out this procedure. We conclude that in practice, a full reconstruction of the functional form of the potential will not be possible within the foreseeable future. However, with a knowledge of the dark matter components, it should soon be possible to combine intermediate-scale data with measurements of large-scale cosmic microwave background anisotropies to yield useful information regarding the potential.Comment: 39 pages plus 2 figures (upon request:[email protected]), LaTeX, FNAL--PUB--93/029-A; SUSSEX-AST 93/3-

A systematic, intensive statistical investigation of data from the Comprehensive Analysis of Reported Drugs (CARD) for compliance and illicit opioid abstinence in substance addiction treatment with buprenorphine/naloxone

BACKGROUND: Buprenorphine and naloxone (bup/nal), a combination partial mu receptor agonist and low-dose delta mu antagonist, is presently recommended and used to treat opioid-use disorder. However, a literature review revealed a paucity of research involving data from urine drug tests that looked at compliance and abstinence in one sample. METHOD: Statistical analysis of data from the Comprehensive Analysis of Reported Drugs (CARD) was used to assess compliance and abstinence during treatment in a large cohort of bup/nal patients attending chemical-dependency programs from eastern USA in 2010 and 2011. RESULTS: Part 1: Bup/nal was present in 93.4% of first (n = 1,282; p \u3c.0001) and 92.4% of last (n = 1,268; p \u3c.0001) urine samples. Concomitantly, unreported illicit drugs were present in 47.7% (n = 655, p =.0261) of samples. Patients who were compliant to the bup/nal prescription were more likely than noncompliant patients to be abstinent during treatment (p =.0012; odds ratio = 1.69 with 95% confidence interval (1.210, 2.354). Part 2: An analysis of all samples collected in 2011 revealed a significant improvement in both compliance (p \u3c 2.2 × 1

BLAST: Correlations in the Cosmic Far-Infrared Background at 250, 350, and 500 microns Reveal Clustering of Star-Forming Galaxies

We detect correlations in the cosmic far-infrared background due to the clustering of star-forming galaxies in observations made with the Balloon-borne Large Aperture Submillimeter Telescope, BLAST, at 250, 350, and 500 microns. We perform jackknife and other tests to confirm the reality of the signal. The measured correlations are well fit by a power law over scales of 5-25 arcminutes, with Delta I/I = 15.1 +/- 1.7%. We adopt a specific model for submillimeter sources in which the contribution to clustering comes from sources in the redshift ranges 1.3 <= z <= 2.2, 1.5 <= z <= 2.7, and 1.7 <= z <= 3.2, at 250, 350, and 500 microns, respectively. With these distributions, our measurement of the power spectrum, P(k_theta), corresponds to linear bias parameters, b = 3.8 +/- 0.6, 3.9 +/- 0.6 and 4.4 +/- 0.7, respectively. We further interpret the results in terms of the halo model, and find that at the smaller scales, the simplest halo model fails to fit our results. One way to improve the fit is to increase the radius at which dark matter halos are artificially truncated in the model, which is equivalent to having some star-forming galaxies at z >= 1 located in the outskirts of groups and clusters. In the context of this model we find a minimum halo mass required to host a galaxy is log (M_min / M_sun) = 11.5 (+0.4/-0.1), and we derive effective biases $b_eff = 2.2 +/- 0.2, 2.4 +/- 0.2, and 2.6 +/- 0.2, and effective masses log (M_eff / M_sun) = 12.9 +/- 0.3, 12.8 +/- 0.2, and 12.7 +/- 0.2, at 250, 350, and 500 microns, corresponding to spatial correlation lengths of r_0 = 4.9, 5.0, and 5.2 +/- 0.7 h^-1 Mpc, respectively. Finally, we discuss implications for clustering measurement strategies with Herschel and Planck.Comment: Accepted for publication in the Astrophysical Journal. Maps and other results available at http://blastexperiment.info

Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery: a multicenter, randomized, controlled, double-blinded trial.

UNLABELLED: In this randomized, prospective, double-blinded clinical trial, we sought to investigate whether diaspirin-crosslinked hemoglobin (DCLHb) can reduce the perioperative use of allogeneic blood transfusion. One-hundred-eighty-one elective surgical patients were enrolled at 19 clinical sites from 1996 to 1998. Selection criteria included anticipated transfusion of 2-4 blood units, aortic repair, and major joint or abdomino-pelvic surgery. Once a decision to transfuse had been made, patients received initially up to 3 250-mL infusions of 10% DCLHb (n = 92) or 3 U of packed red blood cells (PRBCs) (n = 89). DCLHb was infused during a 36-h perioperative window. On the day of surgery, 58 of 92 (64%; confidence interval [CI], 54%-74%) DCLHb-treated patients received no allogeneic PRBC transfusions. On Day 1, this number was 44 of 92 (48%; CI, 37%-58%) and decreased further until Day 7, when it was 21 of 92 (23%; CI, 15%-33%). During the 7-day period, 2 (1-4) units of PRBC per patient were used in the DCLHb group compared with 3 (2-4) units in the control patients (P = 0.002; medians and 25th and 75th percentiles). Mortality (4% and 3%, respectively) and incidence of suffering at least one serious adverse event (21% and 15%, respectively) were similar in DCLHb and PRBC groups. The incidence of jaundice, urinary side effects, and pancreatitis were more frequent in DCLHb patients. The study was terminated early because of safety concerns. Whereas the side-effect profile of modified hemoglobin solutions needs to be improved, our data show that hemoglobin solutions can be effective at reducing exposure to allogeneic blood for elective surgery. IMPLICATIONS: In a randomized, double-blinded red blood cell controlled, multicenter trial, diaspirin-crosslinked hemoglobin spared allogeneic transfusion in 23% of patients undergoing elective noncardiac surgery. The observed side-effect profile indicates a need for improvement in hemoglobin development

Increased ventral striatal volume in college-aged binge drinkers

BACKGROUND Binge drinking is a serious public health issue associated with cognitive, physiological, and anatomical differences from healthy individuals. No studies, however, have reported subcortical grey matter differences in this population. To address this, we compared the grey matter volumes of college-age binge drinkers and healthy controls, focusing on the ventral striatum, hippocampus and amygdala. METHOD T1-weighted images of 19 binge drinkers and 19 healthy volunteers were analyzed using voxel-based morphometry. Structural data were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Cluster-extent threshold and small volume corrections were both used to analyze imaging data. RESULTS Binge drinkers had significantly larger ventral striatal grey matter volumes compared to controls. There were no between group differences in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal volumes were also negatively related to AUDIT scores across groups. CONCLUSIONS Our findings stand in contrast to the lower ventral striatal volume previously observed in more severe forms of alcohol use disorders, suggesting that college-age binge drinkers may represent a distinct population from those groups. These findings may instead represent early sequelae, compensatory effects of repeated binge and withdrawal, or an endophenotypic risk factor