Human DNA methylation data have been used to develop biomarkers of ageing, referred to as 'epigenetic clocks', which have been widely used to identify differences between chronological age and ...biological age in health and disease including neurodegeneration, dementia and other brain phenotypes. Existing DNA methylation clocks have been shown to be highly accurate in blood but are less precise when used in older samples or in tissue types not included in training the model, including brain. We aimed to develop a novel epigenetic clock that performs optimally in human cortex tissue and has the potential to identify phenotypes associated with biological ageing in the brain. We generated an extensive dataset of human cortex DNA methylation data spanning the life course (n = 1397, ages = 1 to 108 years). This dataset was split into 'training' and 'testing' samples (training: n = 1047; testing: n = 350). DNA methylation age estimators were derived using a transformed version of chronological age on DNA methylation at specific sites using elastic net regression, a supervised machine learning method. The cortical clock was subsequently validated in a novel independent human cortex dataset (n = 1221, ages = 41 to 104 years) and tested for specificity in a large whole blood dataset (n = 1175, ages = 28 to 98 years). We identified a set of 347 DNA methylation sites that, in combination, optimally predict age in the human cortex. The sum of DNA methylation levels at these sites weighted by their regression coefficients provide the cortical DNA methylation clock age estimate. The novel clock dramatically outperformed previously reported clocks in additional cortical datasets. Our findings suggest that previous associations between predicted DNA methylation age and neurodegenerative phenotypes might represent false positives resulting from clocks not robustly calibrated to the tissue being tested and for phenotypes that become manifest in older ages. The age distribution and tissue type of samples included in training datasets need to be considered when building and applying epigenetic clock algorithms to human epidemiological or disease cohorts.
AbstractAn efficient multiple tuned sloshing damper (MTSD) system is installed in a tall building in Toronto, Canada. The building is monitored before and after water is added to the tanks to measure ...wind-induced building motion, and evaluate the performance of the MTSD. To the authors’ knowledge, this is the first time an MTSD system has been installed in a tall building, and one of the few times the as-built performance of a tall building supplementary damping system has been evaluated and reported in the literature. Monitoring of the building motion before commissioning the MTSD indicated that the structural frequencies were very close to those originally predicted by the structural engineer’s finite element model. Only 0.8% inherent structural damping was measured for the first mode when the peak building acceleration was 7 milli-g. The measured and wind tunnel predicted wind-induced building accelerations are in good agreement. After commissioning the MTSD system, the measured building accelerations and MTSD wave heights are found to be well-aligned with predictions. Several techniques are used to evaluate the performance of the MTSD system using the measured data. Each technique confirms that the MTSD system reduced building accelerations by approximately 50%. Full-scale structural monitoring has therefore shown that MTSDs can significantly reduce the motion of tall buildings.
The use of voltages to control magnetisation via the inverse magnetostriction effect in piezoelectric/ferromagnet heterostructures holds promise for ultra-low energy information storage technologies. ...Epitaxial galfenol, an alloy of iron and gallium, has been shown to be a highly suitable material for such devices because it possesses biaxial anisotropy and large magnetostriction. Here we experimentally investigate the properties of galfenol/spacer/galfenol structures in which the compositions of the galfenol layers are varied in order to produce different strengths of the magnetic anisotropy and magnetostriction constants. Based upon these layers, we propose and simulate the operation of an information storage device that can operate as an energy efficient multilevel memory cell.
We demonstrate spin pumping, i.e., the generation of a pure spin current by precessing magnetization, without the application of microwave radiation commonly used in spin pumping experiments. We use ...femtosecond laser pulses to simultaneously launch the magnetization precession in each of two ferromagnetic layers of a galfenol-based spin valve and monitor the temporal evolution of the magnetizations. The spin currents generated by the precession cause a dynamic coupling of the two layers. This coupling has a dissipative character and is especially efficient when the precession frequencies in the two layers are in resonance, where coupled modes with strongly different decay rates are formed.
AbstractTuned mass dampers (TMDs) are increasingly being used to reduce the motion of tall buildings during common wind events. Despite TMDs receiving extensive theoretical research for many decades, ...dissemination of the practical aspects of designing and installing these devices is severely lacking. Since they are relatively new to the high-rise construction industry, TMD installations may be viewed by design and construction teams as having considerable risk. This paper describes the process of implementing a TMD in a tall building to demystify the devices for practicing structural engineers, architects, general contractors, and owners. It is hoped that this demystification will help these parties understand and control the real and perceived risks associated with TMD implementations. Since prescriptive, code-based procedures are unsuitable for TMD design, a performance-based design approach must be used to ensure the TMD attains specified performance objectives. The TMD implementation process is described in four phases: concept design, detailed design, fabrication and installation, and tuning and commissioning. This paper does not present new theoretical or experimental research but instead provides a broad, practical overview of real-world TMD installations for practitioners. The content of this paper has been obtained from the design and installation of dozens of TMDs in tall buildings around the world.
STREET A.F., COUPER J.W., LOVE A.W., BLOCH S., KISSANE D.W. & STREET B.C. (2010) European Journal of Cancer Care19, 234–242 Psychosocial adaptation in female partners of men with prostate cancer
The ...objective was to explore the psychosocial adaptation of female partners living with men with a diagnosis of either localized or metastatic prostate cancer. Semi‐structured qualitative interviews were conducted with 50 women at two time points (baseline and 6 months later). The interviews examined emotions, experiences, attitudes to sexual and continence issues and treatment decision making. As part of a larger prospective observational study, demographic data and scores for depression and anxiety were collected. Initial analysis demonstrated that the group of 11 women assessed as distressed on the anxiety and depression measures described reduced coping skills and poorer adaptation after 6 months. In contrast, the 39 women in the non‐distressed group reported emotional adaptation that fitted the Lazarus and Folkman pattern of coping through appraisal of the impact of the diagnosis on their partner and themselves, appraisal of coping strategies and reappraisal of the situation. A surprise finding was the high level of resilience displayed by majority of these women. Results suggest that a psychosocial intervention could strengthen healthy adaptation and provide better coping skills for distressed couples.
For many years, the Food and Drug Administration (FDA) regulated botanical dietary-supplement ingredients, in most circumstances, under the provisions for food additives of the Federal Food, Drug, ...and Cosmetic Act to ensure that they were safe and wholesome. Currently, dietary supplements (such as botanical products, vitamins and minerals, amino acids, and tissue extracts) are regulated under the Dietary Supplement Health and Education Act of 1994, which includes several provisions that apply only to dietary supplements and dietary ingredients of dietary supplements. Included in these provisions was the removal of the ingredients of dietary supplements from regulation as food additives and . . .
Diabet. Med. 29, e398–e401 (2012)
Background We describe an unplanned pregnancy in a 19‐year‐old with lipodystrophic diabetes caused by a mutation in the peroxisome proliferator‐activated receptor ...gamma (PPARG) gene. The pregnancy was complicated by poor compliance with treatment, severe hypertriglyceridaemia and pancreatitis.
Case report The patient presented at 6 weeks’ gestation with an HbA1c of 140 mmol/mol (15%), cholesterol 8.1 mmol/l and triglycerides 20.1 mmol/l. She wished to continue the pregnancy so lipid‐lowering therapy was discontinued. She was severely insulin resistant and poorly compliant with diet and medication. A continuous subcutaneous insulin infusion was required for efficient delivery of large doses of basal insulin, alongside injected mealtime boluses, (up to 300 units insulin per day). At 17 weeks’ gestation she developed acute pancreatitis secondary to hypertriglyceridaemia (triglycerides > 100 mmol/l) and required plasmapheresis. Lipid‐lowering therapy was reinstated in the third trimester and plasmapheresis was required repeatedly to maintain triglycerides < 10 mmol/l. Delivery was arranged at 32 weeks, because of deteriorating glycaemic and lipid control (blood pressure was normal). Following betamethasone for fetal lung maturation, 20 units/h of intravenous insulin were required to maintain glycaemic control. A baby boy with significant subsequent developmental delay was delivered.
Discussion The features of PPARG mutations are discussed, with literature on lipodystrophy and pancreatitis in pregnancy reviewed. There are few documented cases of pregnancy in women with PPARG mutations. The notable features of this case include the consequences of non‐concordance with treatment, the use of continuous subcutaneous insulin infusion to treat insulin‐resistant diabetes and the need for repeated plasmapheresis during pregnancy to avert pancreatitis.
Abstract Background Long-term survival of knee replacement depends on accurate alignment. Despite improvements in cut accuracy mal-alignment of 3° or more is still seen. All methods share common ...implantation techniques. This study examines the effect of implantation on overall limb alignment relating it to cut alignment and trial alignment. Methods A retrospective review of navigated primary knee replacements was undertaken (n = 113). Overall coronal limb alignments for the aggregated cuts, trial and final implanted components were examined. Results All 113 knees had coronal aggregated cut alignment within 2° of neutral (range: 2° varus to 2° valgus). With trial components 99 knees (88%) had an overall coronal limb alignment within 2° of neutral (range: 3° varus to 4° valgus). After final implantation 106 knees (94%) were within 2° of neutral (range: 4° varus to 4° valgus). Forty eight knees (42%) showed no alignment deviation occurring between trial and the final implanted prostheses and 16 knees (14%) shoed a deviation of 2° or more. There was a correlation of both aggregated cut (r = 0.284, p = 0.002) and trial (r = 0.794, p < 0.001) with final alignment. There was no significant difference between the final alignment and the aggregated cut alignment(mean difference = − 0.15°, p = 0.254) or trial alignment (mean difference − 0.13°, p = 0.155). Conclusions Even when the aggregated alignment produced by the bone cuts is accurate, inaccuracy in final alignment can result from the implantation process. It may be productive for surgeons to concentrate on the implantation process to improve alignment and reduce outliers.
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