Urban Evolution: The Role of Water

The structure, function, and services of urban ecosystems evolve over time scales from seconds to centuries as Earth’s population grows, infrastructure ages, and sociopolitical values alter them. In order to systematically study changes over time, the concept of “urban evolution” was proposed. It allows urban planning, management, and restoration to move beyond reactive management to predictive management based on past observations of consistent patterns. Here, we define and review a glossary of core concepts for studying urban evolution, which includes the mechanisms of urban selective pressure and urban adaptation. Urban selective pressure is an environmental or societal driver contributing to urban adaptation. Urban adaptation is thesequential process by which an urban structure, function, or services becomes more fitted to its changing environment or human choices. The role of water is vital to driving urban evolution as demonstrated by historical changes in drainage, sewage flows, hydrologic pulses, and long-term chemistry. In the current paper, we show how hydrologic traits evolve across successive generations of urban ecosystems via shifts in selective pressures and adaptations over time. We explore multiple empirical examples including evolving: (1) urban drainage from stream burial to stormwater management; (2) sewage flows and water quality in response to wastewater treatment; (3) amplification of hydrologic pulses due to the interaction between urbanization and climate variability; and (4) salinization and alkalinization of fresh water due to human inputs and accelerated weathering. Finally, we propose a new conceptual model for the evolution of urban waters from the Industrial Revolution to the present day based on empirical trends and historical information. Ultimately, we propose that water itself is a critical driver of urban evolution that forces urban adaptation, which transforms the structure, function, and services of urban landscapes, waterways, and civilizations over time

Local industrial strategy and skills policy in England: Assessing the linkages and limitations – a case study of the Sheffield City Deal

This paper examines changes in local economic development policy which occurred between 2010 and 2015, with a focus on the relationship between industrial strategy and skills policy. Under the Coalition Government, Local Enterprise Partnerships were established and tasked with facilitating local growth, and to do so many identified a set of (potential) growth sectors for industrial strategy to support. These sectors tended to be drawn from a relatively narrow range of industries which therefore often excluded a large proportion of the local economy. An important focus of the support for growth sectors for many has been through an ambition to influence the local skills system. Skills policy more broadly has been an important dimension of devolution, and a number of City Deals have included elements of skills policy. Echoing previous national policy however, the focus of local concerns with skills under devolution has been framed largely with reference to skills gaps and shortages. While specific skills gaps and shortages can be identified, this paper questions whether this default position is reflected widely, and as such, if a narrow focus on skills supply is a sufficient approach. It is argued that to support local growth across a broad base, greater attention needs to be paid to stimulating employer demand for skills through better integrating industrial and innovation policy with skills policymaking across a wider section of the local economy. To support these arguments we present a case study of the Sheffield City Deal

Analysis of multiple single nucleotide polymorphisms closely positioned in the ovine PRNP gene using linear fluorescent probes and melting curve analysis

<p>Abstract</p> <p>Background</p> <p>Resistance and susceptibility to scrapie has been associated with single nucleotide polymorphisms located within codons 136, 154 and 171 of the ovine prion protein gene (<it>PRNP</it>). Dual-labelled HyBeacon probes were developed to analyse single and clustered polymorphisms within these and neighbouring codons.</p> <p>Methods</p> <p>Extracted DNAs and unpurified blood samples were genotyped with respect to polymorphisms in <it>PRNP </it>codons 136, 141, 154 and 171. PCR amplicons were investigated using a LightTyper instrument, measuring the stability of probe/target hybridisation through peak melting temperatures and determining the sequence of nucleotides at polymorphic sites.</p> <p>Results</p> <p>The performance of HyBeacon assays was evaluated in a validation study comparing genotypes with those obtained using a primer extension assay (Sequenom MassEXTEND) analysed on a MALDI-ToF mass spectrometer. Over 12,000 sheep samples were successfully genotyped, reliably detecting A¹³⁶, V¹³⁶, T¹³⁶, T¹³⁷, L¹⁴¹, F¹⁴¹R¹⁵⁴, H¹⁵⁴, L¹⁶⁸, R¹⁷¹, Q¹⁷¹, H¹⁷¹and K¹⁷¹sequence variants using only 4 HyBeacon probes.</p> <p>Conclusion</p> <p>HyBeacon assays provide an extremely robust and accurate method for the analysis of single and clustered <it>PRNP </it>polymorphisms in a high-throughput format. The flexibility of the diagnostic tests ensures that samples are correctly genotyped even in the presence of additional sequence variations that flank the polymorphisms of interest. Such sequence variations may also be neutralised using universal bases such as 5-nitroindole if required.</p

Practice variation and outcomes of minimally invasive minor liver resections in patients with colorectal liver metastases:a population-based study

Introduction: In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM). Methods: This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan–Meier analysis on patients operated until 2018. Results: Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50–0.75, p &lt; 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50–0.67, p &lt; 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99–0.99, p &lt; 0.01), cardiac complications (aOR 0.29, CI:0.10–0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50–0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94–0.99, p &lt; 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21. Conclusion: Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery. Graphical abstract: [Figure not available: see fulltext.].</p

A nationwide assessment of hepatocellular adenoma resection:Indications and pathological discordance

Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs 50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size <50 mm (adjusted odds ratio [aOR], 3.4; p < 0.01), male sex (aOR, 3.7; p = 0.03), and lack of hepatobiliary contrast-enhanced magnetic resonance imaging (CE-MRI) (aOR, 1.8; p = 0.04). Resection for small (suspected) HCAs was mainly indicated by suspicion of (pre)malignancy, whereas for large (suspected) HCAs, tumor size was the most prevalent indication. Male sex, tumor size <50 mm, and lack of hepatobiliary CE-MRI were independent risk factors for postoperative change in tumor diagnosis

Trends and overall survival after combined liver resection and thermal ablation of colorectal liver metastases:a nationwide population-based propensity score-matched study

Background: In colorectal liver metastases (CRLM) patients, combination of liver resection and ablation permit a more parenchymal-sparing approach. This study assessed trends in use of combined resection and ablation, outcomes, and overall survival (OS). Methods: This population-based study included all CRLM patients who underwent liver resection between 2014 and 2022. To assess OS, data was linked to two databases containing date of death for patients treated between 2014 and 2018. Hospital variation in the use of combined minor liver resection and ablation versus major liver resection alone in patients with 2–3 CRLM and ≤3 cm was assessed. Propensity score matching (PSM) was applied to evaluate outcomes. Results: This study included 3593 patients, of whom 1336 (37.2%) underwent combined resection and ablation. Combined resection increased from 31.7% in 2014 to 47.9% in 2022. Significant hospital variation (range 5.9–53.8%) was observed in the use of combined minor liver resection and ablation. PSM resulted in 1005 patients in each group. Major morbidity was not different (11.6% vs. 5%, P = 1.00). Liver failure occurred less often after combined resection and ablation (1.9% vs. 0.6%, P = 0.017). Five-year OS rates were not different (39.3% vs. 33.9%, P = 0.145). Conclusion: Combined resection and ablation should be available and considered as an alternative to resection alone in any patient with multiple metastases.</p

Volume–outcome relationship of liver surgery: a nationwide analysis

Background: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. Methods: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien–Dindo grade IIIA or higher) and 30-day or in-hospital mortality. Results: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. Conclusion: Hospital volume and postoperative outcomes were not associated

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system