Release of Ciprofloxacin and Moxifloxacin From Daily Disposable Contact Lenses From an In Vitro Eye Model

Bajgrowicz, M., Phan, C.-M., Subbaraman, L. N., & Jones, L. (2015). Release of Ciprofloxacin and Moxifloxacin From Daily Disposable Contact Lenses From an In Vitro Eye Model. Investigative Opthalmology & Visual Science, 56(4), 2234. https://doi.org/10.1167/iovs.15-16379Purpose.: To analyze the release of two fluoroquinolones, ciprofloxacin and moxifloxacin, from conventional hydrogel (CH) and silicone hydrogel (SH) daily disposable contact lenses (CLs), comparing release from a fixed-volume vial and a novel in vitro eye model. Methods.: Four CH CLs (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three SH CLs (somofilcon A, narafilcon A, delefilcon A) were used. The lenses were incubated in drug solutions for 24 hours. After the incubation period, the lenses were placed in two release conditions: (1) a vial containing 4.8 mL PBS for 24 hours and (2) an in vitro eye model with a flow rate at 4.8 mL over 24 hours. Results.: Release in the vial for both drugs was rapid, reaching a plateau between 15 minutes and 2 hours for all lenses. In contrast, under physiological flow conditions, a constant and slow release was observed over 24 hours. The amounts of ciprofloxacin released from the lenses ranged between 49.6 ± 0.7 and 62.8 ± 0.3 μg per lens in the vial, and between 35.0 ± 7.0 and 109.0 ± 5.0 μg per lens in the eye model. Moxifloxacin release ranged from 24.0 ± 4.0 to 226.0 ± 2.0 μg per lens for the vial, and between 13.0 ± 2.0 and 151.0 ± 10.0 μg per lens in the eye model. In both systems and for both drugs, HEMA-based CLs released more drugs than other materials. Conclusions.: The parameters of the release system, in particular the volume and flow rate, have a significant influence on measured release profiles. Under physiological flow, release profiles are significantly slower and constant when compared with release in a vial

Release of Moxifloxacin from Contact Lenses Using an In Vitro Eye Model: Impact of Artificial Tear Fluid Composition and Mechanical Rubbing

Phan, C.-M., Bajgrowicz-Cieslak, M., Subbaraman, L. N., & Jones, L. (2016). Release of Moxifloxacin from Contact Lenses Using an In Vitro Eye Model: Impact of Artificial Tear Fluid Composition and Mechanical Rubbing. Translational Vision Science & Technology, 5(6), 3. https://doi.org/10.1167/tvst.5.6.3Purpose: The aim of this study was to evaluate and compare the release of moxifloxacin from a variety of daily disposable (DD) contact lenses (CLs) under various conditions using a novel in vitro eye model. Methods: Four commercially available DD conventional hydrogel (CH) CLs (nelfilcon A, omafilcon A, etafilcon A, and ocufilcon B) and three silicone hydrogel (SH) CLs (somofilcon A, narafilcon A, and delefilcon A) were evaluated. These lenses were incubated in moxifloxacin for 24 hours. The release of the drug was measured using a novel in vitro model in three experimental conditions: (1) phosphate buffered saline (PBS); (2) artificial tear solution (ATS) containing a variety of proteins and lipids; and (3) ATS with mechanical rubbing produced by the device. Results: Overall, CH CLs had a higher drug release than SH CLs (P < 0.05) under all conditions. Typically, a higher drug release was observed in PBS than ATS (P < 0.05). For CH, drug release was found to be higher in ATS with rubbing than PBS or ATS (P < 0.05). For most lens types, ATS with rubbing produced higher drug release than ATS alone (P < 0.05). Generally, the release kinetics for all conditions were sustained over the 24-hour testing period, and no burst release was observed (P < 0.05). Conclusions: Moxifloxacin release from a CL into ATS is lower when compared to release into PBS. When mechanical rubbing is introduced, the amount of drugs released is increased. Translational Relevance: Results suggest that sophisticated in vitro models are necessary to adequately model on-eye drug release from CL materials

First results of the LARES 2 space experiment to test the general theory of relativity

The LAGEOS 3 (today LARES 2) space experiment was proposed in the eighties by the Physics Department and by the Center of Space Research (CSR) of the University of Texas (UT) at Austin and by the Italian Space Agency (ASI) to test and accurately measure frame-dragging, with the strong support of John Archibald Wheeler, director of the Center for Theoretical Physics of UT Austin. Frame-dragging is an intriguing phenomenon predicted by Einstein's theory of general relativity which has fundamental implications in high energy astrophysics and in the generation of gravitational waves by spinning black holes. LAGEOS 3 was reproposed in 2016 to the Italian Space Agency and to the European Space Agency as a technologically much improved version of LAGEOS 3 under the name LARES 2 (LAres RElativity Satellite 2) and then successfully launched in 2022 with the new launch vehicle VEGA C of ASI, ESA and AVIO. Today, after almost forty years since the original proposal, we report the first results of the LARES 2 space experiment to test general relativity. The results are in complete agreement with the predictions of Einstein's gravitational theory. Whereas previous results already confirmed the frame-dragging prediction, the conceptual relative simplicity of the LARES 2 experiment with respect to the previous tests with the LARES and LAGEOS satellites provides a significant advance in the field of tests of general relativity.Comment: 11 page

Optical glucose sensors based on hexagonally-packed 2.5-dimensional photonic concavities imprinted in phenylboronic acid functionalized hydrogel films

Continuous glucose monitoring aims to achieve accurate control of blood glucose concentration to prevent hypo/hyperglycaemia in diabetic patients. Hydrogel-based systems have emerged as a reusable sensing platform to quantify biomarkers in high-risk patients at clinical and point-of-care settings. The capability to integrate hydrogel-based systems with optical transducers will provide quantitative and colorimetric measurements via spectrophotometric analyses of biomarkers. Here, we created an imprinting method to rapidly produce 2.5D photonic concavities in phenylboronic acid functionalized hydrogel films. Our method exploited diffraction properties of hexagonally-packed 2.5D photonic microscale concavities having a lattice spacing of 3.3 μm. Illumination of the 2.5D hexagonally-packed structure with a monochromatic light source in transmission mode allowed reversible and quantitative measurements of variation in the glucose concentration based on first order lattice interspace tracking. Reversible covalent phenylboronic acid coupling with cis-diols of glucose molecules expanded the hydrogel matrix by ∼2% and 34% in the presence of glucose concentrations of 1 mM and 200 mM, respectively. A Donnan osmotic pressure induced volumetric expansion of the hydrogel matrix due to increasing glucose concentrations (1–200 mM), resulted in a nanoscale modulation of the lattice interspace, and shifted the diffraction angle (∼45° to 36°) as well as the interspacing between the 1st order diffraction spots (∼8 to 3 mm). The sensor exhibited a maximum lattice spacing diffraction shift within a response time of 15 min in a reversible manner. The developed 2.5D photonic sensors may have application in medical point-of-care diagnostics, implantable chips, and wearable continuous glucose monitoring devices

On the high accuracy to test dragging of inertial frames with the LARES 2 space experiment

In this paper we treat some aspects of the LARES 2 space experiment to test the general relativistic phenomenon of dragging of inertial frames, or frame-dragging, in particular we discuss some aspects of its relative accuracy which can approach one part in a thousand. We then, once again respond to the criticisms of the author of a recent paper about the accuracy in the measurement of frame-dragging with LARES 2. The claims of such a paper are not reproducible in any independent analyses. Indeed, it claims that the accuracy in the test of frame-dragging, which can be reached by the LARES 2 space experiment, is several orders of magnitude larger than previously estimated in a number of papers. Here we show that such a paper is based on a number of significant misunderstandings and conceptual mistakes. Furthermore, it is puzzling to observe that previous papers by the same author contained completely opposite statements about the accuracy which can be reached using two satellites with supplementary inclinations, such as in the LARES 2 space experiment, and in general with laser-ranged satellites

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Interpretation of wire-scanner asymmetric profiles in a low-energy ring

In the CERN PS Booster, wire-scanner profile measurements performed at injection energy are affected by a strong asymmetry. The shape was reproduced with the code PyORBIT, assuming that the effect is due to the beam evolution during the scans, under the influence of space-charge forces and Multiple Coulomb Scattering at the wire itself. Reproducing the transverse profiles during beam evolution allows to use them reliably as input for simulation benchmarking

Tail Repopulation Measurements in the PSB

The PS Booster (PSB) is the first circular accelerator in the LHC injector chain providing protons for the full CERN complex. Each of its four rings provides beams in a range of intensities varying from 40 e11 p/cycle to 0.8 e13 p/cycle. Low intensity beams are produced by transverse shaving, that is by scraping the tails, in order to tailor the intensity and transverse emittances. Eventually, tails repopulate and the beam profile reshapes, under the effect of space charge, which is dominant at low energy in the PS Booster. This paper describes the results of the measurements after the shaving process, where the tails are scraped but finally re-appear in the transverse profile, and it provides a first benchmark with space-charge simulations. It highlights the challenges encountered and the lessons learned, to guide the future experiments. The final outcome of these studies is the characterisation of the halo creation mechanism and the determination of the diffusion speed, important for the design of the future PS Booster scraping system

Resource-Based Internet Intervention (Med-Stress) to Improve Well-Being Among Medical Professionals : Randomized Controlled Trial

BACKGROUND: Medical professionals are exposed to multiple and often excessive demands in their work environment. Low-intensity internet interventions allow them to benefit from psychological support even when institutional help is not available. Focusing on enhancing psychological resources-self-efficacy and perceived social support-makes an intervention relevant for various occupations within the medical profession. Previously, these resources were found to operate both individually or sequentially with self-efficacy either preceding social support (cultivation process) or following it (enabling process). OBJECTIVE: The objective of this randomized controlled trial is to compare the efficacy of 4 variants of Med-Stress, a self-guided internet intervention that aims to improve the multifaceted well-being of medical professionals. METHODS: This study was conducted before the COVID-19 pandemic. Participants (N=1240) were recruited mainly via media campaigns and social media targeted ads. They were assigned to 1 of the following 4 groups: experimental condition reflecting the cultivation process, experimental condition reflecting the enabling process, active comparator enhancing only self-efficacy, and active comparator enhancing only perceived social support. Outcomes included 5 facets of well-being: job stress, job burnout, work engagement, depression, and job-related traumatic stress. Measurements were taken on the web at baseline (time 1), immediately after intervention (time 2), and at a 6-month follow-up (time 3). To analyze the data, linear mixed effects models were used on the intention-to-treat sample. The trial was partially blinded as the information about the duration of the trial, which was different for experimental and control conditions, was public. RESULTS: At time 2, job stress was lower in the condition reflecting the cultivation process than in the one enhancing social support only (d=-0.21), and at time 3, participants in that experimental condition reported the lowest job stress when compared with all 3 remaining study groups (ds between -0.24 and -0.41). For job-related traumatic stress, we found a significant difference between study groups only at time 3: stress was lower in the experimental condition in which self-efficacy was enhanced first than in the active comparator enhancing solely social support (d=-0.24). The same result was found for work engagement (d=-0.20), which means that it was lower in exactly the same condition that was found beneficial for stress relief. There were no differences between study conditions for burnout and depression neither at time 2 nor at time 3. There was a high dropout in the study (1023/1240, 82.50% at posttest), reflecting the pragmatic nature of this trial. CONCLUSIONS: The Med-Stress internet intervention improves some components of well-being-most notably job stress-when activities are completed in a specific sequence. The decrease in work engagement could support the notion of dark side of this phenomenon, but further research is needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT03475290; https://clinicaltrials.gov/ct2/show/NCT03475290. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3401-9