Evaluation of the Factors Contributing to Levonorgestrel Binding in Addition Cure Silicone Elastomer Vaginal Rings

Background: Following progress of the dapivirine (DPV)-releasing silicone elastomer (SE) vaginal ring (VR) into Phase III clinical studies, there is now interest in developing next-generation rings that additionally provide contraception. Levonorgestrel (LNG) is a safe and effective progestin that is being widely considered for use as a hormonal contraceptive agent in future multipurpose prevention technology (MPT) products. Although LNG has previously been incorporated into various controlled release SE devices, minimal attention has focused on its propensity to irreversibly react with addition cure SE systems. Here, for the first time, we investigate this LNG binding phenomenon and outline strategies for overcoming it.
Methods: VRs containing various loadings of DPV and LNG were manufactured and in vitro release assessed. Different LNG-only SE samples were also prepared to assess the following parameters: (i) addition cure vs. condensation cure SEs; (ii) different types of addition cure SEs; (iii) mixing time, (iv) cure temperature, (v) cure time; and (vi) LNG particle size. After manufacture, the LNG-only samples were assayed for total drug content using a solvent extraction method. The SE curing reaction and the LNG binding reaction was probed using nuclear magnetic resonance (NMR) spectroscopy. Results:
Under certain drug/formulation/processing conditions, LNG was not recoverable from VRs. Further studies using non-ring samples showed that: (a) the phenomenon was only observed with addition cure SEs (and not condensation cure SEs); (b) the extent of binding was dependent upon the type of addition cure SE; (c) micronised LNG showed significantly greater binding than non-micronised LNG; (d) the extent of binding correlated with increased mixing time, cure time and cure temperature.
Conclusions: Careful control of the API characteristics, the SE composition, and the manufacturing conditions will be necessary to establish a practical VR formulation for controlled release of LNG.

Evaluation of infilled frames: an updated in-plane-stiffness macro-model considering the effects of vertical loads

The influence of masonry infills on the in-plane behaviour of RC framed structures is a central topic in the seismic evaluation and retrofitting of existing buildings. Many models in the literature use an equivalent strut member in order to represent the infill but, among the parameters influencing the equivalent strut behaviour, the effect of vertical loads acting on the frames is recognized but not quantified. Nevertheless a vertical load causes a non-negligible variation in the in-plane behaviour of infilled frames by influencing the effective volume of the infill. This results in a change in the stiffness and strength of the system. This paper presents an equivalent diagonal pin-jointed strut model taking into account the stiffening effect of vertical loads on the infill in the initial state. The in-plane stiffness of a range of infilled frames was evaluated using a finite element model of the frame-infill system and the cross-section of the strut equivalent to the infill was obtained for different levels of vertical loading by imposing the equivalence between the frame containing the infill and the frame containing the diagonal strut. In this way a law for identifying the equivalent strut width depending on the geometrical and mechanical characteristics of the infilled frame was generalized to consider the influence of vertical loads for use in the practical applications. The strategy presented, limited to the initial stiffness of infilled frames, is preparatory to the definition of complete non-linear cyclic laws for the equivalent strut.

Non-covalent hydrogels of cyclodextrins and poloxamines for the controlled release of proteins

Different types of gels were prepared by combining poloxamines (Tetronic), i.e. poly(ethylene oxide)/poly(propylene oxide) (PEO/PPO) octablock star copolymers, and cyclodextrins (CD). Two different poloxamines with the same molecular weight (ca. 7000) but different molecular architectures were used. For each of their four diblock arms, direct Tetronic 904 presents PEO outer blocks while in reverse Tetronic 90R4 the hydrophilic PEO blocks are the inner ones. These gels were prepared by combining alpha-CD and poloxamine aqueous solutions. The physicochemical properties of these systems depend on several factors such as the structure of the block copolymers and the Tetronic/alpha-CD ratio. These gels were characterized using differential scanning calorimetry (DSC), viscometry and X-ray diffraction measurements. The 90R4 gels present a consistency that makes them suitable for sustained drug delivery. The resulting gels were easily eroded: these complexes were dismantled when placed in a large amount of water, so controlled release of entrapped large molecules such as proteins (Bovine Serum Albumin, BSA) is feasible and can be tuned by varying the copolymer/CD ratio. 

Evaluation of information extraction techniques to label extracted data from e-commerce web page

Automatically determining and assigning shared and meaningful text labels to data extracted from an e-Commerce web page is a challenging problem. An e-Commerce web page can display a list of data records, each of which can contain a combination of data items (e.g. product name and price) and explicit labels, which describe some of these data items. Recent advances in extraction techniques have made it much easier to precisely extract individual data items and labels from a web page, however, there are two open problems: 1. assigning an explicit label to a data item, and 2. determining labels for the remaining data items. Furthermore, improvements in the availability and coverage of vocabularies, especially in the context of e-Commerce web sites, means that we now have access to a bank of relevant, meaningful and shared labels which can be assigned to extracted data items. However, there is a need for a technique which will take as input a set of extracted data items and assign automatically to them the most relevant and meaningful labels from a shared vocabulary. We observe that the Information Extraction (IE) community has developed a great number of techniques which solve problems similar to our own. In this work-in-progress paper we propose our intention to theoretically and experimentally evaluate different IE techniques to ascertain which is most suitable to solve this problem.

Critical evaluation of pulse-echo ultrasonic test method for the determination of setting and mechanical properties of acrylic bone cement: Influence of mixing technique

Currently there is no reliable objective method to quantify the setting properties of acrylic bone cements within an operating theatre environment. Ultrasonic technology can be used to determine the acoustic properties of the polymerising bone cement, which are linked to material properties and provide indications of the physical and chemical changes occurring within the cement. The focus of this study was the critical evaluation of pulse-echo ultrasonic test method in determining the setting and mechanical properties of three different acrylic bone cement when prepared under atmospheric and vacuum mixing conditions. Results indicated that the ultrasonic pulse-echo technique provided a highly reproducible and accurate method of monitoring the polymerisation reaction and indicating the principal setting parameters when compared to ISO 5833 standard, irrespective of the acrylic bone cement or mixing method used. However, applying the same test method to predict the final mechanical properties of acrylic bone cement did not prove a wholly accurate approach. Inhomogeneities within the cement microstructure and specimen geometry were found to have a significant influence on mechanical property predictions. Consideration of all the results suggests that the non-invasive and non-destructive pulse-echo ultrasonic test method is an effective and reliable method for following the full polymerisation reaction of acrylic bone cement in real-time and then determining the setting properties within a surgical theatre environment. However the application of similar technology for predicting the final mechanical properties of acrylic bone cement on a consistent basis may prove difficult.

A techno-economic evaluation of changing from conventional vehicles to range extended electric vehicles

Transportation accounts for 22% of greenhouse gas emissions in the UK, and increases to 25% in Northern Ireland. Surface transport carbon dioxide emissions, consisting of road and rail, are dominated by cars. Demand for mobility is rising rapidly and vehicle numbers are expected to more than double by 2050. Car manufacturers are working towards reducing their carbon footprint through improving fuel efficiency and controlling exhaust emissions. Fuel efficiency is now a key consideration of consumers purchasing a new vehicle. While measures have been taken to help to reduce pollutants, in the future, alternative technologies will have to be used in the transportation industry to achieve sustainability. There are currently many alternatives to the market leader, the internal combustion engine. These alternatives include hydrogen fuel cell vehicles and electric vehicles, a term which is widely used to cover battery electric vehicles, plug-in hybrid electric vehicles and extended-range electric vehicles. This study draws direct comparisons measuring the differing performance in terms of fuel consumption, carbon emissions and range of a typical family saloon car using different fuel types. These comparisons will then be analysed to see what effect switching from a conventionally fuelled vehicle to a range extended electric vehicle would have not only on the end user, but also the UK government.

Bioinformatic evaluation of transcriptional regulation of WNT pathway genes with reference to diabetic nephropathy

Objective: Diabetic nephropathy (DN) is a microvascular complication of diabetes. Members of the WNT/ β-catenin pathways have been implicated in interstitial fibrosis and glomerular sclerosis, characteristic hallmarks of DN. These processes are controlled, in part, by transcription factors (TFs), proteins which bind to gene promoter regions attenuating their regulation. We sought to identify predicted cis-acting transcription factor binding sites (TFBS) over-represented within the promoter regions of WNT pathway members compared to genes across the genome.Methods: We assessed the frequency of 62 TFBS motifs from the JASPAR databases on 65 WNT pathway genes. P-values were estimated on the hypergeometric distribution for each TF. Gene expression profiles of enriched motifs were examined from DN-related datasets to assess clinical significance.Results: TFBS motifs transcription factor AP-2 alpha (TFAP2A), myeloid zinc finger 1 (MZF1), and specificity protein 1 (SP1) were significantly enriched within WNT pathway genes (P-values<6.83x10-29, 1.34x10-11 and 3.01x10-6 respectively). MZF1 gene expression was significantly increased in DN in a whole kidney dataset (fold change = 1.16; 16% increase; P = 0.03). TFAP2A gene expression was decreased in an independent dataset (fold change = -1.02; P = 0.03). SP1 was not differentially expressed in any datasets examined.Conclusions: Three TFBS profiles are significantly enriched within the WNT pathway genes examined highlighting the use of in silico analyses for identifying key regulators of this pathway. Modification of TF binding to gene promoter regions involved in DN pathology may limit progression, making refinement of targeted therapeutic strategies possible through clearer delineation of their role.

An Evaluation of 1D Loss Model Collections for the Off-Design Performance Prediction of an Automotive Turbocharger Compressor

Abstract. Single-zone modelling is used to assess different collections of impeller 1D loss models. Three collections of loss models have been identified in literature, and the background to each of these collections is discussed. Each collection is evaluated using three modern automotive turbocharger style centrifugal compressors; comparisons of performance for each of the collections are made. An empirical data set taken from standard hot gas stand tests for each turbocharger is used as a baseline for comparison. Compressor range is predicted in this study; impeller diffusion ratio is shown to be a useful method of predicting compressor surge in 1D, and choke is predicted using basic compressible flow theory. The compressor designer can use this as a guide to identify the most compatible collection of losses for turbocharger compressor design applications. The analysis indicates the most appropriate collection for the design of automotive turbocharger centrifugal compressors.

An Evaluation of 1D Design Methods for the Off-Design Performance Prediction of Automotive Turbocharger Compressors

Several one-dimensional design methods have been used to predict the off-design performance of three modern centrifugal compressors for automotive turbocharging. The three methods used are single-zone, two-zone, and a more recent statistical method. The predicted results from each method are compared against empirical data taken from standard hot gas stand tests for each turbocharger. Each of the automotive turbochargers considered in this study have notably different geometries and are of varying application. Due to the non-adiabatic test conditions, the empirical data has been corrected for the effect of heat transfer to ensure comparability with the 1D models. Each method is evaluated for usability and accuracy in both pressure ratio and efficiency prediction. The paper presents an insight into the limitations of each of these models when applied to one-dimensional automotive turbocharger design, and proposes that a corrected single-zone modelling approach has the greatest potential for further development, whilst the statistical method could be immediately introduced to a design process where design variations are limited.

An Evaluation of Vaneless Diffuser Modelling Methods as a Means of Improving the Off-Design Performance Prediction of Centrifugal Compressors

An evaluation of existing 1-D vaneless diffuser design tools in the context of improving the off-design performance prediction of automotive turbocharger centrifugal compressors is described. A combination of extensive gas stand test data and single passage CFD simulations have been employed in order to permit evaluation of the different methods, allowing conclusions about the relative benefits and deficiencies of each of the different approaches to be determined. The vaneless diffuser itself has been isolated from the incumbent limitations in the accuracy of 1-D impeller modelling tools through development of a method to fully specify impeller exit conditions (in terms of mean quantities) using only standard test stand data with additional interstage static pressure measurements at the entrance to the diffuser. This method allowed a direct comparison between the test data and 1-D methods through sharing common inputs, thus achieving the aim of diffuser isolation.

Crucial to the accuracy of determining the performance of each of the vaneless diffuser configurations was the ability to quantify the presence and extent of the spanwise aerodynamic blockage present at the diffuser inlet section. A method to evaluate this critical parameter using CFD data is described herein, along with a correlation for blockage related to a new diffuser inlet flow parameter ⚡, equal to the quotient of the local flow coefficient and impeller tip speed Mach number. The resulting correlation permitted the variation of blockage with operating condition to be captured.

Hospitalization in Geriatric Wards: Considerations on the Evaluation of the Outcome

Within a defined law framework, the Italian central health system dictates the standards for hospitalization to local care units, which are in turn allowed to establish their own effectiveness criteria. The appropriateness of the hospitalization decision is therefore predetermined at patients admission, whereas its effectiveness relies on the ex post patient well-being as a result of the complex system of reciprocal relations between patients and healthcare agents at the ward level. We consider the outcomes in geriatric wards referring to the national health system, with respect both to patients traits at the individual level and wards/hospital settings. The risk that models the healthcare outcome is accordingly adjusted for covariates at the different levels of analysis (Goldstein & Spiegelhalter, 1996), thus allowing to differentiate among outcomes in terms of the hospitalization structure and, when appropriate, of territorial aggregation.

Realistic evaluation of EWS and ALERT: factors enabling and constraining implementation.

Realistic Evaluation of EWS and ALERT: factors enabling and constraining implementation Background The implementation of EWS and ALERT in practice is essential to the success of Rapid Response Systems but is dependent upon nurses utilising EWS protocols and applying ALERT best practice guidelines. To date there is limited evidence on the effectiveness of EWS or ALERT as research has primarily focused on measuring patient outcomes (cardiac arrests, ICU admissions) following the implementation of a Rapid Response Team. Complex interventions in healthcare aimed at changing service delivery and related behaviour of health professionals require a different research approach to evaluate the evidence. To understand how and why EWS and ALERT work, or might not work, research needs to consider the social, cultural and organisational influences that will impact on successful implementation in practice. This requires a research approach that considers both the processes and outcomes of complex interventions, such as EWS and ALERT, implemented in practice. Realistic Evaluation is such an approach and was used to explain the factors that enable and constrain the implementation of EWS and ALERT in practice [1]. Aim The aim of this study was to evaluate factors that enabled and constrained the implementation and service delivery of early warnings systems (EWS) and ALERT in practice in order to provide direction for enabling their success and sustainability. Methods The research design was a multiple case study approach of four wards in two hospitals in Northern Ireland. It followed the principles of realist evaluation research which allowed empirical data to be gathered to test and refine RRS programme theory. This approach used a variety of mixed methods to test the programme theories including individual and focus group interviews, observation and documentary analysis in a two stage process. A purposive sample of 75 key informants participated in individual and focus group interviews. Observation and documentary analysis of EWS compliance data and ALERT training records provided further evidence to support or refute the interview findings. Data was analysed using NVIVO8 to categorise interview findings and SPSS for ALERT documentary data. These findings were further synthesised by undertaking a within and cross case comparison to explain the factors enabling and constraining EWS and ALERT. Results A cross case analysis highlighted similarities, differences and factors enabling or constraining successful implementation across the case study sites. Findings showed that personal (confidence; clinical judgement; personality), social (ward leadership; communication), organisational (workload and staffing issues; pressure from managers to complete EWS audit and targets), educational (constraints on training; no clinical educator on ward) and cultural (routine task delegated) influences impact on EWS and acute care training outcomes. There were also differences noted between medical and surgical wards across both case sites. Conclusions Realist Evaluation allows refinement and development of the RRS programme theory to explain the realities of practice. These refined RRS programme theories are capable of informing the planning of future service provision and provide direction for enabling their success and sustainability. References: 1. McGaughey J, Blackwood B, O’Halloran P, Trinder T. J. & Porter S. (2010) A realistic evaluation of Track and Trigger systems and acute care training for early recognition and management of deteriorating ward–based patients. Journal of Advanced Nursing 66 (4), 923-932. Type of submission: Concurrent session Source of funding: Sandra Ryan Fellowship funded by the School of Nursing & Midwifery, Queen’s University of Belfast

Clinical evaluation of three incision size-dependent phacoemulsification systems.

PURPOSE:

To compare the outcomes of cataract surgery performed with 3 incision size-dependent phacoemulsification groups (1.8, 2.2, and 3.0 mm).

DESIGN:

Prospective randomized comparative study.

METHODS:

One hundred twenty eyes of 120 patients with age-related cataract (grades 2 to 4) were categorized according to the Lens Opacities Classification System III. Eligible subjects were randomly assigned to 3 surgical groups using coaxial phacoemulsification through 3 clear corneal incision sizes (1.8, 2.2, and 3.0 mm). Different intraoperative and postoperative outcome measures were obtained, with corneal incision size and surgically induced astigmatism as the main clinical outcomes.

RESULTS:

There were no statistically significant differences in most of the intraoperative and postoperative outcome measures among the 3 groups. However, the mean cord length of the clear corneal incision was increased in each group after surgery. The mean maximal clear corneal incision thickness in the 1.8-mm group was significantly greater than for the other groups at 1 month. The mean surgically induced astigmatism in the 1.8- and 2.2-mm groups was significantly less than that in the 3.0-mm group after 1 month, without significant difference between the 1.8- and 2.2-mm groups.

CONCLUSIONS:

With appropriate equipment, smaller incisions may result in less astigmatism, but the particular system used will influence incision stress and wound integrity, and may thus limit the reduction in incision size and astigmatism that is achievable.

Evaluation of Restorative Dentistry Specialty Registrars’ Clinical Experience of Developmental Disorders: A Survey

Background

Specialty Registrars in Restorative Dentistry (StRs) should be competent in the independent restorative management of patients with developmental disorders including hypodontia and cleft lip/palate upon completion of their specialist training.1 Knowledge and management may be assessed via the Intercollegiate Specialty Fellowship Examination (ISFE) in Restorative Dentistry.2

Objective

The aim of this study was to collate and compare data on the training and experience of StRs in the management of patients with developmental disorders across different training units within the British Isles.

Methods

Questionnaires were distributed to all StRs attending the Annual General Meeting of the Specialty Registrars in Restorative Dentistry Group, Belfast, in October 2015. Participants were asked to rate their confidence and experience of assessing and planning treatment for patients with developmental disorders, construction of appropriate prostheses, and provision of dental implants. Respondents were also asked to record clinical supervision and didactic teaching at their unit, and to rate their confidence of passing a future ISFE station assessing knowledge of developmental disorders.

Results

Responses were obtained from 32 StRs (n=32) training within all five countries of the British Isles. The majority of respondents were based in England (72%) with three in Wales, and two in each of Scotland, Northern Ireland, and the Republic of Ireland. Approximately one third of respondents (34%) were in the final years of training (years 4-6). Almost half of the StRs reported that they were not confident of independently assessing (44%) new patients with a developmental disorder, with larger numbers (72%) indicating a lack of confidence in treatment planning. Six respondents rated their experience of treating obturator patients as ‘poor’ or ‘very poor’. The majority (56%) rated their experience of implant provision in these cases as ‘good’ or ‘excellent’ with three-quarters (75%) rating clinical supervision at their unit as ‘good’ or ‘excellent’. Less than half (41%) rated the didactic teaching at their unit as ‘good’ or ‘excellent’, and only 8 StRs indicated that they were confident of passing an ISFE station focused on developmental disorders.

Conclusion

Experience and training regarding patients with developmental disorders is inconsistent for StRs across the British Isles with a number of trainees reporting a lack of clinical exposure.

A tool for the evaluation of slaughter horse welfare during unloading

This study aimed to develop a scientific and practical tool to be used to assess horse welfare after commercial transport over long journeys. A set of physical, behavioural and environmental measures was selected, covering welfare aspects of both transport and unloading procedures. The protocol was field-tested on 51 intra-EU commercial transports arriving at different sites in Italy. Univariate analysis was implemented to look for associations between the input variables (environmental hazards potentially affecting the animal well-being during long transports) and the outcome variables (direct evaluation of the animal condition). No severe welfare impairments were recorded (ie dead on arrival, severe injuries, non-ambulatory animals), while milder ones were more frequent at unloading (eg slipping; 36.7%, reluctance to move; 9.6%). Correlations emerged between ramp slope and falling; type of ramp floor and slipping; fast gait and the presence of gaps between the ramp and the floor. The horses' behaviour was also related to the type of handling procedure used. The measures were repeatable and practical to apply and score during real-time unloading. This work provides a sound basis for a new and practical welfare assessment tool for horses travelling over long journeys. Careful and constant application of this protocol would provide stakeholders with the opportunity to track and monitor changes in the industry over time, as well as to identify high risk areas in transport routines.