A Computer-Automated Laboratory System In A University Environment

A computer-automated laboratory system at the University of Missouri-Rolla, Rolla, which serves a wide variety of instruction and research disciplines including Geophysics, Cloud Physics, and Computer Graphics, is described. The system serves as an example for campuses which are relatively small in geographic area and with budget limitations which dictate a step-by-step evolution. The paper describes 1) the constraints and economics realized in the development of the system, 2) the characteristics of the minicomputer network, and 3) an evaluation of the system philosophy and performance. Also included is a description of diverse laboratory projects supported by the computer-automated system. © 1975, IEEE. All rights reserved

Electrically Mediated Plasmid DNA Delivery to Hepatocellular Carcinomas in Vivo

Gene therapy by direct delivery of plasmid DNA has several advantages over viral gene transfer, but plasmid delivery is less efficient. In vivo electroporation has been used to enhance delivery of chemotherapeutic agents to tumors in both animal and human studies. Recently, this delivery technique has been extended to large molecules such as plasmid DNA. Here, the successful delivery of plasmids encoding reporter genes to rat hepatocellular carcinomas by in vivo electroporation is demonstrated

Feather corticosterone content in predatory birds in relation to body condition and hepatic metal concentration

This study investigated the feasibility of measuring corticosterone in feathers from cryo-archived raptor specimens, in order to provide a retrospective assessment of the activity of the stress axis in relation to contaminant burden. Feather samples were taken from sparrowhawk Accipiter nisus, kestrel Falco tinnunculus, buzzard Buteo buteo, barn owl Tyto alba, and tawny owl Strix aluco and the variation in feather CORT concentrations with respect to species, age, sex, feather position, and body condition was assessed. In sparrowhawks only, variation in feather CORT content was compared with hepatic metal concentrations. For individuals, CORT concentration (pg mm-1) in adjacent primary flight feathers (P5 and P6), and left and right wing primaries (P5), was statistically indistinguishable. The lowest concentrations of CORT were found in sparrowhawk feathers and CORT concentrations did not vary systematically with age or sex for any species. Significant relationships between feather CORT content and condition were observed in only tawny owl and kestrel. In sparrowhawks, feather CORT concentration was found to be positively related to the hepatic concentrations of five metals (Cd, Mn, Co, Cu, Mo) and the metalloid As. There was also a negative relationship between measures of condition and total hepatic metal concentration in males. The results suggest that some factors affecting CORT uptake by feathers remain to be resolved but feather CORT content from archived specimens has the potential to provide a simple effects biomarker for exposure to environmental contaminants

A frequency weighting for the evaluation of steering wheel rotational vibration

The human perception of rotational hand-arm vibration has been investigated by means of a test rig consisting of a rigid frame, an electrodynamic shaker unit, a rigid steering wheel, a shaft assembly, bearings and an automobile seat. Fifteen subjects were tested while seated in a driving posture. Four equal sensation tests and one annoyance threshold test were performed using sinusoidal excitation at 18 frequencies in the range from 3 to 315 Hz. In order to guarantee the generality of the equal sensation data the four tests were defined to permit checks of the possible influence of three factors: reference signal amplitude, psychophysical test procedure and temporary threshold shift (TTSv) caused by the test exposure. All equal sens ation tests used a reference sinusoid of 63 Hz at either 1.0 or 1.5 m/s2 r.m.s. in amplitude. The four equal sensation curves were similar in shape and suggested a decrease in human sensitivity to hand-arm rotational vibration with increasing frequency. The slopes of the equal sensation curves changed at transition points of approximately 6.3 and 63 Hz. A frequency weighting, called Ws, was developed for the purpose of evaluating steering wheel rotational vibration. The proposed Ws has a slope of 0 dB per octave over the frequency range from 3 to 6.3 Hz, a slope of -6 dB per octave from 6.3 to 50 Hz, a slope of 0 dB per octave from 50 to 160 Hz and a slope of -10 dB per octave from 160 to 315 Hz. Ws provides a possible alternative to the existing Wh frequency weighting defined in International Standards Organisation 5349-1 (2001) and British Standards Institution 6842 (1987)

A comparison of two methods for the assessment of stress axis activity in wild fish in relation to wastewater effluent exposure

Riverine fish are particularly vulnerable to chemical exposure - rivers receive chemicals of anthropogenic origin from a variety of sources, one of the most significant being the chemically complex effluents discharged by wastewater treatment works (WWTWs). The extent to which non-reproductive components of the endocrine system in fish may be vulnerable to interference by contaminants associated with WWTW effluent is not well understood, but a significant body of evidence does suggest that contaminants present in the aquatic environment may interfere with the normal function of the neuroendocrine stress axis in fish. Field investigations of stress axis function in free-living populations of fish by measurement of hormone concentrations in blood can be confounded by the remoteness of sampling locations and the size of target species. Two methods for assessing stress axis reactivity in situations where blood samples are unavailable were compared in three-spined sticklebacks in relation to their exposure to WWTWs effluent. Sticklebacks were sampled in two successive years at fifteen sites in north-west England impacted by WWTW effluent and the response of each fish to the combined stressor of capture and a brief period of confinement was evaluated using both whole-body immunoreactive cortisol concentrations (WBIC) and the rate of release of cortisol to water (CRTW). A positive relationship between the magnitude of stress-induced CRTW in sticklebacks of both sexes and WWTW effluent concentration at site of capture was observed in both years. However, the relationship between stress-induced WBIC and WWTW effluent concentration was not consistent. These results suggest that components of WWTW effluent can modulate the magnitude of the neuroendocrine stress response in sticklebacks, and by inference in other fish species, but they raise questions about the measurement and interpretation of stress axis responses in fish via endpoints other than blood hormone concentrations. Possible factors underlying the disparity between the CRTW and WBIC results are discussed

Identifying the risk to the aquatic environment of endocrine disrupters derived from agriculture

EXECUTIVE SUMMARY 1. The purpose of this project was to review possible inputs to UK headwater streams of steroid hormones originating from livestock, to investigate hormone contamination in some streams in which concentrations were expected to be maximal, and to draw conclusions about possible risks that these hormones may pose to aquatic organisms. 2. The review concluded that although livestock in the UK excretes more steroid sex hormones (oestradiol and testosterone) than the human population, almost all of the material deposited on soil by livestock and by manure/slurry spreading is likely to be adsorbed and/or degraded in soil before reaching surface waters. Concentrations of oestrogens in field drains are unlikely to exceed 1 ng/l (expressed as 17β-oestradiol equivalents), a concentration that is probably harmless. However, it is possible that direct excretion by livestock into unfenced streams, and direct run-off to surface waters from slurry stores and hard-standing in livestock farms, may contribute higher concentrations. In other words, poor farming practice may lead to significant steroid hormone pollution. 3. The review also concluded that surface waters in some other countries are contaminated with oestrogens at potentially active concentrations, so it was considered that a survey of UK headwater streams for hormonal activity was justified. The literature search clearly showed that pregnant cattle are the single most important source of natural oestrogens on livestock farms. 4. The chosen sampling strategy was to focus on a limited number of predominantly dairy farms that were considered to represent worst-case conditions for hormone translocation to small headwater streams. Criteria that contributed towards the choice of field sites included stocking type and density, soil type and slope, access of livestock to the stream, application of manure or slurry to the land, possible direct drainage to the stream of waste from leaking slurry stores and hard-standing areas used by livestock, and access permission from the land-owner. Confounding factors such as upstream inputs of hormonally active material from sewage treatment works, septic tank soak-aways, and industrial discharges, were excluded as far as possible from the study. 5. In order to obtain semi-quantitative, time-integrated samples of hormones in water, locations up- and downstream of livestock activity were sampled on 10 farms using a passive, solid-phase device known as a Polar Organic Chemical Integrative Sampler (POCIS). These were deployed between November 2004 and January 2005 for 3 to 10 weeks (mean = 39 days). At an eleventh site, a field drain issuing from an experimental plot of cracking clay soil treated solely with dairy cow slurry was also sampled with POCIS. At one site, an automatic flow-driven water sampler was deployed alongside the POCIS to capture water soon after heavy rainfall. 6. POCIS and water extracts were assayed for estrogenic and androgenic activity using the in vitro yeast estrogen screen (YES) and yeast androgen screen (YAS), respectively. As part of a separate project, POCIS extracts were also analysed chemically for oestrone (E1), 17β-oestradiol (E2) and 17α-ethinylestradiol (EE2) by the Environment Agency. 7. The flow from only one rainfall event was captured in its entirety by the autosampler, but this revealed a background concentration (E2 equivalents) of 0-0.3 ng/l, rising to a transient peak of 9.4 ng/l. Average E2 activity at this site as determined from the POCIS samplers was 1.8-2.7 ng E2 equiv./litre, which provides confidence that the POCIS results are reliable. 8. Estimated oestrogenic activity across all sites (with one exception) lay in the range zero-26.5 ng E2 equiv./litre (mean = 2.0 ng/l; standard deviation = 5.1), based on the POCIS samples. The outlier was 292 ng/l, but this could not be specifically linked with intensive livestock rearing. 92% of monitoring stations (at least one on each farm) contained some oestrogenic activity. 9. In 5 of 9 livestock farms where upstream/downstream comparisons were possible, the downstream oestrogenic activity was higher than upstream, implying inputs from the farms under study. There was one case (Farm 3) where there were no known confounding factors whatever, with very little upstream contamination, and the farm increased activity by a factor of 7. 10. However, upstream activity was sometimes higher than downstream, suggesting possible inputs from phyto-oestrogens and scattered septic tank overflows, and in-stream adsorption and/or degradation. There was a low background level of oestrogenic activity in all but two locations. 11. The data did not generally permit discrimination between different potential sources on the farms, but it seems likely that the observed oestrogenic activity was mainly caused by a combination of slurry spreading and farmyard runoff, with direct excretion to pasture by livestock probably contributing less. In one case (Farm 7 slurry application experiment), activity in the field drain was directly attributable to dairy slurry alone. 12. On 8 of the 11 surveyed farms, oestrogenic activity in the stream (or field drain in one case) exceeded the Predicted-No-Effect-Concentration for E2 of 1 ng/l. In two cases, activity was probably high enough to damage reproduction in fish, although in neither case was livestock itself likely to have been the primary cause. 13. Although no EE2 was detected analytically in any stream, E1 and E2 were ubiquitous, with E2 equivalents ranging from 0.04 to 3.62 ng/l across all but two sites. Furthermore, concentrations downstream of livestock were generally higher than upstream, more markedly so than for the YES data. The oestrogen concentrations agree well with the YES data and these observations suggest that most of the detected activity was attributable to E1 and E2 derived from livestock. However, the low levels of oestrogenic activity detected by the YES upstream at several stations, and the much higher upstream levels at Farms 11 and 13, could not be explained by E1 or E2, and it is postulated that phytooestrogens may have contributed to this signal. 14. Although all streams were assayed with the YAS for androgenic activity, this was only detectable in two cases, and at levels which are unlikely to pose a threat to fish. However, it should be noted that uptake of testosterone by the POCIS has not yet been calibrated. 15. On the basis of this survey, the possibility that natural oestrogens (from both livestock and other sources) in headwater streams are causing adverse effects in fish cannot be excluded. 16. Recommendations are made for further research to discriminate between sources, and to evaluate the risks to fish

Seventh Annual Seminar on Legal Issues for Bank Counsel

Outlines of speakers\u27 presentations from the Seventh Annual Seminar on Legal Issues for Bank Counsel held on March 13-14, 1987

Is it feasible and safe to wake cardiac arrest patients receiving mild therapeutic hypothermia after 12 hours to enable early neuro-prognostication. The Therapeutic Hypothermia and eArly Waking (THAW) trial protocol

Mild therapeutic hypothermia (MTH 33°C) post out-of-hospital cardiac arrest (OHCA) is widely accepted as standard of care. However, uncertainty remains around the dose and therapy duration. OHCA patients are usually kept sedated±paralyzed and ventilated for the first 24–36 hours, which allows for targeted temperature management, but makes neurological prognostication challenging. The aim of this study is to investigate the feasibility and safety of assessing the unconscious OHCA patient after 12 hours for early waking/extubation while continuing to provide MTH for 24 hours, and fever prevention for 72 hours by using an intravenous temperature management (IVTM) system and established conscious MTH anti-shiver regimens. This is a single-center, prospective, non-randomized observational study that will compare the results of early awakening (at 12 hours) with historical controls. A total of 50 consecutive unconscious survivors of OHCA, treated with MTH, who meet the Therapeutic Hypothermia and eArly Waking (THAW) inclusion criteria will be enrolled. The patient will receive MTH by using IVTM. After 12 hours of MTH, patients will be assessed by using strict clinical criteria to determine suitability for early waking and extubation. Once awake and extubated, MTH will continue for 24 hours with skin counter-warming and anti-shiver regimen followed fever prevention up to 72 hours. All patients will have serial electroencephalogram (EEG), somatic sensory potential, and neuro-biomarkers performed on admission to intensive care unit, 6 and 12 hours, then every 24 hours until 72 hours. The study has been approved by the National Research Ethics Service, Health Research Authority

Börjeson–Forssman–Lehmann syndrome: Delineating the clinical and allelic spectrum in 14 new families

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported. Six variants were novel. We analysed the clinical and genetic findings in our series and compared them with reported BFLS patients. Affected males had classic features of BFLS including intellectual disability, distinctive facies, large ears, gynaecomastia, hypogonadism and truncal obesity. Carrier female relatives of affected males were unaffected or had only mild symptoms. The phenotype of affected females with de novo variants overlapped with the males but included linear skin hyperpigmentation and a higher frequency of dental, retinal and cortical brain anomalies. Complications observed in our series included keloid scarring, digital fibromas, absent vaginal orifice, neuropathy, umbilical hernias, and talipes. Our analysis highlighted sex-specific differences in PHF6 variant types and locations. Affected males often have missense variants or small in-frame deletions while affected females tend to have truncating variants or large deletions/duplications. Missense variants were found in a minority of affected females and clustered in the highly constrained PHD2 domain of PHF6. We propose recommendations for the evaluation and management of BFLS patients. These results further delineate and extend the genetic and phenotypic spectrum of BFLS