Susan Carson in conversation with Donna Lee Brien on research higher degree examination administration

This paper is the edited transcript of a conversation between Susan Carson and Donna Lee Brien about an administrator’s perspective of the process of examining doctoral theses in the creative industries. Susan was central to the process in the Faculty of Creative Industries from 2008 to 2012, and has overseen the carriage of examination for creative arts theses in the creative industries disciplines of creative writing, performance studies, media and communication, journalism, film and television, visual arts, and interaction and visual design.

Testosterone reinforcement : intravenous and intracerebroventricular self-administration in male rats and hamsters

Rationale: Anabolic steroids are drugs of abuse. However, the potential for addiction remains unclear. Testosterone induces conditioned place preference in rats and oral self-administration in hamsters. Objectives: To determine if male rats and hamsters consume testosterone by intravenous (IV) or intracerebroventricular (ICV) self- administration. Methods: With each nose-poke in the active hole during daily 4-h tests in an operant condi- tioning chamber, gonad-intact adult rats and hamsters received 50 mg testosterone in an aqueous solution of b-cyclodextrin via jugular cannula. The inactive nose- poke hole served as a control. Additional hamsters received vehicle infusions. Results: Rats (n=7) expressed a significant preference for the active nose-poke hole (10.0€2.8 responses/4 h) over the inactive hole (4.7€1.2 responses/4 h). Similarly, during 16 days of testosterone self-administration IV, hamsters (n=9) averaged 11.7€2.9 responses/4 h and 6.3€1.1 responses/4 h in the active and inactive nose-poke holes, respectively. By contrast, vehicle controls (n=8) failed to develop a preference for the active nose-poke hole (6.5€0.5 and 6.4€0.3 responses/4 h). Hamsters (n=8) also self-administered 1 mg testosterone ICV (active hole:39.8€6.0 nose-pokes/ 4 h; inactive hole: 22.6€7.1 nose-pokes/4 h). When testosterone was replaced with vehicle, nose-poking in the active hole declined from 31.1€7.6 to 11.9€3.2 responses/ 4 h within 6 days. Likewise, reversing active and inactive holes increased nose-poking in the previously inactive hole from 9.1€1.9 to 25.6€5.4 responses/4 h. However, reducing the testosterone dose from 1 mg to 0.2 mg per 1 ml injection did not change nose-poking. Conclu- sions: Compared with other drugs of abuse, testosterone reinforcement is modest. Nonetheless, these data support the hypothesis that testosterone is reinforcing.

Olfactory glia enhance neonatal axon regeneration

Olfactory ensheathing cells (OECs) migrate with olfactory axons that extend from the nasal epithelium into the olfactory bulb. Unlike other glia, OECs are thought to migrate ahead of growing axons instead of following defined axonal paths. However it remains unknown how the presence of axons and OECs influences the growth and migration of each other during regeneration. We have developed a regeneration model in neonatal mice to examine whether (i) the presence of OECs ahead of olfactory axons affects axonal growth and (ii) the presence of olfactory axons alters the distribution of OECs. We performed unilateral bulbectomy to ablate olfactory axons followed by methimazole administration to further delay neuronal growth. In this model OECs filled the cavity left by the bulbectomy before new axons extended into the cavity. We found that delaying axon growth increased the rate at which OECs filled the cavity. The axons subsequently grew over a significantly larger region and formed more distinct fascicles and glomeruli in comparison with growth in animals that had undergone only bulbectomy. In vitro, we confirmed (i) that olfactory axon growth was more rapid when OECs were more widely distributed than the axons and (ii) that OECs migrated faster in the absence of axons. These results demonstrate that the distribution of OECs can be increased by repressing by growth of olfactory axons and that olfactory axon growth is significantly enhanced if a permissive OEC environment is present prior to axon growth.

Ghrelin receptor (GHS-R1A) antagonism suppresses both operant alcohol self-administration and high alcohol consumption in rats

The mechanisms involved in alcohol use disorders are complex. It has been shown that ghrelin is an important signal for the control of body weight homeostasis, preferably by interacting with hypothalamic circuits, as well as for drug reward by activating the mesolimbic dopamine system. The ghrelin receptor (GHS-R1A) has been shown to be required for alcohol-induced reward. Additionally, ghrelin increases and GHR-R1A antagonists reduce moderate alcohol consumption in mice, and a single nucleotide polymorphism in the GHS-R1A gene has been associated with high alcohol consumption in humans. However, the role of central ghrelin signaling in high alcohol consumption is not known. Therefore, the role of GHS-R1A in operant self-administration of alcohol in rats as well as for high alcohol consumption in Long-Evans rats and in alcohol preferring [Alko alcohol (AA)] rats was studied here. In the present study, the GHS-R1A antagonist, JMV2959, was found to reduce the operant self-administration of alcohol in rats and to decrease high alcohol intake in Long-Evans rats as well as in AA rats. These results suggest that the ghrelin receptor signaling system, specifically GHS-R1A, is required for operant self-administration of alcohol and for high alcohol intake in rats. Therefore, the GHS-R1A may be a therapeutic target for treatment of addictive behaviors, such as alcohol dependence.

Crushed tablets : does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.

Oral testosterone self-administration in male hamsters

The addiction potential of anabolic steroids remains largely unexplored. Here, we demonstrate voluntary oral testosterone intake in hamsters. Using a 2-bottle choice test, males preferred an aqueous solution of 200 microg/ml testosterone over vehicle. However, the taste of testosterone is not highly preferred. Addition of testosterone at 400 microg/ml increased fluid consumption from the nonpreferred bottle in a 2-bottle choice test, but cholesterol at the same concentration reduced drinking, suggesting that testosterone reward is not common to all sterols. With food-induced drinking, testosterone maintained fluid intake when food was withdrawn. These data demonstrate that oral self-administration of testosterone is reinforcing in hamsters, suggesting the potential for dependence in human users.

Targeted disruption of the JAK2/STAT3 pathway in combination with systemic administration of paclitaxel inhibits the priming of ovarian cancer stem cells leading to a reduced tumor burden

Chemotherapy resistance associated with recurrent disease is the major cause of poor survival of ovarian cancer patients. We have recently demonstrated activation of the JAK2/STAT3 pathway and the enhancement of a cancer stem cell (CSC)-like phenotype in ovarian cancer cells treated in vitro with chemotherapeutic agents. To elucidate further these mechanisms in vivo,we used a two-tiered paclitaxel treatment approach in nude mice inoculated with ovarian cancer cells. In the first approach, we demonstrate that a single intraperitoneal administration of paclitaxel in mice 7 days after subcutaneous transplantation of the HEY ovarian cancer cell line resulted in a significant increase in the expression of CA125, Oct4, and CD117 in mice xenografts compared to control mice xenografts which did not receive paclitaxel. In the second approach, mice were administered once weekly with paclitaxel and/or a daily dose of the JAK2-specific inhibitor, CYT387, over 4weeks. Mice receiving paclitaxel only demonstrated a significant decrease in tumor volume compared to control mice. At the molecular level, mouse tumors remaining after paclitaxel administration showed a significant increase in the expression of Oct4 and CD117 coinciding with a significant activation of the JAK2/STAT3 pathway compared to control tumors. The addition of CYT387 with paclitaxel resulted in the suppression of JAK2/STAT3 activation and abrogation of Oct4 and CD117 expression in mouse xenografts. This coincided with significantly smaller tumors in mice administered CYT387 in addition to paclitaxel, compared to the control group and the group of mice receiving paclitaxel only. These data suggest that the systemic administration of paclitaxel enhances Oct4- and CD117-associated CSC-like marker expression in surviving cancer cells in vivo, which can be suppressed by the addition of the JAK2-specific inhibitor CYT387, leading to a significantly smaller tumor burden. These novel findings have the potential for the development of CSC-targeted therapy to improve the treatment outcomes of ovarian cancer patients.

Duty to the court and the administration of justice : some examples, implications and clarifications

No liberal democracy can survive without popular trust in its judicial system. The legal profession and the judiciary enjoy a level of independence and autonomy from the executive that makes them both powerful and privileged. A UNIQUE AND ORGANIC DUTY: So long as the courts are seen to fulfil their duty to guard against encroachments by the executive on the freedoms and rights of individual citizens with integrity and credibility, they maintain enough public support to retain their normative authority. But support for those with power and privilege is easily undermined. It is contingent upon trust. Lawyers who breach that trust in ways that go to the heart of the legal system ought to expect to be made examples of and to suffer severe penalties. The good news is that the sorts of breach discussed here should be neither difficult to anticipate nor to avoid – in theory. In practice, smart and honest lawyers sometimes fall foul of these duties for all sorts of understandable (if not condonable) reasons. Law does not get practised in a social or cultural vacuum. Lawyers are people, and people have weaknesses, failings and stresses...

Health and guardianship law : guardianship and administration application in the matter of MDC [2014] QCAT 338

The recent decision of the Queensland Civil and Administrative Tribunal (QCAT) in Guardianship and administration application in the matter of MDC [2014] QCAT 338, provides an important ruling on the limits of who can be appointed as an enduring power of attorney under the Powers of Attorney Act 1998 (Qld). In particular, the tribunal adopted a broad interpretation of the term "health provider" when considering the limits on who can be appointed as an enduring power of attorney under the legislation...

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumour-burdened lymph nodes after intravenous and subcutaneous administration in rats

The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

DNA molecules and human therapeutics

Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This review addresses the potential applications of pDNA molecules in vaccine design/development and gene therapy via recombinant DNA technology as well as a staged delivery mechanism for the introduction of plasmid-borne gene to target cells via the nasal route.

Creation of protein loaded biodegradable microparticles via ultrasonic atomization suitable for nasal delivery

Improved biopharmaceutical delivery may be achieved via the use of biodegradable microspheres as delivery vehicles. Biodegradable microspheres offer the advantages of maintaining sustained protein release over time whilst simultaneously protecting the biopharmaceutical from degradation. Particle samples produced by ultrasonic atomization were studied in order to determine a feed stock capable of producing protein loaded poly-ε-caprolactone (PCL) particles suitable for nasal delivery (i.e., less than 20 μm). A 40 kHz atomization system was used with a 6 mm full wave atomization probe. The effect of solids percent, feed flow rate, volumetric ratio of the polymer stock to the protein stock, and protein concentration in the protein stock on particle size characteristics were determined. It was shown that feed stocks containing 100 parts of 0.5 or 1.0% w/v PCL in acetone with one part 100 mg ml -1 BSA and 15 mg ml -1 PVA produced particles with a mass moment diameter (D[4,3]) of 13.17 μm and 9.10 μm, respectively in addition to displaying high protein encapsulation efficiencies of 93 and 95%, respectively. The biodegradable PCL particles were shown to be able to deliver encapsulated protein in vitro under physiological conditions.

Drug administration guides in dysphagia

Aim: The aim of this evaluation was to evaluate the use of Individualised Medication Administration Guides (IMAGs) for patients with dysphagia on one stroke ward over a 6month period. Background: Patients with dysphagia (PWD) are more likely to suffer an administration error than patients without swallowing difficulties. To both standardise and improve medicines administration to patients with dysphagia I-MAGs were introduced on one stroke ward over a 6 month period. Methods: A software package supported with data on current national guidelines on the administration of medicines to PWD was designed by a specialised pharmacist in dysphagia to enable him to create individualised medication administration guides for patients with dysphagia which stated how each medicine should be optimally prepared and administered. On completion of the pilot service a questionnaire was given to all nurses, pharmacist and speech and language therapists who had experienced the I-MAGs. All the professionals received the same questionnaire but questions relevant only to their practice were added to the nurse’s questionnaire. Results: Of 26 Healthcare professionals (HCPs) approached, 19 returned completed questionnaires. Higher variability was found in the 13 responses from the nurse respondents than in the ones from the 3 pharmacist and the 3 SALTs. 8 (61%) of the nurses felt more confident in their practice when I-MAGs were in place. 10 (76%) of the nurses admitted that the guides could sometimes increase the time of the administration, but saw that it made practice safer. All the pharmacists considered the recommendations in the guides useful and all the respondents with the exception of one nurse (12:13) would like this service to continue. Conclusion: I-MAGs were well received on the ward and they support individualised care for patients with dysphagia. But the guides needed additional pharmacist input and greater nursing time. Research to determine the cost effectiveness of I-MAGs is needed.

Implementation of individualised medication administration guides for patients with dysphagia: Results from a pilot controlled trial

Introduction Patients with dysphagia (PWDs) have been shown to be four times more likely to suffer medication administration errors (MAEs).1 2 Individualised medication administration guides (I-MAGs) which outline how each formulation should be administered, have been developed to standardise medication administration by nurses on the ward and reduce the likelihood of errors. This pilot study aimed to determine the recruitment rates, estimate effect on errors and develop the intervention to design a future full scale randomised controlled trial to determine the costs and effects of I-MAG implementation. Ethical approval was granted by local ethics committee. Method Software was developed to enable I-MAG production (based on current best practice)3 4 for all PWDs on two care of the older person wards admitted during a six month period from January to July 2011. I-MAGs were attached to the medication administration record charts to be utilised by nurses when administering medicines. Staff training was provided for all staff on the intervention wards. Two care of the older person wards in the same hospital were used for control purposes. All patients with dysphagia were recruited for follow up purposes at discharge. Four ward rounds at each intervention and control ward were observed pre and post I-MAG implementation to determine the level of medication administration errors. NHS ethical approval for the study was obtained. Results 164 I-MAGs were provided for 75 patients with dysphagia (PWDs) in the two intervention wards. At discharge, 23 patients in the intervention wards and 7 patients in the control wards were approached for recruitment of which 17 (74%) & 5 (71.5%) respectively consented. Discussion Recruitment rates were low on discharge due to the dysphagia remitting during hospitalisation. The introduction of the I-MAG demonstrated no effect on the quality of administration on the intervention ward and interestingly practice improved on the control ward. The observation of medication rounds at least one month post I-MAG removal may have identified a reversal to normal practice and ideally observations should have been undertaken with I-MAGs in place. Identification of the reason for the improvement in the control ward is warranted.