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The mining industry faces a period of increasingly difficult challenges over the next 30 years. The increasing demand for traditional mineral resources will likely continue unabated as developing countries modernize and the transition from fossil fuels to renewable energy sources ramps up. Compounding the challenge will be more rigorous constraints on mining imposed by environmental, social, and corporate governance (ESG) standards and regulations, as well as the progression from open-pit and shallow underground deposits to large, deeper, potentially lower-grade deposits, where underground mass mining methods are the only viable option. The latter change will especially apply to metals that are critical to mass electrification, including the traditionally required metals such as Cu, Ni, Co, Mn, Zn, U, etc. The more expensive-to-produce critical metals, such as Li, rare earths, high-purity alumina, etc., are currently only used in smaller quantities, and thus open-pit mining of these may remain viable until their near-surface resources are depleted. The large-scale mining of Cu, Ni, and Mo in particular will increasingly rely on cave mining methods, as these are the only profitable underground methods capable of yielding the large tonnages necessary to meet global demands, such as raising living standards within developing countries and providing the foundation for mass electrification of modern society, and all at a time when shallow deposits mined by open pit are becoming scarce. The application of cave mining is thus expected to increase in the future for deep mineral deposits with characteristics that are suited to this mining method. However, poor cave mine performance and/or unpredicted rock-mass responses (e.g., mine-induced seismicity) during cave mining can threaten the viability of the mine and will reduce investor confidence in this method. Irrespective of whether mining is of a traditional metal on a very large (mass) scale, or of a presently critical metal that now has lower tonnage requirements, we predict that geology will need to be more comprehensively considered during mine planning and design—right from the early stages of mine study—because of the uncertainties that the host rocks (geology) present to mining. This will be especially important in complying with the ESG constraints that are being applied to mining companies, in addition to the concept of sustainability that they also seek to address. We review—and propose remediation research of—the various geology-related issues that are already causing concern during mass underground mining by caving of Cu ore; some of these issues are equally applicable to other types of mining, such as open-pit and narrow-width extraction.

Context Differences of sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family, and developing a management plan are important. Objective We aimed to better understand the presentation and prevalence of pediatric DSD. Methods A retrospective, observational cohort study was undertaken in a single tertiary pediatric center of all children and young people (CYP) referred to a DSD multidisciplinary team over 25 years (1995-2019). In total, 607 CYP (520 regional referrals) were included. Data were analyzed for diagnosis, sex-assignment, age and mode of presentation, additional phenotypic features, mortality, and approximate point prevalence. Results Among the 3 major DSD categories, sex chromosome DSD was diagnosed in 11.2% (68/607) (most commonly 45,X/46,XY mosaicism), 46,XY DSD in 61.1% (371/607) (multiple diagnoses often with associated features), while 46,XX DSD occurred in 27.7% (168/607) (often 21-hydroxylase deficiency). Most children (80.1%) presented as neonates, usually with atypical genitalia, adrenal insufficiency, undescended testes or hernias. Those presenting later had diverse features. Rarely, the diagnosis was made antenatally (3.8%, n = 23) or following incidental karyotyping/family history (n = 14). Mortality was surprisingly high in 46,XY children, usually due to complex associated features (46,XY girls, 8.3%; 46,XY boys, 2.7%). The approximate point prevalence of neonatal referrals for investigation of DSD was 1 in 6347 births, and 1 in 5101 overall throughout childhood. Conclusion DSD represent a diverse range of conditions that can present at different ages. Pathways for expert diagnosis and management are important to optimize care.

Purpose Limited research exists about the knowledge that adult patients have about their congenital colorectal diagnosis. Methods This was an IRB approved, prospective study of patients in the Adult Colorectal Research Registry who completed surveys between October 2019 and March 2022. Surveys were administered through REDCap after patients consented to being contacted for research purposes. Patients provided demographic data, which was linked to surgical records, and the diagnoses provided by patients were compared with diagnoses recorded by the original surgeons. Results One hundred and thirty-one questionnaires were collected, 115 patients had anorectal malformations (ARM) and 16 had Hirschsprung disease (HD). Seven patients who had ARM were unaware that they had an ARM or HD. The type of ARM recorded by the surgeon was unavailable for comparison with the patient's reported diagnosis in four cases. Of the 111 remaining patients with ARM, only 32 of them (29%) knew what their own type of anomaly was. Female patients recalled their diagnosis more often than male patients (42.4% versus 13.5%). All 16 participants with HD correctly identified their diagnosis severity as HD with or without Total Colonic Aganglionosis. Conclusion The results of this study demonstrate patients’ limited understanding of their type of ARM and highlight the urgent need to enhance communication and education strategies, such as issuing patients with medical diagnosis identification cards. It is critical for clinicians to better communicate with patients to ensure that they and their relatives truly understand their precise diagnosis. Better informed patients should be better able to advocate for themselves, adhere to treatments and precautionary recommendations, navigate the complexities of transitional care, and more effectively manage lifelong complications.

Long-term urinary outcomes for patients born with Hirschsprung disease (HD) and anorectal malformations (ARM) may impact their health and wellbeing into adulthood. This study describes self-reported long-term urinary outcomes in males with HD and ARM.This was a prospective study of male patients in the Adult Colorectal Research Registry who completed surveys on urinary function between October 2019 and March 2022. Self-reported health and functional outcomes were summarized, and differences based on type of condition were compared.Sixty-seven patients completed the questionnaire (response rate: 59.1%), of which 17.9% (12) had HD and 82.1% (55) had an ARM. Rates of urinary incontinence and stress urinary incontinence were 16.4% (11) and 4.5% (3), respectively. On sub-analysis of patients with ARM, patients with sacral ratio (SR) of 0.4-0.69 reported higher UTI rates compared to those with SR ≥ 0.7 (57.9 vs 25.8%, p = 0.023). Renal failure rates were highest among patients with recto-bladder neck fistulas (66.0%, p = 0.012).Patients with HD and ARM report a variety of urological sequelae in adulthood. Outcomes appear to be more common in patients with ARM and may be impacted by both anatomy and sacral ratios. Transitional care to monitor and manage renal and urological function is imperative.

The long-term impact of anorectal malformations (ARM) and Hirschsprung disease (HD) on sexual function is well recognized but understudied. This study evaluated self-reported sexual and fertility outcomes in adult males with ARM and HD.This was an IRB approved, prospective study of males in the Adult Colorectal Research Registry who completed surveys between October 2019 and March 2022. Electronic surveys were administered after consenting to being contacted for research. Patients completed the International Index of Erectile Function (IIEF) questionnaire and provided information on fertility outcomes.Sixty-five patients completed outcome questionnaires: 11 (16.9%) had HD and 54 (83.1%) had an ARM. Nineteen patients reported some degree of erectile dysfunction per IIEF criteria, a greater proportion of whom have ARM (p = 0.046). Twenty (30.7%) have reported having children; there were no differences in rates between HD and ARM patients. Most patients had not attempted to conceive, but eight patients, all of whom have ARM, have pursued fertility investigation or treatments.More patients with ARM reported some degree of erectile dysfunction compared to those with HD. Additionally, some have required fertility treatments. Further investigation is warranted to ensure true low rates of sexual and fertility dysfunction in patients with HD.

Little is known about fertility and pregnancy outcomes in patients with anorectal malformations (ARM), particularly those with long common channel cloaca and cloacal exstrophy who may have impaired fertility. The purpose of this study is to describe pregnancy and offspring data from a cohort of patients with ARM.A retrospective review of female patients with ARM from our database, which includes patients operated on since 1980, was performed as well as a review of the literature. Demographic, operative, and self-reported fertility, obstetric, and offspring data were collected.There were 37 females identified in our database who reported any pregnancy or having children. There were 59 pregnancies, 48 (81.3%) of which resulted in live birth. The most common mode of delivery was cesarean delivery. There were five patients with long channel cloaca (3 cm) and one with cloacal exstrophy that reported 11 total pregnancies, eight of which resulted in live birth. Four cloaca patients in which the native vagina was pulled through were able to conceive spontaneously. Three patients with cloacal anomalies required in vitro fertilization to conceive; one was unsuccessful. No patients who underwent bowel partial vaginal replacement became pregnant. Women with ARM face many unique challenges in assisted reproduction, pregnancy, and delivery owing to their anatomy and associated anomalies.Women with recto-perineal, recto-vestibular, and cloacas in which the native vagina was pulled through are capable of spontaneous pregnancy. Assisted reproduction, however, may be needed those with more complex anomalies and surgical repairs.IV.

Initial management of pediatric patients with neurogenic bladder is focused on clean intermittent catheterization and medical therapies. Those with more hostile or small capacity bladders require surgical intervention including bladder augmentation that can result in significant clinical sequelae. This study examines a rarely described approach wherein the bladder reconstruction is extraperitonealized by bringing bowel segments through a peritoneal window and then closed.The aim of this study was to determine if the rate of bladder rupture and subsequent morbidity differed between patients who have undergone an intraperitoneal versus extraperitoneal bladder augmentation. We hypothesized that an extraperitoneal approach reduced the risk of intraperitoneal bladder perforation, downstream Intensive Care Unit (ICU) admission, small bowel obstruction (SBO) requiring exploratory laparotomy, and ventriculoperitoneal (VP) shunt-related difficulties as compared to the standard intraperitoneal technique.A retrospective chart review was conducted to assess surgical approach and outcomes in patients who underwent bladder augmentation performed between January 2009 and June 2021. Patients were identified through an existing database and manual chart review was conducted to extract data through imaging studies, operative notes, and clinical documentation. The primary outcome was bladder perforation. Secondary outcomes were ICU admission, exploratory laparotomy, and VP shunt externalization, infection, or revision for any cause. Nonparametric statistical analyses were performed.A total of 111 patients underwent bladder augmentation with 37 intraperitoneal and 74 extraperitoneal procedures. Median follow up was 5.8 years [IQR 3.0-8.6 years] and did not vary between groups (P = 0.67). Only one patient was found to have a bladder perforation in the intraperitoneal group (log-rank P = 0.154). There were no significant differences in time to post-augmentation ICU admission, exploratory laparotomy, or VP shunt events between the two groups (log-rank P = 0.294, log-rank P = 0.832, and log-rank P = 0.237, respectively). Furthermore, a Kaplan-Meier analysis assessing time to composite complication demonstrated no significant difference between the two techniques (log-rank P = 0.236).This study provides important data comparing the rate of bladder perforation and subsequent morbidity between intraperitoneal and extraperitoneal bladder augmentation. As expected, with a complex procedure, both groups suffered complications, but these data showed no difference between the two procedures. Rates of prior (abdominal) surgery may influence the decision to perform this procedure extraperitoneal.Outcomes related to bladder perforation and secondary consequences do not differ significantly between patients who had bladder augmentation performed with an intraperitoneal versus extraperitoneal approach. Given the low number of adverse events in this study, larger studies are warranted.

Introduction Bladder exstrophy and epispadias complex (BEEC) is a spectrum of congenital malformations ranging from an isolated epispadias to a full exstrophy. It is an uncommon disease and little is known on how patients cope with its implications later in life. Objective The goal of this study is to assess the sexual, continence and fertility outcomes of BEEC patients, who had reconstructive bladder surgery during childhood. Considering the sensitive nature of these topics, they are not easily spoken about in the doctor's office. Our aim is to shed some light on possible points of improvement in follow-up. Study design 63 patients between 18 and 45 years old were sent an electronic questionnaire based on previous existing standardized questionnaires. They were asked about sexual and psychosexual wellbeing, urinary incontinence and fertility. Data from their medical files (medical history on previous surgeries). and questionnaire answers are linked through an anonymous subject number and put into an Excel file for descriptive representation. Results 22 men and 8 women filled in the questionnaire. All but 2 are sexually active. Reasons to avoid sexual activity are equally divided as BEEC-related and non-BEEC-related. Sexual satisfaction is lower in the male group due to problems with erection, ejaculation, condom usage and embarrassment about physical appearance. In females problems concerning pain and reaching orgasm are mentioned. 30% report depressive feelings. There is a clear correlation between number of reconstructive surgeries and sexual satisfaction. 90% of patients urinate via catheterization, mostly through a Mitrofanoff connection. This leads to complications such as foul odors, infection, embarrassment and sexual dysfunction. 8 out of 13 men conceived a child (with the use of their own sperm), 2 out of 4 women did. Discussion A strength of this study is the use of standardized questionnaires which allow comparison to a control patient group. Our study is one of the first to show how patients cope with the challenges of BEEC by the use of open questions. We see an overall high quality of life yet an important impact on mental health. Conclusion BEEC is associated with many challenges in the adult life of patients. A more holistic and interdisciplinary approach is needed to include sensitive topics in long term follow-up.

Aims To investigate the role of onabotulinumtoxinA (BTX-A) injections in patients with failed augmentation cystoplasty for neuropathic or idiopathic detrusor overactivity (NDO or IDO). Methods A retrospective review of all cystoplasty patients who underwent onabotulinumtoxinA injection at a tertiary center between 2008 and 2019 was performed. Details including indications and time from cystoplasty, video-urodynamic parameters, onabotulinumtoxinA dose, and clinical outcomes were analyzed. Telephone interview was performed for patients that requested repeat onabotulinumtoxinA injections. The interview included a modified PGIC7 and UDI6 questionnaires. A positive clinical response was considered improvement of overactive symptoms sufficient to merit repeat onabotulinumtoxinA injection and a modified PGIC7 of four or above. Results Thirty patients were identified (11 men and 19 women). The indications for augmentation were IDO (n = 18) or NDO (n = 12). Mean age at the time of cystoplasty was 42 years (range, 10-61). Interval between cystoplasty and initial onabotulinumtoxinA was 98 months (range, 3-271). Video-urodynamics before onabotulinumtoxinA revealed low compliance in 13 patients, DO in 22 patients, and combined low compliance/DO in 10. The median maximum cystometric bladder capacity was 338 mL (range, 77-570 mL). Thirteen patients responded to onabotulinumtoxinA injections. Higher peak DO pressure was associated with a significantly higher chance that the patient would experience benefit from the injections P = .026). The patients that responded to onabotulinumtoxin A underwent a total of 115 procedures (mean, 8.8 injections) over a mean 88 months (range, 20-157 months). Conclusions Forty-three percent of patients responded well to intra-detrusor onabotulinumtoxinA injections. This avoided the need for more invasive surgery and had a positive impact on their quality of life.

Improved medical care throughout childhood and adolescence has enabled patients with complex urological abnormalities to live longer into adulthood. These patients are now at risk of developing common, age-related, urological conditions. This review aims to review existing data and make recommendations in areas where expert opinion is currently lacking METHODS: This review represents the joint SIU-ICUD (Société Internationale d'Urologie-International Consultation on Urological Disease) consultation on congenital lifelong urology. The results of this analysis were first presented at a joint consultation of the ICUD and SIU at the 2018 SIU annual conference in Seoul, South Korea.BPH may present differently in patients with neurogenic bladder. Thorough assessment of neurological status, bladder and sphincter function is required before offering any bladder outlet surgery. Prostate specific antigen screening should be offered to men aged 50-69 with neurogenic bladders if they have good life expectancy. Multi-parametric MRI and transperineal biopsy would be the investigations of choice if feasible. Surgery for localized disease should only be done by surgeons with the relevant expertise. Bladder cancer in this patient group is more likely to present at a later stage and have a worse prognosis. Parenthood is achievable for most, but often requires assistance with conception. Pregnant women who have had previous urogenital reconstructive surgery should be managed in appropriate obstetric units with the involvement of a reconstructive urologist.Most evidence regarding complex urogenital abnormalities comes from the pediatric population. Evidence regarding common, age-related urological issues is generally from the 'normal' adult population. As patients with complex congenital urological conditions live longer, more data will become available to assess the long-term benefits of intervention.

Background: The bladder exstrophy epispadias complex (BEEC) is a rare disorder characterised by a number of genito-urinary abnormalities. The condition and subsequent treatment may result in lasting effects on continence, renal function and fertility. There are equally important psychosocial and psychosexual effects as part of overall long-term quality of life. The literature consists largely of small studies with variable methodology; this study aims to consolidate these data. Methods: This study reviews the available literature sourced from the Medline database using the keywords listed below. Results: Patients appear to be high achievers with good overall health-related quality of life. Most form close personal friendships although express anxiety related to revelation of their condition. Data suggest the majority of patients are able to engage in and be satisfied with sexual intercourse. Fertility may be adversely affected, but this can usually be overcome with assisted reproductive techniques and specialist input during pregnancy and delivery. Conclusions: Psychosocial and psychosexual outcomes in patients with BEEC may be excellent. Therefore careful transition and psychological support combined with long-term follow-up is important to allow these patients to maximise their quality of life. Level of evidence: Not applicable.

Background and ObjectivesBladder tumours are rare in young patients. Consequently, the literature is sparse and studies provide con-flicting reports on clinicopathological data and patient outcomes. This study examines, to our knowledge, the largest UK series of patients aged less than 40 years diagnosed with bladder cancer, and examines their risks and outcomes.Material and MethodsA prospectively recorded database (2008-2018) was used to identify patients aged under 40 years diagnosed with bladder cancer. Data were retrospectively analyzed. Patients were then sub-divided into 2 groups based on age: group 1 was aged below 20 years and group 2 was aged 20–39 years.ResultsA total of 27 patients were identified with a median age of 34 years (range 14–39). Male to female ratio was 2.86:1. Median follow-up was 41.5 months (range 3–108). 61.9% presented with visible hematuria and 54.2% had one or more risk factors such as cigarette smoking. A total of 96.3% of patients had urothelial carcinoma and 92.3% of these were non-muscle invasive tumours. 7.7% presented with muscle invasive disease with 3.8% having positive nodes at diagnosis. Patients with non-muscle invasive urothelial tumours were risk-stratified according to the EAU-Guidelines Panel risk grouping with 39.1% low-risk, 4.3% intermediate-risk and 56.5% high-risk of recurrence and/or progression. During follow-up 30.4% recurred and 4.3% progressed to invasive disease. 23.1% underwent cystectomy and overall 11.5% died during follow-up, all due to metastatic disease. Patients in group one showed a statistically significant incidence of lower-grade disease at diagnosis with lower risk-group stratification but there was no significant difference in other parameters.ConclusionThe majority of young patients in our series presented with non-muscle invasive urothelial bladder tumours but a significant proportion of these had high-risk disease. Some patients presented with aggressive, muscle invasive bladder cancer and consequently bladder cancer remains an important differential diagnosis in symptomatic patients regardless of age.

Posterior urethral valves (PUV) are the commonest cause of end-stage renal disease in children, but the genetic architecture of this rare disorder remains unknown. We performed a sequencing-based genome-wide association study (seqGWAS) in 132 unrelated male PUV cases and 23,727 controls of diverse ancestry, identifying statistically significant associations with common variants at 12q24.21 (p=7.8 × 10

Simple Summary Disorders of bladder function can result from congenital spinal cord developmental defects and can remain in a significant number of patients despite surgical improvements to repair the primary defect. We studied the ability of bladder wall muscle from such patients to contract, a function essential to void collected urine and avoid urinary tract infections and potential damage to the kidneys. Tissue was taken when patients were several years old, at the time of surgical operations to improve bladder function. This tissue would otherwise have been discarded and was collected with the full ethical approval and consent of parents or guardians. We found that the ability of the bladder wall samples to contract was impaired and was generally stiffer; both of which would make it more difficult for the bladder to void urine. These functional changes were associated with a replacement of muscle with connective tissue (fibrosis). The experiments provide a pathway to devise strategies that might improve bladder function in these patients through reversal of the intrinsic tissue pathways that increase fibrosis. Abstract Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients, urinary tract dysfunction remains and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders and any association with altered Wnt-signalling pathways that contribute to both foetal development and connective tissue deposition. A comparator group was tissue from children with normally functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions, and multiplex immunohistochemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling components except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. While we cannot speculate about the reasons for these pathophysiological changes, their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor.

Posterior urethral valves (PUV) are the commonest cause of end-stage renal disease in children, but the genetic architecture of this rare disorder remains largely unknown. We analyzed whole-genome sequencing (WGS) data from 132 unrelated PUV cases and 23,727 controls of mixed ancestry and identified statistically significant associations with common variants at 12q24.21 (P=7.8x10-12; OR 0.4) and rare variants at 6p21.1 (P=2x10-8; OR 7.2), that were replicated in an independent European cohort. Bayesian fine mapping and functional annotation mapped these loci to the transcription factor TBX5 and planar cell polarity gene PTK7, respectively, with the encoded proteins detected in the normal human developing urinary tract. These findings represent the first known genetic associations of PUV, providing novel insights into the underlying biology of this poorly understood disorder and demonstrate that a mixed ancestry WGS approach can increase power for disease locus discovery and facilitate fine-mapping of causal variants.

Disorders of sexual development are a complex group of conditions with anomalies of the internal and external genitalia due to abnormal chromosomal and hormonal influences during development. Diagnosis and management, including timing of intervention, and both long-term cosmetic and functional outcomes are discussed in this chapter.

Bladder exstrophy and epispadias are congenital anomalies of the urogenital tract with deformity of the genitals as well as the pelvis, abdominal wall, and bladder in exstrophy. Reconstruction of the anomalies is a complex process with the aims of restoring function and appearance. Fertility and management of pregnancy in the exstrophy patient are also discussed in this chapter.

Hypospadias is a common condition and familiar, though sometimes challenging territory for the pediatric urologist. This review is a summary of hypospadias incidence, epidemiology, surgery, research, and complications intended for the non-specialist. It outlines the history, the principles of surgery for hypospadias, and the long-term outcomes.

Crystallization, often as the final isolation and purification step in drug substance manufacturing, has substantial impact on downstream efficiency and final drug product quality. It is a critical but challenging step in developing end-to-end continuous manufacturing, which has been identified as an emerging technology in the pharmaceutical manufacturing sector by the U.S. Food and Drug Administration (FDA). A traditional stirred tank crystallizer (STC) operated as a mixed-suspension-mixed-product-removal (MSMPR) system is a popular choice for continuous crystallization for its utilization of existing knowledge and equipment. However, there are disadvantages associated with agitational systems like the STC, such as poor local mixing and high shear rate. A commercial dynamic baffle crystallizer (DBC) was studied here as an alternative unit operation. The DBC in this study consists of a jacketed glass vessel with dynamic ‘donut’ shaped baffles to provide oscillatory mixing to improve heat and mass transfer while exerting less shear. Our goal is to compare continuous operation performances in the DBC with the STC as MSMPR systems. First, residence time distribution (RTD) studies of both systems were performed considering single phase (liquid only) and two-phase (solid-liquid) operation. The RTD gives good insights into the mixing dynamics without computationally heavy fluid dynamic simulations. Continuous cooling crystallization of paracetamol was performed in the DBC and the STC. The DBC showed good potential to be used as an MSMPR system producing more uniform RTDs as well as higher quality crystallization products compared to a traditional STC.

Objectives To evaluate functional outcomes of surgery in patients with ectopic ureters diagnosed in adulthood; to review the world literature. Patients and methods Patients were referred over 10 years. Data including surgical history, presenting symptoms, diagnostic modalities, interventions and functional outcomes were collected; and the world literature reviewed. Results 9 women and 1 man had a mean age of 37 (range 20-58). All women were referred with lifelong leakage. The man was referred with storage LUTS. Three women had heminephrectomy/nephrectomy with the distal ureter left in-situ prior to referral. MRI was the predominant diagnostic tool but often took senior review to confirm the diagnosis. Excision of the ectopic ureter was performed with bladder neck reconstruction in 6 women, with concomitant rectus fascial sling in one patient. 4 of 6 (67%) women were cured of their stress incontinence with the bladder neck reconstruction alone, whilst two required further intervention. Three women had nephroureterectomy alone as primary treatment of which two were cured. The single male had heminephrectomy and excision of seminal vesicle. Conclusions Ectopic ureter is a rare diagnosis in adults but should be considered in patients who describe lifelong incontinence. Fine slice MRI is the imaging of choice. Excision of the ureter with bladder neck reconstruction alone was successful in two-thirds of patients, whilst further stress urinary incontinence surgery was required in one-third. Malignancy in ureteric remnants is described in 8% of the world literature. Patients should be counselled of this risk if the ureter is left in-situ.

Editor’s note: The Geology and Mining series, edited by Dan Wood and Jeffrey Hedenquist, is designed to introduce early-career professionals and students to a variety of topics in mineral exploration, development, and mining, in order to provide insight into the many ways in which geoscientists contribute to the mineral industry. Abstract For economic geologists, mineral exploration has a specific objective: the discovery of mineral concentrations that can be recovered economically to provide resources essential for society. This was achieved consistently until the first decade of the current century, but exploration since then has been wealth destructive. This outcome is a major issue for the mining industry unless reversed. We believe the technologies presently used to discover ore deposits will be as useful in making future discoveries as they were previously. However, we argue that a new approach is required in how exploration is conducted and in how these and emerging technologies are applied. The required changes in approach include improved business models for conducting exploration and acceptance that fewer deposits are likely to be discovered near the surface. We argue that discovery of deeper deposits will be facilitated if exploration teams (1) seek to identify subtle evidence of mineralized rock recognizable within 500 m of the surface, (2) conduct follow-up investigations with a clear understanding of the volumetric dimensions of the discovery target, and (3) drill boldly as a critical exploration tool. We propose that improving the way geoscientists think when exploring—being more predictive—is the immediate key to increasing the number of discoveries.

Postdevelopment studies show that, once in operation, about 70% of mines perform below the prediction of their feasibility studies, with underperformance usually caused by deficiencies in the collection of primarily geology related data prior to designing the mine and planning its operation. A major reason for these deficiencies is probably a generally narrow understanding by many geologists of metallurgy as well as geotechnical and mining engineering. Additionally, geologists often do not appreciate the types and quantities of data required by metallurgists, geotechnical engineers, and mining engineers for mine design, planning, and operations. Critically, there is commonly inadequate communication between all four professional groups. For obvious and logical reasons, the principal focus of geologists has generally been considered the discovery of a mineral deposit and subsequent resource definition and estimation of its grade and tonnage, leading to the creation of detailed geologic and grade models of the deposit. While grade and tonnage are cornerstones to mine development, equally important to mine design is the geotechnical model, which is constructed progressively over three stages of mining study using information obtained from four separate geology-related models. Enhanced understanding of mining and metallurgy by geologists plus appreciation of the metallurgical and mining uncertainties inherent in geologic data by metallurgists and geotechnical and mining engineers can contribute to significantly improved mining outcomes.

Background Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. Methods During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. Results 500 patients underwent surgery with median age 62.5 (IQR 51–71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. Conclusion It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration., Highlights • Priority surgeries are being cancelled every week due to the COVID-19 pandemic. • A multicentre surgical referral network was set up as part of an NHS England approach to continuing safe surgery • The referral network consisted of 14 NHS trusts and surgery was performed at a single COVID-19 ‘cold site’. • After 500 surgeries performed, there was a 0% 30-day mortality from COVID-19. • It is safe to continue cancer and priority surgery during the COVID-19 pandemic with appropriate service reconfiguration.

The BJU International paper by van de Grift and colleagues includes important data outlining the long-term cosmetic and functional outcomes for masculinizing surgery in patients born with differences in sex development. This overview highlights some of the important findings and their context in what can be a controversial subject.

Summary Introduction Posterior urethral valves (PUV) is the most common cause of congenital bladder outflow obstruction with persistent lower urinary tract and renal morbidities. There is a spectrum of functional bladder disorders ranging from hypertonia to bladder underactivity, but the aetiology of these clinical conditions remains unclear. Aims and objectives We tested the hypothesis that replacement of detrusor muscle with non-muscle cells and excessive deposition of connective tissue is an important factor in bladder dysfunction with PUV. We used isolated detrusor samples from children with PUV and undergoing primary or secondary procedures in comparison to age-matched data from children with functionally normal bladders. In vitro contractile properties, as well as passive stiffness, were measured and matched to histological assessment of muscle and connective tissue. We examined if a major pathway for fibrosis was altered in PUV tissue samples. Methods Isometric contractions were measured in vitro in response to either stimulation of motor nerves to detrusor or exposure to cholinergic and purinergic receptor agonists. Passive mechanical stiffness was measured by rapid stretching of the tissue and recording changes to muscle tension. Histology measured the relative amounts of detrusor muscle and connective tissue. Multiplex quantitative immunofluorescence labelling using five epitope markers was designed to determine cellular pathways, in particular the Wnt-signalling pathway, responsible for any changes to excessive deposition of connective tissue. Results and Discussion PUV tissue showed equally reduced contractile function to efferent nerve stimulation or exposure to contractile agonists. Passive muscle stiffness was increased in PUV tissue samples. The smooth muscle:connective tissue ratio was also diminished and mirrored the reduction of contractile function and the increase of passive stiffness. Immunofluorescence labelling showed in PUV samples increased expression of the matrix metalloproteinase, MMP-7; as well as cyclin-D1 expression suggesting cellular remodelling. However, elements of a fibrosis pathway associated with Wnt-signalling were either reduced (β-catenin) or unchanged (c-Myc). The accumulation of extracellular matrix, containing collagen, will contribute to the reduced contractile performance of the bladder wall. It will also increase tissue stiffness that in vivo would lead to reduced filling compliance. Conclusions Replacement of smooth muscle with fibrosis is a major contributory factor in contractile dysfunction in the hypertonic PUV bladder. This suggests that a potential strategy to restore normal contractile and filling properties is development of the effective use of antifibrotic agents. Download : Download high-res image (132KB) Download : Download full-size image Summary Figure .