Influence of peritoneal dialysis solution on measurements of fluid status by bioimpedance spectroscopy

Purpose and methods

The accurate estimation of volume status is a central problem in dialysis patients. Recently, a bioimpedance spectroscopy (BIS) device (BCM Body Composition Monitor FMC, Germany) has attained growing interest in this regard. By processing the raw data for extracellular water (ECW) and intracellular water (ICW) by means of a validated body composition model, this device allows a quantification of the individual fluid overload (FO) compared to a representative healthy population. In this study, we addressed the issue whether the presence of peritoneal dialysate has an impact on measurements of FO by BIS in PD patients.

Results

Forty-two BIS measurements using the BCM device were performed both in the absence (D?) and presence (D+) of peritoneal dialysate in 17 stable PD patients. Data for ECW, ICW and FO (D+; D?) were analyzed by paired t test and linear regression. Mean FO was 0.99 ± 1.17 L in D? and 0.94 ± 1.27 in D+ (p = n.s. paired t test). Linear regression demonstrated an excellent degree of conformity between FO (D?) and FO (D+) (r ² = 0.93).

Conclusion

The presence of peritoneal fluid in PD patients has a negligible influence on measurements of FO by BIS. The BIS measurements can be therefore conveniently and reliably done without emptying the peritoneal cavity; this may facilitate the use of BIS in this particular group of patients.     

Estimation of Glomerular Podocyte Number: A Selection of Valid Methods

The podocyte depletion hypothesis has emerged as an important unifying concept in glomerular pathology. The estimation of podocyte number is therefore often a critical component of studies of progressive renal diseases. Despite this, there is little uniformity in the biomedical literature with regard to the methods used to estimate this important parameter. Here we review a selection of valid methods for estimating podocyte number: exhaustive enumeration method, Weibel and Gomez method, disector/Cavalieri combination, disector/fractionator combination, and thick-and-thin section method. We propose the use of the disector/fractionator method for studies in which controlled sectioning of tissue is feasible, reserving the Weibel and Gomez method for studies based on archival or routine pathology material.Podocytes play a key role in the preservation of normal glomerular structure and function.¹ Podocyte loss has been associated with progression of glomerular diseases both in humans^2,3 and in experimental models of glomerular injury.^4–6 The assessment of podocyte number in human renal biopsy samples and in kidney specimens from animal models may therefore be a pivotal component of studies of the pathogenesis and treatment of glomerular disease. Despite this, there is little uniformity in the biomedical literature with regard to the methods used for estimating podocyte number either in experimental models or clinical biopsy specimens. As a result, estimates of podocyte number can vary widely between studies, making meaningful comparisons difficult.The glomerulus and the cells within it are three-dimensional objects. Quantitative assessment of these structures, on the other hand, has traditionally involved measurements on two-dimensional images from histologic sections. Stereology is a body of mathematical/statistical theory and methods wherein three-dimensional characteristics of objects are estimated from lower-dimensional images of those objects. Although stereology is a well developed field, as with other forms of statistically based reasoning, its results can sometimes seem counterintuitive. At the same time, apparently common-sense approaches to the estimation of quantitative structural variables, such as podocyte number, often lack stereologic validity and, as a result, introduce biologic uncertainty.In this review we describe five methods for estimating podocyte number, examine their assumptions and limitations, and indicate some of the circumstances under which they may represent appropriate approaches. These methods occupy a range of increasingly general assumptions and corresponding changes in methodologic design. The main body of this paper provides an overview and motivation for these five methods (the Supplemental Material describes the methods with worked examples in more detail). We also present one example of a commonly used but invalid method and illustrate its shortcomings.     

Use of Computer-Assisted Technologies (CAT) to Enhance Social, Communicative, and Language Development in Children with Autism Spectrum Disorders

Major advances in multimedia computer technology over the past decades have made sophisticated computer games readily available to the public. This, combined with the observation that most children, including those with autism spectrum disorders (ASD), show an affinity to computers, has led researchers to recognize the potential of computer technology as an effective and efficient tool in research and treatment. This paper reviews the use of computer-assisted technology (CAT), excluding strictly internet-based approaches, to enhance social, communicative, and language development in individuals with ASD by dividing the vast literature into four main areas: language, emotion recognition, theory of mind, and social skills. Although many studies illustrate the tremendous promise of CAT to enhance skills of individuals with ASD, most lack rigorous, scientific assessment of efficacy relative to non-CAT approaches.     

Genetic fate mapping of type‐1 stem cell‐dependent increase in newborn hippocampal neurons after electroconvulsive seizures

Electroconvulsive therapy (ECT) is a uniquely effective treatment for major depressive disorder. An increase in hippocampal neurogenesis is implicated in the recovery from depression. We used an inducible genetic mouse model in which only GFAP‐expressing stem‐like cells (type‐1 cells) and their progeny are selectively labeled with the reporter protein β‐galactosidase to track the process of neurogenesis in the dentate gyrus over 3 months following electroconvulsive seizures (ECS), the mouse equivalent of ECT. All ECS protocols tested induced a transient increase in type‐1 cell divisions. While this led to an expansion of the type‐1 cell pool after high‐frequency ECS sessions for 5 consecutive days (5‐ECS), asymmetric divisions drove neurogenesis by giving rise to Doublecortin (DCX)‐expressing neuroblasts that matured into NeuN+ neurons. Significantly, the increase in newly generated DCX+ and NeuN+ cells after 5‐ECS could be traced back to proliferating type‐1 cells. Low‐frequency continuation ECS (c‐ECS) consisting of five single ECS sessions administered every 2 weeks resulted in a similar increase in newborn neurons as the high‐frequency 5‐ECS protocol. Moreover, the combination of 5‐ECS and c‐ECS led to a further significant increase in newborn neurons, suggesting a cellular mechanism responsible for the propitious effects of high‐frequency ECT followed by continuation ECT in severely depressed patients. The ability of high‐ and low‐frequency ECS to induce normally quiescent type‐1 cells to proliferate and generate new neurons sets it apart from other antidepressant treatments and may underlie the superior clinical efficacy of ECT. © 2013 Wiley Periodicals, Inc.     

The LDLR locus in Alzheimer's disease: a family-based study and meta-analysis of case-control data

Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population.     

Alterations in GABA(A) receptor mediated inhibition in adjacent dorsal midline thalamic nuclei in a rat model of chronic limbic epilepsy

There is evidence that the dorsal midline thalamus is involved in the seizures of limbic epilepsy. However, little is known about the inhibitory synaptic function in this region. In the present study, inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors were recorded from the mediodorsal (MD) and paraventricular (PV) nuclei from control and epileptic animals. In the MD, the spontaneous (s)IPSCs for epileptic animals had a lower frequency, prolonged rise time, prolonged decay, but unaltered net charge transfer compared with controls. The miniature (m)IPSC parameters were unaltered in the epileptic animals. In contrast, in the PV, both sIPSCs and mIPSCs in the epileptic animals were more frequent with larger amplitudes and there was an increase in the net charge transfer compared with controls. The rise times of the sIPSCs of the PV neurons were significantly prolonged, whereas the weighted decay time of the mIPSC was significantly shortened in epileptic animals. These findings suggest that the changes associated with inhibitory synaptic transmission in limbic epilepsy are not uniform across regions in the thalamus that are part of the seizure circuit.     

Inflammation in areas of fibrosis: The DeKAF prospective cohort

Inflammation in areas of fibrosis (i‐IFTA) in posttransplant biopsy specimens has been associated with decreased death‐censored graft survival (DC‐GS). Additionally, an i‐IFTA score ≥ 2 is part of the diagnostic criteria for chronic active TCMR (CA TCMR). We examined the impact of i‐IFTA and t‐IFTA (tubulitis in areas of atrophy) in the first biopsy for cause after 90 days posttransplant (n = 598); mean (SD) 1.7 ± 1.4 years posttransplant. I‐IFTA, present in 196 biopsy specimens, was strongly correlated with t‐IFTA, and Banff i. Of the 196, 37 (18.9%) had a previous acute rejection episode; 96 (49%) had concurrent i score = 0. Unlike previous studies, i‐IFTA = 1 (vs 0) was associated with worse 3‐year DC‐GS: (i‐IFTA = 0, 81.7%, [95% CI 77.7 to 85.9%]); i‐IFTA = 1, 68.1%, [95% CI 59.7 to 77.6%]; i‐IFTA = 2, 56.1%, [95% CI 43.2 to 72.8%], i‐IFTA = 3, 48.5%, [95% CI 31.8 to 74.0%]). The association of i‐IFTA with decreased DC‐GS remained significant when adjusted for serum creatinine at the time of the biopsy, Banff i, ci and ct, C4d and DSA. T‐IFTA was similarly associated with decreased DC‐GS. Of these indication biopsies, those with i‐IFTA ≥ 2, without meeting other criteria for CA TCMR had similar postbiopsy DC‐GS as those with CA TCMR. Those with i‐IFTA = 1 and t ≥ 2, ti ≥ 2 had postbiopsy DC‐GS similar to CA TCMR. Biopsies with i‐IFTA = 1 had similar survival as CA TCMR when biopsy specimens also met Banff criteria for TCMR and/or AMR. Studies of i‐IFTA and t‐IFTA in additional cohorts, integrating analyses of Banff scores meeting criteria for other Banff diagnoses, are needed.     

The economic burden of kidney graft failure in the United States

Despite improvements in outcomes for kidney transplant recipients in the past decade, graft failure continues to impose substantial burden on patients. However, the population‐wide economic burden of graft failure has not been quantified. This study aims to fill that gap by comparing outcomes from a simulation model of kidney transplant patients in which patients are at risk for graft failure with an alternative simulation in which the risk of graft failure is assumed to be zero. Transitions through the model were estimated using Scientific Registry of Transplant Recipients data from 1987 to 2017. We estimated lifetime costs, overall survival, and quality‐adjusted life‐years (QALYs) for both scenarios and calculated the difference between them to obtain the burden of graft failure. We find that for the average patient, graft failure will impose additional medical costs of $78 079 (95% confidence interval [CI] $41 074, $112 409) and a loss of 1.66 QALYs (95% CI 1.15, 2.18). Given 17 644 kidney transplants in 2017, the total incremental lifetime medical costs associated with graft failure is $1.38B (95% CI $725M, $1.98B) and the total QALY loss is 29 289 (95% CI 20 291, 38 464). Efforts to reduce the incidence of graft failure or to mitigate its impact are urgently needed.     

Model predictive control of a collaborative manipulator considering dynamic obstacles

Collaborative robots have to adapt its motion plan to a dynamic environment and variation of task constraints. Currently, they detect collisions and interrupt or postpone their motion plan to prevent harm to humans or objects. The more advanced strategy proposed in this article uses online trajectory optimization to anticipate potential collisions, task variations, and to adapt the motion plan accordingly. The online trajectory planner pursues a model predictive control approach to account for dynamic motion objectives and constraints during task execution. The prediction model relates reference joint velocities to actual joint positions as an approximation of built-in robot tracking controllers. The optimal control problem is solved with direct collocation based on a hypergraph structure, which represents the nonlinear program and allows to efficiently adapt to structural changes in the optimization problem caused by moving obstacles. To demonstrate the effectiveness of the approach, the robot imitates pick-and-place tasks while avoiding self-collisions, semistatic, and dynamic obstacles, including a person. The analysis of the approach concerns computation time, constraint violations, and smoothness. It shows that after model identification, order reduction, and validation on the real robot, parallel integrators with compensation for input delays exhibit the best compromise between accuracy and computational complexity. The model predictive controller can successfully approach a moving target configuration without prior knowledge of the reference motion. The results show that pure hard constraints are not sufficient and lead to nonsmooth controls. In combination with soft constraints, which evaluate the proximity of obstacles, smooth and safe trajectories are planned.