Acute bronchitis in Australian general practice - a prescription too far?

OBJECTIVE: To quantify how frequently general practitioners in Australia prescribe antibiotics for acute bronchitis, which antibiotics are used, and whether there are subgroups of patients who might benefit from their use. DESIGN AND SETTING: A retrospective descriptive study using 3 sets of data: Australian Sentinel Practice Research Network, the Bettering the Evaluation and Care of Health (BEACH) Program, and the General Practice Research Network (GPRN). RESULTS: Over 50% of all patients with ‘acute bronchitis’ had either chest or one or more systemic signs on physical examination. The rate of antibiotic prescribing for acute bronchitis was 79.6% of acute bronchitis visits using BEACH data 2001–2002 and varied from 68.6 (95% CI: 62.8–74.5%) in 2001 to 78.7 (95% CI: 72.2–85.2%) in 1999 using GPRN data. Penicillins, followed by macrolides, were the most commonly prescribed antibiotics. DISCUSSION: Australian GPs frequently prescribe antibiotics for ‘acute bronchitis’ despite guidelines to the contrary. One reason may be that many patients present with chest or systemic signs.N.P. Stocks, H. McElroy, G.P. Sayer and K. Duszynsk

Processed meat consumption and Lung function: modification by antioxidants and smoking

This article has supplementary material available from www.erj.ersjournals.com: This study was supported by the Medical Research Council, UK. H. Okubo was supported in part by fellowship of the Astellas Foundation for Research on Metabolic Disorders, Japan and the Naito Memorial Grant for Research Abroad from the Naito Foundation, Japan

Type of milk feeding in infancy and health behaviours in adult life: findings from the Hertfordshire Cohort Study

A number of studies suggest that breast-feeding has beneficial effects on an individual's cardiovascular risk factors in adulthood, although the mechanisms involved are unknown. One possible explanation is that adults who were breastfed differ in their health behaviours. In a historical cohort, adult health behaviours were examined in relation to type of milk feeding in infancy. From 1931 to 1939, records were kept on all infants born in Hertfordshire, UK. Their type of milk feeding was summarised as breastfed only, breast and bottle-fed, or bottle-fed only. Information about adult health behaviours was collected from 3217 of these men and women when they were aged 59–73 years. Diet was assessed using an administered FFQ; the key dietary pattern was a ‘prudent’ pattern that described compliance with ‘healthy’ eating recommendations. Of the study population, 60 % of the men and women were breastfed, 31 % were breast and bottle-fed, and 9 % were bottle-fed. Type of milk feeding did not differ according to social class at birth, and was not related to social class attained in adult life. There were no differences in smoking status, alcohol intake or reported physical activity according to type of milk feeding, but there were differences in the participants' dietary patterns. In a multivariate model that included sex and infant weight gain, there were independent associations between type of feeding and prudent diet scores in adult life (P= 0·009), such that higher scores were associated with having been breastfed. These data support experimental findings which suggest that early dietary exposures can have lifelong influences on food choice

Design, synthesis, and evaluation of peptide-imidazo[1,2-a]pyrazine bioconjugates as potential bivalent inhibitors of the VirB11 ATPase HP0525

Helicobacter pylori (H. pylori) infections have been implicated in the development of gastric ulcers and various cancers: however, the success of current therapies is compromised by rising antibiotic resistance. The virulence and pathogenicity of H. pylori is mediated by the type IV secretion system (T4SS), a multiprotein macromolecular nanomachine that transfers toxic bacterial factors and plasmid DNA between bacterial cells, thus contributing to the spread of antibiotic resistance. A key component of the T4SS is the VirB11 ATPase HP0525, which is a hexameric protein assembly. We have previously reported the design and synthesis of a series of novel 8-amino imidazo[1,2-a]pyrazine derivatives as inhibitors of HP0525. In order to improve their selectivity, and potentially develop these compounds as tools for probing the assembly of the HP0525 hexamer, we have explored the design and synthesis of potential bivalent inhibitors. We used the structural details of the subunit-subunit interactions within the HP0525 hexamer to design peptide recognition moieties of the subunit interface. Different methods (cross metathesis, click chemistry, and cysteine-malemide) for bioconjugation to selected 8-amino imidazo[1,2-a]pyrazines were explored, as well as peptides spanning larger or smaller regions of the interface. The IC50 values of the resulting linker-8-amino imidazo[1,2-a]pyrazine derivatives, and the bivalent inhibitors, were related to docking studies with the HP0525 crystal structure and to molecular dynamics simulations of the peptide recognition moieties

Using novel palaeolimnological techniques to define lake conservation objectives (Phase 1)

This is the final report to Natural England on Contract No: SAE03/02/054 ‘Using novel palaeolimnological techniques to define lake conservation objectives’. The primary objective of this project is to use existing and recently developed palaeoecological techniques to define reference conditions and assess the condition of selected SSSIs in England, and thereby to assist in the setting of conservation objectives and management goals. The eight selected sites are Aqualate Mere, Hawes Water (Silverdale), Cunswick Tarn, Over Water, Sunbiggin Tarn, Malham Tarn, Semer Water and Hornsea Mere. The project is divided into four main tasks with Task 1 essentially involving the collection, processing and dating of cores from the study sites. To date only the latter has been funded and this report describes the outputs of this task

Using novel palaeolimnological techniques to define lake conservation objectives for three Cheshire meres

This is the final report to Natural England on the project „Using novel palaeolimnological techniques to define lake conservation objectives for three Cheshire meres‟: Melchett Mere, Tatton Mere and Comber Mere. The aim is to use existing and recently developed palaeoecological techniques to define reference conditions and assess the condition of selected Sites of Special Scientific Interest (SSSIs) in the Cheshire meres, and thereby assist in the setting of conservation objectives and management goals

Validation of the GRAPE single view aerosol retrieval for ATSR-2 and insights into the long term global AOD trend over the ocean

The Global Retrieval of ATSR Cloud Parameters and Evaluation (GRAPE) project has produced a global data-set of cloud and aerosol properties from the Along Track Scanning Radiometer-2 (ATSR-2) instrument, covering the time period 1995�2001. This paper presents the validation of aerosol optical depths (AODs) over the ocean from this product against AERONET sun-photometer measurements, as well as a comparison to the Advanced Very High Resolution Radiometer (AVHRR) optical depth product produced by the Global Aerosol Climatology Project (GACP). The GRAPE AOD over ocean is found to be in good agreement with AERONET measurements, with a Pearson's correlation coefficient of 0.79 and a best-fit slope of 1.0±0.1, but with a positive bias of 0.08±0.04. Although the GRAPE and GACP datasets show reasonable agreement, there are significant differences. These discrepancies are explored, and suggest that the downward trend in AOD reported by GACP may arise from changes in sampling due to the orbital drift of the AVHRR instruments

Sedimentary macrofossil records reveal ecological change in English lakes: implications for conservation

Aquatic macrophytes play a key role in providing habitat, refuge and food for a range of biota in shallow lakes. However, many shallow lakes have experienced declines in macrophyte vegetation in recent decades, principally due to eutrophication. As changes in macrophyte composition and abundance can affect overall ecological structure and function of a lake, an assessment of the timing and nature of such changes is crucial to our understanding of the wider lake ecosystem. In the typical absence of historical plant records, the macro-remains of macrophytes preserved in lake sediments can be used to assess long-term changes in aquatic vegetation. We generated recent (150–200 years) plant macrofossil records for six English lakes subject to conservation protection to define past macrophyte communities, assess trajectories of ecological change and consider the implications of our findings for conservation targets and strategies. The data for all six lakes reveal a diverse submerged macrophyte community, with charophytes as a key component, in the early part of the sedimentary records. The stratigraphies indicate considerable change to the aquatic vegetation over the last two centuries with a general shift towards species more typically associated with eutrophic conditions. A common feature is the decline in abundance of low-growing charophytes and an increase in tall canopy-forming angiosperms such as fine-leaved Potamogeton species, Zannichellia palustris and Callitriche species. We hypothesise, based on findings from long-term datasets and palaeoecological records from enriched shallow lakes where plants are now absent, that the observed shifts provide a warning to managers that the lakes are on a pathway to complete macrophyte loss such that nutrient load reduction is urgently needed. It is the sound understanding of present-day plant ecology that affords such reliable interpretation of the fossil data which, in turn, provide valuable context for current conservation decisions

Are Labour Markets Necessarily Local? Spatiality, Segmentation and Scale

This paper draws on recent debates about scale to approach the geography of labour markets from a dynamic perspective sensitive to the spatiality and scale of labour market restructuring. Its exploration of labour market reconfigurations after the collapse of a major firm (Ansett Airlines) raises questions about geography’s faith in the inherently ‘local’ constitution of labour markets. Through an examination of the job reallocation process after redundancy, the paper suggests that multiple labour markets use and articulate scale in different ways. It argues that labour market rescaling processes are enacted at the critical moment of recruitment, where social networks, personal aspirations and employer preferences combine to shape workers’ destinations

ARL3 mutations cause Joubert syndrome by disrupting ciliary protein composition

Joubert syndrome (JBTS) is a genetically heterogeneous autosomal recessive neurodevelopmental ciliopathy. We investigated further the underlying genetic etiology of Joubert syndrome by studying two unrelated families in whom JBTS was not associated with pathogenic variants in known JBTSrelated genes. Combined autozygosity mapping of both families highlighted a candidate locus on chromosome 10 (chr10: 101569997-109106128 (hg 19)), and exome sequencing revealed two missense variants in ARL3 within the candidate locus. The encoded protein, ADP Ribosylation Factor-Like GTPase 3, ARL3, is a small GTP-binding protein that is involved in directing lipid-modified proteins into the cilium in a GTP-dependent manner. Both missense variants replace the highly conserved Arg149 residue, which we show to be necessary for the interaction with its guanine nucleotide exchange factor ARL13B, such that the mutant protein is associated with reduced INPP5E and NPHP3 localisation in cilia. We propose that ARL3 provides a potential hub in the network of encoded ciliopathy genes, whereby perturbation of ARL3 results in the mislocalisation of multiple ciliary proteins due to abnormal displacement of lipidated protein cargo