Evaluating methane inventories by isotopic analysis in the London region.

A thorough understanding of methane sources is necessary to accomplish methane reduction targets. Urban environments, where a large variety of methane sources coexist, are one of the most complex areas to investigate. Methane sources are characterised by specific δ13C-CH4 signatures, so high precision stable isotope analysis of atmospheric methane can be used to give a better understanding of urban sources and their partition in a source mix. Diurnal measurements of methane and carbon dioxide mole fraction, and isotopic values at King's College London, enabled assessment of the isotopic signal of the source mix in central London. Surveys with a mobile measurement system in the London region were also carried out for detection of methane plumes at near ground level, in order to evaluate the spatial allocation of sources suggested by the inventories. The measured isotopic signal in central London (-45.7 ±0.5‰) was more than 2‰ higher than the isotopic value calculated using emission inventories and updated δ13C-CH4 signatures. Besides, during the mobile surveys, many gas leaks were identified that are not included in the inventories. This suggests that a revision of the source distribution given by the emission inventories is needed.

Marked long-term decline in ambient CO mixing ratio in SE England, 1997-2014: evidence of policy success in improving air quality.

Atmospheric CO at Egham in SE England has shown a marked and progressive decline since 1997, following adoption of strict controls on emissions. The Egham site is uniquely positioned to allow both assessment and comparison of 'clean Atlantic background' air and CO-enriched air downwind from the London conurbation. The decline is strongest (approximately 50 ppb per year) in the 1997-2003 period but continues post 2003. A 'local CO increment' can be identified as the residual after subtraction of contemporary background Atlantic CO mixing ratios from measured values at Egham. This increment, which is primarily from regional sources (during anticyclonic or northerly winds) or from the European continent (with easterly air mass origins), has significant seasonality, but overall has declined steadily since 1997. On many days of the year CO measured at Egham is now not far above Atlantic background levels measured at Mace Head (Ireland). The results are consistent with MOPITT satellite observations and 'bottom-up' inventory results. Comparison with urban and regional background CO mixing ratios in Hong Kong demonstrates the importance of regional, as opposed to local reduction of CO emission. The Egham record implies that controls on emissions subsequent to legislation have been extremely successful in the UK.

Measurements of δ13C in CH4 and using particle dispersion modeling to characterize sources of Arctic methane within an air mass.

A stratified air mass enriched in methane (CH4) was sampled at ~600 m to ~2000 m altitude, between the north coast of Norway and Svalbard as part of the Methane in the Arctic: Measurements and Modelling campaign on board the UK's BAe-146-301 Atmospheric Research Aircraft. The approach used here, which combines interpretation of multiple tracers with transport modeling, enables better understanding of the emission sources that contribute to the background mixing ratios of CH4 in the Arctic. Importantly, it allows constraints to be placed on the location and isotopic bulk signature of the emission source(s). Measurements of δ13C in CH4 in whole air samples taken while traversing the air mass identified that the source(s) had a strongly depleted bulk δ13C CH4 isotopic signature of -70 (±2.1)‰. Combined Numerical Atmospheric-dispersion Modeling Environment and inventory analysis indicates that the air mass was recently in the planetary boundary layer over northwest Russia and the Barents Sea, with the likely dominant source of methane being from wetlands in that region.

Maternal supplementation with fishmeal protects against late gestation endotoxin-induced fetal programming of the ovine hypothalamic-pituitary-adrenal axis.

Adverse uterine environments caused by maternal stress (such as bacterial endotoxin) can alter programming of the fetal hypothalamic-pituitary-adrenal axis (HPAA) rendering offspring susceptible to various adulthood diseases. Thus, protection against this type of stress may be critical for ensuring offspring health. The present study was designed to determine if maternal supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) during pregnancy helps to protect against stress-induced fetal programming. Briefly, 53 ewes were fed a diet supplemented with fishmeal (FM) or soybean meal (SM) from day 100 of gestation (gd100) through lactation. On gd135, half the ewes from each dietary group were challenged with either 1.2 µg/kg Escherichia coli lipopolysaccharide (LPS) endotoxin, or saline as the control. The offspring's cortisol response to weaning stress was assessed 50 days postpartum by measuring serum cortisol concentrations 0, 6 and 24 h post weaning. Twenty-four hours post-weaning, lambs were subjected to an adrenocorticotropic hormone (ACTH) challenge (0.5 µg/kg) and serum cortisol concentrations were measured 0, 0.25, 0.5, 1 and 2 h post injection. At 5.5 months of age, offspring were also challenged with 400 ng/kg of LPS, and serum cortisol concentrations were measured 0, 2, 4 and 6 h post challenge. Interestingly, female offspring born to FM+LPS mothers had a greater cortisol response to weaning and endotoxin challenge compared with the other treatments, while female offspring born to SM+LPS mothers had a faster cortisol response to the ACTH stressor. Additionally, males born to FM+LPS mothers had a greater cortisol response to the ACTH challenge than the other treatments. Overall, FM supplementation during gestation combined with LPS challenge alters HPAA responsiveness of the offspring into adulthood.

Fetal programming of the neuroendocrine-immune system and metabolic disease.

Adverse uterine environments experienced during fetal development can alter the projected growth pattern of various organs and systems of the body, leaving the offspring at an increased risk of metabolic disease. The thrifty phenotype hypothesis has been demonstrated as an alteration to the growth trajectory to improve the survival and reproductive fitness of the individual. However, when the intrauterine environment does not match the extrauterine environment problems can arise. With the increase in metabolic diseases in both Westernized and developing countries, it is becoming apparent that there is an environmental disconnect with the extrauterine environment. Therefore, the focus of this paper will be to explore the effects of maternal malnutrition on the offspring's susceptibility to metabolic disorders such as obesity, cardiovascular disease, and diabetes with emphasis on programming of the neuroendocrine-immune system.

Comparative anatomy and phylogenetic distribution of the mammalian cecal appendix.

A recently improved understanding of gut immunity has merged with current thinking in biological and medical science, pointing to an apparent function of the mammalian cecal appendix as a safe-house for symbiotic gut microbes, preserving the flora during times of gastrointestinal infection in societies without modern medicine. This function is potentially a selective force for the evolution and maintenance of the appendix, and provides an impetus for reassessment of the evolution of the appendix. A comparative anatomical approach reveals three apparent morphotypes of the cecal appendix, as well as appendix-like structures in some species that lack a true cecal appendix. Cladistic analyses indicate that the appendix has evolved independently at least twice (at least once in diprotodont marsupials and at least once in Euarchontoglires), shows a highly significant (P < 0.0001) phylogenetic signal in its distribution, and has been maintained in mammalian evolution for 80 million years or longer.

The primate appendix: a reassessment.

The presence of a vermiform appendix is often cited as a shared, derived character uniting the Hominoidea (apes and humans). However, appendix-like structures have been reported for many other primate taxa. A review of the literature reveals that the confusion arises because several different, and sometimes contradictory, criteria are enlisted to distinguish an appendix. The measures most frequently used to define this structure are gross shape and certain aspects of histology (e.g., lymphoid concentration). Unfortunately, descriptions of shape lack quantification, and histological thin-sections have not been studied for many primate taxa. In addition, although lymphoid concentration in the human appendix is known to vary considerably with age, this information is rarely reported in the primate literature. Given these complications, additional studies on the morphology and ontogeny of this region are warranted. This research will lead to a more accurate definition of the vermiform appendix. Most authors currently describe this feature as a narrow diverticulum of the cecum with thick walls and concentrated lymphoid tissue. However, the presence of thick mucosal layers and appreciable lymphoid tissue in taxa lacking appendices (e. g., Saguinus, Cercocebus) suggests that these features may be primitive primate traits. If so, wall thickness and lymphoid concentration cannot be used to define the vermiform appendix. These results suggest that a more rigorous definition of the appendix is requisite for this feature to be used in primate systematics.

Prognostic value of myocardial perfusion imaging in patients with high exercise tolerance.

BACKGROUND: Although high exercise tolerance is associated with an excellent prognosis, the significance of abnormal myocardial perfusion imaging (MPI) in patients with high exercise tolerance has not been established. This study retrospectively compares the utility of MPI and exercise ECG (EECG) in these patients. METHODS AND RESULTS: Of 388 consecutive patients who underwent exercise MPI and reached at least Bruce stage IV, 157 (40.5%) had abnormal results and 231 (59.5%) had normal results. Follow-up was performed at 18+/-2.7 months. Adverse events, including revascularization, myocardial infarction, and cardiac death, occurred in 40 patients. Nineteen patients had revascularization related to the MPI results or the patient's condition at the time of MPI and were not included in further analysis. Seventeen patients (12.2%) with abnormal MPI and 4 (1.7%) with normal MPI had adverse cardiac events (P<0.001). Cox proportional-hazards regression analysis showed that MPI was an excellent predictor of cardiac events (global chi2=13.2; P<0.001; relative risk=8; 95% CI=3 to 23) but EECG had no predictive power (global chi2=0.05; P=0.8; relative risk=1; 95% CI=0.4 to 3.0). The addition of Duke's treadmill score risk categories did not improve the predictive power of EECG (global chi2=0.17). The predictive power of the combination of EECG (including Duke score categories) and MPI was no better than that of MPI alone (global chi2=13.5). CONCLUSIONS: Unlike EECG, MPI is an excellent prognostic indicator for adverse cardiac events in patients with known or suspected CAD and high exercise tolerance.

Neural networks in ventilation-perfusion imaging.

PURPOSE: To optimize the performance of artificial neural networks in the prediction of pulmonary embolism from ventilation-perfusion (V-P) scans. MATERIALS AND METHODS: Neural networks were constructed with a set of V-P scan criteria that included sharpness and completeness of perfusion defects and involved quantification of abnormalities by using a continuous numeric scale. Several network parameters were systematically varied. Networks were trained with 150 cases and tested with 30 different cases. Findings were compared with those of pulmonary angiography. RESULTS: Networks capable of performing as well as experienced nuclear medicine physicians could be constructed with few V-P scan features. A brief training period was optimal (50-100 iterations). Further training diminished network performance. CONCLUSION: Effective neural networks can be constructed by using a limited number of unconventional V-P scan features. Several parameters can be adjusted to optimize performance.

Neural networks in ventilation-perfusion imaging. Part II. Effects of interpretive variability.

PURPOSE: To evaluate the usefulness of a neural network developed by one physician and used by another. MATERIALS AND METHODS: Intra- and interobserver variability were analyzed in image categorization of ventilation-perfusion (V-P) scans. This information was used to estimate network performance when it was used by a physician who did not train the network. RESULTS: Network training was optimized by using input parameters that demonstrated both individually high correlations with pulmonary embolism and good reproducibility in multiple interpretations. CONCLUSION: Potential variability exists in the performance of a network when it is supplied with input data by different physicians. The clinical usefulness of a network depends heavily on the similarity of interpretive styles between the network trainer and the user.

Epidemiology and etiology of leukemia.

New clinical and epidemiologic studies provide information about the possible causes of human leukemia. Evidence for a viral etiology continues to appear, and the relationship between myelodysplastic syndrome and the leukemias is now linked through molecular genetic studies. Molecular mechanisms of leukemogenesis are being understood through evaluation of preleukemic conditions and predisposing medical illnesses. Epipodophyllotoxins and, to a lesser extent, cisplatin are being linked causally to secondary leukemia. Potential environmental causes of leukemia are being intensively investigated with both positive and negative results. The literature on the epidemiology of leukemia is growing rapidly, and important leads toward a more complete understanding of its etiology are emerging.

Recognition and management of delayed disruption vesicourethral anastomosis in radical prostatectomy.

We describe 2 cases of delayed disruption of the vesicourethral anastomosis after radical retropubic prostatectomy. Diagnosis was established by fluoroscopic examination. Cystoscopic fixation of a catheter intravesically with suprapubic monofilament suture through the dome of the bladder proved to be the key to resolution of the problem.

The evolution of defective and autonomous parvoviruses.

Because of the small size and genetic simplicity of small DNA viruses, parvoviruses would appear to be excellent models for studying viral evolution and adaptation. In an earlier publication we hypothesized the evolution of sequences of cellular "junk" DNA into protective interfering transposons. These transposons would interfere with invading pathogenic viruses by competing with the pathogen DNA for replicative enzymes. We speculated that a small, defective parvovirus, the adeno-associated virus (AAV), which usually requires the presence of a pathogenic helper virus to replicate, may have evolved from such a piece of cellular "junk" DNA. Our theory predicted that AAVs, as a consequence of their defective nature, developed under pressures favoring maintenance of their transposon like qualities. In contrast, disease-causing, autonomous, non-defective parvoviruses such as the B19 agent of humans and the canine parvovirus, even though their origins may have been in cellular DNA, would appear to have developed under totally different evolutionary pressures. In this paper we will present evidence for a common ancestry for the defective and autonomous parvoviruses and discuss the divergent paths this evolution may have taken in establishing the two genera.

Properties and distribution of single voltage-gated calcium channels in adult hippocampal neurons.

1. The properties of single voltage-gated calcium channels were investigated in acutely exposed CA3 and CA1 pyramidal neurons and granule cells of area dentata in the adult guinea pig hippocampal formation. 2. Guinea pig hippocampal slices were prepared in a conventional manner, then treated with proteolytic enzymes and gently shaken to expose the somata of the three cell types studied. Standard patch-clamp techniques were used to record current flow through calcium channels in cell-attached membrane patches with isotonic barium as the charge carrier. 3. Single-channel current amplitudes were measured at different membrane potentials. Single-channel current-voltage plots were constructed and single-channel slope conductances were found to fall into three classes. These were (approximately) 8, 14, and 25 pS, and were observed in all three cell types. 4. The three groups of channels differed from each other in voltage dependence of activation: from a holding potential of -80, the small-conductance channel began to activate at about -40 to -30 mV, the medium-conductance channel at about -20 mV, and the large-conductance channel at approximately 0 mV. 5. Ensemble averages of single-channel currents during voltage steps revealed differences in voltage-dependent inactivation. The small-conductance channel inactivated completely within approximately 50 ms during steps from -80 to -10 mV or more positive. Steps to less positive potentials resulted in less inactivation. The medium-conductance channel displayed variable inactivation during steps from -80 to 0 mV. Inactivation of this channel during a 160-ms step ranged from virtually zero to approximately 100%. The large-conductance channel displayed no significant inactivation during steps as long as 400 ms. 6. The large-conductance channel was strikingly affected by the dihydropyridine agonist Bay K8644 (0.5-2.0 microM), resulting in a high probability of channel opening, prolonged openings, and an apparent increase in the number of channels available for activation. The medium and small-conductance channels were not noticeably affected by the drug. 7. The large-conductance channel could be induced to open at very negative membrane potentials by holding the patch for several seconds at 20 or 30 mV and stepping to -30 or -40 mV. This process was enhanced by Bay K8644, resulting in prolonged openings at potentials as negative as -100 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Evolution of a defective virus from a cellular defense mechanism.

Adeno-associated virus is a defective DNA virus, requiring the presence of a helper virus in order to replicate. In this paper we consider its origin in light of several observations, most notably the following: its own replication inhibits that of the helper virus; its DNA structure resembles that of transposable (moveable) elements; and extrachromosomal circles of DNA, about the size of adeno-associated virus DNA, have been found recently in eukaryotic cells. We have arrived at a hypothesis consisting of two main ideas: (1) that cells may use transposable DNA as a mechanism of defense against viral attack, and (2) that adeno-associated virus may have evolved directly from this cellular defense mechanism.