James B. Macelwane Award: Citation and Acceptance of Robert Keith O'Nions

I have the pleasure to introduce Robert Keith O'Nions, a young man of 34, for the Macelwane Award, not because I have had anything to do with his education and research, but because I was a member of the committee this year, and we both originate from the same country. Keith O'Nions earned his B.Sc. from the University of Nottingham in 1966, traveled to Alberta for a Ph.D. in 1969, became a Postdoctoral Fellow in Oslo during 1970, joined the faculty at Oxford from 1971–1975, and moved to his present home at Columbia University in 1975. When the time came to find a citationist [sic] for him it turned out that his colleagues at Lamont-Doherty, who were the obvious choices, were all at sea—and I admit that this is how I feel when I read some of Keith's papers. In a sense, this makes me well-suited for this introduction, because I cannot spend time explaining his research to you. Instead, I will read to you a couple of paragraphs from his nomination for the award, written by an anonymous friend

Studies in synthetic carbonatite systems: Solidus relationships for CaO-MgO-CO_2-H_2O to 40 kbar and CaO-MgO-SiO_2-CO_2-H_2O to 10 kbar

The system CaO-MgO-SiO_2-CO_2-H_2O is an important model for many igneous and metamorphic processes, including the generation and differentiation of carbonatite and associated silicate magmas. We have experimentally established the vapor-saturated solidus for the system CaO-MgO-CO_2-H_2O from 595°C/1 kbar to <500°C/40 kbar, about 25°C lower than the corresponding temperatures for the CaO-CO_2-H_2O system. Brucite replaces periclase on the vapor-saturated solidus at about 750 bars pressure, remaining as the stable phase to pressures of at least 40 kbar; no dolomite or magnesite was encountered. At a pressure between 35 and 40 kbar, the assemblage portlandite + brucite + aragonite + vapor changes to one containing phase W, a previously unreported Ca-Mg carbonate. At 20 kbar, the vapor-saturated liquid contains at least 24 wt % H_2O. The vapor-saturated solidus for the system CaO-MgO-SiO_2-CO_2-H_2O ranges from 613°C/1 kbar to 565°C/10 kbar, experimentally indistinguishable from that for CaO-MgO-CO_2-H_2O, about 10°C lower than that for CaO-CO_2-H_2O, and about 25°C lower than that for CaO-SiO_2-CO_2-H_2O. In the quinary system, monticellite is replaced by dellaite and an unidentified silicate on the vapor-saturated solidus above 4.1 kbar. MgO-poor liquids are similar in composition to the magma from which the Magnet Cove calcite carbonatite crystallized. More magnesian magmas would produce dolomite at moderate depths, such as at Alnö Island

Nucleosomes indicate the in vitro radiosensitivity of irradiated bronchoepithelial and lung cancer cells

Nucleosomes, which are typical cell death products, are elevated in the serum of cancer patients and are known to rapidly increase during radiotherapy. As both normal and malignant cells are damaged by irradiation, we investigated to which extent both cell types contribute to the release of nucleosomes. We cultured monolayers of normal bronchoepithelial lung cells (BEAS-2B, n = 18) and epithelial lung cancer cells (EPLC, n = 18), exposed them to various radiation doses (0, 10 and 30 Gy) and observed them for 5 days. Culture medium was changed every 24 h. Subsequently, nucleosomes were determined in the supernatant by the Cell Death Detection-ELISA(plus) ( Roche Diagnostics). Additionally, the cell number was estimated after harvesting the cells in a second preparation. After 5 days, the cell number of BEAS-2B cultures in the irradiated groups (10 Gy: median 0.03 x 10(6) cells/culture, range 0.02-0.08 x 10(6) cells/culture; 30 Gy: median 0.08 x 10(6) cells/culture, range 0.02-0.14 x 10(6) cells/culture) decreased significantly (10 Gy: p = 0.005; 30 Gy p = 0.005; Wilcoxon test) compared to the non-irradiated control group (median 4.81 x 10(6) cells/culture, range 1.50-9.54 x 10(6) cells/culture). Consistently, nucleosomes remained low in the supernatant of nonirradiated BEAS-2B. However, at 10 Gy, BEAS-2B showed a considerably increasing release of nucleosomes, with a maximum at 72 h ( before irradiation: 0.24 x 10(3) arbitrary units, AU, range 0.13-4.09 x 10(3) AU, and after 72 h: 1.94 x 10(3) AU, range 0.11-5.70 x 10(3) AU). At 30 Gy, the release was even stronger, reaching the maximum earlier (at 48 h, 11.09 x 10(3) AU, range 6.89-18.28 x 10(3) AU). In non-irradiated EPLC, nucleosomes constantly increased slightly. At 10 Gy, we observed a considerably higher release of nucleosomes in EPLC, with a maximum at 72 h (before irradiation: 2.79 x 10(3) AU, range 2.42-3.80 x 10(3) AU, and after 72 h: 7.16 x 10(3) AU, range 4.30-16.20 x 10(3) AU), which was more than 3.5 times higher than in BEAS-2B. At 30 Gy, the maximum (6.22 x 10(3) AU, range 5.13-9.71 x 10(3) AU) was observed already after 24 h. These results indicate that normal bronchoepithelial and malignant lung cancer cells contribute to the release of nucleosomes during irradiation in a dose-and time-dependent manner with cancer cells having a stronger impact at low doses. Copyright (C) 2004 S. Karger AG, Basel

Nucleosomes in pancreatic cancer patients during radiochemotherapy

Nucleosomes appear spontaneously in elevated concentrations in the serum of patients with malignant diseases as well as during chemo- and radiotherapy. We analyzed whether their kinetics show typical characteristics during radiochemotherapy and enable an early estimation of therapy efficacy. We used the Cell Death Detection Elisaplus ( Roche Diagnostics) and investigated the course of nucleosomes in the serum of 32 patients with a local stage of pancreatic cancer who were treated with radiochemotherapy for several weeks. Ten of them received postsurgical therapy, 21 received primary therapy and 1 received therapy for local relapse. Blood was taken before the beginning of therapy, daily during the first week, once weekly during the following weeks and at the end of radiochemotherapy. The response to therapy was defined according to the kinetics of CA 19-9: a decrease of CA 19-9 650% after radiochemotherapy was considered as `remission'; an increase of >= 100% ( which was confirmed by two following values) was defined as `progression'. Patients with `stable disease' ranged intermediately. Most of the examined patients showed a decrease of the concentration of nucleosomes within 6 h after the first dose of radiation. Afterwards, nucleosome levels increased rapidly, reaching their maximum during the following days. Patients receiving postsurgery, primary or relapse therapies did not show significant differences in nucleosome values during the time of treatment. Single nucleosome values, measured at 6, 24 and 48 h after the application of therapy, could not discriminate significantly between patients with no progression and those with progression of disease. However, the area under the curve of the first 3 days, which integrated all variables of the initial therapeutic phase, showed a significant correlation with the progression-free interval ( p = 0.008). Our results indicate that the area under the curve of nucleosomes during the initial phase of radiochemotherapy could be valuable for the early prediction of the progression-free interval. Copyright (C) 2005 S. Karger AG, Basel

A Universal Model of Unsaturated Hydraulic Conductivity with Complementary Adsorptive and Diffusive Process Components

Accurate estimation of unsaturated hydraulic conductivity (HC) is one of the most challenging problems in soil science. Here, we propose a novel approach to model HC using percolation theory. Transient behavior of water transport phenomena at low moisture contents requires additional physical process representation, beside capillary conductivity, to ensure accurate prediction of unsaturated HC. We augment the capillary model from percolation theory with two additional components, namely, (1) film flow, which is the product of volumetric flow rate per perimeter by specific perimeter of solid particles, and (2) isothermal vapor HC, derived from the Fick\u27s law of vapor diffusion and relative humidity. The fractal characteristics of last fractal regime are used to model tortuosity and ultimately HC of vapor flow. Since the typical pressure head range of universal scaling from percolation theory is analogous to the range of vapor flow, we demonstrate that the universal scaling presented in previous studies is not sufficient to model HC for water contents below a crossover point. We also, by analyzing the scaled water retention properties, demonstrate that most studied soils exhibit three fractal regimes. Therefore, a piecewise HC function of capillary flow is developed to account for three fractal regimes, providing more flexibility for soils with multimodal characteristics. The proposed joint HC function is more accurate compared to the model of Peters‐Durner‐Iden and predecessor percolation theory models

A 5 Gb/s Radiation Tolerant Laser Driver

A laser driver for data transmission at 5 Gb/s has been developed as a part of the Giga Bit Transceiver (GBT) project. The Giga Bit Laser Driver (GBLD) targets High Energy Physics (HEP) applications for which radiation tolerance is mandatory. The GBLD ASIC can drive both VCSELs and some types of edge emitting lasers. It is essentially composed of two drivers capable of sinking up to 12 mA each from the load at a maximum data rate of 5 Gb/s, and of a current sink for the laser bias current. The laser driver include also pre-emphasis and duty cycle control capabilities

Timing and documentation of key events in neonatal resuscitation

Only a minority of babies require extended resuscitation at birth. Resuscitations concerning babies who die or who survive with adverse outcomes are increasingly subject to medicolegal scrutiny. Our aim was to describe real-life timings of key resuscitation events observed in a historical series of newborns who required full resuscitation at birth. Twenty-seven babies born in our centre over a 10-year period had an Apgar score of 0 at 1 min and required full resuscitation. The median (95% confidence interval) postnatal age at achieving key events were commencing cardiac compressions, 2.0 (1.5–4.0) min; endotracheal intubation, 3.8 (2.0–6.0) min; umbilical venous catheterisation 9.0 (7.5–12.0) min; and administration of first adrenaline dose 10.0 (8.0–14.0) min. Conclusion: The wide range of timings presented from real-life cases may prove useful to clinicians involved in medical negligence claims and provide a baseline for quality improvements in resuscitation training

Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog

Background: Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of nonchromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences. Objective: To characterise genetic and clinical findings in individuals with SHH mutations. Methods: Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases. Results: This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p<0.0001 compared to ZIC2 or SIX3). Individuals with truncating mutations were significantly more likely to have frank HPE than those with non-truncating mutations (49% vs 35%, respectively; p¼0.012). While mutations were significantly more common in the N-terminus than in the C-terminus (including accounting for the relative size of the coding regions, p¼0.00010), no specific genotype―phenotype correlations could be established regarding mutation location. Conclusions: SHH mutations overall result in milder disease than mutations in other common HPE related genes. HPE is more frequent in individuals with truncating mutations, but clinical predictions at the individual level remain elusive