Equipping for risk: Lessons learnt from the UK shale-gas experience on assessing environmental risks for the future geoenergy use of the deep subsurface.

findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 ± 1.4 t CH4). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term.

Improving recorded volume in mesial temporal lobe by optimizing stereotactic intracranial electrode implantation planning.

PURPOSE: Intracranial electrodes are sometimes implanted in patients with refractory epilepsy to identify epileptic foci and propagation. Maximal recording of EEG activity from regions suspected of seizure generation is paramount. However, the location of individual contacts cannot be considered with current manual planning approaches. We propose and validate a procedure for optimizing intracranial electrode implantation planning that maximizes the recording volume, while constraining trajectories to safe paths. METHODS: Retrospective data from 20 patients with epilepsy that had electrodes implanted in the mesial temporal lobes were studied. Clinical imaging data (CT/A and T1w MRI) were automatically segmented to obtain targets and structures to avoid. These data were used as input to the optimization procedure. Each electrode was modeled to assess risk, while individual contacts were modeled to estimate their recording capability. Ordered lists of trajectories per target were obtained. Global optimization generated the best set of electrodes. The procedure was integrated into a neuronavigation system. RESULTS: Trajectories planned automatically covered statistically significant larger target volumes than manual plans [Formula: see text]. Median volume coverage was [Formula: see text] for automatic plans versus [Formula: see text] for manual plans. Furthermore, automatic plans remained at statistically significant safer distance to vessels [Formula: see text] and sulci [Formula: see text]. Surgeon's scores of the optimized electrode sets indicated that 95% of the automatic trajectories would be likely considered for use in a clinical setting. CONCLUSIONS: This study suggests that automatic electrode planning for epilepsy provides safe trajectories and increases the amount of information obtained from the intracranial investigation.

Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in healthy geriatric cats fed reduced protein foods enriched with fish oil, L-carnitine, and medium-chain triglycerides.

The purpose of this study was to determine whether feeding cats reduced protein and phosphorus foods with added fish oil, L-carnitine, and medium-chain triglycerides (MCT) altered serum biomarkers of renal function. Thirty-two healthy cats, mean age 14.0 (8.3-19.6) years, were fed control food or one of two experimental foods for 6 months. All foods had similar concentrations of moisture, protein, and fat (approximately 8.0%, 26.5%, and 20.0%, respectively). Both experimental foods contained added fish oil (1.5%) and L-carnitine (500 mg/kg). Experimental-food 2 also contained increased MCT (10.5% from coconut oil), 1.5% added corn oil, and reduced animal fat. Glomerular filtration rate (GFR), serum biochemistries, renal function biomarkers including serum creatinine (sCr) and symmetrical dimethylarginine (SDMA), and plasma metabolomic profiles were measured at baseline, and at 1.5, 3, and 6 months. Body composition was determined by dual-energy X-ray absorptiometry. Although both experimental foods altered plasma fatty acids, carnitine and related metabolites, and lysophospholipid concentrations, there were no changes in renal function biomarkers. There was, however, a benefit in using SDMA versus sCr to assess renal function in older cats with less total lean mass. Compared with cats <12 years, those >15 years had lower total lean mass (P < 0.01), lower GFR (P = 0.04), and lower sCr concentrations (P < 0.01). However, SDMA concentrations (P < 0.01) were higher in older cats. This study shows that in cats, serum SDMA concentration is more highly correlated with GFR than sCr concentration, and, unlike sCr, which declines with age because of muscle wasting, SDMA increases as GFR declines with age.

Effect of transport on blood selenium and glutathione status in feeder lambs.

Stress from transport may be linked to increased generation of reactive oxygen species, the removal of which requires reduced glutathione and selenium. The aim of this experiment was to examine the effect of transport on glutathione and Se status of feeder lambs. Recently weaned lambs (n = 40) were blocked by gender and BW on d 0 of the experiment and randomly assigned to 2 treatment groups: group 1, no transport and full access to feed and water (control), and group 2, 8-h road transport followed by another 16 h of feed deprivation (transport). After 24 h, both treatment groups were treated the same. All lambs were weighed, and blood samples were collected at 0, 8, 24, and 72 h and analyzed for whole-blood (WB) and serum Se concentrations, serum NEFA concentrations, and erythrocyte concentrations of glutathione. Transport of feeder lambs for 8 h followed by another 16 h of feed deprivation transiently (significant at 24 h but no longer different at 72 h) decreased BW and erythrocyte glutathione concentrations and increased serum NEFA and blood Se concentrations compared with control lambs. Our results suggest that 8 h of transport followed by another 16 h of feed deprivation results in fatty acid and Se mobilization from tissue stores with a coincident decrease in erythrocyte glutathione concentrations.

Organic and inorganic selenium: IV. passive transfer of immunoglobulin from ewe to lamb.

Newborn lambs depend on their dams for passive transfer of immunoglobulins, primarily IgG, for protection from harmful pathogens until their own immunological defenses have developed. Previous studies have suggested that supplementation with Se results in a modest increase in IgG concentration in serum of newborn calves and lambs. To evaluate the effect of the Se source and supplementation rate in ewes during pregnancy on passive transfer of IgG to their lambs, 210 Polypay, Suffolk, or Suffolk × Polypay cross ewes were divided into 7 treatment groups (n = 30 each) and drenched weekly with no Se, at the maximum FDA-allowed concentration with inorganic Na-selenite or organic Se-yeast (4.9 mg Se/wk), or with inorganic Na-selenite and organic Se-yeast at supranutritional concentrations (14.7 and 24.5 mg Se/wk). Ewe serum IgG concentrations were measured within 30 d of parturition, ewe colostrum and lamb serum IgG concentrations were measured at parturition before suckling, and lamb serum IgG concentrations were measured again at 48 h postnatal. Ewes receiving 24.5 mg Se/wk tended to have or had, independent of Se source, greater colostral IgG concentrations than ewes receiving 4.9 mg Se/wk overall (81.3 vs. 66.2 mg/mL; P = 0.08) and for Polypay ewes only (90.1 vs. 60.7 mg/mL; P = 0.03). Polypay ewes receiving Se-yeast at 24.5 mg Se/wk transferred a greater calculated total IgG amount to their lambs than Polypay ewes receiving Se-yeast at 4.9 mg Se/wk (15.5 vs. 11.6 g; P = 0.02), whereas the converse was true (interaction between Se source and dose concentration; P = 0.03) for Polypay ewes receiving inorganic Na-selenite at 24.5 mg Se/wk vs. Na-selenite at 4.9 mg/wk (11.6 vs. 15.7 g; P = 0.08). Our results suggest that supranutritional Se supplementation of Polypay ewes during pregnancy increases colostral IgG concentrations but that the optimal supplementation rate for IgG transfer from ewe to lamb may differ for Na-selenite and Se-yeast.

External validation of established risk adjustment models for procedural complications after percutaneous coronary intervention.

BACKGROUND: Workable risk models for patients undergoing percutaneous coronary intervention (PCI) are needed urgently. OBJECTIVE: To validate two proposed risk adjustment models (Mayo Clinic Risk Score (MC), USA and North West Quality Improvement Programme (NWQIP), UK models) for in-hospital PCI complications on an independent dataset of relatively high risk patients undergoing PCI. SETTING: Tertiary centre in northern England. METHODS: Between September 2002 and August 2006, 5034 consecutive PCI procedures (validation set) were performed on a patient group characterised by a high incidence of acute myocardial infarction (MI; 16.1%) and cardiogenic shock (1.7%). Two external models-the NWQIP model and the MC model-were externally validated. MAIN OUTCOME MEASURE: Major adverse cardiovascular and cerebrovascular events: in-hospital mortality, Q-wave MI, emergency coronary artery bypass grafting and cerebrovascular accidents. RESULTS: An overall in-hospital complication rate of 2% was observed. Multivariate regression analysis identified risk factors for in-hospital complications that were similar to the risk factors identified by the two external models. When fitted to the dataset, both external models had an area under the receiver operating characteristic curve >or=0.85 (c index (95% CI), NWQIP 0.86 (0.82 to 0.9); MC 0.87(0.84 to 0.9)), indicating overall excellent model discrimination and calibration (Hosmer-Lemeshow test, p>0.05). The NWQIP model was accurate in predicting in-hospital complications in different patient subgroups. CONCLUSIONS: Both models were externally validated. Both predictive models yield comparable results that provide excellent model discrimination and calibration when applied to patient groups in a different geographic population other than that in which the original model was developed.

Prospective, randomised, controlled trial to study the effect of intracoronary injection of verapamil and adenosine on coronary blood flow during percutaneous coronary intervention in patients with acute coronary syndromes.

OBJECTIVES: To study the impact of injection of verapamil and adenosine in the coronary arteries on TIMI (Thrombolysis in Myocardial Infarction) frame count (TFC) after percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome (ACS). METHODS: Prospective, randomised, controlled study of the intracoronary administration of normal saline versus verapamil versus adenosine in patients undergoing PCI in the setting of an ACS, even when flow is visually established to be normal or near normal. Patients were randomised to receive verapamil (n = 49), adenosine (n = 51) or normal saline (n = 50) after PCI. Quantitative angiography, TIMI flow grade (TFG), TFC and myocardial blush grade were assessed before PCI, after PCI and after drugs were given. Wall motion index (WMI) was measured at days 1 and 30. RESULTS: 9 patients in the verapamil group developed transient heart block, not seen with adenosine (p

Chemorepellent signaling through the PACAP/lysozyme receptor is mediated through cAMP and PKC in Tetrahymena thermophila.

Pituitary adenylate cyclase-activating peptide and lysozyme are potent chemorepellents which act through the same receptor in Tetrahymena. Using in vivo behavioral studies, we have found that the pituitary adenylate cyclase-activating peptide/lysozyme receptor appears to signal through a G-protein pathway which is mediated through both adenosine 3'5'monophosphate and protein kinase C. Avoidance to pituitary adenylate cyclase-activating peptide and lysozyme is inhibited by the G-protein inhibitor, guanosine 5'-O-(2thiodiphosphate), the adenosine 3'5'monophate analog, Rp-adenosine-3', 5' cyclic monophosphorothioate, and the protein kinase C inhibitors, calphostin C and bisindolylmaleimide IV. A proposed model for signaling through the pituitary adenylate cyclase-activating peptide/lysozyme receptor is briefly outlined.

Transmembrane segment 11 of UhpT, the sugar phosphate carrier of Escherichia coli, is an alpha-helix that carries determinants of substrate selectivity.

In Escherichia coli, transport of hexose 6-phosphates is mediated by the P(i)-linked antiport carrier, UhpT, a member of the major facilitator superfamily. We showed earlier that Lys(391), a member of an intrahelical salt bridge (Asp(388)/Lys(391)) in the eleventh transmembrane segment (TM11) of this transporter, can function as a determinant of substrate selectivity (Hall, J. A., Fann, M.-C., and Maloney, P. C. (1999) J. Biol. Chem. 274, 6148-6153). Here, we examine in detail the role of TM11 in setting substrate preference. Derivatives having an uncompensated cationic charge at either position 388 or 391 (the D388C, D388V, or D388K/K391C variants) are gain-of-function mutants in which phosphoenolpyruvate, not sugar 6-phosphate, is the preferred organic substrate. By contrast, when an uncompensated anionic charge is placed at position 388 (K391C), we observed behavior consistent with an increased preference for monovalent rather than divalent sugar 6-phosphate. Because positions 388 and 391 lie deep within the UhpT hydrophobic sector, these findings suggested that an extended length of TM11 may be accessible to external substrates and probes. To explore this issue, we used a panel of TM11 single cysteine variants to examine the transport of glucose 6-phosphate in the presence and absence of the membrane-impermeant, thiol-reactive agent p-chloromercuribenzosulfonate (PCMBS). Accessibility to PCMBS, together with the pattern of substrate protection against PCMBS inhibition, leads us to conclude that TM11 spans the membrane as an alpha-helix, with approximately two-thirds of its surface lining a substrate translocation pathway. We suggest that this feature is a general property of carrier proteins in the major facilitator superfamily and that for this reason residues in TM11 will serve to carry determinants of substrate selectivity.

Severe left main stem stenosis in a cardiac transplant recipient: successful treatment by coronary stenting.

A 58-year-old male underwent orthotopic cardiac transplantation for ischemic cardiomyopathy. At routine coronary angiography 2 years later, he was found to have severe concentric stenosis of the left main coronary artery but was asymptomatic. Revascularization was recommended on prognostic grounds and after discussion with his cardiac transplant surgeon, percutaneous coronary intervention with elective stenting was offered. This was performed successfully with a single stent and a good angiographic result was maintained 6 and 18 months later.

Cerebellar hypoactivity in frequent marijuana users.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using PET, regional cerebral blood flow was compared in frequent marijuana users and comparable, non-using controls after at least 26 h of monitored abstention by all subjects. Marijuana users showed substantially lower brain blood flow than controls in a large region of posterior cerebellum, indicating altered brain function in frequent marijuana users. A cerebellar locus of some chronic and acute effects of marijuana is plausible, e.g. the cerebellum has been linked to an internal timing system, and alterations of time sense are common following marijuana smoking.

Effect of pharmaceuticals on radiographic appearance of selected examinations of the abdomen and thorax.

Pharmacologic agents may have a significant effect on the outcome of radiographic interpretation in small animal imaging. Alterations in the abdomen and thorax may represent artifactual or transient changes or changes reflecting cytotoxicity. Examples of agents that may influence the appearance of radiographs include anticonvulsants, sedatives, anesthetics, analgesics, antiinflammatories, gastrointestinal prokinetic drugs, antineoplastics, and hormones such as megestrol acetate. Radiographic studies may be part of a disease-monitoring process. It is important to understand how pharmaceuticals (e.g., chemotherapeutics or therapy for an underlying medical condition) affect the radiographic appearance. Caution should be exercised in the interpretation of radiographic studies because the findings may relate to the drug therapy rather than the underlying condition.

Effects of frequent marijuana use on brain tissue volume and composition.

To investigate CNS effects of frequent marijuana use, brain tissue volume and composition were measured using magnetic resonance imaging (MRI) in 18 current, frequent, young adult marijuana users and 13 comparable, non-using controls. Automated image analysis techniques were used to measure global and regional brain volumes, including, for most regions, separate measures of gray and white matter. The marijuana users showed no evidence of cerebral atrophy or global or regional changes in tissue volumes. Volumes of ventricular CSF were not higher in marijuana users than controls, but were, in fact, lower. There were no clinically significant abnormalities in any subject's MRI. Sex differences were detected in several global volume measures.

Effect of acute gastric dilatation on gastric myoelectic and motor activity in dogs.

OBJECTIVE: To investigate the effects of experimentally induced acute gastric dilatation on electrical and mechanical activities of the stomach in dogs. ANIMALS: 7 healthy dogs. PROCEDURE: Electrodes and strain-gauge force transducers were implanted on the serosal surface of the antrum and pylorus. Eight days later, baseline gastric electrical and contractile activities were recorded. The dogs were anesthetized and mechanically ventilated to maintain normocapnia while the stomach was distended (intragastric pressure, 30 mm Hg) for 180 minutes, using a thin compliant bag. Gastric electrical and contractile activities were recorded again on days 1 and 10 after dilatation. Recordings were analyzed to determine gastric slow-wave frequency, slow-wave dysrhythmia, propagation velocity of slow-waves, coupling of contractions to slow waves, motility index on the basis of relative contractile amplitudes, and onset of contractions after a standardized meal. RESULTS: Electrical or contractile activities were not significantly different 18 hours after acute gastric dilatation (day 1). Arrhythmias were evident before and after gastric dilatation in dogs from which food was withheld and in dogs after consumption of a meal. CONCLUSIONS: Variables for assessing gastric electrical and contractile activities were unaffected 18 hours after acute gastric dilatation. CLINICAL RELEVANCE: Analysis of results of this study indicated that altered electrical and contractile activities in dogs with short-term gastric dilatation are not likely to be secondary to the process of acute gastric dilatation.

Altered substrate selectivity in a mutant of an intrahelical salt bridge in UhpT, the sugar phosphate carrier of Escherichia coli.

Site-directed and second site suppressor mutagenesis identify an intrahelical salt bridge in the eleventh transmembrane segment of UhpT, the sugar phosphate carrier of Escherichia coli. Glucose 6-phosphate (G6P) transport by UhpT is inactivated if cysteine replaces either Asp388 or Lys391 but not if both are replaced. This suggests that Asp388 and Lys391 are involved in an intrahelical salt bridge and that neither is required for normal UhpT function. This interpretation is strengthened by the finding that mutations at Lys391 (K391N, K391Q, and K391T) are recovered as revertants of the inactive D388C variant. Further work shows that although the D388C variant is null for G6P transport, movement of 32Pi by homologous Pi/Pi exchange is unaffected. This raises the possibility that this derivative may have latent function, a possibility confirmed by showing that D388C is a gain-of-function mutation in which phosphoenolpyruvate (PEP) is the preferred substrate. Added study of the Pi/Pi exchange shows that in wild type UhpT this partial reaction is readily blocked by G6P but not PEP. By contrast, in the D388C variant, Pi/Pi exchange is unaffected by G6P but is inhibited by both PEP and 3-phosphoglycerate. These latter substrates are used by PgtP, a related Pi-linked antiporter, which lacks the Asp388-Lys391 salt bridge but has instead an uncompensated arginine at position 391. For this reason, we conclude that in both UhpT and PgtP position 391 can serve as a determinant of substrate selectivity by acting as a receptor for the anionic carboxyl brought into the translocation pathway by PEP.

Effectiveness of interventions to improve patient compliance: a meta-analysis.

OBJECTIVES: This article summarizes the results of 153 studies published between 1977 and 1994 that evaluated the effectiveness of interventions to improve patient compliance with medical regimens. METHODS: The compliance interventions were classified by theoretical focus into educational, behavioral, and affective categories within which specific intervention strategies were further distinguished. The compliance indicators broadly represent five classes of compliance-related assessments: (1) health outcomes (eg, blood pressure and hospitalization), (2) direct indicators (eg, urine and blood tracers and weight change), (3) indirect indicators (eg, pill count and refill records), (4) subjective report (eg, patients' or others' reports), and (5) utilization (appointment making and keeping and use of preventive services). An effect size (ES) r, defined as Fisher's Z transformation of the Pearson correlation coefficient, representing the association between each intervention (intervention versus control) and compliance measure was calculated. Both an unweighted and weighted r were calculated because of large sample size variation, and a combined probability across studies was calculated. RESULTS: The interventions produced significant effects for all the compliance indicators (combined Z values more than 5 and less than 32), with the magnitude of effects ranging from small to large. The largest effects (unweighted) were evident for refill records and pill counts and in blood/urine and weight change studies. Although smaller in magnitude, compliance effects were evident for improved health outcomes and utilization. Chronic disease patients, including those with diabetes and hypertension, as well as cancer patients and those with mental health problems especially benefited from interventions. CONCLUSIONS: No single strategy or programmatic focus showed any clear advantage compared with another. Comprehensive interventions combining cognitive, behavioral, and affective components were more effective than single-focus interventions.

Open surgical biopsy for nonpalpable mammographic abnormalities: still an option compared with core needle biopsy.

OBJECTIVE: Our purpose was to present information about open surgical biopsy. It is hoped that this will be helpful when reviewing information about core needle biopsy STUDY DESIGN: Review of 461 open surgical biopsies for nonpalpable mammographic abnormalities was performed. All patients were managed by the Women's Health Center of Logansport. Core needle biopsy data came from the literature. RESULTS: Open surgical biopsy compared favorably to core needle biopsy with regard to accuracy, cost, patient convenience, recovery, adequacy of specimen, identification of primary site, and cosmetics. CONCLUSION: Despite core needle biopsy marketing, open surgical biopsy has its advantages and should not be relegated to the museum.

Two modes of ligand binding in maltose-binding protein of Escherichia coli. Electron paramagnetic resonance study of ligand-induced global conformational changes by site-directed spin labeling.

Binding of ligands to the maltose-binding protein (MBP) of Escherichia coli often causes a global conformational change involving the closure of its two lobes. We have introduced a cysteine residue onto each of these lobes by site-directed mutagenesis and modified these residues with spin labels. Using EPR spectroscopy, we examined the changes, caused by the ligand binding, in distance between the two spin labels, hence between the two lobes. The binding of both maltose and maltotetraose induced a considerable closure of the N- and C-terminal lobes of MBP. Little closure occurred upon the binding of maltotetraitol or beta-cyclodextrin. Previous study by fluorescence and UV differential absorbance spectroscopy (Hall, J. A., Gehring, K., and Nikaido, H. (1997) J. Biol. Chem. 272, 17605-17609) showed that maltose and a large portion of maltotetraose bound to MBP via one mode (R mode or "end-on" mode), which is physiologically active and leads to the subsequent transport of the ligands across the cytoplasmic membrane. In contrast, maltotetraitol and beta-cyclodextrin bound to MBP via a different mode (B mode or "middle" mode), which is physiologically inactive. The present work suggests that the B mode is nonproductive because ligands binding in this manner prevent the closure of the two domains of MBP, and, as a result, the resulting ligand-MBP complex is incapable of interacting properly with the inner membrane-associated transporter complex.