Impairment of cerebrovascular hemodynamics in patients with severe and milder forms of sickle cell disease

In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVRCBF and CVRATT) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbS beta(0)-thal), 20 patients with mild SCD (HbSC and HbS beta(+)-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBFpostACZ was linearly related to CBFpreACZ, CVRCBF decreased with disease severity. CVRATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBFpostACZ than men (p < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVRCBF and CVRATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.Neuro Imaging Researc

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

9 MJ/Pulse Air Core Compulsator

One of the most critical issues in taking electromagnetic gun technology from the laboratory to field applications is the compactness and portability of very high energy, pulsed power supplies. The air core compulsator which is under development at CEM-UT addresses these requirements. The rotor of this machine is made from fiber reinforced epoxy composites and spins at a tip speed of 500 m/s which is substantially higher than is possible with a ferromagnetic rotor. The higher tip speed greatly increases the energy density of the rotor thus reducing the size of the prime power source. The special structural features of this machine, the electrical design, and the cooling system design are discussed.Center for Electromechanic

Design of a Self-Excited, Air-Core Compulsator for a Skid-Mounted, Repetitive Fire 9 MJ Railgun System

The design of a lightweight, compulsator-driven 9-MJ electromagnetic (EM) launcher has been completed and is in the fabrication phase. Scheduled for initial field testing in early 1989, the system will be capable of firing a salvo of nine rounds in three minutes at muzzle velocities between 2.5 and 4.0 km/s. Prime power for the compulsator is supplied by a 5000-hp gas turbine engine through a gearbox and clutch arrangement, and auxiliary power is provided by a small 750-hp turbine. Electrical power generation and pulse conditioning for the launcher are performed by the compulsator, which features a self-excited, air-core magnetic circuit and selectively passive armature compensation designed to minimize peak projectile acceleration. Peak power from the machine is 27 GW, and a total of 30 MJ is extracted from the rotor during each firing of the gun. System mass, including gun, compulsator, prime power, and auxiliary systems, is less than 22 tons and will be mounted on a 36-ton concrete slab which simulates the mass of an armored vehicle on which the system will eventually be integratedCenter for Electromechanic

Design of a 20 GW, Self-Excited, Air-Core Compensated Pulsed Alternator Railgun Power Supply

A compact compensated pulsed alternator (compulsator) has been designed as a power supply for a 9 MJ kinetic energy railgun in conjunction with the Electromagnetic Gun Weapons System Program sponsored by the U.S. Army and the Defense Advanced Research Projects Agency. The prototype machine, which is presently in fabrication, is to operate at 8,600 rpm and has design ratings of 3.2 MA peak current and 20 GW peak power into the matched railgun load. Rotor kinetic energy at full speed is 210 MJ of which 30 MJ is delivered during the 6 ms discharge pulse. A two-pole configuration is used for pulse length considerations and selectively passive compensation is employed to produce a relatively flat pulse as required by the railgun to limit maximum projectile acceleration. Distinguishing features include an air core magnetic circuit, separate rotor armature windings for self-excitation and railgun firing, ambient temperature aluminum field coils, and excitation field magnetic energy recovery capability. The rotor is made by interference assembly of fiber reinforced epoxy composite rings and is supported by high strength metal stub shafts which are shielded from the excitation field by water cooled copper sleeves. Evacuation of the rotor cavity is required to reduce windage losses since the peripheral velocity of the rotor is about 500 m/s at full speed. Both rotor armature windings are formed from aluminum litz wire to minimize conductor mass and eddy current losses. A stationary compensating winding, used to control the internal impedance of the generator during a discharge, is supported by a laminated stainless steel stator structure to which the ambient temperature aluminum field coils are attached. Hydrostatic oil film bearings support the rotor and are sealed against the evacuated rotor cavity with segmented carbon ring seals. Separate brush mechanisms are employed to collect excitation and railgun currents. A unique transposition of brushring conductors in the main discharge circuit is used to ensure uniform current division between brushes. Self-excitation to a nominal 2.4 T air gap flux density is accomplished in the 800 ms prior to discharge by rectifying the 17 kV ac excitation armature output with a combination of series and parallel diodes. After the discharge, the diodes are triggered to regenerate the magnetic energy stored by the field coils back into the rotor. The compulsator mounts are designed to allow the machine to rotate against linear dampers during discharge to minimize peak torque transmission to the machine mount.Center for Electromechanic

Prevention and Noninvasive Management of Coronary Atherosclerosis in Patients with Diabetes

Diabetes mellitus (DM) is a worldwide epidemic. Its prevalence is rapidly increasing in both developing and developed countries. Coronary heart disease (CHD) is highly prevalent and is the major cause of morbidity and mortality in patients with diabetes. Individuals with prediabetes states, with or without known CHD, should undergo lifestyle modifications aimed at preventing DM. In patients with CHID and DM, routine use of aspirin and an angiotensin-converting enzyme inhibitor, along with strict glycemic, blood pressure, and lipid control, is strongly recommended. Intense insulin therapy may be needed for glycemic control, and high-dose statin therapy may be needed for lipid control. For blood pressure control, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are considered first-line therapy. Noncompliance with medications and/or lifestyle measures and, underprescription of evidence-based therapies remain important unsolved problems