Developing locally-driven (shoreline) monitoring programs in the Salish Sea (and beyond)

During the development of the Bainbridge Island Shoreline Monitoring Program (SMP), a volunteer group of scientists and engineers (Bainbridge Island Environmental Technical Advisory (ETAC)), provided the City of Bainbridge Island (COBI) City Council and staff with advice and recommendations on relevant shoreline science and the SMP. One of the recommendations was for COBI to adopt and initiate a locally–driven and -managed monitoring program to address both the effectiveness of the SMP over time, and uncertainties in knowledge of specific Bainbridge Island shoreline drivers and processes. The program would be designed to integrate past and current studies by COBI and other agencies and researchers and historical data, initiate new studies as needed, develop partnerships, and leverage multiple resources to assess baseline and future conditions of the Bainbridge shoreline. This presentation will provide a background of how the monitoring program initially evolved; how it seeks to integrate a variety of tools (including citizen science, local knowledge, interagency coordination, joint fact-finding); why such a program is important for locally-driven decision-making about shoreline management in Puget Sound; how it adds to and balances Partnership efforts to manage the Salish Sea; and will provide some lessons learned in gaining buy-in from local and state officials, scientists and stakeholders on monitoring programs managed by local governments

Letter of Intent

The purpose of this project is to design test systems for a Spaceport America Cup capable rocket. Specifically, to design a test system for the recovery systems and test system for the motor. The rocket must be capable of reaching an apogee of 10,000 feet and recovered using a dual deployment recovery system. The motor test will be used to determine if the actual thrust from the selected motor will be sufficient to launch a rocket carrying an 8.8 pound payload to an apogee of 10,000 feet. Using a load cell and designed static launch stand, the team will be able to determine the actual thrust of the motor and calculate a trajectory for the rocket. The recovery system test will be designed to mimic the atmospheric pressure across the flight of the rocket. This will allow the altimeters and dual deployment systems to be tested at an accurate replication of flight. Testing in this manor will insure against failure during actual launch

Direct ortho-Arylation of Pyridinecarboxylic Acids: Overcoming the Deactivating Effect of sp2-Nitrogen

Direct arylations of pyridines are challenging transformations due to the high Lewis basicity of the sp²-nitrogen. The use of carboxylates as directing groups is reported, facilitating the Pd-catalyzed C–H arylation of this difficult class of substrates. This methodology allows regioselective C3/C4 arylation, without the need to use solvent quantities of the pyridine, and using low-cost chloro- and bromoarenes as coupling partners. Furthermore, carboxylates could be employed as traceless directing groups through a one-pot C–H arylation/Cu­(I)-mediated decarboxylation sequence, thereby accessing directing-group-free pyridine biaryls

Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

BackgroundBudesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis.AimThe aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam.MethodsData from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam.ResultsA similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration.ConclusionsThis integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis

Application of a single-objective, hybrid genetic algorithm approach to pharmacokinetic model building.

A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds. Both manual stepwise and single-objective, hybrid genetic algorithm approaches to model building were applied, blinded to the results of the other approach, for selection of the compartment structure as well as inclusion and model form of inter-individual and inter-occasion variability, residual error, and covariates from a common set of model options. For the simulated dataset, stepwise covariate modeling identified three of four true covariates and two spurious covariates; Lasso identified two of four true and 0 spurious covariates; and the single-objective, hybrid genetic algorithm identified three of four true covariates and one spurious covariate. For the clinical datasets, the Akaike information criterion was a median of 22.3 points lower (range of 470.5 point decrease to 0.1 point decrease) for the best single-objective hybrid genetic-algorithm candidate model versus the final manual stepwise model: the Akaike information criterion was lower by greater than 10 points for four compounds and differed by less than 10 points for three compounds. The root mean squared error and absolute mean prediction error of the best single-objective hybrid genetic algorithm candidates were a median of 0.2 points higher (range of 38.9 point decrease to 27.3 point increase) and 0.02 points lower (range of 0.98 point decrease to 0.74 point increase), respectively, than that of the final stepwise models. In addition, the best single-objective, hybrid genetic algorithm candidate models had successful convergence and covariance steps for each compound, used the same compartment structure as the manual stepwise approach for 6 of 7 (86 %) compounds, and identified 54 % (7 of 13) of covariates included by the manual stepwise approach and 16 covariate relationships not included by manual stepwise models. The model parameter values between the final manual stepwise and best single-objective, hybrid genetic algorithm models differed by a median of 26.7 % (q₁ = 4.9 % and q₃ = 57.1 %). Finally, the single-objective, hybrid genetic algorithm approach was able to identify models capable of estimating absorption rate parameters for four compounds that the manual stepwise approach did not identify. The single-objective, hybrid genetic algorithm represents a general pharmacokinetic model building methodology whose ability to rapidly search the feasible solution space leads to nearly equivalent or superior model fits to pharmacokinetic data

RANK/RANKL/OPG pathway: genetic associations with stress fracture period prevalence in elite athletes

Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations. Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes. Design, Participants, and Methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group, and were sub-stratified into male and cases of multiple stress fracture group. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays. Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (p<0.05). 8.1% of stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (p<0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes to have suffered a stress fracture while 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188, and individuals possessing at least one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (p<0.05). Conclusions: The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health, and offers potential targets for therapeutic interventions