RESUMEN
Industry desires a digital thread of information that aligns as-designed, as-planned, as-executed, and as-inspected viewpoints. An experiment was conducted to test selected open data standards' ability to integrate the lifecycle stages of engineering design, manufacturing, and quality assurance through a thorough implementation of a small scale model-based enterprise. The research team set out to answer: from design, through production, and final inspections, what are the hurdles that a manufacturer would face during the development of a fully linked and integrated information chain? The research team was not able to fully link all the required information, but value for industry was still identified. This paper presents the results of the experiment, provides guidance on how to overcome or mitigate identified challenges, and discusses the benefits or incentives to be gained from tracing or linking information through multiple stages a product lifecycle.
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Engineering change is a significant cost sink in many projects. While avoiding and mitigating the risk of change is the ideal approach, mistakes and improvements are recognized inevitably as more is learned over time about the quality of the decisions made in a product's design. This paper presents a feasibility and performance analysis of automating engineering change requests to demonstrate the promise for increasing speed, efficiency, and effectiveness of product-lifecycle-wide engineering-change-request processes. To explore this idea, a comparatively simple case study is examined both to mimic the reduced set of alterable aspects of a typical change request and to highlight the need of appropriate search algorithms as brute force methods quickly prohibitively resource intensive. Although such cases may seem trivial for human agents, with the volume of expected change requests in a typical facility, the potential opportunity gain by eliminating or reducing the amount of human effort in low level change requests accumulate into significant returns for industry on time and money. Within this work, the genetic algorithm is selected to demonstrate feasibility due to its broad scope of applicability and low barriers to deployment. Future refinement of this or other sophisticated algorithms leveraging the nature of the standard representations and qualities of alterable design features could produce tools with strong implications for process efficiency and industry competitiveness in the execution of its projects.
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Ethyl ether was detected in the blood of a deceased individual who had inhaled it from a mask while hanging himself. This case led to an investigation into the stability of ether in stored blood samples as described herein. Ether was spiked, at three concentrations, into batches of porcine blood. The blood was apportioned into grey-stoppered collection tubes and stored refrigerated until analysis. The concentration of ether in the blood was assessed at intervals over a two-month period. Analysis was performed by headspace gas chromatography. This study has shown, for a concentration range of 0.1 to 5.0 mg/mL, ether is stable in preserved, refrigerated blood for at least two months.
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Éter/sangre , Éter/envenenamiento , Solventes/análisis , Solventes/envenenamiento , Suicidio , Administración por Inhalación , Adulto , Animales , Conservación de la Sangre , Éter/metabolismo , Humanos , Masculino , Refrigeración , Sensibilidad y Especificidad , Solventes/metabolismo , Manejo de Especímenes , Porcinos , Factores de TiempoRESUMEN
A headspace gas chromatographic (GC) screen for common volatile organic compounds in biological fluids is reported. Common GC phases, DB-1 and DB-WAX, with split injection provide separation and identification of more than 40 compounds in a single 20-min run. In addition, this method easily accommodates quantitation. The screen detects commonly encountered volatile compounds at levels below 4 mg%. A control mixture, providing qualitative and semiquantitative information, is described. For comparison, elution of the volatiles on a specialty phase, DB-624, is reported. This method is an expansion and modification of a screen that had been used for more than 20 years. During its first year of use, the expanded screen has proven to be advantageous in routine forensic casework.
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Cromatografía de Gases/métodos , Medicina Legal/métodos , Compuestos Orgánicos/análisis , Automatización , Humanos , Valores de Referencia , Sensibilidad y Especificidad , VolatilizaciónRESUMEN
A rapid high resolution gas chromatographic method for screening acidic and neutral drugs in blood is described. The procedure involves a single extraction with ethyl acetate. Using flame ionization detection, without derivatization and with on-column methylation, more than 60 drugs of toxicologic importance are detected.
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Preparaciones Farmacéuticas/sangre , Cromatografía de Gases/métodos , Humanos , Concentración de Iones de Hidrógeno , MetilaciónRESUMEN
Two synthetic peptides were evaluated to develop radioligands for midregion-specific radioimmunoassay (RIA) of human parathyroid hormone (hPTH). Both contained the 44-68 sequence of hPTH (no tyrosine residues); one contained a tyrosine residue added to the amino-terminus, (Tyr43)hPTH(43-68). The purified radioligands showed similar chemical properties (stability to storage, efficient phase separation with dextran-coated charcoal, low adsorption to glassware). Both radioligands were tested using three anti-PTH sera of proven clinical utility. While each of these midregion-directed antisera showed unique specificity, they all reacted with high affinity with both radioligands and none of them discriminated significantly between the two synthetic midregion peptides. 125I-(Tyr43)hPTH(43-68) gave RIAs that were 15-50% more sensitive to hPTH(1-84) and the unlabelled synthetic midregion peptides than RIAs using 125I-hPTH(44-68) with all three antisera examined. 125I-(Tyr43)hPTH(43-68) was more susceptible than 125I-hPTH(44-68) to degradation from plasma or serum; this susceptibility was reduced by the peptidase inhibitor aprotinin (500 KIU/ml). Simultaneous RIAs of a series of patient plasmas using either of the two radioligands with antiserum NG5/5 produced indistinguishable discrimination between samples (r = 0.984). Analysis of data on the relation of serum calcium and hPTH midregion immunoreactivity showed a useful separation hyperparathyroidism, primary hypoparathyroidism and secondary hypoparathyroidism.
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Hormona Paratiroidea/análisis , Secuencia de Aminoácidos , Especificidad de Anticuerpos , Cromatografía en Gel , Humanos , Sueros Inmunes , Radioisótopos de Yodo , Fragmentos de Péptidos/análisis , RadioinmunoensayoRESUMEN
The effect of changes in bicarbonate ion concentration on calcium ion concentration was examined in vitro in serum and protein-free solution. The findings in this study support the formation of a calcium-bicarbonate complex (CaHCO3+) that has a KA of 5.20 in protein-free solution. [Ca++] varied inversely with [HCO3-] in both serum and protein-free solution. This variation was independent of the known variation of [Ca++] with pH. In serum [Ca++] varied 0.0036 mM Ca++ per 1 mM change in [HCO3-] compared with a variation of 0.0060 mM Ca++ per 0.01 unit change in pH. Addition of bicarbonate to serum (Pco2 constant) produced a 50% greater decrease in [Ca++] than that produced by a reduction in Pco2 which gave the same pH change. These findings indicate that abnormal bicarbonate concentrations should be considered when ionized calcium concentrations are estimated from total plasma calcium values in acid-base disorders. In metabolic acid-base disorders, the bicarbonate effect adds to the pH effect on calcium ion concentration. In compensated respiratory acid-base disorders, the bicarbonate effect subtracts from the pH effect on calcium ion concentration.
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Bicarbonatos/farmacología , Calcio/sangre , Desequilibrio Ácido-Base/sangre , Bicarbonatos/sangre , Dióxido de Carbono/sangre , Humanos , Concentración de Iones de Hidrógeno , Hipercalcemia/sangre , Presión Parcial , Bicarbonato de SodioRESUMEN
A preliminary investigation was undertaken to determine the feasibility of monitoring saliva levels of drugs for forensic purposes. Single oral doses of the title compounds were administered to healthy volunteers. Plasma and saliva levels were measured and ratios calculated for all drugs except diazepam. Saliva/plasma ratios for methaqualone, diphenhydramine and secobarbital were all less than one and reasonably consistent between collection times and subjects. The saliva/plasma ratios for codeine were more variable, but always greater than one. Although more detailed investigation is necessary, saliva may be a useful medium for forensic monitoring of drug ingestion.
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Drogas Ilícitas/análisis , Preparaciones Farmacéuticas/análisis , Saliva/análisis , Administración Oral , Adulto , Cromatografía de Gases/métodos , Codeína/análisis , Diazepam/análisis , Difenhidramina/análisis , Femenino , Humanos , Drogas Ilícitas/sangre , Masculino , Metacualona/análisis , Secobarbital/análisisRESUMEN
We radioiodinated a synthetic fragment representing residues 44-68 from the middle region of human parathyroid hormone (hPTH). At least 90% of the purified [125I]-hPTH-(44-68) was able to bind to anti-hPTH serum. Antibody-bound [125I]hPTH-(44-68) could be rapidly and efficiently separated from nonbound radioligand by dextran-coated charcoal. [125I]hPTH-(44-68) was not degraded after a 72-h incubation in undiluted plasma at 7 C, and it was stable for many weeks at -20 C in a 1% albumin buffer. [125I]hPTH-(44-68) was used to develop midregion specific PTH RIAs. The immunoreactive PTH concentration in plasma was above the upper limit of the normal range in 39 of 43 patients with primary hyperparathyroidism. Values from the midregion assay and an established carboxy-terminus assay correlated using peripheral plasma from 17 patients with primary hyperparathyroidism (r = 0.84; P less than 0.0001) or using parathyroid gland venous effluent plasma from the same 17 patients (r = 0.79; P less than 0.0005). Gel filtration analysis of peripheral plasma from 2 patients with primary hyperparathyroidism and azotemia suggested peptides possessing midregion immunoreactivity but deficient in carboxyterminus immunoreactivity. Similar peptides were present at higher concentrations in parathyroid gland venous effluent plasma than in peripheral plasma, indicating release from the parathyroid gland. In conclusion, [125I]hPTH-(44-68) had properties favorable for the development of RIAs reactive solely with the midregion of PTH. Fragments secreted in vivo by two human parathyroid glands were reactive in midregion assays but nonreactive in a carboxy-terminus assay.
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Hormona Paratiroidea/sangre , Fragmentos de Péptidos/inmunología , Fenómenos Químicos , Química , Cromatografía en Gel , Humanos , Hiperparatiroidismo/sangre , Radioisótopos de Yodo , Hormona Paratiroidea/inmunología , Radioinmunoensayo/métodos , Uremia/sangreAsunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Sulfanilamidas/sangre , Sulfapiridina/sangre , Sulfasalazina/uso terapéutico , Acetilación , Adolescente , Adulto , Anciano , Antiinfecciosos/sangre , Colitis/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Saliva/análisis , Sulfapiridina/análogos & derivados , Sulfapiridina/orinaRESUMEN
We investigated cAMP metabolism during and after a 15-min infusion of parathyroid hormone (PTH) in 7 normals, 13 patients with typical primary hyperparathyroidism (1HPT), and 6 patients with familial hypocalciuric hypercalcemia (FHH). Nephrogenous urinary cAMP excretion rate reached a peak during the first or second 30 min urine collection interval after the start of the PTH infusion in all subjects. cAMP concentration in plasma reached a peak within 5--20 min of the start of the infusion and then decreased with an initial half-time of 15 min. The peak value of nephrogenous urinary cAMP excretion rate was lower in the group with 1HPT than in the group with FHH or in normals (119 vs, 275 vs. 204 nmol/100 ml glomerular filtrate; P less than 0.0 5 for both comparisons). Similarly, the peak value of plasma cAMP concentration was less in 1HPT subjects than in FHH patients or in normals (11.1 vs. 17.1 vs. 16.6 nmol/100 ml, respectively; P less than 0.05 for both comparisons). For purposes of diagnostic classification, the two hypercalcemia groups could be more completely separated by the values of either the renal calcium to creatinine clearance ratio or the plasma PTH concentration than by the values of inidices of cAMP response to PTH. The differences in cAMP response to PTH between FHH and 1HPT patients could be secondary to differences in circulating PTH concentrations (these are lower in subjects with FHH) or could reflect a renal lesion more closely related to the underlying etiology of FHH.