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Activators of protein kinase C (PKC) stimulate Na+ transport (JNa) across frog skin. We have examined the effect of Ca2+ on PKC stimulation of JNa. Both the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the diacyl-glycerol sn-1,2-dioctanoylglycerol (DiC8) were used as PKC activators. Blocking Ca2+ entry into the cytosol (either from external or internal stores) reduced the subsequent natriferic effect of the PKC activators. This negative interaction did not simply reflect saturation of activation of the apical Na+ channels, since the stimulations produced by blocking Ca2+ entry and adding cyclic AMP were simply additive. The Ca2+ dependence of the natriferic effect could have reflected either a direct action of cytosolic Ca2+ on PKC or an indirect action on the final receptor site (the Na+ channel). To distinguish between these possibilities, the TPA- and phospholipid-dependent kinase activity of broken-cell preparations was assayed. The kinase activity was not stimulated by physiological levels of Ca2+, and in fact was inhibited at millimolar concentrations of Ca2+. We conclude that the effects of Ca2+ on the natriferic response to PKC activators are indirect. Reducing cytosolic uptake of Ca2+ may have stimulated Na+ transport by a chemical modification of the apical channels observed in other tight epithelia. The usual stimulation of Na+ transport produced by PKC activators in frog skin may reflect the operation of a nonconventional form of PKC. This enzyme is Ca2+ independent and seems related to the nPKC or PKC epsilon observed in other systems.

Although levels of high density lipoprotein (HDL) cholesterol in males decrease during adolescence and after treatment with testosterone derivatives, several studies have reported that levels of HDL cholesterol are positively associated with endogenous levels of testosterone in men. This association was further examined using data collected during 1985 and 1986 from 3,562 white and 500 black men who ranged in age from 31 to 45 years. Black men had higher mean levels of both HDL cholesterol (8 mg/dl) and total testosterone (33 ng/dl) than white men, and positive associations were observed between testosterone and HDL cholesterol levels (r = 0.22, whites; r = 0.26, blacks). In addition, levels of testosterone were related positively to alcohol consumption and cigarette smoking and negatively to age, Quetelet index, and use of beta-blockers. We used stratification and regression analyses to determine if any of these characteristics could account for the positive association between levels of HDL cholesterol and total testosterone. Although controlling for most factors had little influence, adjusting for Quetelet index reduced the strength of the association between levels of testosterone and HDL cholesterol by approximately 30%. These findings suggest that the positive association between levels of testosterone and HDL cholesterol may not be causal. Multivariable analyses that control for obesity and other potentially confounding characteristics should be used in studies that assess the relation of testosterone levels to coronary heart disease.

A tapered composite laminate subjected to tension load was analyzed using the finite element method. The {[07/(±45)]/1[(±45)3]/[0/(±45)/0]}5 glass/epoxy laminate has a (±45)3 group of plies dropped in three distinct steps, each 20 ply-thicknesses apart, thus forming a taper angle of 5.71 degrees. Steep gradients of interlaminar normal and shear stress on a potential delamination interface suggest the existence of stress singularities at the points of material and geometric discontinuities created by the internal plydrops. The delamination was assumed to initiate at the thin end of the taper on the-45/+45 interface indicated by the arrow in the laminate layup and the delamination growth was simulated in both directions, i.e., along the taper and into the thin region. The total strain-energy-release rate, G, and the mode I and mode II components of G, were computed at the delamination tips using the virtual crack closure technique. In addition, G was calculated from a global energy balance method. The strain-energy-release rate for a delamination growing into the thin laminate consisted predominantly of mode I (opening) component. For a delamination growing along the tapered region, the strain-energy-release rate was initially all mode I, but the proportion of mode I decreased with increase in delamination size until eventually total G was all mode II. The total G for both delamination tips increased with increase in delamination size, indicating that a delamination initiating at the end of the taper will grow unstably along the taper and into the thin laminate simultaneously.

Available techniques for determining age from human cranial remains are limited. This study examines the efficacy of Meindl and Lovejoy's (1985) method of determining age based on ectocranial suture closure patterns as compared to a baseline of ages developed from a multifactorial approach employing various age determining factors from across the skull. What makes this study different is that the sample upon which this comparison is performed contains a large number of artificially deformed crania. Our hypothesis is that aging techniques that rely on suture closure patterns as markers are complicated by the results of artificial modification of the cranial vault. The study is conducted on adult, human crania from prehispanic archaeological sites in South America. Results demonstrate a significant difference between the two aging methods, more particularly when applied to deformed skulls. We conclude that when a skull is deformed age should be estimated utilizing multiple factors that exclude Meindl and Lovejoy's ectocranial suture aging technique.

Glycogen synthase kinase 3 beta (GSK-3beta) was one of the first kinases identified and studied, initially for its role in the regulation of glycogen synthesis. Over the past decade, interest in GSK-3beta has grown far beyond glycogen metabolism, and this is due in large measure to the critical role that GSK-3beta plays in the regulation of many other cellular processes, particularly cell proliferation and apoptosis. GSK-3beta has been shown to regulate the proteolysis and sub-cellular compartmentalization of a number of proteins directly involved in the regulation of cell cycling, proliferation, differentiation and apoptosis. GSK-3beta also regulates the degradation of proteins that regulate gene expression and thus affects a variety of important cell functions. Specifically, GSK-3beta controls the degradation of beta-catenin, the main effector of Wnt that regulates haematopoiesis and stem cell function. In this case GSK-3beta is a negative regulator of Wnt. In contrast, GSK-3beta positively regulates NF-kappaB, another important biochemical pathway also involved in the regulation of multiple aspects of normal and aberrant haematopoiesis. GSK-3beta regulates degradation of IkappaB, a central inhibitor of NF-kappaB. In this way, GSK-3beta acts to control the resistance of leukaemic cells to chemotherapy through the modulation of NF-kappaB, a critical factor in maintaining leukaemic cell growth. In addition, GSK-3beta regulates the pro-inflammatory activity of NF-kappaB. As GSK-3beta is a pleiotropic regulator, inhibitors may increase the range of novel anti-leukaemic and anti-inflammatory drugs that control immune response.

pip92 is a cellular immediate-early gene inducible by serum growth factors in fibroblasts. It is also induced in the rat pheochromocytoma cell line PC12 by agents that cause proliferation, neuronal differentiation, and membrane depolarization. We show that the pip92-encoded polypeptide is a proline-rich protein of 221 amino acids, has an extremely short half-life, and is localized in the cytoplasm. We hypothesize that Pip92 plays a role in mediating the cellular responses to a variety of extracellular signals.

Ten stifles from 5 clinically sound adult horses were scanned by high-resolution ultrasound. Normal anatomic structures seen consistently included the subcutaneous tissue, the medial, middle and lateral patellar ligaments, the medial and lateral collateral ligaments, the femoral trochlear ridges, and menisci. Cruciate ligaments could not be visualized in the standing horse. Four stifle specimens obtained from 2 of these normal horses at necropsy were scanned in a water bath to create optimal technical conditions. The sonographic appearance of stifle specimens was similar to that found in live horses. Results from ultrasonographic examination of 3 horses with stifle abnormalities were described to illustrate some applications of ultrasonography in the evaluation of the equine stifle. In these horses, ultrasound was a valuable diagnostic tool to study joint effusion, synovial thickening, articular cartilaginous and subchondral defects, and soft tissue/bony injuries.

Thin-skinned composite honeycomb sandwich structures from the trailing edge of the U.S. Army's Apache and Chinook helicopters have been tested to ascertain their susceptibility to water intrusion as well as such intrusions' effects on impact damage and cyclic loading. Minimum-impact and fatigue conditions were determined which would create microcracks sufficiently large to allow the passage of water through the skins; damage sufficient for this to occur was for some skins undetectable under a 40X-magnification optical microscope. Flow rate was a function of moisture content, damage, applied strain, and pressure differences.

We present extended x-ray-absorption fine structure (EXAFS) data at the $\mathrm{Mn}\phantom{\rule{0.2em}{0ex}}K$ and $\mathrm{Tb}\phantom{\rule{0.2em}{0ex}}{L}_{3}$ edges that provide upper limits on the possible displacements of any atoms in $\mathrm{Tb}\mathrm{Mn}{\mathrm{O}}_{3}$. The displacements must be less than $0.005--0.01\phantom{\rule{0.3em}{0ex}}\mathrm{\AA{}}$ for all atoms, which eliminates the possibility of moderate distortions $(0.02\phantom{\rule{0.3em}{0ex}}\mathrm{\AA{}})$ with a small $c$-axis component, but for which the displacements in the $ab$ plane average to zero. Assuming the polarization arises from a displacement of the O2 atoms along the $c$ axis, the measured polarization then leads to an O2 displacement that is at least $6\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}4}\phantom{\rule{0.3em}{0ex}}\mathrm{\AA{}}$, well below our experimental limit. Thus, a combination of the EXAFS and the measured electrical polarization indicate that the atomic displacements likely lie in the range $6\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}4}--5\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}\phantom{\rule{0.3em}{0ex}}\mathrm{\AA{}}$.

A temperature-dependent EXAFS investigation of La{sub 1.2}Sr{sub 1.8}Mn{sub 2}O{sub 7}, with x rays polarized parallel to the c axis and in the ab plane, has shown an extremely sharp and anisotropic jump in the broadening {sigma} of the Mn-O pair-distribution function (PDF) near the ferromagnetic transition temperature, T{sub c}. This jump is associated with an increase in Jahn-Teller (JT) distortions as the temperature increases through T{sub c}. The data show that changes in {sigma}{sup 2} as T is lowered below T{sub c} is linearly correlated with the sample magnetization, and that there is a break in the slope of this correlation when the sample is {approx}80% magnetized, consistent with the recently proposed dimeron model. A JT distortion clearly exists well above T{sub c} and some distortions still remain for a range of temperatures below T{sub c}. In agreement with recent work on the La{sub 1-x}Ca{sub x}MnO{sub 3} (LCMO) system, the data indicate that two types of distorted sites must occur; one is associated with the hole charge carriers (two-site polaron called a dimeron) and has a very small distortion/site; the second is associated with unpaired electron sites and has a similar distortion/site as observed for corresponding sites in LCMO. Furthermore,more » the broadening of the Mn-O PDF shows a second and more subtle increase above T{sub c} near T{sup *}{approx_equal}250 K, a change in structure that correlates well with features in several other experiments.« less

In many systems there is a significant coupling between the local structure and other properties of the system such as magnetism, electrical and thermal transport, metal/insulator transitions etc. In such materials, a detailed temperature‐dependent study of the width of the Pair Distribution Function (PDF), σ, can separate different contributions and provide a connection between the observed macroscopic observations and the underlying atomic interactions that produce them. The usual model for simple systems is that the T‐dependence of σ2 is described by an Einstein or Correlated Debye model, with one characteristic temperature for the system; in such models σ2(T) increases smoothly with T and has a slowly increasing slope. However that is not always the case: in structures with large unit cells containing several types of atoms, some atoms in the crystal can have a low Einstein temperature while others have a very high correlated Debye temperature as observed in a number of thermoelectric systems (skutterudites and clathrates). In others systems such as the negative thermal expansion material ZrW2O8, the same atom cam be involved in both low and high temperature Einstein modes. Vibrations of atoms (or molecular unit) described by a low Einstein temperature often control/determine the lattice properties. In other systems there are deviations from the T‐dependence expected for either the Einstein or correlated Debye models — such as a small increase in σ2 at low temperatures for the Ru‐Ru pair in PrRu4Sb12 which has a metal/insulator transition near 60K, or a very sharp step in σ2(T) observed in the bilayer colossal magnetoresistance system La2−2xSr1+2xMn2O7 at the ferromagnetic transition. We discuss broadening of the PDF in more complex systems, show some simulations and then present several recent examples.

[1] Following the work of Koons (2001), we examine the statistical properties of extremely high fluxes of MeV electrons in the outer zone. We extend the analysis to include a variety of timescales and energies using observations from Los Alamos monitors at geosynchronous orbit and to include outer zone fluxes observed from L ∼ 2–8 by spacecraft in highly elliptical Molniya orbits. We use the statistical formalism of the generalized extreme value distribution, which represents the probability distribution of the maximum value taken out of a sample of fixed size. By taking the maximum flux observed in many nonoverlapping intervals of several hours to several days, we can determine whether the maximum flux is likely to have a finite upper limit or an exponential or power law tail. Our analysis indicates that MeV electron fluxes over a broad range of energies, L shells, and timescales have a finite upper limit, a true worst case. However, the statistical estimate of this upper limit is inherently uncertain. We compare our upper limits to the internal charging specifications provided by Fennell et al. (2000). We discuss several possible physical explanations for the flux limits.

[1] During January, 2005, there were several large X-class solar flares and associated solar energetic particle (SEP) events. Coincidentally, the MINIS balloon campaign had multiple payloads aloft in the stratosphere above Antarctica measuring dc electric fields, conductivity and x-ray flux. One-to-one increases in the electrical conductivity and decreases to near zero of both the vertical and horizontal electric field components were observed in conjunction with an increase in particle flux at SEP onset. Combined with an atmospheric electric field mapping model, these data are consistent with a shorting out of the global electric circuit and point toward substantial ionospheric convection modifications. Additionally, two subsequent, rapid changes were detected in the vertical electric field component several hours after SEP onset. These changes result in similar fluctuations in the calculated vertical current density. We will describe how rigidity cut-off dynamics may be crucial in understanding these sudden jumps in the vertical electric field.

[1] We explore the statistical limits on the complexity of data-derived models of magnetic storm phenomena, including magnetic indices, plasmapause evolution, and outer radiation belt dynamics. Specifically, we estimate the limits on the number of free parameters justifiable by application of Occam's razor, or the rule of parsimony. These limits arise from the strong intercorrelation of geomagnetic phenomena, which decimates the effective sample size of independent observations of magnetic storm phenomena. We show that the resulting paucity of distinct magnetic storms over the history of magnetic indices and satellite observations severely limits the justifiable complexity of data-derived models. Our analysis applies to a wide variety of models with a finite number of constant free parameters but not to models with time-varying parameters nor to nearest-neighbors models.

[1] The relativistic electron dropout event on 20 November 2003 is studied using data from a number of satellites including SAMPEX, HEO, ACE, POES, and FAST. The observations suggest that the dropout may have been caused by two separate mechanisms that operate at high and low L-shells, respectively, with a separation at L ∼ 5. At high L-shells (L > 5), the dropout is approximately independent of energy and consistent with losses to the magnetopause aided by the Dst effect and outward radial diffusion which can deplete relativistic electrons down to lower L-shells. At low L-shells (L < 5), the dropout is strongly energy-dependent, with the higher-energy electrons being affected most. Moreover, large precipitation bands of both relativistic electrons and energetic protons are observed at low L-shells which are consistent with intense pitch angle scattering driven by electromagnetic ion cyclotron (EMIC) waves and may result in a rapid loss of relativistic electrons near the plasmapause in the dusk sector or in plumes of enhanced density.

[1] A remarkable correlation between the inner edge of the outer radiation belt electrons and the innermost plasmapause location is demonstrated by using 12 years of measurements of MeV electrons from the Solar, Anomalous, and Magnetospheric Particle Explorer (SAMPEX) and the Combined Radiation and Release Experiment Satellite (CRRES) during its entire mission (July 1990–October 1991). An empirical model of the plasmapause location, Lpp, by O'Brien and Moldwin (2003) as well as the measured Lpp during the CRRES mission is used for the comparison. This correlation suggests that the innermost Lpp is the innermost limit of the outer radiation belt penetration. We discuss the possible scenarios that might explain this correlation.

[1] Energetic electrons in the outer radiation belt can resonate with intense bursts of whistler-mode chorus emission leading to microburst precipitation into the atmosphere. The timescale for removal of outer zone MeV electrons during the main phase of the October 1998 magnetic storm has been computed by comparing the rate of microburst loss observed on SAMPEX with trapped flux levels observed on Polar. Effective lifetimes are comparable to a day and are relatively independent of L shell. The lifetimes have also been evaluated by theoretical calculations based on quasi-linear scattering by field-aligned waves. Agreement with the observations requires average wide-band wave amplitudes comparable to 100 pT, which is consistent with the intensity of chorus emissions observed under active conditions. MeV electron scattering is most efficient during first-order cyclotron resonance with chorus emissions at geomagnetic latitudes above 30 degrees. Consequently, the zone of MeV microbursts tends to maximize in the prenoon (0400–1200 MLT) sector, since nightside chorus is more strongly confined to the equator.

[1] The trapped radiation specifications, such as AE-8 and AP-8, are based upon a simple and reasonable framework that happens to be insufficient to the modern demands placed upon them. This manuscript outlines an improved framework for the next generation of radiation models. While existing radiation specifications tend to provide mean fluxes on a grid in magnetic coordinates, scientific and engineering users are starting to demand capabilities that are far beyond this simple framework, such as error bars on total mission dose and real-time data assimilation. One framework that can provide these added capabilities while still remaining fairly simple is the joint probability distribution, described here. The joint distribution can describe the behavior of individual fluxes on a grid in magnetic coordinates while also describing how those fluxes vary together. This covariance is a crucial ingredient for data assimilation and for proper error bars and percentiles on composite quantities like dose or fluence to a shielded device. This manuscript describes the core math of the proposed framework, an approach to building the model from in situ observations and/or numerical simulations, how to use the model to calculate error bars and percentiles on composite quantities, how to use the model in data assimilation, and how to make a first estimate of the dependence of worst case fluences on aggregation time.

Steady magnetospheric convection (SMC) also known as convection bays, is a particular mode of response of the magnetosphere to solar wind coupling. It is characterized by convection lasting for times longer than a typical substorm recovery during which no substorms expansions can be identified. It is generally believed that the solar wind must be unusually steady for the magnetosphere to enter this state. However, most previous studies have assumed this is true and have used such conditions to identify events. In a preliminary investigation using only the AE and AL indices to select events we have shown that these expectations are generally correct. SMC events seem to be associated with slow speed solar wind and moderate, stable IMF Bz. In this report we extend our previous study including additional parameters and the time variations in various statistical quantities. For the intervals identified as SMCs we perform a detailed statistical analysis of the properties of different solar wind variables. We compare these statistics to those determined from all data, and from intervals in which substorms but not SMCs are present. We also consider the question of whether substorms are required to initiate and terminate an SMC. We conclude that the intervals we have identified as SMC are likely to be examples of the original Dungey concept of balanced reconnection at a pair of x-lines on the day and night side of the Earth.

[1] We investigate how relativistic electrons are lost from the Earth's magnetosphere in order to better understand the dynamic variability of the radiation belts. We identify 52 events where the >2 MeV electron flux at geostationary orbit decreases rapidly and use a superposed epoch analysis of multispacecraft data to characterize the accompanying solar wind and geomagnetic conditions and examine the relevance of potential loss mechanisms. The results show that the flux decrease events follow a common sequence. The electron flux is reduced first in the dusk sector concurrent with the stretching of the magnetic field to a more tail-like configuration. The extreme stretching at dusk is caused by the formation of a partial ring current driven by changing solar wind conditions. We investigate three possible causes of the ensuing flux decrease: adiabatic electron motion in response to the changing magnetic field topology, drift out the magnetopause boundary, and precipitation into the atmosphere. The analysis reveals that the flux depletion is likely due to enhanced precipitation into the atmosphere, but the exact cause of the enhanced precipitation is still uncertain.

[ 1] It has been suggested that whistler mode chorus waves play a role in the acceleration and loss of radiation belt electrons during geomagnetic storms. In a previous statistical study of chorus received at Halley station, Antarctica (76degreesS 27degreesW, L = 4.3), during storms of the solar cycle 1992-2002, we found that on average, chorus intensities were significantly enhanced in the storm recovery phase. In this paper we extend that study to provide stronger evidence of the link between chorus and electron acceleration. We selected a set of 244 storms in 1992-2002 having a minimum D-st less than -50 nT, for which average 1.8-3.5 MeV electron fluxes 2-3 days after the storm were available from the LANL satellites. This set was classified into two subsets according to whether the flux was less than or greater than an arbitrary threshold of 0.5 electrons cm(-2) s(-1) sr(-1) keV(-1), near to the median value. A superposed epoch analysis of the whole set, using the times of minimum Dst as the set of epochs, reproduced the results of the earlier study, but when the two subsets were analyzed separately, it was found that for the lower-frequency channels, 0.5-1.0 kHz, characteristic of the main chorus band, the average intensities of chorus observed were larger for storms when the poststorm flux was high. The long-enduring ( several days) poststorm depression of wave power at frequencies above the chorus band, found in the previous study and attributed to increased precipitation from the radiation belts, was again noted. The depression was greater for the set of storms characterized by high poststorm fluxes, which strengthens this interpretation. It was accompanied by longer-lasting geomagnetic and substorm activity after the storm, as indicated by the K-p and AE indices, consistent with recent suggestions that relativistic electron acceleration is more likely to occur in storms with substantial substorm activity in the recovery phase.

[1] Bursty precipitation of relativistic electrons has been implicated as a major loss process during magnetic storms. One type of precipitation, microbursts, appears to contain enough electrons to empty the prestorm outer radiation belt in approximately a day. During storms that result in high fluxes of trapped relativistic electrons, microbursts continue for several days into the recovery phase, when trapped fluxes are dramatically increasing. The present study shows that this apparent inconsistency is resolved by observations that the number of electrons lost through microbursts is 10–100 times larger during the main phase than during the recovery phase of several magnetic storms chosen by the Geospace Environment Modeling (GEM) program.

Vulvovaginitis in the prepubertal child may present with itch, irritation, pain, dysuria or discharge as a result of poor hygiene, contact irritants, sexual abuse or skin disease involving the genital area. Common infectious causes include threadworms, group A beta-haemolytic streptococci and Haemophilus influenzae. A full history and examination are essential. Investigations may include swabs, midstream urine, biopsy, ultrasound and examination under anaesthesia.

Management of bacterial keratitis: beyond exorcism towards consideration of organism and host factors

To assess the significance of ultrasonographically detected hypoechoic lesions of the testis when the clinical examination is normal, and to highlight the management difficulties thereafter.Over a 2-year period four patients underwent radical orchidectomy where the sole indication for surgery was a hypoechoic lesion detected on ultrasonography (US). The indications for US were persistent scrotal discomfort in two men, contralateral orchitis, and the follow-up of testicular microlithiasis. The lesions were 4-11 mm in size and one man had several. None of the lesions were palpable; the tumour markers were normal in all patients.Three of the testes contained seminoma; in one there were two foci of seminoma and in all intratubular germ cell neoplasia was also identified. The remaining case was a Leydig-cell tumour. All tumours were staged as pT1 after radical inguinal orchidectomy.Impalpable lesions of the testis are likely to be malignant if they are hypoechoic on US and should be considered as seminoma until proved otherwise. The management thereafter is not straightforward, but must ensure an adequate histological diagnosis if the US appearances do not resolve.

[1] We examine signatures of two types of waves that may be involved in the acceleration of energetic electrons in Earth's outer radiation belts. We have compiled a database of ULF wave power from SAMNET and IMAGE ground magnetometer stations for 1987–2001. Long-duration, comprehensive, in situ VLF/ELF chorus wave observations are not available, so we infer chorus wave activity from low-altitude SAMPEX observations of MeV electron microbursts for 1996–2001 since microbursts are thought to be caused by interactions between chorus and trapped electrons. We compare the ULF and microburst observations to in situ trapped electrons observed by high-altitude satellites from 1989–2001. We find that electron acceleration at low L shells is closely associated with both ULF activity and MeV microbursts and thereby probably also with chorus activity. Electron flux enhancements across the outer radiation belt are, in general, related to both ULF and VLF/ELF activity. However, we suggest that electron flux peaks observed at L ∼ 4.5 are likely caused by VLF/ELF wave acceleration, while ULF activity probably produces the dominant electron acceleration at geosynchronous orbit and beyond.

To estimate the likelihood of poor surgical results being explained by chance rather than under-performance.The 30-day mortality rates after radical cystectomy for bladder cancer were analysed theoretically. Surgical competence was defined as a mortality rate of 4%, excellence as 2% and under-performance as 8%, 12%, 20% or 40%. Four scenarios were explored for surgeons of different competence: first, the sample size required to show that a given level of under-performance is very unlikely to be due to chance; second, the likelihood of two or more consecutive deaths in a series of cases; third, the likelihood of clustering of deaths, defined as two deaths in five or in 10 cases; and last, the likelihood of outstanding surgical results (i.e. no deaths) being achieved in small cohorts by surgeons of differing competence.For surgeons with a mortality rate of 8%, 12%, 20% or 40%, the sample sizes needed to prove under-performance are 211, 65, 21 and seven, respectively. For consecutive deaths, 0.4% of excellent, 1.4% of competent and 21% of surgeons with a mortality rate of 12% will experience two or more consecutive deaths in the next 10 cases. For clustered deaths, 1% of excellent, 5% of competent and 23% of seriously under-performing surgeons (mortality ratesor = 12%) will experience two deaths in their next 10 cases. Lastly, for the likelihood of outstanding results, only 3.6% of surgeons with an 8% mortality rate and1% of surgeons with a mortality rateor = 12% will experience no deaths over 40 consecutive cases.Very large cohorts are needed to confirm even significant under-performance. Consecutive deaths are very unlikely events for competent surgeons. Clustered deaths (two deaths in 10 cases) are very unlikely events for excellent surgeons but plausible for competent ones. Analysis of consecutive/clustered deaths is limited by low statistical sensitivity; only up to a quarter of seriously under-performing surgeons are identified. No deaths in 40 consecutive cases implies competence.

We have previously described an indicator dilution technique of measuring cardiac output in which lithium chloride is injected as a bolus via a central venous catheter and cardiac output derived from the arterial lithium dilution curve recorded from a lithium-selective electrode, which we have developed for this purpose. It would be an advantage if the lithium could be injected via the basilic vein (in the antecubital fossa) in those patients who do not need central venous catheterisation for other reasons. We have therefore compared cardiac output measurements made using these two routes of lithium chloride administration.Lithium dilution cardiac output was measured 10 times in each of 10 patients, injecting the lithium chloride alternately via the basilic or central venous catheter.The mean difference was 0.8 +/- 5.2% (SD) (range -8.5 to +7.0%) over a range of cardiac output of 4.5-13 l/min.Injection of lithium chloride via the basilic vein in the antecubital fossa allows accurate lithium dilution cardiac output measurements to be made in patients who do not have central venous catheters in place.

[1] We use a database of CRRES in situ observations of plasmapause crossings to build empirical models of the plasmapause location as a function of geomagnetic indices. Previous models used the maximum value in Kp during the hours to days leading up to the plasmapause crossing. We find that a recent maximum in AE or minimum in Dst provides a better model of the plasmapause radius than does maximum Kp. AE and Dst measure specific current systems (the auroral electrojet and ring current, respectively). The AE model suggests that substorms may be involved in the erosion of the plasmapause. The Dst model suggests that ring current may be formed by the same electric field that erodes the plasmapause. In more complex models, Kp and AE can describe local time structure in the plasmapause, with the furthest plasmapause before dawn at quiet times, premidnight at active times.

This paper reports on a study and comparison of two techniques and notations suitable for the analysis and design of Web-based electronic commerce (ecommerce) applications. Some of the challenges facing developers of Webbased e-commerce applications are identified, examined and discussed. Individually these challenges are not unique but their combination and severity make the development of applications for the WWW a rather difficult softwareengineering problem. Techniques and notations devised to address some of these challenges are identified from the literature. The Technique for Analysing and Specifying Transactional Internet Sites of Beaudet et al. (1998) and the Object-Oriented Hypermedia Design Method (OOHDM) of Schwabe and Rossi (1998) were selected to analyse and design a typical e-commerce application. The results of this study are then used to evaluate the suitability of the two approaches for the development of Web-based applications. The paper concludes that the Beaudet et al. approach is more suited to rapid development projects and OOHDM to situations where comprehensiveness of specification is more important than speed. Both approaches need to be supplemented by additional techniques and supporting notations, particularly in the area of physical design.

[1] We develop an empirical dynamic equation for the hourly evolution of 1.8–3.5 MeV energetic electron flux at local noon at geosynchronous altitude. We use a genetic algorithm combined with a neural network to identify the magnetospheric quantities that can be used to model the time evolution of hourly energetic electron fluxes. We then apply a statistical technique to analyze how these quantities modify the evolution of energetic electron flux through phase space. We fit this evolution to an analytical dynamic equation. We show that the ring current index Dst and a Pc 5 ULF wave power index together can produce a meaningful model of the noon energetic electron flux. We also use this model to demonstrate how the magnetosphere would respond to a hypothetical increase in ULF wave power without a storm in Dst. We demonstrate that while the model electrons do respond to any enhancement in ULF wave power, their response is much larger in the presence of a magnetic storm with sustained ULF wave power.

[1] In recent years the debate over the causes of seasonal and diurnal variations in magnetic activity has been revived. Popular explanations rely primarily on the orientation of the terrestrial magnetic dipole relative to heliospheric topology. We investigate the signatures of this geometry in the dynamics of Dst, the ring current index. We show that the Russell-McPherron effect is present; however, enhancements in Dst, as measured by the Dst index, exhibit a seasonal and diurnal pattern that is significantly different from the Russell-McPherron (RM) effect. Specifically, the dynamics of Dst, which accommodate the RM effect, demonstrate seasonal and diurnal variations associated with ψ the magnetic colatitude of the subsolar point. Specifically, it is primarily the diurnal signature that distinguishes between various mechanisms for semiannual variations. We suggest that these variations are most consistent with the hypothesis that ψ modulates the depth of penetration of the magnetosheath field into the magnetopause and thereby the amount of magnetic merging and the strength and orientation of magnetopause currents.

Previous angiographic and radiological studies have suggested that the peroneal artery is the best preserved of the calf vessels in peripheral vascular disease and should be a site of preference for a femorodistal bypass graft. Calf vessel run-off assessed by pulse generated run-off (PGR) provides a more accurate prediction of graft success or failure than angiography and may therefore give a better functional picture of vessel patency than angiography. This study compares the presence and degree of preservation of the three calf vessels in patients with severe peripheral vascular disease using both intra-arterial digital subtraction angiography (IADSA) and PGR. Thirty-four limbs in patients with either ischaemic rest pain, ulceration or gangrene were studied and the results were scored according to the extent and severity of disease in the peroneal, posterior tibial and anterior tibial arteries. On IADSA, the peroneal artery was patent significantly more often (79%) than the posterior tibial artery (47%) or the anterior tibial artery (38%). Conversely, PGR examination showed no difference in patency between the three vessels (peroneal 91%, posterior tibial 88%, anterior tibial 79%). The peroneal artery was also significantly better preserved on IADSA (65%) compared to the posterior tibial artery (38%) and the anterior tibial artery (23%). PGR studies again showed no difference in the best preserved vessel between peroneal (47%), posterior tibial (50%) and anterior tibial (50%) arteries. Thus, the peroneal artery appears the better preserved vessel on angiography but this appearance may be misleading because the more functional PGR studies show no significant difference in the patency or degree of preservation of the three calf vessels.

When there is a genetic mutation in a major cardiac protein, SCD is often an unfortunate part of the clinical phenotype. In the majority of common cardiac diseases, even though the nature or degree of genetic influence is not understood their importance cannot be denied. Although advancing by one gene or gene interaction at a time is arduous, it is the only apparent way to begin to unravel as complex a clinic syndrome as SCD.

The cellular responses to carcinogen exposure influence cellular fate, which in turn modulates the neoplastic response. Certain hexavalent chromium [Cr(VI)] compounds are implicated as occupational respiratory carcinogens at doses that are both genotoxic and cytotoxic. We examined the mechanism of Cr(VI)-induced apoptosis in normal human fibroblasts (BJ) immortalized by human telomerase gene transfection (BJ-hTERT), and we assessed the spectrum of cumulative cellular fates [(a) regaining of replicative potential; (b) terminal growth arrest; or (c) apoptosis] for a narrow range of increasingly genotoxic doses of Cr(VI). Exposure of BJ-hTERT cells to Cr(VI) resulted in a dose-dependent increase in apoptosis that involved mitochondrial disruption as evidenced by mitochondrial membrane depolarization and cytochrome c release. The initial response to Cr(VI) exposure was inhibition of cell cycle progression. At the lowest dose tested (1 microM; 32% clonogenic survival), the cell cycle inhibition led to terminal growth arrest but no apoptosis. The fraction of terminally growth arrested cells increased as the dose was increased to 3 microM but then decreased at 4, 5, and 6 microM as apoptosis became the predominant cell fate. Our results suggest that cell populations exposed to Cr(VI) have a different spectrum of responses, depending on the extent of DNA damage, and that the regaining of replicative potential after relatively higher genotoxic exposures may be attributable to either escape from, or resistance to, terminal growth arrest or apoptosis.

We investigated the relationship between cyclin E mRNA overexpression and p53 protein accumulation in epithelial ovarian cancers.mRNA was isolated and cDNA was prepared from 36 epithelial ovarian tumors (three adenomas, three low malignant potential tumors, and 30 carcinomas), and six normal ovaries. The cyclin E mRNA expression levels relative to an internal control, beta-tubulin, were determined by semiquantitative polymerase chain reaction (PCR). Cyclin E and p53 protein expression in ovarian cancer tissues were examined by immunohistochemistry using the same series of samples. Fisher exact test of significance and an unpaired t test were used for statistical analysis.Considerable levels of cyclin E mRNA were detected in all normal ovaries and ovarian tumor samples examined by semiquantitative PCR amplification. mRNA levels of cyclin E were significantly higher in nine of 30 (30%) ovarian cancers compared with those in normal ovaries. The immunohistochemical expression of cyclin E protein was confirmed in the nuclei of tumor cells in 13 of 30 (43%) ovarian cancers. p53 protein accumulation was detected in 12 of 30 (40%) ovarian cancers examined. There was a significant inverse correlation between cyclin E mRNA overexpression and p53 protein accumulation (P.01, Fisher exact test).Cyclin E mRNA overexpression frequently occurs in ovarian cancers without p53 protein accumulation. Cyclin E might have an important effect on the development of a limited number of ovarian cancers.

Delamination is one of the most commonly observed failure modes in composite materials. This article describes the three fundamental fracture failure modes of composite delamination, namely, opening, in-plane shearing, and tearing or scissoring shearing modes. It discusses the characterization and analysis of delamination. The article also reviews the prediction of delamination factors, such as flexbeam fatigue life, and skin/stiffener pull-off strength and life.

A fast photosignal has been obtained from epitaxial superconducting ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{\mathit{x}}$ thin films when a small alternating magnetic field was applied in the film plane. No bias current was required to observe this response. Pulsed infrared radiation at a wavelength of 10.6 \ensuremath{\mu}m and of 150-ns duration yielded nonlinear signals: the voltage pulses had approximately half the duration of the laser output. Signal polarity was found to depend on the sign of dH/dt. For an applied magnetic field amplitude of 1600 A/m and a frequency of 20 Hz, a maximum signal amplitude of 0.5 mV was observed at 74 K for an absorbed energy of 1 \ensuremath{\mu}J. The response originates from the motion of radiation depinned fluxoids across the plane of the film. These fluxoids are subject to a driving force arising from the flux-line density gradient established in the sample by the alternating magnetic field. The resulting net flux movement generates the photosignal by Faraday's law.

Objective: To compare the results of cardiac output measurements obtained by lithium dilution and transpulmonary thermodilution in paediatric patients. Design: A prospective study.¶Setting: Paediatric intensive care unit in a university teaching hospital.¶Patients: Twenty patients (age 5 days–9 years; weight 2.6–28.2 kg) were studied.¶Interventions: Between two and four comparisons of lithium dilution cardiac output (LiDCO) and transpulmonary thermodilution (TPCO) were made in each patient.¶Measurements and results: Results from three patients were excluded: in one patient there was an unsuspected right-to-left shunt, in two patients there was a problem with blood sampling through the lithium sensor. There were 48 comparisons of LiDCO and TPCO in the remaining 17 patients over a range of 0.4–6 l/min. The mean of the differences (LiDCO–TPCO) was –0.1 ± 0.3 (SD) l/min. Linear regression analysis gave LiDCO = 0.11 + 0.90 × TPCO l/min (r 2 = 0.96). There were no adverse effects in any patient.¶Conclusions: These results suggest that the LiDCO method can be used to provide safe and accurate measurement of cardiac output in paediatric patients. The method is simple and quick to perform, requiring only arterial and venous catheters, which will already have been inserted for other reasons in these patients.

In a continued effort to identify and characterize secreted proteases that are overexpressed in ovarian carcinomas, we discovered the testisin protease as such a candidate. When this discovery was originally made, no data existed in the literature or in the GenBank database that identified such a gene. Our main objective was to determine whether this gene was overexpressed exclusively in ovarian tumor tissues compared with normal ovary and whether it was expressed in any other normal tissues.mRNA was isolated and cDNA was prepared from 34 ovarian tumors (four adenomas, three low malignant potential tumors, and 27 carcinomas) and seven normal ovaries. The testisin mRNA expression level relative to internal control, beta-tubulin, was determined by Northern blot analysis and semiquantitative polymerase chain reaction (PCR).Northern blot hybridization showed that the testisin transcript was abundant in ovarian carcinoma but was not detected in normal ovary. On examination of Northern blots from normal fetal and adult tissues, only adult testis showed abundant transcripts of testisin. Semiquantitative PCR examination showed that the testisin mRNA levels in ovarian tumors of low malignant potential and in ovarian carcinomas were significantly higher than in normal ovaries (P.01). Testisin mRNA level in ovarian carcinomas was also significantly higher than in ovarian adenomas (P.05). Testisin overexpression rates in advanced stage (stage 2 or 3) diseases were significantly higher than that in early stage diseases (stage 1) in ovarian carcinoma samples (P.05).The induction of the testisin transcript might contribute to the development, progression, and invasive or metastatic capacity of ovarian carcinomas.

It has been known for10 years that there are two alleles of the human ornithine decarboxylase (ODC) gene, defined by a polymorphic PstI RFLP in intron 1. We have sequenced a large portion of each of the two alleles, including some of the 5' promoter region, exon 1, intron 1, and exon 2, and determined that a single nucleotide polymorphism at base +317 (relative to transcription start site) is responsible for the presence or absence of the PstI restriction site. We have developed two genotyping assays, a PCR-RFLP assay and a high-throughput TaqMan-based method, and determined the ODC genotype distribution in900 North American DNA samples. On the basis of its location between two closely spaced Myc/Max binding sites (E-boxes), we speculated that the single nucleotide polymorphism at base +317 could have functional significance. Results of transfection assays with allele-specific reporter constructs support this hypothesis. The promoter/regulatory region derived from the minor ODC allele (A allele) was more effective in driving luciferase expression in these assays than the identical region from the major allele (G allele). Our results suggest that individuals homozygous for the A allele may be capable of greater ODC expression after environmental exposures, especially those that up-regulate c-MYC expression.

Objective To determine the functional and radiographic outcome of low Weber C ankle fractures and to evaluate the contribution of the syndesmotic screw in their outcome. Design Prospective evaluation of a consecutive series. Setting Level I trauma center. Patients Forty-five patients divided into two groups matched for age, sex, and severity of injury. Twenty-six patients were treated with open reduction, internal fixation, and a supplemental syndesmotic screw, and nineteen patients were treated without a syndesmotic screw. Minimum time to follow-up was three years. Methods A subjective, objective, and radiographic ankle scoring system was used. Logistical regression analysis was performed to determine whether the presence or absence of a syndesmotic screw was a predictor of a poor outcome. The likelihood ratio test was used to evaluate the significance of each variable in both univariate and multivariate analyses. Results There was no statistically significant difference between either group, either using subjective outcome criteria (p = 0.86) or in ankle range of motion (p = 0.94). Logistical regression analysis indicated that fracture dislocation could be used as a predictor of a poor outcome for either group. Inadequate reduction and advancing age were also found to be significant predictors of a poorer outcome regardless of the use of a syndesmotic screw (p = 0.003, p = 0.004). Conclusions Judicious fixation of Weber C type injuries within five centimeters of the ankle joint, with or without a syndesmotic screw, gives similar results. Obligatory fixation of these fractures with syndesmotic screws appears to have no benefit and creates the need for an additional procedure.

Wide use of a succession of different manufactured antimicrobial agents during the past 60 years has prompted the eventual emergence and progressive spread through the world's interconnecting bacterial populations of a growing variety of genes expressing resistance to those agents. The complex processes that spread and link resistance genes into different distributions at different times and places are driven by antimicrobial selection and by contagion. Management of resistance by reducing selection and contagion in a coordinated way requires better information. Most of the information about the spread of resistance exists in laboratory files of isolates at medical centers, and the information about patient antimicrobial use is found in pharmacy files at the same centers. Putting these in a combined database at each center would give a valuable tool to each center's antimicrobial resistance management team. Merging such databases from multiple centers would provide a public health resource for benchmarking, overview surveillance, and general resistometrics.