The traffic and behavioral effects of the I-35W Mississippi River bridge collapse

The collapse, on August 1, 2007, of the I-35W bridge over the Mississippi River in Minneapolis, abruptly interrupted the usual route of about 140,000 daily vehicle trips and substantially disturbed the ßow pattern on the network. It took several weeks for the network to re-equilibrate, during which period, travelers continued to learn and adjust their travel decisions. A good understanding of this process is crucial for traffic management and designing mitigation schemes. A survey collected behavioral responses to the bridge collapse. Traffic data were also collected to understand the traffic conditions experienced by road users. Data from both resources are analyzed and compared. Findings of behavioral effects of capacity changes could have significant implications for travel demand modeling, especially of day-to-day travel demandMinnesota, Minneapolis, I-35W bridge collapse, travel behavior, travel survey

Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression.

BackgroundNovel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models.MethodsLevels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes.ResultsBoth primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib.ConclusionsNeuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify patients that may respond to MEK inhibition. MEK inhibition therefore represents a potential new therapeutic strategy for neuroblastoma

Management of hyperkalemia in the acutely ill patient.

PURPOSE:To review the mechanisms of action, expected efficacy and side effects of strategies to control hyperkalemia in acutely ill patients. METHODS:We searched MEDLINE and EMBASE for relevant papers published in English between Jan 1, 1938, and July 1, 2018, in accordance with the PRISMA Statement using the following terms: "hyperkalemia," "intensive care," "acute kidney injury," "acute kidney failure," "hyperkalemia treatment," "renal replacement therapy," "dialysis," "sodium bicarbonate," "emergency," "acute." Reports from within the past 10 years were selected preferentially, together with highly relevant older publications. RESULTS:Hyperkalemia is a potentially life-threatening electrolyte abnormality and may cause cardiac electrophysiological disturbances in the acutely ill patient. Frequently used therapies for hyperkalemia may, however, also be associated with morbidity. Therapeutics may include the simultaneous administration of insulin and glucose (associated with frequent dysglycemic complications), β-2 agonists (associated with potential cardiac ischemia and arrhythmias), hypertonic sodium bicarbonate infusion in the acidotic patient (representing a large hypertonic sodium load) and renal replacement therapy (effective but invasive). Potassium-lowering drugs can cause rapid decrease in serum potassium level leading to cardiac hyperexcitability and rhythm disorders. CONCLUSIONS:Treatment of hyperkalemia should not only focus on the ability of specific therapies to lower serum potassium level but also on their potential side effects. Tailoring treatment to the patient condition and situation may limit the risks