Controlled release of bioactive chemicals

This project has been concerned with the development of controlled release formulations of the herbicide atrazine and the pesticide chlorpyrifos. The results of both chemical and biological evaluation show that these controlled release formulations can significantly reduce leaching and therefore ground water pollution of atrazine without losing herbicidal potency in the early stages after application.

Promoting "critical awareness" and critiquing "cultural competence" : towards disrupting received professional knowledges

There is a compelling argument that universities should be committed to advancing the Indigenous agenda. With respect to social work, as well as to nursing, psychology, and allied health, this commitment is often translated into a single goal: that graduates should be ‘‘culturally competent’’. While acknowledging that there can be tactical advantages in pursuing this goal the current paper develops a practical critique of the expectation that cultural competence is an unproblematic ‘‘add on’’ to professional education. Using a single case study as an example*how the subject ‘‘individual development’’ is transmitted as a monocultural and unproblematic formation*we argue that it is impossible to learn to work cross-culturally without developing a capacity for reflective self-scrutiny. Less likely to be a flag of convenience than ‘‘cultural competence’’, an allegiance to ‘‘critical awareness’’ prompts the interrogation of received knowledge, for example how human development and personhood is understood, as well stimulating an engagement in the lifelong process of reflecting on one’s own ideological and cultural location.

Disrupting disordered neurocircuitry : treating refractory psychiatric illness with neuromodulation

Despite the premature and somewhat infamous rise and fall of psychosurgery in the mid-20th century, the current era of functional neuromodulation proffers immense opportunity for surgical intervention in treatment-resistant psychiatric disorders. On the basis of recent successes with novel, focused, less invasive, and reversible treatment strategies for movement disorders, several therapeutic trials have been conducted to investigate the effectiveness of deep brain stimulation (DBS) in treatment-resistant depression, obsessive-compulsive disorder (OCD), and Tourette syndrome. The many anatomic targets for these psychiatric disorders are indicative of both the system-wide effects of DBS and the network-level dysfunction mediating the emotional and cognitive disturbances. To gain insight into the application of neuromodulation therapies and their further advancement, we must elucidate neuroanatomic networks involved in refractory psychiatric illness, the neurophysiological anomalies that contribute to disordered information processing therein, and the local and system-wide modulatory effects of DBS. This review discusses the history of psychosurgical procedures, recent DBS clinical data, current anatomic models of psychopathology, and possible therapeutic mechanisms of action of DBS neuromodulation. Our search criteria for PubMed included combinations of the following terms: neuromodulation, DBS, depression, OCD, Tourette syndrome, mechanism of action, and history. Dates were not restricted. As clinical and basic scientific investigations probe the neuromodulatory effects of DBS in the treatment of refractory neuropsychiatric illness, our knowledge of these disorders and our potential to treat them are rapidly expanding. Indeed, this modern era of neuromodulation may provide the key that unlocks many of the mysteries pertaining to the biological basis of disordered emotional neurocircuitry.

The politics of gendered emotions : disrupting men's emotional investment in privilege

This paper explores the implications of the neglect of emotions in critical masculinity studies and profeminist masculinity politics. This neglect in part results from feminist and profeminist critiques of the literature on emotional inexpressiveness as a tragedy for men that ignores male privilege and men's social power. To focus on men's emotions is seen by some profeminist commentators as psychologising men at the expense of sociological understandings of men's social power. However, in neglecting the place of emotions in men's lives, critical masculinity studies has overlooked the ways in which men's emotional attachment to privilege can perpetuate oppressive gender relations and male violence against women. By exploring men's emotional investment in unequal gender relations, the article outlines ways in which emotions can also be used as a catalyst to disrupt men's attachment to male privilege.

Progression of cardiovascular and endocrine dysfunction in a rabbit model of obesity

In rabbits, mean arterial pressure (MAP) increases in response to fat feeding, but does not increase further with progressive weight gain. We documented the progression of adiposity and the alterations in endocrine/cardiovascular function in response to fat feeding in rabbits, to determine whether stabilization of MAP after 3 weeks could be explained by stabilization of neurohormonal factors. Rabbits were fed a control diet or high-fat diet for 9 weeks (n¼23). Fat feeding progressively increased body mass and adiposity. Heart rate (HR) was elevated by week 3 (15±3%) but changed little thereafter. The effects of fat feeding on MAP were dependent on baseline MAP and peaked at 3 weeks. From baseline, MAP p80mmHg, MAP had increased by 8.1±1.3, 4.7±1.7 and 5.6±1.2mmHg, respectively, 3, 6 and 9 weeks after commencing the high-fat diet, but by only 2.6±1.5, 3.0±1.7 and 3.9±1.4mmHg, respectively, in control rabbits. Fat feeding did not increase MAP from a baseline 480mmHg. Plasma concentrations of leptin and insulin increased during the first 3–6 weeks of fat feeding and then stabilized (increasing by 111±17% and 731±302% by week 9, respectively), coinciding with the pattern of changes in MAP and HR. Plasma total cholesterol, triglycerides, renin activity, aldosterone and atrial natriuretic peptide were not significantly altered by fat feeding. Given that the changes in plasma leptin and insulin mirrored the changes in MAP and HR, leptin and insulin may be important factors in the development of hypertensionand tachycardia in the rabbit model of obesity.

Cleanup worker exposures to hazardous chemicals at a former nuclear weapons plant : piloting of an exposure surveillance system

Cleanup of former U.S. Department of Energy (DOE) nuclear weapons production facilities involves potential exposures to various hazardous chemicals. We have collaboratively developed and piloted an exposure database and surveillance system for cleanup worker hazardous chemical exposure data with a cleanup contractor at the Rocky Flats Environmental Technology Site (RFETS). A unique system feature is the incorporation of a 34-category work task-coding scheme. This report presents an overview of the data captured by this system during development and piloting from March 1995 through August 1998. All air samples collected were entered into the system. Of the 859 breathing zone samples collected, 103 unique employees and 39 unique compounds were represented. Breathing zone exposure levels were usually low (86% of breathing zone samples were below analytical limits of detection). The use of respirators and other exposure controls was high (87 and 88%, respectively). Occasional high-level excursions did occur. Detailed quantitative summaries are provided for the six most monitored compounds: asbestos, beryllium, carbon tetrachloride, chromium, lead, and methylene chloride. Task and job title data were successfully collected for most samples, and showed specific cleanup activities by pipe fitters to be the most commonly represented in the database. Importantly, these results demonstrate the feasibility of the implementation of integrated exposure database and surveillance systems by practicing industrial hygienists employed in industry as well as the preventive potential and research uses of such systems. This exposure database and surveillance system--the central features of which are applicable in any industrial work setting--has enabled one of the first systematic quantitative characterizations of DOE cleanup worker exposures to hazardous chemicals.

Disrupting the encoding of misinformation delivered in closed specific and open presumptive questions

To determine whether the encoding of misleading information presented in two different types of leading questions (closed specific and open presumptive questions) could be disrupted, participants took part in a misinformation experiment. They viewed an event before answering questions that had a closed specific structure (e.g. “Did the robber have a shotgun that had a black barrel and a brown stock?”) or an open presumptive structure (e.g. “Tell me about the shotgun”). Half the questions contained misleading information and half did not. For some of the questions, participants completed a concurrent distractor task. Finally, they completed a recognition memory test about the original event. Results showed that the concurrent distractor task during the interview reduced the size of the misinformation effect for the closed specific questions, but had no impact on the misinformation effect for the open presumptive questions. The results suggest that open presumptive questions encourage participants to encode and process the misleading information more deeply than the closed specific questions. The misinformation effect was more difficult to disrupt with a concurrent task during the encoding of the misleading information for open presumptive questions than for closed specific questions. The implications for interviewing are discussed.

Monotreme lactation : characterisation of a novel protein, endocrine regulation and miRNAs in milk

My dissertation is about the fascinating Australian mammals, platypus and echidna milk components function and milk production. I have investigated the platypus and echidna milk proteins and miRNAs that involved in protection or development of the immature monotreme hatchlings, and investigated the hormonal control of monotreme milk production.

Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents

Background Cabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians. Objective To describe the antitumour activity of cabazitaxel after docetaxel and next-generation endocrine agents. Design, setting, and participants We report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide. Outcome measurements and statistical analysis Changes in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy. Results and limitations The post-endocrine-therapy patients received abiraterone (n = 32), sequential abiraterone and enzalutamide (n = 5) or enzalutamide (n = 4). These patients received a median of 7 mo of abiraterone and 11 mo of enzalutamide. A median of six cabazitaxel cycles (range: 1-10 cycles) were delivered, with ≥50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abiraterone- and enzalutamide-naïve cohort (n = 18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis. Conclusions This is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting. Patient summary We looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments. © 2013 European Association of Urology.

Lipid abundance in zebrafish embryos is regulated by complementary actions of the endocannabinoid system and retinoic acid pathway

The endocannabinoid system (ECS) and retinoic acid (RA) signaling have been associated with influencing lipid metabolism. We hypothesized that modulation of these pathways could modify lipid abundance in developing vertebrates and that these pathways could have a combinatorial effect on lipid levels. Zebrafish embryos were exposed to chemical treatments altering the activity of the ECS and RA pathway. Embryos were stained with the neutral lipid dye Oil-Red-O (ORO) and underwent whole-mount in situ hybridization. Mouse 3T3-L1 fibroblasts were differentiated under exposure to RA modulating chemicals and subsequently stained with ORO and analyzed for gene expression by qRT-PCR. ECS activation and RA exposure increased lipid abundance and the expression of lipoprotein lipase. Additionally, RA treatment increased expression of CCAAT/enhancer binding protein alpha. Both ECS receptors and RA receptor subtypes were separately involved in modulating lipid abundance. Finally, increased ECS or RA activity ameliorated the reduced lipid abundance caused by peroxisome proliferator-activated receptor gamma (PPARγ) inhibition. Therefore, the ECS and RA pathway influence lipid abundance in zebrafish embryos and have an additive effect when treated simultaneously. Furthermore, we demonstrated that these pathways act downstream or independently of PPARγ to influence lipid levels. Our study shows for the first time that the RA and ECS pathways have additive function in lipid abundance during vertebrate development.

The effects of bed-rest and countermeasure exercise on the endocrine system in male adults: evidence for immobilization-induced reduction in sex hormone-binding globulin levels

BACKGROUND AND AIM: There is limited data on the effects of inactivity (prolonged bed-rest) on parameters of endocrine and metabolic function; we therefore aimed to examine changes in these systems during and after prolonged (56- day) bed-rest in male adults. SUBJECTS AND METHODS: Twenty healthy male subjects underwent 8 weeks of strict bed-rest and 12 months of follow-up as part of the Berlin Bed Rest Study. Subjects were randomized to an inactive group or a group that performed resistive vibration exercise (RVE) during bed-rest. All outcome parameters were measured before, during and after bed-rest. These included body composition (by whole body dual X-ray absorptiometry), SHBG, testosterone (T), estradiol (E2), PRL, cortisol (C), TSH and free T3 (FT3). RESULTS: Serum SHBG levels decreased in inactive subjects but remained unchanged in the RVE group (p<0.001). Serum T concentrations increased during the first 3 weeks of bed-rest in both groups (p<0.0001), while E2 levels sharply rose with re-mobilization (p<0.0001). Serum PRL decreased in the control group but increased in the RVE group (p=0.021). C levels did not change over time (p≥0.10). TSH increased whilst FT3 decreased during bed-rest (p all ≤0.0013). CONCLUSIONS: Prolonged bed-rest has significant effects on parameters of endocrine and metabolic function, some of which are related to, or counteracted by physical activity.