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Vertical profiles of aerosols, NO2, and SO2 were retrieved from Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) measurements at a field site in northern Alberta, Canada, during August and September 2013. The site is approximately 16 km north of two mining operations that are major sources of industrial pollution in the Athabasca oil sands region. Pollution conditions during the study ranged from atmospheric background conditions to heavily polluted with elevated plumes, according to the meteorology. This study aimed to evaluate the performance of the aerosol and trace gas retrievals through comparison with data from a suite of other instruments. Comparisons of aerosol optical depths (AODs) from MAX-DOAS aerosol retrievals, lidar vertical profiles of aerosol extinction, and the AERONET sun photometer indicate good performance by the MAX-DOAS retrievals. These comparisons and modelling of the lidar S ratio highlight the need for accurate knowledge of the temporal variation in the S ratio when comparing MAX-DOAS and lidar data. Comparisons of MAX-DOAS NO2 and SO2 retrievals to Pandora spectral sun photometer vertical column densities (VCDs) and active DOAS mixing ratios indicate good performance of the retrievals, except when vertical profiles of pollutants within the boundary layer varied rapidly, temporally, and spatially. Near-surface retrievals tended to overestimate active DOAS mixing ratios. The MAX-DOAS observed elevated pollution plumes not observed by the active DOAS, highlighting one of the instrument's main advantages. Aircraft measurements of SO2 were used to validate retrieved vertical profiles of SO2. Advantages of the MAX-DOAS instrument include increasing sensitivity towards the surface and the ability to simultaneously retrieve vertical profiles of aerosols and trace gases without requiring additional parameters, such as the S ratio. This complex dataset provided a rare opportunity to evaluate the performance of the MAX-DOAS retrievals under varying atmospheric conditions.

Aircraft-based lidar measurements of atmospheric aerosol and ozone were conducted to study air pollution from the oil sands extraction industry in northern Alberta. Significant amounts of aerosol were observed in the polluted air within the surface boundary layer, up to heights of 1 to 1.6 km above ground. The ozone mixing ratio measured in the polluted boundary layer air directly above the oil sands industry was equal to or less than the background ozone mixing ratio. On one of the flights, the lidar measurements detected a layer of forest fire smoke above the surface boundary layer in which the ozone mixing ratio was substantially greater than the background. Measurements of the linear depolarization ratio in the aerosol backscatter were obtained with a ground-based lidar and this aided in the discrimination between the separate emission sources from industry and forest fires. The retrieval of ozone abundance from the lidar measurements required the development of a method to account for the interference from the substantial aerosol content within the polluted boundary layer.

Introduction Lower gastrointestinal bleeds (LGIB) are defined by having a bleeding point in the gastrointestinal tract beyond the ligament of Treitz. The most common causes include diverticular bleeds, tumours, and colitis. There are no National Institute for Health and Care Excellence (NICE) guidelines regarding safe discharge of patients with LGIB. The aim of this study was to investigate the effectiveness and safety of the Oakland score, as suggested by the British Society of Gastroenterology (BSG) guidelines, in patients presenting with LGIB at William Harvey Hospital. Methods Patients with LGIB who presented to Accident & Emergency or inpatient referral from January to December 2023 were included in this retrospective study. Data was extracted from patients' Sunrise documentation. The Oakland score for each patient was calculated. Those with a score of ≤8 were deemed safe for discharge; those with a higher score were deemed unsuitable. Patients' admission, discharges, and adverse outcomes, such as representation, blood transfusion, or further intervention, were investigated. Patients with no adverse outcomes were deemed to have had a safe discharge. The area under the receiver-operating characteristic curve (AUROC) for the Oakland score and adverse outcome (and therefore safe discharge) were calculated. Results A total of 123 patients were included. These led to a total of 144 LGIB presentations to the hospital. Twenty-nine patients had an Oakland score of ≤8; 21 (72.4%) cases were initially discharged with four representations (19.0%) and eight (27.6%) were admitted although none of these suffered from any adverse outcomes. For those who scored ≤8, 25 (86.2%) were therefore deemed to have had a safe discharge. A total of 115 had a score >8; 43 (37.4%) were initially discharged, 72 (62.6%) admitted and 41 (35.7%) experienced at least one adverse outcome including 16 (13.9%) representations, 21 (18.3%) blood transfusions, three (2.6%) surgical interventions and one (0.9%) endoscopic haemostasis. Out of the 115 cases which scored >8, 74 (64.3%) were deemed to have had a safe discharge. The AUROC for safe discharge was 0.84. Conclusion The Oakland score seems to be a safe and reliable tool for identifying LGIB patients who could be safely discharged home without hospital intervention. However, further research is required to assess whether a score of >8 could be used as many patients with a higher score did not experience adverse outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Whiteway et al.)

We present water vapor vertical distributions on Mars retrieved from 3.5 years of solar occultation measurements by Nadir and Occultation for Mars Discovery onboard the ExoMars Trace Gas Orbiter, which reveal a strong contrast between aphelion and perihelion water climates. In equinox periods, most of water vapor is confined into the low-middle latitudes. In aphelion periods, water vapor sublimated from the northern polar cap is confined into very low altitudes-water vapor mixing ratios observed at the 0-5 km lower boundary of measurement decrease by an order of magnitude at the approximate altitudes of 15 and 30 km for the latitudes higher than 50°N and 30-50°N, respectively. The vertical confinement of water vapor at northern middle latitudes around aphelion is more pronounced in the morning terminators than evening, perhaps controlled by the diurnal cycle of cloud formation. Water vapor is also observed over the low latitude regions in the aphelion southern hemisphere (0-30°S) mostly below 10-20 km, which suggests north-south transport of water still occurs. In perihelion periods, water vapor sublimated from the southern polar cap directly reaches high altitudes (>80 km) over high southern latitudes, suggesting more effective transport by the meridional circulation without condensation. We show that heating during perihelion, sporadic global dust storms, and regional dust storms occurring annually around 330° of solar longitude ( L S ) are the main events to supply water vapor to the upper atmosphere above 70 km., (© 2022. The Authors.)

Global dust storms on Mars are rare 1,2 but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere 3 , primarily owing to solar heating of the dust 3 . In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars 4 . Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes 5,6 , as well as a decrease in the water column at low latitudes 7,8 . Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H 2 O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H 2 O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals 3 . The observed changes in H 2 O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere.

Background: Our objective was to analyse variation in non-metastatic prostate cancer management in the Northern and Yorkshire region of England., Methods: We included 21,334 men aged > or = 55, diagnosed between 2000 and 2006. Principal treatment received was categorised into radical prostatectomy (11%), brachytherapy (2%), external beam radiotherapy (16%), hormone therapy (42%) and no treatment (29%)., Results: The odds ratio (OR) for receiving a radical prostatectomy was 1.53 in 2006 compared with 2000 (95% CI 1.26-1.86), whereas the OR for receiving hormone therapy was 0.57 (0.51-0.64). Age was strongly associated with treatment received; radical treatments were significantly less likely in men aged > or = 75 compared with men aged 55-64 years, whereas the odds of receiving hormone therapy or no treatment were significantly higher in the older age group. The OR for receiving radical prostatectomy, brachytherapy or external beam radiotherapy were all significantly lower in the most deprived areas when compared with the most affluent (0.64 (0.55-0.75), 0.32 (0.22-0.47) and 0.83 (0.74-0.94), respectively) whereas the OR for receiving hormone therapy was 1.56 (1.42-1.71)., Conclusions: This study highlights the variation and inequalities that exist in the management of non-metastatic prostate cancer in the Northern and Yorkshire region of England.

We have characterized 202 lacI(-) mutations, and 158 dominant lacI(-d) mutations following treatment of Escherichia coli strains NR6112 and EE125 with 1-nitroso-6-nitropyrene (1,6-NONP), an activated metabolite of the carcinogen 1,6-dinitropyrene. In all, 91% of the induced point mutations occurred at G:C residues. The -(G:C) frameshifts were the dominant mutational class in the lacI(-) collections of both NR6112 and EE125, and in the lacI(-d) collection of NR6112. Frameshift mutations occurred preferentially in runs of guanine residues, and their frequency increased with the length of the reiterated sequence. In strain EE125, which contained the plasmid pKM101, there was a marked stimulation in the frequency of base substitution mutations that was particularly apparent in the lacI(-d) collection. This study completes a comprehensive analysis of 1194 lacI(-) and 348 lacI(-d) mutations induced by either 1,6-NONP or its positional isomer 1-nitroso-8-nitropyrene (1,8-NONP) in strains of E. coli that differ with regard to their ability to carry out nucleotide excision repair and/or their ability to express the translesion synthesis DNA polymerase RI (MucAB) encoded by plasmid pKM101. Among the mutations are 763 frameshift mutations, 367 base substitutions and 47 deletions; these mutations have been characterized at more than 300 distinct sites in the lacI gene. Our studies provide detailed insight into the DNA sequence alterations and mutational mechanisms associated with dinitropyrene mutagenesis. We review the mutational spectra, and discuss cellular lesion repair or tolerance mechanisms that modulate the observed mutational specificity.

Nitroheterocyclic and nitroaromatic compounds constitute an enormous range of chemicals whose potent biological activity has significant human health and environmental implications. The biological activity of nitro-substituted compounds is derived from reductive metabolism of the nitro moiety, a process catalyzed by a variety of nitroreductase activities. Resistance of bacteria to nitro-substituted compounds is believed to result primarily from mutations in genes encoding oxygen-insensitive nitroreductases. We have characterized the nfsA and nfsB genes of a large number of nitrofuran-resistant mutants of Escherichia coli and have correlated mutation with cell extract nitroreductase activity. Our studies demonstrate that first-step resistance to furazolidone or nitrofurazone results from an nfsA mutation, while the increased resistance associated with second-step mutants is a consequence of an nfsB mutation. Inferences made from mutation about the structure-function relationships of NfsA and NfsB are discussed, especially with regard to the identification of flavin mononucleotide binding sites. We show that expression of plasmid-carried nfsA and nfsB genes in resistant mutants restores sensitivity to nitrofurans. Among the 20 first-step and 53 second-step mutants isolated in this study, 65 and 49%, respectively, contained insertion sequence elements in nfsA and nfsB. IS1 integrated in both genes, while IS30 and IS186 were found only in nfsA and IS2 and IS5 were observed only in nfsB. Insertion hot spots for IS30 and IS186 are indicated in nfsA, and a hot spot for IS5 insertion is evident in nfsB. We discuss potential regional and sequence-specific determinants for insertion sequence element integration in nfsA and nfsB.

We have examined the mutational specificity of 1-nitroso-6-nitropyrene (1,6-NONP), an activated metabolite of the carcinogen 1,6-dinitropyrene, in the lacI gene of Escherichia coli strains which are deficient in nucleotide excision repair (strain NR6113, delta uvrB; strain CM6114, delta uvrB, plasmid pKM101). Separate collections of lacI- mutations and dominant lacI-d mutations, which contain DNA sequence alterations in the region of the lacI gene that encodes the DNA binding domain of the lacI repressor, were made following 1,6-NONP treatment. The DNA sequence of 418 mutations was determined, of which 228 were lacI- mutations and 190 were lacI-d mutations. Ninety three percent of the induced point mutations occurred at G:C residues.0 -(G:C) frameshifts were the dominant mutational class in the lacI- collections of both NR6113 and CM6114, and in the lacI-d collection of NR6113. The frameshift mutations occurred preferentially in runs of guanine residues and their frequency increased markedly with the length of the reiterated sequence. In strain CM6114, which contained the plasmid pKM101, there was a marked stimulation in the frequency of G:C-->T:A transversions that was particularly apparent in the lacI-d collection. We discuss models which might account for the apparent differences in mutational specificity resulting from the presence of the UmuD/C and MucA/B proteins. The results suggest that major classes of mutation are recovered in both the lacI- and lacI-d collections. However, the proportions of the major classes of mutations within the two collections can differ significantly. Depending on the genetic background of the host strain, the relative ratios of base substitutions to frameshift mutations in the lacI-d target can differ by almost an order of magnitude as compared with the lacI- target. This is primarily a function of the relative mutational target size of the different classes of mutation.

Selection of patients with ulcerating rectal cancer for treatment by local excision has been governed by a policy based on clinical and histological criteria; if these criteria are not fulfilled, major resection is recommended. This policy was re-examined in three groups of patients treated by local excision: Group 1 for cure (27 patients), Group 2 due to unfitness for major surgery (13 patients), Group 3 for local tumour control in the presence of metastatic disease (6 patients). When the policy was fulfilled, there was a cancer-specific death rate of 8.3 per cent in Group 1 (two patients with poorly differentiated tumours) and 0 per cent in Group 2. Unavoidable policy breaches occurred when patients refused major surgery or were too unfit: in the latter elderly group, this did not have the adverse effect expected. It is concluded that pre-operative clinical digital assessment and histological grading are a satisfactory means of identifying a small group of tumours appropriate for local treatment and that the results justify local excision where the policy is observed.

Diverticular disease of the sigmoid colon is an increasingly common clinical problem in the ageing population of western industrialised countries but the mechanism by which the disease develops remains unknown. The muscular abnormality is the most striking and consistent feature and this has been studied by light and electron microscopy in 25 surgical specimens of uncomplicated diverticular disease and in 25 controls. This is the first ultrastructural study of human colonic muscle to be published and shows that the muscle cells in diverticular disease are normal; neither hypertrophy nor hyperplasia is present. There is, however, an increase in the elastin content of the taeniae coli by greater than 200% compared with controls: elastin is laid down between the muscle cells and the normal fascicular pattern of the taeniae coli is distorted. There is no alteration in the elastin content of the circular muscle. As elastin is laid down in a contracted form, this elastosis may be responsible for the shortening or 'contracture' of the taeniae which in turn leads to the characteristic concertina-like corrugation of the circular muscle. Such a structural change could explain the altered behaviour of the colon wall in diverticular disease and its failure to change on treatment with bran.

The correlation of increased incidence of diverticular disease with age is well documented. Such a correlation results from the development of a structural change in the taeniae coli, a progressive elastosis. The consequences of this elastosis are a shortening of the taeniae coli and a subsequent change in the circular muscle layer secondary to this. This type of structural alteration takes time to develop and thus explains the time lag experienced between a change in diet and an altered incidence of the disease. Eastwood et al (1982) have suggested that diverticular disease is merely a normal concomitant of ageing which is degenerative in nature. However, the changes in structure in this condition appear to be dynamic, being associated with an altered intraluminal environment. Such a concept is crucial to our understanding of the pathology of ageing in general. Atherogenesis is associated with muscle cell hypertrophy, another dynamic change, which also leads to elastin formation. This suggests that treatment of such conditions should not just be limited to the control of an inevitable deterioration but should be directed to the investigation of the stimuli that may trigger such conditions. For example, it is interesting to speculate exactly when the changes that lead to diverticular disease begin: not only is a high fibre diet eaten in Africa, but breast-feeding may continue until the age of two years. The greatest increase in thickness in the normal colon occurs in this period and it may be that early weaning distorts this proliferation. The initiating factor in the aetiology of elastogenesis could be the small stools produced on a 'Western' diet which only intermittently distend the colon. Arterial smooth muscle cells increase their uptake of elastin precursors (particularly proline) when subjected to intermittent distension (Leung et al, 1976) and this may form a common link in the changes generated in vascular and colonic muscle tissue with time. This type of change is independent of alterations in motility and thus explains why asymptomatic patients have a normal motility index (Weinreich and Anderson, 1976). The muscular thickening in uncomplicated diverticular disease can therefore be explained in terms of elastosis and contracture of the taeniae coli in the presence of normal muscle cells. This does not exclude the possibility that hypertrophy and hyperplasia of these cells can develop in response to subsequent pericolic inflammation and fibrosis.