bluuebunny/crossref_metadata_2025 huggingface dataset:
Ondansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC)
Authors: Damkier Per , Kaplan Yusuf Cem , Shechtman Svetlana , Diav‐Citrin Orna , Cassina Matteo , Weber‐Schoendorfer Corinna
Published: December 2020

Ondansetron is an effective antiemetic that is being widely used as a second‐line treatment option for severe nausea and vomiting of pregnancy in accordance with clinical guidelines. The safety of ondansetron during pregnancy has—following publication of controversial and seemingly contradictory results—been subject to considerable academic turmoil, specifically with respect to the risk of congenital cardiac malformations and oral cleft. In July 2019, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) released an updated, comprehensive assessment report on the use of ondansetron in the first trimester. The ensuing Summary of Product Characteristics (SmPC) was updated in November 2019 with important changes to section on “Fertility, pregnancy and lactation.” The SmPC now states that ondansetron should not be used in the first trimester of pregnancy. ENTIS, The European Network of Teratology Information Services, believes that the implementation of this regulatory step—which has important clinical consequences—is insufficiently substantiated and is not serving the interest of pregnant women with severe nausea and vomiting. Herein, we discuss the underlying evidence and argue the case against the EMA decision.
Contemporary duration of spontaneous labor and association with maternal characteristics: A French national population‐based study
Authors: Girault Aude , Blondel Béatrice , Goffinet François , Le Ray Camille
Published: December 2020

Background

The objective of this study was to describe labor duration of women managed with current obstetric practices in a French national population‐based cohort and to assess the association of age and BMI on this duration.

Methods

All women in the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. Duration of labor was defined as time between admission to the labor ward and birth. Duration of total labor and first and second stage of labor were described. Then, duration of labor was estimated according to maternal age and BMI, using Kaplan‐Meier's method and compared with the log‐rank test after stratification on parity. Intrapartum cesarean birth was considered as a censoring event. Multivariable modeling was performed using Cox's proportional hazard's method.

Results

Data of 3120 nulliparous and 4385 multiparous women were analyzed. Median labor duration was 6.1 hours ([5th; 95th percentile]) [1.4; 12.6] and 3.1 hours [0.3; 8.5] in nulliparous and multiparous women. Multivariable Cox analysis showed no independent association of maternal age and duration of labor. Nulliparous obese women had significantly lower odds of having a shorter labor than women with a BMI < 25 kg/m2, HR: 0.75; 95% CI [0.64‐0.88], but BMI was not associated with labor duration in multiparous women.

Conclusions

Our study provides important information for both women and care practitioners on what to expect when entering the labor ward. There appears to be little association between maternal characteristics and labor duration, with the exception of BMI in nulliparous women.
Comparative effectiveness of neoadjuvant chemotherapy in bladder and upper urinary tract urothelial carcinoma
Authors: D’Andrea David , Matin Surena , Black Peter C. , Petros Firas G. , Zargar Homayoun , Dinney Colin P. , Cookson Michael S. , Kassouf Wassim , Dall'Era Marc A. , McGrath John S. , Wright Jonathan L. , Thorpe Andrew C. , Morgan Todd M. , Holzbeierlein Jeffrey M. , Bivalacqua Trinity J. , Sridhar Srikala S. , North Scott , Barocas Daniel A. , Lotan Yair , Stephenson Andrew J. , van Rhijn Bas W. , Spiess Philippe E. , Daneshmand Siamak , Shariat Shahrokh F.
Published: December 2020

Objective

To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery.

Patients and Methods

Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post‐treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0‐Ta‐Tis‐T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer‐specific survival (CSS) was evaluated using Cox regression analyses.

Results

A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27–0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89–2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64–0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49–0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45–0.82; P < 0.01), but not with OS.

Conclusions

Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.
Global Assessment of Urological Endoscopic Skills (GAUES): development and validation of a novel assessment tool to evaluate endourological skills
Authors: Biyani Chandra Shekhar , Kailavasan Mithun , Rukin Nicholas , Palit Victor , Somani Bhaskar , Jain Sunjay , Myatt Andy , Nabi Ghulam , Patterson Jake
Published: December 2020

Objective

To develop and evaluate an assessment tool for endourological skills during simulation including cystoscopy, ureteroscopy (URS) and transurethral resection (TUR) procedures.

Methods

We designed a Global Assessment of Urological Endoscopic Skills (GAUES) tool, comprised of nine endourology task‐specific and two global‐rating skills items. The tool was developed through two rounds of the Delphi process. The GAUES tool was used to assess acquisition of URS and TUR skills of novices (Year 2 core surgical trainees, CT2) and intermediate level trainees (residents at the start of the UK higher surgical training programme in Urology, Speciality Trainee Year 3, ST3) at the Urology Simulation Boot Camp (USBC) between 2016 and 2018. Validity was evaluated by comparing scores between trainees with different levels of urological experience. Inter‐rater reliability was also assessed.

Results

We evaluated 130 residents, 52% of trainees were at an intermediate stage of training and 39% were novices. In all, 9% of the anonymous forms were missing demographics. The completion rate of the GAUES tool during the USBC for URS and TUR was 85% and 89%, respectively. Our analysis demonstrated a significant difference in all domains between intermediates and novices at assessment in URS, except for one domain more suited to clinical assessment (P = 0.226). There was excellent intraclass correlation (ICC) overall between the two experts’ judgements, ICC = 0.841 (95% confidence interval 0.767–0.893; P < 0.001, n = 88).

Conclusions

We have developed the novel GAUES tool for cystoscopic, URS and TUR skills. Overall, we demonstrated good face, content and construct validity and excellent reliability, suggesting that the GAUES tool can be useful for endourological skills assessment.
Nephrometry scores: a validation of three systems for peri‐operative outcomes in retroperitoneal robot‐assisted partial nephrectomy
Authors: Crockett Matthew G. , Giona Simone , Whiting Danielle , Whitehurst Lily , Agag Ayman , Malki Manar , Hussain Muddassar , Barber Neil J.
Published: December 2020

Objective

To externally validate the RENAL, PADUA and SPARE nephrometry scoring systems for use in retroperitoneal robot‐assisted partial nephrectomy (RAPN).

Materials and Methods

Nephrometry scores were calculated for 322 consecutive patients receiving retroperitoneal RAPN at a tertiary referral centre from 2017. Patients with multiple tumours were excluded. Scores were correlated with peri‐operative outcomes, including the trifecta (warm ischaemia time <25 min, no peri‐operative complications and a negative surgical margin), both as continuous and categorical variables. Comparisons were performed using Spearman correlation and ability to predict the trifecta was assessed using binomial logistical regression.

Results

All three scoring systems correlated significantly with the main variables (operating time, warm ischaemia time and estimated blood loss), both as continuous and categorical variables. Only PADUA and SPARE were able to predict achievement of the trifecta (PADUA area under the curve [AUC] 0.623, 95% confidence interval [CI] 0.559–0.668; SPARE AUC 0.612, 95% CI 0.548–0.677).

Conclusion

This study validates the RENAL, PADUA and SPARE scoring systems to predict key intra‐operative outcomes in retroperitoneal RAPN. Only PADUA and SPARE were able to predict achievement of the trifecta. As a simplified version of the PADUA scoring system with comparable outcomes, we recommend using the SPARE system.
Holmium laser enucleation of the prostate using Moses 2.0 vs non‐Moses: a randomised controlled trial
Authors: Nevo Amihay , Faraj Kassem S. , Cheney Scott M. , Moore Jonathan P. , Stern Karen L. , Borofsky Michael , Gnessin Ehud , Humphreys Mitchell R.
Published: December 2020

Objectives

To compare the enucleation efficiency of Moses 2.0 with non‐Moses technology in patients undergoing holmium laser enucleation of the prostate (HoLEP).

Patients and Methods

A double‐blinded, randomised study of patients undergoing HoLEP at the Mayo Clinic in Arizona, using the Lumenis Pulse™ 120H laser system. Patients were randomised to either right lobe enucleation using Moses 2.0 and left lobe enucleation using non‐Moses, or the opposite. The primary outcome was individual lobe enucleation efficiency. Secondary outcomes included individual lobe laser time, laser energy, individual enucleation and haemostasis laser energies, and fibre burn back. Two independent reviewers watched videos of the procedures and provided a subjective evaluation of the technologies.

Results

A total of 27 patients were included in the study. For the entire cohort, Moses 2.0 had less fibre degradation (3.5 vs 16.8 mm, P < 0.01) compared to non‐Moses. When HoLEP procedures were performed by an expert, Moses 2.0 resulted in shorter enucleation time (21 vs 36.7 min, P = 0.016) and higher enucleation efficiency (1.75 vs 1.05 g/min, P = 0.05) compared to non‐Moses. When HoLEP was performed by trainees, the Moses 2.0 cohort had a shorter haemostasis laser time (4.1 vs 9 min, P = 0.035) compared to the non‐Moses. Fibre degradation was lower with Moses 2.0 compared to non‐Moses for both experts and trainees. Moses 2.0 received a higher score than the standard technology for the incision sharpness, fibre control, tissue separation, tissue damage, haemostasis, visibility, and charring. The overall inter‐observer correlation coefficient was 0.63.

Conclusion

Moses 2.0 has higher enucleation efficiency compared to non‐Moses when used by experts. The subjective evaluation favoured Moses 2.0.
The rising worldwide impact of benign prostatic hyperplasia
Authors: Launer Bryn M. , McVary Kevin T. , Ricke William A. , Lloyd Granville L.
Published: December 2020

Objectives

To describe the trend in the impact of lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH) on a global scale using the Global Burden of Disease (GBD) database.

Materials and Methods

Using the GBD database, worldwide data aggregated from registries and health systems from 1990 to 2017 were filtered for LUTS/BPH diagnoses. Calculation of years lived with disability (YLD) were compared with other urological diseases. YLD were calculated by a standardized method using assigned disability weights. The GBD‐defined sociodemographic index (SDI) was used to assess impact of LUTS/BPH by global SDI quintile.

Results

Global Burden of Disease data over the 1990–2017 study period were summarized and global numbers and trends noted with other urological diseases for comparison. A total of 2 427 334 YLD were attributed to BPH in 2017 alone, almost three times more than those attributed to the next highest urological disease, prostate cancer (843 227 YLD). When stratified by SDI quintile, a much lower impact of BPH was found in the bottom three quintiles, despite this subset representing 66.9% of the 2017 world population.

Conclusions

Lower urinary tract symptoms attributed to benign prostatic hyperplasia exert a rapidly rising human burden far exceeding other urological diseases. As the population ages and men in a lower SDI enjoy increased life expectancy and decreased competing mortalities, a continually accelerating wave of LUTS/BPH can be forecast. These epidemiological trends have serious implications for the future allocation of resources and the global urological workforce.
Management of patients who opt for radical prostatectomy during the coronavirus disease 2019 (COVID‐19) pandemic: an international accelerated consensus statement
Authors: Tandogdu Zafer , Collins Justin , Shaw Greg , Rohn Jennifer , Koves Bela , Sachdeva Ashwin , Ghazi Ahmed , Haese Alexander , Mottrie Alex , Kumar Anup , Sivaraman Ananthakrishnan , Tewari Ashutosh , Challacombe Benjamin , Rocco Bernardo , Giedelman Camilo , Wagner Christian , Rogers Craig G. , Murphy Declan G. , Pushkar Dmitry , Ogaya‐Pinies Gabriel , Porter James , Seetharam Kulthe Ramesh , Graefen Markus , Orvieto Marcelo A. , Moschovas Marcio Covas , Schatloff Oscar , Wiklund Peter , Coelho Rafael , Valero Rair , de Reijke Theo M. , Ahlering Thomas , Rogers Travis , van der Poel Henk G. , Patel Vipul , Artibani Walter , Wagenlehner Florian , Maes Kris , Rha Koon H. , Nathan Senthil , Bjerklund Johansen Truls Erik , Hawkey Peter , Kelly John
Published: December 2020

Objective

Coronavirus disease‐19 (COVID‐19) pandemic caused delays in definitive treatment of patients with prostate cancer. Beyond the immediate delay a backlog for future patients is expected. The objective of this work is to develop guidance on criteria for prioritisation of surgery and reconfiguring management pathways for patients with non‐metastatic prostate cancer who opt for surgical treatment. A second aim was to identify the infection prevention and control (IPC) measures to achieve a low likelihood of coronavirus disease 2019 (COVID‐19) hazard if radical prostatectomy (RP) was to be carried out during the outbreak and whilst the disease is endemic.

Methods

We conducted an accelerated consensus process and systematic review of the evidence on COVID‐19 and reviewed international guidance on prostate cancer. These were presented to an international prostate cancer expert panel (n = 34) through an online meeting. The consensus process underwent three rounds of survey in total. Additions to the second‐ and third‐round surveys were formulated based on the answers and comments from the previous rounds. The Consensus opinion was defined as ≥80% agreement and this was used to reconfigure the prostate cancer pathways.

Results

Evidence on the delayed management of patients with prostate cancer is scarce. There was 100% agreement that prostate cancer pathways should be reconfigured and measures developed to prevent nosocomial COVID‐19 for patients treated surgically. Consensus was reached on prioritisation criteria of patients for surgery and management pathways for those who have delayed treatment. IPC measures to achieve a low likelihood of nosocomial COVID‐19 were coined as ‘COVID‐19 cold’ sites.

Conclusion

Reconfiguring management pathways for patients with prostate cancer is recommended if significant delay (>3–6 months) in surgical management is unavoidable. The mapped pathways provide guidance for such patients. The IPC processes proposed provide a framework for providing RP within an environment with low COVID‐19 risk during the outbreak or when the disease remains endemic. The broader concepts could be adapted to other indications beyond prostate cancer surgery.
Estimating the health‐related quality of life of kidney stone patients: initial results from the Wisconsin Stone Quality of Life Machine‐Learning Algorithm (WISQOL‐MLA)
Authors: Nguyen David‐Dan , Luo Jack W. , Lu Xing Han , Bechis Seth K. , Sur Roger L. , Nakada Stephen Y. , Antonelli Jodi A. , Streeper Necole M. , Sivalingam Sri , Viprakasit Davis P. , Averch Timothy D. , Landman Jaime , Chi Thomas , Pais Vernon M. , Chew Ben H. , Bird Vincent G. , Andonian Sero , Canvasser Noah E. , Harper Jonathan D. , Penniston Kristina L. , Bhojani Naeem
Published: December 2020

Objective

To build the Wisconsin Stone Quality of Life Machine‐Learning Algorithm (WISQOL‐MLA) to predict urolithiasis patients’ health‐related quality of life (HRQoL) based on demographic, symptomatic and clinical data collected for the validation of the Wisconsin Stone Quality‐of‐Life (WISQOL) questionnaire, an HRQoL measurement tool designed specifically for patients with kidney stones.

Material and Methods

We used data from 3206 stone patients from 16 centres. We used gradient‐boosting and deep‐learning models to predict HRQoL scores. We also stratified HRQoL scores by quintile. The dataset was split using a standard 70%/10%/20% training/validation/testing ratio. Regression performance was evaluated using Pearson’s correlation. Classification was evaluated with an area under the receiver‐operating characteristic curve (AUROC).

Results

Gradient boosting obtained a test correlation of 0.62. Deep learning obtained a correlation of 0.59. Multivariate regression achieved a correlation of 0.44. Quintile stratification of all patients in the WISQOL dataset obtained an average test AUROC of 0.70 for the five classes. The model performed best in identifying the lowest (0.79) and highest quintiles (0.83) of HRQoL. Feature importance analysis showed that the model weighs in clinically relevant factors to estimate HRQoL, such as symptomatic status, body mass index and age.

Conclusions

Harnessing the power of the WISQOL questionnaire, our initial results indicate that the WISQOL‐MLA can adequately predict a stone patient’s HRQoL from readily available clinical information. The algorithm adequately relies on relevant clinical factors to make its HRQoL predictions. Future improvements to the model are needed for direct clinical applications.
Long‐term multicentre experience of adjuvant radiotherapy for pN3 squamous cell carcinoma of the penis
Authors: Ager Michael , Njoku Kelechi , Serra Maria , Robinson Angus , Pickering Lisa , Afshar Mehran , Vyas Lona , Eardley Ian , Kayes Oliver , Elmamoun Mamoun , Khoo Vincent , Ayres Benjamin , Henry Ann , Watkin Nick , Tree Alison C.
Published: December 2020

Objective

To present the long‐term adjuvant radiotherapy outcomes of patients with pN3 squamous cell carcinoma of the penis (SCCp) treated at two UK centres.

Patients and Methods

We conducted a retrospective audit of all pN3 SCCp patients, deemed suitable for adjuvant therapy by a specialist multidisciplinary team at St George’s and Leeds Hospitals, who received adjuvant radiotherapy. Primary outcomes were recurrence‐free survival (RFS), cancer‐specific survival (CSS) and overall survival (OS). Secondary outcomes were time to adjuvant treatment, frequency of in‐field recurrence, site and side of recurrence, and dose and schedule of radiotherapy.

Results

A total of 146 patients were included: 121 completed radiotherapy, 4 did not complete radiotherapy and 21 did not start it. The median (interquartile range [IQR]) age was 59 (54–70)years. The 5‐year RFS was 51%, CSS was 51% and OS was 44%. Adjuvant radiotherapy was started at a median (IQR) of 75 (48–106) days. A dose of 45 Gy in 20 fractions was most commonly used. Of the 125 patients who started adjuvant treatment, 55 relapsed. Of these relapses, 30 occurred in an inguinal or pelvic nodal station and 26 of the 30 were in a radiation field. Relapses in 18 of the 55 cases were in visceral sites only and seven were in both nodal (non‐irradiated sites) and visceral sites. Doses of <50 Gy were used more commonly before 2013 and higher doses (>50 Gy) were more commonly used after 2013.

Conclusions

Application of a standard radiotherapy protocol within a centralized supra‐network setting has achieved survival outcomes that would appear better than those previously documented for either radiotherapy or chemotherapy in a cohort with solely pN3 disease. The addition of adjuvant chemotherapy may improve these outcomes further. These data suggest that adjuvant radiotherapy has a role to play in the management of men with pN3 SCCp.
Changes in UK renal oncological surgical practice from 2008 to 2017: implications for cancer service provision and surgical training
Authors: Devlin Conor M. , Fowler Sarah , Biyani Chandra Shekhar , Forster James A.
Published: December 2020

Objective

To determine and analyse the temporal changes in oncological nephrectomy practice and training opportunities using data obtained from the UK British Association of Urological Surgeons nephrectomy register from 2008 to 2017.

Patient and Methods

All nephrectomies within the dataset for this time period were analysed (n = 54 251). Cases were divided into radical nephrectomy (RN), partial nephrectomy (PN) and nephroureterectomy (NU). Simple nephrectomy, donor nephrectomy and benign PN were excluded. The annual frequencies for each oncological nephrectomy method, surgical approach, grade of surgeon, hospital caseload numbers and short‐term surgical outcomes were determined.

Results

Reported annual nephrectomy numbers increased by 2.5‐fold in the 9‐year time period. The number of hospitals performing nephrectomies decreased by 22%, however, more than 40% of centres performed more than 70 cases a year. There was a trend towards a decrease in overall length of hospital stay (9 vs 5 days; P < 0.01) and decreased transfusion rates. The proportion of minimally invasive procedures increased from 57% to 75%, with nephron‐sparing rates increasing from 8.9% overall to 24.8%. With regard to surgical technique, robot‐assisted surgery saw a mean annual increase of 222%. Overall, there was a 10% decrease in the proportion of PNs performed by trainee surgeons.

Conclusions

Renal surgery has changed considerably with regard to volume and also surgical approach, with rates of nephron‐sparing surgery and minimally invasive surgery significantly increasing. Increasing hospital centralization and institutional experience, and a shift to robot‐assisted surgery appear to have contributed to the observed improved patient outcomes. The increasing utilization of robot‐assisted surgery has potential implications and challenges for the training of future urology surgeons.
Objective assessment of intraoperative skills for robot‐assisted radical prostatectomy (RARP): results from the ERUS Scientific and Educational Working Groups Metrics Initiative
Authors: Mottrie Alexandre , Mazzone Elio , Wiklund Peter , Graefen Markus , Collins Justin W. , De Groote Ruben , Dell’Oglio Paolo , Puliatti Stefano , Gallagher Anthony G.
Published: December 2020

Objective

To develop and seek consensus from procedure experts on the metrics that best characterise a reference robot‐assisted radical prostatectomy (RARP) and determine if the metrics distinguished between the objectively assessed RARP performance of experienced and novice urologists, as identifying objective performance metrics for surgical training in robotic surgery is imperative for patient safety.

Materials and methods

In Study 1, the metrics, i.e. 12 phases of the procedure, 81 steps, 245 errors and 110 critical errors for a reference RARP were developed and then presented to an international Delphi panel of 19 experienced urologists. In Study 2, 12 very experienced surgeons (VES) who had performed >500 RARPs and 12 novice urology surgeons performed a RARP, which was video recorded and assessed by two experienced urologists blinded as to subject and group. Percentage agreement between experienced urologists for the Delphi meeting and Mann–Whitney U‐ and Kruskal–Wallis tests were used for construct validation of the newly identified RARP metrics.

Results

At the Delphi panel, consensus was reached on the appropriateness of the metrics for a reference RARP. In Study 2, the results showed that the VES performed ~4% more procedure steps and made 72% fewer procedure errors than the novices (P = 0.027). Phases VIIa and VIIb (i.e. neurovascular bundle dissection) best discriminated between the VES and novices. Limitations: VES whose performance was in the bottom half of their group demonstrated considerable error variability and made five‐times as many errors as the other half of the group (P = 0.006).

Conclusions

The international Delphi panel reached high‐level consensus on the RARP metrics that reliably distinguished between the objectively scored procedure performance of VES and novices. Reliable and valid performance metrics of RARP are imperative for effective and quality assured surgical training.
Toward improved endoscopic examination of urinary stones: a concordance study between endoscopic digital pictures vs microscopy
Authors: Estrade Vincent , Denis de Senneville Baudouin , Meria Paul , Almeras Christophe , Bladou Franck , Bernhard Jean‐Christophe , Robert Gregoire , Traxer Olivier , Daudon Michel
Published: December 2020

Objective

To improve endoscopic recognition of the most frequently encountered urinary stone morphologies for a better aetiological approach in lithiasis by urologists.

Materials and Methods

An expert urologist intraoperatively and prospectively (between June 2015 and June 2018) examined the surface, the section, and the nucleus of all encountered kidney stones. Fragmented stones were subsequently analysed by a biologist based on both microscopic morphological (i.e. binocular magnifying glass) and infrared (i.e. Fourier transform‐infrared spectroscopy) examinations (microscopists were blinded to the endoscopic data). Morphological criteria were collected and classified for the endoscopic and microscopic studies. The Wilcoxon–Mann–Whitney test was used to detect differences between the endoscopic and microscopic diagnoses. A diagnosis for a given urinary stone was considered ‘confirmed’ for a non‐statistically significant difference.

Results

A total of 399 urinary stones were included in this study: 51.4% of the stones had only one morphological type, while 48.6% were mixed stones (41% had at least two morphologies and 7.6% had three morphologies). The overall matching rate was 81.6%. Diagnostics were confirmed for the following morphologies: whewellite (Ia or Ib), weddellite (IIa or IIb), uric acid (IIIa or IIIb), carbapatite‐struvite association (IVb), and brushite (IVd).

Conclusions

Our preliminary study demonstrates the feasibility of using endoscopic morphology for the most frequently encountered urinary stones and didactic boards of confirmed endoscopic images are provided. The present study constitutes the first step toward endoscopic stone recognition, which is essential in lithiasis. We provide didactic boards of confirmed endoscopic images that pave the way for automatic computer‐aided in situ recognition.
Expanding genetic spectrum and discriminatory role of steroid profiling by LC‐MS/MS in 11β‐hydroxylase deficiency
Authors: Karlekar Manjiri Pramod , Sarathi Vijaya , Lila Anurag , Rai Khushnandan , Arya Sneha , Bhandare Vishwambhar Vishnu , Atluri Sridevi , Patil Virendra , Ramteke‐Jadhav Swati , Shah Nalini S. , Kunwar Ambarish , Bandgar Tushar
Published: December 2020

Objective

To report clinical, hormonal and structural effects of CYP11B1 pathogenic variations in Indian patients with 11β‐hydroxylase deficiency (11βOHD) and find hormonal criteria that accurately distinguish 11βOHD from 21α‐hydroxylase deficiency (21OHD).

Design

Retrospective record review of genetically diagnosed patients with 11βOHD.

Patients and Measurements

Clinical features, hormonal parameters at diagnosis (by immunoassay) and recent follow‐up of 13 genetically proven 11βOHD patients managed at our centre were retrospectively reviewed. ACTH‐stimulated serum adrenal steroids (measured by LC‐MS/MS) of 11βOHD were compared with those of simple virilizing and non‐classic 21OHD. Structural analysis of the observed pathogenic variations was performed by computational modelling.

Results

Nine (four females) and four (all females) patients had classic and non‐classic disease, respectively. All 11βOHD patients had elevated ACTH‐stimulated serum 11‐deoxycortisol (26.5–342.7 nmol/L) whereas none had elevated serum 17‐hydroxyprogesterone (4.2–21.2 nmol/L); both hormonal parameters distinguished 11βOHD from 21OHD with 100% accuracy. ACTH‐stimulated serum cortisol, but not 11‐deoxycortisol, clearly distinguished classic (<70 nmol/L) from non‐classic (>160 nmol/L) disease. Thirteen (eight novel, two recurrent) pathogenic variants were observed. Only missense mutations were observed among patients with non‐classic disease. Computational modelling predicted the possible affection of enzyme structure and function for all the observed missense mutations.

Conclusions

This first Indian study describes 13 11βOHD patients, including four with the rarer non‐classic variant. A total of eight novel pathogenic variants were identified in our study, highlighting regional genetic heterogeneity. Measurement of ACTH‐stimulated adrenal steroids by LC‐MS/MS will help avoid the misdiagnosis of 11βOHD as 21OHD and has potential to distinguish classic from non‐classic 11βOHD.
Building a better baseline to estimate 160 years of avian population change and create historically informed conservation targets
Authors: Hallman Tyler A. , Robinson W. Douglas , Curtis Jenna R. , Alverson Edward R.
Published: December 2020

Globally, anthropogenic land‐cover change has been dramatic over the last few centuries and is frequently invoked as a major cause of wildlife population declines. Baseline data currently used to assess population trends, however, began well after major changes to the landscape. In the United States and Canada, breeding bird population trends are assessed by the North American Breeding Bird Survey, which began in the 1960s. Estimates of distribution and abundance prior to major habitat alteration would add historical perspective to contemporary trends and allow for historically based conservation targets. We used a hindcasting framework to estimate change in distribution and abundance of 7 bird species in the Willamette Valley, Oregon (United States). After reconciling classification schemes of current and 1850s reconstructed land cover, we used multiscale species distribution models and hierarchical distance sampling models to predict spatially explicit densities in the modern and historical landscapes. We estimated that since the 1850s, White‐breasted Nuthatch (Sitta carolinensis) and Western Meadowlark (Sturnella neglecta) populations, 2 species sensitive to fragmentation of oak woodlands and grasslands, declined by 93% and 97%, respectively. Five other species we estimated nearly stable or increasing populations, despite steep regional declines since the 1960s. Based on these estimates, we developed historically based conservation targets for amount of habitat, population, and density for each species. Hindcasted reconstructions provide historical perspective for assessing contemporary trends and allow for historically based conservation targets that can inform current management.
Plastic pollution is killing marine megafauna, but how do we prioritize policies to reduce mortality?
Authors: Roman Lauren , Schuyler Qamar , Wilcox Chris , Hardesty Britta Denise
Published: December 2020

Pollution by plastic and other debris is a problem affecting the world's oceans and is increasing through time. The problem is so large that prioritizing solutions to effect meaningful change may seem overwhelming to the public and policy makers. Marine megafauna are known to mistakenly eat anthropogenic debris and die from consequent gastrointestinal blockages, perforations and malnutrition, as well as suffer sublethal impacts. We collated information on which specific items were ingested and responsible for causing death across 80 marine species, including cetaceans, pinnipeds, sea turtles, and seabirds. We evaluated which items were responsible for the highest mortality, and which, if reduced by policy responses or other means, could result in the largest reduction in debris mortality. A limited number of consumer items were shown to be responsible for most megafauna deaths. Flexible plastic is responsible for the largest proportion of debris deaths, primarily due to gastric obstructions. Disproportionately lethal items included plastic bags/sheets/packaging, rope/fishing nets, fishing tackle and balloons/latex. Smaller items, including “microplastics,” though abundant, were seldom implicated in mortality. We provide suggestions to directly curb debris deaths of marine megafauna by prioritizing policies that would reduce or eliminate the input of disproportionately hazardous items into the marine system.
“Si Dios Quiere:” Instability, Sustainability, and Wellness in a Vermont Migrant Worker Health Clinic
Authors: Smith Kelsey
Published: December 2020

The political health ecology of Vermont is shaped by its status as a rural, borderland state and its dependence upon dairy for agricultural revenue in a fluctuating neoliberal market. The Care Center, a free clinic serving uninsured patients in Cherry County, is the primary medical provider for the growing Latinx migrant worker population that supports the majority of Vermont dairy farms. My findings demonstrate the gendered nature of how Latinx migrant dairy workers and healthcare professionals navigate the compounding precarities in Vermont that make safety and wellness difficult to establish. I contend that the layered use of structural vulnerability, political health ecology, and ecofeminist situated sustainability offers a perspective on the hidden interconnectedness between healthcare work and sustainability, ultimately providing directions for collaboration.
Quality issues in georeferencing: From physical collections to digital data repositories for ecological research
Authors: Marcer Arnald , Haston Elspeth , Groom Quentin , Ariño Arturo H. , Chapman Arthur D. , Bakken Torkild , Braun Paul , Dillen Mathias , Ernst Marcus , Escobar Agustí , Fichtmüller David , Livermore Laurence , Nicolson Nicky , Paragamian Kaloust , Paul Deborah , Pettersson Lars B. , Phillips Sarah , Plummer Jack , Rainer Heimo , Rey Isabel , Robertson Tim , Röpert Dominik , Santos Joaquim , Uribe Francesc , Waller John , Wieczorek John R.
Published: December 2020

Natural history collections constitute an enormous wealth of information of Life on Earth. It is estimated that over 2 billion specimens are preserved at institutions worldwide, of which less than 10% are accessible via biodiversity data aggregators such as GBIF. Moreover, they are a very important resource for eco‐evolutionary research, which greatly depends on knowing the precise location where the specimens were collected in order to characterize the environment in which they lived. Yet, only about 55% of the accessible records are georeferenced and only 31% have coordinate uncertainty information, which is critical for conducting rigorous studies. The awareness of this gap of knowledge which hinders the enormous potential of such data in research led to the organization of a workshop which brought together key players in georeferencing of natural history collections. The discussion and outcomes of this workshop are here presented.
Bergson on Kant and the freedom of the moi en général
Authors: Watt Robert
Published: December 2020

This article provides the first detailed discussion of an objection to Kant's theory of freedom in Henri Bergson's 1904‐05 lectures at the Collège de France. According to Bergson, if Kant succeeds in defending the possibility of human freedom, this is not the freedom of any particular human being, but rather the freedom of the ‘moi en général’. I compare this objection to arguments against Kant's theory of freedom by other late nineteenth/early twentieth century French philosophers such as Émile Boutroux, Charles Renouvier and Victor Delbos, as well as to one of the best known objections to this theory in the subsequent anglophone literature. I argue that Bergson's objection rests on the false assumption that, according to Kant, “there is no difference in nature… between time and space.”
Oxytetracycline associated acute kidney injury in a neonatal foal
Authors: Fletcher J. R. , Bertin F. R. , Owen H. , Fraser N. S. , Rose A. M. , Stewart A. J.
Published: December 2020

A 3‐day‐old Australian Stock Horse filly presented with fulminant acute kidney injury after receiving 4 g of intravenous oxytetracycline at 24 and 48 h of age for medical management of flexural deformities. The filly’s clinical status initially improved, but worsening azotaemia prompted euthanasia after 55 h of supportive care. Necropsy confirmed proximal tubular necrosis. Nephropathy in association with oxytetracycline administration has been rarely reported. This case describes severe nephropathy in an apparently normal foal and highlights the need for thorough case evaluation prior to use of high‐dose oxytetracycline therapy for correction of flexural deformities in foals.
Opposing pressures of climate and land‐use change on a native bee
Authors: Kelemen Evan P. , Rehan Sandra M.
Published: December 2020

Anthropogenic activities are rapidly changing the environment, and species that do not respond face a higher risk of extinction. Species may respond to environmental changes by modifying their behaviors, shifting their distributions, or changing their morphology. Recent morphological responses are often measured by changes in body size. Changes in body size are often attributed to climate change, but may instead be due to differences in available resources associated with changes in local land‐use. The effects of temperature and land‐use can be uncoupled in populations of the small carpenter bee Ceratina calcarata, which have experienced changes in agricultural and urban cover independent of climate change. We studied how the morphology of this bee has changed over the past 118 years (1902–2019) in relation to climate change and the past 45 years (1974–2019) in relation to agricultural and urban cover. Over this time, summer temperatures increased. We found that male and female size decreased with increasing temperature. Male size also decreased with agricultural expansion. Female size, however, increased with agricultural expansion. These results suggest that rising temperatures correlate with a decrease in female body size, while, opposite to predicted, agricultural land‐use may select for increased female body size. These opposing pressures act concurrently and may result in bee extirpation from agricultural habitats if selection for large sizes is unsustainable as temperatures continue to increase. Furthermore, this study emphasizes the need to consider multiple environmental stressors when examining the effects of climate change due to their interactions.
Plants with less chlorophyll: A global change perspective
Authors: Genesio Lorenzo , Bassi Roberto , Miglietta Franco
Published: December 2020

The necessary reduction of greenhouse gas (GHG) emissions may lead in the future to an increase in solar irradiance (solar brightening). Anthropogenic aerosols (and their precursors) that cause solar dimming are in fact often co‐emitted with GHGs. While the reduction of GHG emissions is expected to slow down the ongoing increase in the greenhouse effect, an increased surface irradiance due to reduced atmospheric aerosol load might occur in the most populated areas of the earth. Increased irradiance may lead to air warming, favour the occurrence of heatwaves and increase the evaporative demand of the atmosphere. This is why effective and sustainable solar radiation management strategies to reflect more light back to space should be designed, tested and implemented together with GHG emission mitigation. Here we propose that new plants (crops, orchards and forests) with low‐chlorophyll (Chl) content may provide a realistic, sustainable and relatively simple solution to increase surface reflectance of large geographical areas via changes in surface albedo. This may finally offset all or part of the expected local solar brightening. While high‐Chl content provides substantial competitive advantages to plants growing in their natural environment, new plants with low‐Chl content may be successfully used in agriculture and silviculture and be as productive as the green wildtypes (or even more). The most appropriate strategies to obtain highly productive and highly reflective plants are discussed in this paper and their mitigation potential is examined together with the challenges associated with their introduction in agriculture.
Context matters: Problematizing the policy‐practice interface in the enactment of gender equality action plans in universities
Authors: Ní Laoire Caitríona , Linehan Carol , Archibong Uduak , Picardi Ilenia , Udén Maria
Published: December 2020

This study argues for recognition of the constitutive role of context in shaping the dynamics of the policy‐practice interface in the field of gender equality in universities. Using a comparative and reflective case‐study approach, we draw on our experiences, as action‐researchers, of developing and implementing Gender Equality Action Plans (GEAPs) in four universities in four different European countries and we explore the role of national and local context in the mediation and translation of the GEAP model. Drawing on the concepts of gendered organizations, dialogic organizational change, and policy mobilities, we argue for the need to be critical of approaches to gender equality in higher education (HE) that presume policy measures and good practice models transfer unproblematically to different HE organizations in different international contexts; instead, we draw attention to the contingent ways in which uneven gender relations articulate and manifest in different contexts, shaping possibilities for, and obstacles to, gender equality intervention. Thus, we argue that context plays a crucial constitutive role in the interpretation, enactment, and impact of gender equality policy in HE.
Reduced erythrocyte lifespan measured by chromium‐51 in patients with type 2 diabetes undergoing long‐term hemodialysis
Authors: Bomholt Tobias , Oturai Peter , Rix Marianne , Almdal Thomas , Knop Filip K. , Rosthøj Susanne , Feldt‐Rasmussen Bo , Hornum Mads
Published: December 2020

Introduction

A reduced erythrocyte lifespan potentially explains the low hemoglobin A1c values found in hemodialysis patients. However, data supporting this notion in patients with type 2 diabetes is unclear. We evaluated the erythrocyte lifespan in patients with type 2 diabetes undergoing long‐term hemodialysis and investigated potential predictors of erythrocyte lifespan.

Methods

Long‐term hemodialysis patients with type 2 diabetes and type 2 diabetes patients without nephropathy (estimated glomerular filtration rate > 60 mL/min/1.73 m2) were included. The erythrocyte lifespan was measured using chromium‐51 (51Cr)‐labeled erythrocytes. Blood radiotracer activity was measured six to nine times over a period of 3–5 weeks to determine the erythrocyte lifespan of each patient. Biochemical markers were obtained five times over 16 weeks and associated with the erythrocyte lifespan.

Findings

Type 2 diabetes patients undergoing hemodialysis (N = 13) had a significantly shorter median erythrocyte lifespan of 49.7 (interquartile range [IQR] = 44.1–58.6) days compared with 64.2 (IQR = 62.6–83.5) days in the control group (N = 10) (P ˂ 0.001) with a difference between medians of 14.5 (95% confidence interval = 8.1–38.8) days. In the hemodialysis group, no association could be detected between the erythrocyte lifespan and markers of hemolysis, level of inflammation, or urea.

Discussion

A reduced erythrocyte lifespan was detected in type 2 diabetes patients undergoing long‐term hemodialysis. This may contribute to the reduced hemoglobin A1c values observed in the type 2 diabetic hemodialysis population. An association could not be detected between the erythrocyte lifespan and biochemical markers of hemolysis or inflammation.
Association between dental factors and mortality
Authors: Liljestrand J. M. , Salminen A. , Lahdentausta L. , Paju S. , Mäntylä P. , Buhlin K. , Tjäderhane L. , Sinisalo J. , Pussinen P. J.
Published: December 2020

Aim

To study whether oral parameters such as endodontic infections, root canal fillings, number of teeth or wearing removable dentures at baseline are associated with cardiovascular‐ and all‐cause mortality in a follow‐up of approximately 8 years.

Methodology

The Finnish Parogene cohort consists of 508 Finnish adults (mean age 63.3 years, SD 9.1) with cardiac symptoms, all of whom had undergone coronary angiography for accurate baseline coronary status. Extensive clinical and radiographic oral examinations were performed, and additional data were acquired from medical records and questionnaires. Root canal fillings and endodontic lesions, as well as their co‐occurrence, were determined from panoramic radiographs. The mortality data were assessed via record linkage with the Finnish Causes of Death register (mean follow‐up time 7.81 years, SD 1.45 years). A total of n = 471 dentate patients were included in the statistical analyses.

Results

A total of n = 69 deaths were recorded, of which n = 41 were due to cardiovascular diseases (CVDs, ICD‐10 I00–I99). The deceased had fewer root canal fillings (mean 1.57; SD 1.64 vs. mean 2.30; SD 2.34, P = 0.03) than the survivors. The number of missing teeth was associated with smoking, occluded coronary arteries and diabetes. Cox regression with Firth's penalized maximum‐likelihood method using age as timescale revealed an inverse association (HR; 95%CI) between mortality and number of teeth (all‐cause 0.91; 0.86–0.96, CVD mortality 0.89; 0.83–0.96), use of removable dentures (all‐cause 0.24; 0.09–0.62, CVD mortality 0.20; 0.06–0.72), root canal fillings (all‐cause 0.82; 0.70–0.94, CVD mortality 0.79; 0.63–0.96) and having root canal fillings in all teeth with apical rarefactions (all‐cause 0.27; 0.06–0.79, CVD mortality 0.09; 0.01–0.63), when gender, smoking, occluded coronary arteries, periodontal inflammatory burden index and the number of teeth were adjusted for.

Conclusions

The number of missing teeth appeared to be the strongest predictor of mortality in this study, whereas endodontic infections per se had no independent association. Nevertheless, signs of professional intervention in these problems, such as root canal fillings and removable dentures, appeared to be associated with improved survival, which might partly be explained by the utilization of healthcare services.
Phase equilibria and stability of intermediate phases in the Sm2O3–BaO–Fe2O3 system
Authors: Volkova Nadezhda E. , Tolstov Konstantin S. , Gavrilova Ludmila Ya. , Raveau Bernard , Maignan Antoine , Cherepanov Vladimir A.
Published: December 2020

Phase equilibria in the ½ Sm2O3–BaO–½ Fe2O3 system were systematically studied at 1100°C in air. Two individual compounds: Sm1.875Ba3.125Fe5O15‐δ and Ba3SmFe2O7.5+δ have been detected in the studied system at 1100°C in air. One more complex oxide with double perovskite structure SmBaFe2O5+w has been obtained under reduced oxygen partial pressure. Thermodynamic stability of SmBaFe2O5+w and its thermal stability in metastable state in air were determined. The subsolidus phase diagram for the ½ Sm2O3 – BaO – ½ Fe2O3 system at 1100°C in air has been constructed.