RANITIDINE CONTROLLED RELEASE ANTI-REFLUX SUSPENSION FOR GASTRO-OESOPHAGEAL REFLUX DISEASE AND IT’S IN VITRO EVALUATION

Objective: The aim of this work was to develop triple action controlled release anti-reflux suspension of ranitidine and its in-vitro evaluation of anti-reflux and controlled release properties. Methods: The formulation was optimized using sodium alginate as a gelling agent along with calcium carbonate, sodium bicarbonate, magnesium hydroxide, aluminium hydroxide as alkalizing agents and colloidal microcrystalline cellulose (MCC) as a suspending agent at various concentrations and arrived at an optimized formulation for its best quality attributes. To avoid initial release in water before administration, ranitidine coated MCC sphere was incorporated into powder formulation and subjected to in vitro characteristics like raft strength, acid neutralizing capacity, pH, viscosity and dissolution study. The obtained results were assessed using Minitab 17 statistical software to conclude the study design. Results: Formulation containing 300 mg of ranitidine along with 750 mg alginate has shown better anti-reflux characteristics like raft strength 18±2g, acid neutralizing capacity 17±1 mEq compared to other formulations. This formulation has also shows zero-order controlled release in the simulated gastric fluid (SGF) up to 10 h compared to the formulation without alginate. Further, to this optimized formulation has shown negligible change in the assay of ranitidine even after 3 mo at 40 °C temperature and 75% RH. Conclusion: The developed stable sustained release powder for suspension has the combined therapeutic efficacy as an antacid and anti-reflux drug suitable for the management and treatment of gastro-oesophageal reflux disease (GERD) unlike the existing drugs possessing only reflux resistance action

Long-Term Observations Of The Pulsars In 47 Tucanae – I. A Study Of Four Elusive Binary Systems

For the past couple of decades, the Parkes radio telescope has been regularly observing the millisecond pulsars in 47 Tucanae (47 Tuc). This long-term timing program was designed to address a wide range of scientific issues related to these pulsars and the globular cluster where they are located. In this paper, the first of a series, we address one of these objectives: the characterization of four previously known binary pulsars for which no precise orbital parameters were known, namely 47 Tuc P, V, W and X (pulsars 47 Tuc R and Y are discussed elsewhere). We determined the previously unknown orbital parameters of 47 Tuc V and X and greatly improved those of 47 Tuc P and W. For pulsars W and X we obtained, for the first time, full coherent timing solutions across the whole data span, which allowed a much more detailed characterization of these systems. 47 Tuc W, a well-known tight eclipsing binary pulsar, exhibits a large orbital period variability, as expected for a system of its class. 47 Tuc X turns out to be in a wide, extremely circular, 10.9-day long binary orbit and its position is ~3.8 arcmin away from the cluster center, more than three times the distance of any other pulsar in 47 Tuc. These characteristics make 47 Tuc X a very different object with respect to the other pulsars of the cluster

Long-term observations of the pulsars in 47 Tucanae - II. Proper motions, accelerations and jerks

This paper is the second in a series where we report the results of the long-term timing of the millisecond pulsars (MSPs) in 47 Tucanae with the Parkes 64-m radio telescope. We obtain improved timing parameters that provide additional information for studies of the cluster dynamics: a) the pulsar proper motions yield an estimate of the proper motion of the cluster as a whole ($\mu_{\alpha}\, = \, 5.00\, \pm \, 0.14\, \rm mas \, yr^{-1}$, $\mu_{\delta}\, = \, -2.84\, \pm \, 0.12\, \rm mas \, yr^{-1}$) and the motion of the pulsars relative to each other. b) We measure the second spin-period derivatives caused by the change of the pulsar line-of-sight accelerations; 47 Tuc H, U and possibly J are being affected by nearby objects. c) For ten binary systems we now measure changes in the orbital period caused by their acceleration in the gravitational field of the cluster. From all these measurements, we derive a cluster distance no smaller than $\sim\,$4.69 kpc and show that the characteristics of these MSPs are very similar to their counterparts in the Galactic disk. We find no evidence in favour of an intermediate mass black hole at the centre of the cluster. Finally, we describe the orbital behaviour of the four "black widow" systems. Two of them, 47 Tuc J and O, exhibit orbital variability similar to that observed in other such systems, while for 47 Tuc I and R the orbits seem to be remarkably stable. It appears, therefore, that not all "black widows" have unpredictable orbital behaviour.Comment: 21 pages in journal format, 9 figures, 4 tables, accepted for publication in MNRAS, several clarifications made and typos fixe

What Matters Most to Patients and Rheumatologists? A Discrete Choice Experiment in Rheumatoid Arthritis

Introduction: To determine patient and rheumatologist preferences for rheumatoid arthritis (RA) treatment attributes in Spain and to evaluate their attitude towards shared decision-making (SDM). Methods: Observational, descriptive, exploratory and cross-sectional study based on a discrete choice experiment (DCE). To identify the attributes and their levels, a literature review and two focus groups (patients [P] = 5; rheumatologists [R] = 4) were undertaken. Seven attributes with 2–4 levels were presented in eight scenarios. Attribute utility and relative importance (RI) were assessed using a conditional logit model. Patient preferences for SDM were assessed using an ad hoc questionnaire. Results: Ninety rheumatologists [52.2% women; mean years of experience 18.1 (SD: 9.0); seeing an average of 24.4 RA patients/week (SD: 15.3)] and 137 RA patients [mean age: 47.5 years (SD: 10.7); 84.0% women; mean time since diagnosis of RA: 14.2 years (SD: 11.8) and time in treatment: 13.2 years (SD: 11.2), mean HAQ score 1.2 (SD: 0.7)] participated in the study. In terms of RI, rheumatologists and RA patients viewed: time with optimal QoL: R: 23.41%/P: 35.05%; substantial symptom improvement: R: 13.15%/P: 3.62%; time to onset of treatment action: R: 16.24%/P: 13.56%; severe adverse events: R: 10.89%/P: 11.20%; mild adverse events: R: 4.16%/P: 0.91%; mode of administration: R: 25.23%/P: 25.00%; and added cost: R: 6.93%/P: 10.66%. Nearly 73% of RA patients were involved in treatment decision-making to a greater or lesser extent; however, 27.4% did not participate at all. Conclusion: Both for rheumatologists and patients, the top three decision-making drivers are time with optimal quality, treatment mode of administration and time to onset of action, although in different ranking order. Patients were willing to be more involved in the treatment decision-making process

Long-term observations of the pulsars in 47 Tucanae. I. A study of four elusive binary systems

For the past couple of decades, the Parkes radio telescope has been regularly observing the millisecond pulsars in 47 Tucanae (47 Tuc). This long-term timing program was designed to address a wide range of scientific issues related to these pulsars and the globular cluster where they are located. In this paper, the first of a series, we address one of these objectives: the characterization of four previously known binary pulsars for which no precise orbital parameters were known, namely 47 Tuc P, V, W and X (pulsars 47 Tuc R and Y are discussed elsewhere). We determined the previously unknown orbital parameters of 47 Tuc V and X and greatly improved those of 47 Tuc P and W. For pulsars W and X we obtained, for the first time, full coherent timing solutions across the whole data span, which allowed a much more detailed characterization of these systems. 47 Tuc W, a well-known tight eclipsing binary pulsar, exhibits a large orbital period variability, as expected for a system of its class. 47 Tuc X turns out to be in a wide, extremely circular, 10.9-day long binary orbit and its position is ~3.8 arcmin away from the cluster center, more than three times the distance of any other pulsar in 47 Tuc. These characteristics make 47 Tuc X a very different object with respect to the other pulsars of the cluster.Comment: Accepted for publication by MNRAS, 18 pages, 11 figure

A Cosmic Census of Radio Pulsars with the SKA

The Square Kilometre Array (SKA) will make ground breaking discoveries in pulsar science. In this chapter we outline the SKA surveys for new pulsars, as well as how we will perform the necessary follow-up timing observations. The SKA's wide field-of-view, high sensitivity, multi-beaming and sub-arraying capabilities, coupled with advanced pulsar search backends, will result in the discovery of a large population of pulsars. These will enable the SKA's pulsar science goals (tests of General Relativity with pulsar binary systems, investigating black hole theorems with pulsar-black hole binaries, and direct detection of gravitational waves in a pulsar timing array). Using SKA1-MID and SKA1-LOW we will survey the Milky Way to unprecedented depth, increasing the number of known pulsars by more than an order of magnitude. SKA2 will potentially find all the Galactic radio-emitting pulsars in the SKA sky which are beamed in our direction. This will give a clear picture of the birth properties of pulsars and of the gravitational potential, magnetic field structure and interstellar matter content of the Galaxy. Targeted searches will enable detection of exotic systems, such as the ~1000 pulsars we infer to be closely orbiting Sgr A*, the supermassive black hole in the Galactic Centre. In addition, the SKA's sensitivity will be sufficient to detect pulsars in local group galaxies. To derive the spin characteristics of the discoveries we will perform live searches, and use sub-arraying and dynamic scheduling to time pulsars as soon as they are discovered, while simultaneously continuing survey observations. The large projected number of discoveries suggests that we will uncover currently unknown rare systems that can be exploited to push the boundaries of our understanding of astrophysics and provide tools for testing physics, as has been done by the pulsar community in the past.Comment: 20 pages, 7 figures, to be published in: "Advancing Astrophysics with the Square Kilometre Array", Proceedings of Science, PoS(AASKA14)04

Accidental carbon monoxide poisoning presenting without a history of exposure: A case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Rotation measure variations in Galactic Centre pulsars

We report the results of an observational campaign using the Effelsberg 100-m telescope of the pulsars J1746$-$2849, J1746$-$2850, J1746$-$2856 and J1745$-$2912 located in the Central Molecular Zone (CMZ) close to the Galactic centre in order to study rotation measure (RM) variations. We report for the first time the RM value of PSR J1746$-$2850 to be $-12234 \pm 181$ rad m$^{-2}$. This pulsar shows significant variations of RM of $300-400$ rad m$^{-2}$ over the course of months to years that suggest a strongly magnetized environment. The structure function analysis of the RM of PSR J1746$-$2850 revealed a steep power-law index of $1.87_{-0.3}^{+0.4}$ comparable to the value expected for isotropic turbulence. This pulsar also showed large dispersion measure (DM) variation of $\sim 50$ pc cm$^{-3}$ in an event lasting a few months where the RM increased by $\sim 200$ rad m$^{-2}$. The large difference in RM between PSR J1746$-$2849 and PSR J1746$-$2850 despite the small angular separation reveals the presence of a magnetic field of at least 70 $\mu$G in the CMZ and can explain the lack of polarization in the radio images of the region. These results contribute to our understanding of the magnetic field in the CMZ and show similarities between the RM behaviours of these pulsars and some fast radio bursts (FRBs).Comment: Accepted for publication on Monthly Notices of the Royal Astronomical Society, 13 pages, 7 figure

Clinical factors associated with discontinuation of ts/bDMARDs in rheumatic patients from the BIOBADASER III registry

Altres ajuts: Spanish Agency of Medicines and Medical Devices (AEMPS); Biogen; Bristol Myers-Squibb (BMS); Celltrion Healthcare; Lilly; Merck; Novartis; Pfizer; Regeneron Pharmaceuticals; Samsung Bioepis.Biologic and targeted synthetic disease-modifying antirheumatic drugs (ts/bDMARDs) play a pivotal role in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Persistence of therapy provides an index of a drug's overall effectiveness. The objective of the study was to identify factors associated with discontinuation of ts/bDMARDs in a real-world dataset. The study population comprised patients diagnosed with RA, PsA, and AS included in the BIOBADASER registry for whom follow-up data were available until November 2019. Patient features and treatment data were included in the analysis. The Kaplan-Meier method was used to study survival of the different drugs according to the reason for discontinuation. Factors associated with discontinuation were studied using Cox regression models and bivariate and multivariate analyses. P values of less than 0.05 were regarded as statistically significant. The study population comprised 4,752 patients who received a total of 8,377 drugs, of which 4,411 (52.65%) were discontinued. The Kaplan-Meier curves showed that survival for first-line treatment was greater in all 3 groups (p < 0.001). Patients with RA had a greater risk of discontinuation if they were younger (HR, 0.99; 95% CI 0.99-1.00), if they were receiving anti-TNFα agents (HR, 0.61; 95% CI 0.54-0.70), and if they had more comorbid conditions (HR, 1.09; 95% CI 1.00-1.17). Patients with PsA had a higher risk if they were women (HR, 1.36; 95% CI 1.15-1.62) and if they were receiving other ts/bDMARDs (HR, 1.29; 95% CI 1.05-1.59). In patients with AS, risk increased with age (HR, 1.01; 95% CI 1.00-1.02), as did the number of comorbid conditions (HR, 1.27; 95% CI 1.12-1.45). The factors that most affected discontinuation of ts/bDMARDs were line of treatment, age, type of drug, sex, comorbidity and the year of initiation of treatment. The association with these factors differed with each disease, except for first-line treatment, which was associated with a lower risk of discontinuation in all 3 diseases