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Trapped electron mode (TEM) is the main source of turbulence predicted for the unique operation regime of a flat temperature profile under low-recycling conditions in the LTX-β tokamak, while ion temperature gradient driven turbulence may also occur with gas fueling from the edge. To investigate mainly TEM scale density fluctuations, a high spatial and time resolution 2D beam emission spectroscopy (BES) diagnostic is being developed. Apart from spatially localized density turbulence measurement, BES can provide turbulence flow and flow shear dynamics. This BES system will be realized using an avalanche photodiode-based camera and narrow band interference filter. The system can acquire data at 2 MHz. Simulations with the Simulation of Spectra (SOS) code indicate that a high signal to noise ratio can be achieved with the proposed system. This will enable sampling the density fluctuations at this high time resolution. The design considerations and system optimization using the SOS code are presented.

Aim Percutaneous tibial nerve stimulation (PTNS) is increasingly being used as a treatment for faecal incontinence (FI). The evidence for its efficacy is limited to a few studies involving small numbers of patients. The aim of the study was to assess the efficacy of PTNS in patients with urge, passive and mixed FI. Method A prospective cohort of 100 patients with FI was studied. Continence scores were determined before treatment and following 12 sessions of PTNS using a validated questionnaire [Cleveland Clinic Florida (CCF)-FI score]. The deferment time and average number of weekly incontinence episodes before and after 12 sessions of treatment were estimated from a bowel dairy kept by the patient. Quality of life was assessed prior to and on completion of 12 sessions of PTNS using a validated questionnaire [Rockwood Faecal Incontinence Quality of Life (QoL)]. Results One hundred patients (88 women) of median age of 57 years were included. Patients with urge FI (n = 25) and mixed FI (n = 60) demonstrated a statistically significant improvement in the mean CCF-FI score (11.0 ± 4.1 to 8.3 ± 4.8 and 12.8 ± 3.7 to 9.1 ± 4.4) with an associated improvement in the QoL score. This effect was not observed in patients with purely passive FI (n = 15). Conclusion The study demonstrates that PTNS benefits patients with urge and mixed FI, at least in the short term.

C. Boyd and D. P. Boyle Molecular diagnosis on tissues and cells: how it affects training and will affect practice in the future On 25th November 2011, a symposium organized by the Royal College of Pathologists, entitled ‘Molecular diagnosis on tissues and cells’, took place in London. As trainees in histopathology and cytopathology, we were stimulated to consider the role that molecular biology is likely to play in future practice and how this is addressed by our own training. The symposium provided a basis for this article. Routine samples requiring molecular analysis are equally relevant to histopathologists and cytopathologists, and molecular biology laboratories are now using cytological as well as histological material for diagnostic testing, allowing different specimen types to be used as and when they are most appropriate. The most widely used types of molecular analysis in routine cellular pathology are EGFR testing in lung cancer, molecular testing of thyroid nodules, fluorescence in situ hybridization testing of urine samples, clonality analysis in lymphoma testing, HER2 testing in breast and gastric cancer, KRAS testing in colorectal cancer, intraoperative assessment of breast cancer sentinel nodes, molecular testing of gastrointestinal stromal tumours and mismatch repair protein analysis. Of these, the majority in the UK are carried out on histopathology samples, although many are applicable to cytological samples if adequate material is obtained. We are particularly encouraged by the potential of molecular diagnostic cytology in traditionally difficult areas, such as intraoperative assessment. We believe that increasing reliance on molecular diagnostic techniques will also herald changes in training.

Soybean (Glycine max L. Merr.) genotype K 03-2897 was grown in a controlled environment to study the effects of high-temperature (HT) stress on ultrastructural changes in leaves and its relationship with photosynthetic rate. The objectives of this study were to (i) quantify the effects of HT stress during fl owering stage on photosynthetic rate and (ii) observe the anatomical and ultrastructural changes in leaves of soybean grown under HT. Plants were exposed to HT (38/28°C) or optimum temperature (OT; 28/18°C) for 14 d at fl owering stage R2. High-temperature stress signifi cantly decreased the leaf photosynthetic rate and stomatal conductance by 20.2 and 12.8%, respectively, compared with those at OT. However, HT stress signifi cantly increased the thicknesses of the palisade and spongy layers and the lower epidermis above those at OT. In addition, HT stress damaged the plasma membrane, chloroplast membrane, and thylakoid membranes. The mitochondrial membranes, cristae, and matrix were distorted under HT stress. High-temperature stress increased the content of leaf reducing sugars by 82.6% above that at OT. Leaves under HT stress had a higher carbon isotope ratio compared with that at OT. Decreases in photosynthesis at HT stress were mediated through anatomical and structural changes in the cell and cell organelles, particularly the chloroplast and mitochondria.

Background: Both actinomycotic granules and pseudoactinomycotic radiate granules (PAMRAGs) occur in the female genital tract, most commonly in the endometrium. It is important to distinguish between these since the former may result in pelvic inflammatory disease and require antibiotic treatment while the latter is non-infectious and does not require specific treatment. Aims: To investigate the coexistence of actinomyces-like organisms and PAMRAGs in the same granules, and describe the presence of PAMRAGs in the cervix and the vulva. Methods: Six cases with actinomyces-like organisms and PAMRAGs in the same granules (four in the endometrium, one in a tubo-ovarian abscess, and one in both the endometrium and a tubo-ovarian abscess) are reported as well as seven examples of PAMRAGs in the cervix and one in a vulval abscess. Results: The combined granules consisted of central basophilic Gram and silver positive filamentous organisms consistent with actinomyces surrounded by radiating eosinophilic club-like formations which were Gram and silver negative, the latter consistent with PAMRAGs. The PAMRAGs in the cervix and vulva consisted entirely of Gram and silver negative radiating eosinophilic club-like formations. Conclusions: Although actinomycotic granules and PAMRAGs are distinct lesions which should be distinguished for patient management, they may coexist in the same granules. It is likely in such cases that the PAMRAGs form around the bacterial colonies which act as a nidus. The presence of radiating eosinophilic club-like formations characteristic of PAMRAGs does not preclude the presence of actinomyces. Careful morphological examination plus supportive Gram and silver stains, if necessary, allows the diagnosis of these combined granules. PAMRAGs also occur in the cervix, where it is likely that they form secondary to encrustation of inspissated mucus, and in the vulva.

Aims: It is generally considered that an unequivocal histological diagnosis of endometriosis requires the presence of endometrioid-type glands and endometrioid-type stroma. However, small nodules or plaques of endometrioid-type stroma without glands have been noticed by the authors in repeated peritoneal biopsies performed for suspected endometriosis. These are often, but not always, accompanied by typical endometriosis with glands. This form of endometriosis has been previously referred to as stromal or micronodular stromal endometriosis. However, there has been little reference to this condition in the literature. Methods: In this study, there was a review of a large series (n = 274) of peritoneal biopsies with a diagnosis of endometriosis with a view to ascertaining the frequency of stromal endometriosis. Results: Stromal endometriosis, characterised histologically by small microscopic nodules or plaques of endometrioid-type stroma, sometimes with a whorled pattern and prominent vascularity and erythrocyte extravasation, was identified in 44.9% of the biopsies. In 6.6% of the biopsies, stromal endometriosis occurred without typical endometriosis. The foci of stromal endometriosis usually had a superficial location just beneath the mesothelial surface or protruding above this. Associated histological features present in some cases included reactive mesothelial proliferation, inflammation, giant cell or granuloma formation, haemosiderin pigment deposition, microcalcification and decidualisation and myxoid change. Conclusions: Stromal endometriosis, usually in the form of superficial nodules or plaques, is a relatively common form of endometriosis which typically occurs in association with typical endometriosis but occasionally on its own. Pathologists should be aware of the existence of this form of endometriosis, the morphological features of which may be subtle. The typical location, intimately associated with surface mesothelium, may suggest that stromal endometriosis derives from mesothelial or submesothelial cells via a metaplastic process.

This review paper presents and places in context findings from 23 manuscripts based on the data sets of the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (SECCYD). The NICHD study tracked the development of more than 1000 children from birth through age 15. The children were born across the USA to families that were diverse in terms of their economic, educational, and ethnic background. The children also varied in terms of the timing, extent, quality, and type of their child care experiences. The findings reported in this review paper pertain to (1) predictors of child-mother attachment; (2) links between child-mother attachment and children's developmental outcomes; and (3) methods for assessing attachment. The review paper also includes suggestions for future attachment research afforded by the data sets of the NICHD SECCYD. Not all the hypotheses tested in the reviewed papers were confirmed, and those that were confirmed were associated with modest effect sizes. Some findings emerged under specific conditions, even though they were expected to be more universal. These findings need to be discussed and aligned with theory. Also, the extent to which the findings generalize beyond the historical period and the country in which the data were collected merits discussion and exploration.

The immunoglobulin degrading enzyme of Streptococcus pyogenes, IdeS, is an unusual cysteine protease produced by group A streptococci for which the only known substrate is immunoglobulin G (IgG). To date, IdeS has not been found to cleave any of the known synthetic substrates that other cysteine proteases hydrolyse, thus making the development of an IdeS detection assay difficult. Furthermore, at high doses of substrate, product generation is inhibited potentially due to the need for a dimeric enzyme complex with IgG. In this study we have developed a mass spectral assay for IdeS activity based on the detection of an Mr approximately 25,300 Fc fragment that retains the ability to bind streptococcal protein G. Using this assay procedure, evidence for a multimeric enzyme-substrate complex was obtained as well as identifying isolated heavy chains as a non-substrate inhibitor of IdeS activity. Under appropriate experimental conditions the assay could be used to detect IdeS activity in bacterial culture media or in human plasma without a requirement for purified reactants. The availability of a rapid and sensitive assay for IdeS should facilitate the detailed biochemical characterization of this unusual bacterial cysteine protease.

Surface-enhanced laser desorption/ionization time-of-flight analysis was used to monitor both the kinetics and heterogeneity of product formation during the biotinylation of a number of model proteins and peptide targets. The selected molecules were the IgG-binding protein, protein A, human serum albumin, and a synthetic peptide corresponding to the N terminus of a streptococcal M1 protein. The extent of biotinylation was determined by kinetic analysis of the shift in molecular mass from the native material. Each residue modified by reaction with N-hydroxysuccinimide biotin resulted in an addition of approximately 341 amu to the native protein or polypeptide. The novelty of the method was in the ability to determine the molecular mass shift, without first separating the targeted molecule from the biotinylating reagent. The analysis was rapid, simple, and provided information on the average number of biotin molecules added and the homogeneity of the resulting product.

Binding proteins that have high affinities for mammalian plasma proteins that are expressed on the surface of bacteria have proven valuable for the purification and detection of several biologically important molecules from human and animal plasma or serum. In this study, we have isolated a high affinity albumin-binding molecule from a group G streptococcal isolate of bovine origin and have demonstrated that the isolated protein can be biotinylated without loss of binding activity and can be used as a tracer for quantification of human serum albumin (HSA). The binding protein can be immobilized and used as a selective capture reagent in a competitive ELISA format using a biotinylated HSA tracer. In this assay format, the sensitivity of detection for 50% inhibition of binding of HSA was less than 1 microg/ml. When attached to the bacterial surface, this binding protein can be used to deplete albumin from human plasma, as analyzed by surface-enhanced laser desorption ionization time of flight mass spectrometry.

A novel immunoproteomic assay, combining specificity of antibody with precision of mass spectral analysis is described, and a number of practical applications are presented. The assay is carried out in three steps. The first step of the assay involves antibody immobilization, using a bacterial Fc binding support. The second step is antigen capture and washing to remove non-specific binding. The third step involves analysis of the captured antigens by SELDI-TOF. The assay has many advantages in sensitivity, speed, and economy of reagents in detection of specific antigens or antibodies. In addition, under appropriate experimental conditions, semi-quantitative data may be obtained. By combining the increasing range of selective specific antibody reagents available, in part due to advances in antibody engineering technology, and the resolving power available, using mass spectrometry, immunoproteomics is a valuable technique in proteomic analysis. A number of examples of the application of this technique to analysis of biological systems are presented.

This study explores the complicated social interactions related to gender that take place at school recess. Using grounded theory methodology and a social constructionist perspective, the researchers observed 67 recesses in New England and then examined the data to determine which themes emerged. Results demonstrate that there is great complexity in preadolescent gender relations and that their incidence and significance is in flux during recess time. Among the results noted were ways in which children reinforce their gender identities; the wide intragender variability in choice of activities especially for girls; and clear evidence of borderwork, that is, those interactions where boys and girls play together but there is something about the play that actually reinforces the gender divisions rather than diminishes them. Future research should examine ways adults can support children in developing relationships based on mutual collegiality and liking, thereby building their sense of competence and self-esteem.

The small karstic watershed of Lanmuchang, in a Hg–Tl mineralized area in SW Guizhou Province, China, exhibits an enrichment of toxic Tl in groundwater and related stream water. This affords an excellent demonstration of the natural processes of Tl dispersion, and the resultant impact on the local ecosystem. The distribution of Tl in the water system follows a decreasing concentration pattern from deep groundwater to stream water to shallow groundwater. Tl shows high levels (13–1100 μg/L) in deep groundwater within the Tl-mineralized area, decreasing with distance away from the mineralized area to background levels (0.005 μg/L). The distribution of Tl in the water system is constrained by Tl mineralization, water–rock interactions and hydrogeological conditions. Tl concentrations in waters generally correlate with concentrations of total dissolved solids, sulphate, Ca and pH values, suggesting the contribution of water-rock interactions to water geochemistry. Water–rock interactions are driven by weathering of Tl-bearing sulfides which decreases pH values in groundwater, and by dissolution of limestone enhanced by acid fluids. Tl in stream water in both the base-flow and flood-flow regimes shows higher concentrations than it does in shallow groundwater that serves as the stream's source (mainly springs, dug-well flows and karstic cave waters). Concentrations of Tl in stream water in the flood-flow regime are generally lower than in the base-flow regime due to dilution effects, but those in the waters of mid-stream are almost the same as in the base-flow regime, probably due to contribution from Tl-rich soil water seepage or from acid mine drainage (AMD). Unexpectedly, Tl concentrations in stream water in both regimes are remarkably higher (2–30 fold) downstream than up- and mid-stream. These pronounced increases of Tl concentration are likely caused by unidentified discharges of deep groundwater through fractured zones to the downstream trace. The groundwater-related Tl transfer processes affect the ecosystem through contamination of water supply and arable soil and ultimately the food chain with undoubted risks to human health. Therefore, the results of this study are important for environmental planning and regulations, and will also serve as baseline data for future research on Tl natural dispersion processes.

Post-translational modification of the antiphagocytic M1 protein of Streptococcus pyogenes can influence its binding properties for human immunoglobulin G subclasses and its invasive potential. Current methods of monitoring this modification event involve N-terminal sequencing and are cumbersome, slow and not amenable to routine analysis. In this study we demonstrate that surface enhanced laser desorption/ionization-time of flight mass spectrometry can be used to monitor modification of the M1 protein by the secreted bacterial cysteine protease, SpeB. This method, when combined with a specific antibody capture step provides a specific, rapid and sensitive assay for key virulence factors of the important human pathogen Streptococcus pyogenes.

Tamoxifen therapy may result in a variety of endometrial proliferative lesions, including adenocarcinoma, and as recently suggested, proliferative changes within endometriosis. This report describes an endometrioid adenocarcinoma arising in ovarian endometriosis in a patient taking tamoxifen. There were also foci of benign and borderline endometrioid adenofibroma in the same ovary and a synchronous endometrioid endometrial adenocarcinoma in the uterus. The spectrum of benign, borderline, and malignant endometrioid neoplasia arising within endometriosis suggests that tamoxifen, as a result of its estrogenic effects, may cause proliferative and, in rare instances, malignant changes in endometriosis.

We have used new gel pore-water profilers and conventional seepage meters to determine the advective flux of water from an underwater saline seep into Lake Kinneret. The gel probes sampled pore waters from medium to coarse sands that could not be sampled by conventional coring methods. The anions Cl, Br, and SO4 were constant at levels just above those for the lake for 3-5 cm into the sediment due to wave action or other turbulent mixing processes. There was then a sharp increase in concentration to values of approximately 8,000 mg Cl liter(-1), 370 mg SO4 liter(-1), and 120 mg Br liter(-1) at a depth of similar to 8.5 cm. Using an advection-diffusion model, the linear interstitial advection velocity (LIV) of the groundwater into the lake was calculated to vary between 140 and 275 cm yr(-1). The LN values from conventional seepage flux meters at the same site were 30 and 164 cm yr(-1). Differences between the LIV measurements of these two methods may be due to a number of possible factors, including groundwater flux heterogeneity.

The most appropriate and widely used source of drinking water for the populations of the upper regions of Ghana is groundwater. In general, groundwater quality is acceptable except for some parts of the Bolgatanga and Bongo Districts, where there are occurrences of elevated levels of natural groundwater fluoride. Concentrations of groundwater fluoride in excess of the World Health Organization (WHO) maximum guideline value (1.5 mg/l) in the Bongo area have been known since 1978. However, the effect of fluoride on people ingesting the water did not receive public and medical attention until October 1993, when health personnel were asked to investigate the cause of stained teeth in school children. The investigation established that 62% of the total population of school children in the Bongo area had dental fluorosis. Against this background, a study was initiated to understand the geochemistry, genesis, and distribution of fluoride in relation to the geology of the area. Groundwater fluoride in the upper regions ranges from 0.11 to 4.60 ppm, with the highest concentrations associated with the fluorine-enriched Bongo coarse-grained hornblende granite and syenite suite. The source of groundwater fluoride within the Bongo granitoids is dissolution of the mineral fluorite and dissolution of and anion exchange with micaceous minerals and their clay products. Applying the WHO recommended guideline values for fluoride in drinking water reveals that 49% of wells in the area deliver water below the optimum level of 0.5 mg/l F–; these populations are thus prone to dental caries. Twenty-eight percent of the wells fall within the optimum interval for good dental health (0.5–1.5 mg/l F–). Twenty-three percent of the wells have concentrations above the recommended maximum guideline limit of 1.5 mg/l F–; this population is susceptible to dental and possibly skeletal fluorosis. Climatic conditions of the area suggest that the individual water consumption is in the order of 3 to 4 l which is higher than the WHO estimate of 2 l/adult/day. In addition, dietary intake for the upper region population is probably higher than WHO baseline values (0.2–0.5 mg/day). This implies that a much higher population is susceptible to developing dental and skeletal fluorosis than originally suspected. Geochemical symbol plot maps help geochemists understand factors controlling the distribution and uptake of fluoride in the upper regions, but they are of minimal value to health officials responsible for planning epidemiological studies and dental health education programs in the region. By casting fluoride data into contoured 'geochemical health-risk maps' using intake interval guidelines more closely aligned to regional climatic and dietary conditions, health officals can better judge the impacts (regional and population based) of fluoride on segments of the population, such as various sex and age groups.

A lakebed seepage meter for measuring groundwater seepage rates in the nonlittoral zones of lakes was designed and field tested. Ease of installation and operation, sampling integrity, and year-round stability in ice-bound lake environments were the main factors governing design. The design of the meter incorporates a lake-bottom seepage meter connected by a flexible conduit hose to a sampling station -2 m below lake surface. The operation and design of the meter includes methods for minimizing and monitoring meter settlement, protecting meter components from trawling fishermen and nibbling fish (seepage bags), visually monitoring flux levels in seepage bags to determine optimum time for sampling, and easy detection by a small boat-mounted sonar unit. Results from a seepage meter survey in a small lake situated in complex glacial stratigraphy show that the system is effective in measuring very low flux rates and mapping complex inflow and outflow groundwater regimes in lake environments. Detailed lake studies in glaciated terrains allow classification of lakes, with regard to characteristics and relative contributions of groundwater and surface water inputs, into the six main types shown in Fig. 1. Although subtypes can be created within this classification, Fig. 1 shows the complexity of relationships that can exist between lakes and surrounding groundwater regimes. In some cases, lakes cannot be classed as one type year-round; for example, Jaquet’s (1976) studies of the groundwater regime around Snake Lake (Wisconsin) show that this lake has a hydrology much like type d (Fig. 1) in late summer, fall, and winter, but in spring the flow characteristics are represented better by type b. The lake I use to evaluate a new seepage meter design (Alexander Lake) was, from initial analyses, thought to be type d or type b. Later detailed seepage meter analysis showed it to be type b. Figure 2 schematically depicts two extremes of limnological regimes and groundwater processes on a continuum of lakes in glaciated environments. Although hydrologists generally accept that most groundwater that enters a lake system does so through the littoral zone

The Eighth Survey of Staffing in Cardiology was conducted with an index date of 30 September 1992. The total number of cardiologists in England and Wales, defined as individuals trained in the specialty and spending at least 40% of their professional time working in it, was 358. Of these 11 were part time, defined as six sessions or less, giving a number in whole time (or near whole time) equivalents of 352.5. The number of individuals increased from 1991 by 18 (5.3%). There were 71 cardiologists in Scotland and Northern Ireland, making a total for the United Kingdom of 429 individuals (423.5 whole time equivalents), which is 7.3 per million population. A total of 44 Districts serving 8.8 million people have no resident cardiologist. There has been little improvement since the 1991 survey. An additional 34 Districts with populations greater than 250,000 have only one cardiologist: we have clear evidence of inadequate provision of care in most of these, a situation that is inevitable within the resources provided. A wider threat to the provision of a satisfactory level of cardiological care throughout the United Kingdom will follow from changes in the organisation of the National Health Service and in the new requirements for training of future cardiologists because these changes will make major new demands on consultant time which cannot be met within existing resources. A crisis will be averted only if a rapid and major expansion of the consultant grade can be achieved.

There is evidence that many pathogens co-evolve with their hosts. This is often reflected in species specific virulence factors that can selectively interfere with host defense mechanisms, innate and acquired as well as a range of interactions with host homeostatic pathways that contribute to the course and severity of an infection. In this review, we highlight a number of select examples of these interactions and suggest that understanding of molecular pathogenesis requires a broad systems approach that can evaluate the multiple and dynamics interactions that are occurring during infection.

The Sixth Biennial Survey of Staffing in Cardiology was conducted in July 1990. This report summarises the data that were collected, together with the results of a survey of facilities in cardiology made in 1989. The total number of cardiologists in the United Kingdom, defined as individuals trained in the specialty and spending at least 40% of their time working in it, is now 323. Six individuals work part time only, making 320 whole time posts. This number has increased over the two years from 1988 to 1990 by 32, of which 23 work only in the specialty and nine as general physicians with a major interest in cardiology. The rate of increase in numbers over the past decade has been reasonably consistent with an average of approximately 4.4% per year. Thirty one districts in England and Wales still have no cardiologist and 13 other districts have little provision with an average of three (visiting) sessions each per week. The population in these 44 districts is 8.3 million. Scotland also has an inadequate distribution of service in the specialty. If recommendations for cardiac surgery and angioplasty made in the Fourth Report of a Joint Cardiology Committee of the Royal College of Physicians of London and the Royal College of Surgeons of England are to be met, we calculate that we need 63 more cardiologists in our major centres. To provide one cardiologist in every district hospital and two for larger districts would require 94 more specialists, making a total shortfall of 157 individuals. We have no excess of senior registrars to provide for a major expansion at consultant level. Time spent within the senior registrar (or academic equivalent) grade has tended steadily to decline and very few now reach the end of their contracts. The need for more individuals to pass through the senior registrar grade will be met in part by a planned reduction in the training period to three years. This will be inadequate, however, because projected retirements show that the number of consultant vacancies will increase sharply from 1997. We believe that additional senior registrar posts must be created if a serious shortfall in service provision by consultants is to be avoided. The provision of non-invasive facilities in cardiology is reasonable. The need for additional equipment for invasive cardiology has not been assessed. The number of physiological measurement technicians varies considerably between regions and is generally inadequate.

The c protein (Ibc) of group B streptococci (GBS) is associated with at least four antigens (alpha, beta, gamma, delta). To assess the virulence potential of these antigens, 255 GBS isolates recovered from septic neonates, healthy neonates, and pregnant women were serotyped and surveyed for reactivity with sera to c protein and the four associated antigens. A radioimmunoassay using intact bacteria was used to detect the GBS antigens. In contrast to earlier reports, most (66%) of the type III strains expressed the c protein. Except for the gamma antigen, none of the other c protein-associated antigens showed an increased association with pathogenic strains independent of the polysaccharide antigens. The gamma antigen was expressed by 15 of 41 c protein-positive early-onset strains and by 4 of 38 c protein-positive late-onset strains (P = .007). This association was independent of the type-specific antigen, suggesting a potential role for the gamma antigen as a virulence factor in GBS strains causing early-onset sepsis.

This paper reports an assessment of the tolerance of STC’s bipolar, CMOS and ‘merged’ bipolar/CMOS processes to gamma total dose, dose rate and neutron fluence radiation effects. The objective of the assessment was to characterise process performance under worst case and near to worst case criteria when subjected to nuclear radiation up to the tactical level in accordance with BS 9000. Total dose irradiation was performed on the bipolar, CMOS and BiCMOS technologies with 9 Mrads (Si), 10-12 krads (Si) and 10-30 krads (Si) performance levels reported, respectively. Under dose rate conditions, transient upset, latch-up and photocurrent are reported with latch-up immunity reported for the bipolar 2 process and simultaneous latch-up and transient upset reported for both the bulk CMOS and BiCMOS processes. Neutron fluence testing was performed with the onset of failure for the CMOS reported at the 5 × 1014 neutrons/cm level and onset of failure for the bipolar and BiCMOS reported in the range 5 × 1014 to 5 × 1014 neutrons/cm2.

Eight commercial semiconductor grade epoxy compounds that are used to encapsulate 1C (integrated circuit) devices have been evaluated for their ability to minimize the development of thermal stresses which can cause failure during device temperature cycling. Thermal expansion, dynamic modulus and adhesion studies are used to describe the mechanical interaction between the plastic package and the silicon device it surrounds. A “figure of merit” is defined for the development of stress on the 1C device as it is cooled after the packaging process. The stress is shown to be proportional to the product of three terms: (αp-αs) Ep (Tanch-T) where αp and αs are the expansion coefficients for the plastic and silicon, respectively, Ep is the modulus of the epoxy and Tanch is the temperature at which the epoxy becomes anchored to the silicon device during transfer molding. In addition, the importance of good adhesion between the epoxy encapsulant and the silicon device to prevent package cracking has been demonstrated by finite element analysis and a novel adhesion test.

Preventive and/or therapeutic vaccines against Human Immunodeficiency Virus (HIV-1) are urgently required. Induction of cellular immunity is favoured since these responses correlate with control of HIV-1. Recombinant fowlpoxvirus (FPV) vaccines encoding both HIV-1 gag/pol and interferon-gamma (FPV gag/pol-IFNgamma) were hypothesised to enhance HIV-specific cellular immunity and were further evaluated in macaques previously infected with HIV-1. A novel assay to detect IFNgamma secretion following HIV antigen stimulation of whole blood was developed to further assess the safety and immunogenicity of the FPV gag/pol-IFNgamma vaccine. Immunisation with FPV gag/pol-IFNgamma safely enhanced HIV-specific IFNgamma secretion following ex vivo stimulation of whole blood, greater than that observed following FPV gag/pol vaccination not co-expressing IFNgamma. Both HIV-specific IFNgamma-spot-forming cells by ELISPOT and CD69 expression by CD4+ lymphocytes were also enhanced following FPV gag/pol-IFNgamma vaccination. Hence, the FPV-HIV vaccine co-expressing IFNgamma stimulated HIV-specific T cell responses in macaques, and should be further evaluated as a therapeutic or preventive HIV vaccine.

A survey of sheep and goat producers in the state of Maharashtra, India, was undertaken to ascertain the extent and economic impact of sheep pox and goat pox (SGP). One thousand one hundred and sixteen owners were interviewed. Eighty owners (7.2%) reported that they had experienced an outbreak of the disease in the previous 6 years. The results showed that, while producers ranked SGP below other infectious diseases such as foot-and-mouth disease, rinderpest and enterotoxaemia, when SGP occurred it had a major impact, with average morbidity and mortality rates of 63.5% and 49.5%, respectively. Modelling studies suggested it would take about 6 years for a flock or herd to recover from an outbreak, with average annual losses in income of 30-43%, depending on flock type and the owner's actions. Statewide, it is estimated that around 5000 flocks and herds are affected by SGP annually in Maharashtra, costing up to INR 107.5 million. The highest losses occurred in the Aurangabad region.

Studies were performed to determine if p53 mutations identified in rheumatoid arthritis (RA) synovial tissue are dominant negative.Site-directed mutagenesis was used to produce 2 RA-derived mutants: asparagine--serine at codon 239 (N239S) and arginine--stop at codon 213 R213*). HS68 dermal fibroblasts were transfected with either empty vector, wild-type p53 cDNA (wt), or the N239S or R213* mutant p53 cDNA clones. Interleukin-6 (IL-6) and bax gene expression were determined by Northern blot analysis. Bax transcription was determined using a bax promoter/reporter gene construct (bax-luc).Transfection of HS68 cells with wt increased bax mRNA levels. This process was blocked by cotransfection with either mutant. The mutant p53 genes also increased IL-6 gene expression. Low levels of bax promoter activity were detected in HS68 cells co-transfected with bax-luc and empty vector, N239S, or R213*, indicating that the RA mutants lacked transcriptional activity. Transfection with wt and bax-luc led to a 10-fold increase in luciferase expression. When the wt gene was cotransfected with either of the mutants, there was a dose-dependent inhibition of bax promoter activity.These data indicate that at least 2 of the p53 mutants identified in RA joint samples are dominant negative and suppress endogenous wild-type p53 function.

The p53 tumor suppressor gene is overexpressed in synovial tissue (ST) from patients with longstanding rheumatoid arthritis (RA), and may contain somatic mutations. The aim of this study was to determine p53 expression in ST from RA patients in different stages of the disease, compared with disease controls.ST biopsy specimens were obtained from the knee joints of 31 RA patients in varying disease phases, 8 patients with reactive arthritis (ReA), 10 patients with inflammatory osteoarthritis (OA), and 6 control patients (4 with meniscus pathology, 2 with vascular insufficiency). ST was also obtained from the clinically uninvolved knee joints of 9 RA patients. Expression of p53 was determined by immunohistology with DO1 monoclonal antibody (mAb) in all patients and by Western blot analysis with DO7 mAb in a subgroup of the patients.The p53 protein was detected by immunohistology in 10 of the 13 patients with early RA (duration6 months) and in 12 of the 14 patients with longstanding RA (duration5 years). The p53 protein was also demonstrated in clinically uninvolved knee joints. Western blots revealed immunoreactive p53 in ST extracts from all RA patients. Expression of p53 was about twice as high in ST from patients with longstanding RA as in early RA samples, but the difference did not reach statistical significance. Small amounts of p53 were also detected in ST from ReA and OA patients, although the expression in RA synovium was significantly higher. Immunohistologic analysis of normal ST gave negative results for p53.This study shows that p53 overexpression is specific for RA, compared with OA and ReA. This phenomenon is probably secondary to increased production of wild-type p53 protein in response to DNA damage and secondary to somatic mutations caused by the genotoxic local environment in inflamed ST. Of interest, p53 overexpression can also be found in the earliest stages of RA and in clinically uninvolved joints.

The present study examined the extent to which generalized versus spouse-specific anger/hostility was associated with partner violence in 263 men seeking conjoint marital therapy. Clinic men were classified as nonviolent (NV), moderately violent (MV), and severely violent (SV). A community comparison group of relationship-satisfied, non-violent men (CO) was also included. All clinic men reported higher levels of generalized and spouse-specific anger, spouse-specific aggression/hostility, depressive symptomatology and lower spouse-specific assertiveness than community men. SV men reported higher levels of spouse-specific anger/hostility, relationship discord, depressive symptomatology, and lower general problem-solving ability than NV men. Regression analyses confirmed that spouse-specific anger/hostility, low problem-solving ability, and relationship discord were significant predictors of men's violence. Overall, generalized anger and hostility were not unique predictors of men's violence against intimates.

The majority of residents of Manitoba (Canada) outside of the capital, Winnipeg, rely on groundwater for their drinking water. Between lakes Winnipeg and Winnipegosis, most aquifers occur in Paleozoic carbonate lithologies. Proximal to the town of Gypsumville, however, lithologies associated with the Lake St. Martin impact structure and younger basin-filling red bed and evaporite (gypsum/anhydrite) sedimentary rocks complicate the hydrology and hydrochemistry. Here, domestic wells have elevated salinities (up to 8000 mg/L total dissolved solids), elevated sulfate (up to 4000 mg/L), and elevated fluoride concentrations that are in excess of health limits (F − up to 15.2 mg/L, with 20% over 1.5 mg/L). Groundwaters with elevated fluoride occur exclusively within the impact structure. The impact melt rocks and younger red beds consistently have the highest fluoride abundances, up to 2160 ppm. Groundwater pH values are alkaline, ranging up to 10.7, with highest groundwater pH from wells in the impact melt rocks. The spatial associations of impact melt rocks and red beds with elevated fluoride, strong positive correlations between fluoride and pH, sodium, chloride, sulfate, boron and lithium, greater Fe 2 O 3 and Al 2 O 3 concentrations of the host rocks, and cation exchange capacity (CEC) all indicate that fluoride concentrations in groundwaters are enhanced as a result of anion exchange wherein OH − and \(CO_{3}^{2{-}}\) displace F − adsorbed onto Fe- and Al-oxyhydroxide surfaces. Thus, the elevated fluoride contents of groundwaters at Gypsumville are a consequence of the composition of the impact melt rocks and enhanced permeability and grain-size reduction produced by bolide impact.

The absolute bioavailability and dose proportionality of betaxolol [(+/-)-1-(p-[2-cyclopropylmethoxy)ethyl]phenoxy]-3- (isopropylamino)-2-propanol hydrochloride], a cardioselective beta-adrenergic antagonist effective in the treatment of angina and hypertension, was studied in 12 healthy male subjects using a four-way crossover Latin Square design. Each subject received a 10-mg iv dose administered by constant-rate infusion over a period of 30 min and three oral doses (10, 20, and 40 mg). Blood and urine were collected over a 48-h period and analyzed for betaxolol using gas-liquid chromatography with electron capture detection. Maximum concentrations occurred 3-4 h after the dose. The maximum mean (+/- SD) blood concentrations normalized to the 10-mg oral dose were 21.6 +/- 3.7, 21.1 +/- 3.7, and 22.5 +/- 4.0 micrograms/L following the 10-, 20-, and 40-mg doses, respectively. A significant lag time of 10-80 min was observed after oral doses but was not related to dose size. The terminal slope (ts), absolute bioavailability (F), and renal clearance (CLr) were likewise not affected to an important degree by dose (ts: 0.043 +/- 0.006, 0.044 +/- 0.005, 0.046 +/- 0.006 h-1; F: 0.88 +/- 0.08, 0.82 +/- 0.06, 0.84 +/- 0.07; CLr: 0.68 +/- 0.22, 0.69 +/- 0.19, 0.65 +/- 0.22 mL/min kg). Unlike many beta-adrenergic antagonists, betaxolol has a long half-life (13-20 h) and high and consistent bioavailability (70-90%), and its disposition is independent of the size of the administered dose.

There is a need for the accurate identification of a group of patients with myocardial infarction (MI) who are not going to die in the ensuing three months. These patients should be discharged within four days of their coronary attack. Using data on 298 patients with myocardial infarction a prognostic index (CPI) was derived based on a discriminant function analysis. This index correctly allocated 56.4% of the total into a low risk group (mortality 1.2%) and 43.6% into a high risk group (mortality 36.1%) at three months. The factors were ST segment elevation greater than 2 mm at any time, more than 40 ventricular ectopic beals/h, the presence of R on T ectopics, persistent sinus tachycardia, blood urea above 12 mmol/l. X-ray signs of heart failure and age. The index was verified prospectively on two groups of consecutive patients and has been successfully used to select patients for discharge on the fourth day

DSC analysis of acrylonitrile-butadiene-styrene (ABS) samples either weathered outdoors for up to 10 years or aged at 71°C has shown that these plastics deteriorate most readily through the polybutadiene (BD) component. Oxidation of the BD in ABS leads to an increasing and broadening Tgas well as a decrease in ΔCp at Tg. The latter quantity can be used to quantitatively assay the amount of unoxidized rubber in a photo- or thermal-oxidized sample. The loss of impact strength of these resins with chemical aging can be correlated with the oxidation of the polybutadiene phase. Studies of rubber content as a function of sample thickness have revealed that an embrittled layer containing oxidized BD develops at the surface of an aged, 100 mil. ABS plaque (natural) and grows to a thickness of about 10 mils after 3 years exposure to sunlight. ABS containing carbon black is effectively screened from this photo induced degradation and consequently has much better retention of its initial impact strength values. In addition, carbon black was observed to retard thermal oxidation in some ABS samples. Lastly, it appears possible to do accelerated aging studies at elevated temperatures to evaluate the relative stabilities of various ABS formulations.

Gelatin encapsulated nitrogen microbubbles were effective ultrasonic contrast agents in in vitro phantom and in vivo rabbit V2 carcinoma studies. Intra-arterial injection of 80-micrometer gelatin encapsulated nitrogen microbubbles appeared to improve tumor visualization by rim enhancement, which persisted for several minutes.

The population of peritoneal macrophages from mice immunised with allogeneic tumor cells contains two types of cytotoxic cell. One lyses the specific target cell, the other initiates activation of macrophages and hence leads to inhibition of growth of the specific target cell. The yield of lytic effector macrophages was found to depend on the route and the nature of the cell used for immunisation and the condition of the mice. The yield correlated with the yield of complement-dependent cytotoxic antibodies. In contrast, production of specific "activator" macrophages did not depend critically on these factors. The results underline the difference between the two types of cell and suggest that they are produced independently of one another.

Alterations in the PV relationships of isolated rabbit lungs which are dependent on the minimal deflation pressure (Pmin) have been studied. When Pmin remains positive both inflation and deflation limbs of the PV loop are shifted toward lower transpulmonary (P1) pressures throughout most of the cycle. In addition, Pmin(+) conditions eliminate the deflation inflection and increase deflation compliance at low and mid-lung volumes. Results from indicator washout and spontaneous deflation reveal that Pmin(+) conditions produce a more even inflation of the lung parenchyma and dilate airways at low lung volumes. These effects cause a stabilization of the parenchyma and a delay in airway closure resulting in the increased deflation compliance and a decrease in the trapped gas volume during Pmin(+) conditions. The relevance of Pmin(+) and (−) conditions are discussed for several clinical conditions.

A double blind randomized study of 800 patients was carried out to determine if very early intervention with metoprolol (15 mg I.V. followed by oral administration) in suspected acute myocardial infarction affected overall mortality in selected subgroups, (age, site of infarct, delay to intervention). Sudden death occurred less frequently in patients allocated to metoprolol but there was no significant difference in total mortality on discharge, at three months and at twelve months. Ventricular fibrillation after intervention was not significantly reduced. Adverse reactions did not occur significantly more frequently in patients assigned to metoprolol.

This review highlighted several problems associated with the use of antibody and complement in the elimination of tumor cells from bone marrow that was to be used for transplantation, and it discussed some of the difficulties encountered in developing this approach in model systems. These problems should be seriously considered by any clinician contemplating this method for bone marrow purging.

A two-stage radioimmunoassay (RIA) has been developed that identifies type-specific antigens on the surfaces of group B streptococci. In addition to detecting the type-specific carbohydrate antigens Ia, Ib, II, and III, the RIA identified four unique antigens reactive with the Centers for Disease Control's c-protein typing antiserum. Analysis of hot-acid extracts by immunoelectrophoresis confirmed that two of these reactivities corresponded to the reported alpha and beta antigens of the c-protein marker. In addition, the identification of two heretofore unidentified antigens, gamma and delta, by the two-stage RIA is detailed in this report. The assay uses intact bacteria and does not require hot-acid extraction, a procedure thus enabling detection of acid-labile antigens in their native unmodified form. The semiquantitative RIA requires less typing reagent than does precipitin testing and is more objective, reproducible, and rapid. The assay described here could be applied to the detection of any cell surface antigen for which a monospecific antiserum is available.