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This Article challenges the conventional wisdom that states are always free to choose whether to participate in multilateral regimes. International law often mandates multilateralism to ensure that state laws and practices are compatible with sovereign equality and joint stewardship. The Article maps mandatory multilateralism's domain, defines its requirements, and examines its application to three controversies: the South China Sea dispute, the United States’ withdrawal from the 2015 Paris Agreement, and Bolivia's case against Chile in the International Court of Justice.
Borsboom et al. confuse biological approaches with extreme biological reductionism and common-cause models of psychopathology. In muddling these concepts, they mistakenly throw the baby out with the bathwater. Here, we highlight recent work underscoring the unique value of clinical and translational neuroscience approaches for understanding the nature and origins of psychopathology and for developing improved intervention strategies.
OBJECTIVES/SPECIFIC AIMS: The development of new anti-cancer agents for children requires an inherently longer timeline than in adults. The 3+3 study design for Phase 1 dose escalation trials is commonly used to estimate the maximum tolerated dose and assess safety. The Rolling 6 study design was developed to shorten the study conduct timeline. METHODS/STUDY POPULATION: This study compares twenty Phase 1 COG Pilot and Phase 1 Consortium trials that employed the Rolling 6 design with hypothetical results under the assumption that a 3+3 design had been executed. The number of evaluable patients required to complete the study, number of DLTs, number of inevaluable patients, overall study duration, time suspended to enrollment (i.e., waiting for DLT evaluation), and DLT risk are compared between study designs using Wilcoxon’s signed rank test. RESULTS/ANTICIPATED RESULTS: The Rolling 6 study design required less time to complete the studies compared with 3+3 design (median 273 vs. 297 days, P = 0.01). In general, the Rolling 6 study design required more patients, had more inevaluable patients, and there were more dose limiting toxicity (DLT) events. However, there was no significant difference in DLT risk (median 0.15 vs. 0.17, P = 0.72). DISCUSSION/SIGNIFICANCE OF IMPACT: The Rolling 6 study design effectively shortens the study conduct timeline compared with the traditional 3+3 design for Phase 1 COG Pilot and Phase 1 Consortium trials without increasing the risk of toxicity.
Flexible piezoelectric generators (PEGs) present a unique opportunity for renewable and sustainable energy harvesting. Here, we present a low-temperature and low-energy deposition method using solvent evaporation-assisted three-dimensional printing to deposit electroactive poly(vinylidene fluoride) (PVDF)-trifluoroethylene (TrFE) up to 19 structured layers. Visible-wavelength transmittance was above 92%, while ATR-FTIR spectroscopy showed little change in the electroactive phase fraction between layer depositions. Electroactivity from the fabricated PVDF-TrFE PEGs showed that a single structured layer gave the greatest output at 289.3 mV peak-to-peak voltage. This was proposed to be due to shear-induced polarization affording the alignment of the fluoropolymer dipoles without an electric field or high temperature.