Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

Short emergency department length of stay attributed to full-body digital radiography - a review of 3 paediatric cases

Multiple casualties strain the resources of emergency departments. Two polytraumatised patients arriving simultaneously can overwhelm a small community hospital, while the capacity of a large urban emergency department does not extend beyond the treatment of 3 - 4 severely injured patients at the same time using the routine trauma protocol.1 Emergency department overcrowding because of multiple casualties leads to increased length of stay and can have an adverse effect on patient outcome. Variations from the norm in trauma management, particularly during the initial assessment and resuscitation phase of care, during a multiple casualty incident, has been associated with 10% and 9% incidence of preventable morbidity and mortality, respectively.2 Inadequate evaluation may contribute to up to 30% of early deaths in children with polytrauma.

Short emergency department length of stay attributed to full-body digital radiography - a review of 3 paediatric cases

Multiple casualties strain the resources of emergency departments. Two polytraumatised patients arriving simultaneously can overwhelm a small community hospital, while the capacity of a large urban emergency department does not extend beyond the treatment of 3 - 4 severely injured patients at the same time using the routine trauma protocol.1 Emergency department overcrowding because of multiple casualties leads to increased length of stay and can have an adverse effect on patient outcome. Variations from the norm in trauma management, particularly during the initial assessment and resuscitation phase of care, during a multiple casualty incident, has been associated with 10% and 9% incidence of preventable morbidity and mortality, respectively.2 Inadequate evaluation may contribute to up to 30% of early deaths in children with polytrauma.

Terminus-driven retreat of a major southwest Greenland tidewater glacier during the early 19th century : insights from glacier reconstructions and numerical modelling

Peer reviewedPublisher PD

The Association between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE B Study

Several studies have demonstrated the association between acute and late radiotherapy toxicity in prostate cancer using older radiotherapy techniques. However, whether this association is present with newer techniques such as stereotactic body radiotherapy (SBRT), remains unclear. We use univariable and multivariable logistic regression to analyse the association between grade 2 or worse acute gastrointestinal (GI) and genitourinary (GU) toxicities with equivalent late toxicities in patients treated with SBRT and conventional or moderately fractionated radiotherapy (CRT) within the PACE-B study. 842 patients were included in this analysis. Common Terminology Criteria for Adverse Events (CTCAE) was the primary clinician reported outcome measure used in this analysis. In univariable analysis, experiencing a grade 2+ acute GU toxicity was significantly associated with developing a grade 2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96–7.25), p < 0.0001) and CRT (OR 2.83, 95% CI (1.69–4.71), p < 0.0001). This association remained significant in multivariable analysis. In univariable analysis, experiencing a grade 2+ acute GI toxicity was also associated with developing a grade 2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91–7.03), p < 0.0001) and CRT (OR 4.4, 95% CI (2.04–9.47), p < 0.0001). This association also remained significant in multivariable analysis. Grade 2+ baseline GU symptoms were also associated with grade 2+ late urinary toxicity in both univariable and multivariable analysis. Overall, acute toxicity is an important predictor variable for late GU/GI toxicity after localised prostate radiotherapy using SBRT and CRT. Future work should test whether optimising symptoms pre-treatment and early intervention in those with significant acute toxicities could mitigate the development late of toxicity

A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.

A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals

Investigation of engineering properties of normal and high strength fly ash based geopolymer and alkali-activated slag concrete compared to ordinary Portland cement concrete

Fly ash-based geopolymer (FAGP) and alkali-activated slag (AAS) concrete are produced by mixing alkaline solutions with aluminosilicate materials. As the FAGP and AAS concrete are free of Portland cement, they have a low carbon footprint and consume low energy during the production process. This paper compares the engineering properties of normal strength and high strength FAGP and AAS concrete with OPC concrete. The engineering properties considered in this study included workability, dry density, ultrasonic pulse velocity (UPV), compressive strength, indirect tensile strength, flexural strength, direct tensile strength, and stress-strain behaviour in compression and direct tension. Microstructural observations using scanning electronic microscopy (SEM) are also presented. It was found that the dry density and UPV of FAGP and AAS concrete were lower than those of OPC concrete of similar compressive strength. The tensile strength of FAGP and AAS concrete was comparable to the tensile strength of OPC concrete when the compressive strength of the concrete was about 35 MPa (normal strength concrete). However, the tensile strength of FAGP and AAS concrete was higher than the tensile strength of OPC concrete when the compressive strength of concrete was about 65 MPa (high strength concrete). The modulus of elasticity of FAGP and AAS concrete in compression and direct tension was lower than the modulus of elasticity of OPC concrete of similar compressive strength. The SEM results indicated that the microstructures of FAGP and AAS concrete were more compact and homogeneous than the microstructures of OPC concrete at 7 days, but less compact and homogeneous than the microstructures of OPC concrete at 28 days for the concrete of similar compressive strength

Membrane Sigma-Models and Quantization of Non-Geometric Flux Backgrounds

We develop quantization techniques for describing the nonassociative geometry probed by closed strings in flat non-geometric R-flux backgrounds M. Starting from a suitable Courant sigma-model on an open membrane with target space M, regarded as a topological sector of closed string dynamics in R-space, we derive a twisted Poisson sigma-model on the boundary of the membrane whose target space is the cotangent bundle T^*M and whose quasi-Poisson structure coincides with those previously proposed. We argue that from the membrane perspective the path integral over multivalued closed string fields in Q-space is equivalent to integrating over open strings in R-space. The corresponding boundary correlation functions reproduce Kontsevich's deformation quantization formula for the twisted Poisson manifolds. For constant R-flux, we derive closed formulas for the corresponding nonassociative star product and its associator, and compare them with previous proposals for a 3-product of fields on R-space. We develop various versions of the Seiberg-Witten map which relate our nonassociative star products to associative ones and add fluctuations to the R-flux background. We show that the Kontsevich formula coincides with the star product obtained by quantizing the dual of a Lie 2-algebra via convolution in an integrating Lie 2-group associated to the T-dual doubled geometry, and hence clarify the relation to the twisted convolution products for topological nonassociative torus bundles. We further demonstrate how our approach leads to a consistent quantization of Nambu-Poisson 3-brackets.Comment: 52 pages; v2: references adde

Weekly ultra-hypofractionated radiotherapy in localised prostate cancer

Background: Moderately hypofractionated radiotherapy regimens or stereotactic body radiotherapy (SBRT) are standard of care for localised prostate cancer. However, some patients are unable or unwilling to travel daily to the radiotherapy department and do not have access to, or are not candidates for, SBRT. For many years, The Royal Marsden Hospital NHS Foundation Trust has offered a weekly ultra-hypofractionated radiotherapy regimen to the prostate (36 Gy in 6 weekly fractions) to patients unable/unwilling to travel daily. Methods: The current study is a retrospective analysis of all patients with non-metastatic localised prostate cancer receiving this treatment schedule from 2010 to 2015. Results: A total of 140 patients were included in the analysis, of whom 86 % presented with high risk disease, with 31 % having Gleason Grade Group 4 or 5 disease and 48 % T3 disease or higher. All patients received hormone treatment, and there was often a long interval between start of hormone treatment and start of radiotherapy (median of 11 months), with 34 % of all patients having progressed to non-metastatic castrate-resistant disease prior to start of radiotherapy. Median follow-up was 52 months. Median progression-free survival (PFS) and overall survival (OS) for the whole group was 70 months and 72 months, respectively. PFS and OS in patients with hormone-sensitive disease at time of radiotherapy was not reached and 75 months, respectively; and in patients with castrate-resistant disease at time of radiotherapy it was 20 months and 61 months, respectively. Conclusion: Our data shows that a weekly ultra-hypofractionated radiotherapy regimen for prostate cancer could be an option in those patients for whom daily treatment or SBRT is not an option