Non-steroidal anti-inflammatory drug use and brain tumour risk:a case-control study within the Clinical Practice Research Datalink

Purpose: The aetiology of primary brain tumours is largely unknown; the role of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin use and glioma risk has been inconclusive, but few population-based studies with reliable prescribing data have been conducted, and the association with meningioma risk has yet to be assessed. Methods: The UK Clinical Practice Research Datalink was used to assess the association between aspirin and non-aspirin NSAID use and primary brain tumour risk using a nested case-control study design. Conditional logistic regression analysis was performed on 5,052 brain tumour patients aged 16 years and over, diagnosed between 1987 and 2009 and 42,678 controls matched on year of birth, gender and general practice, adjusting for history of allergy and hormone replacement therapy use in the glioma and meningioma models, respectively.

Results: In conditional logistic regression analysis, excluding drug use in the year preceding the index date, there was no association with non-aspirin NSAID use (OR 0.96, 95 % CI 0.81-1.13) or glioma risk comparing the highest category of daily defined dose to non-users; however, non-aspirin NSAID use was positively associated with meningioma risk (OR 1.35, 95 % CI 1.06-1.71). No association was seen with high- or low-dose aspirin use irrespective of histology.

Conclusions: This large nested case-control study finds no association between aspirin or non-aspirin NSAID use and risk of glioma but a slight increased risk with non-aspirin NSAIDs and meningioma. © 2013 Springer Science+Business Media Dordrecht.

TRACE observations of driven loop oscillations

Aims: On 13 June 1998, the TRACE satellite was fortuitously well placed to observe the effects of a flare-induced EIT wave in the corona, and its subsequent interaction with coronal magnetic loops. In this study, we use these TRACE observations to corroborate previous theoretical work, which determined the response of a coronal loop to a harmonic driver in the context of ideal magnetohydrodynamics, as well as estimate the magnetic field strength and the degree of longitudinal inhomogeneity. Methods: Loop edges are tracked, both spatially and temporally, using wavelet modulus maxima algorithms, with corresponding loop displacements from its quiescent state analysed by fitting scaled sinusoidal functions. The physical parameters of the coronal loop are subsequently determined using seismological techniques. Results: The studied coronal loop is found to oscillate with two distinct periods, 501 ± 5 s and 274 ± 7 s, which could be interpreted as belonging to the fundamental kink mode and first harmonic, or could reflect the stage of an overdriven loop. Additional scenarios for explaining the two periods are listed, each resulting in a different value of the magnetic field and the intrinsic and sub-resolution properties of the coronal loop. When assuming the periods belong to the fundamental kink mode and its first harmonic, we obtain a magnetic field strength inside the oscillating coronal loop of 2.0 ± 0.7 G. In contrast, interpreting the oscillations as a combination of the loop's natural kink frequency and a harmonic EIT wave provides a magnetic field strength of 5.8 ± 1.5 G. Using the ratio of the two periods, we find that the gravitational scale height in the loop is 73 ± 3 Mm. Conclusions: We show that the observation of two distinct periods in a coronal loop does not necessarily lead to a unique conclusion. Multiple plausible scenarios exist, suggesting that both the derived strength of the magnetic field and the sub-resolution properties of the coronal loop depend entirely on which interpretation is chosen. The interpretation of the observations in terms of a combination of the natural kink mode of the coronal loop, driven by a harmonic EIT wave seems to result in values of the magnetic field consistent with previous findings. Other interpretations, which are realistic, such as kink fundamental mode/first harmonic and the oscillations of two sub-resolution threads result in magnetic field strengths that are below the average values found before.

Age-Associated Changes of Brain Copper, Iron, and Zinc in Alzheimer's Disease and Dementia with Lewy Bodies

Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia with Lewy bodies (n = 15), and normal age-matched control subjects (n = 26). Copper was lower (20%; p < 0.001) and iron higher (10–16%; p < 0.001) in severe AD compared with controls. Intriguingly significant Group*Age interactions were observed for both copper and iron, suggesting gradual age-associated decline of these metals in healthy non-cognitively impaired individuals. Zinc was unaffected in any disease pathologies and no age-associated changes were apparent. Age-associated changes in brain elements warrant further investigation.

Analysis of Transonic Limit Cycle Oscillations under Uncertainty

For the computation of limit cycle oscillations (LCO) at transonic speeds, CFD is required to capture the nonlinear flow features present. The Harmonic Balance method provides an effective means for the computation of LCOs and this paper exploits its efficiency to investigate the impact of variability (both structural a nd aerodynamic) on the aeroelastic behaviour of a 2 dof aerofoil. A Harmonic Balance inviscid CFD solver is coupled with the structural equations and is validated against time marching analyses. Polynomial chaos expansions are employed for the stochastic investiga tion as a faster alternative to Monte Carlo analysis. Adaptive sampling is employed when discontinuities are present. Uncertainties in aerodynamic parameters are looked at first followed by the inclusion of structural variability. Results show the nonlinear effect of Mach number and it’s interaction with the structural parameters on supercritical LCOs. The bifurcation boundaries are well captured by the polynomial chaos.

Quantitative Measurement of [Na+] and [K+] in Postmortem Human Brain Tissue Indicates Disturbances in Subjects with Alzheimer's Disease and Dementia with Lewy Bodies

Alzheimer’s disease (AD) is associated with significant disturbances in the homeostasis of Na+ and K+ ions as well as reduced levels of Na+/K+ ATPase in the brain. This study used ICP-MS to accurately quantify Na+ and K+ concentrations in human postmortem brain tissue. We analyzed parietal cortex (Brodmann area 7) from 28 cognitively normal age-matched controls, 15 cases of moderate AD, 30 severe AD, and 15 dementia with Lewy bodies (DLB). Associations were investigated between [Na+] and [K+] and a number of variables including diagnosis, age, gender, Braak tangle stage, amyloid-β (Aβ) plaque load, tau load, frontal tissue pH, and APOE genotype. Brains from patients with severe AD had significantly higher (26%; p<0.001) [Na+] (mean 65.43 ± standard error 2.91 mmol/kg) than controls, but the concentration was not significantly altered in moderate AD or DLB. [Na+] correlated positively with Braak stage (r=0.45; p<0.0001), indicating association with disease severity. [K+] in tissue was 10% lower (p<0.05) in moderate AD than controls. However, [K+] in severe AD and DLB (40.97±1.31 mmol/kg) was not significantly different from controls. There was a significant positive correlation between [K+] and Aβ plaque load (r=0.46; p=0.035), and frontal tissue pH (r=0.35; p=0.008). [Na+] was not associated with [K+] across the groups, and neither ion was associated with tau load or APOE genotype. We have demonstrated disturbances of both [Na+] and [K+] in relation to the severity of AD and markers of AD pathology, although it is possible that these relate to late-stage secondary manifestations of the disease pathology.

Prediction of Limit Cycle Oscillations Using an Implicit Aeroelastic-Harmonic Balance Method

This work proposes a extends a novel approach to compute tran sonic Limit Cycle Oscillations using high fidelity analysis. CFD based Harmonic Balance methods have proven to be efficient tools to predict periodic phenomena. This paper’s contribution is to present a methodology to determine the unknown frequency of oscillations using an implicit for- mulation of the HB method to accurately capture Limit Cycle Oscillations (LCOs); this is achieved by defining a frequency updating procedure based on a coupled CFD/CSD Harmonic Balance formulation to find the LCO condition. A pitch/plunge aerofoil and respective linear structural models is used to exercise the new method. Results show consistent agreement between the proposed and time-marching methods for both LCO amplitude and frequency.

Investigation of Limit Cycle Oscillations Using Aeroelastic-Harmonic Balance Method

This work investigates limit cycle oscillations in the transonic regime. A novel approach to predict Limit Cycle Oscillations using high fidelity analysis is exploited to accelerate calculations. The method used is an Aeroeasltic Harmonic Balance approach, which has been proven to be efficient and able to predict periodic phenomena. The behaviour of limit cycle oscillations is analysed using uncertainty quantification tools based on polynomial chaos expansions. To improve the efficiency of the sampling process for the polynomial-chaos expansions an adaptive sampling procedure is used. These methods are exercised using two problems: a pitch/plunge aerofoil and a delta-wing. Results indicate that Mach n. variability is determinant to the amplitude of the LCO for the 2D test case, whereas for the wing case analysed here, variability in the Mach n. has an almost negligible influence in amplitude variation and the LCO frequency variability has an almost linear relation with Mach number. Further test cases are required to understand the generality of these results.

Prediction of limit cycle oscillations under uncertainty using a Harmonic Balance method

The Harmonic Balance method is an attractive solution for computing periodic responses and can be an alternative to time domain methods, at a reduced computational cost. The current paper investigates using a Harmonic Balance method for simulating limit cycle oscillations under uncertainty. The Harmonic Balance method is used in conjunction with a non-intrusive polynomial-chaos approach to propagate variability and is validated against Monte Carlo analysis. Results show the potential of the approach for a range of nonlinear dynamical systems, including a full wing configuration exhibiting supercritical and subcritical bifurcations, at a fraction of the cost of performing time domain simulations.

Bladder continence management in adult acquired brain injury

Purpose: Persistence of urinary incontinence post acquired brain injury (ABI) carries important prognostic significance. We undertook to document the incidence of urinary incontinence, its management and complications in rehabilitation inpatients following ABI and to assess adherence to post ABI bladder management guidelines. 

Method: A retrospective chart survey of a convenience sample of consecutive admissions to two adult neurorehabilitation units Forster Green Hospital, Belfast, and the Scottish Brain Injury Rehabilitation Service, Edinburgh (SBIRSE). Bladder continence and management on transfer to and discharge from rehabilitation, trial removal of catheter, use of bladder drill, ultrasound investigation, anticholinergic medication and complications were recorded. 

Results: One hundred and forty six patients were identified. Seventy-seven (52.7%) were independent and continent of urine at rehabilitation admission and 109 (74.7%) on discharge. In all, 13 patients had urinary tract infection, 7 had urethral stricture and 1 developed haematuria whilst catheterised. Ultrasound of renal tracts was underused. Trial removal of catheter after transfer to rehabilitation occurred at a median of 10 days. 

Conclusions: Urinary continence was achieved in almost half of incontinent ABI patients during rehabilitation. There is potential for increased use of investigation of the renal tracts. Rehabilitation physicians should consider urethral stricture in the management of continence post ABI. 

Implications for Rehabilitation:

- Persisting urinary incontinence post ABI is associated with increased morbidity.

- Urethral stricture is an under-recognised complication after ABI and should be considered as a potential cause of incontinence in this patient group.

- Gains in urinary continence are seen in patients post ABI, managed with various interventions.

- Goal setting offers an opportunity to focus on bladder management rather than simply continence and may allow improvement in rate of appropriate investigation