79 research outputs found

    Comparison of saturated areas mapping methods in the Jizera Mountains, Czech Republic

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    Understanding and modelling the processes of flood runoff generation is still a challenge in catchment hydrology. In particular, there are issues about how best to represent the effects of the antecedent state of saturation of a catchment on runoff formation and flood hydrographs. This paper reports on the experience of mapping saturated areas using measured water table by piezometers and more qualitative assessments of the state of the moisture at soil surface or immediately under it to provide information that can usefully condition model predictions. Vegetation patterns can also provide useful indicators of runoff source areas, but integrated over much longer periods of time. In this way, it might be more likely that models will get the right predictions for the right reasons

    Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

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    Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention

    Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

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    Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

    Crystallization and diffraction analysis of thioredoxin reductase from Streptomyces coelicolor

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    Thioredoxin reductases are homodimeric flavoenzymes that catalyze the transfer of electrons from NADPH to oxidized thioredoxin substrate. Bacterial thioredoxin reductases represent a promising target for the development of new antibiotics. Recombinant thioredoxin reductase TrxB from Streptomyces coelicolor was crystallized using the hanging-drop vapour-diffusion method. X-­ray diffraction data were collected from cryocooled crystals to 2.4 Å resolution using a synchrotron-radiation source. The crystals belonged to the primitive monoclinic space group P2(1), with unit-cell parameters a = 82.9, b = 60.6, c = 135.4 Å, α = γ = 90.0, β = 96.5°

    Fractionated dose of 60 Gy changes molecular response of HL-60 cells to irradiation

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    Objective: The cells of human promyelocyte leukaemia HL-60 lack functional protein p53 and react to ionizing radiation in doses up to 10 Gy by long cell cycle arrest in G2 phase, during which they repair radiation-induced DNA damage. Abrogation of G2 cell cycle arrest has radiosensitizing effect. In this work we evaluated changes in molecular response of HL-60-R cells (HL-60 irradiated by 10 cycles of radiation with total dose of 60 Gy, given over a period of 3 months) to irradiation by the dose of 2 and 8 Gy. Results: Both types of cells (HL-60 and HL-60-R) have high basal level of ERK1/2 phosphorylated on serine 202/204. This corresponds with their quick proliferation. Irradiation by the doses of 2 and 8 Gy induces decrease of ERK1/2 phosphorylation after 4 h in both cell types. However, after irradiation by the dose of 2 Gy in HL-60-R cells ERK1/2 phosphorylation is restored after 24 h, while in HL-60 cells the decrease is longer and ERK1/2 phosphorylation is restored only after 72 h. This may be related to different repair capacity, as the dose of 2 Gy is not lethal. This dose also induces in HL-60-R cells upregulation of cdk inhibitor p21, which is not detectable in HL-60 cells. Increased p21 is responsible for cell cycle arrest. On the other hand, in HL-60 cells the phosphorylation of check-point kinase 2 (chk-2) on threonine 68 occurs, while it is not observed in HL-60-R cells. Apoptosis induction by the dose of 8 Gy was lower in HL-60-R then in HL-60 cells. No difference in expression of anitiapoptotic mitochondrial protein Mcl-1 was found. Conclusion: In contrary to HL-60 cells, the HL-60 irradiated by 10 cycles of radiation with total dose of 60 Gy, given over a period of 3 months (HL-60-R) react to irradiation by p53 independent increase in p21, and not by activation of chk-2. Also kinetics of Erk1/2 phosphorylation is different in these cell types. HL-60-R are more resistant to radiation-induced apoptosis, but significant difference in D0 was not found (HL-60 2.5 Gy, HL-60-R 2.6 Gy). P21 might prevent apoptosis induction and trigger permanent cell-cycle arrest, which can also contribute to regression of this leukemia after therapy

    Structural insight into DNA recognition by bacterial transcriptional regulators of the SorC DeoR family

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    The SorC DeoR family is a large family of bacterial transcription regulators that are involved in the control of carbohydrate metabolism and quorum sensing. To understand the structural basis of DNA recognition, structural studies of two functionally characterized SorC DeoR family members from Bacillus subtilis were performed the deoxyribonucleoside regulator bsDeoR and the central glycolytic genes regulator bsCggR. Each selected protein represents one of the subgroups that are recognized within the family. Crystal structures were determined of the N terminal DNA binding domains of bsDeoR and bsCggR in complex with DNA duplexes representing the minimal operator sequence at resolutions of 2.3 and 2.1 amp; 8197; , respectively. While bsDeoRDBD contains a homeodomain like HTH type domain, bsCggRDBD contains a winged helix turn helix type motif. Both proteins form C2 symmetric dimers that recognize two consecutive major grooves, and the protein DNA interactions have been analyzed in detail. The crystal structures were used to model the interactions of the proteins with the full DNA operators, and a common mode of DNA recognition is proposed that is most likely to be shared by other members of the SorC DeoR famil

    Crystallization and diffraction analysis of the serpin IRS 2 from the hard tick Ixodes ricinus

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    IRS-2 from the hard tick Ixodes ricinus belongs to the serpin family of protease inhibitors. It is produced in the salivary glands of the tick and its anti-inflammatory activity suggests that it plays a role in parasite-host interaction. Recombinant IRS-2 prepared by heterologous expression in a bacterial system was crystallized using the hanging-drop vapour-diffusion method. The crystals belonged to the primitive tetragonal space group P4(3) and diffracted to 1.8 Å resolution. Mass-spectrometric and electrophoretic analyses revealed that IRS-2 was cleaved by contaminating proteases during crystallization. This processing of IRS-2 mimicked the specific cleavage of the serpin by its target protease and resulted in a more stable form (the so-called relaxed conformation), which produced well diffracting crystals. Activity profiling with specific substrates and inhibitors demonstrated traces of serine and cysteine proteases in the protein stock solution
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