We performed a cross-sectional study using a representative sample of 140 unrelated Bahraini patients with T2DM and 66 non-diabetic healthy subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the distribution of allele and genotype frequency of the SNP +45T>G polymorphism (exon2) and SNP +276G>T polymorphism (intron 2) in ADIPOQ. Lipid profile was measured by enzymatic methods. An ELISA was used to determine serum adiponectin and resistin levels.

It was observed that obesity, insulin resistance and T2DM are associated with low serum adiponectin levels. Compared with the control group, the T2DM group exhibited lower adiponectin levels and higher resistin levels. The G allele and TG/GG genotype of SNP +45T>G occurred more frequently than the common T allele and TT genotype in T2DM patients compared to the controls (PSNP +45T>G were associated with lower serum adiponectin levels. There was no statistically significant difference in allele and genotype frequencies of SNP +276G>T comparing control group with T2DM group.

No association with metabolic parameters was detected with either of the SNPs. In summary, our results demonstrated that, adiponectin SNP +45T>G, rather than SNP +276G>T is more associated with adiponectin levels. However, we could not confirm an association of these two SNPs with metabolic parameters of the metabolic syndrome.

Aim: The aim of this study is to extrapolate and illuminate the lived experience for patients with ALSMND, their carers and their health-care professionals regarding end-of-life decisions and advance care directives and to identify if the experiences of the participants concur.

Methods: A qualitative hermeneutic approach, guided by the philosophy of Hans Georg Gadarner, was the chosen methodology for this study as it illuminates the meaning and understanding of the lived experience of contemplating end-of-life decisions and advance care directives for patients with ALSIMND, their carers and their healthcare professionals. Purposive sampling was used to identify participants for this study. All the participants had experience pertaining to the phenomenon under investigation and included patients with ALSIMND, their carers and their health-care professionals, including nurses, Palliative Care Consultants and Consultant Neurologists.

Results: The study identified the difficulties and complexities in initiating and discussing end-of-life issues for all involved. It highlighted the importance of family consensus and support throughout the disease trajectory. The study revealed that there was ambivalence regarding legalising advance care directives and that the participants had a preference for disease specific advance care directives. The study highlighted that in relation to revisiting end-of-life discussions the participants views did not concur. The health-care professionals expressed a wish to revisit end-of-life discussions periodically. However, the carers did not wish to revisit them fearing that the decisions made may be revoked. The study identified the need to improve communication between the various multidisciplinary teams. It highlighted the need to increase public information and awareness regarding end-of-life decisions and advance care directives whereby it does not have to be a sentinel event before these discussions take place. The study identified that referral to the ALSIMND clinic would result in timely and appropriate end-of-life discussions and advance care directives taking place. It identified that patients who wish to invoke an advance care directive and have their end-of-life wishes respected are completely dependent on the attending physician.

Conclusions: The discussion of end-of-life issues and advance care directives appears to be fraught with difficult challenges. The potential for conflict may lead health-care professionals to avoid open discussions and advance care planning. End-of-life decisions and advance care directives are an extremely important process that emerges in the context of the patient, carer and health-care professional relationship. This study has identified that the use of advance care directives cannot promise or guarantee patients with Amyotrophic Lateral Sclerosis/Motor Neurone Disease a say in their end-of-life care.

Numerous microencapsulation techniques have been developed. One of the most commonly used techniques in the pharmaceutical and food industries is spray drying primarily because it is a one step continuous process which is easily scalable (Masters, 1991). Microencapsulation of actives using spray drying is a well established technology and the formulation and process parameters influencing microencapsulation varying activelpolymer combinations for oral, pulmonary and parenteral drug delivery have been studied extensively (Rattes & Oliveira, 2007b), (Learoyd, Burrows, French, & Seville, 2008) and (Mu, Teo, Ning, Tan, & Feng, 2005). In general, spray dried microparticles of drug and polymer tend to consist of a matrix structure where the drug is distributed within the polymer matrix giving rise to controlled release of the active by diffusion from the polymer matrix (Rattes & Oliveira, 2007a). While these matrix microparticles serve the purpose of controlled release and stabilisation, part of the active is usually available at the particle surface giving rise to a fast initial drug release or burst release andlor potential degradation of surface exposed labile molecules (He, Davis, & Illum, 1999) and (Freiberg & Zhu, 2004).

Traditionally, the spray drying process is carried out by spray drying a solution or suspension of the drug and polymer through a nozzle into heated air or nitrogen which dries the droplets formed resulting in the formation of drug/polymer matrix particles. In this research project, we examined the possibility of forming microparticles where the active would be coated or encapsulated by the coating polymer to give a 2 layered particle consisting of a core of the active and a polymer coat. The conventional nozzle was replaced with a novel nozzle configuration which allows the feeding of 2 separate streams of liquid, active and polymer solutions (Ramtoola, 2008). The microencapsulation of 3 model drugs; diclofenac sodium, omeprazole and simvastatin for oral delivery was examined using the polymers; ethylcellulose, hydroxypropylmethylcellulose (HPMC), poly (methyl methacrylate) (EudragitB L100) dissolved in either water or ethanol as the vehicle. Microparticles were prepared using the novel nozzle configuration and were compared with corresponding microparticles formulated using the conventional nozzle. The microencapsulation of Insulin, as a model protein by the biodegradable polymer, chitosan, was also studied using the novel nozzle configuration and was compared with corresponding microparticles formulated using the conventional nozzle.

The influence of process and formulation variables including the ratio of polymer to drug flow rates, the polymer to drug concentrations and percent total solid content of feed solutions on the properties of the microparticles were examined. The fluorescent markers; sodium fluorescein or rhodamine were added to the polymer (coat) and drug (core) feed solutions to allow visualisation of the internal morphology of the particles formulated. Microparticles formed were characterised for their morphology using various microscopy techniques. The size and size distribution, thermal properties, drug content and drug release properties of the micro particles were evaluated.

The results show that the novel double nozzle attachment successfully allowed the formation of microparticles which consisted of a defined core and coat as was shown by confocal and transmission electron microscopy. In contrast using the conventional nozzle, particles formed were shown to consist of a homogenous matrix with no defined drug/polymer regions.

Increasing the feed flow rates from 2ml to 8 ml per minute showed little increase in microparticle size for either the conventional or the novel nozzle configuration used. The particle size and size distribution of microparticles formulated using the novel double feed nozzle configuration were similar to corresponding microparticles spray dried using the single nozzle configuration. As the concentration of feed solutions increased to 10% wlv total solids, an increase in median particle size from 10-12 microns to >30 microns and a corresponding size distribution, Span value, was observed. As was expected, the effect of varying the feed flow rates of the polymer and drug solutions for similar polymer and drug concentrations was found to result in microparticles containing a drug to polymer ratio which was proportional to the feed flow ratio.

The internal morphology of the microparticles formulated using the novel nozzle configuration was markedly different to the internal morphology of the microparticles formulated using the conventional nozzle. Confocal microscopy and transmission electron microscopy showed a defined two layered structure analogous with a core and coat structure for particles spray dried using the novel nozzle. In contrast, a homogenous structure was observed for particles formulated using the conventional nozzle. Interestingly, scanning electron microscopy showed the outer morphology of the microparticles to be similar in most cases.

In general the drug content of microparticles were high with an encapsulation efficiency of >80% and were within expected levels for spray drying. Some deviations were observed as for chitosan and insulin microparticles where a low encapsulation efficiency of 20% was observed for the single nozzle microparticles. This was explained as a result of the poor extraction of the INS from the matrix structure microparticles during the analysis.

Drug release properties showed that while drug release was in general slower than for the pure drug, the rate of drug release from the microparticles was fast with release complete over 1-7 hours and were similar irrespective of the nozzle configuration used. This was probably related to the small particle size, hence large surface area of the microparticles formulated. At the lower drug loadings of 10% W/W, the initial burst release was lower and the subsequent release rate slower than at higher loadings as was expected.

While further work is required to better understand the impact of process and formulation variables on the particle characteristics and in particular drug release properties, the results from this research work show that this novel nozzle can be used to formulate drug and polymer microcapsules or reservoir type microparticles in comparison ta the matrix type of particles formulated when using the standard conventional nozzle configuration. The potential of this novel nozzle to formulate particles with enhanced stability, greater control of release of active and for targeted release and delivery of actives allows its application across a wide range of products including pharmaceutical, food, cosmetic and other consumer products.

Tumourigenesis is a multistep process which includes the transformation of healthy cells into extremely malignant cells, caused by the disruption of normal tissue homeostasis. Hanahan and Weinberg propose that there are a common set of 'acquired capabilities' that most if not all cancers posses's in order to survive and proliferate despite changes in their normal cell physiology during cancer development (Hanahan and Weinberg, 2000). These "Hallmarks of Cancer", according to Hanahan and Weinberg, are the six essential physiological alterations which lead to malignant growth: self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis and tissue invasion and metastasis.

Evasion of apoptosis is a cleverly employed alteration by cancer to enhance their survival and proliferation. Most tumours have defective apoptotic machinery and for this reason therapies which are specifically targeted at promoting apoptosis are particularly effective in the treatment of cancer. This aspect of cancer biology will be the primary focus of this thesis.

Prostate cancer

It is estimated around 913,000 cases of prostate cancer were diagnosed worldwide in 2008. Of these, 338,000 cases were diagnosed in the EU with the highest incidence in Ireland (Ferlay et a/., 2008). Although there are several etiological factors (genetics, environment etc.) associated with prostate cancer, the most prominent risk factor is age with a rapid steep rise in incidences, more than any other cancer (Jemal eta/., 2003; Wang et a/., 2008).

There are several treatment options for prostate cancer including surgery, radiotherapy, hormone therapy and chemotherapy. Some patients can avail of surgery to remove the prostate-nerve sparing prostatectomy, but this is not option for every patient. Brachytherapy is another option which involves the placement of hundreds of radioactive seeds into the prostate. Ultrasound technology is used to ensure careful placement and to better control the effect on surrounding healthy tissue. The most common therapy for prostate cancer is Androgen Deprivation Therapy (ADT), as this cancer is highly reliant on androgens for proliferation (Miyamoto et a/., 2004). ADT can prolong patient's life expectancy, but nearly all patients progress to an androgen independent state which has no current effective therapy (Assikis and Simons, 2004).

In prostate cancer, chemotherapy is used to treat advanced cancers usually after radiotherapy or surgery have failed, or when the cancer progresses to a hormone refractory state and no longer responds to ADT. Docetaxel is one such chemotherapeutic drug used to treat advanced prostate cancer. Docetaxel is a member of the taxane class of drugs and acts by binding to microtubules causing them to become hyper-stabilized (Mollinedo and Gajate, 2003; Stein, 1999). This prevents depolymerisation of the microtubules, inhibiting mitotic cell division. It is cytotoxic to all quickly dividing cells including bone marrow and hair follicles as well as the cancer cells. Due to this extensive cytotoxicity which is not localised to cancer cells, there are adverse side effects associated with all chemotherapy, with alopecia being a very common side effect.

There is constant on-going research to develop new treatments that more specifically target cancer cells. This is likely to be a much more effective approach; it will try to limit the damage to surrounding healthy cells and help reduce the side effects associated with standard chemotherapy while still providing effective treatment to the patient. One of these promising new class of drugs currently in trials are the BH3 mimetics. They aim to promote apoptosis in cells with defective apoptotic machinery. These drugs will be discussed in more detail in section 1.4.

The Androgen Independent DU 145 prostate cancer cell line is one of the "classical" cell lines used to study prostate cancer (Alimirah et a/., 2006). It was originally derived from a 69 year old male with metastatic prostate cancer (Stone et a/., 1978). The DU 145 cell line completely lacks Bax expression.

Falls and fractures are a major concern for the elderly population as they can result in decreased functional abilities and more dependence to complete activities of daily living within the community.

The use of valid, reliable and sensitive outcome measures is essential to observe functional abilities over time and assess the risk of falls in the future. Eighty-one patients consented to participate in this study with thirty three participating in the early assessment group; these patients were assessed at three and 15 months. For the 81 subjects, the average age was 81 years with a standard deviation of 8.00 years (60 - 96 years). The average age of the 33 subjects was 81 years (sd 8.00, range 65 - 94). A range of measures assessing movement, strength, balance, endurance and extended activities of daily living were applied.

The types of fracture, surgery, length of stay to surgery, types of anaesthesia used, surgical approach used, pain reported, discharge plan from the acute hospital, length of stay were reviewed in both the acute hospital and rehabilitation facility.

At three months the mean Berg balance score was 39.16 (sd12.98, range 18 - 56) and 15 months 38.44 (sd 14.04; range 11 -55) but no significant differences were found (p>0.05).

The mean Timed Up and Go score was 29.90 (sd 18.99; range 0 - 69.18) at three months and 27.27 (sd 18.76; range 0 - 66.38) at fifteen months but no significant differences were found (p>0.05).

The mean six minute walk test scores for the early assessment group were 165.84m (sd 85.34; range 0 - 359.20) at three months and at 15-months 193.72m (sd 110.98; range 0 - 3 84.69), the change was not significant (p>0.05).

At three months the right hand dynamometry mean score was 25.56 (sd 13.57; range 0 - 65) lbs and left hand mean score was 25.48 (sd 10.88; range 6.00 - 46.00) lbs. At fifteen months the right hand dynamometry score was 23.80 (sd 12.67 range 8.67 - 59.33) lbs and left hand dynamometry score was 25.48 (sd 8.47; range 11 - 37.67) lbs. No significant differences were found in grip strength (p>0.05).

The mean pre-fracture Nottingham Extended activities of daily living (NEADL) score was 47.61 (sd 13.14; range 18 - 63) while at three months the mean score was 32.55 (sd 17.26; range 3 - 63) and at fifteen months was 39.45 (sd 18.45; range 1 - 63). Significant differences were found between pre fracture and 3 months (p

In conclusion, no significant functional improvements were observed after 3 months despite significant in-patient input (compared with other countries) and further physiotherapy/rehabilitation input post discharge. Therefore, the findings from this study highlight the need to re-evaluate the current model of care for elderly post hip fracture patients.

In this research we aim to use a polymer conjugate of K³º for the delivery of small interfering RNA (siRNA), a new exciting alternative to gene therapy, which operates downstream in the transcription pathway, through modulation of mRNA to produce gene silencing. Once optirnised, it is hoped that PEGylated K³º can be used as a universal delivery agent for any number of siRNA therapeutics in vivo.

K³º can be classified as a 'difficult peptide sequence'. This so-called terminology is used in the literature to describe any peptide which cannot be synthesised by classical means, involving rvutine automated peptide synthesis.[4-7] Generally, automated synthesis is reliable to a length of approxiinately twenty residues[8], so it is not surprising that K³º has been difficult to make by these means.

Various methods were attempted towards the synthesis of K³º, including (i) modification of the standard automated procedure with double coupling from a PEG-polystyrene composite resin, (ii) stepwise synthesis of two unprotected fragments to be ligated orthogonal to amide bond chemistry, and (iii) the synthesis of protected fragments to be coupled in solution to form the amide bond. [8]

In the end, monitoring of the sequence assembly was used to overcome the limitations associated with the solid phase synthesis of this peptide and the polylyshe sequence was successfully elongated by this approach.

After a certain point, about 18 residues, the peptide begins to aggregate on the solid support, preventing the reagents from reaching and reacting with the N-terminal of the peptide. To overcome this aggregation, a resin with a high hydrophilic content and a low substitution was chosen. The hydrophilicity of this resin repels the growing hydrophobic, protected chain. Furthermore the sparsity of linkers reduces the contact between adjacent chains. This NovaPEG Low Loading resin, combined with double coupling chemistry yielded the peptide K³º.

Other work included synthesis of host defence and cell penetrating peptide P17, peptide PEGylation by thiol-maleimide ligation and azo-modified amino acids for use in Click chemistry with alkynyl PEG.

Methods: TB4 cell monolayers were mounted in Ussing chambers and CI- secretion was measured as changes in short-circuit current. Gene and protein expressionlphosphorylation was measured by RT-PCR, confocal microscopy and western blotting. Surface protein expression was determined by cell surface biotinylation. lntracellular ca2' levels were measured by Fura-2 fluorescence and cAMP levels by ELlSA assays.

Results: Acute treatment with EGF (100 nglml; 15 minutes) increased CI- secretory responses to the ca2+ and CAMP-dependent agonists, carbachol (CCh; 100 pM) and forskolin (FSK; 10 pM) when measured 24 hours later. Acute treatment with EGF did not chronically alter CCh-induced induced elevations in intracellular ca2' but significantly potentiated FSK-induced cAMP accumulation. The effects of EGF are mediated by a heat-labile soluble factor. Treatment with EGF did not affect the membrane expression or activity of KCNN4, KCNQI, the ~ a ' - K'-ATPase or CFTR. In contrast, under conditions that specifically isolate apical CI- currents through ca2'-activated channels (CaCC), EGF potentiated CCh-induced responses. Furthermore, mRNA and protein expression of the CaCC, transmembrane protein 16A (TMEMI 6A), was increased by EGF TMEM16A expression and CaCC currents were inhibited by the phosphatidylinositol 3-kinase inhibitor, LY290042 (25 pM). A general protein kinase C inhibitor, GF109203X (5 pM), also inhibited EGF-induced potentiation of CI- secretion. However, while the PKCaIP inhibitor, Go6976 (1 pM) and a PKCE translocation inhibitor (200 pM) were without effect, EGF-induced increases in CI- secretion, CaCC currents and TMEM16A expression were significantly reduced in the presence of the PKCG inhibitor, rottlerin (20 pM). Furthermore, EGF significantly increased phosphorylation of PKCG, but not PKCa, with a maximal effect occurring 1 hour after treatment. Moreover, the P13-K inhibitor, LY290042 (25 pM) inhibited the effects of EGF on PKC6 activation. Inhibition of extracellular regulated kinase 112 with PD98059 (25 pM) abolished EGF-induced increases in ca2'- and CAMP-stimulated CI- secretion, whereas Src kinase inhibition with PP2 (20 pM) and p38 kinase inhibition with SB203580 (10 pM) inhibited effects of the growth factor on CAMP-stimulated CI- secretion only.

Conclusions: EGF chronically enhances epithelial secretory capacity through a mechanism that involves P13K and PKCG-dependent induction of the novel CaCC, TMEM16A. Our results suggest that targeting EGFR-dependent signalling pathways represents a good approach for development of new drugs to treat intestinal transport disorders.

1.1 Introduction

1.2 Results and Discussion

1.3 Conclusion and Future work

1.4 References

Chapter 2: Gold 1 NHC Catalysis

2.1 Introduction

2.2 Results and Discussion

2.3 Conclusion

2.4 References

Chapter 3: Synthesis of NHC based on Deoxyribose Scaffold

3.1 Introduction

3.2 Results and Discussion

3.3 Conclusion and Future work

3.4 References

Conclusion

Experimental Section

General Experimental details

Experimental for Chapter 2

Experimental for Chapter 3

Appendix-NMR spectra

NMR spectra for Chapter 2

NMR spectra for Chapter 3

A method was designed and optimised for the processing, homogenisation and reliable extraction of good quality total RNA from fresh frozen bone tissue. Amplification of rniRNA from this total RNA was achieved. The miRNA profiles of trabecular and cortical femoral bone tissue from osteopenic and osteoporotic hip fracture patients were assessed and compare to controls. miRNA consistently differentially expressed with disease were short-listed and cross referenced to identify their predicted mRNA targets of interest in bone dynamics and disease. 76 miRNA were demonstrated to be consistently differentially expressed in diseased bone tissue, with most being specifically differentially expressed in either cortical or trabecular bone. Only 5 miRNA were differentially regulated in both bone types. The differential expression of miRNA with disease state indicates a role for miRNA in bone dynamics and disease, with miRNA short-listed linked to predicted target mRNA previously shown to be key in osteoblast and osteoclast differentiation and proliferation.

Two of the miRNA short-listed by profiling, miR-532-3p and miR-877, were specifically experimentally up- and down-regulated in a human osteoblast cell line. The promotion and suppression of these two miRNA was shown to have no effect on alkaline phosphatase and collagen type 1 A1 expression levels over the course of a 6 day study in-vitro.

Methods: Aspirin non-responding patients were identified using laboratory based methods (Light Transmission Aggregometry with arachidonic acid, VerifyNow™-Aspirin, serum thromboxane B2) to screen a cardiovascular diseased patient population. Interventions (interview and education) were used to encourage and ensure compliance and aspirin brands were switched from 75 mg enteric-coated to 75 mg un-coated and increased to a max. dose of 300 mg un-coated aspirin until premium in vitro aspirin response was achieved by all three assays.

Results: 248 (65±10yr, 79±14kg) patients were screened for their response to aspirin by at least one of three in vitro platelet function tests. 29% (71 patients) (64±13yr, 87±18kg) were identified as non-responding. 16% of the cohort (41 patients) (65±12yrs, 85±16kg) responded to aspirin following interventions to improve compliance. After ensuring patient compliance, only 6% (1 6 patients) (57±12yr, 98±23kg), all taking 75 mg enteric coated aspirin, remained non-responsive and were switched to 75 mg un-coated aspirin and increased to 300 mg un-coated aspirin until optimum aspirin response achieved. All but 0.4% (1 patient) responded. 6% of the entire cohort (16 patients) were lost to follow-up.

Conclusion: Our study shows that patient non-compliance is the primary cause of AR, accounting for 58% (41 patients) of perceived "resistance". With compliance assured, 6% of the cohort, one-in-four patients >90 kg, show an insufficient response to, and are thus unsuitably protected by, 75 mg enteric-coated aspirin. These heavier patients are not resistant to aspirin as they respond following substitution to 75 mg un-coated aspirin. In some cases (in 12.5% of patients >I00 kg) increasing to 150 mg un-coated aspirin is required to achieve cardiovascular protection. These data show that the maximum prevalence of true AR is 1.5% (95% confidence interval).

CP is a lifelong condition that challenges the individual child and their family. The majority of children with CP will walk either with or without the need for assistive mobility aids. These children will, however, all display some degree of pathological or abnormal gait. As a result, the management of the condition is often directed towards changing or controlling the effect CP has on gait and function.

The use of valid, reliable and sensitive outcome measures in the clinical environment is essential for evaluating the efficacy of interventions and goals. The FWT was designed to specifically describe the functional walking ability of the child with CP. It consists of 11 items, divided into 5 categories: (1) Kneeling (2) From Kneeling (3) Standing (4) Walking (5) Stairs. The maximum score is 23. The FWT was however lacking in psychometric data.

In relation to the reliability of the FWT; the inter-rater reliability was determined through comparison of scores obtained by 8 of raters. The intra-rater reliability was determined through comparison of the raters' scores over two intervals. The raters were given one month to score all 56 participants. One month after the initial scoring, the raters were asked to repeat the scoring.

The validity and sensitivity was assessed through comparison of the performance of the FWT against another measure of established validity, the Gross Motor Function Measure (GMFM), in respect of the same subjects at the same time. The FJVT and GMFM section D and E were administered to all 56 participants by the principal investigator on two occasions over a six month period.

There were 56 children in the study group. The mean age was 9.6 years with a standard deviation of 3.9 years (range 4.2-17.7 years). The subjects were stratified for severity by Gross Motor Function Classification System level (GMFCS), and comprised of 38 GMFCS I, 8 GMFCS II and 10 GMFCS III. Twenty-three participants had CP diplegia (41.2%), twenty two (39.3%) had CP right hemiplegia and 11 (19.5%) had left sided hemiplegia.

The results of the reliability section of the study found that the FWT had high levels of reliability at the levels of individual items and total scoring. Generalisability Correlation that provision of services to those with CP is of the highest standards, and that they are client and family centred at all times.

Stroke is one of the leading causes of death and disability in Ireland. Access to high quality emergency and acute stroke care has beendemonstrated to reduce mortality and improve patient outcomes. Despite the introduction of clot-busting therapies such as thromboiysis, its use remains low in Ireland. Delay in the recognition of stroke warning signs and in seeking medical attention contribute to treatment delay. Previous studies indicate that knowledge of stroke risk factors and warning signs in the general public ispoor, resulting in delay in responding and seeking medical care.

Aim

To study knowledge of risk factors and warning signs for stroke in adults in Ireland and to identify factors contributing to delay in seeking medicalattention following a suspected stroke.

Method

A representative sample of 1000 adults selected using random-digit dialling took part. Information relating to the public's knowledge of stroke wasgathered by interview administered telephone questionnaire.

Results

Findings show that knowledge of the risk factors and warning signs for stroke in Ireland is poor. While 70% of participants could correctly list twoor more of the risk factors for stroke, only 4O0/0 could list two or more warning signs. Less than 50% of participants stated that they would call an ambulance if they were having a stroke. Overall, there were significant gaps in knowledge with poorest levels evident in those aged over 65.

Conclusion

Knowledge deficits highlighted by this study suggest that there is no coherent view of stroke held by the general public, which may contribute to inappropriate response to stroke and subsequent prolonged treatment delays. Targeted public health messages are urgently required in order to improvepopulation knowledge of stroke, especially among the over 65s. Further research in this area is needed.