Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release

Global coverage of cetacean line-transect surveys : status quo, data gaps and future challenges

Knowledge of abundance, trends and distribution of cetacean populations is needed to inform marine conservation efforts, ecosystem models and spatial planning. We compiled a geo-spatial database of published data on cetacean abundance from dedicated visual line-transect surveys and encoded >1100 abundance estimates for 47 species from 430 surveys conducted worldwide from 1975-2005. Our subsequent analyses revealed large spatial, temporal and taxonomic variability and gaps in survey coverage. With the exception of Antarctic waters, survey coverage was biased toward the northern hemisphere, especially US and northern European waters. Overall, <25% of the world’s ocean surface was surveyed and only 6% had been covered frequently enough (≥ 5 times) to allow trend estimation. Almost half the global survey effort, defined as total area (km2) covered by all survey study areas across time, was concentrated in the Eastern Tropical Pacific (ETP). Neither the number of surveys conducted nor the survey effort had increased in recent years. Across species, an average of 10% of a species’ predicted range had been covered by at least one survey, but there was considerable variation among species. With the exception of three delphinid species, <1% of all species’ ranges had been covered frequently enough for trend analysis. We use a data-rich species, sperm whale, as an example to illustrate the challenges of using available data from line-transect surveys for the detection of trends or for spatial planning. Finally, we propose and contrast several field and analytical methods to fill in data gaps to improve future cetacean conservation management efforts.Publisher PDFPeer reviewe

Hands-on versus hands-off techniques for the prevention of perineal trauma during vaginal delivery: a systematic review and meta-analysis of randomized controlled trials

Background: Perineal trauma at the time of vaginal delivery is common, and when the anal sphincter is included, these injuries can be associated with additional morbidity including incontinence, pelvic pain, and sexual dysfunction. Objective: The aim of this systematic review with meta-analysis was to evaluate whether a hands-on technique during vaginal delivery results in less incidence of perineal trauma than a hands-off technique. Methods: Electronic databases were searched from their inception until June 2018. No restrictions for language or geographic location were applied. The reference lists of identified articles were examined to identify studies not captured by electronic searches. Randomized controlled trials comparing a hands-on technique of perineal support during vaginal delivery (i.e. intervention group) with a hands-off technique (i.e. control group) were included in the meta-analysis. Hands-on was defined as involving one hand on the fetal head, applying pressure to control expulsion, with the other hand applying pressure on the maternal perineum. The primary outcome was severe perineal trauma, defined as either third- or fourth-degree lacerations. The meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI). Results: Five trials, including 7287 women, were analyzed. All studies included singleton gestations with cephalic presentation at term undergoing spontaneous vaginal delivery. Women randomized to the hands-on technique had similar incidence of severe perineal trauma (1.5 versus 1.3%; RR 2.00, 95% CI 0.56-7.15). There was no significant between-group difference in the incidence of intact perineum, first-, second- and fourth-degree laceration. Hands-on technique was associated with increased risk of third-degree lacerations (2.6 versus 0.7%; RR 3.41, 95% CI 1.39-8.37) and of episiotomy (13.6 versus 9.8%, RR 1.59, 95% CI 1.14-2.22) compared to the hands-off technique. Conclusions: Hands-on technique during spontaneous vaginal delivery of singleton gestations results in similar incidence of several perineal traumas compared to a hands-off technique. The incidence of third-degree lacerations and of episiotomy increases with the hands-on technique. Key Message A hands-on technique during vaginal delivery results in similar incidence of severe lacerations compared to hands-off

White Screen/White Noise: Racism on the Internet

The Internet is critical for disseminating information, but it does not discriminate against information it carries. Hate speech and racist representations proliferate in social media, online news comment sections and community forums. What can information workers do to counteract those messages? How can critical race consciousness enhance on- and off-line library services? This article attempts to explore how information in the age of rapid technology innovation contributes to structural racism and what librarians and other information professionals can do about it

White Screen/White Noise: Racism and the Internet

The Internet is critical for disseminating information, but it does not discriminate against information it carries. Hate speech and racist representations proliferate in social media, online news comment sections and community forums. What can information workers do to counteract those messages? How can critical race consciousness enhance on- and off-line library services? This article attempts to explore how information in the age of rapid technology innovation contributes to structural racism and what librarians and other information professionals can do about it

Canyon formation constraints on the discharge of catastrophic outburst floods of Earth and Mars

Catastrophic outburst floods carved amphitheater-headed canyons on Earth and Mars, and the steep headwalls of these canyons suggest that some formed by upstream headwall propagation through waterfall erosion processes. Because topography evolves in concert with water flow during canyon erosion, we suggest that bedrock canyon morphology preserves hydraulic information about canyon-forming floods. In particular, we propose that for a canyon to form with a roughly uniform width by upstream headwall retreat, erosion must occur around the canyon head, but not along the sidewalls, such that canyon width is related to flood discharge. We develop a new theory for bedrock canyon formation by megafloods based on flow convergence of large outburst floods toward a horseshoe-shaped waterfall. The model is developed for waterfall erosion by rock toppling, a candidate erosion mechanism in well fractured rock, like columnar basalt. We apply the model to 14 terrestrial (Channeled Scablands, Washington; Snake River Plain, Idaho; and Ásbyrgi canyon, Iceland) and nine Martian (near Ares Vallis and Echus Chasma) bedrock canyons and show that predicted flood discharges are nearly 3 orders of magnitude less than previously estimated, and predicted flood durations are longer than previously estimated, from less than a day to a few months. Results also show a positive correlation between flood discharge per unit width and canyon width, which supports our hypothesis that canyon width is set in part by flood discharge. Despite lower discharges than previously estimated, the flood volumes remain large enough for individual outburst floods to have perturbed the global hydrology of Mars

Using pH abnormalities in diseased skin to trigger and target topical therapy

Abstract Purpose: The pH discrepancy between healthy and atopic dermatitis skin was identified as a site specific trigger for delivering hydrocortisone from microcapsules. Methods: Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed and preliminary stability data was determined. Results: Drug release from microparticles was pH-dependent though the particles produced by spray drying also gave significant non-pH dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In-vitro studies showed 4 to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5. Conclusions: Permeation studies showed that the oil-in-oil generated particles deliver essentially no drug at normal (intact) skin pH (5.0 – 5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin

Polygenic and socioeconomic risk for high body mass index:69 years of follow-up across life

Genetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. We thus used a birth cohort study to investigate differences in association and explained variance in polygenic risk for high BMI across infancy to old age (2-69 years). A secondary aim was to investigate how the association between BMI and a key purported environmental determinant (childhood socioeconomic position) differed across life, and whether this operated independently and/or multiplicatively of genetic influences. Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured BMI at 12 timepoints from 2-69 years. We used multiple polygenic indices from GWAS of adult and childhood BMI, and investigated their associations with BMI at each age. For polygenic liability to higher adult BMI, the trajectories of effect size (β) and explained variance (R2) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; quantile regression analyses showed that effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction. Our findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance ('non-shared') environmental influences on BMI across life

Non-Hawaiian lithostratigraphy of Louisville seamounts and the formation of high-latitude oceanic islands and guyots

Guyots are large seamounts with a flat summit that is generally believed to form due to constructional biogenic and/or erosional processes during the formation of volcanic islands. However, despite their large abundance in the oceans, there are still very few direct constraints on the nature and formation of guyots, in particular those formed at high latitude that lack a thick cap of shallow-marine carbonate rocks. It is largely accepted based on geophysical constraints and surficial observations/sampling that the summit platform of these guyots is shaped by wave abrasion during post-volcanic subsidence of volcanic islands. Here we provide novel constraints on this hypothesis and the summit geology of guyots with a lithostratigraphic analysis of cores from three Louisville seamounts (South Pacific) collected during Expedition 330 of the Integrated Ocean Drilling Program (IODP). Thirteen lithofacies of sedimentary and volcanic deposits are described, which include facies not previously recognized on the top of guyots, and offer a new insight into the formation of high-latitude oceanic islands on a fast-moving plate. Our results reveal that the lithostratigraphy of Louisville seamounts preserves a very consistent record of the formation and drowning of volcanic islands, with from bottom to top: (i) volcaniclastic sequences with abundant lava-fed delta deposits, (ii) submarine to subaerial shield lava flows, (iii) post-volcanic shallow to deeper marine sedimentary rocks lacking thick reef deposits, (iv) post-erosional rejuvenated volcanic rocks, and (v) pelagic sediments. Recognition of erosional boundaries between subaerial lava flows and shallow-marine sedimentary rocks provides novel support for post-volcanic wave planation of guyots. However, the summit geology of Louisville seamounts is dissimilar to that of high-latitude Hawaiian-Emperor guyots that have emplaced in a similar tectonic and environmental setting and that include thicker lava stacks with apparently little lava-fed delta deposits. To explain observed lithostratigraphic discrepancy we propose that Louisville seamounts represent a distinct type of intraplate ocean volcano characterized by formation of a smaller island, with a central shield volcano surrounded by extended shallow-marine shelves formed by lava-fed deltas. In this interpretation the summit platform of Louisville-type guyots results from early (syn-volcanic) subaerial to shallow-marine constructional volcanic processes and marine erosion, enhanced by later (post-volcanic) wave planation. This contrasts with larger Hawaiian edifices that are capped by thicker shield volcanoes, and that develop an extended wave planation surface during post-volcanic subsidence (in the absence of efficient coral growth). The difference between Hawaiian- and Louisville-type volcanic islands and guyots can be explained by contrasted dynamic disequilibrium between magmatic growth, erosion, and subsidence during the island-building stage. Unlike Hawaiian-type volcanoes, Louisville seamounts are characterized by alkaline magmatism that extends from the late seamount to island stages. This supports more limited magmatic growth during the formation of Louisville islands, and we hypothesize that this promotes the formation of ephemeral shallow-marine platforms and extended lava-fed deltas. Hawaiian-type volcanoes and guyots are unusually large in the population of intraplate ocean volcanoes. Louisville-type guyots as defined in this study could therefore represent a very common but yet poorly documented mode of oceanic island formation in the Pacific Ocean and other similar fast-moving plate settings