Spray-dried dispersions (SDDs) of low-solubility drugs have been prepared using the polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). For a variety of drug structures, these SDDs ...provide supersaturation in in vitro dissolution determinations and large bioavailability increases in vivo. In bile-salt/lecithin in vitro solutions, these SDDs provide amorphous drug/polymer colloids and an increased concentration of free drug and drug in micelles relative to crystalline or amorphous drug. As dry powders, the SDDs are a single amorphous phase in which the drug remains amorphous and dispersed and does not crystallize over storage times relevant for practical drug products. A melting temperature (T m)/glass-transition temperature (T g) (K/K) versus log P map for 139 compounds formulated as SDDs provides a perspective on an appropriate formulation strategy for low-solubility drugs with various physical properties.
A new experimental apparatus was built at Oregon State University to perform high resolution stimulated Raman spectroscopy in a pulsed molecular jet at state densities of the order of 10$\sp{11}$ ...cm$\sp{-3}.$ The technique uses a stimulated Raman step to first populate a vibrational/rotational level and then a resonantly enhanced multiphoton ionization (REMPI) step to subsequently probe the Raman pumped upper state. The resulting ions are accelerated down a Wiley-McLaren time of flight mass spectrometer (with mass resolution of 182 amu) and are detected with a home built microchannel plate detector, making mass selective Raman spectroscopy possible. Instrumental linewidths of 0.001 cm$\sp{-1}$ were demonstrated for benzene transitions, possibly being the highest resolution yet obtained for stimulated Raman spectroscopy. One reason for this narrow linewidth is that all the spectroscopy is performed in a cold molecular beam. This is advantageous because the rotationally resolved spectra are simplified to a great extent due to the low rotational temperatures (on the order of 10 K) and the collisional and Doppler contributions to the linewidths are reduced to less than the instrumental resolution. This form of ionization-detected stimulated Raman spectroscopy (IDSRS) was performed on N$\sb2$ for the first time. This is important because nitrogen was ionized using a difficult 2 + 2 REMPI step for detection of the Raman signal. Even so, the detection limit was improved by a factor of 10$\sb4$ over optical stimulated Raman spectroscopy. These results demonstrate that IDSRS is not limited to the aromatic molecular systems (which are easily ionized with 1 + 1 REMPI) that have been studied almost exclusively to date. Finally, the unusually high resolution of this experiment has enabled a qualitative study of the AC Stark splittings that come about through the induced dipole moment of the benzene molecule. To model the experimental spectra it was determined that good fits can only be achieved by including saturation and temporal/spatial broadening with the Stark splittings. Due to the unique power dependent lineshapes of the Stark split rotational transitions, the Stark effect can be a useful spectroscopic tool for Raman rotational assignments within a particular vibrational band.
Marshall Crew, PhD, President & CEO, Agere Pharmaceuticals, Inc., continues his multiple-part series discussing today's most challenging issues in solubility.
Marshall Crew, PhD, President & CEO, Agere Pharmaceuticals, Inc., begins his multiple-part series discussing today's most challenging issues in solubility.
In the D‐region, the ionization rate cannot be detected directly with any known measurement technique, therefore it must be estimated. Starting from space‐based measurements of precipitating particle ...flux, we estimate the ionization rate in the atmosphere using the Electron Precipitation Monte Carlo transport method. This ionization rate is used to calculate the expected electron density in the D‐region with the Glukhov‐Pasko‐Inan five species (GPI5) atmospheric chemistry model. We then compare the simulated electron density with that measured by the Poker Flat Incoherent Scatter Radar (PFISR). From ground‐based radar measurements of electron density enhancements due to sub‐relativistic and relativistic electron precipitation, we present a method to extract the ionization rate altitude profiles using inverse theory. We use this estimation of ionization rate to find the energy distribution of the precipitating particles. With this inverse method, we are able to link ground measurements of electron density to the precipitating flux in a time dependent manner and with uncertainty in the inverted parameters. The method was tested on synthetic data and applied to specific PFISR data sets. The method is able to retrieve the ionization rate altitude profiles that, when forward modeled, return the expected electron densities within ∼7% error as compared to the PFISR data. For the case presented here, the arbitrary energy distribution inversion results are comparable in magnitude and shape to those presented in Turunen et al. (2016, https://doi.org/10.1002/2016jd025015) for the inversion of a single event of pulsating aurora observed by EISCAT.
Plain Language Summary
Electrons expelled from the Earth's radiation belts by electromagnetic waves enter the upper atmosphere and travel through it. Interactions of these electrons with atmospheric constituents lead to the ionization of the atmospheric species. This ionization produces enhancements of electron density in certain altitude ranges that depend on the incoming particles' energy. Satellites orbiting Earth at an altitude of a few hundred km can measure the flux of the entering particles. We use a modeling technique to simulate their behavior in the atmosphere, including the electron density modification, starting from the satellite measurements. Radars at ground stations on Earth can detect the electron density enhancements in the atmosphere. We use inverse theory to estimate the ionization rate and flux of precipitating particles starting from the radar electron density measurements.
Key Points
We compare D‐region radar measurements of electron density to a forward‐modeled electron precipitation flux and spectrum
A method is presented to infer ionization rates from D‐region electron density measurements made by radar, accounting for time dependence and to infer precipitating flux from D‐region ionization rates with exponential or arbitrary energy distributions
We establish a time‐dependent inversion from radar‐observed electron density to an estimate of the precipitating energetic electron source
Assessing the association of the newborn metabolic state with severity of subsequent respiratory tract infection may provide important insights on infection pathogenesis. In this multi-site birth ...cohort study, we identified newborn metabolites associated with lower respiratory tract infection (LRTI) in the first year of life in a discovery cohort and assessed for replication in two independent cohorts. Increased citrulline concentration was associated with decreased odds of LRTI (discovery cohort: aOR 0.83 95% CI 0.70-0.99,
= 0.04; replication cohorts: aOR 0.58 95% CI 0.28-1.22,
= 0.15). While our findings require further replication and investigation of mechanisms of action, they identify a novel target for LRTI prevention and treatment.
Expert knowledge is often shared among multidisciplinary academic teams at tumor boards (TBs) across the country, but these conversations exist in silos and do not reach the wider oncology community.
...Using an oncologist-only question and answer (Q&A) website, we sought to document expert insights from TBs at National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs) to provide educational benefits to the oncology community.
We designed a process with the NCI-CCCs to document and share discussions from the TBs focused on areas of practice variation on theMednet, an interactive Q&A website of over 13,000 US oncologists. The faculty translated the TB discussions into concise, non-case-based Q&As on theMednet. Answers were peer reviewed and disseminated in email newsletters to registered oncologists. Reach and engagement were measured. Following each Q&A, a survey question asked how the TB Q&As impacted the readers' practice.
A total of 23 breast, thoracic, gastrointestinal, and genitourinary programs from 16 NCI-CCC sites participated. Between December 2016 and July 2021, the faculty highlighted 368 questions from their TBs. Q&As were viewed 147,661 times by 7381 oncologists at 3515 institutions from all 50 states. A total of 277 (75%) Q&As were viewed every month. Of the 1063 responses to a survey question on how the Q&A affected clinicians' practices, 646 (61%) reported that it confirmed their current practice, 163 (20%) indicated that a Q&A would change their future practice, and 214 (15%) reported learning something new.
Through an online Q&A platform, academics at the NCI-CCCs share knowledge outside the walls of academia with oncologists across the United States. Access to up-to-date expert knowledge can reassure clinicians' practices, significantly impact patient care in community practices, and be a source of new knowledge and education.
ASCA observations of the gravitational lens and Butcher-Oemler cluster Abell 370 (z = 0.37) give kT = 8.8 +/- 0.8 keV and A = 0.5 +/- 0.1 cosmic. If the gas were isothermal the implied cluster mass ...would be M(sub vir) = (1.5 +/- 0.4) x 10(exp 15) solar masses, a value consistent with the optically-determined virial mass. We detect iron K line emission with high confidence. This measurement increases, by a large factor, the lookback time at which the presence of iron in the intracluster medium has been established. The iron abundance is marginally higher than that of low-redshift clusters of similar temperature, so our results are consistent with models in which all enrichment occurs before the epoch corresponding to z = 0.37.
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