Overload Profile Research Articles

Prevalence of HFE-related haemochromatosis and secondary causes of hyperferritinaemia and their association with iron overload in 1059 French patients treated by venesection.

Venesection is the key therapy in haemochromatosis, but it remains controversial in hyperferritinaemia with moderate iron accumulation. There is substantial evidence that the results of HFE genotyping are routinely misinterpreted, while elevated serum ferritin has become more frequent in recent years in white adult populations following the increase of obesity and metabolic traits. To examine the reasons for prescribing venesection in 1,059 French patients during the period 2012-2015, determine the true prevalence of HFE-related haemochromatosis, and compare iron overload profiles between haemochromatosis and non-haemochromatosis patients. Only 258 of the 488 patients referred for haemochromatosis had the p.[Cys282Tyr];[Cys282Tyr] disease causative genotype (adjusted prevalence: 24.4%). Of the 801 remaining patients, 112 (14.0%) had the debated p.[Cys282Tyr];[His63Asp] compound heterozygote genotype, 643 (80.3%) had central obesity, 475 (59.3%) had metabolic syndrome (MetS) and 93 (11.6%) were heavy drinkers. The non-haemochromatosis patients started therapeutic venesection 9years later than haemochromatosis patients (P<0.001). Despite similar serum ferritin values, they had lower transferrin saturation (41.1% vs 74.3%; P<0.001), lower amounts of iron removed by venesection (1.7 vs 3.2g; P<0.001) and lower hepatic iron concentrations (107 vs 237µmol/g; P<0.001). Haemochromatosis is over-diagnosed and is no longer the main reason for therapeutic venesection in France. Obesity and other metabolic abnormalities are frequently associated with mild elevation of serum ferritin, the MetS is confirmed in ~50% of treated patients. There is a minimal relationship between serum ferritin and iron overload in non-p.Cys282Tyr homozygotes. Our observations raise questions about venesection indications in non-haemochromatosis patients.

Meso-scopic model for progressive failure of resin impregnated yarns in composite overwrapped pressure vessels (COPVs)

ABSTRACT Composite Overwrapped Pressure Vessels (COPVs) are widely used in space launch vehicles and the automotive industry. Due to the potential for catastrophic loss caused by failure of COPVs, improved understanding of its mechanical and damage growth behavior is necessary to ensure its safe operation. In this paper, we described a developed mesoscopic model with the capability of modeling tows/yarns with inserted, in-ply interface elements and interface layers as resin rich zones. Furthermore, the model realizes 1) arbitrary winding angle build-up of overwrap plies, 2) controllable detailed dimensions, and 3) user defined material behavior for all regions. These features are critical for potential studies of in-situ and parametric overwrap failure in COPVs. In the present work, stress profiles and progressive failure around a single tow break are shown by case studies involving various interface and damage evolution properties. The investigation indicates that the strength and damage evolution law of interface elements both have direct effect on the stress concentration factors and damage evolution around a tow break/fracture. Resulting physical phenomena and stress overload profile are discussed as well.

New optimization method based on energy management in microgrids based on energy storage systems and combined heat and power

AbstractMicrogrids can be assumed as a solution model for green energy sources, energy storage systems, and combined heat and power (CHP) systems. In this work, the cost and emission minimization based on a demand response (DR) program is considered an optimization problem. To solve the mentioned problem a new multiobjective optimization algorithm (improved particle swarm optimization) is proposed based on a fuzzy mechanism to select the optimal value. The microgrid system includes two CHP units, fuel cell and battery systems, and the heat buffer tank. In this problem, two different feasible operating regions have been assumed in CHPs. Accordingly, to decrease the operational cost, time‐of‐use, and real‐time pricing DR programs have been simulated, and the impacts of the mentioned models are evaluated overload profiles. The effectiveness of proposed models has been applied on different cases studies by different scenarios. The proposed model solved the DR program, time of use‐DR and real‐time pricing‐DR problems. The proposed model could reduce the cost about 10%.

Pulmonary Iron Homeostasis in Hepcidin Knockout Mice.

Pulmonary iron excess is deleterious and contributes to a range of chronic and acute inflammatory diseases. Optimal lung iron concentration is maintained through dynamic regulation of iron transport and storage proteins. The iron-regulatory hormone hepcidin is also expressed in the lung. In order to better understand the interactions between iron-associated molecules and the hepcidin-ferroportin axis in lung iron balance, we examined lung physiology and inflammatory responses in two murine models of systemic iron-loading, either hepcidin knock-out (Hepc KO) or liver-specific hepcidin KO mice (Hepc KOliv), which do (Hepc KOliv) or do not (Hepc KO) express lung hepcidin. We have found that increased plasma iron in Hepc KO mice is associated with increased pulmonary iron levels, consistent with increased cellular iron uptake by pulmonary epithelial cells, together with an increase at the apical membrane of the cells of the iron exporter ferroportin, consistent with increased iron export in the alveoli. Subsequently, alveolar macrophages (AM) accumulate iron in a non-toxic form and this is associated with elevated production of ferritin. The accumulation of iron in the lung macrophages of hepcidin KO mice contrasts with splenic and hepatic macrophages which contain low iron levels as we have previously reported. Hepc KOliv mice with liver-specific hepcidin deficiency demonstrated same pulmonary iron overload profile as the Hepc KO mice, suggesting that pulmonary hepcidin is not critical in maintaining local iron homeostasis. In addition, the high iron load in the lung of Hepc KO mice does not appear to enhance acute lung inflammation or injury. Lastly, we have shown that intraperitoneal LPS injection is not associated with pulmonary hepcidin induction, despite high levels of inflammatory cytokines. However, intranasal LPS injection stimulates a hepcidin response, likely derived from AM, and alters pulmonary iron content in Hepc KO mice.

Volume Overload Profiles in Patients With Preserved and Reduced Ejection Fraction Chronic Heart Failure: Are There Differences? A Pilot Study

ObjectivesThis study aimed to characterize volume profiles and their differences in heart failure (HF) patients with preserved (HFpEF) and reduced (HFrEF) ventricular systolic function. BackgroundThe extent and distribution of volume overload and the associated implications for volume management have not been studied in decompensated HFpEF compared with HFrEF. MethodsTotal blood volume (TBV) was quantitated using a standardized computer-based radiolabeled albumin dilution technique. ResultsTwenty HFpEF and 35 HFrEF patients were evaluated at hospital admission. TBV was expanded by 27 ± 21% (range -5.2% to 77%; p = 0.002) and 37 ± 25% (0% to 107%; p < 0.001), respectively, above normal volumes. Red cell mass (RBCM) was expanded in HFrEF (24 ± 31%; p = 0.004) but within normal limits in HFpEF (8 ± 34%; p = 0.660) with, however, large variability in both groups. RBCM excess was more prominent in HFrEF (63% vs. 45%) than the RBCM deficit in HFpEF (35% vs.14%). With diuresis, TBV decreased to 25 ± 20% (p = 0.029) in HFrEF but was not changed in HFpEF (18 ± 20% [p = 0.173]). Body weight declined 6.6 ± 4.4 kg in HFrEF and 10.5 ± 8.3 kg (p = 0.026) in HFpEF. Interstitial fluid losses accounted for 85 ± 13% (HFrEF) and 93 ± 6% (HFpEF) (p = 0.012) of total volume removed. ConclusionsTBV profiles differ between HFpEF and HFrEF patients with DCHF. Quantitated volume analysis revealed both significant RBCM (polycythemia) and plasma volume excess in HFrEF, whereas a higher RBCM deficit (true anemia) was demonstrated in HFpEF. Diuresis produced only a modest reduction in intravascular volumes with persistent hypervolemia in both groups at discharge, but overall more total body fluid was lost in HFpEF. These profile differences have implications for individualizing volume management.

Experimental investigation of initial and subsequent yield surfaces for laminated metal matrix composites

The aim of this work is to construct yield surfaces to describe initial yielding and characterize hardening behavior of a highly anisotropic material. A methodology for constructing yield surfaces for isotropic materials using axial–torsion loading is extended to highly anisotropic materials. The technique uses a sensitive definition of yielding based on permanent strain rather than offset strain, and enables multiple yield points and multiple yield surfaces to be conducted on a single specimen. A target value of 20 × 10 −6 is used for Al 2O 3 fiber reinforced aluminum laminates having a fiber volume fraction of 0.55. Sixteen radial probes are used to define the yield locus in the axial–shear stress plane. Initial yield surfaces for [0 4], [90 4], and [0/90] 2 fibrous aluminum laminates are well described by ellipses in the axial–shear stress plane having aspect ratios of 10, 2.5, and 3.3, respectively. For reference, the aspect ratio of the Mises ellipse for an isotropic material is 1.73. Initial yield surfaces do not have a tension–compression asymmetry. Four overload profiles (plus, ex, hourglass, and zee) are applied to characterize hardening of a [0/90] 2 laminate by constructing 30 subsequent yield surfaces. Parameters to describe the center and axes of an ellipse are regressed to the yield points. The results clearly indicate that kinematic hardening dominates so that material state evolution can be described by tracking the center of the yield locus. For a nonproportional overload of ( σ, τ) = (500, 70) MPa, the center of the yield locus translated to ( σ, τ) = (430, 37) MPa and the ellipse major axis was only 110 MPa.

Effect of mobile phase anionic additives on selectivity, efficiency, and sample loading capacity of cationic drugs in reversed-phase liquid chromatography

In the present work, we study the effect of mobile phase anionic additive type and concentration on the selectivity, efficiency, and sample loading capacity of cationic drugs in reversed-phase liquid chromatography (RPLC). The type and concentration of an anionic additive are known to have a strong effect on the absolute retention of cations in RPLC; in contrast they have only a small effect on the selectivity of one cation relative to a second as seen here. This is mainly due to the similarity of the ion pair formation constants between the selected cations. The limiting retention factors of cations (i.e. the retention factor of the fully ion-paired analyte at very high additive concentration) are roughly proportional to their inherent hydrophobicities (i.e. the retention factor of the analyte in the absence of the anionic additive). With a given anion, differences in ion pairing strength between the solutes are required for effective selectivity adjustment. Based on the Wade–Lucy–Carr (W–L–C) kinetic model of overload peaks, the approach we developed in our previous work was used to study the effect of mobile phase anionic additives type and concentration on the limiting plate count ( N 0) and sample loading capacity ( ω 0.5) of various cationic drugs. Under linear chromatographic conditions, where the analyte exhibits its smallest peak width and thus maximum apparent plate count, the type and concentration of anionic additives have almost no effect on peak width. In comparison to neutral analytes the sorption isotherms of cationic species are very easily overloaded even when many fewer moles of cations as compared to neutrals are injected. We showed that different anionic additives profoundly affect the cations’ “overload profiles” (i.e. plots of plate count versus amount injected) by changing the sample loading capacities. The increase in sample loading capacities with different anions show the same order as the extent of ion pairing between the anions and the basic analytes. The detrimental effect of sample overloading on peak width can be greatly diminished by using either a stronger ion pairing agent or a higher concentration of a given ion pairing agent. Both effects operate by increasing the sample loading capacity, thereby allowing more solute to be injected. We believe that the increase in sample loading capacity described above is due in part to the increase in the number of ion-exchange sites as more anions sorb to the stationary phase. At the same time, the formation of a neutral ion-paired analyte also increases the amount of cation which can be loaded onto the stationary phase by allowing a greater fraction of the analyte to be present in the stationary phase as an electrically neutral (i.e. ion-paired) species.

A new approach to the determination of column overload characteristics in reversed-phase liquid chromatography

Column overloading is very common during the separations of basic analytes in analytical scale reversed-phase liquid chromatography (RPLC). Due to the complex interactions of ionic analytes with stationary and mobile phases, only a very small amount of ionized sample compared to the amount of nonpolar solute can be injected before the peak shape is distorted by non-linear chromatographic processes. Often the amount that can be injected before overload is observed is so small that the signal is quite noisy, thereby making the measured plate count imprecise and possibly inaccurate. The purpose of the present study was to develop a practical method for the precise measurement of the plate count and a column overload parameter using a simple but mathematically rigorous model of Langmuirian non-linear chromatography. An “overload profile”, i.e. a plot of apparent plate count versus amount injected, is characterized by two parameters: the limiting plate count ( N 0) and the column sample loading capacity ( ω 0.5). The limiting plate count is the plate count that should be observed when the amount of sample injected is so small that a linear isotherm pertains. The column sample loading capacity, which is taken as the sample load that leads to a plate count equal to half of the limiting plate count, is a measure of the maximum amount of sample that can be injected into that column. The approach was tested by applying it to the study of cationic analytes in RPLC. We show that N 0 under constant conditions (column length, flow rate, mobile phase composition, etc.) is almost independent of column type (manufacturer); however, different column types (at the same length, diameter and flow rate) exhibit clear differences in their sample loading capacity ( ω 0.5). We believe that for most well packed type B columns, the column sample loading capacity and not the limiting plate count is the more important property that accounts for most of the apparent differences in peak width when different types of columns are examined.

Existe-t-il un intérêt à étudier par électrophorèse les protéinuries « quantitativement normales » ?

In this retrospective study over 6 years (658 patients, M/F: N=353/N=305, age: 60±16 years), the usefulness of investigating « quantitatively normal » (<0.15 g/24 hours) proteinuria by electrophoresis using the Hydragel protéinurie® kit (Sebia) was evaluated. Total proteinuria was 0.08 g/L (median: 0.05–0.89 g/L). In 83.7% of cases, urinary electrophoresis (EP) was normal; pathologic profiles were free light chain overload (N=93), intact immunoglobulin overload (N=8), mixed profiles (glomerular and tubular) and one case of Plasmion® interference. All patients (except two from hematology) with an overload profile had an abnormality in the β- or γ-globulins by serum EP, most frequently a monoclonal peak (median: 24.1 g/L, <0.5–75.2 g/L). Free light chains quantification by densitometry was possible in 26% of cases and when proteinuria was above 0.08 g/L. Mixed profiles corresponded to incomplete or inaccurate 24 hours urinary volume. EP analysis of quantitatively normal proteinuria (<0.15 g/24 hours) thus appears useless in the absence of an associated abnormality of the β- or γ-globulin by serum EP (monoclonal peak, hypogammaglobulinemia). In the presence of a monoclonal peak in the serum or an hypo-γ-globulinemia, the Hydragel protéinurie® kit allows the detection (and in some cases the quantification) of free light chains when their concentration is above ~15 mg/L.

Influence of pressure on the chromatographic behavior of insulin variants under nonlinear conditions

The effect of pressure on the chromatographic behavior of two insulin variants in RPLC was investigated on a YMC-ODS C 18 column, under nonlinear conditions. The adsorption isotherm data of porcine insulin and Lispro were measured at average column pressures ranging from 52 to 242 bar. These data fit well to the Toth and the bi-Langmuir isotherm models. The saturation capacity increases rapidly with increasing pressure while the affinity (or equilibrium) constant and the parameter characterizing the surface heterogeneity decrease. It is noteworthy that the distribution coefficient of the insulin variants increases with increasing pressure whereas their equilibrium constant b decreases for porcine insulin and increases for Lispro. The association constant b ds, which characterizes the adsorption and desorption equilibrium of insulin in the system, increases with increasing pressure. The excellent agreement between the experimental overloaded profiles recorded under different pressures and those calculated using the POR model suggests that the chromatographic behavior of insulin is controlled more by equilibrium thermodynamics than by the mass transfer kinetics. The latter seems to be nearly independent of the average column pressure. Thus, increasing the average column pressure is an efficient, albeit costly, way to increase the loading capacity of the column, hence the production rate in preparative chromatography.

Influence of sample mass on the performance of reversed-phase columns in the analysis of strongly basic compounds by high-performance liquid chromatography

The overloading behaviour of two different silica-based ODS columns was investigated using six basic probe compounds with methanolic mobile phases buffered at pH 3.0 and pH 7.0. At pH 3.0, peak shape deteriorated seriously in most cases when the sample mass was increased above about 0.5 μg, as has been reported previously. The rate at which efficiency loss occurred varied with the solute and column, as reflected in values for the saturation capacity w s calculated for the solute/column combination. The model proposed by Snyder and co-workers was shown to allow prediction of the column overload profile for five of the basic solutes, although pyridine gave anomalous behaviour. Whereas peak shapes at pH 7.0 were generally worse than at pH 3.0, no deterioration was shown with sample masses up to at least 10 μg. In some cases peak shape showed significant improvement as sample mass was increased. Thus, at high sample loading, analysis at pH 7.0 may be preferred for some solutes. It was shown that while overloading has not influenced our previous column evaluation studies, great care is needed to avoid confounding the results of such studies by these effects.

Stress concentrations around multiple fiber breaks in an elastic matrix with local yielding or debonding using quadratic influence superposition

A new computational technique, called the quadratic influence superposition (QIS) technique, is developed to study the stresses around arbitrary arrays of fiber breaks in a unidirectional composite loaded in simple tension, and consisting of elastic fibers in a matrix, which is either elastic-perfectly plastic or which can debond at the interface leaving residual friction. The method involves extending a recently developed break influence superposition (BIS) technique, where to model the behavior of damaged (yielded or debonded) matrix elements, we use special compensating shear stress profiles and develop the corresponding influence functions. The QIS technique appears to be at least an order of magnitude more efficient than other numerical schemes as the computation time is tied mainly to the amount of damage, and it is more accurate than a simpler version of this technique developed earlier. In illustrative examples, the method determines the Mode I fiber and matrix stress distributions around a “center crack” consisting of up to 31 contiguous fiber breaks. Incremental treatment is needed to establish the extent of the inelastic regions and the results, which achieve excellent agreement with exact shear lag analyses, clearly show that QIS calculated these correctly. Results show that the extent of the matrix damage region increases approximately linearly with applied load and nonlinearly with the number of breaks. The stress concentrations and overload profiles along nearby unbroken fibers are altered as compared to the fully elastic case with magnitudes reduced but length scales increased.

Assessment of overload profiles and interfacial shear strength in unidirectional fibre composites via quantitative fractography

A stereometric method for digitising the fracture surface of unidirectional fibre composites is used to calculate the breaking height differences of each fibre to its six nearest neighbours. From this height distribution the overload profile along the fibres, the critical length, interfacial shear strength, and the characteristic strength of the fibres are derived. This method is applied to ceramic fibre reinforced aluminium matrix composites tested in three point bending.MST/3004

Diminished tolerance of prehypertrophic, cardiomyopathic Syrian hamster hearts to Ca2+ stresses.

Although abnormal myocardial calcium homeostasis in the cardiomyopathic hamster (CMH) has been documented in the hypertrophic stage of the disease, the Ca2+ tolerance before the hypertrophic stage has not been investigated. We studied isovolumic contractile function in response to a variety of Ca2+ stresses including increases in perfusate [Ca2+] (Cao), the Ca2+ channel agonist Bay K 8644, and alpha- or beta-adrenergic agonists of isolated perfused hamster hearts from 24-45-day-old male CMH, BIO 14.6 strain, and age- and sex-matched F1B strain controls. The coronary flow at a constant perfusion pressure did not differ between two groups at baseline or after any Ca2+ stress. At a Cao of 1.0 mM, neither end-diastolic pressure (EDP) nor developed pressure (DP) nor half relaxation time (RT1/2) during stimulation at 1-3 Hz differed between the two groups; as Cao was increased up to 10 mM, CMH hearts showed a lower threshold for the occurrence of a Ca2+ overload profile: EDP and RT1/2 increased to a greater, and DP to a lesser, extent in CMH than in control hearts. To determine whether calcium influx via Ca2+ channels mediates the lower threshold for Ca2+ overload in CMH hearts, we measured resting pressure and scattered laser light intensity fluctuation (SLIF) in unstimulated hearts. Prior studies have shown that SLIF is generated by microscopic tissue motion caused by diastolic spontaneous sarcoplasmic reticulum Ca2+ release and that SLIF amplitude reflects the extent of cell and sarcoplasmic reticulum Ca2+ loading. The Ca(2+)-dependent increase in resting pressure in unstimulated hearts was highly correlated with an increase in SLIF, and this relation was steeper in CMH than in control hearts. CMH hearts also showed a reduced threshold for the occurrence of a Ca2+ overload profile in response to the adrenergic receptor agonists and the Ca2+ channel agonist during electrical stimulation in a Cao of 2.0 mM: maximum DP achieved with each agonist was significantly less and the dose-response curves to each agonist were shifted leftward in CMH versus control hearts. In CMH hearts EDP began to increase at a significantly lower concentration of each agonist, and the maximum extent of increase in EDP in response to all agonists was significantly enhanced compared with control hearts. In response to beta-adrenergic or Ca2+ channel agonists, neither resting pressure nor SLIF in unstimulated hearts increased in control or in CMH hearts. In contrast, in response to alpha-adrenergic stimulation, both SLIF and resting pressure increased to a greater extent in CMH than in control hearts.(ABSTRACT TRUNCATED AT 400 WORDS)