Application of Scan Statistics to Detect Suicide Clusters in Australia

Background

Suicide clustering occurs when multiple suicide incidents take place in a small area or/and within a short period of time. In spite of the multi-national research attention and particular efforts in preparing guidelines for tackling suicide clusters, the broader picture of epidemiology of suicide clustering remains unclear. This study aimed to develop techniques in using scan statistics to detect clusters, with the detection of suicide clusters in Australia as example.

Methods and Findings

Scan statistics was applied to detect clusters among suicides occurring between 2004 and 2008. Manipulation of parameter settings and change of area for scan statistics were performed to remedy shortcomings in existing methods. In total, 243 suicides out of 10,176 (2.4%) were identified as belonging to 15 suicide clusters. These clusters were mainly located in the Northern Territory, the northern part of Western Australia, and the northern part of Queensland. Among the 15 clusters, 4 (26.7%) were detected by both national and state cluster detections, 8 (53.3%) were only detected by the state cluster detection, and 3 (20%) were only detected by the national cluster detection.

Conclusions

These findings illustrate that the majority of spatial-temporal clusters of suicide were located in the inland northern areas, with socio-economic deprivation and higher proportions of indigenous people. Discrepancies between national and state/territory cluster detection by scan statistics were due to the contrast of the underlying suicide rates across states/territories. Performing both small-area and large-area analyses, and applying multiple parameter settings may yield the maximum benefits for exploring clusters.     

Evidence of intragenic recombination in G1 rotavirus VP7 genes

The G1 rotavirus is the most widespread genotype causing acute gastroenteritis in children. In an attempt to investigate the occurrence of intragenic recombination, 131 complete coding region sequences of VP7 genes of the G1 rotaviruses in GenBank were examined. Three hitherto-unreported intragenic recombinant rotaviruses were identified. It was noteworthy that two different types (interlineage and intersublineage) of intragenic recombination in rotaviruses were also found. This is the first report to demonstrate the existence of intragenic recombinations between interlineage and intersublineage in G1 rotaviruses.     

Potent and selective agonists of alpha-melanotropin (alphaMSH) action at human melanocortin receptor 5; linear analogs of alpha-melanotropin

Alpha-melanotropin, Ac-Ser(1)-Tyr-Ser-Met-Glu-His(6)-Phe(7)-Arg(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2)(1), is a non-selective endogenous agonist for the melanocortin receptor 5; the receptor present in various peripheral tissues and in the brain, cortex and cerebellum. Most of the synthetic analogs of alphaMSH, including a broadly used and more potent the NDP-alphaMSH peptide, Ac-Ser(1)-Tyr-Ser-Nle(4)-Glu-His(6)-D-Phe(7)-Arg(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2), are also not particularly selective for MC5R. To elucidate physiological functions of the melanocortin receptor 5 in rodents and humans, the receptor subtype selective research tools are needed. We report herein syntheses and pharmacological evaluation in vitro of several analogs of NDP-alphaMSH which are highly potent and specific agonists for the human MC5R. The new linear peptides, of structures and solubility properties similar to those of the endogenous ligand alphaMSH, are exemplified by compound 7, Ac-Ser(1)-Tyr-Ser-Met-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2) (Oic: octahydroindole-2-COOH, 4,4'-Bip: 4,4'-biphenylalanine, Pip: pipecolic acid), shortly NODBP-alphaMSH, which has an IC(50)=0.74 nM (binding assay) and EC(50)=0.41 (cAMP production assay) at hMC5R nM and greater than 3500-fold selectivity with respect to the melanocortin receptors 1b, 3 and 4. A shorter peptide derived from NODBP-alphaMSH: Ac-Nle-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8)-Trp(9) -NH(2) (17) was measured to be an agonist only 10-fold less potent at hMC5R than the full length parent peptide. In the structure of this smaller analog, the Nle-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8) segment was found to be critical for high agonist potency, while the C-terminal Trp(9) residue was shown to be required for high hMC5R selectivity versus hMC1b,3,4R.     

Role of PKA in the anti-Thy-1 antibody-induced neurite outgrowth of dorsal root ganglionic neurons

Thy-1 is highly expressed in the mammalian nervous system. Our previous study showed that addition of anti-Thy-1 antibody to cultured dorsal root ganglionic (DRG) neurons promotes neurite outgrowth. In this study, we identified a novel signaling pathway mediating this event. Treatment with function-blocking anti-Thy-1 antibodies enhanced neurite outgrowth of DRG neurons in terms of total neurite length, longest neurite length, and total neurite branching points. To elucidate the possible signal transduction pathway involved, activation of kinases was evaluated by Western blotting. Transient phosphorylation of protein kinase A (PKA) and mitogen-activated kinase kinase (MEK) was induced after 15 min of anti-Thy-1 antibody treatment. Pretreatment with a PKA inhibitor (PKI) or an MEK inhibitor, PD98059, significantly decreased the neurite outgrowth response triggered by anti-Thy-1 antibody, indicating the involvement of both kinases. In addition, anti-Thy-1 antibody treatment also induced transient phosphorylation of cyclic AMP-response element-binding protein (CREB) and this effect was also blocked by a PKI or PD98059. Furthermore, the fact that PKI abolished anti-Thy-1 antibody-induced MEK phosphorylation showed that PKA acts upstream of the MEK-CREB cascade. In summary, the PKA-MEK-CREB pathway is a new pathway involved in the neurite outgrowth-promoting effect of anti-Thy-1 antibody.     

PECAM‐1 supports leukocyte diapedesis by tension‐dependent dephosphorylation of VE‐cadherin

Leukocyte extravasation is an essential step during the immune response and requires the destabilization of endothelial junctions. We have shown previously that this process depends in vivo on the dephosphorylation of VE‐cadherin‐Y731. Here, we reveal the underlying mechanism. Leukocyte‐induced stimulation of PECAM‐1 triggers dissociation of the phosphatase SHP2 which then directly targets VE‐cadherin‐Y731. The binding site of PECAM‐1 for SHP2 is needed for VE‐cadherin dephosphorylation and subsequent endocytosis. Importantly, the contribution of PECAM‐1 to leukocyte diapedesis in vitro and in vivo was strictly dependent on the presence of Y731 of VE‐cadherin. In addition to SHP2, dephosphorylation of Y731 required Ca²⁺‐signaling, non‐muscle myosin II activation, and endothelial cell tension. Since we found that β‐catenin/plakoglobin mask VE‐cadherin‐Y731 and leukocyte docking to endothelial cells exert force on the VE‐cadherin–catenin complex, we propose that leukocytes destabilize junctions by PECAM‐1‐SHP2‐triggered dephosphorylation of VE‐cadherin‐Y731 which becomes accessible by actomyosin‐mediated mechanical force exerted on the VE‐cadherin–catenin complex.     

Late presentation of recurrent syncope after permanent pacemaker implantation due to Lead−Header malapposition

Permanent pacemaker (PPM) malfunction due to electrical connection problems such as a loose set screw or lead-header malapposition is extremely rare. We present a patient with complete heart block (CHB) who had PPM malfunction and recurrent syncope, late (14 months) after initial implantation, which was caused by the ventricular lead pin disengagement from the header resulting in oversensing due to noise, pacing inhibition and recurrent syncope. PPM due to lead-header malapposition this late after device implantation has previously not been reported.     

Performance of the predatory mite Amblydromalus limonicus on factitious foods

Amblydromalus limonicus Garman & McGregor (Acari: Phytoseiidae) is a generalist predatory mite with economic potential to control thrips and whiteflies in protected cultivation. We tested the development and reproduction of A. limonicus on three food sources with potential for use in laboratory production or to support its populations in a crop: fresh cattail pollen, Typha latifolia L. (Poales: Typhaceae), dry decapsulated cysts of the brine shrimp Artemia franciscana Kellogg (Branchiopoda: Artemiidae) and frozen eggs of the Mediterranean flour moth, Ephestia kuehniella Zeller (Lepidoptera: Pyralidae). The diets were tested both on an artificial substrate and on kidney bean leaves. In the absence of food, all larvae died on the artificial substrate, whereas they succeeded in reaching the protonymphal stage on bean leaves. Immature survival was high (>90 %) on all diet–substrate combinations, except when E. kuehniella eggs were offered on the artificial substrate (35 % survival). Both sexes showed the fastest development when offered E. kuehniella eggs on leaf discs, followed by A. franciscana cysts, whereas the slowest development was achieved on T. latifolia pollen. Fecundity and oviposition rate were higher on E. kuehniella and A. franciscana than on T. latifolia. Amblydromalus limonicus females lived longer on the leaf discs than on the artificial substrates. The intrinsic rate of increase (r_m) was highest when E. kuehniella eggs were offered on leaf discs (0.256 females per female per day), whereas the lowest rate (0.128 females per female per day) was obtained when the eggs were provided on artificial substrates. The intrinsic rate of increase on A. franciscana cysts was not affected by substrate and averaged 0.22 females per female per day. Diet significantly influenced the size of A. limonicus females as measured by the distance between specific setae on the dorsal shield of the idiosoma. The application of the investigated food sources to sustain a colony of predatory mites upon their release in a greenhouse crop is discussed.     

Behavioral Assessment of the Aging Mouse Vestibular System

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements.     

Induction of Adipocyte Differentiation by Polybrominated Diphenyl Ethers (PBDEs) in 3T3-L1 Cells

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants that were extensively used in commercial products. PBDEs are ubiquitous environmental contaminants that are both lipophilic and bioaccumulative. Effects of PBDEs on adipogenesis were studied in the 3T3-L1 preadipocyte cell model in the presence and absence of a known adipogenic agent, dexamethasone (DEX). A PBDE mixture designed to mimic body burden of North Americans was tested, in addition to the technical mixture DE-71 and the individual congener BDE-47. The mixture, DE-71, and BDE-47 all induced adipocyte differentiation as assessed by markers for terminal differentiation [fatty acid binding protein 4 (aP2) and perilipin] and lipid accumulation. Characterization of the differentiation process in response to PBDEs indicated that adipogenesis induced by a minimally effective dose of DEX was enhanced by these PBDEs. Moreover, C/EBPα, PPARγ, and LXRα were induced late in the differentiation process. Taken together, these data indicate that adipocyte differentiation is induced by PBDEs; they act in the absence of glucocorticoid and enhance glucocorticoid-mediated adipogenesis.