Streamflow Forecast of Bear River at Harer, Idaho

The primary objective of this thesis is to make an accurate stream flow forecast for the Bear River at Harer, Idaho in order to provide helpful information for the operation of the largest reservoir in the Bear River System and in guiding cropping programs in the watershed

Dynamically-Coupled Oscillators -- Cooperative Behavior via Dynamical Interaction --

We propose a theoretical framework to study the cooperative behavior of dynamically coupled oscillators (DCOs) that possess dynamical interactions. Then, to understand synchronization phenomena in networks of interneurons which possess inhibitory interactions, we propose a DCO model with dynamics of interactions that tend to cause 180-degree phase lags. Employing an approach developed here, we demonstrate that although our model displays synchronization at high frequencies, it does not exhibit synchronization at low frequencies because this dynamical interaction does not cause a phase lag sufficiently large to cancel the effect of the inhibition. We interpret the disappearance of synchronization in our model with decreasing frequency as describing the breakdown of synchronization in the interneuron network of the CA1 area below the critical frequency of 20 Hz.Comment: 10 pages, 3 figure

Isolation and identification of a male-produced aggregation-sex pheromone for the velvet longhorned beetle, Trichoferus campestris.

The velvet longhorned beetle, Trichoferus campestris (Faldermann) ("VLB"; Coleoptera: Cerambycidae), is native to eastern Asia where it infests and damages a wide range of deciduous and coniferous tree species, including orchard and timber species. Immature stages of VLB are transported to new countries via international commerce, and populations have established outside the native range of the species. Here, we show that identification of pheromones of invasive pest species can be expedited by knowledge of the semiochemistry of related taxa. Histological sectioning revealed subcuticular, male-specific prothoracic glands connected to pits in the cuticle, which, in related species, are diagnostic for production of male-produced aggregation-sex pheromones, usually characterized by 2,3-alkanediol/hydroxyketone structural motifs. However, in preliminary field bioassays, beetles were not attracted by any known cerambycid pheromones. Subsequently, we identified a novel variant of the hydroxyketone motif ("trichoferone") from headspace volatiles of males. In field bioassays, synthetic trichoferone was more attractive to both sexes of VLB than previously developed high-release-rate ethanol lures, and attraction was strongly female biased. This study demonstrated the utility of the prothoracic gland trait for predicting pheromone use in cerambycid species in the subfamily Cerambycinae, and that identification of pheromones of novel species can be expedited by knowledge of pheromones of related species. Trichoferone should prove to be a valuable tool for detection of VLB in regions where the beetle is or may become established

Stress and pore pressure histories in complex tectonic settings predicted with coupled geomechanical-fluid flow models

Most of the methods currently used for pore pressure prediction in sedimentary basins assume one dimensional compaction based on relationships between vertical effective stress and porosity. These methods may be inaccurate in complex tectonic regimes where stress tensors are variable. Modelling approaches for compaction adopted within the geotechnical field account for both the full three dimensional stress tensor and the stress history. In this paper a coupled geomechanical-fluid flow model is used, along with an advanced version of the Cam-Clay constitutive model, to investigate stress,pore pressure and porosity in a Gulf of Mexico style mini-basin bounded by salt subjected to lateral deformation. The modelled structure consists of two depocentres separated by a salt diapir. 20% of horizontal shortening synchronous to basin sedimentation is imposed. An additional model accounting solely for the overpressure generated due to 1D disequilibrium compaction is also defined. The predicted deformation regime in the two depocentres of the mini-basin is one of tectonic lateral compression, in which the horizontal effective stress is higher than the vertical effective stress. In contrast, sediments above the central salt diapir show lateral extension and tectonic vertical compaction due to the rise of the diapir. Compared to the 1D model, the horizontal shortening in the mini-basin increases the predicted present-day overpressure by 50%, from 20 MPa to 30 MPa. The porosities predicted by the mini-basin models are used to perform 1D, porosity-based pore pressure predictions. The 1D method underestimated overpressure by up to 6 MPa at 3400 m depth (26% of the total overpressure) in the well located at the basin depocentre and up to 3 MPa at 1900 m depth (34% of the total overpressure) in the well located above the salt diapir. The results show how 2D/3D methods are required to accurately predict overpressure in regions in which tectonic stresses are important

Optimizing DNA Extraction Methods for Nanopore Sequencing of Neisseria gonorrhoeae Directly from Urine Samples

Empirical gonorrhea treatment at initial diagnosis reduces onward transmission. However, increasing resistance to multiple antibiotics may necessitate waiting for culture-based diagnostics to select an effective treatment. There is a need for same-day culture-free diagnostics that identify infection and detect antimicrobial resistance. We investigated if Nanopore sequencing can detect sufficient Neisseria gonorrhoeae DNA to reconstruct whole genomes directly from urine samples. We used N. gonorrhoeae-spiked urine samples and samples from gonorrhea infections to determine optimal DNA extraction methods that maximize the amount of N. gonorrhoeae DNA sequenced while minimizing contaminating host DNA. In simulated infections, the Qiagen UCP pathogen mini kit provided the highest ratio of N. gonorrhoeae to human DNA and the most consistent results. Depletion of human DNA with saponin increased N. gonorrhoeae yields in simulated infections but decreased yields in clinical samples. In 10 urine samples from men with symptomatic urethral gonorrhea, ≥92.8% coverage of an N. gonorrhoeae reference genome was achieved in all samples, with ≥93.8% coverage breath at ≥10-fold depth in 7 (70%) samples. In simulated infections, if ≥104 CFU/ml of N. gonorrhoeae was present, sequencing of the large majority of the genome was frequently achieved. N. gonorrhoeae could also be detected from urine in cobas PCR medium tubes and from urethral swabs and in the presence of simulated Chlamydia coinfection. Using Nanopore sequencing of urine samples from men with urethral gonorrhea, sufficient data can be obtained to reconstruct whole genomes in the majority of samples without the need for culture

A Flexible Multi-Metric Bayesian Framework for Decision-Making in Phase II Multi-Arm Multi-Stage Studies

We propose a multi-metric flexible Bayesian framework to support efficient interim decision-making in multi-arm multi-stage phase II clinical trials. Multi-arm multi-stage phase II studies increase the efficiency of drug development, but early decisions regarding the futility or desirability of a given arm carry considerable risk since sample sizes are often low and follow-up periods may be short. Further, since intermediate outcomes based on biomarkers of treatment response are rarely perfect surrogates for the primary outcome and different trial stakeholders may have different levels of risk tolerance, a single hypothesis test is insufficient for comprehensively summarizing the state of the collected evidence. We present a Bayesian framework comprised of multiple metrics based on point estimates, uncertainty, and evidence towards desired thresholds (a Target Product Profile, TPP) for 1) ranking of arms and 2) comparison of each arm against an internal control. Using a large public-private partnership targeting novel TB arms as a motivating example, we find via simulation study that our multi-metric framework provides sufficient confidence for decision-making with sample sizes as low as 30 patients per arm, even when intermediate outcomes have only moderate correlation with the primary outcome. Our reframing of trial design and the decision-making procedure has been well-received by research partners and is a practical approach to more efficient assessment of novel therapeutics.Comment: 16 pages, 6 main text figures, 3 supplemental figure

External and internal noise surveys of London primary schools

Internal and external noise surveys have been carried out around schools in London, UK, to provide information on typical levels and sources to which children are exposed while at school. Noise levels were measured outside 142 schools, in areas away from flightpaths into major airports. 86% of the schools surveyed were exposed to noise from road traffic, the average external noise level outside a school being 57 dB LAeq. Detailed internal noise surveys have been carried out in 140 classrooms in 16 schools, together with classroom observations. It was found that noise levels inside classrooms depend upon the activities in which the children are engaged, with a difference of 20 dB LAeq between the 'quietest' and 'noisiest' activities. The average background noise level in classrooms exceeds the level recommended in current standards. The number of children in the classroom was found to affect noise levels. External noise influenced internal noise levels only when children were engaged in the quietest classroom activities. The effects of the age of the school buildings and types of window upon internal noise were examined but results were inconclusive

Electron-beam propagation in a two-dimensional electron gas

A quantum mechanical model based on a Green's function approach has been used to calculate the transmission probability of electrons traversing a two-dimensional electron gas injected and detected via mode-selective quantum point contacts. Two-dimensional scattering potentials, back-scattering, and temperature effects were included in order to compare the calculated results with experimentally observed interference patterns. The results yield detailed information about the distribution, size, and the energetic height of the scattering potentials.Comment: 7 pages, 6 figure

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)Publisher PDFPeer reviewe