The speaking vocabulary of 454 third grade children.

Thesis (Ed.M.)--Boston Universit

Timing and placing samplings to optimally calibrate a reactive transport model: exploring the potential for <i>Escherichia coli</i> in the Scheldt estuary

For the calibration of any model, measurements are necessary. As measurements are expensive, it is of interest to determine beforehand which kind of samples will provide the maximum of information. Using a criterion related to the Fisher information matrix, it is possible to design a sampling scheme that will enable the most precise model parameter estimates. This approach was applied to a reactive transport model (based on SLIM) of Escherichia coli in the Scheldt Estuary. As this estuary is highly influenced by the tide, it is expected that careful timing of the samples with respect to the tidal cycle will have an effect on the quality of the data. The timing and also the positioning of samples were optimised according to the proposed criterion. In the investigated case studies the precision of the estimated parameters could be improved by up to a factor of ten, confirming the usefulness of this approach to maximize the amount of information that can be retrieved from a fixed number of samples

Prognostic factors and treatment-effect modifiers in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with Type 1 SMA do not achieve major motor milestones, and death from respiratory failure typically occurs before 2 years. Individuals with Types 2 and 3 SMA exhibit milder phenotypes and have better functional and survival outcomes. Herein, a systematic literature review was conducted to identify factors that influence the prognosis of Types 1, 2 and 3 SMA. In untreated infants with Type 1 SMA, absence of symptoms at birth, a later symptom onset and a higher survival of motor neuron 2 (SMN2) copy number are all associated with increased survival. Disease duration, age at treatment initiation and, to a lesser extent, baseline function were identified as potential treatment-modifying factors for survival, emphasizing that early treatment with disease-modifying therapies (DMT) is essential in Type 1 SMA. In patients with Types 2 and 3 SMA, factors considered prognostic of changes in motor function were SMN2 copy number, age and ambulatory status. Individuals aged 6-15 years were particularly vulnerable to developing complications (scoliosis and progressive joint contractures) which negatively influence functional outcomes and may also affect the therapeutic response in patients. Age at the time of treatment initiation emerged as a treatment-effect modifier on the outcome of DMTs. Factors identified in this review should be considered prior to designing or analyzing studies in an SMA population, conducting population matching or summarizing results from different studies on the treatments for SMA

Spectrometric Monitoring of Atmospheric Carbon Tetrafluoride (CF4) Above the Jungfraujoch Station Since 1989: Evidence of Continued Increase But at a Slowing Rate

The long-term evolution of the vertical column abundance of carbon tetrafluoride (CF4) above the high-altitude Jungfraujoch station (Swiss Alps, 46.5 ° N, 8.0 ° E, 3580 ma.s.l.) has been derived from the spectrometric analysis of Fourier transform infrared solar spectra recorded at that site between 1989 and 2012. The investigation is based on a multi-microwindow approach, two encompassing pairs of absorption lines belonging to the R-branch of the strong ν3 band of CF4 centered at 1283 cm-1, and two additional ones to optimally account for weak but overlapping HNO3 interferences. The analysis reveals a steady accumulation of the very long-lived CF4 above the Jungfraujoch at mean rates of (1.38 ± 0.11) x 1013 molec cm-2 yr-1 from 1989 to 1997, and (0.98 +/- 0.02) x 1013 molec cm-2 yr-1 from 1998 to 2012, which correspond to linear growth rates of 1.71 ± 0.14 and 1.04 ± 0.02% yr-1 respectively referenced to 1989 and 1998. Related global CF4 anthropogenic emissions required to sustain these mean increases correspond to 15.8 ±1.3 and 11.1 ± 0.2 Gg yr-1 over the above specified time intervals. Findings reported here are compared and discussed with respect to relevant northern mid-latitude results obtained remotely from space and balloons as well as in situ at the ground, including new gas chromatography mass spectrometry measurements performed at the Jungfraujoch since 2010

FIRST PALAEOBOTANICAL DATA FROM THE UPPER DEVONIAN BOLLONCILLOS FORMATION (ZARAGOZA PROVINCE, NE IBERIAN PENINSULA)

peer reviewe

Carbon monoxide (CO) and ethane (C₂H₆) trends from ground-based solar FTIR measurements at six European stations, comparison and sensitivity analysis with the EMEP model

Trends in the CO and C2H6 partial columns (~0–15 km) have been estimated from four European groundbasedsolar FTIR (Fourier Transform InfraRed) stations for the 1996–2006 time period. The CO trends from the four stations Jungfraujoch, Zugspitze, Harestua and Kiruna have been estimated to −0.45±0.16%yr−1, −1.00 ± 0.24%yr−1, −0.62±0.19%yr−1 and −0.61±0.16%yr−1, respectively. The corresponding trends for C2H6 are−1.51±0.23%yr−1, −2.11±0.30%yr−1, −1.09±0.25%yr−1 and −1.14±0.18%yr−1. All trends are presented with their 2-σ confidence intervals. To find possible reasons for the CO trends, the global-scale EMEP MSC-W chemical transport model has been used in a series of sensitivity scenarios. It is shown that the trends are consistent with the combination of a 20% decrease in the anthropogenic CO emissions seen in Europe and North America during the 1996–2006 period and a 20% increase in the anthropogenic CO emissions in East Asia, during the same time period. The possible impacts of CH4 and biogenic volatile organic compounds (BVOCs) are also considered. The European and global-scale EMEP models have been evaluated against the measured CO and C2H6 partial columns from Jungfraujoch, Zugspitze, Bremen, Harestua, Kiruna and Ny-Ålesund. The European model reproduces, on average the measurements at the different sites fairly well and within 10–22% deviation for CO and 14–31% deviation for C2H6. Their seasonal amplitude is captured within 6–35% and 9–124% for CO and C2H6, respectively. However, 61–98% of the CO and C2H6 partial columns in the European model are shown to arise from the boundary conditions, making the globalscale model a more suitable alternative when modeling these two species. In the evaluation of the global model the average partial columns for 2006 are shown to be within 1–9% and 37–50% of the measurements for CO and C2H6, respectively. The global model sensitivity for assumptions made in this paper is also analyzed

Risdiplam in Type 1 Spinal Muscular Atrophy

BACKGROUND: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. METHODS: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. RESULTS: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. CONCLUSIONS: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.)

Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer

Background Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promote tumor development and to be a good target for cancer treatment. Most studies to date have used human mesothelin in immunocompromised mice. Since these models do not allow for study of the natural immune response to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so the effects of this protein can be assessed in immunocompetent mouse strains. Methods We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo. Results We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorage-independent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice. Conclusion The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice