Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis

Background Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). Methods A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. Results No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. Conclusions Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

Survey and Mapping Infrastructure Regulation 2004- Comments Relating to a 10-Year Review

Democratic governments raise taxes and charges and spend revenue on delivering peace, order and good government. The delivery process begins with a legislature as that can provide a framework of legally enforceable rules enacted according to the government’s constitution. These rules confer rights and obligations that allow particular people to carry on particular functions at particular places and times. Metadata standards as applied to public records contain information about the functioning of government as distinct from the non-government sector of society. Metadata standards apply to database construction. Data entry, storage, maintenance, interrogation and retrieval depend on a controlled vocabulary needed to enable accurate retrieval of suitably catalogued records in a global information environment. Queensland’s socioeconomic progress now depends in part on technical efficiency in database construction to address queries about who does what, where and when; under what legally enforceable authority; and how the evidence of those facts is recorded. The Survey and Mapping Infrastructure Act 2003 (Qld) addresses technical aspects of where questions – typically the officially recognised name of a place and a description of its boundaries. The current 10-year review of the Survey and Mapping Regulation 2004 provides a valuable opportunity to consider whether the Regulation makes sense in the context of a number of later laws concerned with management of Public Sector Information (PSI) as well as policies for ICT hardware and software procurement. Removing ambiguities about how official place names are to be regarded on a whole-of-government basis can achieve some short term goals. Longer-term goals depend on a more holistic approach to information management – and current aspirations for more open government and community engagement are unlikely to occur without such a longer-term vision.

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis : protocol for a randomised controlled trial

Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW(135)) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and >= 6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged >= 6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine-related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged >= 6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

Queensland diabetic foot hospitalisations (2005-10) : in what state is our foot hospital problem?

Background Diabetes foot complications are a leading cause of overall avoidable hospital admissions. Since 2006, the Queensland Diabetes Clinical Network has implemented programs aimed at reducing diabetes-related hospitalisation. The aim of this retrospective observational study was to determine the incidence of diabetes foot-related hospital admissions in Queensland from 2005 to 2010. Methods Data on all primary diabetes foot-related admissions in Queensland from 2005-2010 was obtained using diabetes foot-related ICD-10-AM (hospital discharge) codes. Queensland diabetes foot-related admission incidences were calculated using general population data from the Australian Bureau of Statistics. Furthermore, diabetes foot-related sub-group admissions were analysed. Chi-squared tests were used to assess changes in admissions over time. Results Overall, 24,917 diabetes foot-related admissions occurred, resulting in the use of 260,085 bed days or 1.4% of all available Queensland hospital bed days (18,352,152). The primary reasons for these admissions were foot ulcers (49.8%), cellulitis (20.7%), peripheral vascular disease (17.8%) and osteomyelitis (3.8%). The diabetes foot-related admission incidence among the general population (per 100,000) reduced by 22% (103.0 in 2005, to 80.7 in 2010, p < 0.001); bed days decreased by 18% (1,099 to 904, p < 0.001). Conclusion Diabetes foot complications appear to be the primary reason for 1.4 out of every 100 hospital beds used in Queensland. There has been a significant reduction in the incidence of diabetes foot-related admissions in Queensland between 2005 and 2010. This decrease has coincided with a corresponding decrease in amputations and the implementation of several diabetes foot clinical programs throughout Queensland.

A randomized controlled trial of a 10 percent CPP-ACP cream to reduce mutans streptococci colonization

Purpose The purpose of this study was to investigate the effectiveness of a 10 percent casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) cream to reduce mutans streptococci (MS) colonization and prevent early childhood caries. Methods The cohort was randomized at mean age of 11 days old to receive once-daily CPP-ACP cream (n=102) or no product (comparison group; n=89) from the time of first tooth eruption. All mothers were contacted by telephone at six, 12, and 18 months and advised to brush their children's teeth twice daily with low-dose fluoride toothpaste. At 24 months, all children were examined at a community clinic. Results At 24 months old, one out of 65 (2 percent) children in the CPP-ACP group had caries vs. four out of 58 (seven percent) in the comparison group (difference not statistically significant). There were fewer MS-positive children in the CPP-ACP group (26 percent) vs. the comparison group (47 percent; P=.02). A dose-response effect of CPP-ACP usage on MS was observed, where MS was present in eight percent of regular CPP-ACP users, 28 percent of irregular users, and 47 percent of non-users (P<.02). Conclusions CPP-ACP reduced the percentages of mutans streptococci-positive 24-month-old children, although it did not reduce caries prevalence.

Preliminary characterisation of tumor necrosis factor alpha and interleukin-10 responses to chlamydia pecorum infection in the koala (Phascolarctos cinereus)

Debilitating infectious diseases caused by Chlamydia are major contributors to the decline of Australia's iconic native marsupial species, the koala (Phascolarctos cinereus). An understanding of koala chlamydial disease pathogenesis and the development of effective strategies to control infections continue to be hindered by an almost complete lack of species-specific immunological reagents. The cell-mediated immune response has been shown to play an influential role in the response to chlamydial infection in other hosts. The objective of this study, hence, was to provide preliminary data on the role of two key cytokines, pro-inflammatory tumour necrosis factor alpha (TNFα) and anti-inflammatory interleukin 10 (IL10), in the koala Chlamydia pecorum response. Utilising sequence homology between the cytokine sequences obtained from several recently sequenced marsupial genomes, this report describes the first mRNA sequences of any koala cytokine and the development of koala specific TNFα and IL10 real-time PCR assays to measure the expression of these genes from koala samples. In preliminary studies comparing wild koalas with overt chlamydial disease, previous evidence of C. pecorum infection or no signs of C. pecorum infection, we revealed strong but variable expression of TNFα and IL10 in wild koalas with current signs of chlamydiosis. The description of these assays and the preliminary data on the cell-mediated immune response of koalas to chlamydial infection paves the way for future studies characterising the koala immune response to a range of its pathogens while providing reagents to assist with measuring the efficacy of ongoing attempts to develop a koala chlamydial vaccine.

Rediscovering the double Friedel-Crafts acylation : an expedient entry to phenanthrene-9,10-diones

The double Friedel–Crafts acylation of readily accessible biaryls with oxalyl chloride delivers the respective phenanthrene-9,10-diones, providing an alternative to the traditional methods, which require harsh oxidizing conditions and multistep sequences. This simple method allows the synthesis of various symmetrical and non-symmetrical targets, and is even effective for the synthesis of the parent ring system from (unactivated) biphenyl.

A vibrational spectroscopic study of the phosphate mineral lulzacite Sr2Fe2+(Fe2+,Mg)2Al4(PO4)4(OH)10

The mineral lulzacite from Saint-Aubin des Chateaux mine, France, with theoretical formula Sr2Fe2+(Fe2+,Mg)2Al4(PO4)4(OH)10 has been studied using a combination of electron microscopy with EDX and vibrational spectroscopic techniques. Chemical analysis shows a Sr, Fe, Al phosphate with minor amounts of Ga, Ba and Mg. Raman spectroscopy identifies an intense band at 990 cm�1 with an additional band at 1011 cm�1. These bands are attributed to the PO3� 4 m1 symmetric stretching mode. The m3 antisymmetric stretching modes are observed by a large number of Raman bands. The Raman bands at 1034, 1051, 1058, 1069 and 1084 together with the Raman bands at 1098, 1116, 1133, 1155 and 1174 cm�1 are assigned to the m3 antisymmetric stretching vibrations of PO3� 4 and the HOPO2� 3 units. The observation of these multiple Raman bands in the symmetric and antisymmetric stretching region gives credence to the concept that both phosphate and hydrogen phosphate units exist in the structure of lulzacite. The series of Raman bands at 567, 582, 601, 644, 661, 673 and 687 cm�1 are assigned to the PO3� 4 m2 bending modes. The series of Raman bands at 437, 468, 478, 491, 503 cm�1 are attributed to the PO3� 4 and HOPO2� 3 m4 bending modes. No Raman bands of lulzacite which could be attributed to the hydroxyl stretching unit were observed. Infrared bands at 3511 and 3359 cm�1 are ascribed to the OH stretching vibration of the OH units. Very broad bands at 3022 and 3299 cm�1 are attributed to the OH stretching vibrations of water. Vibrational spectroscopy offers insights into the molecular structure of the phosphate mineral lulzacite.

The Torrent : Toowoomba and the Lockyer Valley, 10 January 2011

Of all the stories to emerge from Queensland’s catastrophic summer of 2011, the most dramatic and starkly tragic were those that took place in Toowoomba and the Lockyer Valley. On January 10, 2011, after weeks of heavy rain and as floodwaters began to overwhelm much of south-east Queensland, an ‘inland tsunami’ hit the city of Toowoomba, the rural districts of Spring Bluff and Postmans Ridge, and the towns of Murphys Creek, Withcott, Helidon, and Grantham. The Torrent:Toowoomba and the Lockyer Valley, 10 January 2011 tells, for the first time, the extraordinary stories of survival and loss that emerged from that terrible day. Official figures state that twenty-four people died. Many escaped death only because they were rescued by members of the community or through sheer good fortune. Based on exclusive interviews with survivors, rescuers and with the families and friends of victims of the disaster, The Torrent is a unique and powerful account of human courage in the face of the devastating force of nature, and the enduring resilience of ordinary Australians.

The 10 Australian ecosystems most vulnerable to tipping points

We identify the 10 major terrestrial and marine ecosystems in Australia most vulnerable to tipping points, in which modest environmental changes can cause disproportionately large changes in ecosystem properties. To accomplish this we independently surveyed the coauthors of this paper to produce a list of candidate ecosystems, and then refined this list during a 2-day workshop. The list includes (1) elevationally restricted mountain ecosystems, (2) tropical savannas, (3) coastal floodplains and wetlands, (4) coral reefs, (5) drier rainforests, (6) wetlands and floodplains in the Murray-Darling Basin, (7) the Mediterranean ecosystems of southwestern Australia, (8) offshore islands, (9) temperate eucalypt forests, and (10) salt marshes and mangroves. Some of these ecosystems are vulnerable to widespread phase-changes that could fundamentally alter ecosystem properties such as habitat structure, species composition, fire regimes, or carbon storage. Others appear susceptible to major changes across only part of their geographic range, whereas yet others are susceptible to a large-scale decline of key biotic components, such as small mammals or stream-dwelling amphibians. For each ecosystem we consider the intrinsic features and external drivers that render it susceptible to tipping points, and identify subtypes of the ecosystem that we deem to be especially vulnerable. © 2011 Elsevier Ltd.

10,000 steps Rockhampton : (1) building a whole community approach to increasing levels of physical activity

10,000 Steps Rockhampton is a multi-strategy health promotion program which aims to develop sustainable community-based strategies to increase physical activity.The central coordinating focus of the project is the use of pedometers to raise awareness of and provide motivation for physical activity, around the theme of '10,000 steps/day - Every step counts.' To date, five key strategies have been implemented: (1) a media-based awareness raising campaign; (2) promotion of physical activity by health professionals; (3) improving social support for physical activity through group-based programs; (4) working with local council to improve environmental support for physical activity, and; (5) establishment of a ‘micro-grants’ fund to which community groups could apply for assistance with small, innovative physical activity enhancing projects. Strategies were introduced on a rolling basis beginning in February 2002 with 'layering' of interventions designed to address the multi-level individual social and environmental determinants of physical activity. The project was quasi-experimental in design, involving collection of baseline and two year follow-up data from community based surveys in Rockhampton and in a matched regional Queensland town. In August 2001,the baseline CATI survey (N=1281)found that 47.9% of men and 33.0% of women were meeting the national guidelines for physical activity. In August 2002, a smaller survey (N=400) found an increase in activity levels among women (39.7% active) but not in men (48.5%). Data from the two year follow up survey, to be conducted in August 2003, will be presented, with discussion of the major successes and challenges of this landmark physical activity intervention. Acknowledgement: This project is supported by a grant from Health Promotion Queensland.

10,000 steps Rockhampton: a whole community approach to increasing levels of physical activity

10,000 Steps Rockhampton is a multi-strategy health promotion program which aims to develop sustainable community-based strategies to increase physical activity.The central coordinating focus of the project is the use of pedometers to raise awareness of and provide motivation for physical activity, around the theme of '10,000 steps/day - Every step counts.' To date, five key strategies have been implemented: (1) a media-based awareness raising campaign; (2) promotion of physical activity by health professionals; (3) improving social support for physical activity through group-based programs; (4) working with local council to improve environmental support for physical activity, and; (5) establishment of a ‘micro-grants’ fund to which community groups could apply for assistance with small, innovative physical activity enhancing projects. Strategies were introduced on a rolling basis beginning in February 2002 with 'layering' of interventions designed to address the multi-level individual social and environmental determinants of physical activity. The project was quasi-experimental in design, involving collection of baseline and two year follow-up data from community based surveys in Rockhampton and in a matched regional Queensland town. In August 2001,the baseline CATI survey (N=1281)found that 47.9% of men and 33.0% of women were meeting the national guidelines for physical activity. In August 2002, a smaller survey (N=400) found an increase in activity levels among women (39.7% active) but not in men (48.5%). Data from the two year follow up survey, to be conducted in August 2003, will be presented, with discussion of the major successes and challenges of this landmark physical activity intervention. Acknowledgement: This project is supported by a grant from Health Promotion Queensland