The UK MPharm (1) - are we over reliant on traditional teaching methods?

Introduction-The design of the UK MPharm curriculum is driven by the Royal Pharmaceutical Society of Great Britain (RPSGB) accreditation process and the EU directive (85/432/EEC).[1] Although the RPSGB is informed about teaching activity in UK Schools of Pharmacy (SOPs), there is no database which aggregates information to provide the whole picture of pharmacy education within the UK. The aim of the teaching, learning and assessment study [2] was to document and map current programmes in the 16 established SOPs. Recent developments in programme delivery have resulted in a focus on deep learning (for example, through problem based learning approaches) and on being more student centred and less didactic through lectures. The specific objectives of this part of the study were (a) to quantify the content and modes of delivery of material as described in course documentation and (b) having categorised the range of teaching methods, ask students to rate how important they perceived each one for their own learning (using a three point Likert scale: very important, fairly important or not important). Material and methods-The study design compared three datasets: (1) quantitative course document review, (2) qualitative staff interview and (3) quantitative student self completion survey. All 16 SOPs provided a set of their undergraduate course documentation for the year 2003/4. The documentation variables were entered into Excel tables. A self-completion questionnaire was administered to all year four undergraduates, using a pragmatic mixture of methods, (n=1847) in 15 SOPs within Great Britain. The survey data were analysed (n=741) using SPSS, excluding non-UK students who may have undertaken part of their studies within a non-UK university. Results and discussion-Interviews showed that individual teachers and course module leaders determine the choice of teaching methods used. Content review of the documentary evidence showed that 51% of the taught element of the course was delivered using lectures, 31% using practicals (includes computer aided learning) and 18% small group or interactive teaching. There was high uniformity across the schools for the first three years; variation in the final year was due to the project. The average number of hours per year across 15 schools (data for one school were not available) was: year 1: 408 hours; year 2: 401 hours; year 3: 387 hours; year 4: 401 hours. The survey showed that students perceived lectures to be the most important method of teaching after dispensing or clinical practicals. Taking the very important rating only: 94% (n=694) dispensing or clinical practicals; 75% (n=558) lectures; 52% (n=386) workshops, 50% (n=369) tutorials, 43% (n=318) directed study. Scientific laboratory practices were rated very important by only 31% (n=227). The study shows that teaching of pharmacy to undergraduates in the UK is still essentially didactic through a high proportion of formal lectures and with high levels of staff-student contact. Schools consider lectures still to be the most cost effective means of delivering the core syllabus to large cohorts of students. However, this does limit the scope for any optionality within teaching, the scope for small group work is reduced as is the opportunity to develop multi-professional learning or practice placements. Although novel teaching and learning techniques such as e-learning have expanded considerably over the past decade, schools of pharmacy have concentrated on lectures as the best way of coping with the huge expansion in student numbers. References [1] Council Directive. Concerning the coordination of provisions laid down by law, regulation or administrative action in respect of certain activities in the field of pharmacy. Official Journal of the European Communities 1985;85/432/EEC. [2] Wilson K, Jesson J, Langley C, Clarke L, Hatfield K. MPharm Programmes: Where are we now? Report commissioned by the Pharmacy Practice Research Trust., 2005.

Pharmaceutical process optimisation of bulk lyophilisates:implications of powder handling

Lyophilisation or freeze drying is the preferred dehydrating method for pharmaceuticals liable to thermal degradation. Most biologics are unstable in aqueous solution and may use freeze drying to prolong their shelf life. Lyophilisation is however expensive and has seen lots of work aimed at reducing cost. This thesis is motivated by the potential cost savings foreseen with the adoption of a cost efficient bulk drying approach for large and small molecules. Initial studies identified ideal formulations that adapted well to bulk drying and further powder handling requirements downstream in production. Low cost techniques were used to disrupt large dried cakes into powder while the effects of carrier agent concentration were investigated for powder flowability using standard pharmacopoeia methods. This revealed superiority of crystalline mannitol over amorphous sucrose matrices and established that the cohesive and very poor flow nature of freeze dried powders were potential barriers to success. Studies from powder characterisation showed increased powder densification was mainly responsible for significant improvements in flow behaviour and an initial bulking agent concentration of 10-15 %w/v was recommended. Further optimisation studies evaluated the effects of freezing rates and thermal treatment on powder flow behaviour. Slow cooling (0.2 °C/min) with a -25°C annealing hold (2hrs) provided adequate mechanical strength and densification at 0.5-1 M mannitol concentrations. Stable bulk powders require powder transfer into either final vials or intermediate storage closures. The targeted dosing of powder formulations using volumetric and gravimetric powder dispensing systems where evaluated using Immunoglobulin G (IgG), Lactate Dehydrogenase (LDH) and Beta Galactosidase models. Final protein content uniformity in dosed vials was assessed using activity and protein recovery assays to draw conclusions from deviations and pharmacopeia acceptance values. A correlation between very poor flowability (p<0.05), solute concentration, dosing time and accuracy was revealed. LDH and IgG lyophilised in 0.5 M and 1 M mannitol passed Pharmacopeia acceptance values criteria with 0.1-4 while formulations with micro collapse showed the best dose accuracy (0.32-0.4% deviation). Bulk mannitol content above 0.5 M provided no additional benefits to dosing accuracy or content uniformity of dosed units. This study identified considerations which included the type of protein, annealing, cake disruption process, physical form of the phases present, humidity control and recommended gravimetric transfer as optimal for dispensing powder. Dosing lyophilised powders from bulk was demonstrated as practical, time efficient, economical and met regulatory requirements in cases. Finally the use of a new non-destructive technique, X-ray microcomputer tomography (MCT), was explored for cake and particle characterisation. Studies demonstrated good correlation with traditional gas porosimetry (R2 = 0.93) and morphology studies using microscopy. Flow characterisation from sample sizes of less than 1 mL was demonstrated using three dimensional X-ray quantitative image analyses. A platinum-mannitol dispersion model used revealed a relationship between freezing rate, ice nucleation sites and variations in homogeneity within the top to bottom segments of a formulation.

Use of medications with anticholinergic activity and self-reported injurious falls in older community-dwelling adults

Objectives: To assess the association between the use of medications with anticholinergic activity and the subsequent risk of injurious falls in older adults. Design: Prospective, population-based study using data from The Irish Longitudinal Study on Ageing. Setting: Irish population. Participants: Community-dwelling men and women without dementia aged 65 and older (N = 2,696). Measurements: Self-reported injurious falls reported once approximately 2 years after baseline interview. Self-reported regular medication use at baseline interview. Pharmacy dispensing records from the Irish Health Service Executive Primary Care Reimbursement Service in a subset (n = 1,553). Results: Nine percent of men and 17% of women reported injurious falls. In men, the use of medications with definite anticholinergic activity was associated with greater risk of subsequent injurious falls (adjusted relative risk (aRR) = 2.55, 95% confidence interval (CI) = 1.33-4.88), but the risk of having any fall and the number of falls reported were not significantly greater. Greater anticholinergic burden was associated with greater injurious falls risk. No associations were observed for women. Findings were similar using pharmacy dispensing records. The aRR for medications with definite anticholinergic activity dispensed in the month before baseline and subsequent injurious falls in men was 2.53 (95% CI = 1.15-5.54). Conclusion: The regular use of medications with anticholinergic activity is associated with subsequent injurious falls in older men, although falls were self-reported after a 2-year recall and so may have been underreported. Further research is required to validate this finding in men and to consider the effect of duration and dose of anticholinergic medications.

How education should link with career paths

How good is your pharmacy practice? And what does “good” look like? Take a look back at the education and training you have received in your career to date. Has it stood you in good stead? Certainly there is a need to establish a model of professional education and development that produces good pharmacists — you should be able to demonstrate your competence regardless of your sector of work. It may help if we move away from the view that excellence in pharmacy practice is primarily defined by where you practise and the kind of job that you do. The Modernising Pharmacy Careers programme’s aspirations to integrate the undergraduate degree with the preregistration training year are bold and to be applauded — provided the outcome delivers changes that are more than superficial. The new model needs to deliver greater integration of education with practice, while retaining an adequate science base. Theory should be put into the context of practice-based, cross-sector learning needs and opportunities. For example, is the classroom really the best environment in which to learn dispensing? Pharmacokinetic theory could be put into context through creatively designed work placements. And it might make more sense to learn patient counselling in a community pharmacy, and so on. Is it resources we lack to make this happen? Or do we lack the collective will to be imaginative, to be radical and to conceive new approaches to professional education? Implicit in this new approach to education is the expectation that pharmacists should teach and mentor and, conversely, that those who teach should also engage in relevant practice. University education must produce graduates whose knowledge and competence are useful to employers. Moreover, graduates must be adequately prepared to enter any area of the profession endowed with professional self-confidence (something, arguably, that needs further development within the pharmacy psyche). Of course, becoming qualified is just the beginning. Post-qualification, pharmacists need structured career paths that foster this professional confidence, support learning and ensure recognition. To this end, the Royal Pharmaceutical Society-led professional curriculum group is working to define knowledge, skills and experience for all areas of advanced practice. More than ever, the profession needs to adopt a culture of learning, teaching and practice research that is unified. The question is: how do we move away from merely collecting qualifications (trophies) to developing meaningful careers? Pharmacists in all areas and at all levels of the profession need to consider their own willingness to make this shift. The RPS and MPC are leading the way, but are we following?

Survey of General Optical Council disciplinary and fitness to practise hearings:2001-2011

The aim of this survey was to review 187 transcripts from the United Kingdom’s General Optical Council (GOC) Disciplinary and Fitness To Practise (FTP) Committee hearings from 2001 to 2011 in order to identify common themes and thereby help practitioners to avoid the more frequently occurring pitfalls that were recorded during this period. The study covered changes in GOC FTP regulations in 2005, which involved a change from a disciplinary to a fitness to practise process. The number of cases was very small compared to the total number of optometrist and dispensing optician registrants, which was 13709 in 2001-02 rising to 18582 in 2010-11. The main findings indicated that between 2001 and 2011 there was a three times greater likelihood that male registrants versus female registrants would be brought in front of a GOC Disciplinary or FTP Committee. In terms of erasures from the GOC registers between 2001 and 2011, male registrants were also more likely to be erased than females. The male: female split for erasures between 2001 and 2011 was five: one, increasing to seven: one when considering the situation post the 2005 GOC FTP rule change. Of the cases brought before the Disciplinary and FTP Committees between 2001 and 2011, it was noted that cases implicating theft and fraud were most frequent representing 27% of hearings examined (17% involving NHS fraud and 10% theft or fraud from an employer). The examination of transcripts revealed other hearings were more complex. These hearings often had a primary reason for the investigation that highlighted further secondary concerns that also required investigation.

Student independent Projects Environmental Studies 2007: An Environmental Levy for Disposable Cups in NL: A preliminary Investigation

Human ability to impact Planet Earth appears to know no bounds. Adherence to polices of managed resource extraction combined with unbridled consumption, have fostered a disposable culture contributing to mass production of garbage. Eco-taxation may provide the economic tools required to reduce the amount of waste generated. Keys to eco-tax success are vision, education, and flexibility. Success must be measured in societal gains, not simply in monetary terms. Public opinion is initially opposed to consumer charges. Education and viable personal options are crucial to overcome resistance. With one coffee shop dispensing over 800,000 disposable cups annually, an eco-tax is an attractive option to simultaneously raise revenue to waste management programs and reduce one sector of waste production.

Development of a dissolvable microneedle influenza vaccine patch

Delivery of large molecular weight biological molecules to the epidermis and dermis is constrained by the tough outer layer of the epidermis, the stratum corneum (sc). Microneedle technologies attempt to overcome this physical barrier using sharp micron-size projections to penetrate the sc. Dissolvable microneedles (DMN), are a particular microneedle design whereby the needle structure is composed of a soluble matrix that upon application to the skin, dissolves releasing the vaccine load into skin. This thesis examines (1) the formulation and processing considerations around DMN fabrication, (2) the immunogenicity of DMN containing trivalent influenza vaccine (TIV) in pre-clinical mouse and pig models and (3) the thermostability of these DMN formulations during storage. The results demonstrate the importance of formulation for microneedle formation and mechanical strength. Trehalose and polyvinylalcohol based formulations produced optimal microneedle structures and were amenable to piezoelectric dispensing; allowing for precise multi-layered DMN to be fabricated. The effect of drying conditions was assessed and found to be critical for DMN mechanical strength and skin penetration. The antibody responses to TIV generated by DMN-mediated vaccination were comparable or greater to those induced by immunization with a commercial TIV via the IM route in mice. DMN mediated immunisation resulted in a significantly broader humoral response to heterotypic influenza viruses compared to IM delivery. Stored at 40°C, a licensed seasonal influenza vaccine incorporated into DMN array was thermostable for at least 6 month as determined by Single Radial Immunodiffusion and immunogenicity in mice. The thesis advances the field of DMN influenza vaccination by elucidating important processing and formulation considerations in the fabrication of highly reproducible DMN. It also demonstrated that DMN can induce broader, larger humoral responses than conventional IM administration while demonstrating enhanced accelerated stability. Crucially, this works advances an automated fabrication system that will allow for clinical translation of DMN.

Drug prescribing patterns in the General Medical Services Scheme in Ireland and projected costs to 2026

The primary objective is to investigate the main factors contributing to GMS expenditure on pharmaceutical prescribing and projecting this expenditure to 2026. This study is located in the area of pharmacoeconomic cost containment and projections literature. The thesis has five main aims: 1. To determine the main factors contributing to GMS expenditure on pharmaceutical prescribing. 2. To develop a model to project GMS prescribing expenditure in five year intervals to 2026, using 2006 Central Statistics Office (CSO) Census data and 2007 Health Service Executive{Primary Care Reimbursement Service (HSE{PCRS) sample data. 3. To develop a model to project GMS prescribing expenditure in five year intervals to 2026, using 2012 HSE{PCRS population data, incorporating cost containment measures, and 2011 CSO Census data. 4. To investigate the impact of demographic factors and the pharmacology of drugs (Anatomical Therapeutic Chemical (ATC)) on GMS expenditure. 5. To explore the consequences of GMS policy changes on prescribing expenditure and behaviour between 2008 and 2014. The thesis is centered around three published articles and is located between the end of a booming Irish economy in 2007, a recession from 2008{2013, to the beginning of a recovery in 2014. The literature identified a number of factors influencing pharmaceutical expenditure, including population growth, population aging, changes in drug utilisation and drug therapies, age, gender and location. The literature identified the methods previously used in predictive modelling and consequently, the Monte Carlo Simulation (MCS) model was used to simulate projected expenditures to 2026. Also, the literature guided the use of Ordinary Least Squares (OLS) regression in determining demographic and pharmacology factors influencing prescribing expenditure. The study commences against a backdrop of growing GMS prescribing costs, which has risen from e250 million in 1998 to over e1 billion by 2007. Using a sample 2007 HSE{PCRS prescribing data (n=192,000) and CSO population data from 2008, (Conway et al., 2014) estimated GMS prescribing expenditure could rise to e2 billion by2026. The cogency of these findings was impacted by the global economic crisis of 2008, which resulted in a sharp contraction in the Irish economy, mounting fiscal deficits resulting in Ireland's entry to a bailout programme. The sustainability of funding community drug schemes, such as the GMS, came under the spotlight of the EU, IMF, ECB (Trioka), who set stringent targets for reducing drug costs, as conditions of the bailout programme. Cost containment measures included: the introduction of income eligibility limits for GP visit cards and medical cards for those aged 70 and over, introduction of co{payments for prescription items, reductions in wholesale mark{up and pharmacy dispensing fees. Projections for GMS expenditure were reevaluated using 2012 HSE{PCRS prescribing population data and CSO population data based on Census 2011. Taking into account both cost containment measures and revised population predictions, GMS expenditure is estimated to increase by 64%, from e1.1 billion in 2016 to e1.8 billion by 2026, (ConwayLenihan and Woods, 2015). In the final paper, a cross{sectional study was carried out on HSE{PCRS population prescribing database (n=1.63 million claimants) to investigate the impact of demographic factors, and the pharmacology of the drugs, on GMS prescribing expenditure. Those aged over 75 (ẞ = 1:195) and cardiovascular prescribing (ẞ = 1:193) were the greatest contributors to annual GMS prescribing costs. Respiratory drugs (Montelukast) recorded the highest proportion and expenditure for GMS claimants under the age of 15. Drugs prescribed for the nervous system (Escitalopram, Olanzapine and Pregabalin) were highest for those between 16 and 64 years with cardiovascular drugs (Statins) were highest for those aged over 65. Females are more expensive than males and are prescribed more items across the four ATC groups, except among children under 11, (ConwayLenihan et al., 2016). This research indicates that growth in the proportion of the elderly claimants and associated levels of cardiovascular prescribing, particularly for statins, will present difficulties for Ireland in terms of cost containment. Whilst policies aimed at cost containment (co{payment charges, generic substitution, reference pricing, adjustments to GMS eligibility) can be used to curtail expenditure, health promotional programs and educational interventions should be given equal emphasis. Also policies intended to affect physicians prescribing behaviour include guidelines, information (about price and less expensive alternatives) and feedback, and the use of budgetary restrictions could yield savings.

PIPc study: development of indicators of potentially inappropriate prescribing in children (PIPc) in primary care using a modified Delphi technique

Objective There is limited evidence regarding the quality of prescribing for children in primary care. Several prescribing criteria (indicators) have been developed to assess the appropriateness of prescribing in older and middle-aged adults but few are relevant to children. The objective of this study was to develop a set of prescribing indicators that can be applied to prescribing or dispensing data sets to determine the prevalence of potentially inappropriate prescribing in children (PIPc) in primary care settings.


Design Two-round modified Delphi consensus method.


Setting Irish and UK general practice.


Participants A project steering group consisting of academic and clinical general practitioners (GPs) and pharmacists was formed to develop a list of indicators from literature review and clinical expertise. 15 experts consisting of GPs, pharmacists and paediatricians from the Republic of Ireland and the UK formed the Delphi panel.


Results 47 indicators were reviewed by the project steering group and 16 were presented to the Delphi panel. In the first round of this exercise, consensus was achieved on nine of these indicators. Of the remaining seven indicators, two were removed following review of expert panel comments and discussion of the project steering group. The second round of the Delphi process focused on the remaining five indicators, which were amended based on first round feedback. Three indicators were accepted following the second round of the Delphi process and the remaining two indicators were removed. The final list consisted of 12 indicators categorised by respiratory system (n=6), gastrointestinal system (n=2), neurological system (n=2) and dermatological system (n=2).


Conclusions The PIPc indicators are a set of prescribing criteria developed for use in children in primary care in the absence of clinical information. The utility of these criteria will be tested in further studies using prescribing databases.

Assessment of the quality of sample labelling for clinical research

Objective: To assess the quality of the labels for clinical trial samples through current regulations, and to analyze its potential correlation with the specific characteristics of each sample. Method: A transversal multicenter study where the clinical trial samples from two third level hospitals were analyzed. The eleven items from Directive 2003/94/EC, as well as the name of the clinical trial and the dose on the label cover, were considered variables for labelling quality. The influence of the characteristics of each sample on labelling quality was also analyzed. Outcome: The study included 503 samples from 220 clinical trials. The mean quality of labelling, understood as the proportion of items from Appendix 13, was of 91.9%. Out of these, 6.6% did not include the name of the sample in the outer face of the label, while in 9.7% the dose was missing. The samples with clinical trial-type samples presented a higher quality (p < 0.049), blinding reduced their quality (p = 0.017), and identification by kit number or by patient increased it (p < 0.01). The promoter was the variable which introduced the highest variability into the analysis. Conclusions: The mean quality of labelling is adequate in the majority of clinical trial samples. The lack of essential information in some samples, such as the clinical trial code and the period of validity, is alarming and might be the potential source for dispensing or administration errors.

Usability and Security in Medication Administration Applications

The traditional process of filling the medicine trays and dispensing the medicines to the patients in the hospitals is manually done by reading the printed paper medicine chart. This process can be very strenuous and error-prone, given the number of sub-tasks involved in the entire workflow and the dynamic nature of the work environment. Therefore, efforts are being made to digitalise the medication dispensation process by introducing a mobile application called Smart Dosing application. The introduction of the Smart Dosing application into hospital workflow raises security concerns and calls for security requirement analysis. This thesis is written as a part of the smart medication management project at Embedded Systems Laboratory, A° bo Akademi University. The project aims at digitising the medicine dispensation process by integrating information from various health systems, and making them available through the Smart Dosing application. This application is intended to be used on a tablet computer which will be incorporated on the medicine tray. The smart medication management system include the medicine tray, the tablet device, and the medicine cups with the cup holders. Introducing the Smart Dosing application should not interfere with the existing process carried out by the nurses, and it should result in minimum modifications to the tray design and the workflow. The re-designing of the tray would include integrating the device running the application into the tray in a manner that the users find it convenient and make less errors while using it. The main objective of this thesis is to enhance the security of the hospital medicine dispensation process by ensuring the security of the Smart Dosing application at various levels. The methods used for writing this thesis was to analyse how the tray design, and the application user interface design can help prevent errors and what secure technology choices have to be made before starting the development of the next prototype of the Smart Dosing application. The thesis first understands the context of the use of the application, the end-users and their needs, and the errors made in everyday medication dispensation workflow by continuous discussions with the nursing researchers. The thesis then gains insight to the vulnerabilities, threats and risks of using mobile application in hospital medication dispensation process. The resulting list of security requirements was made by analysing the previously built prototype of the Smart Dosing application, continuous interactive discussions with the nursing researchers, and an exhaustive stateof- the-art study on security risks of using mobile applications in hospital context. The thesis also uses Octave Allegro method to make the readers understand the likelihood and impact of threats, and what steps should be taken to prevent or fix them. The security requirements obtained, as a result, are a starting point for the developers of the next iteration of the prototype for the Smart Dosing application.

Usability and Security in Medication. Administration Applications

The traditional process of filling the medicine trays and dispensing the medicines to the patients in the hospitals is manually done by reading the printed paper medicinechart. This process can be very strenuous and error-prone, given the number of sub-tasksinvolved in the entire workflow and the dynamic nature of the work environment.Therefore, efforts are being made to digitalise the medication dispensation process byintroducing a mobile application called Smart Dosing application. The introduction ofthe Smart Dosing application into hospital workflow raises security concerns and callsfor security requirement analysis. This thesis is written as a part of the smart medication management project at EmbeddedSystems Laboratory, A˚bo Akademi University. The project aims at digitising the medicine dispensation process by integrating information from various health systems, and making them available through the Smart Dosing application. This application is intended to be used on a tablet computer which will be incorporated on the medicine tray. The smart medication management system include the medicine tray, the tablet device, and the medicine cups with the cup holders. Introducing the Smart Dosing application should not interfere with the existing process carried out by the nurses, and it should result in minimum modifications to the tray design and the workflow. The re-designing of the tray would include integrating the device running the application into the tray in a manner that the users find it convenient and make less errors while using it. The main objective of this thesis is to enhance the security of the hospital medicine dispensation process by ensuring the security of the Smart Dosing application at various levels. The methods used for writing this thesis was to analyse how the tray design, and the application user interface design can help prevent errors and what secure technology choices have to be made before starting the development of the next prototype of the Smart Dosing application. The thesis first understands the context of the use of the application, the end-users and their needs, and the errors made in everyday medication dispensation workflow by continuous discussions with the nursing researchers. The thesis then gains insight to the vulnerabilities, threats and risks of using mobile application in hospital medication dispensation process. The resulting list of security requirements was made by analysing the previously built prototype of the Smart Dosing application, continuous interactive discussions with the nursing researchers, and an exhaustive state-of-the-art study on security risks of using mobile applications in hospital context. The thesis also uses Octave Allegro method to make the readers understand the likelihood and impact of threats, and what steps should be taken to prevent or fix them. The security requirements obtained, as a result, are a starting point for the developers of the next iteration of the prototype for the Smart Dosing application.

Study on adherence to treatment with imatinib in chronic myeloid leukaemia and its association with therapeutic response

Objective: To assess the level of adherence to treatment with imatinib in patients with chronic myeloid leukaemia and its association with therapeutic response. Materials and methods: Study conducted on October, 2013 - March, 2014, including patients diagnosed with Chronic Myeloid Leukaemia on treatment with imatinib in the hospital. Therapeutic adherence was assessed through the standard Morisky-Green Questionnaire and the medication dispensing record. Those patients who did not complete 6 months of treatment and/or did not complete the questionnaire were excluded. Therapeutic response was assessed following clinical guidelines. The descriptive analysis of variables and correlation was conducted through Pearsons's Chi-Square Test. Results: The study included 31 patients. When assessing the level of association between response variables and therapeutic adherence: 1. The highest molecular response was reached by 68.4% of those patients with high adherence, and by 75% of those patients with intermediate adherence. 2. Complete molecular response was achieved by 57.9% of patients with high adherence, and by 58.3% of patients with intermediate adherence. No statistically significant differences were found in response variables between patients with high and intermediate therapeutic adherence. No association was observed between level of adherence and therapeutic response. Conclusions: We cannot confirm that a different level of therapeutic adherence might have an impact on response to imatinib, though this should be taken into account in cases of therapeutic failure or sub-optimal response.

Direct Write Fabrication of Waveguides and Interconnects for Optical Printed Wiring Boards

Current copper based circuit technology is becoming a limiting factor in high speed data transfer applications as processors are improving at a faster rate than are developments to increase on board data transfer. One solution is to utilize optical waveguide technology to overcome these bandwidth and loss restrictions. The use of this technology virtually eliminates the heat and cross-talk loss seen in copper circuitry, while also operating at a higher bandwidth. Transitioning current fabrication techniques from small scale laboratory environments to large scale manufacturing presents significant challenges. Optical-to-electrical connections and out-of-plane coupling are significant hurdles in the advancement of optical interconnects. The main goals of this research are the development of direct write material deposition and patterning tools for the fabrication of waveguide systems on large substrates, and the development of out-of-plane coupler components compatible with standard fiber optic cabling. Combining these elements with standard printed circuit boards allows for the fabrication of fully functional optical-electrical-printed-wiring-boards (OEPWBs). A direct dispense tool was designed, assembled, and characterized for the repeatable dispensing of blanket waveguide layers over a range of thicknesses (25-225 µm), eliminating waste material and affording the ability to utilize large substrates. This tool was used to directly dispense multimode waveguide cores which required no UV definition or development. These cores had circular cross sections and were comparable in optical performance to lithographically fabricated square waveguides. Laser direct writing is a non-contact process that allows for the dynamic UV patterning of waveguide material on large substrates, eliminating the need for high resolution masks. A laser direct write tool was designed, assembled, and characterized for direct write patterning waveguides that were comparable in quality to those produced using standard lithographic practices (0.047 dB/cm loss for laser written waveguides compared to 0.043 dB/cm for lithographic waveguides). Straight waveguides, and waveguide turns were patterned at multimode and single mode sizes, and the process was characterized and documented. Support structures such as angled reflectors and vertical posts were produced, showing the versatility of the laser direct write tool. Commercially available components were implanted into the optical layer for out-of-plane routing of the optical signals. These devices featured spherical lenses on the input and output sides of a total internal reflection (TIR) mirror, as well as alignment pins compatible with standard MT design. Fully functional OEPWBs were fabricated featuring input and output out-of-plane optical signal routing with total optical losses not exceeding 10 dB. These prototypes survived thermal cycling (-40°C to 85°C) and humidity exposure (95±4% humidity), showing minimal degradation in optical performance. Operational failure occurred after environmental aging life testing at 110°C for 216 hours.

Bionano Electronics: Magneto-Electric Nanoparticles for Drug Delivery, Brain Stimulation and Imaging Applications

Nanoparticles are often considered as efficient drug delivery vehicles for precisely dispensing the therapeutic payloads specifically to the diseased sites in the patient’s body, thereby minimizing the toxic side effects of the payloads on the healthy tissue. However, the fundamental physics that underlies the nanoparticles’ intrinsic interaction with the surrounding cells is inadequately elucidated. The ability of the nanoparticles to precisely control the release of its payloads externally (on-demand) without depending on the physiological conditions of the target sites has the potential to enable patient- and disease-specific nanomedicine, also known as Personalized NanoMedicine (PNM). In this dissertation, magneto-electric nanoparticles (MENs) were utilized for the first time to enable important functions, such as (i) field-controlled high-efficacy dissipation-free targeted drug delivery system and on-demand release at the sub-cellular level, (ii) non-invasive energy-efficient stimulation of deep brain tissue at body temperature, and (iii) a high-sensitivity contrasting agent to map the neuronal activity in the brain non-invasively. First, this dissertation specifically focuses on using MENs as energy-efficient and dissipation-free field-controlled nano-vehicle for targeted delivery and on-demand release of a anti-cancer Paclitaxel (Taxol) drug and a anti-HIV AZT 5’-triphosphate (AZTTP) drug from 30-nm MENs (CoFe2O4-BaTiO3) by applying low-energy DC and low-frequency (below 1000 Hz) AC fields to separate the functions of delivery and release, respectively. Second, this dissertation focuses on the use of MENs to non-invasively stimulate the deep brain neuronal activity via application of a low energy and low frequency external magnetic field to activate intrinsic electric dipoles at the cellular level through numerical simulations. Third, this dissertation describes the use of MENs to track the neuronal activities in the brain (non-invasively) using a magnetic resonance and a magnetic nanoparticle imaging by monitoring the changes in the magnetization of the MENs surrounding the neuronal tissue under different states. The potential therapeutic and diagnostic impact of this innovative and novel study is highly significant not only in HIV-AIDS, Cancer, Parkinson’s and Alzheimer’s disease but also in many CNS and other diseases, where the ability to remotely control targeted drug delivery/release, and diagnostics is the key.