Developmental toxicity study of sodium molybdate dihydrate administered in the diet to Sprague Dawley rats

AbstractMolybdenum is an essential nutrient for humans and animals and is a constituent of several important oxidase enzymes. It is normally absorbed from the diet and to a lesser extent from drinking water and the typical human intake is around 2μg/kg bodyweight per day. No developmental toxicity studies to contemporary standards have been published and regulatory decisions have been based primarily on older studies where the nature of the test material, or the actual dose levels consumed is uncertain.In the current study the developmental toxicity of sodium molybdate dihydrate as a representative of a broad class of soluble molybdenum(VI) compounds, was given in the diet to Sprague Dawley rats in accordance with OECD Test Guideline 414. Dose levels of 0, 3, 10, 20 and 40mgMo/kgbw/day were administered from GD6 to GD20. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed. The NOAEL observed in this study was 40mgMo/kgbw/day, the highest dose tested

Natural history of chronic mitral insufficiency: Relation of peak systolic pressure/end-systolic volume ratio to morbidity and mortality

The ratio of peak systolic pressure to end-systolic volume (PSP/ESV) is a measure of contractility that is relatively independent of loading conditions. To define the relation of this index to the natural history of chronic mitral insufficiency, follow-up studies were performed in 76 patients. All had isolated mitral insufficiency and were followed up for an average of 48 months. None underwent surgery. Cardiac volumes, ejection fraction and PSP/ESV ratio were calculated and Cox multiple regression analyses were performed to determine the relation of functional status, ejection fraction and PSP/ESV ratio to morbidity and mortality.Twenty-three patients died during follow-up; in 70% of those who died, the PSP/ESV ratio was reduced below the 20th percentile. However, as an independent predictor of mortality, this ratio was less sensitive (p>0.05) than ejection fraction (p < 0.01). Similarly, functional status change was predicted more accurately by ejection fraction (p < 0.01) than by the PSP/ESV ratio (p>0.05). Thus, although a decreased PSP/ESV ratio was associated with a higher mortality rate, other clinical and laboratory variables were superior to this index for determining morbidity and mortality in patients with isolated mitral insufficiency

Antibiotic prophylaxis is associated with subsequent resistant infections in children with an initial extended-spectrum-cephalosporin-resistant Enterobacteriaceae infection

ABSTRACT The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae . We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged &lt;22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and fumC-fimH ( E. coli ) or tonB ( Klebsiella pneumoniae ) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections. </jats:p

Survival and growth responses of eight Everglades tree species along an experimental hydrological gradient on two tree island types

Questions: How are the early survival and growth of seedlings of Everglades tree species planted in an experimental setting on artificial tree islands affected by hydrology and substrate type? What are the implications of these responses for broader tree island restoration efforts? Location: Loxahatchee Impoundment Landscape Assessment (LILA), Boynton Beach, Florida, USA. Methods: An experiment was designed to test hydrological and substrate effects on seedling growth and survivorship. Two islands – a peat and a limestone-core island representing two major types found in the Everglades – were constructed in four macrocosms. A mixture of eight tree species was planted on each island in March of 2006 and 2007. Survival and height growth of seedlings planted in 2006 were assessed periodically during the next two and a half years. Results: Survival and growth improved with increasing elevation on both tree island substrate types. Seedlings\u27 survival and growth responses along a moisture gradient matched species distributions along natural hydrological gradients in the Everglades. The effect of substrate on seedling performance showed higher survival of most species on the limestone tree islands, and faster growth on their peat-based counterparts. Conclusions: The present results could have profound implications for restoration of forests on existing landforms and artificial creation of tree islands. Knowledge of species tolerance to flooding and responses to different edaphic conditions present in wetlands is important in selecting suitable species to plant on restored tree island

Supersaturating silicon with transition metals by ion implantation and pulsed laser melting

We investigate the possibility of creating an intermediate band semiconductor by supersaturating Si with a range of transition metals (Au, Co, Cr, Cu, Fe, Pd, Pt, W, and Zn) using ion implantation followed by pulsed laser melting (PLM). Structural characterization shows evidence of either surface segregation or cellular breakdown in all transition metals investigated, preventing the formation of high supersaturations. However, concentration-depth profiling reveals that regions of Si supersaturated with Au and Zn are formed below the regions of cellular breakdown. Fits to the concentration-depth profile are used to estimate the diffusive speeds, v D, of Au and Zn, and put lower bounds on v D of the other metals ranging from 10² to 10⁴ m/s. Knowledge of v D is used to tailor the irradiation conditions and synthesize single-crystal Si supersaturated with 10¹⁹ Au/cm³ without cellular breakdown. Values of v D are compared to those for other elements in Si. Two independent thermophysical properties, the solute diffusivity at the melting temperature, D s(T m), and the equilibrium partition coefficient, k e, are shown to simultaneously affect v D. We demonstrate a correlation between v D and the ratio D s(T m)/k e ⁰·⁶⁷, which is exhibited for Group III, IV, and V solutes but not for the transition metals investigated. Nevertheless, comparison with experimental results suggests that D s(T m)/k e ⁰·⁶⁷ might serve as a metric for evaluating the potential to supersaturate Si with transition metals by PLM.Research at Harvard was supported by The U.S. Army Research Office under contracts W911NF-12-1-0196 and W911NF-09-1-0118. M.T.W. and T.B.’s work was supported by the U.S. Army Research Laboratory and the U.S. Army Research Office under Grant No. W911NF-10-1-0442, and the National Science Foundation (NSF) Faculty Early Career Development Program ECCS-1150878 (to T.B.). M.J.S., J.T.S., M.T.W., T.B., and S.G. acknowledge a generous gift from the Chesonis Family Foundation and support in part by the National Science Foundation (NSF) and the Department of Energy (DOE) under NSF CA No. EEC- 1041895. S.C. and J.S.W.’s work was supported by The Australian Research Council. J.M. was supported by a National Research Council Research Associateship

Supersaturating silicon with transition metals by ion implantation and pulsed laser melting

We investigate the possibility of creating an intermediate band semiconductor by supersaturating Si with a range of transition metals (Au, Co, Cr, Cu, Fe, Pd, Pt, W, and Zn) using ion implantation followed by pulsed laser melting (PLM). Structural characterization shows evidence of either surface segregation or cellular breakdown in all transition metals investigated, preventing the formation of high supersaturations. However, concentration-depth profiling reveals that regions of Si supersaturated with Au and Zn are formed below the regions of cellular breakdown. Fits to the concentration-depth profile are used to estimate the diffusive speeds, v [subscript D], of Au and Zn, and put lower bounds on v [subscript D] of the other metals ranging from 10[superscript 2] to 10[superscript 4] m/s. Knowledge of v [subscript D] is used to tailor the irradiation conditions and synthesize single-crystal Si supersaturated with 10[superscript 19] Au/cm[superscript 3] without cellular breakdown. Values of v [subscript D] are compared to those for other elements in Si. Two independent thermophysical properties, the solute diffusivity at the melting temperature, D [subscript s](T [subscript m]), and the equilibrium partition coefficient, k [subscript e], are shown to simultaneously affect v [subscript D]. We demonstrate a correlation between v [subscript D] and the ratio D [subscript s](T [subscript m])/k [subscript e] [superscript 0.67], which is exhibited for Group III, IV, and V solutes but not for the transition metals investigated. Nevertheless, comparison with experimental results suggests that D [subscript s](T [subscript m])/k [subscript e] [superscript 0.67] might serve as a metric for evaluating the potential to supersaturate Si with transition metals by PLM.National Science Foundation (U.S.) (Faculty Early Career Development Program ECCS-1150878)Chesonis Family FoundationUnited States. Army Research Laboratory (United States. Army Research Office Grant W911NF-10-1-0442)National Science Foundation (U.S.) (United States. Dept. of Energy NSF CA EEC-1041895

OGLE-2005-BLG-071Lb, the Most Massive M-Dwarf Planetary Companion?

We combine all available information to constrain the nature of OGLE-2005-BLG-071Lb, the second planet discovered by microlensing and the first in a high-magnification event. These include photometric and astrometric measurements from Hubble Space Telescope, as well as constraints from higher order effects extracted from the ground-based light curve, such as microlens parallax, planetary orbital motion and finite-source effects. Our primary analysis leads to the conclusion that the host of Jovian planet OGLE-2005-BLG-071Lb is an M dwarf in the foreground disk with mass M= 0.46 +/- 0.04 Msun, distance D_l = 3.3 +/- 0.4 kpc, and thick-disk kinematics v_LSR ~ 103 km/s. From the best-fit model, the planet has mass M_p = 3.8 +/- 0.4 M_Jup, lies at a projected separation r_perp = 3.6 +/- 0.2 AU from its host and so has an equilibrium temperature of T ~ 55 K, i.e., similar to Neptune. A degenerate model less favored by \Delta\chi^2 = 2.1 (or 2.2, depending on the sign of the impact parameter) gives similar planetary mass M_p = 3.4 +/- 0.4 M_Jup with a smaller projected separation, r_\perp = 2.1 +/- 0.1 AU, and higher equilibrium temperature T ~ 71 K. These results from the primary analysis suggest that OGLE-2005-BLG-071Lb is likely to be the most massive planet yet discovered that is hosted by an M dwarf. However, the formation of such high-mass planetary companions in the outer regions of M-dwarf planetary systems is predicted to be unlikely within the core-accretion scenario. There are a number of caveats to this primary analysis, which assumes (based on real but limited evidence) that the unlensed light coincident with the source is actually due to the lens, that is, the planetary host. However, these caveats could mostly be resolved by a single astrometric measurement a few years after the event.Comment: 51 pages, 12 figures, 3 tables, Published in Ap

Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities