The Dilemma of Standard Setting for the OSCE

Background: Recently disparities between the OSCE raw scores and global scores have resulted in the need treatment of the raw scores in different ways such as borderline regression and borderline group regression. The object of this paper is to present station scoring forms designed to satisfy predetermined criteria and minimum pass levels.Methods: Available samples of marking sheets and checklists designed by variousexamining bodies were scrutinized. Criteria were prioritized according to commonly used grading systems. The station rating scale (check list) was designed to allow the observer to concentrate on checking the performance of the candidate without marking at the same time. The station marks form enables entry of marks based on the criteria in the Station rating scale.Results: Three forms were designed. Forms 1 & 2 should be prepared beforehand with real or standardized patients. Form 3 is a combination to be used when last minute stations are introduced. The mark allocated to each observable criterion is made within the limits of the specified criteria. The global score has been retained to check for inconsistencies and for longitudinal studies on validity and reliability.Conclusions: Prototype forms are presented; using predetermined, categorized grading criteria. The forms enable examiners to separate the observation stage from the actual allocation of marks. As in all OSCE settings, objectivity, validity and reliability will depend on prioritizing the selection of stations, clarity of the selected criteria and the training of examiners

GM-CSF production from human airway smooth muscle cells is potentiated by human serum.

Recent evidence suggests that airway smooth muscle cells (ASMC) actively participate in the airway inflammatory process in asthma. Interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1) allergic asthmatic serum (AAS) modulates ASMC mediator release in response to IL-1beta and TNF-alpha, and (2) IL-1beta/TNF-alpha prime ASMC to release mediators in response to AAS. IL-5 and GM-CSF were quantified by ELISA in culture supernatants of; (1) ASMC pre-incubated with either AAS, nonallergic non-asthmatic serum (NAS) or Monomed (a serum substitute) and subsequently stimulated with IL-1beta and TNF-alpha and (2) ASMC stimulated with IL-1beta/TNF-alpha and subsequently exposed to either AAS, NAS or Monomed. IL-1beta and TNF-alpha induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or Monomed. IL-1beta and TNF-alpha, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL-1beta/TNF-alpha and serum exposure (AAS or NAS) was significantly greater than that following IL-1beta/TNF-alpha and Monomed exposure or IL-1beta/TNF-alpha exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage

Hydrodynamics, Mass and Heat Transferin Reactive Distillation

The ethyl acetate synthesis via heterogeneous reactive distillation is studied experimentally using ethanol and acetic acid. Three types of cation exchanging resins were used as catalysts: Zerolit 225, Zerolit 226 and Ambylite 400. Experiments were carried out in two units of the same dimensions. Each unit consisted of three sections: rectifying, reactive and stripping sections of heights (60+25+20) cm respectively and 2.5cm column diameter. The first unit (column-A-) was a fractionation type and the second unit (column-B-) was packed column. The packing type was hollow glass cylinders with 10 mm height, and 4, 5 mm inner and outer diameter respectively. <br /> The experiments were carried out by using two operation modes. The semi-batch and continuous operation mode. In the first part of present investigation, the semi-batch mode was used to evaluate the catalyst type and to evaluate the performance of reactive distillation unit configuration (Fractionation and packed column). Results show that, the column-B- gave higher conversion rates than column-A-. This is attributed to the high surface area available for liquid vapour contact in packed type column, which leads to increasing mass transfer rates. On the other hand, Ambylite 400 catalyst showed higher activity for esterification reaction than other two types of catalysts. <br /> The second part of work continued with column -B- only. It is well known that, the esterification process is regarded one of exothermic reactions. Therefore, the monitoring of the temperature distribution along column axial for all three types of catalysts showed that the temperature distribution was essentially the same due to steady state operation in continuous operation mode. On the other hand, the effect of reflux ratio on temperature distribution was clearly noted, that is as the reflux ratio increased the temperature distribution along the column was reduced for each type of catalysts.<br /> On the other hand, the experimental results point that, as a reflux ratio increases the conversion rates of acetic acid is increased too because such increasing is related to high mass transfer rates between vapour and liquid along reactive distillation column. <br /

Effects of ischaemic conditioning on major clinical outcomes in people undergoing invasive procedures: systematic review and meta-analysis.

OBJECTIVE:  To summarise the benefits and harms of ischaemic conditioning on major clinical outcomes in various settings. DESIGN:  Systematic review and meta-analysis. DATA SOURCES:  Medline, Embase, Cochrane databases, and International Clinical Trials Registry platform from inception through October 2015. STUDY SELECTION:  All randomised controlled comparisons of the effect of ischaemic conditioning on clinical outcomes were included. DATA EXTRACTION:  Two authors independently extracted data from individual reports. Reports of multiple intervention arms were treated as separate trials. Random effects models were used to calculate summary estimates for all cause mortality and other pre-specified clinical outcomes. All cause mortality and secondary outcomes with P<0.1 were examined for study quality by using the GRADE assessment tool, the effect of pre-specified characteristics by using meta-regression and Cochran C test, and trial sequential analysis by using the Copenhagen Trial Unit method. RESULTS:  85 reports of 89 randomised comparisons were identified, with a median 80 (interquartile range 60-149) participants and median 1 (range 1 day-72 months) month intended duration. Ischaemic conditioning had no effect on all cause mortality (68 comparisons; 424 events; 11 619 participants; risk ratio 0.96, 95% confidence interval 0.80 to 1.16; P=0.68; moderate quality evidence) regardless of the clinical setting in which it was used or the particular intervention related characteristics. Ischaemic conditioning may reduce the rates of some secondary outcomes including stroke (18 trials; 5995 participants; 149 events; risk ratio 0.72, 0.52 to 1.00; P=0.048; very low quality evidence) and acute kidney injury (36 trials; 8493 participants; 1443 events; risk ratio 0.83, 0.71 to 0.97; P=0.02; low quality evidence), although the benefits seem to be confined to non-surgical settings and to mild episodes of acute kidney injury only. CONCLUSIONS:  Ischaemic conditioning has no overall effect on the risk of death. Possible effects on stroke and acute kidney injury are uncertain given methodological concerns and low event rates. Adoption of ischaemic conditioning cannot be recommended for routine use unless further high quality and well powered evidence shows benefit

Reaction Kinetics of Acetic Acid and n-Butanol Esterification Catalyzed by Dowex 50 Catalyst

The reaction kinetics of the n-butanol esterification and acetic acid on acidic solid catalyst named Dowex 50 under atmospheric pressure was investagated in this work. Reaction experiments were carried out in a stirred batch reactor at temperature range of 343 to 363 K, under various catalyst loads and various starting reactants feed ratios. The experimental data were fitted to estimate the kinetic parameters for reaction mechanisms by using MATLAB 7 software. The chemical equilibrium composition was measured and kinetic information was obtained at the same temperature range. The results show that the activation energy of n-butanol esterification reaction was found to be 39.975 kJ/mol. Finally the results of produced reaction mechanisms were compared with experimental results to validate the reaction mechanism. Then it was conclud that the model results with the regressed kinetic parameters are in excellent agreement with the experimental results

Anti-hypothalamus autoantibodies in anorexia nervosa: a possible new mechanism in neuro-physiological derangement?

Purpose: Anorexia nervosa (AN) is a serious and complex mental disorder affecting mainly young adult women. AN patients are characterized by low body weight in combination with self-induced starvation, intense fear of gaining weight, and distortion of body image. AN is a multifactorial disease, linked by recent evidence to a dysregulation of the immune system. Methods: In this pilot study, 22 blood serums from AN patients were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. Cellular fluorescence suggests the presence of autoantibodies which are able to recognize these neurons (both to body cell and fiber levels). By means of ELISA, these autoantibodies are quantitatively evaluated. In addition, orexigenic and anorexigenic molecules were measured by ELISA. As control, 18 blood serums from healthy age matched woman were analysed. Results: All AN patients showed a reactivity against hypothalamic neurons both by immunofluorescence and ELISA. In addition, ghrelin, pro-opiomelanocortin (POMC), and agouti-related peptide (AGRP) were significantly higher than in control serums (p &lt; 0.0001). In contrast, leptin was significantly lower in AN patients than controls (p &lt; 0.0001). Conclusions: Immunoreaction and ELISA assays on AN blood serum suggest the presence of autoantibodies AN related. However, it is not easy to determine the action of these antibodies in vivo: they could interact with specific ligands expressed by hypothalamic cells preventing their physiological role, however, it is also possible that they could induce an aspecific stimulation in the target cells leading to an increased secretion of anorexigenic molecules. Further studies are needed to fully understand the involvement of the immune system in AN pathogenesis

The nasal delivery of nanoencapsulated statins – An approach for brain delivery

© 2016 Clementino et al. Purpose: Along with their cholesterol-lowering effect, statins have shown a wide range of pleiotropic effects potentially beneficial to neurodegenerative diseases. However, such effects are extremely elusive via the conventional oral administration. The purpose of the present study was to prepare and characterize the physicochemical properties and the in vivo biodistribution of simvastatin-loaded lecithin/chitosan nanoparticles (SVT-LCNs) suitable for nasal administration in view of an improved delivery of the statins to the brain. Materials and methods: Chitosan, lecithin, and different oil excipients were used to prepare nanocapsules loaded with simvastatin. Particle size distribution, surface charge, structure, simvastatin loading and release, and interaction with mucus of nanoparticles were determined. The nanoparticle nasal toxicity was evaluated in vitro using RPMI 2651 nasal cell lines. Finally, in vivo biodistribution was assessed by gamma scintigraphy via Tc99m labeling of the particles. Results: Among the different types of nanoparticles produced, the SVT-LCN_MaiLab showed the most ideal physicochemical characteristics, with small diameter (200 nm), positive surface charge (+48 mV) and high encapsulation efficiency (EE; 98%). Size distribution was further confirmed by nanoparticle tracking analysis and electron microscopy. The particles showed a relatively fast release of simvastatin in vitro (35.6%±4.2% in 6 hours) in simulated nasal fluid. Blank nanoparticles did not show cytotoxicity, evidencing that the formulation is safe for nasal administration, while cytotoxicity of simvastatin-loaded nanoparticles (IC50) was found to be three times lower than the drug solution (9.92 vs 3.50 μM). In rats, a significantly higher radioactivity was evidenced in the brain after nasal delivery of simvastatin-loaded nanoparticles in comparison to the administration of a similar dose of simvastatin suspension. Conclusion: The SVT-LCNs developed presented some of the most desirable characteristics for mucosal delivery, that is, small particle size, positive surface charge, long-term stability, high EE, and mucoadhesion. In addition, they displayed two exciting features: First was their biodegradability by enzymes present in the mucus layer, such as lysozyme. This indicates a new Trojan-horse strategy which may enhance drug release in the proximity of the nasal mucosa. Second was their ability to enhance the nose-to-brain transport as evidenced by preliminary gamma scintigraphy studies

Prior Cardiovascular Treatments-A Key Characteristic in Determining Medication Adherence After an Acute Myocardial Infarction.

Objective: To investigate long-term adherence to guideline-recommended cardioprotective medications following hospitalization for an acute myocardial infarction (AMI), and identify characteristics associated with adherence. Methods: An Australian population-based cohort study was used to identify participants who had their first AMI between 2006 and 2014 and were alive after 12 months. Linked routinely collected hospital, and prescription medication claims data was used to study adherence over time. Predictors and rates of adherence to both lipid-lowering medication and renin-angiotensin system blockade at 12 months post-AMI was assessed. Results: 14,200 people (mean age 69.9 years, 38.7% female) were included in our analysis. At 12 months post-AMI, 29.5% (95% CI: 28.8-30.3%) of people were adherent to both classes of medication. Individuals receiving treatment with both lipid-lowering medication and renin-angiotensin system blockade during the 6 months prior to their AMI were over 9 times more likely to be adherent to both medications at 12 months post-AMI (66.2% 95% CI: 64.8-67.5%) compared to those with no prior medication use (treatment naïve) (7.1%, 95% CI: 6.4-7.9%). Prior cardiovascular treatment was the strongest predictor of long-term adherence even after adjusting for age, sex, education and income. Conclusions: Despite efforts to improve long-term medication adherence in patients who have experienced an acute coronary event, considerable gaps remain. Of particular concern are people who are commencing guideline-recommended cardioprotective medication at the time of their AMI. The relationship between prior cardiovascular treatments and post AMI adherence offers insight into the support needs for the patient. Health care intervention strategies, strengthened by enabling policies, are needed to provide support to patients through the initial months following their AMI

Investigation Nano coating for Corrosion Protection of Petroleum Pipeline Steel Type A106 Grade B; Theoretical and Practical Study in Iraqi Petroleum Sector

In the present investigation, titania (TiO2) nano-thin films were deposited on steel type A106-B, by using the Pulse Laser Deposition (PLD) technique to obtain passive layers of nano-coating. Electrochemical methods (Tafel completion) are used for study corrosion behavior of steel coating. The A106-B specimens were evaluated in 3.5 wt. % NaCl aqueous solution by using polarization technique with pH adjustment to 4.0 in order to determine the corrosion rate. The samples of TiO2 thin films were characterized by SEM, AFM, XRD, and FTIR. The input parameters were substrate temperature (100, 200 and 300) ’0C’, number of pulse (300, 400 and 500) and fluencies energy (800, 900 and 1000) mJ/cm2, have been investigated to detect their impact on corrosion reduction rate using Taguchi methodology orthogonal array and Analysis of Variance (ANOVA).The ANOVA results indicates that number of shoots pulse significantly affecting the corrosion rate in PLD technique, which is highest among the contributions of the other parameters which is (58.03%) about three times of the fluencies energy (19.12%).The results show that the TiO2 deposition on steels offers an excellent corrosion resistance about 99 times as compared with uncoated steel. The optimum conditions to minimum values corrosion rate are: temperature of 300ºC, number of laser pulses at 300, and fluencies energy equal to 1000 mJ/cm2. Finally the optimal parameters that was used to predict the conclusions were (98.6) to the response of corrosion rate

Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) – A Strategic Option for India

The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable, other better formulations and second line ARVs for adults and more drugs and formulations for paediatric groups, that are still to be widely available in India and other developing countries. To examine whether strong intellectual property (IP) protection systems are to be considered important barriers for the limited or lack of access to ARVs, we studied the patent profile of the ARVs of the originator companies within and outside India. We could record 93 patents in the United States Patent & Trademark Office (USPTO). The originator companies have been also aggressively filing and enforcing patents in India. There have been a few efforts by companies like Gilead and GSK to grant licenses to generic manufacturers in developing countries, ostensibly to promote access to ARVs through lower (two-tier) pricing. These steps are considered as too little and too late. There is an urgent need to look for alternative strategies to promote access to ARVs both linked to and independent of IPRs. Patent pooling as a viable strategy mooted by the UNITAID should be seriously explored to promote access to ARVs. India is ideally suited for trying out the patent pool strategy as most of the global requirement of affordable ARV drugs for HIV/AIDS treatment is sourced from Indian generic companies