The atherogenic lipoprotein phenotype in renal disease

Nephrotic range proteinuria and chronic renal failure are associated with both qualitative and quantitative changes in lipoproteins and increased cardiovascular risk. LDL exhibits heterogeneity with increased small dense LDL (LDLIII) associated with increased risk of coronary heart disease (CHD). In normal populations, production of small dense LDL is physiologically linked to mild hypertriglyceridaemia and low HDL, a combination that has been labelled 'the atherogenic lipoprotein phenotype'. This thesis aimed to explore abnormalities in the metabolism of triglyceride-rich lipoproteins in patients with chronic renal dysfunction, with particular reference to changes in LDL subfraction distribution and remnant lipoprotein particles. The main population investigated were patients with nephrotic range proteinuria secondary to primary glomerular disease, however this work was extended to examine changes in lipoproteins in patients with proteinuria secondary to diabetic nephropathy in type 2 diabetes, and also patients with end-stage renal failure. Our hypothesis was that in patients with proteinuria, hypertriglyceridaemia occurs as a result of impaired catabolism of VLDL. The consequence is the generation of small dense LDL (LDLIII) and remnant lipoproteins, both of which are pathogenic agents which may contribute to accelerated vascular disease and to the rate of progression of renal failure. Quantitative analysis of both LDLIII and remnant lipoproteins was performed in 27 patients with nephrotic range proteinuria and well preserved renal function. This revealed a marked increased in plasma LDLIII concentration, to levels that are noted to be atherogenic in normal populations. This increase primarily due to a shift in particle size towards smaller denser particles. Remnant lipoproteins (RLP) were V similarly increased in proteinuric patients. The excess of both of these atherogenic particles was independently related to the increase in plasma triglyceride prevalent in this population, an increase that previously been demonstrated to result in part, from delayed clearance of the VLDL1 subfraction of very-low density lipoprotein (VLDL). The 27 patients studied were found to have normal in vitro lipase activity, however marked abnormalities in the lipid and apolipoprotein content of the VLDLI particles was observed. Despite apparently normal plasma concentration of both apolipoprotein (apo) CII and apoCIII, the patients with proteinuria possessed VLDLI particles that were deficient in both of these apolipoproteins. This deficiency was accompanied by a relative deficiency in both plasma and VLDLI apoE. VLDLI particles were also found to be smaller than those in the control group with a higher surface ratio of free cholesterol: phospholipid. The presence of smaller, free cholesterol enriched, apolipoprotein deficient particles could easily account for the observed delay in clearance of VLDLI observed in this population. 12 patients with >1.5g/24hrs of urinary albumin, hypercholesterolaemia and plasma triglyceride >1.5mmol/l were studied in a randomised crossover trial comparing the effects of a statin (cerivastatin) and a fibrate (fenofibrate) on the concentration of LDLIII and remnant lipoproteins (RLP). Fenofibrate produced a significant reduction in both LDLIII and RLP. Cerivastatin reduced LDLIII but not RLP, moreover the reduction in LDLIII was greater on fenofibrate than following cerivastatin. The two treatments also differed in the manner in which plasma LDLIII was reduced, thus the reduction in LDLIII following fenofibrate correlated with plasma triglyceride reduction whilst the LDLIII reduction on cerivastatin was associated with LDL-C reduction. Therefore fenofibrate seemed to reduce LDLIII by removing the excess triglyceride essential for formation of small dense LDL, with cerivastatin reducing LDLIII by decreasing the total amount of LDL present. (Abstract shortened by ProQuest.)

Applications of Wavelet Transforms to the Suppression of Coherent Noise from Seismic Data in the Pre-Stack Domain

The wavelet transform, a relatively new mathematical technique, allows the analysis of non-stationary signals by using basis functions which are compact in time and frequency. The variables in the wavelet domain, scale (a frequency range), and translation (a temporal increment) can be associated with time-frequency, and so in the wavelet transform we have the potential to filter seismic signals in a pseudo time-frequency sense. The one dimensional discrete multiresolution form of the wavelet transform can be effectively used to suppress low frequency coherent noise on seismic shot records. This process, achieved by the muting or weighting of coefficients in the wavelet transform domain, is demonstrated by suppressing low velocity, low frequency ground roll from land- based seismic data, the benefits of which are visible at both the shot and stack stages of the seismic processing stream. The extension of this technique to the suppression of higher frequency coherent noise is limited by the octave band splitting of frequency space by the transform. The wavelet packet transform, an extension of the wavelet transform, allows a more adaptable tiling of the time frequency domain which in turn allows the suppression of noise containing high frequencies whilst minimising signal distortion. This technique is demonstrated to be effective in suppressing airblast from land based common receiver gathers, whilst minimising the distortion of reflected signals. These filtering techniques can be extended to two dimensions, filtering data in the two dimensional wavelet and wavelet packet domains. This technique involves muting the transform coefficients in the wavelet/wavelet packet transform space which has four variables: temporal translation, offset translation, frequency scale and wavenumber scale. As for the one-dimensional case the two dimensional wavelet transform suffers from poor resolution due to the octave splitting of f-k space, but when used in combination with a velocity based shift such as normal moveout, can be used to filter data with minimal distortion to the residual signal. Extending the process to using the two-dimensional wavelet packet transform eliminates the shift requirement and leads to more effective filtering in the four variable transform space. The wavelet packet filtering technique is effective in suppressing low velocity noise from land based seismic records showing visible improvement in both the common shot records and resultant stack. The non-stationary properties of the wavelet transform allows the filtering across geophone arrays (that is, the common shot record) by the application of the transform in the offset domain. Filtering of the wavelet coefficients, in combination with a linear or hyperbolic shift applied before and removed after filtering, allows discrimination against linear noise on common shot records associated with first breaks and hyperbolic events on common midpoint records such as multiples. The use of a simple muting technique in the wavelet domain effectively suppresses these forms of coherent noise. Where the velocity contrast between signal and noise is high, noise suppression is possible whilst preserving reflector amplitudes. Where the velocity contrast is smaller, weighting of the wavelet coefficients (based on transforms of the input signal after translation) allows noise suppression whilst preserving the amplitude versus offset relationships of the primary signal. This is shown to be effective on synthetic, marine and land based data, with improvements observed on common shot records and resultant stacks. The results of all these wavelet transform based filtering techniques are sensitive to the choice of wavelet transform kernel wavelet. The suitability of a kernel wavelet for filtering can be related to the frequency spectra of the kernel wavelet. A fast rate of frequency amplitude fall-off at the edge of a given scale of basis wavelet minimises frequency overlap between neighbouring kernel wavelet scales and so minimises contamination by noise associated with aliasing in the filtered signal, a process that is inherent in the transform process. A flat amplitude response across the frequency range of a given scale also leads to improved filtering results

Obstetric and long-term kidney outcomes in renal transplant recipients: a 40 year single-centre study

Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case−cohort study was performed identifying 83 pairs of pregnant and non-pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre-eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre-pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non-pregnant controls and a pregnancy was not associated with poorer 10-yr transplant or 20-yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long-term transplant function

Reproducibility of an isokinetic eccentric muscle endurance task

Despite the widespread use of isokinetic eccentric muscle endurance protocols, no research has examined the absolute and relative reliability of such tests. The aim of this study was to examine the reliability of an isokinetic eccentric knee muscle endurance task. Fifteen healthy untrained males volunteered to take part in the study and written informed consent was obtained. The procedures received approval from the University Research Ethics Committee. Participants visited the laboratory on three separate occasions: 2 weeks before testing to familiarize them with the experimental procedures, and on two separate occasions, 2 weeks apart and at the same time of day. Isokinetic eccentric knee extension and flexion movements of the dominant limb were performed using a calibrated dynamometer (Biodex System 3). Range of motion during testing was set using voluntary maximal full extension (0 rad) to 1.57 rad of knee flexion and testing was conducted at 1.56 rad . s(-1). Participants performed four maximal efforts to determine maximal peak torque. After 2 min rest, participants completed the all-out endurance test of 50 continuous eccentric repetitions. Data were gravity corrected and windowed to only include constant velocity periods. Repeated-measures analyses of variance were used to examine differences in maximal peak extension and flexion torque and the maximal torque measurement recorded during the endurance test. Absolute and relative reliability of the torque fatigue index, work fatigue index, and total work were assessed through calculation of intra-class correlation coefficients, coefficients of variation, and absolute 95% limits of agreement using the methods described by Bland and Altman (1986). Differences between the strength test and the endurance trial for peak torque were found to be non-significant for both quadriceps (323 vs. 323 N . m) and hamstrings (183 vs. 178 N . m). The intra-class correlation coefficients revealed significant (P<0.05) positive moderate to strong correlations (r=0.44-0.94) across repeated trials for all parameters except hamstring torque fatigue (P=0.11) and hamstring work fatigue index (P=0.08). Coefficients of variation ranged from 6% to 48% and were large for the work fatigue index and torque fatigue index but acceptable for total work for both the extensors and flexors. The 95% limits of agreement indicated systematic bias in repeated trials for both the work fatigue index and torque fatigue index for extensors and flexors, ranging from -3% to -10%, with less fatigue evident in the second test. There was also systematic bias for total work, with more work being performed during the second than the first test for both extensors and flexors. The random error was large for all variables and there was greater random error in the hamstrings compared with the quadriceps. Together with moderate to strong intra-class correlation coefficients and large coefficients of variation, the data suggest that there is small systematic bias in repeated eccentric muscle actions for both the quadriceps and hamstrings, although the random error was large despite habituation procedures. Therefore, data from an isokinetic eccentric muscle endurance task should be viewed with some caution even when participants receive considerable habituation before assessment

'Nordic' Hamstrings Exercise - Engagement Characteristics and Training Responses

The present study examined the neuromuscular activation characteristics of the hamstrings during the 'Nordic' hamstrings exercise (NHE) and changes in the eccentric strength of the knee flexors with NHE training. Initially, the normalised root mean square electromyographic (EMG) activity of the hamstrings of both limbs during various phases (90-61 degrees, 60-31 degrees and 30-0 degrees of knee extension) of the NHE were determined in 18 soccer players. Subsequently participants were randomly allocated to either a training (n = 10) or control group. The isokinetic eccentric peak torques of the dominant and non-dominant limbs were recorded at 60, 120 and 240 degrees/s pre- and post-training. The EMG values of both limbs were comparable (P = 0.184) and greater EMG activity was recorded at more extended knee positions of the NHE (P = 0.001). 4 weeks of NHE training significantly improved peak torque by up to 21% in all assessment conditions. Data indicate the hamstrings of both limbs are engaged identically during the NHE and training results in gains in the eccentric peak torque of the hamstrings of both limbs; these gains may augment the force that the hamstrings can withstand when forcefully stretched, attenuating injury risk

Proton Aurora on Mars: A Dayside Phenomenon Pervasive in Southern Summer

We present observations of proton aurora at Mars made using the Imaging UltraViolet Spectrograph (IUVS) onboard the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft. Martian proton aurora display a prominent intensity enhancement in the hydrogen Lyman‐alpha (121.6 nm) emission between ~110 and 150 km altitude. Using altitude‐intensity profiles from periapsis limb scan data spanning nearly two Martian years, we create a comprehensive database of proton aurora and characterize their phenomenology. Due to Mars\u27 lack of a global dipole magnetic field, Martian proton aurora are expected to form on the dayside via electron stripping and charge exchange between solar wind protons and the neutral corona. We observe proton aurora in ~14% of dayside periapsis profiles (with notable seasonal variability), making proton aurora the most commonly observed type of aurora at Mars. We determine that the primary factors influencing proton aurora occurrence rates are solar zenith angle and season. The highest proton aurora occurrence rates are at low solar zenith angles on the Mars dayside, consistent with known formation processes. Proton aurora have highest emission enhancements, peak intensities, peak altitudes, and occurrence rates (nearing 100%) around southern summer solstice. This time period corresponds with the seasonal inflation of the neutral lower atmosphere, the onset of Martian dust storm season, seasonally increased coronal hydrogen column densities, and higher atmospheric temperature and solar wind flux following perihelion. The results of our study provide a new understanding of the primary factors influencing proton aurora, and the long‐term variability of these phenomena as observed over multiple Mars years

Hot oxygen escape from Mars: Simple scaling with solar EUV irradiance

The evolution of the atmosphere of Mars and the loss of volatiles over the lifetime of the solar system is a key topic in planetary science. An important loss process for atomic species, such as oxygen, is ionospheric photochemical escape. Dissociative recombination of O2+ ions (the major ion species) produces fast oxygen atoms, some of which can escape from the planet. Many theoretical hot O models have been constructed over the years, although a number of uncertainties are present in these models, particularly concerning the elastic cross sections of O atoms with CO2. Recently, the Mars Atmosphere and Volatile Evolution mission has been rapidly improving our understanding of the upper atmosphere and ionosphere of Mars and its interaction with the external environment (e.g., solar wind), allowing a new assessment of this important loss process. The purpose of the current paper is to take a simple analytical approach to the oxygen escape problem in order to (1) study the role that variations in solar radiation or solar wind fluxes could have on escape in a transparent fashion and (2) isolate the effects of uncertainties in oxygen cross sections on the derived oxygen escape rates. In agreement with several more elaborate numerical models, we find that the escape flux is directly proportional to the incident solar extreme ultraviolet irradiance and is inversely proportional to the backscatter elastic cross section. The amount of O lost due to ion transport in the topside ionosphere is found to be about 5–10% of the total.Key PointsPhotochemistry dominates oxygen escape from MarsMartian oxygen escape rate scales linearly with solar activityDependence of O escape rate from Mars on elastic cross section is describedPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136315/1/jgra53155.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136315/2/jgra53155_am.pd

Martian Thermospheric Warming Associated With the Planet Encircling Dust Event of 2018

We report the first observations of Martian thermospheric warming associated with the Planet Encircling Dust Event (PEDE) of 2018. We used dayglow observations made by the Imaging Ultraviolet Spectrograph instrument aboard the MAVEN spacecraft to retrieve the upper atmosphere temperature structures. Our analysis shows that the two‐cell meridional circulation pattern may be operating before the PEDE‐2018, which resulted in the cooling of lower/middle latitudes and warming at higher latitudes. However, after the onset, the existing circulation pattern gets dampened, resulted in a weaker latitudinal temperature structure. We saw that mean temperatures rose by about 20 K for the same local time after the onset of the dust storm. Our 3‐D Mars General Ionosphere Thermosphere Model calculations were able to reproduce the temperatures during the predust and early dust storm but failed to fully capture the temperature trend during the growth phase of the PEDE of 2018.Key PointsThe IUVS Observations show potential thermospheric warming associated with a global dust stormOur analysis shows active two-cell meridional circulation in the Martian thermosphere before the PEDE-2018Temperature observations show breakdown of nominal circulation during the dust stormPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154332/1/grl60064.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154332/2/grl60064_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154332/3/grl60064-sup-0002-Table_SI-S01.pd

Hot oxygen escape from Mars: Simple scaling with solar EUV irradiance

The evolution of the atmosphere of Mars and the loss of volatiles over the lifetime of the solar system is a key topic in planetary science. An important loss process for atomic species, such as oxygen, is ionospheric photochemical escape. Dissociative recombination of O2+ ions (the major ion species) produces fast oxygen atoms, some of which can escape from the planet. Many theoretical hot O models have been constructed over the years, although a number of uncertainties are present in these models, particularly concerning the elastic cross sections of O atoms with CO2. Recently, the Mars Atmosphere and Volatile Evolution mission has been rapidly improving our understanding of the upper atmosphere and ionosphere of Mars and its interaction with the external environment (e.g., solar wind), allowing a new assessment of this important loss process. The purpose of the current paper is to take a simple analytical approach to the oxygen escape problem in order to (1) study the role that variations in solar radiation or solar wind fluxes could have on escape in a transparent fashion and (2) isolate the effects of uncertainties in oxygen cross sections on the derived oxygen escape rates. In agreement with several more elaborate numerical models, we find that the escape flux is directly proportional to the incident solar extreme ultraviolet irradiance and is inversely proportional to the backscatter elastic cross section. The amount of O lost due to ion transport in the topside ionosphere is found to be about 5–10% of the total