Cerebral microbleeds and cognitive decline in a hemodialysis patient: Case report and review of literature

Cerebral microbleeds (CMBs) are small hemosiderin deposits indicative of prior cerebral microscopic hemorrhage and previously thought to be clinically silent. Recent population‐based cross‐sectional studies and prospective longitudinal cohort studies have revealed association between CMB and cognitive dysfunction. In the general population, CMBs are associated with age, hypertension, and cerebral amyloid angiopathy. In the chronic kidney disease (CKD) population, diminished estimated glomerular filtration rate has been found to be an independent risk factor for CMB, raising the possibility that a uremic milieu may predispose to microbleeds. In the end‐stage renal disease (ESRD) population on hemodialysis, the incidence of microbleeds is significantly higher compared with a control group without history of CKD or stroke. We present an ESRD patient on chronic hemodialysis with a history of gradual cognitive decline and progressive CMBs. Through this case and literature review, we illustrate the need to develop detection and prediction models to treat this frequent development in ESRD patients.     

Supply-side hurdles in Internet B2C e-commerce: an empirical investigation

Given Hong Kong's special circumstances of small physical size, advanced infrastructure, and low shopping cost, a survey is designed under which supply-side problems in Internet business-to-consumer (B2C) e-commerce are indirectly revealed by responses on the demand side. Difficulties arising from the reluctance to answer questionnaires on the part of e-firms wary about trade and innovation secrets and their small number at the outset are thereby overcome. Survey data on demand-side obstacle factors in the form of perceived low e-shopping comparability, e-shopping inconvenience, e-transaction insecurity, and poor Internet privacy, together with orientation toward social interaction and low awareness on the part of consumers, translate into information on notionally matching supply-side hurdles. Regression analysis and hypothesis testing indicate statistical significance for the above hurdle factors in terms of impact on individual unwillingness to shop online. These results add to the inductive basis for future research into a general demand-supply theory of Internet B2C e-commerce and offer an empirically-grounded position against which the effects of later supply-side changes can be evaluated. Useful information also follows for engineer-managers seeking to compare marginal improvements in supply-side problems, particularly in the form of estimated substitution ratios.     

A 1-V 10.7-MHz switched-opamp bandpass /spl Sigma//spl Delta/ modulator using double-sampling finite-gain-compensation technique

A 1 V switched-capacitor (SC) bandpass sigma-delta (/spl Sigma//spl Delta/) modulator is realized using a high-speed switched-opamp (SO) technique with a sampling frequency of up to 50 MHz, which is improved ten times more than prior 1 V SO designs and comparable to the performance of the state-of-the-art SC circuits that operate at much higher supply voltages. On the system level, a fast-settling double-sampling SC biquadratic filter architecture is proposed to achieve high-speed operation. A low-voltage double-sampling finite-gain-compensation technique is employed to realize a high-resolution /spl Sigma//spl Delta/ modulator using only low-DC-gain opamps to maximize the speed and to reduce power dissipation. On the circuit level, a fast-switching methodology is proposed for the design of the switchable opamps to achieve a switching frequency up to 50 MHz. Implemented in a 0.35-/spl mu/m CMOS process (V/sub TP/=0.82 V and V/sub TN/=0.65 V) and at 1 V supply, the modulator achieves a measured peak signal-to-noise-and-distortion ratio (SNDR) of 42.3 dB at 10.7 MHz with a signal bandwidth of 200 kHz, while dissipating 12 mW and occupying a chip area of 1.3 mm/sup 2/.     

Insulinomimetic effect on glucose transport by epidermal growth factor when combined with a major histocompatibility complex class I-derived peptide

Peptides derived from the alpha 1-region of the murine H-2Dk molecule enhance glucose uptake in rat adipose cells above the maximum obtained with insulin stimulation alone (Stagsted, J., Reaven, G. M., Hansen, T., Goldstein, A., and Olsson, L. (1990) Cell 62, 297-307). We now describe that epidermal growth factor (EGF) in combination with the same peptides, Dk-(61-85) and Dk-(62-85), stimulates cellular glucose uptake 5-7 times over the basal level, i.e. to 30-50% of the maximal insulin effect. EGF alone increased glucose uptake by only approximately 50% above basal and the peptide alone by 100% above basal. Maximal effect of EGF and peptide was reached in 10-20 min with 30 microM peptide (EC50 10-15 microM) and 50 nM EGF (EC50 1-2 nM). The effect of EGF and peptide on glucose uptake was additive to that of insulin and peptide until the maximal level attained with insulin and peptide was reached. The combined effect of EGF plus peptide on glucose transport was associated with a recruitment of GLUT4 molecules to the plasma membrane. However, the phosphatidylinositol (PI) kinase which is activated by insulin was not activated by EGF plus peptide. Thus, the effect of EGF plus peptide on glucose uptake seems independent of the activity status of the insulin receptor. 125I-Labeled EGF bound specifically to rat adipose cells with an apparent affinity of approximately 2 nM and Bmax approximately 5 x 10(3). However, the major histocompatibility complex (MHC) peptides did not affect EGF-stimulated internalization of EGF receptor, in contrast to their effect on the insulin receptors. Transforming growth factor alpha had an effect similar to EGF on glucose uptake. Three other peptides derived from other parts of murine MHC class I had no effect on glucose uptake in combination with EGF. Thus, EGF in combination with certain MHC class I-derived peptides is insulinomimetic concerning glucose transport and this effect is independent of the insulin receptor activity.     

Trends and variations in neonatal length of in-hospital stay in Canada

The objectives of this study were to evaluate the possible mechanisms involved in prolongation of bleeding time in pre-eclamptic patients receiving a magnesium sulfate infusion to prevent convulsions. Eighteen pre-eclamptic patients near term or at term (4 cases 33 to 35 weeks; the remainder > 36 weeks) were studied. Fifteen of them received magnesium sulfate infusion; 3 did not and served as controls. Bleeding time (modified Ivy method with Surgicutt), platelet count, platelet aggregation pattern, as well as serum arachidonic acid metabolites [thromboxane B2 (TxB2) and 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1 alpha)] werde done on admission to the labor floor (before magnesium infusion) and repeated at discontinuation of the infusion, 12-24 hours postpartum; the controls received the second test 24 hours postpartum. Thirteen of 15 patients receiving magnesium sulfate had an increase in bleeding time from an average of 6 minutes 31 seconds to 11 minutes 56 seconds, an 82% rise (p < 0.004). In 2 there was a decrease. Among the 3 controls the averages were 6 minutes 38 seconds and 6 minutes 3 seconds. The total magnesium given ranged from 52.5 to 145 grams. Platelet counts averaged 251,000/mm3 (range 145,000-519,000). Platelet aggregation pattern done in 11 patients and was normal and unchanged after magnesium in 10 of the patients with increased bleeding time and one control. TxB2 and 6-Keto-PGF1 alpha levels did not change significantly either after magnesium administration (688 and 135 pgm/ml, to 654 and 117) or in controls (695 and 230 pgm/ml, to 445 and 225). Likewise, the ratio of these 2 substances did not change in either group (6.3 to 6.6, and 4.2 to 2.2). There was no correlation between duration of infusion or total magnesium given and directions of small changes observed. This study confirms a prior preliminary observation that magnesium sulfate infusion, as currently used to prevent eclamptic convulsions, induces a significant prolongation of bleeding time. This effect is mediated neither by changes in platelets count or aggregation pattern, nor by changing the level or ratios of serum arachidonic acid metabolites (TxB2 and 6-Keto-PGF1 alpha). Further studies are needed to clarify the mechanism of this clinically important observation of increased bleeding following magnesium sulfate infusion.     

A high-linearity 100-element diode grid mixer

Grid-mixer arrays can achieve high linearity and dynamic range through quasi-optical power combining. We present a 100-element single-ended diode grid mixer operating at 2.45 GHz. Each element incorporates two diodes in series. We measure an input third-order intercept of 11 W (40.5 dBm), and output third-order intercept of 3.4 W (35.4 dBm), and an associated conversion loss of 5.1 dB. The power-handling capability of the array is 100 times larger than that of a microstrip mixer using a single element. The local oscillator (LO) drive requirement for the entire array is 1.4 W (31.6 dBm). The angular dependence of the array's IF power is also presented and is in agreement with theory     

Solution of Helmholtz equation by Trefftz method

The application of the Trefftz method for calculating wave forces on offshore structures is presented. Indirect and direct formulations using complete and non-singular systems of Trefftz functions for the Helmholtz equation are posed in this paper. An effective technique using different interpolation functions for the velocity potential and wave force are suggested to improve the computational accuracy of the wave force. The numerical examples show that the present method is highly efficient and accurate.     

Optimal transfer trees and distinguishing trees for testing observable nondeterministic finite-state machines

The fault-state detection approach for blackbox testing consists of two phases. The first is to bring the system under test (SUT) from its initial state to a targeted state t and the second is to check various specified properties of the SUT at t. This paper investigates the first phase for testing systems specified as observable nondeterministic finite-state machines with probabilistic and weighted transitions. This phase involves two steps. The first step transfers the SUT to some state t' and the second step identifies whether t' is indeed the targeted state t or not. State transfer is achieved by moving the SUT along one of the paths of a transfer tree (TT) and state identification is realized by using diagnosis trees (DT). A theoretical foundation for the existence and characterization of TT and DT with minimum weighted height or minimum average weight is presented. Algorithms for their computation are proposed.     

Mutational analysis of the three cysteines and active-site aspartic acid 103 of ketosteroid isomerase from Pseudomonas putida biotype B

In order to clarify the roles of three cysteines in ketosteroid isomerase (KSI) from Pseudomonas putida biotype B, each of the cysteine residues has been changed to a serine residue (C69S, C81S, and C97S) by site-directed mutagenesis. All cysteine mutations caused only a slight decrease in the k(cat) value, with no significant change of Km for the substrate. Even modification of the sulfhydryl group with 5,5'-dithiobis(2-nitrobenzoic acid) has almost no effect on enzyme activity. These results demonstrate that none of the cysteines in the KSI from P. putida is critical for catalytic activity, contrary to the previous identification of a cysteine in an active-site-directed photoinactivation study of KSI. Based on the three-dimensional structures of KSIs with and without dienolate intermediate analog equilenin, as determined by X-ray crystallography at high resolution, Asp-103 was found to be located within the range of the hydrogen bond to the equilenin. To assess the role of Asp-103 in catalysis, Asp-103 has been replaced with either asparagine (D103N) or alanine (D103A) by site-directed mutagenesis. For D103A mutant KSI there was a significant decrease in the k(cat) value: the k(cat) of the mutant was 85-fold lower than that of the wild-type enzyme; however, for the D103N mutant, which retained some hydrogen bonding capability, there was a minor decrease in the k(cat) value. These findings support the idea that aspartic acid 103 in the active site is an essential catalytic residue involved in catalysis by hydrogen bonding to the dienolate intermediate.