Study of gains made through remedial reading instruction

Thesis (Ed. M.)--Boston University, 1940. N.B.: page 18 appears to be missing from this thesis. We believe this to be a page numbering error on the author's part. No actual content seems to be missing

Erratum to: The in vitro toxicity of venoms from South Asian Hump-nosed pit vipers (Viperidae: Hypnale)

Hump-nosed pit vipers (Genus Hypnale) are venomous snakes from South India and Sri Lanka. Envenoming by Hypnale species may cause significant morbidity and is characterized by local envenoming and less commonly coagulopathy and acute renal failure. Currently there are three nominal species of this genus: H. hypnale, H. zara and H. nepa. This study investigates the biochemical and pharmacological properties of the venoms from the three Hypnale species in Sri Lanka. The three Hypnale venoms had similar chromatographic profiles using reverse phase high performance liquid chromatography and fractions with procoagulant activity were identified. Hypnale venoms had potent cytotoxicity in cultured rat aorta smooth muscle cells with similar IC50 values. The venoms had weak neurotoxic and myotoxic activity in the isolated chick biventer muscle preparation. They had mild procoagulant activity with close MCC5 values and also phospholipase activity. Locally available polyvalent antivenom did not neutralise any venom effects. The study demonstrates that the three Hypnale venoms are similar and cytotoxicity appears to be the most potent effect, although they have mild procoagulant activity. These findings are consistent with clinical reports

Hypervelocity Stars: From the Galactic Center to the Halo

Hypervelocity stars (HVS) traverse the Galaxy from the central black hole to the outer halo. We show that the Galactic potential within 200 pc acts as a high pass filter preventing low velocity HVS from reaching the halo. To trace the orbits of HVS throughout the Galaxy, we construct two forms of the potential which reasonably represent the observations in the range 5--100,000 pc, a simple spherically symmetric model and a bulge-disk-halo model. We use the Hills mechanism (disruption of binaries by the tidal field of the central black hole) to inject HVS into the Galaxy and compute the observable spatial and velocity distributions of HVS with masses in the range 0.6--4 Msun. These distributions reflect the mass function in the Galactic Center, properties of binaries in the Galactic Center, and aspects of stellar evolution and the injection mechanism. For 0.6--4 Msun main sequence stars, the fraction of unbound HVS and the asymmetry of the velocity distribution for their bound counterparts increases with stellar mass. The density profiles for unbound HVS decline with distance from the Galactic Center approximately as r^{-2} (but are steeper for the most massive stars which evolve off the main sequence during their travel time from the Galactic Center); the density profiles for the bound ejecta decline with distance approximately as r^{-3}. In a survey with a limiting visual magnitude V of 23, the detectability of HVS (unbound or bound) increases with stellar mass.Comment: 32 pages of text, 5 tables, 12 figures, ApJ, accepted; revisions: corrected typos, added references, clarified some aspects of potential model and physical processes affecting relative frequency of HVS

Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study

Background: The presence of measles virus (MV) RNA in bowel tissue from children with autism spectrum disorders (ASD) and gastrointestinal (GI) disturbances was reported in 1998. Subsequent investigations found no associations between MV exposure and ASD but did not test for the presence of MV RNA in bowel or focus on children with ASD and GI disturbances. Failure to replicate the original study design may contribute to continued public concern with respect to the safety of the measles, mumps, and rubella (MMR) vaccine. Methodology/Principal Findings: The objective of this case-control study was to determine whether children with GI disturbances and autism are more likely than children with GI disturbances alone to have MV RNA and/or inflammation in bowel tissues and if autism and/or GI episode onset relate temporally to receipt of MMR. The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls) were evaluated by real-time reverse transcription (RT)-PCR for presence of MV RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported. The temporal order of onset of GI episodes and autism relative to timing of MMR administration was examined. We found no differences between case and control groups in the presence of MV RNA in ileum and cecum. Results were consistent across the three laboratory sites. GI symptom and autism onset were unrelated to MMR timing. Eighty-eight percent of ASD cases had behavioral regression. Conclusions/Significance: This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

A turbidimetric assay for the measurement of clotting times of procoagulant venoms in plasma

Assessment of the procoagulant effect of snake venoms is important for understanding their effects. The aim of this study was to develop a simple automated method to measure clotting times to assess procoagulant venoms. A turbidimetric assay was developed which monitors changes in optical density when plasma and venom are mixed. Plasma was added simultaneously to venom solutions in a 96 well microtitre plate. After mixing, the optical density at 340 nm was monitored in a microplate reader every 30 s over 30 min. The clotting time was defined as the lag time until the absorbance sharply increased. The turbidimetric method was compared to manual measurement of the clotting time defined as the time when a strand of fibrin can be drawn out of the mixture. The two methods were done simultaneously, with the same venom and plasma, and compared by plotting the manual versus turbidimetric clotting times. Within-day and between-day runs were done and the coefficient of variation (CV) was calculated. Plots comparing manual clotting times to the lag time in the turbidimetric assay showed good correlation between the two methods for brown snake (Pseudonaja textilis) venom, including 24 determinations in triplicate over six days for seven different venom concentrations. Good correlation was also found for four other venoms: tiger snake (Notechis scutatus), Carpet viper (Echis carinatus), Russell's viper (Daboia russelii) and Malaysian pit piper (Calloselasma rhodostoma). Between-day CV was in the range 10–20% for both methods, while within-day CV < 10%. The turbidimetric assay appears to be a simple and convenient automated method for the measurement of clotting times to assess the effects of procoagulant venoms

Diagnosis of snake envenomation using a simple phospholipase A₂ assay

Diagnosis of snake envenomation is challenging but critical for deciding on antivenom use. Phospholipase A₂ enzymes occur commonly in snake venoms and we hypothesized that phospholipase activity detected in human blood post-bite may be indicative of envenomation. Using a simple assay, potentially a bedside test, we detected high phospholipase activity in sera of patients with viper and elapid envenomation compared to minimal activity in non-envenomed patients

Tiger snake (Notechis spp) envenoming: Australian Snakebite Project (ASP-13)

Objectives: To describe the clinical syndrome associated with definite tiger snake (Notechis spp) envenoming and to examine the ability of tiger snake antivenom (TSAV) to bind free venom in vivo. Design, setting and participants: We conducted a prospective cohort study within the Australian Snakebite Project, reviewing all definite tiger snake envenoming cases between October 2004 and June 2011. Definite cases were identified by venom-specific enzyme immunoassay or expert snake identification. Main outcome measures: Clinical effects of tiger snake envenoming; peak venom concentrations; number of vials of antivenom administered. Results: Fifty-six definite tiger snake envenomings were identified. Clinical effects included venom-induced consumption coagulopathy (VICC) (n=53), systemic symptoms (n = 45), myotoxicity (n =11) and neurotoxicity (n=17). Thrombotic microangiopathy occurred in three patients, all of whom developed acute renal failure. There were no deaths. A bite-site snake venom detection kit test was done in 44 patients, but was positive for tiger snake in only 33 cases. Fifty-three patients received TSAV and eight of these patients had immediate hypersensitivity reactions, severe enough in one case to satisfy diagnostic criteria for severe anaphylaxis. The median peak venom concentration in 50 patients with pretreatment blood samples available was 3.2 ng/mL (interquartile range [IQR], 1–12 ng/mL; range 0.17–152 ng/mL). In 49 patients with post-treatment blood samples available, no venom was detected in serum after the first antivenom dose. Ten patients were given 1 vial of TSAV; the median dose was 2 vials (range, 1–4 vials). Pretreatment serum venom concentrations did not vary significantly between patients given 1 vial of TSAV and those given 2 or more vials. Conclusion: Tiger snake envenoming causes VICC, systemic symptoms, neurotoxicity and myotoxicity. One vial of TSAV, the dose originally recommended when the antivenom was first made available, appears to be sufficient to bind all circulating venom

Efficacy of Indian polyvalent snake antivenoms against Sri Lankan snake venoms: lethality studies or clinically focussed <i>in vitro</i> studies

<i>In vitro</i> antivenom efficacy studies were compared to rodent lethality studies to test two Indian snake antivenoms (VINS and BHARAT) against four Sri Lankan snakes. <i>In vitro</i> efficacy was tested at venom concentrations consistent with human envenoming. Efficacy was compared statistically for one batch from each manufacturer where multiple vials were available. In binding studies EC₅₀ for all VINS antivenoms were less than BHARAT for <i>D. russelii</i> [553 μg/mL vs. 1371 μg/mL;p=0.016), but were greater for VINS antivenoms compared to BHARAT for <i>N. naja</i> [336 μg/mL vs. 70 μg/mL;p<0.0001]. EC₅₀ of both antivenoms was only slighty different for <i>E. carinatus</i> and <i>B. caeruleus</i>. For procoagulant activity neutralisation, the EC₅₀ was lower for VINS compared to BHARAT - 60 µg/mL vs. 176 µg/mL (p<0.0001) for Russell's viper and 357 µg/mL vs. 6906µg/mL (p<0.0001) for Saw-scaled viper. Only VINS antivenom neutralized <i>in vitro</i> neurotoxicity of krait venom. Both antivenoms partially neutralized cobra and didn't neutralize Russell's viper neurotoxicity. Lethality studies found no statistically significant difference in ED₅₀ values between VINS and BHARAT antivenoms. VINS antivenoms appeared superior to BHARAT at concentrations equivalent to administering 10 vials antivenom, based on binding and neutralisation studies. Lethality studies were inconsistent suggesting rodent death may not measure relevant efficacy outcomes in humans