Frequency and risk factors for incident and redetected Chlamydia trachomatis infection in sexually active, young, multi-ethnic women: a community based cohort study.

OBJECTIVE: To investigate the frequency and risk factors for incident and redetected Chlamydia trachomatis infection in sexually active, young, multi-ethnic women in the community. DESIGN: Cohort study. SETTING: 20 London universities and Further Education colleges. PARTICIPANTS: 954 sexually experienced women, mean age 21.5 years (range 16-27), 26% from ethnic minorities, who were recruited to the Prevention of Pelvic Infection (POPI) chlamydia screening trial between 2004 and 2006, and returned repeat postal self-taken vaginal swabs 11-32 (median 16) months after recruitment. RESULTS: The estimated annual incidence of chlamydia infection among 907 women who tested negative at baseline was 3.4 per 100 person-years (95% CI 2.5 to 4.6 per 100 person-years), but 6.6 per 100 person-years (95% CI 4.5 to 9.3 per 100 person-years) in the 326 teenagers (<20 years). Predictors of incident chlamydia infection were age <20 years (relative risk (RR) 4.0, 95% CI 2.1 to 7.5), and (after adjusting for age) a new sexual partner during 12 months follow-up (RR 4.4, 95% CI 2.0 to 9.9), smoking (RR 2.2 95% CI 1.2 to 3.9), concurrent bacterial vaginosis (RR 2.0 95% CI 1.1 to 3.9) and high risk carcinogenic human papillomavirus (RR 2.2, 95% CI 1.1 to 4.3). Of 47 women positive for chlamydia at baseline, 12 (25.5%, 95% CI 13.9% to 40.3%) had redetected infection at a median of 16 months follow-up. Taking into account follow-up time (65 person-years), the annual redetection rate was 18.5 per 100 person-years (95% CI 9.9 to 30.0 per 100 person-years). CONCLUSIONS: One in four women with chlamydia infection at baseline retested positive, supporting recent recommendations to routinely retest chlamydia positives

Chlamydia related bacteria (Chlamydiales) in early pregnancy: community-based cohort study.

OBJECTIVES: Serological case-control studies suggest that certain chlamydia-related bacteria (Chlamydiales) which cause cows to abort may do the same in humans. Chlamydiales include Waddlia chondrophila, Chlamydia abortus and Chlamydia trachomatis. Data on prevalence of Chlamydiales in pregnancy are sparse. Using stored urine samples from a carefully characterised cohort of 847 newly pregnant women recruited from 37 general practices in London, UK, we aimed to investigate the prevalence and types of Chlamydiales infections. We also explored possible associations with miscarriage or spontaneous preterm birth. METHODS: Samples were tested using W. chondrophila and pan-Chlamydiales specific real-time PCRs targeting the 16S rRNA gene. Samples positive on either PCR were subjected to DNA sequencing and C. trachomatis PCR. RESULTS: The overall prevalence of Chlamydiales was 4.3% (36/847, 95% CI 3.0% to 5.8%). The prevalence of W. chondrophila was 0.6% (n = 5), C. trachomatis 1.7% (n = 14), and other Chlamydiales species 2.0% (n = 17). Infection with C. trachomatis was more common in women aged <25, of black ethnicity or with bacterial vaginosis, but this did not apply to W. chondrophila or other Chlamydiales. Follow up was 99.9% at 16 weeks gestation and 90% at term. No infection was significantly associated with miscarriage at ≤12 weeks (prevalence 10%, 81/827) or preterm birth <37 weeks (prevalence 4%, 23/628). Of 25 samples sequenced, seven (28%) were positive for Chlamydiales bacterium sequences associated with respiratory tract infections in children. CONCLUSION: In the first study to use the pan-Chlamydiales assay on female urine samples, 4% of pregnant women tested positive for Chlamydiales, including species known to be pathogenic in mothers and neonates

Base-mediated cascade rearrangements of aryl-substituted diallyl ethers.

Two base-mediated cascade rearrangement reactions of diallyl ethers were developed leading to selective [2,3]-Wittig-oxy-Cope and isomerization-Claisen rearrangements. Both diaryl and arylsilyl-substituted 1,3-substituted propenyl substrates were examined, and each exhibits unique reactivity and different reaction pathways. Detailed mechanistic and computational analysis was conducted, which demonstrated that the role of the base and solvent was key to the reactivity and selectivity observed. Crossover experiments also suggest that these reactions proceed with a certain degree of dissociation, and the mechanistic pathway is highly complex with multiple competing routes.We thank Eli Lilly (Dr Magnus Walter and Dr Maria Whatton) for a CASE award to C.A.M. and Queen’s University Belfast for funding. We also thank Girton College, Cambridge (Research Fellowship to M.N.G.) and Unilever for support.This is the accepted manuscript of a paper published in The Journal of Organic Chemistry, 2015, 80 (3), pp 1472–1498, DOI: 10.1021/jo502403n, Publication Date (Web): December 16, 201

Congenital bovine spinal dysmyelination is caused by a missense mutation in the SPAST gene

Bovine spinal dysmyelination (BSD) is a recessive congenital neurodegenerative disease in cattle (Bos taurus) characterized by pathological changes of the myelin sheaths in the spinal cord. The occurrence of BSD is a longstanding problem in the American Brown Swiss (ABS) breed and in several European cattle breeds upgraded with ABS. Here, we show that the disease locus on bovine chromosome 11 harbors the SPAST gene that, when mutated, is responsible for the human disorder hereditary spastic paraplegia (HSP). Initially, SPAST encoding Spastin was considered a less likely candidate gene for BSD since the modes of inheritance as well as the time of onset and severity of symptoms differ widely between HSP and BSD. However, sequence analysis of the bovine SPAST gene in affected animals identified a R560Q substitution at a position in the ATPase domain of the Spastin protein that is invariant from insects to mammals. Interestingly, three different mutations in human SPAST gene at the equivalent position are known to cause HSP. To explore this observation further, we genotyped more than 3,100 animals of various cattle breeds and found that the glutamine allele exclusively occurred in breeds upgraded with ABS. Furthermore, all confirmed BSD carriers were heterozygous, while all affected calves were homozygous for the glutamine allele consistent with recessive transmission of the underlying mutation and complete penetrance in the homozygous state. Subsequent analysis of recombinant Spastin in vitro showed that the R560Q substitution severely impaired the ATPase activity, demonstrating a causal relationship between the SPAST mutation and BSD

The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin

&lt;b&gt;Aim&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To examine the relationship between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined. Plasma 25 (OH) D concentrations were measured using standard methods. Intra and between assay imprecision was &#60;10%.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt;&lt;p&gt;&lt;/p&gt; In the large cohort, plasma 25 (OH) D was significantly associated with CRP (rs = −0.113, p&#60;0.001) and albumin (rs = 0.192, p&#60;0.001). 3711 patients had CRP concentrations ≤10 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were significantly lower from 35 to 28 to 14 nmol/l (p&#60;0.001). This decrease was significant when albumin concentrations were reduced between 25–34 g/L (p&#60;0.001) and when albumin &#60;25 g/L (p&#60;0.001). 1271 patients had CRP concentrations between 11–80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p&#60;0.001). This decrease was significant when albumin concentration were 25–34 g/L (p&#60;0.001) and when albumin &#60;25 g/L (p&#60;0.001). 345 patients had CRP concentrations &#62;80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were not significantly altered varying from 19 to 23 to 23 nmol/l. Similar relationships were also obtained in the cohort of patients with critical illness.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Plasma concentrations of 25(OH) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory response as a major confounding factor in determining vitamin D status.&lt;p&gt;&lt;/p&gt

Identification of hip fracture patients from radiographs using Fourier analysis of the trabecular structure: a cross-sectional study

Peer reviewedPublisher PD

Environmental Controls on Tropical Sea Breeze Convection and Resulting Aerosol Redistribution

Sea breeze fronts propagate inland from the coastline, driving convective initiation and aerosol redistribution. Forecasting sea breezes is challenging due to uncertainties in the initial conditions, as well as the covariance and interaction of various meteorological and surface parameters. Using the Regional Atmospheric Modeling System coupled to an interactive land‐surface model, we conduct an ensemble of 130 idealized cloud‐resolving simulations by simultaneously perturbing six atmospheric and four surface parameters describing the initial conditions. To identify the key parameters impacting the inland characteristics and the intensity of the sea breeze convection in a tropical rainforest, we apply statistical emulation and variance‐based sensitivity analysis techniques. This study extends a previous study which explored the impacts of various parameters on sea breeze characteristics in arid environments devoid of moist convection. Wind speed is identified as the main contributor to the inland extent, similar to the arid environment study. However, the relative impacts of surface properties on the inland extent are less significant in the moist environment where land‐surface heating can be suppressed via moist convective processes and vegetation‐atmosphere interactions. Two sea breeze‐initiated convection regimes are also identified: shallow and deep. Over the shallow regime, where convective available potential energy is limited, the inversion layer strength is the primary control of the convective intensity. Over the deep regime, boundary layer temperature exerts a robust control over the convective available potential energy and hence the convective intensity. The potential vertical redistribution of aerosols is closely related to the convective intensity