Reduced estimated glomerular filtration rate in Alzheimer's disease

OBJECTIVES:

Renal disease is increasingly regarded as an independent risk factor for vascular disease which in itself is believed to influence risk of AD. Alterations in amyloid homeostasis via reduced renal clearance of peripheral beta-amyloid (A|*beta*|) may represent another potential role for variation in renal function leading to increased risk of AD. We sought to examine estimates of glomerular filtration rate in AD and control groups.
METHODS:

AD patients were randomly recruited from the Memory Clinic of the Belfast City Hospital (n = 83). Genomic DNA was extracted from peripheral leucocytes and was genotyped for Apolipoprotein E using standard methods. Using creatinine values, age and gender, estimated Glomerular Filtration Rates (eGFR) were calculated using the isotope dilution mass spectrometry (IDMS)-traceable Modification of Diet in Renal Disease (MDRD) Study equation (using the United Kingdom National External Quality Assessment Scheme (UKNEQAS) correction factor). IDMS eGFR values were then compared between AD and control groups.

RESULTS:

Significant baseline differences in age, diastolic blood pressure, education level attained and APOE |*epsilon*|4 carriage were noted between cases and controls. The AD group had a significantly lower eGFR versus controls (69 vs 77 ml/min) which persisted after adjustment for possible confounders (p = 0.045).

CONCLUSIONS:

This case-control analysis suggests that using a relatively accurate estimate of renal function, patients with AD have greater renal impairment than cognitively normal controls. This may reflect impaired renal clearance of peripheral A|*beta*| or be a marker of shared vascular processes altering cerebral and renal functioning.

Radiotherapy in the presence of contrast agents: a general figure of merit and its application to gold nanoparticles

Delivering sufficient dose to tumours while sparing surrounding tissue is one of the primary challenges of radiotherapy, and in common practice this is typically achieved by using highly penetrating MV photon beams and spatially shaping dose. However, there has been a recent increase in interest in the possibility of using contrast agents with high atomic number to enhance the dose deposited in tumours when used in conjunction with kV x-rays, which see a significant increase in absorption due to the heavy element's high-photoelectric cross-section at such energies. Unfortunately, the introduction of such contrast agents significantly complicates the comparison of different source types for treatment efficacy, as the dose deposited now depends very strongly on the exact composition of the spectrum, making traditional metrics such as beam quality less valuable. To address this, a 'figure of merit' is proposed, which yields a value which enables the direct comparison of different source types for tumours at different depths inside a patient. This figure of merit is evaluated for a 15 MV LINAC source and two 150 kVp sources (both of which make use of a tungsten target, one with conventional aluminium filtration, while the other uses a more aggressive thorium filter) through analytical methods as well as numerical models, considering tissue treated with a realistic concentration and uptake ratio of gold nanoparticle contrast agents (10 mg ml(-1) concentration in 'tumour' volume, 10: 1 uptake ratio). Finally, a test case of human neck phantom is considered with a similar contrast agent to compare the abstract figure to a more realistic treatment situation. Good agreement was found both between the different approaches to calculate the figure of merit, and between the figure of merit and the effectiveness in a more realistic patient scenario. Together, these observations suggest that there is the potential for contrast-enhanced kilovoltage radiation to be a useful therapeutic tool for a number of classes of tumour on dosimetric considerations alone, and they point to the need for further research in this area.

Compact ridge waveguide filter with parallel and series-coupled resonators

A novel 3rd-order compact E-plane ridge waveguide filter is presented. Miniaturization is achieved upon introducing a configuration of parallel-coupled E-plane ridge waveguide resonators. Furthermore, the proposed filter allows for transmission zeros at finite frequencies. Fabrication simplicity and mass producibility of standard E-plane filters is maintained. The numerical and experimental results are presented to validate the proposed configuration. A miniaturisation factor of 2 and very sharp upper cutoff are achieved. 2005 Wiley Periodicals, Inc.

Novel periodically loaded E-plane filters

Novel E-plane waveguide filters with periodically loaded resonators are proposed. The proposed filters make use of the slow wave effect in order to achieve improved stopband performance and size reduction of roughly 50% without introducing any complexity in the fabrication process. Numerical and experimental results are presented to validate the argument.

Effectiveness of filters in reducing consolidation time in routine laboratory testing

The research reported here is based on the standard laboratory experiments routinely performed in order to measure various geotechnical parameters. These experiments require consolidation of fine-grained samples in triaxial or stress path apparatus. The time required for the consolidation is dependent on the permeability of the soil and the length of the drainage path. The consolidation time is often of the order of several weeks in large clay-dominated samples. Long testing periods can be problematic, as they can delay decisions on design and construction methods. Acceleration of the consolidation process would require a reduction in effective drainage length and this is usually achieved by placing filter drains around the sample. The purpose of the research reported in this paper is to assess if these filter drains work effectively and, if not, to determine what modifications to the filter drains are needed. The findings have shown that use of a double filter reduces the consolidation time several fold.

The finding of reduced estimated glomerular filtration rate is associated with increased mortality in a large UK population

BACKGROUND: CKD as defined by KDIGO/KDOQI has been shown to affect ~ 8.5% of the UK population. The prevalence of CKD in the UK is similar to that in the USA, yet incident dialysis rates are dramatically different. This retrospective cohort study investigates the association between reduced kidney function and mortality in a large UK population. METHODS: All serum creatinine results covering Northern Ireland's 1.7 million population were collected between 1 January 2001 and 31 December 2002. Estimated glomerular filtration rates (eGFR) were calculated for all serum creatinine measurements using four-variable MDRD equation (IDMS aligned). Patients were followed up for both all-cause and cardiovascular mortality data until the end of December 2006. Patients on renal replacement therapy were excluded. Subgroup analysis in the 75 345 subjects enrolled within a parallel primary care study permitted additional survival analysis with adjustment for traditional cardiovascular risk factors. RESULTS: A total of 1 967 827 serum creatinine results from 533 798 patients were collected. During the period of follow-up, 59 980 deaths occurred. In multivariate survival analysis, using eGFR as a time-varying covariate, a graded association between CKD (defined by eGFR) and all-cause mortality was identified. Compared with participants with an eGFR of > 60 mL/min/1.73 m(2), the adjusted hazard ratios (and 95% confidence intervals) for participants with an eGFR of 45-59 mL/min/1.73 m(2) was 1.02 (0.99-1.04), an eGFR of 30-44 mL/min/1.73 m(2) was 1.44 (1.40-1.47), an eGFR of 15-29 mL/min/1.73 m(2) was 2.12 (2.05-2.20) and an eGFR of

Prevalence and Management of Anaemia in Renal Transplant Recipients: Data from Ten European Centres.

Background: Although it is a known predictor of mortality, there is a relative lack of recent information about anaemia in kidney transplant recipients. Thus, we now report data about the prevalence and management of post-transplant anaemia (PTA) in Europe 5 years after the TRansplant European Survey on Anemia Management (TRESAM) study. Methods: In a cross-sectional study enrolling the largest number of patients to date, data were obtained from 5,834 patients followed at 10 outpatient transplant clinics in four European countries using the American Society of Transplantation anaemia guideline. Results: More than one third (42%) of the patients were anaemic. The haemoglobin (Hb) concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (r = 0.4, p < 0.001). In multivariate analysis, eGFR, serum ferritin, age, gender, time since transplantation and centres were independently and significantly associated with Hb. Only 24% of the patients who had a Hb concentration <110 g/l were treated with an erythropoiesis-stimulating agent. The prevalence of anaemia and also the use of erythropoiesis-stimulating agents were significantly different across the different centres, suggesting substantial practice variations. Conclusions: PTA is still common and under-treated. The prevalence and management of PTA have not changed substantially since the TRESAM survey.

Robust Estimation of HDR in fMRI using H∞ Filters

Estimation and detection of the hemodynamic response (HDR) are of great importance in functional MRI (fMRI) data analysis. In this paper, we propose the use of three H 8 adaptive filters (finite memory, exponentially weighted, and time-varying) for accurate estimation and detection of the HDR. The H 8 approach is used because it safeguards against the worst case disturbances and makes no assumptions on the (statistical) nature of the signals [B. Hassibi and T. Kailath, in Proc. ICASSP, 1995, vol. 2, pp. 949-952; T. Ratnarajah and S. Puthusserypady, in Proc. 8th IEEE Workshop DSP, 1998, pp. 1483-1487]. Performances of the proposed techniques are compared to the conventional t-test method as well as the well-known LMSs and recursive least squares algorithms. Extensive numerical simulations show that the proposed methods result in better HDR estimations and activation detections.

Characterisation of virus transport and attenuation in epikarst using short pulse and prolonged injection multi-tracer testing

Attenuation processes controlling virus fate and transport in the vadose zone of karstified systems can strongly influence groundwater quality. This research compares the breakthrough of two bacteriophage tracers (H40/1 and T7), with contrasting properties, at subsurface monitoring points following application onto an overlying composite sequence of thin organic soil and weathered limestone (epikarst). Short pulse multi-tracer test results revealed that T7 (Source concentration, Co=1.8x106pfu/mL) and H40/1(Co=5.9x106pfu/mL) could reach sampling points 10m below ground less than 30 minutes after tracer application. Contrasting deposition rates, determined from simulated tracer responses, reflected the potential of the ground to differentially attenuate viruses. Prolonged application of both T7 (Co=2.3x104pfu/mL) and H40/1 (Co=1.3x105pfu/mL) over a five hour period during a subsequent test, in which ionic strength levels observed at monitoring points rose consistently, corresponded to a rapid rise in T7 levels, followed by a gradual decline before the end of tracer injection; this reflected reaction-limited deposition in the system. T7’s response contrasted with that of H40/1, whose concentration remained constant over a three hour period before declining dramatically prior to the end of tracer injection. Subsequent application of lower ionic strength tracer-free flush water generated a rapid rise in H40/1 levels and a more gradual release of T7. Results highlight the benefits of employing prolonged injection multi-tracer tests for identifying processes not apparent from conventional short pulse tests. Study findings demonstrate that despite rapid transport rates, the epikarst is capable of physicochemical filtration of viruses and their remobilization, depending on virus type and hydrochemical conditions.

Parametric FIR Design of Propagation Loss Filters in Digital Waveguide String Models

One of the attractive features of sound synthesis by physical modeling is the potential to build acoustic-sounding digital instruments that offer more flexibility and different options in its design and control than their real-life counterparts. In order to develop such virtual-acoustic instruments, the models they are based on need to be fully parametric, i.e., all coefficients employed in the model are functions of physical parameters that are controlled either online or at the (offline) design stage. In this letter we show how propagation losses can be parametrically incorporated in digital waveguide string models with the use of zero-phase FIR filters. Starting from the simplest possible design in the form of a three-tap FIR filter, a higher-order FIR strategy is presented and discussed within the perspective of string sound synthesis with digital waveguide models.

Data-driven optimal filtering for phase and frequency of noisy oscillations: Application to vortex flow metering

A method for measuring the phase of oscillations from noisy time series is proposed. To obtain the phase, the signal is filtered in such a way that the filter output has minimal relative variation in the amplitude over all filters with complex-valued impulse response. The argument of the filter output yields the phase. Implementation of the algorithm and interpretation of the result are discussed. We argue that the phase obtained by the proposed method has a low susceptibility to measurement noise and a low rate of artificial phase slips. The method is applied for the detection and classification of mode locking in vortex flow meters. A measure for the strength of mode locking is proposed.

Stroma-free hemoglobin increases blood pressure and GFR in the hypotensive rat: role of nitric oxide.

The short-term systemic and renal hemodynamic effects of two stroma-free hemoglobin (SFH) solutions, one unmodified and the other modified by cross-linking, were examined in anesthetized rats after hemorrhagic hypotension. Both forms of SFH increased mean arterial pressure (MAP) and glomerular filtration rate (GFR) to baseline (prehemorrhage) values. The increase in MAP induced by unmodified SFH was greater than the increase in MAP caused by an albumin solution isoncotic to the unmodified SFH solution. Similarly, the increase in MAP caused by the modified SFH was also substantially greater than that induced by an albumin solution of comparable oncotic pressure to the modified SFH solution. Both unmodified and modified SFH increased GFR. As with MAP, the increase in GFR induced by both SFH solutions was greater than that associated with the oncotically matched albumin solutions. In separate experiments, the effects of nitric oxide (NO) inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) on MAP after hemorrhagic hypotension and subsequent infusion of unmodified SFH or albumin were also examined. In the albumin-infused rats, L-NAME increased MAP. In marked contrast, NO inhibition with L-NAME had no further effect on MAP when infused after SFH. We conclude that both unmodified and modified SFH solutions acutely improve MAP and GFR by the combined effects of intravascular volume expansion resulting from the colloid effect of the protein and by inactivation of NO.