RIFAMPICIN LOADED SPRAY-DRIED OLIBANUM GUM RESIN PULMOSPHERES FOR LUNG DELIVERY

Pulmospheres of Rifampicin were prepared successfully with cyclodextrin using olibanum gum resin as a rate controlling biodegradable natural polymer by novel spray drying technique. Hydroxypropyl-β-cyclodextrin was used as solubilising agent to enhance the solubility and permeation of poorly soluble rifampicin. The physcochemical characteristics of   rifampicin loaded pulmospheres were evaluated for mean particle size, thermal behaviour and surface morphology. The mean particle size for optimized formulation F1 was found to be 3.5 µm and spray-dried pure rifampicin also showed same value. Scanning Electron Microphotographs of pure drug has shown a typical and regular size indicated crystalline nature, whereas, spray dried pure drug and formulation F1 have shown spherical particles with porous surface indicated the conversion of crystalline drug into amorphous form. Rifampicin loaded spray-dried pulmospheres using olibanum gum resin showed drug release up to 72 hours. The release of rifampicin was greater in simulated physiological fluid of pH 7.4 which was 94 % as compared to simulated lung fluid of pH 5.2 at the end of 72 hours. Rifampicin loaded spray-dried microspheres were proposed for pulmonary drug delivery.   Keywords: Rifampicin, Lung targeting, Olibanum gum resin, Spray-drying, Pulmosphere

A preliminary study on perioperative hemostatic effect of spray dried powder of <i>Chromolaena odorata</i> leaf extract

547-555Accidents or surgery often cause internal haemorrhage in liver and arteries which may lead to patient morbidity and mortality. The current hemostatic agents used for treatment like collagen, oxidized cellulose, and chitosan suffer from side effects which include infection, inflammation and even sepsis. In the present study, we studied the spray dried powder (SDP) of the aqueous extract of the leaves of Chromolaena odorata (L.) R.M.King & H.Rob., commonly known as Siam weed or Common floss flower and also Christmas bush, for its hemostatic efficacy in two experimental models of surgery. Firstly, the SDP was screened through standard pharmacognostical parameters, and a part of the liver was lacerated in rats and femoral artery was transected in rabbits to assess the blood loss in pre-weighed gauze with and without treatment. In the liver laceration model, an effective blood loss reduction of 54.30 % was observed with oral administration of SDP 7 days prior to surgery. Similarly, application of SDP at the site of artery transection caused 70.36% reduction in blood loss as compared to the control rabbit artery. The results suggest that oral delivery and/or application of SDP of C. odorata by formulating it in a suitable drug delivery tool could minimize perioperative bleeding in hepatic and arterial tissue and improve recovery

Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study

Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3&nbsp;days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3&nbsp;days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60\u20131.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14\u20131.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure

Photo-Stabilisation and UV Blocking Efficacy of Coated Macro and Nano-Rutile Titanium Dioxide Particles in Paints and Coatings

Surface treated macro and nanoparticle TiO2samples have been prepared, characterised and their efficiency as UV blockers evaluated in clear coatings and paints. The particle size of the ‘base’ TiO2has been optimised to block UV radiation and the surface treatment developed to deactivate the photocatalytic activity of the surface of the TiO2particles. The resultant UV blockers have been evaluated in both solvent and water-based clear coatings. Nanoparticle TiO2has been prepared from ‘seed’ and the particle size was controlled by calcination. It was found that the choice of particle size is a compromise between UVA absorption, UVB absorption, visible transmission and photoactivity. It has been demonstrated that TiO2with a crystallite size of 25 nm yields a product with the optimum properties. A range of dispersants was successfully used to disperse and mill the TiO2. Both organic and inorganic dispersants were used; 2-amino-2-methyl-1-propanol and 1-amino-2-propanol (MIPA) and P2O5and Na2SiO3respectively. The surface of the nano-TiO2was coated with mixed oxides of silicon, aluminium, zirconium and phosphorous. Addition of the resultant coated nano-rutiles to an Isocyanate Acrylic clear coating prolonged the lifetime of that coating compared to the blank. Generally, a surface treatment based on SiO2, Al2O3and P2O5was more successful than one based on ZrO2, Al2O3and P2O5. Higher addition levels of the surface treatment were beneficial for protecting the polymeric coating. The UV blocker products were also evaluated in a water-based acrylic, first a water-based dispersion of the UV blocker was prepared before addition to the acrylic. The dispersions and resultant acrylic thin films were evaluated using UV/Vis spectroscopy and durability assessed. The ratio of absorbance at 300:500 nm for the water-based dispersion was shown to be a good predictor of both the transparency of the resultant acrylic thin film and the durability of that film, in terms of weight loss. Macro grade titanium dioxide pigments were also prepared and coated with treatments of silica, alumina and siloxane and their photo-stabilising activity in alkyd paint film assessed and found to be directly related to the electron–hole pair mobility and trapping as determined by micro-wave spectroscopy

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM