Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis. © 2011 Macmillan Publishers Limited. All rights reserved.

The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis

Multiple sclerosis (MS) is an autoimmune disease with a genetic component, caused at least in part by aberrant lymphocyte activity. The whole blood mRNA transcriptome was measured for 99 untreated MS patients: 43 primary progressive MS, 20 secondary progressive MS, 36 relapsing remitting MS and 45 age-matched healthy controls. The ANZgene Multiple Sclerosis Genetics Consortium genotyped more than 300 000 SNPs for 115 of these samples. Transcription from genes on translational regulation, oxidative phosphorylation, immune synapse and antigen presentation pathways was markedly increased in all forms of MS. Expression of genes tagging T cells was also upregulated (P < 10-12) in MS. A T cell gene signature predicts disease state with a concordance index of 0.79 with age and gender as co-variables, but the signature is not associated with clinical course or disability. The ANZgene genome wide association screen identified two novel regions with genome wide significance: one encoding the T cell co-stimulatory molecule, CD40; the other a region on chromosome 12q13-14. The CD40 haplotype associated with increased MS susceptibility has decreased gene expression in MS (P < 0.0007). The second MS susceptibility region includes 17 genes on 12q13-14 in tight linkage disequilibrium. Of these, only 13 are expressed in leukocytes, and of these the expression of one, FAM119B, is much lower in the susceptibility haplotype (P tdthomlt; 10-14). Overall, these data indicate dysregulation of T cells can be detected in the whole blood of untreated MS patients, and supports targeting of activated T cells in therapy for all forms of MS.

Spatio-temporal patterns in maturation of the chokka squid (Loligo vulgaris reynaudii) off the coast of South Africa

Knowledge of the temporal and spatial characteristics of chokka squid (Loligo vulgaris reynaudii) biology in South African waters is limited, so the possibility of there being a geographically fragmented stock was examined by investigating the distribution of maturity patterns for the species, covering all known spawning areas and using both historical and recent data. Gonadosomatic indices (GSI) varied between year-round consistency and apparent seasonal peaks in both summer and winter; there was no clear spatial pattern. Monthly percentage maturity provided further evidence for two peak reproductive periods each year, although mature squid were present throughout. Sex ratios demonstrated great variability between different areas and life history stages. Male-biased sex ratios were only apparent on the inshore spawning grounds and ranged between 1.118:1 and 4.267:1. Size at sexual maturity was also seasonal, squid maturing smaller in winter/spring than in summer/autumn. Also, squid in the east matured smaller than squid in the west. Although the results from the present study do not provide conclusive evidence of distinct geographic populations, squid likely spawn over a significantly larger area of the Agulhas Bank than previously estimated, and squid on the west coast of South Africa may return to spawn on the western portion of the Agulhas Bank. It remains likely, however, that the east and west coast populations are a single stock and that migration of juveniles to the west coast and their subsequent return as sub-adults is an integral but non-essential and variable part of the life history.

Spatial patterns in the biology of the chokka squid, Loligo reynaudii on the Agulhas Bank, South Africa

Although migration patterns for various life history stages of the chokka squid (Loligo reynaudii) have been previously presented, there has been limited comparison of spatial variation in biological parameters. Based on data from research surveys; size ranges of juveniles, subadults and adults on the Agulhas Bank were estimated and presented spatially. The bulk of the results appear to largely support the current acceptance of the life cycle with an annual pattern of squid hatching in the east, migrating westwards to offshore feeding grounds on the Central and Western Agulhas Bank and the west coast and subsequent return migration to the eastern inshore areas to spawn. The number of adult animals in deeper water, particularly in autumn in the central study area probably represents squid spawning in deeper waters and over a greater area than is currently targeted by the fishery. The distribution of life history stages and different feeding areas does not rule out the possibility that discrete populations of L. reynaudii with different biological characteristics inhabit the western and eastern regions of the Agulhas Bank. In this hypothesis, some mixing of the populations does occur but generally squid from the western Agulhas Bank may occur in smaller numbers, grow more slowly and mature at a larger size. Spawning occurs on the western portion of the Agulhas Bank, and juveniles grow and mature on the west coast and the central Agulhas Bank. Future research requirements include the elucidation of the age structure of chokka squid both spatially and temporally, and a comparison of the statolith chemistry and genetic characterisation between adults from different spawning areas across the Agulhas Bank.

An investigation of structural, magnetic and dielectric properties of R2NiMnO6 (R = rare earth, Y)

We have investigated the structure, magnetic and dielectric properties of the double perovskite oxides, R2NiMnO6 (R = Pr, Nd, Sm, Gd, Tb, Dy, Ho and Y). We could refine powder X-ray diffraction patterns of all the phases on the basis of monoclinic (P2(1)/n) double perovskite structure where Ni and Mn atoms are ordered at 2c and 2d sites, respectively. All the phases are ferromagnetic insulators exhibiting relatively low dielectric loss and dielectric constants in the range 15-25. The ferromagnetic ordering temperature of the R2NiMnO6 series seems to correlate better with the radius of R3+ atoms than with the average Ni-O-Mn angle (phi) in the double perovskite structure. These results are consistent with all samples having Mn4+ and Ni2+ With minimal antisite disorder.

Queensland pharmacist immunisation pilot phase 1 pharmacist vaccination - Influenza final report

The results of the pilot demonstrated that a pharmacist delivered vaccinations services is feasible in community pharmacy and is safe and effective. The accessibility of the pharmacist across the influenza season provided the opportunity for more people to be vaccinated, particularly those who had never received an influenza vaccine before. Patient satisfaction was extremely high with nearly all patients happy to recommend the service and to return again next year. Factors critical to the success of the service were: 1. Appropriate facilities 2. Competent pharmacists 3. Practice and decision support tools 4. In-­‐store implementation support We demonstrated in the pilot that vaccination recipients preferred a private consultation area. As the level of privacy afforded to the patients increased (private room vs. booth), so did the numbers of patients vaccinated. We would therefore recommend that the minimum standard of a private consultation room or closed-­‐in booth, with adequate space for multiple chairs and a work / consultation table be considered for provision of any vaccination services. The booth or consultation room should be used exclusively for delivering patient services and should not contain other general office equipment, nor be used as storage for stock. The pilot also demonstrated that a pharmacist-­‐specific training program produced competent and confident vaccinators and that this program can be used to retrofit the profession with these skills. As vaccination is within the scope of pharmacist practice as defined by the Pharmacy Board of Australia, there is potential for the universities to train their undergraduates with this skill and provide a pharmacist vaccination workforce in the near future. It is therefore essential to explore appropriate changes to the legislation to facilitate pharmacists’ practice in this area. Given the level of pharmacology and medicines knowledge of pharmacists, combined with their new competency of providing vaccinations through administering injections, it is reasonable to explore additional vaccines that pharmacists could administer in the community setting. At the time of writing, QPIP has already expanded into Phase 2, to explore pharmacists vaccinating for whooping cough and measles. Looking at the international experience of pharmacist delivered vaccination, we would recommend considering expansion to other vaccinations in the future including travel vaccinations, HPV and selected vaccinations to those under the age of 18 years. Overall the results of the QPIP implementation have demonstrated that an appropriately trained pharmacist can deliver safely and effectively influenza vaccinations to adult patients in the community. The QPIP showed the value that the accessibility of pharmacists brings to public health outcomes through improved access to vaccinations and the ability to increase immunisation rates in the general population. Over time with the expansion of pharmacist vaccination services this will help to achieve more effective herd immunity for some of the many diseases which currently have suboptimal immunisation rates.

Means are the Ends: The Command Issue

Means are the Ends: The Command Issue (2014) was an exhibition of sculptural works exhibited at LEVEL Artist-Run Initiative, Brisbane. The exhibition playfully critiqued the portrayal of women’s desire in cultural production and symbolic discourse through a focus on fetish sensibilities. Developed during a summer residency, the artworks looked to the rituals, materials and iconographies associated with certain divergent subcultures. Employing strategies of sculptural intervention and appropriation, the exhibition consisted of found objects, which had been deconstructed, altered and intervened; a dildo became a faux drawing machine, a butt-plug a makeshift horn. Reconstructing these visual codes through the formal and theoretical language of contemporary sculptural practice, Means are the Ends: The Command Issue spoke to the problematic, humorous and often paradoxical relationship between depictions of the feminine and women’s desire and agency.

Towards (dis)Satisfaction

Hosted at Blindside Artist-Run Initiative (Melbourne) the exhibition Towards (dis)Satisfaction (2015) was a re-staging of earlier sculptural works from the exhibitions Means are the Ends: The Command Issue and Crude Tools (2014), Feeble Actions (2013). The forms humorously interrogated representations of gender and sexuality via strategies of sculptural intervention. A stripper’s pole oozes grease from its stainless surface, fluted with holes. A dildo vibrates on a glass tabletop; propped up by simulated testicles, the intensity of the dildo’s vibrations makes the form spin. With its continual circling, the phallus drags Vaseline over the table, performing a drawing and redrawing of a smeared circle. In Towards (dis)Satisfaction fetish is used as an instrumental strategy, employed as a mode to work across different theoretical and material discourses. In the works the play between explicit and implicit depiction creates an ambiguity that has suggestive potency, where fragmentation and dysfunction initiate diverse readings. These material dialogues make apparent the anxiety and desire inherent in the viewer and question how the visual conventions of erotica and art history are mutually informative.

Sepulchre

The work in Sepulchre (2015) came from my research into female ritual practices and my fascination with specific mythological and historical narratives. These themes were explored during a month-long Summer Residency at Boxcopy Contemporary Artspace. Of particular note were the chronicles and rituals from the terrain around the Adriatic Sea, including Greece and Italy. During the residency, I kept referring to specific mythological texts, which had women as the main protagonists. I kept returning to female characters whose representation was framed by aspects of their sexuality. When looking at these women together, they seemed to sit within a greater narrative archetype, a communal dialogue of shared characteristics, repetitious narrative components and mutual landscapes. Sepulchre became my attempt to develop a conversation between these women by drawing from their commonality, and reimagining these collective elements into sculptural objects and moving images. The video explores an apotropaic gesture, a Baubo-style ‘flashing’. A glass star chart rests on white cliffs, speaking to the narrative of Andromeda and her position as both a celestial and terrene landscape. Another object, a wall mounted copper light burst, pays homage to the framing device used by Gian Lorenzo Bernini in The Ecstasy of Saint Teresa. By reconciling these dialogues, I was interested in exploring expanded portrayals of female sexuality and depictions of subversive and authorial femininity, developed through connotations with mysticism, ritual practice and women’s knowledge.

Biomass for aviation fuel production in the Fitzroy Basin, Queensland: a preliminary assessment of native and plantation forest potential

SummaryThis scoping study assesses the contribution that woody biomass could make to feedstock supply for an aviation biofuel industry in Queensland. The inland 600?900 mm rainfall zone, including the Fitzroy Basin region, is identified as an area that is particularly worthy of closer study as it has potential for supply of woody biomass from existing native regrowth (brigalow and other species) as well as from new plantings. New analyses carried out for this study of Corymbia citriodora subsp. variegata trials suggest biomass plantings could produce harvestable yield of aboveground dry mass of about 85 t ha?1 over a 10-year rotation at relatively low-rainfall (600?750 mm mean annual precipitation) sites and about 115 t ha?1 at medium-rainfall (750?900 mm) sites. Estimates of productivity for native regrowth suggest potential productivity should be around 40 t ha?1 during the initial decade after clearing when systems are managed for bioenergy rather than grazing. In this paper, potential production systems are described, and sustainability issues are briefly considered. It is concluded that more detailed studies focused particularly on biomass production would be worthwhile, and further research requirements are briefly discussed.

The Instabooth

The InstaBooth is a portable demountable interactive installation for situated community engagement. Its aim is to give a voice to communities who can share their thoughts and ideas in an unstructured and playful way that combines digital technology with tangible materials. It is constructed from standard CNC-cut plywood stock and plans for its construction are available for others to download and use. Its modular design accommodates a range of bespoke interactive technologies, both analogue and digital, designed to facilitate the engagement process by providing means to present different materials and offer different ways to collect feedback. The appearance and interactions of the booth are designed to appeal to different demographics and foster an interactive discussion about a range of different topics such as change management, policy development, and urban planning.

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN.

Submarine landslides : selected studies in the U.S. Exclusive Economic Zone

Submarine Landslides: An Introduction 1 By RIo Lee, W.C. Schwab, and J.S. Booth U.S. Atlantic Continental Slope Landslides: Their Distribution, General Anributes, and Implications 14 By J.S. Booth, D.W. O'Leary, Peter Popenoe, and W.W. Danforth Submarine Mass Movement, a Formative Process of Passive Continental Margins: The Munson-Nygren Landslide Complex and the Southeast New England Landslide Complex 23 By D.W. O'Leary The Cape Fear Landslide: Slope Failure Associated with Salt Diapirism and Gas Hydrate Decomposition 40 By Peter Popenoe, E.A. Schmuck, and W.P. Dillon Ancient Crustal Fractures Control the Location and Size of Collapsed Blocks at the Blake Escarpment, East of Florida 54 By W.P. Dillon, J.S. Risch, K.M. Scanlon, P.C. Valentine, and Q.J. Huggett Tectonic and Stratigraphic Control on a Giant Submarine Slope Failure: Puerto Rico Insular Slope 60 By W.C. Schwab, W.W. Danforth, and K.M. Scanlon Slope Failure of Carbonate Sediment on the West Florida Slope 69 By D.C. Twichell, P.C. Valentine, and L.M. Parson Slope Failures in an Area of High Sedimentation Rate: Offshore Mississippi River Delta 79 By J.M. Coleman, D.B. Prior, L.E. Garrison, and H.J. Lee Salt Tectonics and Slope Failure in an Area of Salt Domes in the Northwestern Gulf of Mexico 92 By B.A. McGregor, R.G. Rothwell, N.H. Kenyon, and D.C. Twichell Slope Stability in Regions 01 Sea-Floor Gas Hydrate: Beaufort Sea Continental Slope 97 By R.E. Kayen and H.J. Lee Mass Movement Related to Large Submarine Canyons Along the Beringian Margin, Alaska 104 By P.R. Carlson, H.A. Karl, B.D. Edwards, J.V. Gardner, and R. Hall Comparison of Tectonic and Stratigraphic Control of Submarine Landslides on the Kodiak Upper Continental Slope, Alaska 117 By M.A. Hampton Submarine Landslides That Had a Significant Impact on Man and His Activities: Seward and Valdez, Alaska 123 By M.A. Hampton, R.W. Lemke, and H.W. Coulter Processes Controlling the Style of Mass Movement in Glaciomarine Sediment: Northeastern Gulf of Alaska 135 By W.C. Schwab and H.J. Lee Contents V VI Contents Liquefaction of Continental Shelf Sediment: The Northern California Earthquake of 1980 143 By M.E. Field A Submarine Landslide Associated with Shallow Sea-Floor Gas and Gas Hydrates off Northern California 151 By M.E. Field and J.H. Barber, Jr. Sur Submarine Landslide, a Deep-Water Sediment Slope Failure 158 By C.E. Gutmacher and W.R. Normark Seismically Induced Mudflow in Santa Barbara Basin, California 167 By B.D. Edwards, H.J. Lee, and M.E. Field Submarine Landslides in a Basin and Ridge Setting, Southern California 176 By M.E. Field and B.D. Edwards Giant Volcano-Related Landslides and the Development of the Hawaiian Islands 184 By W.R. Normark, J.G. Moore, and M.E. Torresan Submarine Slope Failures Initiated by Hurricane Iwa, Kahe Point, Oahu, Hawaii 197 By W.R. Normark, Pat Wilde, J.F. Campbell, T.E. Chase, and Bruce Tsutsui (PDF contains 210 pages)

Hypoxic and low pH water in the nearshore marine environments of Monterey Bay, California: characterizing a decade of oxygen and pH, and drivers of variability.

A decade-long time series recorded in southern Monterey Bay, California demonstrates that the shallow, near-shore environment (17 m depth) is regularly inundated with pulses of cold, hypoxic and low pH water. During these episodes, oxygen can drop to biologically threatening levels, and pH levels were lower than expected. Weekly water chemistry monitoring revealed that the saturation state of aragonite (the more soluble form of calcium carbonate) was often below saturation and had a moderate positive relationship with pH, however, analytical and human error could be high. Pulses of hypoxia and low pH water with the greatest intensity arise at the onset of the spring upwelling season, and fluctuations are strongly semidurnal (tidal) and diurnal. Arrival of cold, hypoxic water on the inner shelf typically occurs 3 days after the arrival of a strong upwelling event and appears to be driven by upwelling modulated by internal tidal fluctuations. I found no relationship between the timing of low-oxygen events and the diel solar cycle nor with terrestrial nutrient input. These observations are consistent with advection of hypoxic water from the deep, offshore environment where water masses experience a general decline of temperature, oxygen and pH with depth, and inconsistent with biochemical forcing. Comparisons with concurrent temperature and oxygen time series taken ~20 km away at the head of the Monterey Canyon show similar patterns but even more intense hypoxic events due to stronger semidiurnal forcing there. Analysis of the durations of exposure to low oxygen levels establishes a framework for assessing the ecological relevance of these events. Increasing oceanic hypoxia and acidification of both surface and deep waters may increase the number, intensity, duration and spatial extent of future intrusions along the Pacific coast. Evaluation of the resiliency of nearshore ecosystems such as kelp forests, rocky reefs and sandy habitats, will require consideration of these events.