The Separate or Concurrent Effects of Methylphenidate and Alcohol on Acquisition and Retention of the Morris Water Maze in Adolescent Rats

Alcohol’s (A) capacity to impair learning and memory has been well documented in the Morris Water Maze (MWM) but few studies have examined methylphenidate’s (MPH) impact on MWM performance (Haidun et al., 2010; Zeise et al., 2007). Even fewer studies have evaluated concurrent administration of these two drugs in adolescent rats (see Markwiese, et al., 1998). This project used a rat model of adolescent drug use to examine individual effects of MPH and A, as well as polypharmacy interactions between MPH and A, on MWM spatial acquisition and retention. Thirty-two adolescent (P30) male Long-Evans hooded rats were used. Subjects were assigned to one of 4 conditions based on drug administered prior to 6 consecutive acquisition sessions. Animals received 2 i.p. injections prior to each session. The methylphenidate group (MPH+S) received 2 mg/kg MPH and 1 ml/kg saline solution (S), the alcohol group (A+S) received 2 g/kg ethanol and S, the methylphenidate and alcohol group (MPH+A) received both MPH and A, and the saline control group (S+S) received S injections. MPH was administered 50 mins prior to each session and A administered 20 mins prior to each session. Each session consisted of 4 trials and rats swam from one of four start locations (N,E,S,W) to a submerged platform in the NE quadrant. Trial duration was 60 seconds and rats remained on the platform for 10 secs. Performances were video recorded, and latency and swim accuracy scored. Whishaw Corridors established a direct swim path from start location to platform and an error was recorded when swim paths exited the corridor. On day 7, the submerged platform was removed and a single, 60 sec retention test was conducted with no drug administered prior to test. Amount of time spent swimming in the NE quadrant was analyzed to assess retention. Acquisition: Both dependent measures, latency and swim accuracy, yielded similar outcomes. Factorial ANOVAs and post hoc tests showed improvement across training sessions for all groups. Importantly, the MPH+A group was impaired relative to all other conditions, and the S+S group performed better than the A group. No significant differences were observed between S+S and MPH+S groups. Retention: A one-way ANOVA of swim time in the NE quadrant revealed longer swim times for the S+S group compared to the A+S group, and longer swim times for the MPH+S group compared to the A+S group. No other significant differences were observed. While all groups improved performance during acquisition, methylphenidate + alcohol compromised spatial learning, and alcohol alone impaired learning relative to controls. Interestingly, measures of retention indicated only alcohol diminished spatial memory in adolescent rats

The Role of the 1994-95 Coffee Boom in Uganda's Recovery

This paper reports a CGE analysis that explores the consequences of the 1994-95 rise in the international price of coffee for Uganda´s economy. Evidence is found for a small effect on medium-term growth and poverty reduction. Aid dependence is among the reasons why this effect is not found to be larger. Major beneficiary groups are not only the farmers to which the windfall initially accrued but also urban wage earners and the urban self-employed.Computable General Equilibrium, Coffee; Uganda; Dutch Disease

Work-family Capitalization: How Sharing Positive Work Events May Lead to Greater Perceptions of Work-family Enrichment and Associated Outcomes

This poster describes a research project that explored how discussing one\u27s positive work events with responsive family members may contribute to greater perceptions of work-family enrichment in employees, and in turn, how greater perceptions of work-family enrichment may predict more positive work outcomes including higher job satisfaction, fewer turnover intentions, less worker burnout, and higher supervisor ratings of job performance. Results are based on survey data from 131 direct-support workers employed at a local non-profit organization providing community-based residential services to the intellectually disabled. The results, along with the practical and theoretical implications of the research will be discussed

Gestational diabetes mellitus- right person, right treatment, right time?

Background: Personalised treatment that is uniquely tailored to an individual’s phenotype has become a key goal of clinical and pharmaceutical development across many, particularly chronic, diseases. For type 2 diabetes, the importance of the underlying clinical heterogeneity of the condition is emphasised and a range of treatments are now available, with personalised approaches being developed. While a close connection between risk factors for type 2 diabetes and gestational diabetes has long been acknowledged, stratification of screening, treatment and obstetric intervention remains in its infancy. Conclusions: Although there have been major advances in our understanding of glucose tolerance in pregnancy and of the benefits of treatment of gestational diabetes, we argue that far more vigorous approaches are needed to enable development of companion diagnostics, and to ensure the efficacious and safe use of novel therapeutic agents and strategies to improve outcomes in this common condition

Characterisation of experimentally induced and spontaneously occurring disease within captive bred dasyurids

Neosporosis is a disease of worldwide distribution resulting from infection by the obligate intracellular apicomplexan protozoan parasite Neospora caninum, which is a major cause of infectious bovine abortion and a significant economic burden to the cattle industry. Definitive hosts are canid and an extensive range of identified susceptible intermediate hosts now includes native Australian species. Pilot experiments demonstrated the high disease susceptibility and the unexpected observation of rapid and prolific cyst formation in the fat-tailed dunnart (Sminthopsis crassicaudata) following inoculation with N. caninum. These findings contrast those in the immunocompetent rodent models and have enormous implications for the role of the dunnart as an animal model to study the molecular host-parasite interactions contributing to cyst formation. An immunohistochemical investigation of the dunnart host cellular response to inoculation with N. caninum was undertaken to determine if a detectable alteration contributes to cyst formation, compared with the eutherian models. Selective cell labelling was observed using novel antibodies developed against Tasmanian devil proteins (CD4, CD8, IgG and IgM) as well as appropriate labelling with additional antibodies targeting T cells (CD3), B cells (CD79b, PAX5), granulocytes, and the monocyte-macrophage family (MAC387). Toluidine blue labelling of mast cells complemented results. Effective labelling was not obtained with CD79a, interleukin-4, interferon-γ, or MHCII antibodies. Descriptions of pathology such as the site and extent of tissue necrosis in S. crassicaudata resemble those reported in immunocompromised rodent models. The exception is the lack of major involvement of the brain and associated neurological signs. Immunohistopathologic findings suggest the dunnart host cell response resembles that described in eutherians – strongly neutrophilic with fewer macrophages focused on sites of tissue necrosis, with a predominantly T cell nature to any lymphoid response inclusive of CD4 positive T helper cells. Intracellular parasite replication is frequently observed in the absence of a detectable host cellular response. More sensitive alternative techniques such as real time polymerase chain reaction using effective cytokine labelling is recommended to further define the host response to neosporosis. Active surveillance of disease to further define the animal model involved collecting cadavers over 28 months from the dunnart colony maintained at the University of Sydney. An additional 66 S. crassicaudata and S. macroura animals were examined. Of the 28.3% of animals diagnosed with a disorder of growth (n=15), 80.0% were diagnosed with a malignancy (n=12), and the most frequently diagnosed neoplasm was squamous cell carcinoma. Lesions were seen on the rostral mandible (2), pouch (2), distal limb (1), and tail (1) and five of six of these tumours were diagnosed in S. macroura. The single squamous cell carcinoma diagnosed in the pouch of an S. crassicaudata showed a distinctive verrucous growth pattern, prompting consideration of a viral causation. Immunohistochemical investigation of carcinomatous proliferations using multiple bovine papillomavirus markers and an antibody targeting the p16 cell protein found no supportive evidence for a viral association. Additional colony pathology included single or multicentric nodular pyogranulomatous or suppurative disease (botryomycosis) – sometimes a comorbidity of carcinoma. In S. crassicaudata eight cases of gastric dilatation were also identified – with and without trichobezoar formation. Collection and examination of specimens from the colony is ongoing

ENGAGEMENT AND PHILOSOPHY

This article explores these two keywords through the approach of placing “school” on a continuum between the two extremes of a transactional, instrumental organisation and a transformational community. The variety of stakeholder groups are redefined to include personification of abstract concepts and the model of community is considered including these stakeholders. School is looked at here as a verb rather than a noun and the extent to which school must by definition be, or have the form of, an organisation, is seen as a manifestation of the will of the community, with the levers of transaction pulled by the Head on behalf of the community. The 1994 UNESCO international conference on education provides a framework for discussion about culture and the purpose of education, which is reconciled with the evolving model described and envisioned in this short paper

The Western Stemmed Point Tradition: Evolutionary Perspectives on Cultural Change in Projectile Points During the Pleistocene-Holocene Transition

In this thesis I analyze the cultural techniques of Paleoindians in North America by examining the diversification and fusion of stemmed projectile point traditions using an evolutionary analysis. The Western Stemmed Point tradition has an extensive regional and temporal distribution throughout the Intermountain West and High Plains during the Paleoindian period. In an effort to determine how stemmed projectile point technologies relate to each other, I applied a phylogenetic approach to construct heritable patterns of projectile point histories. By measuring the physical traits of those points and using a macro-evolutionary theoretical approach, changes in artifact form can be acquired and heritable processes understood. This process was further complicated by our understanding of how culture is learned and shared. Techniques can be learned as individual units or even as sets of units, resulting in the differential persistence of individual traits. This analysis indicated that projectile point traits for blade and haft characteristics evolved in a mosaic fashion creating distinct patterns of vertical and horizontal transmission across space and time. Furthermore, the haft characteristics created important results that support the eastward expansion of stemmed projectile point traditions from the west

Reversal of cardiac dysfunction by selective ET-A receptor antagonism

1. The effectiveness of a selective endothelin receptor-A (ET-A) antagonist, A-127722 (approximately 10 mg kg-1 day-1 as 200 mg kg-1 powdered food), to reverse existing cardiac remodelling and prevent further remodelling was tested in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. 2. Uninephrectomised rats (UNX) administered DOCA (25mg every 4th day sc) and 1% NaCl in drinking water for 28 days developed hypertension (systolic BP: UNX 128 6, DOCA-salt 182 5* mmHg; *P<0.05 vs UNX), left ventricular hypertrophy (UNX 1.99 0.06, DOCA-salt 3.30 0.08* mg/kg body wt), decreased left ventricular internal diameter (UNX 6.69 0.18, DOCA-salt 5.51 0.37* mm), an increased left ventricular monocyte/macrophage infiltration together with an increased interstitial collagen from 2.7 0.3 to 11.7 1.3%, increased passive diastolic stiffness (UNX 21.1 0.5, DOCA-salt 30.1 1.3*), prolongation of the action potential duration at 20% and 90% of repolarization (APD20 - UNX 6.8 1.1, DOCA-salt 10.1 1.5* msec; APD90 - UNX 34.4 3.5, DOCA-salt 64.3 10.4* msec) and vascular dysfunction (2.6 fold decrease in maximal contractile response to noradrenaline, 3.5 fold decrease in maximal relaxation response to acetylcholine). 3. Administration of A-127722 for 14 days starting 14 days after surgery attenuated the increases in systolic blood pressure (150 6** mmHg, **P<0.05 vs DOCA-salt), left ventricular wet weight (2.65 0.06** mg/kg body wt) and internal diameter (6.39 0.31** mm), prevented left ventricular monocyte/macrophage accumulation, attenuated the increased left ventricular interstitial collagen (7.6 1.3%**), reversed the increased passive diastolic stiffness (22.1 1.2**), attenuated the action potential duration prolongation (APD20 - 7.6 1.4**, APD90 - 41.5 6.9** msec) and normalized changes in vascular function. 4. ET-A receptor antagonism both reverses and prevents the cardiac and vascular remodelling in DOCA-salt hypertension and improves cardiovascular function

Mechanisms of memory retrieval in slow-wave sleep : memory retrieval in slow-wave sleep

Study Objectives: Memories are strengthened during sleep. The benefits of sleep for memory can be enhanced by re-exposing the sleeping brain to auditory cues; a technique known as targeted memory reactivation (TMR). Prior studies have not assessed the nature of the retrieval mechanisms underpinning TMR: the matching process between auditory stimuli encountered during sleep and previously encoded memories. We carried out two experiments to address this issue. Methods: In Experiment 1, participants associated words with verbal and non-verbal auditory stimuli before an overnight interval in which subsets of these stimuli were replayed in slow-wave sleep. We repeated this paradigm in Experiment 2 with the single difference that the gender of the verbal auditory stimuli was switched between learning and sleep. Results: In Experiment 1, forgetting of cued (vs. non-cued) associations was reduced by TMR with verbal and non-verbal cues to similar extents. In Experiment 2, TMR with identical non-verbal cues reduced forgetting of cued (vs. non-cued) associations, replicating Experiment 1. However, TMR with non-identical verbal cues reduced forgetting of both cued and non-cued associations. Conclusions: These experiments suggest that the memory effects of TMR are influenced by the acoustic overlap between stimuli delivered at training and sleep. Our findings hint at the existence of two processing routes for memory retrieval during sleep. Whereas TMR with acoustically identical cues may reactivate individual associations via simple episodic matching, TMR with non-identical verbal cues may utilise linguistic decoding mechanisms, resulting in widespread reactivation across a broad category of memories

Sleep preserves original and distorted memory traces

Retrieval facilitates the long-term retention of memories, but may also enable stored representations to be updated with new information that is available at the time of retrieval. However, if information integrated during retrieval is erroneous, future recall can be impaired: a phenomenon known as retrieval-induced distortion (RID). Whether RID causes an “overwriting” of existing memory traces or leads to the co-existence of original and distorted memory traces is unknown. Because sleep enhances memory consolidation, the effects of sleep after RID can provide novel insights into the structure of updated memories. As such, we investigated the effects of sleep on memory consolidation following RID. Participants encoded word locations and were then tested before (T1) and after (T2) an interval of sleep or wakefulness. At T2, the majority of words were placed closer to the locations retrieved at T1 than to the studied locations, consistent with RID. After sleep compared with after wake, the T2-retrieved locations were closer to both the studied locations and the T1-retrieved locations. These findings suggest that RID leads to the formation of an additional memory trace that corresponds to a distorted variant of the same encoding event, which is strengthened alongside the original trace during sleep. More broadly, these data provide evidence for the importance of sleep in the preservation and adaptive updating of memories