Global Vertical Distribution of Water Vapor on Mars: Results From 3.5 Years of ExoMars-TGO/NOMAD Science Operations.

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.

Trends in non-metastatic prostate cancer management in the Northern and Yorkshire region of England, 2000-2006.

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.

H2O at the Phoenix landing site.

The Phoenix mission investigated patterned ground and weather in the northern arctic region of Mars for 5 months starting 25 May 2008 (solar longitude between 76.5 degrees and 148 degrees ). A shallow ice table was uncovered by the robotic arm in the center and edge of a nearby polygon at depths of 5 to 18 centimeters. In late summer, snowfall and frost blanketed the surface at night; H(2)O ice and vapor constantly interacted with the soil. The soil was alkaline (pH = 7.7) and contained CaCO(3), aqueous minerals, and salts up to several weight percent in the indurated surface soil. Their formation likely required the presence of water.

Mars water-ice clouds and precipitation.

The light detection and ranging instrument on the Phoenix mission observed water-ice clouds in the atmosphere of Mars that were similar to cirrus clouds on Earth. Fall streaks in the cloud structure traced the precipitation of ice crystals toward the ground. Measurements of atmospheric dust indicated that the planetary boundary layer (PBL) on Mars was well mixed, up to heights of around 4 kilometers, by the summer daytime turbulence and convection. The water-ice clouds were detected at the top of the PBL and near the ground each night in late summer after the air temperature started decreasing. The interpretation is that water vapor mixed upward by daytime turbulence and convection forms ice crystal clouds at night that precipitate back toward the surface.

Cellular determinants of the mutational specificity of 1-nitroso-6-nitropyrene and 1-nitroso-8-nitropyrene in the lacI gene of Escherichia coli.

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.

Oxygen-insensitive nitroreductases: analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli.

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.

The mutational specificity of 1-nitroso-6-nitropyrene in the lacI gene of Escherichia coli strains deficient in nucleotide excision repair.

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.

Correction for nonlinear photon-counting effects in lidar systems.

A useful analytic model describing the response of a photon-counting (PC) system has been developed. The model describes the nonlinear count loss and apparent count gain arising from the overlap of photomultiplier tube (PMT) pulses, taking into account the distribution in amplitude of the PMT output pulses and the effect of the pulse-height discrimination threshold. Comparisons between the model and Monte Carlo simulations show excellent agreement. The model has been applied to a PC lidar system with favorable results. Application of the model has permitted us to extend the linear operating range of the PC system and to quantify accurately the response of the system in its nonlinear operating regime, thus increasing the useful dynamic range of the system by 1 order of magnitude.

Assessment of the results of Stamey bladder neck suspension.

A total of 48 patients with genuine stress incontinence underwent endoscopic bladder neck suspension; 36 patients (75%) were completely cured of their incontinence but 12 (25%) suffered recurrent leakage. In 2 cases this was due to infection and erosion of the vaginal sutures; in 4 cases failure was ascribed to a small capacity bladder and "pipe-stem" urethra. In the remaining 6 unsuccessful cases the Stamey sutures had cut through flimsy endopelvic fascia. It was concluded that endoscopic bladder neck suspension has advantages over colposuspension in terms of reduced dissection and hospital stay, but its success rate is lower than originally reported. Failures due to suture infection and buttress displacement may be avoided by not using Dacron and, instead, by picking up vaginal subdermis with nylon sutures--the same tissue used to provide support in a Burch colposuspension.

Extracorporeal shock wave lithotripsy. Is sessional access worthwhile?

One hundred and fifty-three patients with renal stones referred to one teaching hospital have received extracorporeal shock wave lithotripsy (ESWL) treatment as a result of a monthly sessional arrangement organised with a neighbouring lithotripter unit. The results of treatment, assessed 3 months after lithotripsy, showed results comparable with those from any lithotripter centre. Sessional access for lithotripsy may provide a satisfactory way of increasing the number of patients who are treated with lithotripsy by reducing the demand for beds at the hospitals where a lithotripter is sited.

Practical aspects of endoscopic management of malignant polyps.

World experience now overwhelmingly supports the policy of conservative management by endoscopic snare polypectomy of "focal" cancer in polyps (malignancy in adenomas and polypoid carcinomas), providing that the polyp is pedunculated and that endoscopic and histological criteria are favorable. Invasion to within 2-3 mm of the snare-resection line is acceptable, providing that the advancing tumour margin is well-circumscribed. Unfavourable characteristics include poorly differential tumour, involvement of stalk vessels, and sessile configuration. This management policy applied to 90 patients between 1971 and 1981 resulted in successful 5-year follow-up of the 74 patients treated by polypectomy alone. Among the 16 patients managed surgically, no local lymph nodes were involved in any case, although 4 patients were found to have residual local tumour at the polypectomy site.

Pathology of the ageing--diverticular disease.

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.

The role of surgical local excision in the treatment of rectal cancer.

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.

Elastosis in diverticular disease of the sigmoid colon.

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.

Histopathology and prognosis of malignant colorectal polyps treated by endoscopic polypectomy.

The histopathological features and results of treatment of malignant polyps removed by endoscopic polypectomy from 60 patients are presented. The patients were followed for a minimum of five years. Forty six patients were treated by polypectomy alone as local excision was judged complete and the invasive carcinoma was well or moderately well differentiated. Thirty seven of these patients are alive and well after five years and the remaining nine have died of other causes up to four years later: there was no evidence of recurrence in any of these cases. Fourteen patients underwent a subsequent major surgical resection and residual tumour was found at the site of polypectomy in two cases but regional lymph nodes were not involved. Only one patient from this group with a high grade tumour developed metastases although the operative specimen was free of tumour. Malignant polyps can be successfully treated by polypectomy alone provided both the laboratory techniques of examination and the histopathological criteria are strictly applied.