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Although spores from most macrofungi are wind- or water-dispersed, dispersal may also occur via biotic vectors. The Eastern box turtle (Terrapene carolina carolina) is a facultative mycovore that may play an important role in fungal spore dispersal although, to date, no information exists on fungi occurring in fecal samples of box turtles or on the ecological significance of box turtles as spore dispersal vectors. Consequently, a study of the potential for Eastern box turtles to act as vectors for spore dispersal was initiated by capturing wild turtles and collecting fecal samples. Serial dilutions from fecal samples were made to enumerate spores, quantify the number of spores per gram of fecal material and to isolate and identify fungi. Fungal spores were found to be extremely abundant throughout all samples. Fecal samples from 36 turtles yielded a total of 23 different fungal taxa in the Zygomycota, Ascomycota and Basidiomycota. Two yeasts that were isolated, Cryptococcus albidus and Rhodotorula mucilaginosa, are reported to naturally occur on Trifolium seeds found in fecal samples. A mold previously unreported from fecal material, Aspergillus wentii, was also found in fecal samples. Data collected suggests Eastern box turtles influence fungal spore dispersal by browsing on plant materials and defecating large numbers of fungal spores within their home ranges.

The ordinary refractive index of sapphire, at 532 nm, was measured in single crystals subjected to elastic, uniaxial tensile (and compressive) strain along the c axis in plate impact experiments. The refractive index under both tension and compression was determined from the difference between the uncorrected particle velocities from velocity interferometer measurements and the known particle velocities in symmetric impact experiments. Results to a peak stress of 100 kbar in tension and compression show that the refractive index has an overall monotonic, nonlinear dependence on density that is asymmetric about the ambient density. In compression, the refractive index decreases by an extremely small amount; in contrast, the change is relatively larger in tension. These refractive index results at large tensile stresses suggest that sapphire polarizability is quite different under compression and tension. Compression measurements by themselves can be approximated well by a linear refractive index–density relation, resulting in a window correction (at 532 nm) that is a constant fraction of the true particle velocity up to at least 115 kbar longitudinal stress. The present data also provide high-precision shock velocity results in compression and demonstrate the appropriateness of using second and third order elastic constants for calculating the elastic response of sapphire under uniaxial tensile strain loading.

Object: To determine if vulvar melanosis progressed to melanoma over a period of 20 years or more. Methods: In 2010 the hospital records from the Royal Brisbane Hospital Vulvar Clinic between 1976 and 1988 were reviewed and cross checked with the state wide Queensland Centre for Gynaecological Cancer (QCGC) data base to determine if any patient had been lost to follow up and subsequently developed a vulvar melanoma. Data collected were stored and analysed using the computer software Statistical Package for the Social Sciences (SPSS) 11.0. Results: None of the 12 patients developed vulval melanoma in the years up to 2010. Conclusion: In this small group, followed for more than 20 years, melanosis was not a precursor of melanoma. One patient, who attended the Vulvar Clinic but was not included in this melanosis study, was found to have co-existing melanosis well away from her melanoma in situ and malignant melanoma at presentation. It was not possible to determine if these findings represented a progression of the benign to malignant. Biopsy of abnormal hyper pigmented vulvar skin is recommended. Current knowledge suggests that vulvar melanosis is a benign condition but to be on the safe side follow up of all hyper pigmented vulval lesions to detect early malignant change is recommended.

A combination of geologic carbon dioxide (CO2) sequestration and CO2 enhanced oil recovery (CO2EOR) can address the two of Trinidad and Tobago's energy sector challenges: falling oil production and increasing CO2 emissions. Geologic storage of CO2 in heavy oil reservoirs can increase oil production while injected CO2 is effectively sequestered. Our investigations are based on 225 ft (~69 m) of the unconsolidated Lower Forest sand, average porosity and permeability of 32% and 125 md, respectively, found within the Forest reserve field, Trinidad. The middle section of this sand package contains a 26 ft (8m) thick layer of shaly sand with average permeability 70 md and average porosity 28%. We used reservoir simulations to determine the impact of dip and reduced transmissibility on the performance of the water over gas injection strategy using CO2. From our results we conclude that the reduced vertical transmissibility and dip affects the formation of the oil bank, water underride and the rate of CO2 migration.

Sapphire crystals were shocked to 190 kbar along the a axis to characterize their use as optical windows, for velocity interferometry measurements, up to their Hugoniot elastic limit. When partially polarized light is incident on the samples, birefringence in the material is manifested as a beat frequency in the probe light that is returned from the specimens. Proper procedures for interpreting the velocity interferometry data for various polarization conditions were developed. The refractive indices at 514.5 nm wavelength decreased linearly with the density. The data were analyzed to yield three photoelastic coefficients: p12, p31, and p41. Calibration is developed for any polarization state of the probe light. Particle velocity wave forms are consistent with elastic behavior up to 170 kbar shock stress, and evidence of deviation from elastic behavior is present at 190 kbar impact stress. High precision shock velocity measurements are reported to 170 kbar stress along the a axis.

Shock wave experiments were performed to characterize z-cut, α-quartz as an optical window for velocity interferometry measurements. Refractive index changes and shock velocities were determined to 60 kbar peak stress. Results indicate that the window correction to velocity measurements is a constant fraction of the actual particle velocity, Δu/u=0.081 07. Shock velocity measurements provide the Hugoniot curve to 60 kbar, and yield the fourth-order elastic constant, C3333=174 810 kbar. By combining the velocity correction factor and the shock velocity measurements, the refractive index is determined to be a linear function of density. This finding is used to show that the velocity correction appropriate for a step jump may be applied to monotonically time-dependent wave forms with negligible error. The present work has demonstrated the use of z-cut quartz as an optical window to 60 kbar.

Summary Aims Altered proximal tubular cell growth and interstitial fibrosis are features of diabetic nephropathy and correlate with disease progression. These observations are poorly understood, although it has been suggested that they are secondary to glomerular disease. The primary aim of this study was to assess the direct effects of high extracellular glucose concentrations on the human tubulointerstitium. Methods Primary cultures of human proximal tubule cells (PTCs) and cortical fibroblasts (CFs) were grown for 6 days in media containing either 6.1 mmol/l or 25 mmol/l glucose. Cell proliferation, thymidine uptake (a marker of DNA synthesis), protein content and collagen synthesis were measured. Results In PTCs, exposure to high glucose was associated with a 410 ± 108% increase in cell numbers (P

This pilot study investigated the frequency, cause and progress of abnormal liver function tests (LFTs) in severe anorexia nervosa. Six consecutive cases of anorexia nervosa severe enough to require hospital admission and 14 outpatients with anorexia nervosa had LFTs performed. All inpatients had abnormal LFTs, with grossly elevated liver enzymes in four patients. All normalized quickly with weight gain apart from one whose alanine transaminase (ALT) remained slightly elevated. Investigations failed to reveal any other cause of liver disease. ALT values were slightly elevated in three outpatients. Abnormal LFTs occur in some patients with anorexia nervosa. Most resolve quickly and are not associated with hepatic failure. A larger study is required to determine the frequency of occurrence, cause and natural history. Copyright © 1999 John Wiley & Sons, Ltd and Eating Disorders Association.

Skin entrance doses of patients undergoing interventional x-ray procedures are capable of causing skin damage and should be monitored routinely. Single TLD chips are not suitable because the location of maximum skin exposure cannot be predicted. Most photographic films are too sensitive at diagnostic x-ray energies for dosimetry, exhibit temporal changes in response, and require special packaging by the user. We have investigated the suitability of laser heated MgB 4 O 7 TLDs in a polyimide binder in the range of 0.2–20 Gy. These are available in radioluscent arrays up to 30×30 cm for direct measurement of patient skin dose. Dose response was compared with a calibrated ion chamber dosimeter. Exposures were made at 60, 90, and 120 kVp, at low (fluoroscopy) and high (DSA) dose rates, and at different beam incidence angles. Longitudinal reproducibility and response to temperature changes during exposure were also checked. The dose response is linear below approximately 6 Gy where the slope starts to increase 2% per Gy. Errors were less than ±2% over a 0–80 degree range of beam incidence angles; less than ±3% for both dose rate variations and kVp differences between 70 and 120 kVp. The response was unaffected by temperature changes between 20 and 37 °C. Reproducibility is currently ±7%. MgB 4 O 7 TLD arrays are suitable for patient dosimetry in high dose fluoroscopy procedures if appropriate calibrations are used. Uncertainty in skin dose measurement is less than 10%, which is substantially better than film dosimetry.

Laparoscopic assisted vaginal hysterectomy (LAVH) performed in 109 cases has been reviewed. In this series the mean operative time was 89 minutes and mean inpatient hospitalization was 3.7 days. Throughout the review, 6 patients were considered to have major complications and each is discussed. The association of previous caesarean section and bladder damage is noted. LAVH widens the indications available for vaginal hysterectomy in younger women in whom the abdominal approach would previously be indicated, but extra caution is advised when this technique is first introduced to a gynaecological service.

To describe the mechanism, injury pattern and management of women who present to the ED with non-obstetric vulval trauma.A retrospective, single-institution case series was carried out. Data were sourced from medical records of women who presented to the ED and Royal Brisbane and Women's Hospital between 2007 and 2011. Records of possible injuries to the vulva were assessed to determine incidence, age, site, type of injury, mechanism of injury and whether urinary retention required treatment. This information was analysed using the computer software Statistical Package for the Social Sciences 11.0.Vulval non-obstetric trauma was found in 19 of 519 cases, resulting in haematoma formation, lacerations, tears or a combination of the three in 16 of the 19 cases. Injuries were due to falling astride a firm object, consensual coitus, sexual assault, cold waxing and tight clothing. Urinary retention occurred in three cases. Site of injury, whether anterior or posterior, was evenly distributed irrespective of the mechanism of injury. Haematomas were treated conservatively and bleeding lacerations sutured. None required resuscitation.Non-obstetric vulval injuries are uncommon (incidence 3.7%). All cases require assessment for vaginal, urethral, anal and bony pelvis injuries. This might require examination under anaesthesia. Conservative management of haematomas in the absence of acute haematoma expansion is favoured. The need to screen for sexually transmissible infections and pregnancy is important. Social worker and psychological support is important to reduce the incidence of long-term psychological problems.

Physiologically optimized processes, such as respiration, walking, and cardiac function, usually show a range of variability about the optimized value. Airway resistance has, in the past, been noted as variable, and this variability has been connected to pulmonary disease (e.g., asthma). A hypothesis was presented many years ago that postulated airway resistance as an optimized parameter in healthy individuals, and we have noticed that respiratory measurements made with the airflow perturbation device (APD) tend to be variable in nature. It was posited that this variability indicates that respiratory resistance is optimized similarly to other physiological processes. Fifty subjects with a wide range of demographics volunteered to have 100 measurements made of their respiratory resistances. Resistances were separated into inhalation and exhalation phases. These were plotted and shown to have frequency distributions that were consistent with expectations for an optimized process. The frequency distributions were not quite symmetrical, being skewed slightly toward upper resistances. Comparison between subject data and data from a mechanical respiratory analog showed that subject resistance variation is overwhelmingly from the respiratory system and not from the APD.

While children's magazines 'blur the lines' between editorial content and advertising, this medium has escaped the calls for government restrictions that are currently associated with food advertisements aired during children's television programming. The aim of this study was to address significant gaps in the evidence base in relation to commercial food messages in children's magazines by systematically investigating the nature and extent of food advertising and promotions over a 12-month period.All issues of Australian children's magazines published in the calendar year 2009 were examined for references to foods or beverages.Approximately 16% of the 1678 food references identified were portrayals of branded food products (or food brands). However, only 83 of these 269 were clearly identified as advertisements. Of these 269 branded food references, 86% were for non-core (broadly, less healthy) foods, including all but seven of the advertisements.It appears that recent reductions in televised promotions for non-core foods, and industry initiatives to reduce the targeting of children, have not carried through to magazine advertising. This study adds to the evidence base that the marketing of unhealthy food to children is widespread, and often covert, and supports public health calls for the strengthening of advertising regulation.

Despite the high prevalence of asthma in the elderly, its development, diagnosis, and treatment are under-researched. This paper provides a comprehensive review of the current state of knowledge in relation to management of asthma in the elderly - focusing on barriers to diagnosis and treatment and the central role of self-management. Asthma prevalence increases with age, as does the risk of dying from asthma, and with the ageing of the population and increasing life expectancy, the prevalence of (diagnosed and undiagnosed) asthma in older adults is expected to increase drastically, placing an increasing burden on sufferers, the community and health budgets. Asthma sufferers are more likely to be psychologically distressed and at a higher risk of anxiety and depression, more likely to experience a sense of lack of control over their health and to have lower self-reported quality of life. Asthma is under-diagnosed, and under-treated, in the elderly, further exacerbating these negative consequences. The review concludes, among other things, that there is a need to better understand the development and impact of asthma in the elderly, to increase community awareness of asthma in the elderly, to improve both 'medical management' and 'self-management' in this population and to develop more effective tools for diagnosis and treatment of asthma in the elderly. The paper concludes with key recommendations for future research and practice in this area.

Anaemia occurs in 25% of people attending hospital diabetes clinics, but this may not be representative of all people with diabetes. We aimed to determine the prevalence of anaemia in a prospective population-based sample stratified by estimated glomerular filtration rate (eGFR) using the 4-point Modification of Diet in Renal Disease (MDRD) formula.All 7331 patients on our district register were stratified by eGFR. Seven hundred and thirty were approached by letter on two occasions. Two hundred and thirty-four (32%) returned questionnaires and blood samples. Responders (R), non-responders (NR) and the whole cohort (C) were similar: mean +/- sd age R 61.7 +/- 12.7 years; NR 61.3 +/- 15.1 years; C 61.8 +/- 14.2 years; diabetes duration R 8.8 +/- 8.6 years; NR 8.2 +/- 7.9 years; C 7.5 +/- 7.8 years, Type 1 diabetes R 10.1%, NR 10.8%, C 9.4%. Anaemia was defined using World Health Organization criteria: haemoglobin13 g/dl for men,12 g/dl for women.Previously undiagnosed anaemia was present in 15% of the whole group, 36% with eGFR60 ml/min per 1.73 m(2) and 9% of those with eGFR60 ml/min per 1.73 m(2). Anaemia was as a result of erythropoietin deficiency in 34%, abnormal haematinics in 40% and was unexplained in 26% of patients. Five per cent of the patients had anaemia below the treatment threshold of 11 g/dl.The prevalence of unrecognized anaemia in population-based cohorts is lower than that in hospital-based studies. Current clinical surveillance in the UK is failing to detect anaemia in stage 3-5 chronic kidney disease (eGFR60 ml/min per 1.73 m(2)) and current guidelines will not detect 9% of diabetic patients with anaemia and an eGFR60 ml/min per 1.73 m(2).

SPIRE, the Spectral and Photometric Imaging Receiver, is the Herschel Space Observatory's submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 {\mu}m, and an imaging Fourier transform spectrometer (FTS) covering 194-671 {\mu}m (447-1550 GHz). In this paper we describe the initial approach taken to the absolute calibration of the SPIRE instrument using a combination of the emission from the Herschel telescope itself and the modelled continuum emission from solar system objects and other astronomical targets. We present the photometric, spectroscopic and spatial accuracy that is obtainable in data processed through the "standard" pipelines. The overall photometric accuracy at this stage of the mission is estimated as 15% for the photometer and between 15 and 50% for the spectrometer. However, there remain issues with the photometric accuracy of the spectra of low flux sources in the longest wavelength part of the SPIRE spectrometer band. The spectrometer wavelength accuracy is determined to be better than 1/10th of the line FWHM. The astrometric accuracy in SPIRE maps is found to be 2 arcsec when the latest calibration data are used. The photometric calibration of the SPIRE instrument is currently determined by a combination of uncertainties in the model spectra of the astronomical standards and the data processing methods employed for map and spectrum calibration. Improvements in processing techniques and a better understanding of the instrument performance will lead to the final calibration accuracy of SPIRE being determined only by uncertainties in the models of astronomical standards., Comment: Accepted for publication in Astronomy&Astrophysics, Herschel First Results special issue

The non-linear behaviour of bolometric detectors can lead to significant radiometric errors in Fourier spectroscopy if left uncorrected. We discuss preliminary investigation of this effect and its correction.

We examined interspecific aggression between two subterranean termite species, Heterotermes aureus (Snyder) (Rhinotermitidae) and Gnathamitermes perplexus (Banks) (Termitidae). In laboratory tests with worker termites, neither species was the inherently superior fighter, but rather the outcome of interspecific encounters depended on the number of conspecifics. We then investigated patterns of resource use by these species during a 13-month period in the Sonoran Desert. Baits consisted of toilet-paper rolls, which have been shown to be a mutually acceptable food source. Analyses of foraging activity demonstrated that the two species did not forage independently of each other. Not only were the two species negatively associated spatially, but extended periods of temporal segregation were observed. G. perplexus took significantly longer to return to sites that it had simultaneously occupied with H. aureus than to sites that G. perplexus had occupied alone. The pattern of co-occurrence of these two species is consistent with the hypothesis that interspecific interference competition affects their spatial and temporal distribution.

The presence of mRNA for epidermal growth factor (EGF) and transforming growth factor-α (TGFα) was demonstrated in small fragments of human endometrium and decidua by use of the technique of reverse transcriptase-polymerase chain reaction with nested oligonucleotide primers. The presence of mRNA encoding EGF and TGFα has not been shown in human endometrium previously. Other studies using conventional techniques, such as Northern blot or in-situ hybridization, showed the presence in low copy number of EGF but not TGFα in murine endometrium. Messenger RNA for EGF was not present in peripheral leukocytes or platelets, suggesting an endometrial source for the message. Messenger RNA for TGFα was found in these blood components, thus preventing confirmation of the source of TGFα mRNA.

The response of blood flow to choroid plexus (CPBF) during hypercapnia is controversial. The goal of this study was to determine the effect of hypercapnia on CPBF in unanesthetized rats. Rats breathed air or a mixture of 5-8% CO2 in air, and CPBF was measured with [14C]isopropyliodoamphetamine and quantitative autoradiography. In hypercapnic rats [arterial PCO2 61.6 +/- 1.6 (SE) mmHg; n = 7] CPBF was similar to that of normocapnic control rats (525 +/- 39 ml.min-1.100 g-1; arterial PCO2 42.7 +/- 0.6 mmHg; n = 5). In contrast, blood flow to cerebral cortex increased 67% during hypercapnia. CPBF in normocapnic rats that were treated with phentolamine was similar to untreated normocapnic and hypercapnic rat CPBF. However, during hypercapnia, CPBF in phentolamine-treated rats increased 29%. Responses were similar in blood flow to choroid plexus of lateral, third, and fourth ventricles. Our findings indicate that hypercapnia has no effect on CPBF when alpha-adrenergic receptors are intact. In contrast, after blockade of alpha-adrenergic receptors, hypercapnia increases CPBF. These findings suggest that, during hypercapnia, levels of sympathetic activity or blood-borne catecholamines are increased that prevent increases in CPBF.

A portion of the pig epidermal growth factor (EGF) gene has been isolated and characterized. The nucleotide sequencies of exons 20 and 21, which encode the EGF region of the precursor protein, show 85% similarity with the human EGF gene sequence. In addition, conservation of the intron—exon boundaries between the two species was generally observed. Although the pig exon 21 appeared to lack a single nucleotide at its 5′ end relative to the human gene, sequences obtained by direct amplification of the genomic DNA around the 5′ end of this exon using the polymerase chain reaction, and from a pig EGF cDNA recombinant isolated from a kidney library, indicated that the deletion was probably a cloning artifact. Comparison of the predicted amino acid sequence of pig EGF with that of EGF from other species, as well as with several other polypeptides which bind to the EGF receptor, indicated conservation of Gly18, Tyr37, Gly39 and Arg41 in addition to all six cysteine residues and Leu47, which are known to be critical for biological activity. A synthetic gene encoding the predicted amino acid sequence of pig EGF was expressed in yeast. The recombinant polypeptide was shown to compete with 125I-labelled mouse EGF for binding to cells and to stimulate DNA synthesis in quiescent monolayers of Swiss 3T3 cells.

Atrial fibrillation (AF) may be present within a subset of patients with presumed cryptogenic TIA or stroke and remains undetected by standard diagnostic methods. We hypothesized that AF may be an under-recognized mechanism for cryptogenic TIA/stroke.A consecutive series of 56 patients with cryptogenic TIA/stroke was analyzed after diagnostic evaluation and Mobile Cardiac Outpatient Telemetry (MCOT) for up to 21 days. Demographic, radiographic, echocardiographic, and MCOT results were reviewed. Predictors of AF detection by MCOT were determined by univariate analysis including Student t test and Fisher exact tests and multivariate analysis.The median MCOT monitoring duration was 21 (range 5-21) days resulting in an AF detection rate of 23% (13/56). AF was first detected after a median of 7 (range 2-19) days of monitoring. Twenty-seven asymptomatic AF episodes were detected in the 13 patients, of which 85% (23/27) were30 seconds and the remaining 15% (4/27) were 4-24 hours in duration. Diabetes was predictive of AF detection by both univariate (p = 0.024) and multivariate analysis (OR 6.15; 95% CI 1.16 to 32.73; p = 0.033).There is a high rate of atrial fibrillation (AF) detection by Mobile Cardiac Outpatient Telemetry (21 days) in patients with cryptogenic TIA/stroke that may be related to extended monitoring duration, patient selection, and inclusion of all new onset AF episodes. Brief AF episodes (30 seconds) may be biomarkers of more prolonged and clinically significant AF.

Complementary gas‐gun and electromagnetic pulse tests conducted in Sandia's Dynamic Integrated Compression Experimental (DICE) Facility have, respectively, probed the behavior of electronic‐grade Kovar® samples under controlled impact and intermediate‐strain‐rate ICE (Isentropic Compression Experiment) loading. In all experiments, velocity interferometer (VISAR) diagnostics provided time‐resolved measurements of sample response for conditions involving one‐dimensional (i.e., uniaxial strain) compression and release. Wave‐profile data from the gas‐gun impact experiments have been analyzed to assess the Hugoniot Elastic Limit (HEL), Hugoniot equation of state, spall strength, and high‐pressure yield strength of shocked Kovar®. The ICE wave‐profile data have been interpreted to determine the locus of isentropic stress‐strain states generated in Kovar® for deformation rates substantially lower than those associated with a shock process. The impact and ICE results have been compared to examine the influence of loading rate on high‐pressure yield strength.

A significant percentage of tympanic membrane (TM) perforations require some form of therapy to heal. Topical application of epidermal growth factor (EGF), a potent mitogen for epidermal and mesodermal cells, promotes healing of injuries in tissues histologically similar to TM, such as cornea and skin. We evaluated TM as a target tissue for EGF action. Specific, high affinity receptors for EGF were detected in TM (Kd = 3.1 nM, 150 fmol receptor/mg protein). Autoradiography of iodine 125-EGF binding to intact TMs revealed that EGF receptors were present on cells in the stratified squamous epithelial layer and in the stromal/mucoepithelial layer. Repetitive treatment of perforated cat TMs with 20 micrograms of EGF formulated in saline induced substantial hyperplasia of epithelial and stromal layers compared to paired TMs treated with saline. A single treatment of perforated cat TMs with 50 micrograms of EGF formulated in a hydrogel or in shredded Gelfoam produced significantly (p less than .05) smaller perforations at 6 days following the operation compared to paired TMs treated with vehicles. These results demonstrate that TM is a target tissue for EGF and that topical treatment with EGF stimulates healing of TM perforations.

A series of gas‐gun experiments has probed the planar (uniaxial strain) impact response of six different commercial brazing alloys that were subjected to a peak shock stress in the range of 5.5 – 7.2 GPa. The alloys studied were copper + gold (65/35 wt%), copper + gold (50/50 wt%), Cusil®, Nicusil®‐3, Nicoro® + titanium (98/2 wt%), and silver zirconate. Both as‐received and annealed samples of each alloy were tested under ambient (room temperature) and preheated (100 C) initial conditions. Velocity interferometer data acquired during this investigation have been evaluated to determine the dynamic yield strength (i.e., Hugoniot Elastic Limit), shock Hugoniot state, and spall strength for baseline alloy samples (i.e., unheated, as‐received material) and for samples whose initial condition involved annealing and/or preheating.

Pi Technology and the Ford Motor Company are using MATLAB Simulink/Stateflow model based design and automatic code generation in C, for the main software development for three electronic control units targeted at the FordFocus fuel cell vehicle. The automatic generation of code for embedded automotive applications offers a number of potential advantages over traditional methods. These include faster development, the avoidance of coding errors and avoiding inconsistencies with the design specification. However, the use of automatically generated code in production-intent safety-related systems requires at least the same standard of validation and verification. If code generation were perfect, one could validate only the design. However, it is impractical to require that the code generator must be validated for all possible input designs. Furthermore it must be assumed that the compiler and the hardware can also introduce faults. Therefore we adopt the approach of testing output code for the particular designs we wish to implement, in the same manner as we would test hand-written code for production systems [1]. This retains the additional benefits of exposing the design to further detailed scrutiny in test preparation, and encouraging designs that are straightforward to test. This paper discusses the development lifecycle employed on this project, highlighting the particular benefits, issues, and challenges surrounding the use of automatically generated code for these production-quality safety-related automotive controllers.

Static mixers are increasingly being used to mix coagulants like alum in water treatment plants. This study investigates static mixers for this application using two complementary approaches. In the computational approach, a state-of-the-art computational fluid dynamics model was developed to predict the turbulent fluid flow in a helical static mixer for flow rates near those found in these mixers in water treatment plants. The model predictions show that a complex, three-dimensional fluid flow is produced within the mixer. In the experimental approach, a variety of static mixers of different design and different scales were tested for mixing alum for coagulation in a pilot plant study.

Cadmium sulfide crystals were shocked along the c-axis to peak instantaneous stresses ranging from 27 to 53 kbar, above and below the phase transition stress of 32 kbar. Particle velocity measurements, using a VISAR system with nanosecond temporal resolution, were used to determine the time dependent mechanical response at the impact surface at higher time resolutions than those reported by Tang and Gupta, and to complement the recent electronic spectroscopy measurements. For experiments with longitudinal stresses above 32 kbar, but below 53 kbar, the instantaneous impact stress of the initial wurtzite phase is maintained for significant times before relaxing to a metastable state, and then further relaxing to the final rock salt phase. Transition rates and metastable state lifetimes are observed to be stress dependent. At 53.5 kbar impact stress, transition to a metastable state appears to be complete within 3 ns of impact, and the full relaxation to the rock salt phase indicates that the phase transition may proceed through multiple metastable states. Epoxy bonds with VISAR windows degrade the ability to accurately measure fast, stress-relaxing phenomena.

Aims/hypothesis. We investigated the effects of constant and intermittently increased glucose concentrations on human proximal tubule cells and cortical fibroblasts in primary culture. Methods. Cells were grown to confluence and then exposed for 4 days to 6.1 mmol/l d-glucose (normal), 25 mmol/l d-glucose (high), or 6.1 mmol/l alternating with 25 mmol/l d-glucose on a daily basis. Results. In proximal tubular cells, exposure to high glucose caused an 11 % increase in thymidine uptake (p < 0.05), a 230 % increase in secretion of transforming growth factor beta 1 (TGF-β1; p < 0.05) and a 393 % increase in platelet derived growth factor. Intermittent exposure to high glucose caused thymidine uptake to further increase by 42 % (p < 0.01) and TGF-β1 secretion by 352 % (p < 0.01) but no additional increase in platelet-derived growth factor secretion was observed. Cellular protein content increased by 27 % (p < 0.05) and collagen synthesis by 29 % (p < 0.05), changes that were not observed in cells constantly exposed to high glucose. In cortical fibroblasts constant exposure to high glucose caused a 35 % increase in thymidine uptake (p < 0.01). Intermittently high glucose increased thymidine incorporation a further 58 % (p < 0.001), collagen synthesis by 65 % (p < 0.01) and insulin-like growth factor binding protein 3 secretion by 216 % (p < 0.01). Conclusion/interpretation. In cultured human tubulointerstitial cells, increased glucose concentrations change cell growth, collagen synthesis and cytokine secretion. These effects are enhanced following intermittent exposure to high glucose, indicating that short lived excursions in glycaemic control have important pathological effects on the human tubulointerstitium. [Diabetologia (1999) 42: 1113–1119]

Transforming growth factor alpha (TGF-alpha) and its receptor (EGF-R) may regulate normal and malignant epithelial cell growth by an autocrine mechanism. We investigated the role of TGF-alpha in regulating head and neck SCC tumor growth.TGF-alpha and EGF-R levels were measured in 7 SCC cell lines and 14 SCC biopsies by RIA, Scatchard, and Western analysis. TGF-alpha autocrine stimulation of DNA synthesis in SCC cell lines was assessed by incubation with TGF-alpha neutralizing antibodies and tyrphostin AG 1478, a selective and potent inhibitor of EGF-R kinase.All SCC cell lines synthesized TGF-alpha and expressed elevated EGF-R levels compared to normal keratinocytes. Twelve of the 14 SCC biopsies contained TGF-alpha protein and 8 had specific EGF-R. Exogenous TGF-alpha or EGF significantly increased DNA synthesis in 4 of 5 SCC cell lines. TGF-alpha neutralizing antibodies or tyrphostin AG 1478 reduced DNA synthesis in the two SCC cell lines (FaDu and SCC9) tested.These results indicate that SCC cell lines and tumors usually synthesize TGF-alpha, have elevated levels of EGF-R, and are mitogenically stimulated by a TGF-alpha autocrine system. Selective inhibition of the TGF-alpha system by EGF-R kinase inhibitors or TGF-alpha neutralizing antibodies may be useful strategies for treating SCC that overexpress TGF-alpha and its receptor.

A new thermal system using constant heating power for continuous measurement of cerebral perfusion is presented. It is designed and implemented for optimal perfusion sensitivity and dynamic response based on heat-transfer analysis of perfused brain tissue with thermistors on the cortical surface. Two matched thermistors are used, one to serve as a perfusion sensor and the other to compensate for the base-line temperature changes. To improve the signal-to-noise ratio of the measurement system, lock-in amplifiers are used to minimise long-term drift and low-frequency noise. Errors in the measurement caused by electrical and thermal fluctuations are tested and analysed. In vitro tests show that the measurement accuracy of temperature change is better than 10(-3) degrees C, and the temperature resolution is even greater. In vivo evaluation confirms that the system is responsive to cerebral perfusion changes associated with sudden changes in mean arterial blood pressure caused by bolus injection of norepinephrine, blood withdrawal and blood infusion. The dynamic response of the system is sufficient to detect the autoregulatory perfusion changes in response to arterial blood pressure alteration and the oscillations of cerebral blood flow.

We have studied modulation of mucosal interleukin-6 (IL-6) secretion by T-cell activation and by anti-inflammatory agents in inflammatory bowel disease.In vitro secretion of IL-6 by biopsy specimens from patients with active ulcerative colitis was investigated in the presence of cyclosporin-A (CsA) and drugs that have other anti-inflammatory actions. Biopsy specimens from patients with quiescent ulcerative colitis or controls were stimulated with anti-CD3 antibody to activate mucosal T cells.Stimulation of control specimens increased IL-6 secretion (median increase, 147%; p0.003), which was prevented by CsA. In quiescent ulcerative colitis there was enhanced spontaneous secretion of IL-6 but a smaller, non-significant increase after T-cell activation (125%). Dexamethasone inhibited secretion in active ulcerative colitis (p0.006). 5-Aminosalicylic acid, 6-mercaptopurine, methotrexate, and indomethacin had no effect. There also tended to be a small reduction with CsA, but this just failed to reach statistical significance.In quiescent ulcerative colitis the enhanced spontaneous secretion of IL-6 may be a consequence of mucosal T-cell or macrophage activation: the smaller increase after T-cell stimulation suggests that one or both of these two cell types are already pre-activated.

Magnetic resonance diffusion-weighted imaging (MR-DWI) is sensitive to the diffusibility of water and may offer characterization and anatomical localization of stroke leading to early tailored therapeutic intervention. We compared DWI, the apparent diffusion constant (ADC), and autoradiographic cerebral blood flow (CBF) in a model of focal cerebral ischemia in the rat. Sprague-Dawley rats were embolized with a single silicone cylinder injected into the internal carotid artery. Both common carotids were permanently ligated. The animals were anesthetized (isoflurane in O2), and paralyzed (gallamine). MR-DWI were obtained with a GE 4.7 T magnet (TE = 3 s, TR = 80 msec, b = 2393.10(-3) mm2/s, slice thickness 3 mm). DWI and CBF autoradiograms were compared visually. ADC was assessed in various regions, including ischemic cortex and a region homologous to ischemic cortex. Imaging times from stroke onset were 50 +/- 6 min (mean +/- SEM) for DWI, 185 +/- 17 min for a second DWI. CBF was determined at 258 +/- 15 min. The specificity was 100% at both 50 min and 185 min, indicating that there were no false positives; in 3 animals ischemia was not present. However, the sensitivity analysis indicated that early DWI yields some false negatives; at 50 min the sensitivity was 60%. We attribute our result of low early sensitivity to small infarcts in relation to the slice thickness. Later, at 185 min, sensitivity was 100%. The first ADCs were higher than the second ADC values in ischemic cortex. For infarcts larger than the slice thickness, early MR-DWI is highly sensitive for imaging evolving ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

AIMS--To investigate the cellular source of the cytokine interleukin-6 (IL-6) in the small and large intestines of patients with inflammatory bowel disease, coeliac disease, and in controls. METHODS--IL-6 was detected in frozen sections of bowel by single and double label indirect immunofluorescence using rabbit polyclonal and murine monoclonal anti-IL-6 antibodies. The murine monoclonal antibodies RFDR1 (anti-MHC class II) and UCHT1 (anti-CD3) were used to localise macrophages and T lymphocytes, respectively. Lipopolysaccharide stimulated peripheral blood monocytes were used as positive control cells for IL-6 protein. RESULTS--IL-6 was demonstrated in the small and large intestine of patients with inflammatory bowel disease, coeliac disease, and in controls. The protein was present predominantly in enterocytes and colocytes in normal and inflamed mucosa, but not in the infiltrating inflammatory cells of the lamina propria. There were no discernable differences between patients with inflammatory bowel disease or coeliac disease and controls, nor between small and large bowel mucosa. Incubation of antibody with recombinant human IL-6 protein abolished the labelling. IL-6 protein was also present in lipopolysaccharide stimulated peripheral blood monocytes. CONCLUSIONS--The data suggest that enterocytes and colocytes may play an active part in the immune response of the gut. The presence of IL-6 in both inflamed and non-inflamed small and large intestine requires further investigation into the function of this cytokine in the gut.

Publisher Summary This chapter focuses on the fluorescent and radioactive solid-phase dideoxy sequencing of polymerase chain reaction (PCR) products in microtiter plates. The reactions presented are easy to perform and are reproducible, using various different sources of DNA template. Both short and long PCR products can be readily sequenced and oligo walking along the solid-phase-bound template is demonstrated. A further advantage of solid-phase sequencing is the high quality of the sequence data produced. The chapter discusses the development of a robust technique for directly sequencing terminally biotinylated PCR products by selective immobilization to streptavidin-coated magnetic beads. This technique can be applied with different labeling approaches either [α- 35 S] deoxyadenosine triphosphate (dATP), fluorescently labeled dideoxynucleoside triphosphates, or fluorescently labeled sequencing primers. It has been used to generate DNA sequences amounting in excess of 200 kb in total. The method is applicable to short and long templates, and the semi automation of the technique is described in this chapter.

Eighty-five patients with non-organic abdominal pain, were interviewed with the help of a questionnaire. Those who responded to a high fibre diet were excluded from the study. Twenty-seven patients had multiple pains and 58 described a single pain, which was intermittent in 39. A detailed analysis of the symptoms and family history of the latter group suggested that in 19 patients the symptoms might have been caused by abdominal migraine. Six of these 19 had typical migraine-associated symptoms during the attack, characteristic abdominal pain and a family or personal history of classical migraine. Abdominal migraine should be considered in patients with non-organic abdominal pain where symptoms are not typical of irritable bowel syndrome and when organic disease has been excluded.

A family with the autosomal dominant form of familial visceral myopathy is described involving four generations. The members illustrate several different clinical presentations including severe constipation, diarrhea, alternating constipation and diarrhea, volvulus, urinary tract infection, and retention of urine. One patient's history suggested that the uterus may have been involved. Diagnosis of this rare disease requires an awareness of the variable presentation and a careful histological examination of full-thickness sections of bowel. The potential pitfalls in both histological and clinical diagnosis of this condition are demonstrated in this family's history. The extensive involvement of small and large bowel in at least two family members is unusual in the autosomal dominant form of the disease, but their course has so far been favorable, lending further evidence to the impression that prognosis is good. This is of importance for genetic counseling of families who have this very rare disease.

Neurologic complications are a major cause of morbidity, complicating open heart surgery, cardiac catheterization, and interventional techniques. Global or focal brain ischemia related to embolism or hypoperfusion predominates. Breakthrough cerebral hemorrhage and infection can complicate cardiac transplantation. Identifying individuals at risk for cerebrovascular complications may lead to more effective preventative and treatment measures.

Abdominal migraine is well recognised in children, but in spite of anecdotal reports migraine is not well established as a cause of abdominal pain in adults. Functional abdominal pain is usually classified as either irritable bowel syndrome or nonulcer dyspepsia, but some patients have intermittent abdominal pain associated with headache or other migraine accompaniments and, in these, a diagnosis of abdominal migraine should be considered. It is possible that some patients with functional abdominal pain have migraine presenting with few or even no migraine accompaniments. There is no nonclinical objective standard for diagnosing migraine, and research in this area is therefore very difficult. Nevertheless, some patients with functional abdominal pain may respond to antimigraine medication and, if their symptoms are suggestive, a trial of therapy may be desirable.

Low molecular weight dextran 40 (D40), 40,000 daltons, is a potential therapeutic agent for cerebral ischemia because it increases local cerebral blood flow. However, the evaluation of D40 in the rat has been difficult due to systemic effects. We evaluated the effects of isovolumic hemodilution with D40 on the development of peripheral edema, mean arterial pressure, hematocrit (Hct) and total blood volume in 18 rats, during 30 min or 4 hr i.v. infusions, in animals with and without previous challenge with D40. Reduction of Hct without peripheral edema to a mean of approximately 31% was only achieved in the animals challenged with i.p. D40 24 hr before hemodilution and who received D40 over a period of 4 hr. Infusion of D40 over a period of 30 min was associated with shorter survival time, compared to the 4-hr infusion group (P less than .005). In the pretreated, rapidly infused group, total blood volume per body weight decreased significantly over time (P less than .005) and the mean arterial blood pressure dropped, but not significantly (P less than .07), whereas no change in Hct was detected and there was a trend toward increased peripheral edema, relative to the slowly infused groups. We conclude that reduction of Hct can be achieved successfully with i.p. administration of D40 24 hr before the study combined with infusion of the agent during a 4-hr period, without significant peripheral edema and early hypotension. This procedure should be used to avoid allergic reactions when evaluating hemodilution with D40 in rats.

In this paper we describe a rapid method for the direct generation of DNA sequencing templates from phage or bacteria. Sequencing of these PCR products can be performed by radioactive and fluorescent methods. The non-radioactive method has been used to sequence a total of approximately 100 kb of human DNA fragments generated by digestion with HpaII and subsequent cloning. The method depends on direct small scale amplification using a biotinylated primer, and the binding of the product to streptavidin coated magnetic beads. All the procedures are carried out in a microtitre plate thus facilitating the handling of large numbers of clones and has potential for automation.