Pediatric reference intervals for endocrine markers in healthy children and adolescents on the Liaison XL (DiaSorin) immunoassay system.

OBJECTIVES: Prominent physiological changes occurring throughout childhood and adolescence necessitate the consideration of age and sex in biomarker interpretation. Critical gaps exist in pediatric reference intervals (RIs) for specialized endocrine markers, despite expected influence of growth and development. The current study aimed to establish and/or verify RIs for six specialized endocrine markers on a specialized immunoassay system. METHODS: Samples were collected from healthy children and adolescents (5 to <19 years) and apparently healthy outpatients (0 to <5 years) as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER). Serum samples were analysed for aldosterone, renin (plasma), thyroglobulin, anti-thyroglobulin, growth hormone, and insulin-like growth factor-1 (IGF-1) on the Liaison XL (DiaSorin) immunoassay platform. RIs (2.5th and 97.5th percentiles) were established for aldosterone, renin, thyroglobulin, anti-thyroglobulin, and growth hormone. Manufacturer-recommended pediatric RIs for IGF-1 were verified. RESULTS: Age-specific RIs were established for aldosterone, renin, and thyroglobulin, while no age-specific differences were observed for anti-thyroglobulin or growth hormone. IGF-1 was the only endocrine marker studied that demonstrated significant sex-specific differences. Manufacturer-recommended IGF-1 RIs were verified for children aged 6 to <19 years, while those for children aged 0 to <6 years did not verify. CONCLUSIONS: This study marks the first time that pediatric RIs for aldosterone and renin were established in the CALIPER cohort and highlights the dynamic changes that occur in water and sodium homeostasis during the first years of life. Overall, these data will assist pediatric clinical laboratories in test result interpretation and improve clinical decision-making for patients tested using Liaison immunoassays.

To skim or splice? Comparing the quantification of M-proteins using two peak-integration protocols across multiple electrophoresis platforms.

OBJECTIVES: M-protein quantification by peak integration in serum protein electrophoresis (SPE) plays a central role in diagnosing, prognosing and monitoring monoclonal gammopathies. The conventional perpendicular drop (PD) integration approach integrates M-spikes from the baseline, which performs acceptably when the M-protein concentration is relatively high compared to the amount of background proteins present. The alternative peak-integration protocol by tangential skim (TS), however, allows for more accurate M-protein estimations by excluding background proteins. Despite some guideline recommendations, TS has been poorly adopted, making an understanding of the differences between the two protocols and their potential impacts paramount when considering a change from PD to TS. DESIGN & METHODS: We conducted retrospective investigations of the differences in M-protein quantification over large concentration ranges between PD and TS on 3 of the most popular electrophoresis platforms. RESULTS: Compared to PD, TS gave consistently lower results; the differences between the two methods increased tremendously and became more sporadic as M-protein concentrations dropped below 15 g/L in all 3 platforms. At < 15 g/L, the average % difference ranged from -81 % to -95 %, while above 15 g/L, the average % difference was only -13 to -31 %. Medical decision point analyses using linear regression predicted statistically significant and platform-dependent differences, which could impact clinical interpretation. CONCLUSIONS: Careful consideration of the magnitude of concentration changes and the potential impacts on patient classification and management should be made when switching to TS for M-protein quantification.

Diabetic mitochondria are resistant to palmitoyl CoA inhibition of respiration, which is detrimental during ischemia.

The bioactive lipid intermediate palmitoyl CoA (PCoA) can inhibit mitochondrial ADP/ATP transport, though the physiological relevance of this regulation remains unclear. We questioned whether myocardial ischemia provides a pathological setting in which PCoA regulation of ADP/ATP transport would be beneficial, and secondly, whether the chronically elevated lipid content within the diabetic heart could make mitochondria less sensitive to the effects of PCoA. PCoA acutely decreased ADP-stimulated state 3 respiration and increased the apparent Km for ADP twofold. The half maximal inhibitory concentration (IC50 ) of PCoA in control mitochondria was 22 µM. This inhibitory effect of PCoA on respiration was blunted in diabetic mitochondria, with no significant difference in the Km for ADP in the presence of PCoA, and an increase in the IC50 to 32 µM PCoA. The competitive inhibition by PCoA was localised to the phosphorylation apparatus, particularly the ADP/ATP carrier (AAC). During ischemia, the AAC imports ATP into the mitochondria, where it is hydrolysed by reversal of the ATP synthase, regenerating the membrane potential. Addition of PCoA dose-dependently prevented this wasteful ATP hydrolysis for membrane repolarisation during ischemia, however, this beneficial effect was blunted in diabetic mitochondria. Finally, using 31 P-magnetic resonance spectroscopy we demonstrated that diabetic hearts lose ATP more rapidly during ischemia, with a threefold higher ATP decay rate compared with control hearts. In conclusion, PCoA plays a role in protecting mitochondrial energetics during ischemia, by preventing wasteful ATP hydrolysis. However, this beneficial effect is blunted in diabetes, contributing to the impaired energy metabolism seen during myocardial ischemia in the diabetic heart.

Short-term legacy effects of feedlot manure application on soil mesofauna.

Little research exists on short-term legacy effects of feedlot manure application on soil mesofauna. This long-term (since 1998) study was on an irrigated clay loam soil in southern Alberta cropped to barley (Hordeum vulgare L.). We sampled the soil 3-4 yr (2017-2018) into the legacy period following 17 annual manure applications (1998-2014). The selected treatments sampled were stockpiled feedlot manure containing straw bedding applied at 0, 13, 39, and 77 Mg ha-1 (dry wt.). Intact soil cores were taken at three depth intervals (0-3, 3-6, and 6-9 cm) in the fall over 2 yr to determine the densities of Acari (mites) suborders and Collembola (springtails) families. Significant (P ≤ .05) application rate effects occurred on Oribatida and Astigmata after 3 yr (but not after 4 yr) into the legacy phase, whereas Prostigmata were unaffected. Densities of Astigmata after 3 yr were 3.2- to 4.1-fold greater at the 77 Mg ha-1 rate compared with three lower rates. Significant application rate effects occurred on Entomobryidae, Isotomidae, and Onychiuridae after 4 yr (but not after 3 yr), with no treatment effects on Neelidae. Densities of mesofauna were generally greater at higher than at lower rates, except for Entomobryidae in 2018, where the reverse trend occurred. Significant application rate effects were attributed to lower soil bulk density and greater volumetric soil water content and soil organic carbon. Therefore, legacy effects of feedlot manure application generally persisted on soil mesofauna 3-4 yr into the legacy phase but depended on mesofauna type, year, and depth.

A relevancy algorithm for curating earth science data around phenomenon.

Earth science data are being collected for various science needs and applications, processed using different algorithms at multiple resolutions and coverages, and then archived at different archiving centers for distribution and stewardship causing difficulty in data discovery. Curation, which typically occurs in museums, art galleries, and libraries, is traditionally defined as the process of collecting and organizing information around a common subject matter or a topic of interest. Curating data sets around topics or areas of interest addresses some of the data discovery needs in the field of Earth science, especially for unanticipated users of data. This paper describes a methodology to automate search and selection of data around specific phenomena. Different components of the methodology including the assumptions, the process, and the relevancy ranking algorithm are described. The paper makes two unique contributions to improving data search and discovery capabilities. First, the paper describes a novel methodology developed for automatically curating data around a topic using Earth science metadata records. Second, the methodology has been implemented as a stand-alone web service that is utilized to augment search and usability of data in a variety of tools.

Influence of Organic Amendment and Compaction on Nutrient Dynamics in a Saturated Saline-Sodic Soil from the Riparian Zone.

Cattle grazing in wet riparian pastures may influence nutrient dynamics due to nutrient deposition in feces and urine, soil compaction, and vegetation loss. We conducted a lab incubation study with a saline-sodic riparian soil to study nutrient (N, P, S, Fe, Mn, Cu, and Zn) dynamics in soil pore water using Plant Root Simulator (PRS) probes and release of nutrients into the overlying ponded water during flooding. The treatment factors were organic amendment (manure, roots, and unamended control), compaction (compacted, uncompacted), and burial time (3, 7, and 14 d). Amendment treatment had the greatest impact on nutrient dynamics, followed by burial time, whereas compaction had little impact. The findings generally supported our hypothesis that organic amendments should first increase nitrate loss, then increase Mn mobility, then Fe mobility and associated release of P, and finally increase sulfate loss. Declines in nitrate due to amendment addition were small because nitrate was at low levels in all treatments due to high denitrification potential instead of being released to soil pore water or overlying water. Addition of organic amendment strongly increased Mn and Fe concentrations in overlying water and of adsorbed Fe on PRS probes but only increased Mn on PRS probes on Day 3 due to subsequent displacement from ion exchange membranes. Transport of P to overlying water was increased by organic amendment addition but less so for manure than roots despite higher P on PRS probes. The findings showed that saline-sodic soils in riparian zones are generally a nutrient source for P and are a nutrient sink for N as measured using PRS probes after 3 to 7 d of flooding.

Mechanisms of cell migration in the adult brain: modelling subventricular neurogenesis.

Neurogenesis has been the subject of active research in recent years. Although the majority of neurons form during the embryonic period, neurogenesis continues in restricted regions of the mammalian brain well into adulthood. In rodent brains, neuronal migration is present in the rostral migratory stream (RMS), connecting the subventricular zone to the olfactory bulb (OB). The migration in the RMS is characterised by a lack of dispersion of neuroblasts into the surrounding tissues and a highly directed motion towards the OB. This study uses a simple mathematical model to investigate several theories of migration of neuroblasts through the RMS proposed in the literature, including chemo-attraction, chemorepulsion, general inhibition and the presence of a migration-inducing protein. Apart from the general inhibition model, all the models were able to provide results in good qualitative correspondence with the experimental observations.

Transport of Residual Nitrogen and Carbon through Intact Soil Cores Amended with Stockpiled Feedlot Manure with Wood-Chip or Straw Bedding.

The environmental impact of using wood chips instead of straw bedding with feedlot manure on transport and leaching potential from feedlot manure is unknown. Our main objective was to determine if transport of total N, total organic N, NO-N, and nonpurgeable organic C (NPOC) to subsurface soil was lower for soils amended with feedlot manure if combined with wood chips compared with straw. A secondary objective was to compare transport of N and NPOC with organic amendments versus inorganic fertilizer. Stockpiled feedlot manure (SM) with wood chip (SM-WD) or barley straw (SM-ST) bedding at 39 Mg (dry wt.) ha, and inorganic fertilizer (IN) at 100 kg N ha, was applied annually for 13 yr to a clay loam soil in a replicated field experiment in southern Alberta, Canada. Intact soil cores were taken in fall 2011 (0-30 cm depth) from the three treatments, and the residual N and NPOC were eluted from the soil cores. Total N, total organic N, and NPOC were determined on filtered (1.0 µm) effluent samples that are primarily dissolved fraction but may contain some small particulate N and C. Peak concentrations, flow-weighted mean concentrations, and mass loss of total N, total organic N, NO-N, and NPOC were significantly ( ≤ 0.05) lower by 35 to 86% for SM-WD compared with SM-ST. Mean recoveries were also significantly lower for SM-WD than SM-ST by 0.07 to 8% (absolute difference). The transport behavior was similar for SM-WD and IN treatment, but solute transport was greater for SM-ST than for IN. Application of stockpiled feedlot manure with wood chips instead of straw bedding may be a beneficial management practice to reduce transport and leaching potential of N fractions and NPOC.

A mathematical model of adult subventricular neurogenesis.

Neurogenesis has been the subject of active research in recent years and many authors have explored the phenomenology of the process, its regulation and its purported purpose. Recent developments in bioluminescent imaging (BLI) allow direct in vivo imaging of neurogenesis, and in order to interpret the experimental results, mathematical models are necessary. This study proposes such a mathematical model that describes adult mammalian neurogenesis occurring in the subventricular zone and the subsequent migration of cells through the rostral migratory stream to the olfactory bulb (OB). This model assumes that a single chemoattractant is responsible for cell migration, secreted both by the OB and in an endocrine fashion by the cells involved in neurogenesis. The solutions to the system of partial differential equations are compared with the physiological rodent process, as previously documented in the literature and quantified through the use of BLI, and a parameter space is described, the corresponding solution to which matches that of the rodent model. A sensitivity analysis shows that this parameter space is stable to perturbation and furthermore that the system as a whole is sloppy. A large number of parameter sets are stochastically generated, and it is found that parameter spaces corresponding to physiologically plausible solutions generally obey constraints similar to the conditions reported in vivo. This further corroborates the model and its underlying assumptions based on the current understanding of the investigated phenomenon. Concomitantly, this leaves room for further quantitative predictions pertinent to the design of future proposed experiments.

Automated spike sorting algorithm based on Laplacian eigenmaps and k-means clustering.

This study presents a new automatic spike sorting method based on feature extraction by Laplacian eigenmaps combined with k-means clustering. The performance of the proposed method was compared against previously reported algorithms such as principal component analysis (PCA) and amplitude-based feature extraction. Two types of classifier (namely k-means and classification expectation-maximization) were incorporated within the spike sorting algorithms, in order to find a suitable classifier for the feature sets. Simulated data sets and in-vivo tetrode multichannel recordings were employed to assess the performance of the spike sorting algorithms. The results show that the proposed algorithm yields significantly improved performance with mean sorting accuracy of 73% and sorting error of 10% compared to PCA which combined with k-means had a sorting accuracy of 58% and sorting error of 10%.A correction was made to this article on 22 February 2011. The spacing of the title was amended on the abstract page. No changes were made to the article PDF and the print version was unaffected.

Influence of streambank fencing on the environmental quality of cattle-excluded pastures.

Limited information exists on the effect of streambank fencing on riparian zone pastures. The objective of this study was to test the hypothesis that 4 to 6 yr of streambank fencing would improve the environmental quality of the cattle-excluded pasture compared with the grazed pasture and cause the fenced pasture to act as a buffer or filter strip. Rangeland health, vegetative and soil properties, and rainfall simulation runoff were measured in the cattle-excluded and adjacent grazed native pastures along the fenced reach of the Lower Little Bow River in southern Alberta, Canada, for 3 yr (2005-2007). Rangeland health was improved (health score increase from 55 to 72%); vegetation cover (13-21%) and standing litter (38-742%) were increased; and bare soil (72-93%) and soil bulk density (6-8%) were decreased under cattle exclusion, indicating an improvement in environmental quality from streambank fencing. In contrast, other vegetation (total and live basal area, fallen litter) and soil properties (soil water and soil C, N, and P) were not improved by cattle exclusion. Cattle exclusion significantly (P

Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers.

Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema. A total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance). Emphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV(1)), FEV(1)/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George's Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution. Distribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.

Increased arterial stiffness in patients with chronic obstructive pulmonary disease: a mechanism for increased cardiovascular risk.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with a 2-3-fold increase in the risk of ischaemic heart disease, stroke and sudden death. The mechanisms responsible for this association are not clear and appear to be independent of smoking history. OBJECTIVE: We test the hypothesis that patients with COPD have increased arterial stiffness and blood pressure in comparison with age and smoking matched controls. METHODS: In a prospective case control study, we recruited 102 patients with COPD and 103 healthy controls matched for age and smoking status. Patients were assessed by clinical history and spirometry, with arterial stiffness and blood pressure determined using radial artery applanation tonometry and sphygmomanometry. RESULTS: Patients with COPD had increased arterial stiffness compared with matched controls, with elevated augmentation pressure (17 (1) vs 14 (1) mm Hg; p = 0.005) and a reduced time to wave reflection (131 (1) vs 137 (2) ms; p = 0.004). These differences were associated with increases in both diastolic (82 (1) vs 78 (1) mm Hg; p = 0.005) and systolic blood pressure (147 (2) vs 132 (2) mm Hg; p<0.001). Serum C reactive protein concentrations were threefold higher in patients (6.1 (0.9) vs 2.3 (0.4) mg/l; p = 0.001). Data are presented as mean (SEM). CONCLUSIONS: Patients with COPD have increased arterial stiffness and blood pressure in comparison with controls matched for age and smoking status. We speculate that increased systemic inflammation and vascular dysfunction could potentially explain the excess cardiovascular morbidity and mortality associated with COPD.

Diagnosis and treatment of overactive bladder.

Overactive bladder is a very common condition, affecting an estimated 50 to 100 million people worldwide. More than 90% of women with overactive bladder have no recognizable pathology. Several risk factors have been recognized for overactive bladder syndrome and incontinence including age, diabetes, Caucasian race, and hormone replacement therapy. The gold standard for diagnosing detrusor overactivity is multichannel urethrocystometry, although single channel cystometry or even simple cystometry may be used. A variety of interventions are available for the treatment of the overactive bladder syndrome. These include behavioral interventions, pelvic floor electrical stimulation, electromagnetic innervation, neuromodulation, intravesical instillations and injections, operative bladder augmentation, and pharmacotherapy. In any therapy for overactive bladder symptoms, expectations play a pivotal role in success or failure, and communication between the healthcare provider and the patient is essential for setting and achieving treatment goals.

Aberration correction by maximizing generalized sharpness metrics.

The technique of maximizing sharpness metrics has been used to estimate and compensate for aberrations with adaptive optics, to correct phase errors in synthetic-aperture radar, and to restore images. The largest class of sharpness metrics is the sum over a nonlinear point transformation of the image intensity. How the second derivative of the point nonlinearity varies with image intensity determines the effects of various metrics on the imagery. Some metrics emphasize making shadows darker, and other emphasize making bright points brighter. One can determine the image content needed to pick the best metric by computing the statistics of the image autocorrelation or of the Fourier magnitude, either of which is independent of the phase error. Computationally efficient, closed-form expressions for the gradient make possible efficient search algorithms to maximize sharpness.

Hydrological properties of a clay loam soil after long-term cattle manure application.

Limited information exists on the effect of long-term application of beef cattle (Bos taurus) manure on soil hydrological properties in the Great Plains region of North America. A site on a clay loam soil (Typic Haploboroll) was used to examine the effect of manure addition on selected soil hydrological properties in 1997 and 1998. The manure was annually applied in the fall for 24 yr at one, two, and three times the recommended rates (in 1973) under dryland (0, 30, 60, and 90 Mg ha(-1) wet basis) and irrigation (0, 60, 120, and 180 Mg ha(-1)). Manure significantly (P < or = 0.05) increased soil water retention (0-5 and 10-15 cm) by 5 to 48% compared with the control at most potentials between 0 and -1500 kPa. Field soil water content (0-5 and 10-15 cm) was increased by 10 to 22% in the summers of 1997 and 1998. Manure increased ponded infiltration by more than 200% at 90 Mg ha(-1) under dryland (1998) and at rates > or = 120 Mg ha(-1) under irrigation (1997). Field-saturated hydraulic conductivity (Kfs) of surface soil (1-cm depth) was significantly increased by 76 to 128% under dryland (1998) and irrigation (1997), as were number of pores > 1120 microm in diameter (37-128% increase). In contrast, manure rate had little or no effect on unsaturated hydraulic conductivity [K(psi)] values (-0.3, -0.5, -0.7, and -1.0 kPa) in 1997 and 1998. Overall, soil hydrological parameters generally had a neutral or positive response to 24 yr of annual manure addition.

Preischemic hyperglycemia-aggravated damage: evidence that lactate utilization is beneficial and glucose-induced corticosterone release is detrimental.

Aerobic lactate utilization is crucial for recovery of neuronal function posthypoxia in vitro. In vivo models of cerebral ischemia pose a conceptual challenge when compared to in vitro models. First, the glucose paradox of cerebral ischemia, namely, the aggravation of delayed neuronal damage by preischemic hyperglycemia, cannot be reproduced in vitro. Second, in vitro elevated glucose levels protect against ischemic (hypoxic) damage, an outcome that has seldom been reproduced in vivo. Employing a rat model of cardiac-arrest-induced transient global cerebral ischemia (TGI), we found that hyperglycemic conditions, when induced 120-240 min pre-TGI, significantly reduced post-TGI neuronal damage as compared to normoglycemic conditions. In contrast, hyperglycemia, when induced 15-60 min pre-TGI, significantly aggravated post-TGI neuronal damage. Brain lactate levels in rats loaded with glucose either 15 min or 120 min pre-TGI were significantly and equally higher than those of control, saline-injected rats. The beneficial effect of 120 min pre-TGI glucose loading was abolished by lactate transport inhibition. A significant increase in blood corticosterone (CT) levels was observed upon glucose loading that peaked at 15-30 min and returned to baseline levels by 60-120 min. When rats loaded with glucose 15 min pre-TGI were treated with metyrapone, a CT synthesis inhibitor, a significantly lower degree of delayed neuronal damage in comparison to both untreated, 15 min glucose-loaded rats and normoglycemic, control rats was observed. Thus, although elevated levels of brain lactate cannot explain the glucose paradox of cerebral ischemia, hyperglycemia-induced, short-lived elevation in CT blood levels could. More importantly, lactate appears to play a crucial role in improving postischemic outcome.

Intracranial surgery: to shave or not to shave?

OBJECTIVE: In an effort to improve patient confidentiality as well as cosmesis, the authors have stopped shaving for all intracranial procedures. The objective was to determine whether this lack of shaving increased the postoperative infection rate. DESIGN: A retrospective study was performed comparing all intracranial surgical procedures performed in the last 2(1/2) years, when hair was not shaved, with the infection rate in patients who did have their hair shaved in the preceding 3(1/2) years. SETTING: An academic tertiary care referral center. PATIENTS: Every patient (children and adults) who underwent an intracranial procedure by the skull base surgery team was included. Similar patient demographics were used for the hair-shaved group. INTERVENTION(S): Intracranial procedures consisted of acoustic tumor removal, vestibular nerve sections, skull base surgery procedures, vascular decompressions, and craniotomies for benign and malignant tumors. MAIN OUTCOME MEASURES: The most essential criterion was to determine whether postoperative wound infection developed in a patient. This was documented as either minor (stitch abscess or wound dehiscence), moderate (wound breakdown requiring inpatient or outpatient therapy, such as oral or intravenous antibiotics), or severe (significant wound breakdown that required hospitalization, with surgical debridement and antibiotics). RESULTS: In all, 150 patients were not shaved for their intracranial procedures; postoperative wound infections developed in 11 (7%). The infections were minor (6), moderate (5), and severe (0). By comparison, 100 patients undergoing intracranial procedures had their hair shaved. In this group, the number of infections noted was 6 (6%). Their categorization into mild, moderate, and severe was 4, 2, and 0, respectively. Statistical analysis did not reveal any significant difference between the two infection rates. CONCLUSIONS: The rate of postoperative wound infection was statistically no greater when the hair was shaved than when it was not. Thus, for patient confidentiality as well as patient esteem, we recommend not shaving hair for intracranial procedures.