Physiological Responses in Reindeer to the Application of a Conducted Electrical Weapon

Conducted Electrical Weapons (CEWs) have potential as effective alternatives to chemical restraint for short-term non-routine capture and handling as well as aversion hazing of wildlife. To assess immediate and delayed physiologic effects of exposure to a CEW, we assigned 15 captive reindeer (Rangifer tarandus tarandus) to one of three treatment groups: immobilized with carfentanil and xylazine (CX), 10 second exposure to a CEW, or exposure to the CEW while immobilized with CX (CEW+CX). Blood samples were collected pre-treatment, immediately post-intervention, 10 min, 20 min, 4 hours, and 24 hours post-intervention. Physiologic effects were evaluated by analysis of blood, clinical observation for signs of physiologic compromise, and vital signs. Parameters that changed significantly (P \u3c 0.05) post-exposure (lactate, glucose, rectal temperature, blood oxygen, cardiac troponin I, cortisol, and catecholamines) were not significantly different from baseline values within 24 hours. Cortisol, glucose, and peak rectal temperature were lower in CEW exposed individuals, while lactate, oxygen, and catecholamines were higher than for the CX exposed individuals. The catecholamine response observed in the CEW only group paralleled the response in the CEW+CX group. No long term health effects were detected from either restraint method. Use of a CEW does not appear to increase the risk of capture myopathy

Seegangsbelastungen (SEELE) – Prozesse der Hydrodynamik bei Interaktion von Richtungsseegang mit Strömung

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Plasma oxalate: comparison of methodologies

Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to transplantation. As no external quality assurance scheme is available for this analyte, we conducted a sample exchange scheme between six laboratories specifcally involved with the investigation of primary hyperoxaluria to compare results. The methodologies compared were gas chromatography/mass spectrometry (GCMS), ion chromatography with mass spectrometry (ICMS), and enzymatic methods using oxalate oxidase and spectrophotometry. Although individual laboratories performed well in terms of reproducibility and linearity, there was poor agreement (absolute values) between centres as illustrated by a longer-term comparison of patient results from two of the participating laboratories. This situation was only partly related to diferences in calibration and mainly refected the lower recoveries seen with the ultrafltration of samples. These fndings lead us to conclude that longitudinal monitoring of primary hyperoxaluria patients with deteriorating kidney function should be performed by a single consistent laboratory and the methodology used should always be defned. In addition, plasma oxalate concentrations reported in registry studies and those associated with the risk of systemic oxalosis in published studies need to be interpreted in light of the methodology used. A reference method and external quality assurance scheme for plasma oxalate analysis would be benefcial

PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2

Chronic kidney disease; Pediatric nephrology; UrologyMalaltia renal crònica; Nefrologia pediàtrica; UrologiaEnfermedad renal crónica; Nefrología pediátrica; UrologíaNedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90–180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs −1664 [1190], respectively; difference, 5172; 95% CI 2929–7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH

Key influence of sex on urine volume and osmolality

Abstract Background Demographics influence kidney stone risk and the type of stone that is more likely to form. Common kidney stone risk factors include having a low urine volume and a high urine concentration. The goal of the current study was to evaluate the effect of demographics on urinary concentration and osmole excretion. Methods Twenty-four-hour urine samples were collected from non-Hispanic white sibships in Rochester, MN. Height, weight, blood pressure, serum creatinine, and cystatin C were measured. Diet was assessed using the Viocare food frequency questionnaire. Effects of demographics and dietary elements on urine osmolality and volume were evaluated in bivariate and multivariable models, as well as models that included dietary interactions with age, sex, and weight. Results Samples were available from 709 individuals (mean age 66 ± 9 years, 59 % female). Across the age spectrum, males had higher urine osmolality (~140 mOsm/kg, p < 0.0001) and total osmole excretion (~270 mOsm, p < 0.0001) compared to females. For any given urine volume, males had a consistently higher urine osmolality (~140 mOsm/kg, p < 0.0001). In multivariable models, urine osmolality declined with age and water intake and remained higher in males than females. Urine osmolality positively associated with weight and animal protein intake. Higher urine volume associated with larger water intake. An interaction revealed that greater body weight was associated with larger changes in urine osmolality as oxalate intake increased (p = 0.04). Conclusion Data from this study support the hypothesis that there are sex differences in thirst and vasopressin action. This trend in urine concentration is also consistent with known epidemiologic patterns of urinary stone disease risk.http://deepblue.lib.umich.edu/bitstream/2027.42/117280/1/13293_2016_Article_63.pd

Association of urinary citrate excretion, pH, and net gastrointestinal alkali absorption with diet, diuretic use, and blood glucose concentration

Urinary citrate (Ucit) protects against urinary stone formation. Acid base status and diet influence Ucit. However, the effect of demographics, diet, and glucose metabolism on Ucit excretion, urinary pH (U‐pH) and net gastrointestinal alkali absorption (NAA) are not known. Twenty‐four hour urine samples, blood glucose, creatinine, and cystatin C were obtained from non‐Hispanic white sibships in Rochester, MN (n = 446; 64.5 ± 9 years; 58% female). Diet was assessed by a food frequency questionnaire. The impact of blood glucose, demographics and dietary elements on Ucit excretion, U‐pH, and NAA were evaluated in bivariate and multivariable models and interaction models that included age, sex, and weight. NAA significantly associated with Ucit and U‐pH. In multivariate models Ucit increased with age, weight, eGFRCys, and blood glucose, but decreased with loop diuretic and thiazide use. U‐pH decreased with serum creatinine, blood glucose, and dietary protein but increased with dietary potassium. NAA was higher in males and increased with age, weight, eGFRCys and dietary potassium. Significant interactions were observed for Ucit excretion with age and blood glucose, weight and eGFRCys, and sex and thiazide use. Blood glucose had a significant and independent effect on U‐pH and also Ucit. This study provides the first evidence that blood glucose could influence urinary stone risk independent of urinary pH, potentially providing new insight into the association of obesity and urinary stone disease.This study demonstrated that blood glucose had a significant and independent effect on urinary pH and also urinary citrate. Thus it provides the first evidence that blood glucose could influence urinary stone risk independent of urinary pH, potentially providing new insight into the association of obesity and urinary stone disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138855/1/phy213411.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138855/2/phy213411_am.pd

TEMPO2, a new pulsar timing package. I: Overview

Contemporary pulsar timing experiments have reached a sensitivity level where systematic errors introduced by existing analysis procedures are limiting the achievable science. We have developed tempo2, a new pulsar timing package that contains propagation and other relevant effects implemented at the 1ns level of precision (a factor of ~100 more precise than previously obtainable). In contrast with earlier timing packages, tempo2 is compliant with the general relativistic framework of the IAU 1991 and 2000 resolutions and hence uses the International Celestial Reference System, Barycentric Coordinate Time and up-to-date precession, nutation and polar motion models. Tempo2 provides a generic and extensible set of tools to aid in the analysis and visualisation of pulsar timing data. We provide an overview of the timing model, its accuracy and differences relative to earlier work. We also present a new scheme for predictive use of the timing model that removes existing processing artifacts by properly modelling the frequency dependence of pulse phase.Comment: Accepted by MNRA

Medical treatment of pediatric urolithiasis

In recent years the incidence of pediatric stone disease has increased several fold, mostly due to hypercalciuria and hypocitraturia. The goal of medical treatment is to protect the patient from formation of new stones and expansion of existing ones. The non-pharmacological means to address stone disease include high fluid intake and, frequently, modification of nutritional habits. The pharmacological treatment is based on the chemical composition of the stone and the biochemical abnormalities causing its formation; hence, chemical analysis of the stone, urine and blood is of paramount importance and should be done when the first stone is detected. This review discusses the current options of medical treatment of pediatric urolithiasis

Strategy and rationale for urine collection protocols employed in the NEPTUNE study

Abstract Background Glomerular diseases are potentially fatal, requiring aggressive interventions and close monitoring. Urine is a readily-accessible body fluid enriched in molecular signatures from the kidney and therefore particularly suited for routine clinical analysis as well as development of non-invasive biomarkers for glomerular diseases. Methods The Nephrotic Syndrome Study Network (NEPTUNE; ClinicalTrials.gov Identifier NCT01209000) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes standardized urine collections across all participating centers for the purpose of discovering non-invasive biomarkers for patients with nephrotic syndrome due to minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Here we describe the organization and methods of urine procurement and banking procedures in NEPTUNE. Results We discuss the rationale for urine collection and storage conditions, and demonstrate the performance of three experimental analytes (neutrophil gelatinase-associated lipocalin [NGAL], retinol binding globulin, and alpha-1 microglobulin) under these conditions with and without urine preservatives (thymol, toluene, and boric acid). We also demonstrate the quality of RNA and protein collected from the urine cellular pellet and exosomes. Conclusions The urine collection protocol in NEPTUNE allows robust detection of a wide range of proteins and RNAs from urine supernatant and pellets collected longitudinally from each patient over 5 years. Combined with the detailed clinical and histopathologic data, this provides a unique resource for exploration and validation of new or accepted markers of glomerular diseases. Trial registration ClinicalTrials.gov Identifier NCT01209000http://deepblue.lib.umich.edu/bitstream/2027.42/116023/1/12882_2015_Article_185.pd