Feasibility of pre-operative mTOR inhibitor Sirolimus in children and young adults with desmoid tumor

Background: • Desmoid tumor represents an intermediate grade neoplasm with a striking predilection for locally invasive growth and recurrence following resection • More effective, well-tolerated non-surgical treatment options are needed • Current approaches • If feasible, watchful waiting is the preferred approach • 20-30% spontaneous regression • In situations where treatment is indicated, the following approaches are utilized • Surgery is the primary approach if minimal morbidity is anticipated • Medical therapies • Cytotoxic drugs • Tyrosine kinase inhibitors • Hydroxyurea • Gamma secretase inhibitors • mTOR Inhibitor Rationale • Desmoid tumor is well-known to be associated with deregulation of the APC/β-catenin pathway • Deregulation of the mTOR cell proliferation/survival pathway may play an important role in tumor biology when the APC/βcatenin pathway is disrupted • The mTOR inhibitor sirolimus is attractive as a potential targeted therapy for desmoid tumor • Well-tolerated in children and young adults • Can be given orally in tablet or liquid formulatio

Phosphoinositide-3 kinase inhibition modulates responses to rhinovirus by mechanisms that are predominantly independent of autophagy

Human rhinoviruses (HRV) are a major cause of exacerbations of airways disease. Aspects of cell signalling responses to HRV infection remain unclear, particularly with regard to signalling via PI3K, and the PI3K-dependent pathway, autophagy. We investigated the roles of PI3K and autophagy in the responses of epithelial cells to major and minor group HRV infection. The PI3K inhibitor 3-MA, commonly used to inhibit autophagy, markedly reduced HRV-induced cytokine induction. Further investigation of potential targets of 3-MA and comparison of results using this inhibitor to a panel of general and class I-selective PI3K inhibitors showed that several PI3Ks cooperatively regulate responses to HRV. Targeting by siRNA of the autophagy proteins Beclin-1, Atg7, LC3, alone or in combination, or targeting of the autophagy-specific class III PI3K had at most only modest effects on HRV-induced cell signalling as judged by induction of proinflammatory cytokine production. Our data indicate that PI3K and mTOR are involved in induction of proinflammatory cytokines after HRV infection, and that autophagy has little role in the cytokine response to HRV or control of HRV replication

Matter-wave Atomic Gradiometer Interferometric Sensor (MAGIS-100)

MAGIS-100 is a next-generation quantum sensor under construction at Fermilab that aims to explore fundamental physics with atom interferometry over a 100-meter baseline. This novel detector will search for ultralight dark matter, test quantum mechanics in new regimes, and serve as a technology pathfinder for future gravitational wave detectors in a previously unexplored frequency band. It combines techniques demonstrated in state-of-the-art 10-meter-scale atom interferometers with the latest technological advances of the world's best atomic clocks. MAGIS-100 will provide a development platform for a future kilometer-scale detector that would be sufficiently sensitive to detect gravitational waves from known sources. Here we present the science case for the MAGIS concept, review the operating principles of the detector, describe the instrument design, and study the detector systematics.Comment: 65 pages, 18 figure

Ultrafast Pulses Produced via Random Quasi-Phase-Matching Measured with Frequency-Resolved Optical Gating

Random quasi-phase-matching (RQPM) is a nonlinear optical phenomenon known to occurnaturally in polycrystalline materials. When driven by a pulsed source in the infrared, RQPM in ZnSe/S can generate second-harmonic light. This second-harmonic generation (SHG) can reach optical powers comparable to those of conventional ultrafast sources, on the order of hundreds of milliwatts. These pulses are not well characterized, nor has a complete analysis on them been done to determine factors such as compressibility. Previous measurements of the light generated by RQPM have focused on the power spectra and have said nothing about the spectral phase, which is required for making predictions about the temporal profile and coherence of the light. Here, we use frequency-resolved optical gating (FROG) to reconstruct a temporal description of a laser pulse produced by SHG via RQPM in ZnS. The experiment is based on a collinear SHG beam geometry that can be easily reconfigured for additional measurements, including linear and interferometric autocorrelations. After measuring the pulse, we perform an additional measurement in order to resolve an ambiguity inherent to SHG FROG. Finally, we will report on an experiment that suggests pulses produced by RQPM in ZnS might be compressible to durations of 35 fs or shorter

Operating room scheduling data base analysis for scheduling

A methodology to determine and maintain the schedule times used in a computer-based OR Scheduling System is presented. State-of-the-art equations to be used for different scheduling situations are presented and discussed with the attendant data base reduction methodology to provide the scheduling parameters. An example is given of the data reduction methodology as well as suggestions for maintenance of the data base.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44989/1/10916_2004_Article_BF00992688.pd

Heroin pipe distribution to reduce high-risk drug consumption behaviors among people who use heroin: a pilot quasi-experimental study.

BACKGROUND Heroin pipe distribution may encourage people who use heroin (PWUH) to transition from injecting to smoking heroin, reducing harms associated with injection drug use. A syringe services program (SSP) in Seattle, Washington, led by people who use drugs developed a heroin pipe distribution program. METHODS We conducted a pretest-posttest quasi-experimental study to evaluate the impact of heroin pipe distribution on drug consumption behaviors among PWUH between March and December 2019. SSP clients were surveyed during three weeklong timepoints before and four weeklong timepoints after heroin pipe distribution. Primary outcomes were change in proportion of SSP clients who exclusively injected heroin, exclusively smoked heroin, and both injected and smoked heroin in the past seven days comparing the pre- and post-intervention periods. RESULTS Across the seven observation timepoints, 694 unique respondents completed 957 surveys. Multiple responses from a single respondent in a given period were collapsed, resulting in 360 pre-intervention and 430 post-intervention records. Heroin use was reported in over half of pre-intervention (56%, 201/360) and post-intervention records (58%, 251/430). Compared to pre-intervention behaviors, the proportion of respondents who exclusively injected heroin was lower after the start of heroin pipe distribution (32%, 80/251 vs 43%, 86/201, p = 0.02), while the proportion of respondents who both injected and smoked heroin was higher (45%, 113/251 vs 36%, 72/201, p = 0.048). Just under half (44%, 110/251) of respondents who used heroin during the post-intervention period used a heroin pipe obtained from the SSP, of which 34% (37/110) reported heroin pipe distribution had reduced their heroin injection frequency. Self-reported hospitalization for a pulmonary cause was not associated with using a heroin pipe. CONCLUSIONS The proportion of SSP clients who exclusively injected heroin was lower after implementation of heroin pipe distribution. Randomized studies with longer follow-up are needed to investigate whether heroin pipe distribution reduces heroin injection and improves health outcomes associated with drug use. Limited intervention exposure, loss to follow-up, and pipe availability from other sources pose methodological challenges to evaluations of route transition interventions in community settings. This pilot highlights the potential for organizations led by people who use drugs to develop, implement, and evaluate novel public health programming

Additional file 3 of Heroin pipe distribution to reduce high-risk drug consumption behaviors among people who use heroin: a pilot quasi-experimental study

Additional file 3: Educational materials distributed to SSP clients describing how the pipe could be used to smoke heroin