Defence diplomacy: is the game worth the candle?

Few defence topics have been as prominent or invested with as much optimism in recent years as defence diplomacy. This paper has been created to explore the issue and help guide policymakers. Foreword Few Defence topics have been as prominent or invested with as much optimism in recent years as defence diplomacy (also called military diplomacy or defence engagement). In response to the growing security challenges of Asia, scholars, policymakers and practitioners have looked for ways to build confidence, decrease the risk and impact of accidents and encourage peaceful dispute resolution. Defence diplomacy, namely the practice of military and defence officials engaging their overseas counterparts, is increasingly regarded as a vital way to achieve these aims. Given the importance of this topic, a special Centre of Gravity paper has been created to explore the issue and help guide policymakers. This edition features six short papers, each with a different take and policy recommendation. The authors were asked the same question ‘Is the game worth the candle?’ and while their answers focus largely on Australia there are lessons and implications from their findings for the entire region. Brendan Taylor, the head of the Strategic & Defence Studies Centre begins the special edition calling for a stocktake of current efforts, in a bid to understand what has worked and what resources it requires. He is joined by two colleagues, John Blaxland who argues strongly in favour of an expanded defence diplomacy program and Hugh White who urges caution about the strategic influence of the practice. To complement these views, Nick Bisley, Executive Director La Trobe Asia, highlights the need for realistic ambitions. Lieutenant General (Ret.) Peter Leahy draws on his distinguished career in the ADF to detail how defence diplomacy occurs in practice and why it matters. Finally, See Seng Tan, Deputy Director of the Institute of Defence and Strategic Studies in Singapore provides a regional perspective on Australia’s defence diplomacy. The authors of these papers don’t agree with each other, and that was precisely why they were invited to contribute. But some common themes are clear. Such as the need for a clear —and public — strategy along with integrating defence diplomacy into the efforts of other parts of government. Together these six papers provide insight into the practice and potential of defence diplomacy. This special edition also marks a re-launch of the Centre of Gravity Series. While some of the design may change, the focus remains the same: inviting some of the best analysts from Australia and around the world to provide short, accessible papers on the key questions facing Australian strategic affairs

Language of Lullabies: The Russification and De-Russification of the Baltic States

This article argues that the laws for promotion of the national languages are a legitimate means for the Baltic states to establish their cultural independence from Russia and the former Soviet Union

Defence Diplomacy: Is the Game Worth the Candle?

Few Defence topics have been as prominent or invested with as much optimism in recent years as defence diplomacy. This special Centre of Gravity paper has been created to explore the issue and help guide policymakers. It features contributions from 6 authors including Brendan Taylor, John Blaxland, Hugh White, Nick Bisley, Peter Leahy and See Seng Tan

The 5-Choice Continuous Performance Test: Evidence for a Translational Test of Vigilance for Mice

Attentional dysfunction is related to functional disability in patients with neuropsychiatric disorders such as schizophrenia, bipolar disorder, and Alzheimer's disease. Indeed, sustained attention/vigilance is among the leading targets for new medications designed to improve cognition in schizophrenia. Although vigilance is assessed frequently using the continuous performance test (CPT) in humans, few tests specifically assess vigilance in rodents.We describe the 5-choice CPT (5C-CPT), an elaboration of the 5-choice serial reaction (5CSR) task that includes non-signal trials, thus mimicking task parameters of human CPTs that use signal and non-signal events to assess vigilance. The performances of C57BL/6J and DBA/2J mice were assessed in the 5C-CPT to determine whether this task could differentiate between strains. C57BL/6J mice were also trained in the 5CSR task and a simple reaction-time (RT) task involving only one choice (1CRT task). We hypothesized that: 1) C57BL/6J performance would be superior to DBA/2J mice in the 5C-CPT as measured by the sensitivity index measure from signal detection theory; 2) a vigilance decrement would be observed in both strains; and 3) RTs would increase across tasks with increased attentional load (1CRT task<5CSR task<5C-CPT).C57BL/6J mice exhibited superior SI levels compared to DBA/2J mice, but with no difference in accuracy. A vigilance decrement was observed in both strains, which was more pronounced in DBA/2J mice and unaffected by response bias. Finally, we observed increased RTs with increased attentional load, such that 1CRT task<5CSR task<5C-CPT, consistent with human performance in simple RT, choice RT, and CPT tasks. Thus we have demonstrated construct validity for the 5C-CPT as a measure of vigilance that is analogous to human CPT studies

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

The mechanism of human monocyte activation by staphylococcal toxic shock syndrome toxin-1 (TSST-1)

Toxic shock syndrome (TSS) is a multisystem disease associated with staphylococcal TSS toxin—1 (TSST-1). TSST—i and the related staphylococcal enterotoxins (SE) A, B, C, D, and E have a number of biological effects on human peripheral blood mononuclear cells (PBMC), including T lymphocyte mitogenicity and induction of IL—1 and TNF from human monocytes. The aim of this thesis is to examine the molecular mechanisms of human monocyte activation by TSST—1 and SE. To gain insight into the mechanism of TSST—i and SEA activation of PBMC, receptor binding assays were performed with ¹²⁵I—labeled toxins. Scatchard analyses revealed similar numbers of receptors and dissociation constants for TSST—l and SEA on human PBMC and on purified monocytes. SEA, but not SEB, SEC, SED or SEE significantly inhibited binding of ¹²⁵I—TSST—1 to PBMC. Crosscompetition between TSST-i and SEA in binding assays suggested that they may be binding to overlapping epitopes on the same receptor. Affinity cross-linking of ¹²⁵I—labeled TSST—1 and SEA to human blood monocytes showed the presence of 2 membrane subunits consistent with the 35 kd alpha and 28 kd beta chains of human HLA—DR. The anti—HLA-DR mb, L243, inhibited radiolabeled TSST—1 and SEA binding to human monocytes and neutralized monocyte—dependent T cell mitogenicity of both toxins, adding further support that HLA—DR is the major receptor. Based on these studies and those of others who demonstrated overlapping receptor epitopes for SEA and SEB (Fraser, Nature 339:221—223, 1989) and distinct epitopes for TSST—1 and SEB (Scholl et al., J. Immunol 143:2583—2588, 1989), we postulate that SEA occupies a binding site within HLA-DR that partially overlaps with both TSST-l and SEB. The role of protein phosphorylation in the activation of normal human monocytes by TSST-l and SE was examined by two—dimensional gel electrophoresis. Examination of ³²P—orthophosphate—labeled monocytes showed that within 5 mm, TSST—1 consistently stimulated the dephosphorylation of several phosphoprotemns in a dose—dependent manner. In contrast, neither SEA nor SEB induced this dephosphorylation pattern, but instead, increased the phosphorylation of a different set of proteins. Phosphorylation patterns induced by two other monocyte agonists, PMA and bacterial LPS, demonstrated little similarity to those induced by TSST—l. Moreover, using an anti-phosphotyrosine mAb, TSST-1 and SE were shown to stimulate the tyrosine—specific phosphorylation of several cytosolic proteins that were distinct from those induced by PMA. This suggests that tyrosine phosphorylation induced by TSST—l or SEA is not mediated by activation of protein kinase C. Collectively, the data suggest that the early intracellular signal transduction pathways utilized by TSST—l, SE, LPS and PMA in monocytes are dissimilar despite common biological consequences such as lymphocyte mitogenesis and cytokine induction. TSST—1 was also tested for its ability to induce the cytokines, IL-i and TNF, from fractionated human PBMC. Highly purified monocytes alone or T lymphocytes alone did not produce IL—lB or TNFa when incubated with TSST—l for up to 72 h. However, TSST—l added to a 1:1 ratio of monocytes and T lymphocytes resulted in significant extracellular TNFa and IL—lB production at 24 h. The nature of the monocyte/T cell interaction did not involve IFN-i- but did require direct cell contact between metabolically active monocytes and T lymphocytes. Furthermore, TSST—l—mediated monocyte/T cell interaction also involved LFA—l since mAbs to this adhesion molecule significantly reduced cytokine secretion. Finally, the functional relevance of protein kinases in cytokine production by TSST—l-stirnulated monocyte/T lymphocyte co—cultures was explored. IL—lB secretion was suppressed by inhibitors of protein kinase C (H7), tyrosine kinases (genistein) and cAMP— and cGMP—dependent kinases (HA1004). In contrast, secretion of TNFa was blocked by only H7 and genistein, suggesting that induction of these two cytokines is differentially regulated. In conclusion, our data are consistent with a superantigen role for both TSST—i and SE and indicate that TSS pathogenesis occurs as a result of TSST-l interaction with both monocytes and T lymphocytes. Further studies focusing on the mechanism of cell activation by this toxin will not only enhance our knowledge of superantigens in general, but will also aid in our understanding of other bacterial toxin—mediated diseases.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat

Clastogenic activity in urine of individuals occupationally exposed to pesticides

Epidemiological evidence suggests that many human cancers may be attributed to environmental factors. Since the number of chemicals introduced into the environment is increasing at an alarming rate, measures must be taken to reduce human exposure. There is thus a growing need for the development of relevant and sensitive procedures for monitoring human exposure to environmental carcinogens and mutagens. The objective of this thesis was to evaluate the feasibility of using urine analysis to monitor individual exposure to pesticides. Pesticides are widely used chemicals in agriculture, and some are known to possess genotoxic properties. In this study, urine samples were collected from 21 orchardists (all non-smokers) in the Okanagan Valley when they were engaged in the application of pesticides during the fruit growing seasons in 1984 and 1985. As controls, urine was collected from these same individuals during the pre-spraying as well as the post-spraying seasons. In addition, 18 individuals from an agricultural research station in the Okanagan region (including 16 non-sprayers and 2 sprayers) were recruited to provide urine samples during the same time periods as the orchardists. As controls outside the fruit growing region, individuals from Vancouver and Grand Forks, B.C. were recruited to provide one urine specimen for this study. The urine samples were concentrated by reversed-phase high pressure liquid chromatography and then tested for their ability to induce chromosome aberrations (i.e., clastogenic activity) in cultured Chinese hamster ovary (CHO) cells. Furthermore, an attempt was made to examine the exfoliated urothelial cells for the presence of micronuclei as a potential in vivo indicator of damage by genotoxic constituents in the urine. Urine samples obtained from the orchardists 16 to 24 hours after pesticide application in 1984 resulted in levels of clastogenic activity undistinguishable from normal control limits. The failure to demonstrate increased clastogenic activity in the urine may have been due to (1) exposure to pesticides below the detection limits of the procedure, (2) the lack of genotoxicity in the agents sprayed, and (3) rapid pesticide metabolism and excretion in the urine. In the follow-up study of 1985, all urine voids were collected on the evening of the day of pesticide spraying (i.e., within 8 hours of exposure). Using this sampling protocol, the assay results showed that (1) urine samples collected from the orchardists and the agricultural research station workers during the non-spraying periods revealed no significant difference in clastogenic activity compared to the reference control group from Vancouver and Grand Forks, and (2) clastogenic activity of urine samples collected during the spraying period in 1985 was significantly elevated for the orchardist group (P<0.001; Tukey's non-parametric multiple comparisons test) but not for the agricultural research station personnel. The high urinary clastogenic activity found for the orchardists was attributed to heavy exposure to pesticides during the mixing, formulation and application process and the lack of compliance by the sprayers to wear full protective gear in hot weather. Cigarette smoking was another factor affecting urine clastogenicity together with pesticide exposure. Cigarette smokers from Grand Forks and the Okanagan agricultural research station demonstrated significantly higher urinary clastogenic activity than non-smokers (P<0.001; Mann-Whitney U test) . No dose-response relationship between the number of cigarettes smoked and urinary clastogenic activity was evident for the group of smokers assayed. All of the above effects were obtained without metabolic activation in vitro, suggesting that the clastogenic agents in the urine were direct-acting. In a large proportion of the urine samples tested, low but significant (relative to solvent controls) levels of clastogenic activity were observed in the urine of unexposed non-smokers, indicating the role of other factors in the appearance of urine clastogenicity. Urinary pH and creatinine did not differ among the study groups. No data were obtained from the analysis of micronuclei in exfoliated urothelial cells. The scarcity of cells among the subjects made it difficult to determine the frequency of micronucleated urothelial cells. On the basis of the present research, the monitoring of urine samples for genotoxicity appears to be a useful tool for assessing human exposure to environmental carcinogens and mutagens. Urine analysis is not only valuable in qualitatively demonstrating exposure to genetically hazardous agents, but is also a promising procedure for assessing the efficacy of preventive measures which are implemented to reduce further exposure.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat