Thermomechanical Modeling of Laser‐Induced Structural Relaxation and Deformation of Glass: Volume Changes in Fused Silica at High Temperatures

A fully coupled thermomechanical model of the nanoscale deformation in amorphous SiO₂ due to laser heating is presented. Direct measurement of the transient, nonuniform temperature profiles was used to first validate a nonlinear thermal transport model. Densification due to structural relaxation above the glass transition point was modeled using the Tool‐Narayanaswamy (TN) formulation for the evolution of structural relaxation times and fictive temperature. TN relaxation parameters were derived from spatially resolved confocal Raman scattering measurements of Si–O–Si stretching mode frequencies. Together, these thermal and microstructural data were used to simulate fictive temperatures which are shown to scale nearly linearly with density, consistent with previous measurements from Shelby et al. Volumetric relaxation coupled with thermal expansion occurring in the liquid‐like and solid‐like glassy states lead to residual stresses and permanent deformation which could be quantified. However, experimental surface deformation profiles between 1700 and 2000 K could only be reconciled with our simulation by assuming a roughly 2 × larger liquid thermal expansion for a‐SiO₂ with a temperature of maximum density ~150 K higher than previously estimated by Bruckner et al. Calculated stress fields agreed well with recent laser‐induced critical fracture measurements, demonstrating accurate material response prediction under processing conditions of practical interest.     

Analytical strategies for assessing comparability of biosimilars

Biosimilar products are required by regulatory authorities to have appropriate and comparable quality, safety and efficacy with a reference biologic product. The analytical techniques that are available to manufacturers of biosimilar medicines are well advanced and present a range of options to characterize the products and compare them with the relevant marketed reference product. This variety of analytical methods can be used to investigate the attributes of a candidate biosimilar and a reference biologic, and ensures that orthogonal methods can be deployed to characterize a single attribute, facilitating rigorous structural characterization and physicochemical evaluation. These analytical methodologies not only enable evidence for bio‐comparability to be amassed but also enable a developer of biosimilars to incorporate risk mitigation into the development strategy. This review discusses the analytical techniques available to support comparability testing, the handling of reference material and the strategic aspects to commercializing biosimilar or follow‐on biological medicinal products. Copyright © 2011 Society of Chemical Industry     

Scapular avulsion fracture of a high school wrestler

A method of management of a dual stenoses affecting the proximal common carotid artery and the internal carotid artery, the tandem lesion, is described in two cases. The combination of a surgical endarterectomy of the internal carotid artery narrowing and percutaneous balloon dilatation of the more proximal common carotid artery narrowing, via the arteriotomy site, with clamping of the internal carotid artery was successfully employed to avoid an extrathoracic bypass procedure.     

Sustainable Biosolids Management

In 1996, the Water Environment Federation of the USA, the European Water Pollution Control Association (now the European Water Association), and the International Association of Water Quality (now the International Water Association) produced a Global Atlas of Waste-water Sludge and Biosolids Use and Disposal. Various ideas have been proposed to interpret the comparisons of international practices; from these, propositions have been derived for policies on sustainable management which, in the UK, would (a) comply with the recent agreement between the water industry and food retailers, and (b) not reach soil metal limits in less than fifty years. Comparisons are made between Europe and the USA, and the differences are found to be less than were previously assumed. However, changes are imminent, which might alter this situation.     

Temperature dependence of kinetic behaviour of sol–gel deposited electrochromics

The kinetic behaviour of sol-gel deposited electrochromic films is affected by temperature in a complex manner and may be modelled by considering the reaction mechanism, and in particular, the rate-limiting steps. If assumptions are made about the rate-limiting steps in a reaction, a model may be formed which can be used to provide information about the kinetic parameters such as diffusion coefficient and charge transfer resistance. Changes in the free energy of a reaction are observed as changes in the electrical potential associated with the cells and electrodes. We have measured changes in the switching characteristics of a sol–gel deposited electrochromic film and modelled these results in order to extract information about the change in lithium chemical diffusion coefficient (D) with temperature. Values of D estimated using the model described in this paper are in close agreement with those determined by other means, however there are some anomalies at high temperatures.     

Maternal corticotropin-releasing hormone levels in the early third trimester predict length of gestation in human pregnancy

OBJECTIVE: Corticotropin releasing hormone, a hypothalamic neuropeptide, plays a major role in regulating pituitary-adrenal function and the physiologic response to stress. During pregnancy corticotropin-releasing hormone is synthesized in large amounts by the placenta and released into the maternal and fetal circulations. Various endocrine, autocrine, and paracrine roles have been suggested for placental corticotropin-releasing hormone. The aim of this study was to prospectively assess the relationship between maternal plasma concentrations of corticotropin-releasing hormone in the early third trimester of pregnancy and the length of gestation in two groups of deliveries, with and without spontaneous labor. STUDY DESIGN: In a sample of 63 women with singleton intrauterine pregnancies, maternal plasma samples were collected between 28 and 30 weeks' gestation and corticotropin-releasing hormone concentrations were determined by radioimmunoassay. Each pregnancy was dated on the basis of last menstrual period and early ultrasonography. Parity, antepartum risk conditions, presence or absence of spontaneous labor, and birth outcomes were abstracted from the medical record. RESULTS: Maternal corticotropin-releasing hormone levels between 28 and 30 weeks' gestation significantly and negatively predicted gestational length (P < .01) after adjustment for antepartum risk. Moreover, subjects who were delivered preterm had significantly higher corticotropin-releasing hormone levels in the early third trimester (P < .01) than did those who were delivered at term. In deliveries preceded by spontaneous onset of labor, maternal third-trimester corticotropin-releasing hormone levels significantly and independently predicted earlier onset of labor (P < .01) and preterm labor (P < .05), whereas in deliveries effected by induction of labor or cesarean delivery, maternal corticotropin-releasing hormone levels were a marker of antepartum risk but not a statistically independent predictor of gestational length. CONCLUSION: These findings support the premise that placental corticotropin-releasing hormone is potentially implicated in the timing of human delivery in at least two ways. First, placental corticotropin-releasing hormone may play a role in the physiology of parturition. Premature or accelerated activation of the placental corticotropin-releasing hormone system, as reflected by precocious elevation of maternal corticotropin-releasing hormone levels, may therefore be associated with earlier onset of spontaneous labor and resultant delivery. Second, placental corticotropin-releasing hormone may be a marker of antepartum risk for preterm delivery and therefore an indirect predictor of earlier delivery. The implications of these findings are discussed in the context of the neuroendocrinology of placental corticotropin-releasing hormone and human parturition. Furthermore, the role of corticotropin-releasing hormone as a possible effector of prenatal stress in producing alterations in the timing of normal delivery is detailed.     

Techno‐Economic Analysis of Methane Pyrolysis in Molten Metals: Decarbonizing Natural Gas

Methane pyrolysis using a molten metal process to produce hydrogen is compared to steam methane reforming (SMR) for the industrial production of hydrogen. Capital and operating cost models for pyrolysis and SMR were used to generate cash‐flow and production costs for several different molten pyrolysis systems. The economics were most sensitive to the methane conversion and the value obtained for the solid carbon by‐product. The pyrolysis system at 1500 °C is competitive with a carbon tax of $78 t^?1; however, if a catalytic process at 1000 °C were developed using a conventional fired heater, it would be competitive with SMR without a carbon dioxide cost penalty. Several pyrolysis alternatives become competitive with increasing carbon dioxide taxes.     

Modulation of cellular adhesion in bovine brain microvessel endothelial cells by a decapeptide

Immunohistochemical assessment was made of nm23 protein expression in pulmonary adenocarcinoma. Of the 147 adenocarcinomas 67% (99/147) were weakly and 33% (48/147) strongly positive for nm23 protein. nm23 protein expression in primary tumors was shown to correlate inversely with advancing pathologic stage and the degree of metastasis in regional lymph nodes (P < 0.05). The staining of tumors without nodal metastasis was more intense than with nodal metastasis (P < 0.02). Nodal metastasis was seen in 37% (55/147) cases examined. The immunoreactivity to nm23 protein in tumor cells of nodal metastasis was essentially the same as in those of primary tumors (P < 0.01). Significant correlation between patient prognosis and immunoreactivity for nm23 in primary tumors (P < 0.05) was demonstrated. But none could be found between immunoreactivity and other parameters such as histologic grading, distant metastasis, tumor size or disease-free survival. Neither was there any significant correlation between pathologic parameters examined and the expression of nm23 in any histologic subtype. Multivariate analysis using Cox's proportional hazards regression model with five variables indicated nm23 and lymph node metastasis to contribute to overall patient survival. Based on risk ratio disadvantageous state/advantageous states, the gravity of prognostic factors was assessed for lymph node metastasis as 9.25, nm23 expression as 2.06, distant metastasis as 1.23, pathologic stage as 0.78 and tumor size as 0.77. The results suggested that in pulmonary adenocarcinoma a reduced expression of nm23 protein was associated with lymph node metastasis and poor patient survival.     

Potential pitfalls of initiating a newborn hearing screening program

To compare auditory and visual P300 amplitude and latency magnitudes and topographies in patients with narcolepsy and normal subjects, 20 patients with polysomnographically-confirmed narcolepsy and 40 normal subjects were administered auditory and visual P300 testing using 31 evenly spaced scalp electrodes. Patients with narcolepsy were then administered baseline polysomnograms and objective (MSLT, Maintenance of Wakefulness Test or MWT) and subjective tests (Epworth Sleepiness Scale, Clinical Global Impression) of daytime sleepiness. Patients had longer 31-electrode mean age-adjusted auditory P300 latencies (406.0 +/- 27.8 vs. 385.7 +/- 28.9 ms, p = 0.012) and visual P300 latencies (427.3 +/- 29.0 vs. 411.4 +/- 27.7 ms., p = 0.044) than 40 normal subjects in the same age range. Age-adjusted auditory P300 latency was correlated with MWT (r = -0.49, p = 0.028), but not with any other clinical variable or measure of sleepiness. Age-adjusted visual P300 latency was not correlated with any clinical variable or measure of sleepiness. Patients with narcolepsy had longer auditory and visual P300 latencies than normal subjects.     

Torsades de pointes: a case with multiple variables

PURPOSE: The human medulloblastoma cell line D283 Med (4-HCR), a line resistant to 4-hydroperoxycyclophosphamide (4-HC), displays enhanced repair of DNA interstrand crosslinks induced by phosphoramide mustard. D283 Med (4-HCR) cells are cross-resistant to 1,3-bis(2-chloroethyl)- -nitrosourea, but partial sensitivity is restored after elevated levels of O6-alkylguanine-DNA alkyltransferase (AGT) are depleted by O6-benzylguanine (O6-BG). Studies were conducted to define the activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide against D283 Med (4-HCR) after AGT is depleted by O6-BG. METHODS: Limiting dilution and xenograft studies were conducted to define the activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide with or without O6-BG. RESULTS: The activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide against D283 Med (4-HCR) was increased after AGT depletion by O6-BG preincubation. Similar studies with Chinese hamster ovary cells, with or without stable transfection with a plasmid expressing the human AGT protein, revealed that the AGT-expressing cells were significantly less sensitive to 4-HC and 4-hydroperoxydidechlorocyclophosphamide. Reaction of DNA with 4-HC, phosphoramide mustard, or acrolein revealed that only 4-HC and acrolein caused a decrease in AGT levels. CONCLUSIONS: We propose that a small but potentially significant part of the cellular toxicity of cyclophosphamide in these cells is due to acrolein, and that this toxicity is abrogated by removal of the acrolein adduct from DNA by AGT.