Variability and origin of seismic anisotropy across eastern Canada: evidence from shear-wave splitting measurements

Measurements of seismic anisotropy in continental regions are frequently interpreted with respect to past tectonic processes, preserved in the lithosphere as “fossil” fabrics. Models of the present-day sublithospheric flow (often using absolute plate motion as a proxy) are also used to explain the observations. Discriminating between these different sources of seismic anisotropy is particularly challenging beneath shields, whose thick (≥200 km) lithospheric roots may record a protracted history of deformation and strongly influence underlying mantle flow. Eastern Canada, where the geological record spans ∼3 Ga of Earth history, is an ideal region to address this issue. We use shear wave splitting measurements of core phases such as SKS to define upper mantle anisotropy using the orientation of the fast-polarization direction ϕ and delay time δt between fast and slow shear wave arrivals. Comparison with structural trends in surface geology and aeromagnetic data helps to determine the contribution of fossil lithospheric fabrics to the anisotropy. We also assess the influence of sublithospheric mantle flow via flow directions derived from global geodynamic models. Fast-polarization orientations are generally ENE-WSW to ESE-WNW across the region, but significant lateral variability in splitting parameters on a ≤100 km scale implies a lithospheric contribution to the results. Correlations with structural geologic and magnetic trends are not ubiquitous, however, nor are correlations with geodynamically predicted mantle flow directions. We therefore consider that the splitting parameters likely record a combination of the present-day mantle flow and older lithospheric fabrics. Consideration of both sources of anisotropy is critical in shield regions when interpreting splitting observations

Understanding the links between hearing impairment and dementia : development and validation of the social and emotional impact of hearing impairment (SEI-HI) questionnaire

Background The links between hearing impairment (HI) and dementia have been well documented, but factors mediating this relationship remain unknown. Major consequences of HI are social and emotional dysfunction, and as the risk of dementia increases linearly with the severity of HI, it is plausible that socio-emotional difficulties may play a role in this association. Objective The aim of this study was to develop and validate a tool to analyse levels of hearing-related disability, to investigate ultimately whether subjective disability contributes to risk of cognitive impairment compared with hearing thresholds alone. Methods Development and validation of the questionnaire, the Social and Emotional Impact of Hearing Impairment (SEI-HI), was conducted in four phases: (1) content; (2) scoring and outcomes; (3) validation; (4) feasibility in a sample of people with cognitive impairment. Results Considerable evidence was found for the internal and external reliability of the tool with high construct validity, concurrent validity and test-retest values of the SEI-HI questionnaire. A feasibility check on 31 patients with mild cognitive impairment or dementia showed the SEI-HI questionnaire was easy to administer and well-received. Conclusion The SEI-HI questionnaire is a relevant instrument to assess hearing-related disability which can be used in people with cognitive decline to assess further impact on risk of developing dementia

Material Need Insecurities, Control of Diabetes Mellitus, and Use of Health Care Resources: Results of the Measuring Economic Insecurity in Diabetes Study

Increasing access to care may be insufficient to improve health for diabetes patients with unmet basic needs. However, how specific material need insecurities relate to clinical outcomes and care utilization in a setting of near-universal care access is unclear

Auditory and cognitive training for cognition in adults with hearing loss: a systematic review and meta-analysis

This systematic review and meta-analysis examined the efficacy of auditory training and cognitive training to improve cognitive function in adults with hearing loss. A literature search of academic databases (e.g., MEDLINE, Scopus) and gray literature (e.g., OpenGrey) identified relevant articles published up to January 25, 2018. Randomized controlled trials (RCTs) or repeated measures designs were included. Outcome effects were computed as Hedge’s g and pooled using random-effects meta-analysis (PROSPERO: CRD42017076680). Nine studies, five auditory training, and four cognitive training met the inclusion criteria. Following auditory training, the pooled effect was small and statistically significant for both working memory (g = 0.21; 95% CI [0.05, 0.36]) and overall cognition (g = 0.19; 95% CI [0.07, 0.31]). Following cognitive training, the pooled effect for working memory was small and statistically significant (g = 0.34; 95% CI [0.16, 0.53]), and the pooled effect for overall cognition was large and significant (g = 1.03; 95% CI [0.41, 1.66]). However, this was dependent on the classification of training approach. Sensitivity analyses revealed no statistical difference between the effectiveness of auditory and cognitive training for improving cognition upon removal of a study that used a combined auditory–cognitive approach, which showed a very large effect. Overall certainty in the estimation of effect was “low” for auditory training and “very low” for cognitive training. High-quality RCTs are needed to determine which training stimuli will provide optimal conditions to improve cognition in adults with hearing loss

Enhanced killing of androgen-independent prostate cancer cells using inositol hexakisphosphate in combination with proteasome inhibitors

Effective treatments for androgen-independent prostate cancer (AIPCa) are lacking. To address this, emerging therapeutics such as proteasome inhibitors are currently undergoing clinical trials. Inositol hexakisphosphate (IP6) is an orally non-toxic phytochemical that exhibits antitumour activity against several types of cancer including PCa. We have previously shown that treatment of PC3 cells with IP6 induces the transcription of a subset of nuclear factor-κB (NF-κB)-responsive and pro-apoptotic BCL-2 family genes. In this study, we report that although NF-κB subunits p50/p65 translocate to the nucleus of PC3 cells in response to IP6, inhibition of NF-κB-mediated transcription using non-degradable inhibitor of κB (IκB)-α does not modulate IP6 sensitivity. Treatment with IP6 also leads to increased protein levels of PUMA, BIK/NBK and NOXA between 4 and 8 h of treatment and decreased levels of MCL-1 and BCL-2 after 24 h. Although blocking transcription using actinomycin D does not modulate PC3 cell sensitivity to IP6, inhibition of protein translation using cycloheximide has a significant protective effect. In contrast, blocking proteasome-mediated protein degradation using MG-132 significantly enhances the ability of IP6 to reduce cellular metabolic activity in both PC3 and DU145 AIPCa cell lines. This effect of combined treatment on mitochondrial depolarisation is particularly striking and is also reproduced by another proteasome inhibitor (ALLN). The enhanced effect of combined MG132/IP6 treatment is almost completely inhibited by cycloheximide and correlates with changes in BCL-2 family protein levels. Altogether these results suggest a role for BCL-2 family proteins in mediating the combined effect of IP6 and proteasome inhibitors and warrant further pre-clinical studies for the treatment of AIPCa

Arginine in Membranes: The Connection Between Molecular Dynamics Simulations and Translocon-Mediated Insertion Experiments

Several laboratories have carried out molecular dynamics (MD) simulations of arginine interactions with lipid bilayers and found that the energetic cost of placing arginine in lipid bilayers is an order of magnitude greater than observed in molecular biology experiments in which Arg-containing transmembrane helices are inserted across the endoplasmic reticulum membrane by the Sec61 translocon. We attempt here to reconcile the results of the two approaches. We first present MD simulations of guanidinium groups alone in lipid bilayers, and then, to mimic the molecular biology experiments, we present simulations of hydrophobic helices containing single Arg residues at different positions along the helix. We discuss the simulation results in the context of molecular biology results and show that the energetic discrepancy is reduced, but not eliminated, by considering free energy differences between Arg at the interface and at the center of the model helices. The reduction occurs because Arg snorkeling to the interface prevents Arg from residing in the bilayer center where the energetic cost of desolvation is highest. We then show that the problem with MD simulations is that they measure water-to-bilayer free energies, whereas the molecular biology experiments measure the energetics of partitioning from translocon to bilayer, which raises the fundamental question of the relationship between water-to-bilayer and water-to-translocon partitioning. We present two thermodynamic scenarios as a foundation for reconciliation of the simulation and molecular biology results. The simplest scenario is that translocon-to-bilayer partitioning is independent of water-to-bilayer partitioning; there is no thermodynamic cycle connecting the two paths