Interactions between apparently ‘primary’ weather--‐driven hazards and their cost

A statistical analysis of the largest weather-driven hazards in the UK contradicts the typical view that each predominates in distinct events that do not interact with those of other hazard types (i.e., are 'primary'); this potentially has implications for any multi-hazard environments globally where some types of severe event are still thought to occur independently. By a first co-investigation of long (1884–2008) meteorological time-series and nationwide insurance losses for UK domestic houses (averaging £1.1 billion/yr), new systematic interactions within a 1 year timeframe are identified between temporally-distinct floods, winter wind storms, and shrink–swell subsidence events (P < 0.03); this increases costs by up to £0.3 billion/yr (i.e., 26%), although impacts will be spatially variable depending upon the interplay of hazards. 'Memory' required in the environmental system to cause these intra-annual links between event types appears to reside in soil moisture and, tentatively, sea surface temperatures. Similar, unidentified interactions between non-synchronous events are likely worldwide, and the analytical methods we have developed to identify and quantify them are suitable for application to meteorological, geological (e.g., volcanic) and cryospheric (e.g., avalanches) hazards

Mycobacterial immunotherapy for prostate cancer: where can we go from here?

The effects of mycobacteria in prostate cancer have not been fully elucidated. Results of early studies indicated that mycobacterial immunotherapy conferred a survival benefit in patients with advanced prostate cancer, and recent evidence supports the safety and efficacy of new mycobacterial agents in many malignancies; thus, modern, carefully designed, randomized controlled trials of mycobacterial immunotherapy for prostate cancer could be warranted

Isothermal microwave biology : catalysis and fermentation

This thesis looks directly into the controversial subject of the microwave field effect by the production of a versatile prototype isothermal microwave reactor for the investigation of enzymatic and microbiological reactions. The observed results from the prototype reactor and experiments conducted conclude that there is a nonthermal, nonlinear response between the exposure microwave power and rate and yield of cellulose saccharification. The nature of the nonthermal response is controversial and may be dependent on the definition of "nonthermal,' leading to ambiguity of exact mechanism. Enzymatic and microbial conversion of cellulosic material to ethanol is a highly desirable industrial process. Whether the demand is for the mitigation of climate change, political obligations or energy independence, the use of arable land for energy crops limits the available glucose carbon sources for conversion to bioproducts. To prevent this limitation, cellulose (~-l,4-linked glucose polymers) are touted as the "silver bullet" to prevent carbon exhaustion or impinging on food crops. The technical constraint for the industrialization of cellulose based processing is the rate limitation in the cellulase enzymatic action on cellulose. The enzyme rate is limited by feedback cycles and limited mechanical freedom, therefore a relatively high enzyme concentration is required to speed up the process. To date, the associated enzyme production costs and infrastructure prevents bulk volume exploitation. Biomolecular advances (amino acid substitutions, recombination of expression vectors etc) have gone some way to increase either enzymatic rate or enzyme concentration. The work presented in this thesis differs by increasing the rate of the enzyme without molecular modification. Using a microwave field, the work presented shows that by separating the system into its base units, irradiation of the enzyme/substrate complex in an aqueous environment can increase both the initial enzyme rate and the saccharification yield without alteration of the temperature set point. This study shows that the rate increase is not proportional to the microwave field power. An optimal power in each study is either found or suggested. The results cited show that in the three systems (Endoglucanase and cellobiohydrolase with cellulose, endoglucanase and cellobiohydrolase and ~- glucosidase with cellulose, and ~-glucosidase with cellobiose) the initial rates can be increased by 201 %, 65.5% and 69% respectively. In the total hydrolytic process (endoglucanase and cellobiohydrolase and ~-glucosidase on a cellulose substrate) the final glucose yield was increased by 43% in comparison to the conventional thermal control reaction. This is shown in Figure 1. 10.000 1 9.000 1 8.000 j 7.000 6.000 o 20 40 60 80 100 120 140 160 180 I I 1 I U 5.000 r:: o u 4.000 3.000 2.000 j i t t , f 1.000 0.000 Time (hours) =->=OOOW Glucose' ?012W Glucose ?p025W Glucose ~050W Glucose ?075W Glucose Figure 1. Microwave irradiated "cellulase" enzymes with cellulose substrate I For development into an industrial system and looking towards simultaneous saccharification and fermentation (SSF), the yeast Saccharomyces cerevisiae was subjected to irradiated microwave fermentations on a glucose substrate. Although inconclusive in terms of rate increase, cell density 1 was comparable across the power range showing that the irradiation does not have a derogatory effect. ! The natural evolution of the conclusions drawn would be development of the system into a SSF or SSCF configuration for bio-product formation is possible with irradiation up to SOW. ii The novelty of the experiments conducted is twofold. Firstly, the reactor has been designed to ensure that the microwave irradiation is independent of the bulk temperature therefore allowing the exploration of the microwave field effect independently to the thermal effect. Secondly, the microwave source is a continuous microwave irradiation (none pulse irradiation) ensuring that the reaction is subjected to the microwave field for the entire reaction

Tumour growth rates of prostate cancer during active surveillance: is there a difference between MRI-visible low and intermediate-risk disease?

OBJECTIVES: The aim of this study was to evaluate the changes in lesion volume on serial multiparametric magnetic resonance (mpMRI) during active surveillance for prostate cancer. METHODS: A total of 160 patients with a targeted biopsy-confirmed visible lesion on mpMRI, stratified by low- and intermediate-risk disease (Gleason Grade Group 1 vs Gleason Grade Group 2), were analysed. The % change per year was calculated using the formula: [(final volume/initial volume) exp (1/interval between scans in years)]-1. RESULTS: There was no significant difference in the annual median percentage change between Gleason Grade Group 1 (18%) and Gleason Grade Group 2 (23%) disease (p = 0.16), and between ≤ 10% (23%) and > 10% (22%) of Gleason pattern 4 (p = 0.78).Assuming a spherical lesion, these changes corresponded to annual increases in mean tumour diameter of 6% and 7% for Gleason Grade Group 1 and Gleason Grade Group 2 respectively, which may be less than the interscan variability of serial mpMRI. CONCLUSION: In an active surveillance cohort, we did not see a significant difference in the annual growth rate of Gleason Grade Group 1 and 2 tumours. ADVANCES IN KNOWLEDGE: In patients on active surveillance, the measured growth rates for visible tumours in Gleason Grade Groups 1 and 2 were similar. The annual growth rate was small in most cases and this may have implications for the MRI follow-up interval in active surveillance

Cellular senescence as a possible link between prostate diseases of the ageing male

Senescent cells accumulate with age in all tissues. Although senescent cells undergo cell-cycle arrest, these cells remain metabolically active and their secretome — known as the senescence-associated secretory phenotype — is responsible for a systemic pro-inflammatory state, which contributes to an inflammatory microenvironment. Senescent cells can be found in the ageing prostate and the senescence-associated secretory phenotype and can be linked to BPH and prostate cancer. Indeed, a number of signalling pathways provide biological plausibility for the role of senescence in both BPH and prostate cancer, although proving causality is difficult. The theory of senescence as a mechanism for prostate disease has a number of clinical implications and could offer opportunities for targeting in the future

Isolated bilateral simplex ureteric ectopia: Bladder capacity as an indicator of continence outcome

INTRODUCTION: Isolated bilateral simplex ectopic ureters (BSEUs) are rare but pose a therapeutic challenge: ureteric reimplantation alone does not accomplish continence in all. Identifying the patients needing additional procedures for continence early could prevent multiple operations. OBJECTIVE: Potential preoperative indicators for postoperative continence are explored in eight BSEU girls without cloacal, anorectal, or spinal anomalies. STUDY DESIGN: With institutional approval, all patients with BSEU between 1985 and 2012 were retrospectively reviewed. Cystoscopy determined the site of ureteric ectopia (6 of 16 at the bladder neck [BN], 5 of 16 below the BN, and 5 of 16 in the distal urethra). Bladders were assessed by a combination of ultrasound, urodynamics, micturating cystourethrogram, cystoscopic, and intraoperative observations. Expected bladder capacity for age (EBCA) was calculated by 30 ml + (30 ml × age in years) or 38 ml + (2.5 ml × age in months) for children greater or less than 2 years, respectively. Continence outcomes were appraised at a minimum of 4 years. The small number of patients precludes credible statistical analysis and therefore raw data are presented. RESULTS: Patients underwent cross-trigonal ureteric reimplantation at 1–5.5 years, in five without BN surgery and in three with a Young–Dees–Leadbetter BN tightening. Of those without BN surgery at reimplantation, four achieved satisfactory continence for their age, but one has had multiple procedures culminating in BN closure, ileocystoplasty, and Mitrofanoff. Among the BN-tightening group, one was in nappies at 4 years, one had residual stress incontinence after two further BN injections, and one proceeded to artificial urinary sphincter after two BN injections. Five patients had significant renal impairment. DISCUSSION: Patients with satisfactory continence after reimplantation alone and those needing further procedures tended to differ in their preoperative observations of bladder capacity and apparent BN competence. This study suggests preoperative observations of an empty bladder on serial ultrasound and/or a wide-open BN with small or even moderate bladder capacity at cystoscopy to indicate the need for BN surgery. In contrast, children with bladder filling to at least 30% of expected bladder capacity for age on preoperative ultrasound or apposition of the BN at cystoscopy may achieve satisfactory continence after ureteric reimplantation alone. Bladder capacity as an indicator of BN competence can also be correlated to continence outcomes in previously published series. Polyuria associated with renal impairment can exacerbate the challenge for continence. CONCLUSION: Preoperative bladder capacity appears to be an indicator of inherent BN function and a thorough assessment of the urinary tract by cystoscopy, ultrasound, micturating cystourethrogram, and functional imaging may guide the surgeon on the need for BN surgery at the time of ureteric reimplantation. Where continence remains elusive, patients should be counselled that a further BN injection is occasionally of value although more significant BN procedures are required for most

Prostate cancer measurements on serial MRI during active surveillance: it’s time to be PRECISE

OBJECTIVE: The PRECISE criteria for reporting multiparametric MRI in patients on active surveillance (AS) for prostate cancer (PCa) score the likelihood of clinically significant change over time using a 1-5 scale, where 4 or 5 indicates radiological progression. According to the PRECISE recommendations, the index lesion size can be reported using different definitions of volume (planimetry or ellipsoid formula) or by measuring one or two diameters. We compared different measurements using planimetry as the reference standard and stratified changes according to the PRECISE scores. METHODS: We retrospectively analysed 196 patients on AS with PCa confirmed by targeted biopsy who had two MR scans (baseline and follow-up). Lesions were measured on T2 weighted imaging (T2WI) according to all definitions. A PRECISE score was assessed for each patient. RESULTS: The ellipsoid formula exhibited the highest correlation with planimetry at baseline (ρ = 0.97) and follow-up (ρ = 0.98) imaging, compared to the biaxial measurement and single maximum diameter. There was a significant difference (p < 0.001) in the yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) for planimetry (39.64%) and for the ellipsoid formula (46.78%). CONCLUSION: The ellipsoid formula could be used to monitor tumour growth during AS. Evidence of a significant yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) has been also observed. ADVANCES IN KNOWLEDGE: The ellipsoid formula is a reasonable surrogate for planimetry in capturing tumour volume changes on T2WI in patients on imaging-led AS. This is also associated with radiological changes using the PRECISE recommendations