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1.  Physical Activity and Bone: May the Force be with You 
Physical activity (PA) is thought to play an important role in preventing bone loss and osteoporosis in older people. However, the type of activity that is most effective in this regard remains unclear. Objectively measured PA using accelerometers is an accurate method for studying relationships between PA and bone and other outcomes. We recently used this approach in the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine relationships between levels of vertical impacts associated with PA and hip bone mineral density (BMD). Interestingly, vertical impacts >4g, though rare, largely accounted for the relationship between habitual levels of PA and BMD in adolescents. However, in a subsequent pilot study where we used the same method to record PA levels in older people, no >4g impacts were observed. Therefore, to the extent that vertical impacts need to exceed a certain threshold in order to be bone protective, such a threshold is likely to be considerably lower in older people as compared with adolescents. Further studies aimed at identifying such a threshold in older people are planned, to provide a basis for selecting exercise regimes in older people which are most likely to be bone protective.
doi:10.3389/fendo.2014.00020
PMCID: PMC3939444  PMID: 24624117
impact loading; bone; physical activity; BMD; exercise
2.  Coordinate Hyperproduction of SmeZ and SmeJK Efflux Pumps Extends Drug Resistance in Stenotrophomonas maltophilia 
A Stenotrophomonas maltophilia mutant that coordinately hyper-expresses three resistance nodulation division-type efflux pump genes, smeZ, smeJ, and smeK, has been identified. SmeZ is responsible for elevating aminoglycoside MICs; SmeJ and SmeK are jointly responsible for elevating tetracycline, minocycline, and ciprofloxacin MICs and conferring levofloxacin resistance. One clinical isolate with this same phenotype was identified from a sample of six, and the isolate also coordinately hyper-expresses smeZ and smeJK, confirming the clinical relevance of our findings.
doi:10.1128/AAC.01020-12
PMCID: PMC3535947  PMID: 23147729
3.  Determinants of fracture risk in a UK-population-based cohort of older women: a cross-sectional analysis of the Cohort for Skeletal Health in Bristol and Avon (COSHIBA) 
Age and Ageing  2011;41(1):46-52.
Background: identification of individuals with high fracture risk from within primary care is complex. It is likely that the true contribution of falls to fracture risk is underestimated.
Methods: cross-sectional analysis of a population-based cohort of 3,200 post-menopausal women aged 73 ± 4 years. Self-reported data were collected on fracture, osteoporosis clinical risk factors and falls/mobility risk factors. Self-reported falls were compared with recorded falls on GP computerised records. Multivariable logistic regression was used to identify independent risk factors for fracture.
Results: a total of 838 (26.2%) reported a fracture after aged 50; 441 reported falling more than once per year, but 69% of these had no mention of falls on their computerised GP records. Only age [odds ratios (OR): 1.37 per 5 year increase, 95% confidence interval (CI): 1.23–1.53], height (1.02 per cm increase, 95% CI: 1.01–1.04), weight (OR: 0.99 per kg increase, 95% CI: 0.98–0.99) and falls (OR: 1.49 for more than once per year compared with less, 95% CI: 1.13–1.94) were independent risk factors for fracture. Falls had the strongest association.
Conclusion: when identifying individuals with high fracture risk we estimate that more than one fall per year is at least twice as important as height and weight. Furthermore, using self-reported falls data is essential as computerised GP records underestimate falls prevalence.
doi:10.1093/ageing/afr132
PMCID: PMC3234077  PMID: 22107913
fractures; falls; COSHIBA; FRAX; cohort study; elderly
4.  Patient-reported history of leg ulceration 12–16 years after total primary knee or hip replacement 
Acta Orthopaedica  2011;82(4):471-474.
Background and purpose
Deep vein thrombosis is common after total joint replacement. It is frequently asymptomatic, and it is unclear whether this leads to longer-term problems such as post-thrombotic syndrome and leg ulceration. We investigated whether the postoperative prevalence of ulceration in patients who had undergone primary total hip replacement (THR) or total knee replacement (TKR) was higher than that found in a control group who had not undergone total joint replacement.
Methods
The study group consisted of patients who had undergone THR or TKR at one orthopedic center 12–16 years previously without routine chemothromboprophylaxis, and who had not undergone revision surgery. The control group was recruited via primary care. All participants were recruited by post and asked to complete a questionnaire. Age- and sex-adjusted prevalence of self-reported leg ulceration was calculated, and logistic regression was used to determine whether there were any associations between THR or TKR and leg ulceration.
Results
Completed questionnaires were received from 441 THR patients (54% response rate), 196 TKR patients (48%) and 967 control participants (36%). No statistically significant differences in age- and sex-adjusted prevalence of ulceration were found between the groups, for either lifetime prevalence or prevalence over the previous 15 years.
Interpretation
Patients who undergo THR and TKR without chemothromboprophylaxis are unlikely to be at a higher risk of long-term venous ulceration than the normal population.
doi:10.3109/17453674.2011.596064
PMCID: PMC3237039  PMID: 21751860
5.  The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants 
Genome Biology  2008;9(4):R74.
The complete Stenotrophomonas maltophilia genome sequence suggests that it can act as a reservoir of antibiotic resistance determinants.
Background
Stenotrophomonas maltophilia is a nosocomial opportunistic pathogen of the Xanthomonadaceae. The organism has been isolated from both clinical and soil environments in addition to the sputum of cystic fibrosis patients and the immunocompromised. Whilst relatively distant phylogenetically, the closest sequenced relatives of S. maltophilia are the plant pathogenic xanthomonads.
Results
The genome of the bacteremia-associated isolate S. maltophilia K279a is 4,851,126 bp and of high G+C content. The sequence reveals an organism with a remarkable capacity for drug and heavy metal resistance. In addition to a number of genes conferring resistance to antimicrobial drugs of different classes via alternative mechanisms, nine resistance-nodulation-division (RND)-type putative antimicrobial efflux systems are present. Functional genomic analysis confirms a role in drug resistance for several of the novel RND efflux pumps. S. maltophilia possesses potentially mobile regions of DNA and encodes a number of pili and fimbriae likely to be involved in adhesion and biofilm formation that may also contribute to increased antimicrobial drug resistance.
Conclusion
The panoply of antimicrobial drug resistance genes and mobile genetic elements found suggests that the organism can act as a reservoir of antimicrobial drug resistance determinants in a clinical environment, which is an issue of considerable concern.
doi:10.1186/gb-2008-9-4-r74
PMCID: PMC2643945  PMID: 18419807
6.  nalD Encodes a Second Repressor of the mexAB-oprM Multidrug Efflux Operon of Pseudomonas aeruginosa▿  
Journal of Bacteriology  2006;188(24):8649-8654.
The Pseudomonas aeruginosa nalD gene encodes a TetR family repressor with homology to the SmeT and TtgR repressors of the smeDEF and ttgABC multidrug efflux systems of Stenotrophomonas maltophilia and Pseudomonas putida, respectively. A sequence upstream of mexAB-oprM and overlapping a second promoter for this efflux system was very similar to the SmeT and TtgR operator sequences, and NalD binding to this region was, in fact, demonstrated. Moreover, increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter.
doi:10.1128/JB.01342-06
PMCID: PMC1698243  PMID: 17028276
7.  Randomized controlled trial of a primary care–based screening program to identify older women with prevalent osteoporotic vertebral fractures: Cohort for skeletal health in Bristol and Avon (COSHIBA) 
Approximately 12% of postmenopausal women have osteoporotic vertebral fractures (VFs); these are associated with excess morbidity and mortality and a high risk of future osteoporotic fractures. Despite this, less than one-third come to clinical attention, partly due to lack of clear clinical triggers for referral for spinal radiographs. The aim of this study was to investigate whether a novel primary care–based screening tool could be used to identify postmenopausal women with osteoporotic VFs and increase appropriate management of osteoporosis. A randomized controlled trial was undertaken in 15 general practices within the Bristol area of the UK. A total of 3200 women aged 65 to 80 years were enrolled, with no exclusion criteria. A simple screening tool was carried out by a nurse in primary care to identify women at high risk of osteoporotic VFs. All identified high-risk women were offered a diagnostic thoracolumbar radiograph. Radiographs were reported using standard National Health Service (NHS) reporting, with results sent back to each participant's general practitioner (GP). Participants in the control arm did not receive the screening tool or radiographs. The main outcome measure was self-reported prescription of medication for osteoporosis at 6 months with a random 5% subsample verified against electronic GP records. Secondary outcome was self-reported incidence of new fractures. Results showed that allocation to screening increased prescription of osteoporosis medications by 124% (odds ratio [OR] for prescription 2.24 at 6 months; 95% confidence interval [CI], 1.16 to 4.33). Allocation to screening also reduced fracture incidence at 12-month follow-up (OR for new fracture 0.60; 95% CI, 0.35–1.03; p = 0.063), although this did not reach statistical significance. This study supports the use of a simple screening tool administered in primary care to increase appropriate prescription of medications for osteoporosis in postmenopausal women in the UK. © 2012 American Society for Bone and Mineral Research
doi:10.1002/jbmr.1478
PMCID: PMC3378696  PMID: 22113935
RANDOMIZED CONTROLLED TRIAL; SCREENING; VERTEBRAL FRACTURES

Results 1-7 (7)