VI‐RADS followed by Photodynamic Transurethral Resection of Non‐Muscle‐Invasive Bladder Cancer vs White‐Light Conventional and Second‐resection: the ‘CUT‐ less ’ Randomised Trial Protocol

Background A second transurethral resection of bladder tumour (Re‐TURBT) is recommended by European Association of Urology (EAU) Guidelines on non‐muscle‐invasive bladder cancers (NMIBCs) due to the risk of understaging and/or persistent disease following the primary resection. However, in many cases this may be unnecessary, potentially harmful, and significantly expensive constituting overtreatment. The CUT‐ less trial aims to combine the preoperative staging accuracy of Vesical Imaging‐Reporting and Data System (VI‐RADS) and the intraoperative enhanced ability of photodynamic diagnosis (PDD) to overcome the primary TURBT pitfalls thus potentially re‐defining criteria for Re‐TURBT indications. Study Design Single‐centre, non‐inferiority, phase IV, open‐label, randomised controlled trial with 1:1 ratio. Endpoints The primary endpoint is short‐term BC recurrence between the study arms to assess whether patients preoperatively categorised as VI‐RADS Score 1 and/or Score 2 (i.e., very‐low and low likelihood of MIBC) could safely avoid Re‐TURBT by undergoing primary PDD‐TURBT. Secondary endpoints include mid‐ and long‐term BC recurrences and progression (i–ii). Also, health‐related quality of life (HRQoL) outcomes (iii) and health‐economic cost–benefit analysis (iv) will be performed. Patients and Methods All patients will undergo preoperative Multiparametric Magnetic Resonance Imaging of the bladder with VI‐RADS score determination. A total of 327 patients with intermediate‐/high‐risk NMIBCs, candidate for Re‐TURBT according to EAU Guidelines, will be enrolled over a 3‐year period. Participants will be randomised (1:1 ratio) to either standard of care (SoC), comprising primary white‐light (WL) TURBT followed by second WL Re‐TURBT; or the Experimental arm, comprising primary PDD‐TURBT and omitting Re‐TURBT. Both groups will receive adjuvant intravesical therapy and surveillance according to risk‐adjusted schedules. Measure of the primary outcome will be the relative proportion of BC recurrences between the SoC and Experimental arms within 4.5 months (i.e., any ‘early’ recurrence detected at first follow‐up cystoscopy). Secondary outcomes measures will be the relative proportion of late BC recurrences and/or BC progression detected after 4.5 months follow‐up. Additionally, we will compute the HRQoL variation from NMIBC questionnaires modelled over a patient lifetime horizon and the health‐economic analyses including a short‐term cost–benefit assessment of incremental costs per Re‐TURBT avoided and a longer‐term cost‐utility per quality‐adjusted life year gained using 2‐year clinical outcomes to drive a lifetime model across the two arms of treatment. Trial Registration ClinicalTrial.gov identifier (ID): NCT05962541; European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) ID: 2023‐507307‐64‐00.

Residents surgical training using metrics for transurethral resection of bladder tumours

Socioeconomic disparities in prostate cancer screening: the impact of the Area Deprivation Index on PSA screening frequency

Objective To investigate the impact of the Area Deprivation Index (ADI) on prostate‐specific antigen (PSA) screening patterns in a North American cohort, as the influence of neighbourhood socioeconomic disadvantage on prostate cancer screening intensity has been scantly analysed. Patients and Methods We included all men receiving care in Henry Ford Health System, aged 50–69 years and without previous prostate cancer diagnosis at the 31 December 2022. Each patient was assigned an ADI score based on their census block group, categorised into quartiles, with the fourth quartile (Q4, ADI 75–100) representing the most disadvantaged areas. The screening rate was calculated as the total number of PSA tests divided by the number of years patients were aged 50 years and older. Multivariable Poisson regression analysis tested the ADI's influence on screening rate. Results Among the 266 203 patients initially included, 75 958 patients had at least one PSA test at our institution. Overall, 20.9% were non‐Hispanic Black. Patients in the most disadvantage quartile (Q4) were more likely to be non‐Hispanic Black ( P  < 0.001), had higher comorbidity rates ( P  < 0.001) and lower probability of receiving two or more PSA tests ( P  < 0.001) compared to the ones in the least disadvantaged quartile (first quartile [Q1]). At Poisson regression analysis, when compared to patients in Q4, patients from Q1, and the second and third quartile had a 1.87‐, 1.70‐, and 1.52‐fold higher probability of receiving screening, respectively ( P  < 0.001). Conclusions Living in more deprived areas was associated with lower rates of PSA screening frequency. These findings highlight how socioeconomic deprivation may limit access to preventive healthcare, reinforcing the need for more inclusive and targeted outreach strategies.

Non‐breeding social behaviour as an investment in reducing future territoriality costs

ABSTRACT Territoriality is costly, and animals should adopt strategies to cope with these costs. Seasonal territoriality for breeding – a common strategy in many groups of animals – can reduce costs during the non‐breeding season but requires establishing new territories every breeding season. Many seasonal breeders also become more tolerant of conspecifics during the non‐breeding season and form social groups containing many individuals. Recent evidence has suggested that these social associations are not random and can entail carry‐over effects extending into the following breeding season. Here, we propose that one strategy that seasonal, territorial breeders may employ is to use non‐breeding social behaviour to reduce future breeding territoriality costs, through a dear‐enemy‐like effect. Specifically, by being social during the non‐breeding season with previous territorial neighbours, individuals can increase both their and their neighbour's survival, and jointly defend and exploit common territorial areas, ultimately reducing neighbourhood turnover. Reduced neighbourhood turnover can then facilitate re‐forming prior territorial boundaries, thereby offsetting the costs of territory establishment and facilitating earlier breeding (which can significantly increase reproductive output). We review evidence supporting our hypothesis and provide predictions and future research directions to bridge current gaps in understanding the link between non‐breeding social behaviours and breeding territoriality.

Effects of Smoking on Macrophage Polarization in Peri‐Implantitis Lesions

ABSTRACT Objectives The study aimed to investigate the relationship between cigarette smoking and macrophage polarization in peri‐implantitis (PI) lesions. Additionally, it sought to characterize clinical, radiological, microbiological, and immunological features of PI in smokers and non‐smokers. Materials and Methods A cross‐sectional study included 40 patients (20 smokers, ≥ 10 cigarettes/day, and 20 non‐smokers) requiring surgical treatment for PI. Samples of peri‐implant crevicular fluid (PICF) and granulation tissue were collected during surgery for immunofluorescence and cytokine analyses. Smoking exposure was assessed through cotinine levels. Macrophage polarization (M1/M2) was determined using immunofluorescence. Clinical, radiological, and microbiological parameters were also evaluated. Results Smokers showed a significantly higher proportion of M1 macrophages (70.23%) compared to non‐smokers (25.09%, p  < 0.005). This pro‐inflammatory shift correlated positively with cotinine levels ( ρ  = 0.694; p  < 0.005) and pack‐years ( ρ  = 0.81; p  < 0.005). No significant differences in M2 macrophage counts, cytokine concentrations, or microbiota diversity were observed between the groups. However, smokers exhibited more severe PI lesions ( p  = 0.04). Conclusions Smoking is associated with a pro‐inflammatory shift at the cellular level due to an increase in M1 macrophage polarization in PI lesions, suggesting a pro‐inflammatory response that may exacerbate tissue destruction and hinder treatment outcomes. These findings highlight the need for incorporating smoking cessation into comprehensive peri‐implant care strategies to improve disease management and implant prognosis.

Fairness Evaluation of Neural Networks Through Computational Profile Likelihood

ABSTRACT Despite high predictive performance, machine learning models can be unfair towards specific demographic subgroups characterized by sensitive attributes such as gender or race. This paper presents a novel approach using Computational Profile Likelihood (CPL) to assess potential bias in neural network decisions with respect to sensitive attributes. CPL estimates the conditional probability of a network's internal neuron excitation levels during predictions. To assess the impact of sensitive attributes on predictions, the CPL distribution of individuals sharing a particular value of a sensitive attribute and a specific outcome (e.g., “women” and “high income”) is compared to a subgroup sharing another value of the sensitive attribute but with the same outcome (e.g., “men” and “high income”). The resulting disparities between distributions can be used to quantify the bias with respect to the sensitive attribute and the outcome class. We also assess the efficacy of bias reduction techniques through their influence on the resulting disparities. Experimental results on three widely used datasets indicate that the CPL of the trained models can be used to characterize significant differences between multiple protected groups, highlighting that these models display quantifiable biases. Furthermore, after applying bias mitigation methods, the gaps in CPL distributions are reduced, indicating a more similar internal representation for profiles of different protected groups.

Board Independence and Bank Risk‐Taking: A Meta‐Analysis of the Role of Formal Institutions

ABSTRACT Research Question/Issue Although scholars drawing on the classic agency framework predict a positive relationship between board independence and bank risk‐taking, scholars adopting a contingency approach predict that such a relationship may not be positive. This theoretical debate is reflected in the inconclusive empirical evidence. In this study, building on the new institutional economics tradition, we go beyond a universal approach to our focal relationship and further advance a contingency approach to the agency framework. Research Findings/Insights In a retrospective meta‐analysis combining 81 primary studies from 2002 to 2022 that cover 106 countries, we find that the board independence–bank risk‐taking relationship is not universal but contingent on the institutional conditions facing the bank. Specifically, we find that our focal relationship is positively moderated by the level of depositor monitoring and negatively moderated by regulatory stringency. Moreover, we find that the effect of depositor monitoring is negatively moderated by regulatory stringency. Theoretical/Academic Implications Our study simultaneously relaxes two central assumptions of classic agency theory and shows that formal institutions, and in particular those protecting stakeholders' interests, can directly affect independent directors' efficacy as shareholder agents. We also point out the ability and incentives of independent directors to monitor in the interest of shareholders as the relevant causal mechanisms. Lastly, we add to research adopting a polycentric view of institutions and complement a burgeoning research stream examining corporate governance bundles. Practice/Policy Implications Our study adds to the debate among practitioners and policymakers on what constitutes good bank governance. It also intersects the debate on the relative merits of market and regulatory discipline in banking.

PET Beta‐Amyloid Tracer Uptake in Leukoencephalopathies: Comparing Metachromatic Leukodystrophy and CADASIL

Migration, the Archive, and the Map

ABSTRACT In recent years, archiving and countermapping have emerged as popular and powerful instruments to represent unauthorized migrations and criticize contemporary border regimes. This resulted in a variety of political projects involving academics, migrants, and advocacy groups, using archiving and mapmaking as vectors of dissensus and affirming politics. This parallel between maps and archives is not just a contemporary trend; it speaks to their longstanding relationship throughout political modernity, as well as the overlap between the archival and cartographic critiques over the past century. This article reviews contemporary projects that mobilize this nexus to challenge contemporary border regimes. In doing so, I direct attention to how their goals, methods, and designs align with different conceptual approaches to archives and maps. The analysis explores the contributions of geographic thought to this conceptual framework, and it encourages further reflection and participation from geographers in projects making political interventions through archival and countermapping methods.

Development and validation of a predictive score for diagnosing prostate cancer in primary care

Abstract Background Prostate cancer (PCa) represents the fifth cause of death in the male population worldwide. The prostate‐specific antigen (PSA) test demonstrated poor accuracy to assess the presence of PCa. Thus, the PSA testing paradigm should be moved from the systematic screening approach to the early identification of men who are harbouring clinically significant disease. Accurate clinical‐based tools to predict PCa should therefore be developed for general practice. We derived and validated a PCa predictive score using a primary care data source. Methods Using the Italian Health Search Database, we formed a cohort of men aged 45–90 years in the period between 2002 and 2015. These patients were followed up until 31 December 2022. Those with less than a 5‐year follow‐up were excluded. The cohort was randomly divided into ‘derivation’ and ‘validation’ samples in a 1:1 ratio. Along with the demographic and clinical determinants forming the score, we investigated the role of PSA kinetics in the prediction accuracy. Results In a cohort of 529,082 men aged 45+ years, we identified 14,524 cases of PCa (incidence rate = 2.71 per 1000 person‐years; 95% confidence interval = 2.67–2.80). The prediction accuracy of the PCa‐HScore featured an explained variation of 12% and a discrimination power of 70%. The calibration slope was almost equal to 1 ( p  = 0.951, tested for equivalence against the ‘perfect’ slope) and the PSA kinetics did not improve the prediction accuracy. Conclusions The PCa‐HScore might guide the prescription of PSA and/or other clinical strategies in those men reporting certain levels of risk. A related decision support system could therefore be implemented in primary care.