Characterizing oil and gas wells with fugitive gas migration through Bayesian multilevel logistic regression.

Oil and gas wells are engineered with barriers to prevent fluid movement along the wellbore. If the integrity of one or more of these barriers fails, it may result in subsurface leakage of natural gas outside the well casing, a process termed fugitive gas migration (GM). Knowledge of the occurrence and causes of GM is essential for effective management of associated potential risks. In the province of British Columbia, Canada (BC), oil and gas producers are required to report well drilling, completion, production, and abandonment records for all oil and gas wells to the provincial regulator. This well data provides a unique opportunity to identify well characteristics with higher likelihoods for GM to develop. Here we employ Bayesian multilevel logistic regression to understand the associations between various well attributes and reported occurrences of GM in 0.6% of the 25,000 oil and gas wells in BC. Our results indicate that there is no association between the occurrence of GM and hydraulic fracturing. Overall, there appears to be no well construction or operation attribute in the study database that is conclusively associated with GM. Wells with GM more frequently exhibit indicators of well integrity loss (i.e., surface casing vent flow, remedial treatments, and blowouts) and geographic location appears to be important. We ascribe the spatial clustering of GM cases to the local geologic environment, and we speculate that there are links between particular intermediate gas-bearing formations and GM occurrence in the Fort Nelson Plains Area. The results of this study suggest that oil and gas wells in high GM occurrence areas and those showing any attribute associated with integrity failure (e.g., surface casing vent flow) should be prioritized for monitoring to improve the detection of GM.

Levels of resilience, anxiety and depression in nurses working in respiratory clinical areas during the COVID pandemic.

BACKGROUND: The delivery of healthcare during the COVID pandemic has had a significant impact on front line staff. Nurses who work with respiratory patients have been at the forefront of the pandemic response. Lessons can be learnt from these nurses' experiences in order to support these nurses during the existing pandemic and retain and mobilise this skilled workforce for future pandemics. METHODS: This study explores UK nurses' experiences of working in a respiratory environment during the COVID-19 pandemic. An e-survey was distributed via professional respiratory societies; the survey included a resilience scale, the GAD7 (anxiety) and the PHQ9 (depression) tools. Demographic data was collected on age, gender, ethnicity, nursing experience and background, clinical role in the pandemic, and home-life and work balance. RESULTS: Two hundred and fifty-five responses were received for the survey, predominately women (89%, 226/255), aged over 35 (79%, 202/255). Nearly 21% (40/191) experiencing moderate to severe or severe symptoms of anxiety. Similar levels are seen for depression (17.2%, 31/181). 18.9% (34/180) had a low or very low resilience score. Regression analysis showed that for both depression and anxiety variables, age and years of qualification provided the best model fit. Younger nurses with less experience have higher levels of anxiety and depression and had lower resilience. CONCLUSION: This cohort experienced significant levels of anxiety and depression, with moderate to high levels of resilience. Support mechanisms and interventions need to be put in place to support all nurses during pandemic outbreaks, particularly younger or less experienced staff.

Myoglobin production in emperor penguins.

Increased oxygen storage is essential to the diving capacities of marine mammals and seabirds. However, the molecular mechanisms underlying this adaptation are unknown. Myoglobin (Mb) and Mb mRNA concentrations were analyzed in emperor penguin (Aptenodytes forsteri) adults and chicks with spectrophotometric and RNase protection assays to evaluate production of their large Mb-bound O(2) stores. Mean pectoral Mb concentration and Mb mRNA content increased throughout the pre-fledging period and were 15-fold and 3-fold greater, respectively, in adults than in 3.5 month old chicks. Mean Mb concentration in 5.9 month old juveniles was 2.7+/-0.4 g 100 g(-1) muscle (44% that of wild adults), and in adults that had been captive all their lives it was 3.7+/-0.1 g 100 g(-1) muscle. The Mb and Mb mRNA data are consistent with regulation of Mb production at the level of transcription as in other animals. Significant Mb and Mb mRNA production occurred in chicks and young juveniles even without any diving activity. The further increase in adult Mb concentrations appears to require the exercise/hypoxia of diving because Mb concentration in captive, non-diving adults only reached 60% of that of wild adults. The much greater relative increase in Mb concentration than in Mb mRNA content between young chicks and adults suggests that there is not a simple 1:1 relationship between Mb mRNA content and Mb concentration. Nutritional limitation in young chicks and post-transcriptional regulation of Mb concentration may also be involved.

A concept for ab initio prediction of cis-regulatory modules.

An important concern in the attempt of understanding the functional code of eukaryotic genes is to elucidate the control structures for regulating gene activation and suppression. One objective in the attempt to understand mechanisms of gene regulation is the elucidation of the regulatory network structure. A preliminary step of a detailed network analysis is identifying the transcription factor binding sites of a regulatory network. Known as cis-regulatory module (CRM), it is understood as part of the genome that comprises a set of short length binding sites. Gene regulatory systems are known to be quite stable during evolution, as compared to relatively frequent replication processes of genes and mutations of the coding sequences. This conservation property of regulatory code can advantageously be used for identifying cis-regulatory modules of potentially co-regulated genes. As the degree of similarity is expected to depend on the phylogenetic distance of homologs or orthologs, we favor an approach that is based on a comparison paradigm. The paper introduces a novel concept for measuring the similarity ofcis-regulatory modules which can then be used in an algorithm for comparing regulatory regions. The proposed algorithm searches for pairs of similar modules, and a prototype implementation is applied to human and mouse liver sequences. The results are compared to that of random sequences, and it is shown that a clear decision about co-regulation is possible at this level.

Neural computing in cancer drug development: predicting mechanism of action.

Described here are neural networks capable of predicting a drug's mechanism of action from its pattern of activity against a panel of 60 malignant cell lines in the National Cancer Institute's drug screening program. Given six possible classes of mechanism, the network misses the correct category for only 12 out of 141 agents (8.5 percent), whereas linear discriminant analysis, a standard statistical technique, misses 20 out of 141 (14.2 percent). The success of the neural net indicates several things. (i) The cell line response patterns are rich in information about mechanism. (ii) Appropriately designed neural networks can make effective use of that information. (iii) Trained networks can be used to classify prospectively the more than 10,000 agents per year tested by the screening program. Related networks, in combination with classical statistical tools, will help in a variety of ways to move new anticancer agents through the pipeline from in vitro studies to clinical application.

Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

BACKGROUND: Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. METHODS: Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. RESULTS: Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. CONCLUSIONS: Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia.

MRI asymmetries and language dominance.

OBJECTIVE: To examine the relationship between language dominance, as measured by Wada testing, and hemispheric asymmetries on MR brain images. BACKGROUND: A previous report that did not include verification of language dominance compared the length of the planum temporale with hemispheric asymmetries seen on CT and inferred that occipital lobe asymmetry is related to language dominance. METHODS: Language dominance was identified by the Wada test in 57 patients evaluated for surgical treatment of epilepsy. Fifty-five had an MRI scan that allowed accurate measurement. In a blinded fashion, two examiners independently measured bilateral frontal, parietal, and occipital lobe lengths on MR scan for each patient. Measurements of asymmetries were compared with language dominance established by the Wada test. RESULTS: Reliability of measurement between the examiners was 97%. Asymmetry of the occipital lobe length on MR scan 10 mm above the tentorium was the only measurement significantly related to language dominance (p < 0.01). Occipital lobe length was longer on the left in 19 (40%) and on the right in 10 (21%) patients with left dominance. The right lobe was longer in six of seven (86%) patients with bilateral dominance. One patient with right hemisphere dominance had a longer left lobe. None of the measurements significantly related to handedness. CONCLUSION: Asymmetries of occipital lobe length relate to language dominance, but such dominance cannot be reliably identified by MR in an individual patient.

Improving education and resources for health care providers.

Workers and citizens are turning increasingly to the health care system for information about occupational and environmental reproductive hazards, yet most primary care providers and specialists know little about the effects of occupational/environmental toxicants on the reproductive system or how to evaluate and manage patients at potential risk. Although it is unrealistic to expect all clinicians to become experts in this area, practitioners should know how to take a basic screening history, identify patients at potential risk, and make appropriate referrals. At present, occupational and environmental health issues are not well integrated into health professional education in the United States, and clinical information and referral resources pertaining to reproductive hazards are inadequate. In addressing these problems, the conference "Working Group on Health Provider Education and Resources" made several recommendations that are detailed in this report. Short-term goals include enhancement of existing expertise and resources at a regional level and better integration of information on occupational/environmental reproductive hazards into curricula, meetings, and publications of medical and nursing organizations. Longer term goals include development of a comprehensive, single-access information and referral system for clinicians and integration of occupational and environmental medicine into formal health professional education curricula at all levels.

Severity of health effects associated with building-related illness.

Building-related illness ranges from mild rhinitis to potentially life-threatening hypersensitivity pneumonitis and legionellosis. Sick-building syndrome, consisting of headache, mucous membrane irritation, and fatigue, may be present in 30% of all office workers. Hypersensitivity pneumonitis, asthma, and legionellosis are less common, and it is difficult from existing studies to estimate the incidence of these more severe illnesses. There are even fewer data on an illness now being called multiple chemical sensitivity and its relationship to indoor environments. New studies are needed to estimate the frequency of all building-associated illnesses, and case definitions for these disorders must be delineated.

Variability in the classification of radiographs using the 1980 International Labor Organization Classification for Pneumoconioses.

This study describes the extent of agreement in classification of chest radiographs using the International Labor Organization (ILO) classification among six readers from the United States and Canada. A set of 119 radiographs was created and read by three Canadian and three US readers. The two ratings of interest were profusion (scored from 0/- to 3/+) and pleural abnormalities consistent with pneumoconiosis (scored with the ILO system, then collapsed into a yes/no). We used a number of approaches to evaluate interreader agreement on profusion and pleural changes, determining concordance, observed agreement, kappa statistic, and a new measure to approximate sensitivity and specificity. This study found that five of six readers had good fair to good agreement for pleural findings and for profusion as a dichotomous variable (> or = 1/0 vs < or = 0/1) using the kappa statistic, while a sixth reader had poor agreement. We found that concordance, expressed as percent agreement, was higher for normal radiographs than for ones that showed disease, and describe the use of the kappa statistic to control for this finding. This analysis adds to the existing literature with the use of the kappa statistic, and by presenting a new measure for "underreading" and "overreading" tendencies.

Engraftment of leukocyte subsets following autologous bone marrow transplantation in acute myeloid leukemia using anti-myeloid (CD14 and CD15) monoclonal antibody-purged bone marrow.

The cell surface phenotype of leukocyte subsets during reconstitution following autologous bone marrow transplantation (ABMT) using bone marrow purged with anti-myeloid monoclonal antibodies (MoAbs) and complement (C') was evaluated in 20 patients with acute myeloid leukemia (AML). Repopulation of B and T lymphocytes, natural killer (NK) cells, and myeloid cells was assessed by phenotypic analysis using two-color cytofluorography of peripheral blood mononuclear cells (PBMNC) at several time points up to 2 years post-transplantation. In spite of removal of the majority of monomyeloid cells of the autograft by purging with anti-CD14 and anti-CD 15, engraftment occurred rapidly. The myeloid cells appeared normal by surface phenotype. An early rise in NK cells, characterized by expression of CD57 and CD 16, was seen. The CD4:CD8 ratio remained low throughout the study period, primarily due to a persistently low CD4 level. ABMT using bone marrow purged with the anti-myeloid MoAbs PM-81 and AML-2-23 and C' resulted in prompt engraftment of neutrophils. Although there was a prolonged time for recovery of lymphocyte subsets, this did not result in an increased risk of early infectious complications. Late infectious complications post-transplantation were limited to herpes zoster infection in one patient 18 months post-transplantation, and bacterial meningitis in that same patient 2 months later. This study demonstrates that ABMT in patients with AML using bone marrow purged with the anti-myeloid MoAbs PM81 (anti-CD15) and AML-2-23 (anti-CD14) and C' results in rapid hematologic engraftment and delayed phenotypic immunologic reconstitution without significant acute or chronic clinical toxicities.

Uropharmacology: VIII. Sympathomimetic agents.

Sympathomimetic drugs stimulate the receptors of the sympathetic nervous system. Although the bladder possesses sympathetic receptors, sympathomimetic drugs, in general, have little effect on bladder function. Their most useful clinical applications on the urinary tract are to increase or decrease bladder resistance.

Uropharmacology: IV. Parasympathomimetic drugs.

Parasympathomimetic drugs include (1) acetylcholine and several synthetic choline esters and related derivatives, and (2) naturally occurring cholinomimetic alkaloids and certain related synthetic compounds. Pharmacology of acetylcholine, the prototype parasympathomimetic, is presented, as well as an introduction to other parasympathomimetic drugs and choline esters.

Uropharmacology: IX. Direct-acting smooth muscle stimulants and depressants.

Agents which exert their effect on the lower urinary tract by stimulating or depressing the activity of smooth muscle directly are discussed. Many of these drugs also exert other actions on the urinary tract mediated via the autonomic nervous system.

Uropharmacology: X. Central nervous system stimulants and depressants.

Several drugs that are utilized primarily for their effects on the central nervous system also affect lower urinary tract function. Most of these effects are produced by the action of these drugs on adrenergic and cholinergic receptors or by direct action of lower urinary tract musculature. Central nervous system stimulants and depressants which are known to affect the storage or evacuation role of the lower urinary tract are discussed.

Transurethral resection of prostate via perineal urethrostomy. Prospective study.

A controlled, prospective clinical study was undertaken to determine the incidence and cause of urethral strictures after transurethral resection. Patients were assigned to 1 of 3 groups. Group A consisted of patients in whom it was considered preferable for various reasons to perform prostatic resection through perineal urethrostomy; therefore, these were excluded from randomization. All other patients were randomized using a sealed-envelope method into Group B who underwent resection via perineal urethrostomy and Group C who underwent resection via the entire urethra. Strictures occurred in 6 of 42 patients in Group C postoperatively while patients in Group B remained free of strictures. This difference was statistically significant (p less than 0.05). It was concluded that strictures which occur result from the use of the resectoscope through the entire urethra and not from the use of indwelling catheters, and that performing prostatic resection via perineal urethrostomy is valuable in preventing the occurrence of such strictures.

Evaluation of Sacks solution for hypothermic preservation of kidneys.

The efficacy of Sacks solution for hypothermic preservation of dog kidneys was determined. Complete ischemia was produced in one kidney for thirty minutes by clamping the renal pedicle in situ, followed by excision and immediate washout with the cold preservation fluid. Kidneys were stored in Sacks solution at 2 degree C. for forty-eight hours, reimplanted in the donor, and the normal, contralateral kidney was removed. Complete reversal of renal impairment with long-term survival was observed in 2 of 9 animals. Of 7 animals with graft failure, 2 showed the beginning of a tendency to reverse a rising serum creatinine at the time of death or sacrifice. In the remaining 5, creatinine rose unrelentingly until death or sacrifice occurred. The observed 22 per cent survival rate was significantly (p less than 0.05) less than the 83 per cent survival reported by Sacks, Petritsch, and Kaufman. Evidence suggestive of intrarenal deposits of MgHPO4-3H2O was found in 2 of 4 dogs sacrificed for graft failure. This raises questions of the solution's safety as well as its efficacy. We are unable to confirm the success of the original investigators with this new preservation solution.

Uropharmacology: part VI. Parasympathetic depressants.

A discussion of the various parasympathetic depressants is presented. Belladonna alkaloids include atropine, the prototype, and scopolamine. Synthetic drugs include quaternary ammonium compounds with antimuscarinic activity such as methantheline, propantheline, and other drugs such as isopropamide, pipenzolate methylbromide, and diphemanil methylsulfate. A miscellaneous class of drugs such as hemicholinium, valethamate, and oxybutynin chloride also possesses parasympathetic depressant activity. The pharmacologic properties and clinical usage of these drugs are discussed.

Uropharmacology: v. choline esters and other parasympathomimetic drugs.

Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response.

Lower urinary tract pharmacology. I. Anatomic considerations.

With this issue Dr. Bissada, Dr. Finkbeiner, and Dr. Welch introduce a series on uropharmacology, starting with the lower urinary tract. Since an understanding of the anatomy, neurophysiology, and basic pharmacology is necessary, Part I is a description of the functional anatomy of the lower urinary tract and the mechanisms of continence and voiding. Part II is a review of the differences between somatic and autonomic reflexes; the afferent and efferent innervation of lower urinary tract; the organization of pelvic ganglionic cells and the spinal and supraspinal control of lower urinary tract function. Subsequent articles will be on basic pharmacology of lower urinary tract and individual drug classes.