Novel Supercritical Carbon Dioxide Impregnation Technique for the Production of Amorphous Solid Drug Dispersions: A Comparison to Hot Melt Extrusion

The formulation of BCS Class II drugs as amorphous solid dispersions has been shown to provide advantages with respect to improving the aqueous solubility of these compounds. While hot melt extrusion (HME) and spray drying (SD) are among the most common methods for the production of amorphous solid dispersions (ASDs), the high temperatures often required for HME can restrict the processing of thermally labile drugs, while the use of toxic organic solvents during SD can impact on end-product toxicity. In this study, we investigated the potential of supercritical fluid impregnation (SFI) using carbon dioxide as an alternative process for ASD production of a model poorly water-soluble drug, indomethacin (INM). In doing so, we produced ASDs without the use of organic solvents and at temperatures considerably lower than those required for HME. Previous studies have concentrated on the characterization of ASDs produced using HME or SFI but have not considered both processes together. Dispersions were manufactured using two different polymers, Soluplus and polyvinylpyrrolidone K15 using both SFI and HME and characterized for drug morphology, homogeneity, presence of drug-polymer interactions, glass transition temperature, amorphous stability of the drug within the formulation, and nonsink drug release to measure the ability of each formulation to create a supersaturated drug solution. Fully amorphous dispersions were successfully produced at 50% w/w drug loading using HME and 30% w/w drug loading using SFI. For both polymers, formulations containing 50% w/w INM, manufactured via SFI, contained the drug in the γ-crystalline form. Interestingly, there were lower levels of crystallinity in PVP dispersions relative to SOL. FTIR was used to probe for the presence of drug-polymer interactions within both polymer systems. For PVP systems, the nature of these interactions depended upon processing method; however, for Soluplus formulations this was not the case. The area under the dissolution curve (AUC) was used as a measure of the time during which a supersaturated concentration could be maintained, and for all systems, SFI formulations performed better than similar HME formulations.

Re-inoculation of autoclaved soil as a non-sterile treatment for xenobiotic sorption and biodegradation studies

Autoclaved soil is commonly used for the study of xenobiotic sorption and as an abiotic control in biodegradation experiments. Autoclaving has been reported to alter soil physico-chemical and xenobiotic sorption characteristics such that comparison of autoclaved with non-autoclaved treatments in soil aging and bioavailability studies may yield misleading results. Experiments could be improved by using autoclaved soil re-inoculated with indigenous microorganisms as an additional or alternative non-sterile treatment for comparison with the sterile, autoclaved control. We examined the effect of autoclaving (3 x 1 h, 121°C, 103.5 KPa) on the physico-chemical properties of a silt loam soil (pH 7.2, 2.3% organic carbon) and the establishment of indigenous microorganisms reintroduced after autoclaving. Sterilisation by autoclaving significantly (p ≤ 0.05) decreased pH (0.6 of a unit) and increased concentrations of water-soluble organic carbon (WSOC; nontreated = 75 mg kg^-1; autoclaved = 1526 mg kg^-1). The initial first-order rate of ¹⁴C-2,4-dichloro-UL-phenol (2,4-DCP) adsorption to non-treated, autoclaved and re-inoculated soil was rapid (K₁ = 16.8-24.4 h^-1) followed by a slower linear phase (K₂). In comparison with autoclaved soil (0.038% day^-1), K₂ values were higher for re-inoculated (0.095% day^-1) and nontreated (0.181% day^-1) soil. This was attributed to a biological process. The Freundlich adsorption coefficient (K(f)) for autoclaved soil was significantly (p ≤ 0.05) higher than for re-inoculated or non-treated soil. Increased adsorption was attributed to autoclaving-induced changes to soil pH and solution composition. Glucose-induced respiration of autoclaved soil after re-inoculation was initially twice that in the non-treated control, but it decreased to control levels by day 4. This reduction corresponded to a depletion of WSOC. 2,4-DCP mineralisation experiments revealed that the inoculum of nonsterile soil (0.5 g) contained 2,4-DCP-degrading microorganisms capable of survival in autoclaved soil. The lag phase before detection of significant 2,4-DCP mineralisation was reduced (from 7 days to ≤3 days) by pre-incubation of re-inoculated soils for 7 and 14 days before 2,4-DCP addition. This was attributed to the preferential utilisation of WSOC prior to the onset of 2,4-DCP mineralisation. Cumulative ¹⁴CO₂ evolved after 21 days was significantly lower (p ≤ 0.05) from non-treated soil (25.3%) than re-inoculated soils (ca 45%). Experiments investigating sorption-biodegradation interactions of xenobiotics in soil require the physico-chemical properties of sterile and non-sterile treatments to be as comparable as possible. For fundamental studies, we suggest using re-inoculated autoclaved soil as an additional or alternative non-sterile treatment.

Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease

BACKGROUND: Heparin therapy may be effective in steroid resistant inflammatory bowel disease.

AIM: A randomized pilot study, to compare unfractionated heparin as a first-line therapy with corticosteroids in colonic inflammatory bowel disease.

METHODS: Twenty patients with severe inflammatory bowel disease (ulcerative colitis, n=17; Crohn's colitis, n=3) were randomized to either intravenous heparin for 5 days, followed by subcutaneous heparin for 5 weeks (n=8), or high-dose intravenous hydrocortisone for 5 days followed by oral prednisolone 40 mg daily, reducing by 5 mg per day each week (n=12). After 5 days, non-responders in each treatment group were commenced on combination therapy. Response to therapy was monitored by: clinical disease activity (ulcerative colitis: Truelove and Witt Index; Crohn's colitis: Harvey and Bradshaw Index), stool frequency, serum C-reactive protein and alpha1 acid glycoprotein, endoscopic and histopathological grading.

RESULTS: The response rates were similar in both treatment groups: clinical activity index (heparin vs. steroid; 75% vs. 67%; P=0.23), stool frequency (75% vs. 67%; P=0.61), endoscopic (75% vs. 67%; P=0.4) and histopathological grading (63% vs. 50%; P=0.67). Both treatments were well-tolerated with no serious adverse events.

CONCLUSION: Heparin as a first line therapy is as effective as corticosteroids in the treatment of colonic inflammatory bowel disease. Large multicentre randomized comparative studies are required to determine the role of heparin in the management of inflammatory bowel disease.

Enquiring about traumatic experiences in psychosis: A comparison of case notes and self-report questionnaires

Purpose: Studies have found an association between a history of trauma and the presence of psychotic symptoms. Despite the research evidence it appears to be the case that many clinicians are not routinely asking about traumatic experiences. This study aims to ascertain the level of agreement between rates of self-reported trauma and that which is recorded in case notes.

Methods: The study population was drawn from all individuals with a confirmed diagnosis of psychosis, residing within a defined catchment area. Rates of childhood trauma, lifetime trauma and trauma related to the Troubles in Northern Ireland recorded in participants’ case notes were compared to their responses on self-report questionnaires: THQ, CTQ and TREQ.

Results: Relatively high levels of trauma were reported by participants on the self-report measures that were administered. The rates of trauma recorded in case note records were similar to that found in other studies. Also in line with other research were poor levels of agreement between self-report and case note data.

Conclusion: High levels of lifetime, childhood and trauma related to the Troubles in Northern Ireland were found when the individuals in the sample were directly assessed for the purposes of this study. In contrast much lower rates were recorded in patient notes on routine clinical assessment. The results suggest that clinicians do not routinely enquire about trauma histories with this population and as a result, case notes underestimate trauma prevalence.

A comparison between accelerated hypofractionation and stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC): Results of a propensity score-matched analysis

BACKGROUND AND PURPOSE: Stereotactic ablative radiotherapy (SABR) has become standard for inoperable early-stage non-small cell lung cancer (NSCLC). However, there is no randomized evidence demonstrating benefit over more fractionated radiotherapy. We compared accelerated hypofractionation (AH) and SABR using a propensity score-matched analysis.

MATERIALS AND METHODS: From 1997-2007, 119 patients (T1-3N0M0 NSCLC) were treated with AH (48-60Gy, 12-15 fractions). Prior to SABR, this represented our institutional standard. From 2008-2012, 192 patients (T1-3N0M0 NSCLC) were treated with SABR (48-52Gy, 4-5 fractions). A total of 114 patients (57 per cohort) were matched (1:1 ratio, caliper: 0.10) using propensity scores.

RESULTS: Median follow-up (range) for the AH cohort was 36.3 (2.5-109.1) months, while that for the SABR group was 32.5 (0.3-62.6)months. Three-year overall survival (OS) and local control (LC) rates were 49.5% vs. 72.4% [p=0.024; hazard ratio (HR): 2.33 (1.28, 4.23), p=0.006] and 71.9% vs. 89.3% [p=0.077; HR: 5.56 (1.53, 20.2), p=0.009], respectively. On multivariable analysis, tumour diameter and PET staging were predictive for OS, while the only predictive factor for LC was treatment cohort.

CONCLUSIONS: OS and LC were improved with SABR, although OS is more closely related to non-treatment factors. This represents one of the few studies comparing AH to SABR for early-stage lung cancer.

A comparison of gold nanoparticle surface co-functionalization approaches using Polyethylene Glycol (PEG) and the effect on stability, non-specific protein adsorption and internalization

To create clinically useful gold nanoparticle (AuNP) based cancer therapeutics it is necessary to co-functionalize the AuNP surface with a range of moieties; e.g. Polyethylene Glycol (PEG), peptides and drugs. AuNPs can be functionalized by creating either a mixed monolayer by attaching all the moieties directly to the surface using thiol chemistry, or by binding groups to the surface by means of a bifunctional polyethylene glycol (PEG) linker. The linker methodology has the potential to enhance bioavailability and the amount of functional agent that can be attached. While there is a large body of published work using both surface arrangements independently, the impact of attachment methodology on stability, non-specific protein adsorption and cellular uptake is not well understood, with no published studies directly comparing the two most frequently employed approaches. This paper compares the two methodologies by synthesizing and characterizing PEG and Receptor Mediated Endocytosis (RME) peptide co-functionalized AuNPs prepared using both the mixed monolayer and linker approaches. Successful attachment of both PEG and RME peptide using the two methods was confirmed using Dynamic Light Scattering, Fourier Transform Infrared Spectroscopy and gel electrophoresis. It was observed that while the 'as synthesized' citrate capped AuNPs agglomerated under physiological salt conditions, all the mixed monolayer and PEG linker capped samples remained stable at 1M NaCl, and were stable in PBS over extended periods. While it was noted that both functionalization methods inhibited non-specific protein attachment, the mixed monolayer samples did show some changes in gel electrophoresis migration profile after incubation with fetal calf serum. PEG renders the AuNP stable in-vivo however, studies with MDA-MB-231 and MCF 10A cell lines indicated that functionalization with PEG, blocks cellular uptake. It was observed that co-functionalization with RME peptide using both the mixed monolayer and PEG linker methods greatly enhanced cellular internalization compared to PEG capped AuNPs.

Comparison of methods of eutrophication assessment in a coastal lagoon (Ria Formosa)

Dissertação de Mestrado, Gestão da Água e da Costa, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2010

Studies on honey from the Algarve in view of its valorization

Tese de dout., Química, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2012

Comparison of Two Pollen Counting Methods of Slides from a Hirst Type Volumetric Trap.

Two of the most frequently used methods of pollen counting on slides from Hirst type traps are evaluated in this paper: the transverse traverse method and the longitudinal traverse method. The study was carried out during June–July 1996 and 1997 on slides from a trap at Worcester, UK. Three pollen types were selected for this purpose: Poaceae, Urticaceae and Quercus. The statistical results show that the daily concentrations followed similar trends (p < 0.01, R-values between 0.78–0.96) with both methods during the two years, although the counts were slightly higher using the longitudinal traverses method. Significant differences were observed, however, when the distribution of the concentrations during 24 hour sampling periods was considered. For more detailed analysis, the daily counts obtained with both methods were correlated with the total number of pollen grains for the taxon over the whole slide, in two different situations: high and low concentrations of pollen in the atmosphere. In the case of high concentrations, the counts for all three taxa with both methods are significantly correlated with the total pollen count. In the samples with low concentrations, the Poaceae and Urticaceae counts with both methods are significantly correlated with the total counts, but none of Quercus counts are. Consideration of the results indicates that both methods give a reasonable approximation to the count derived from the slide as a whole. More studies need be done to explore the comparability of counting methods in order to work towards a Universal Methodology in Aeropalynology.

Effects of Social Media Platform Preference: a Country Comparison of Online University Reputations

Managing an online reputation is critical to higher education. Universities cannot afford to lose enrolment numbers by neglecting to monitor, control, promote and enhance their online presence. It is critical that universities measure their social media reputation scores and presence on the web, as well as those of their competitors. Universities need to continuously review their social engagement strategy and online reputation to ensure they maximize all opportunities to maintain, and improve student enrolment and retention. Universities have embraced social media to enhance their brand reputation. This study examines the use of social media and its effects from a global perspective. It analysed 90 universities in three geographical areas to assess the impact and level of online social media, especially as it relates to “university brand reputation.” Results of the study indicated there was a wide variation among the three geographical regions, and within countries in the three geographical regions. Use of social media communication tools such as Twitter and Google+ by active users also varied widely depending upon country and region.

Review of UK urban freight studies

Report produced as part of the Green Logistics project (EPSRC and Department for Transport funded). This report is based on a review of UK studies in which data has been collected to obtain an understanding of road-based urban freight transport activities and patterns of operation. Urban freight remains relatively under researched by comparison with passenger transport both in the UK and worldwide. However, in the UK there have been a number of studies that have attempted to investigate road-based freight operations since the 1960s. But no attempt has been made to draw together the results of these various studies and compare them. This is what is presented in this report. The report has studied the results of 30 UK urban freight studies carried out in the last decade in order to attempt to provide insight into urban freight activities in our towns and cities. It presents this current knowledge about urban freight transport activities in the UK from these studies, and compares the similarities and differences between study findings.

Liberalization of Labor Relations in Germany and the United States: A firm-centered comparison of cross-national labor organizing at Amazon and Volkswagen

Thesis (Master's)--University of Washington, 2015

Comparison of virus dispersal and aerosolization by different hand-drying devices

Background World Health Organization and EU hand hygiene guidelines state that if electric hand dryers are used, they should not aerosolize pathogens. Previous studies have investigated the dispersal by different hand-drying devices of chemical indicators, fungi and bacteria on the hands. This study assessed the aerosolization and dispersal of virus on the hands to determine any differences between hand-drying devices in their potential to contaminate other occupants of public washrooms and the washroom environment. Methods A suspension of MS2, an Escherichia coli bacteriophage virus, was used to artificially contaminate the hands of participants prior to using three different hand-drying devices: jet air dryer, warm air dryer, paper towel dispenser. Virus was detected by plaque formation on agar plates layered with the host bacterium. Vertical dispersal of virus was assessed at a fixed distance (0.4 m) and over a range of different heights (0.0 – 1.8 m) from the floor. Horizontal dispersal was assessed at different distances of up to three metres from the hand-drying devices. Virus aerosolization and dispersal was also assessed at different times up to 15 minutes after use by means of air sampling at two distances (0.1 and 1.0 m) and at a distance behind and offset from each of the hand-drying devices. Results Over a range of heights, the jet air dryer was shown to produce over 60 times greater vertical dispersal of virus from the hands than a warm air dryer and over 1300 times greater than paper towels; the maximum being detected between 0.6 and 1.2 metres from the floor. Horizontal dispersal of virus by the jet air dryer was over 20 times greater than a warm air dryer and over 190 times greater than paper towels; virus being detected at distances of up to three metres. Air sampling at three different positions from the hand-drying devices 15 minutes after use showed that the jet air dryer produced over 50-times greater viral contamination of the air than a warm air dryer and over 110-times greater than paper towels. Conclusions Due to their high air speed, jet air dryers aerosolize and disperse more virus over a range of heights, greater distances, and for longer times than other hand drying devices. If hands are inadequately washed, they have a greater potential to contaminate other occupants of a public washroom and the washroom environment. Main messages: Jet air dryers with claimed air speeds of over 600 kph have a greater potential than warm air dryers or paper towels to aerosolize and disperse viruses on the hands of users. The choice of hand-drying device should be carefully considered. Jet air dryers may increase the risk of transmission of human viruses, such as norovirus, particularly if hand washing is inadequate.

Structure to function studies in UDP-glucose dehydrogenases and nitroreductases

The thesis is divided into two parts corresponding to structural studies on two different proteins. The first part concerns the study of two UDP-glucose dehydrogenases (UGDs) from Sphingomonas elodea ATCC 31461 and Burkholderia cepacia IST 408, both involved in exopolysaccharide production. Their relevance arises because some of these bacterial exopolysaccharides are valuable as established biotechnological products, the former case, whilst others are highly problematic, when used by pathogens in biofilm formation over biological surfaces, as the latter case, namely in the human lungs. The goal of these studies is to increase our knowledge regarding UGDs structural properties, which can potentiate either the design of activity enhancers to respond to the increased demand of useful biofilms, or the design of inhibitors of biofilm production, in order to fight invading pathogens present in several infections. The thesis reports the production and crystallisation of both proteins, the determination of initial phases by single-wavelength anomalous dispersion (SAD) in S. elodea crystals using a seleno-methionine isoform, and phasing of B. cepacia crystals by molecular replacement (MR) using the S. elodea model, as well as the refinement, structural analysis and comparison between the several UGDs structures available during this work.(...)

Children’s Indoor Exposures to (Ultra)Fine Particles in an Urban Area: Comparison Between School and Home Environments

Due to their detrimental effects on human health, scientific interest in ultrafine particles (UFP), has been increasing but available information is far from comprehensive. Children, who represent one of the most susceptible subpopulation, spend the majority of time in schools and homes. Thus, the aim of this study is to (1) assess indoor levels of particle number concentrations (PNC) in ultrafine and fine (20–1000 nm) range at school and home environments and (2) compare indoor respective dose rates for 3- to 5-yr-old children. Indoor particle number concentrations in range of 20–1000 nm were consecutively measured during 56 d at two preschools (S1 and S2) and three homes (H1–H3) situated in Porto, Portugal. At both preschools different indoor microenvironments, such as classrooms and canteens, were evaluated. The results showed that total mean indoor PNC as determined for all indoor microenvironments were significantly higher at S1 than S2. At homes, indoor levels of PNC with means ranging between 1.09 × 104 and 1.24 × 104 particles/cm3 were 10–70% lower than total indoor means of preschools (1.32 × 104 to 1.84 × 104 particles/cm3). Nevertheless, estimated dose rates of particles were 1.3- to 2.1-fold higher at homes than preschools, mainly due to longer period of time spent at home. Daily activity patterns of 3- to 5-yr-old children significantly influenced overall dose rates of particles. Therefore, future studies focusing on health effects of airborne pollutants always need to account for children’s exposures in different microenvironments such as homes, schools, and transportation modes in order to obtain an accurate representation of children overall exposure.