bluuebunny/crossref_metadata_2025 huggingface dataset:
Slope and aspect controls on soil climate: Field documentation and implications for large‐scale simulation of critical zone processes
Authors: Seyfried Mark , Flerchinger Gerald , Bryden Sage , Link Tim , Marks Danny , McNamara Jim
Published: September 2021

Soil climate, as quantified by soil temperature (TS) and water content (θ), exerts important controls on critical zone processes. It may be sensitive to variations in local slope and aspect (SA), but this attribute remains poorly quantified at the local scale and unresolved in large‐scale models. Estimation of SA effects on soil climate across multiple scales may facilitated using topographically modified, incoming clear‐sky solar radiation (SR,CS,T). We established six paired automated soil climate monitoring stations on opposing north‐facing (NF) and south‐facing (SF) slopes (4 yr) and collected spatialTSand θ data within the hectare surrounding four stations (2 yr) to measure SA effects on soil climate. Results were compared with physically based simulations and evaluated in the context ofSR,CS,T. Spatial θ data were more variable thanTs, and both were consistent with values from continuous monitoring stations. On average, the SFTSwas much greater (4.7 °C) and the annual summer drought longer (36 d) than on the adjacent NF aspect. Seasonal variations ofTSand θ were different from each other and also different fromSR,CS,T. Local conditions, including snow cover, precipitation patterns, and soil properties, largely controlled seasonal variations ofTSand θ, which cannot be predicted fromSR,CS,T. This indicates that realistic simulation of many critical zone processes requires high‐resolution inputs. Simulations captured first‐order SA effects and could be useful for estimating SA effects in lieu of field monitoring.
Green infrastructure: The future of urban flood risk management?
Authors: Green Daniel , O'Donnell Emily , Johnson Matthew , Slater Louise , Thorne Colin , Zheng Shan , Stirling Ross , Chan Faith K. S. , Li Lei , Boothroyd Richard J.
Published: September 2021

Urban flooding is a key global challenge which is expected to become exacerbated under global change due to more intense rainfall and flashier runoff regimes over increasingly urban landscapes. Consequently, many cities are rethinking their approach to flood risk management by using green infrastructure (GI) solutions to reverse the legacy of hard engineering flood management approaches. The aim of GI is to attenuate, restore, and recreate a more natural flood response, bringing hydrological responses closer to pre‐urbanized conditions. However, GI effectiveness is often difficult to determine, and depends on both the magnitude of storm events and the spatial scale of GI infrastructure. Monitoring of the successes and failures of GI schemes is not routinely conducted. Thus, it can be difficult to determine whether GI provides a sustainable solution to manage urban flooding. This article provides an international perspective on the current use of GI for urban flood mitigation and the solutions it offers in light of current and future challenges. An increasing body of literature further suggests that GI can be optimized alongside gray infrastructure to provide a holistic solution that delivers multiple co‐benefits to the environment and society, while increasing flood resilience. GI will have to work synergistically with existing and upgraded gray infrastructure if urban flood risk is to be managed in a futureproof manner. Here, we discuss a series of priorities and challenges that must be overcome to enable integration of GI into existing stormwater management frameworks that effectively manage flood risk.

This article is categorized under:

Engineering Water > Sustainable Engineering of Water

Engineering Water > Planning Water

Science of Water > Water Extremes
Alternative polyadenylation: An enigma of transcript length variation in health and disease
Authors: Mohanan Neeraja K. , Shaji Feba , Koshre Ganesh R. , Laishram Rakesh S.
Published: September 2021

Alternative polyadenylation (APA) is a molecular mechanism during a pre‐mRNA processing that involves usage of more than one polyadenylation site (PA‐site) generating transcripts of varying length from a single gene. The location of a PA‐site affects transcript length and coding potential of an mRNA contributing to both mRNA and protein diversification. This variation in the transcript length affects mRNA stability and translation, mRNA subcellular and tissue localization, and protein function. APA is now considered as an important regulatory mechanism in the pathophysiology of human diseases. An important consequence of the changes in the length of 3′‐untranslated region (UTR) from disease‐induced APA is altered protein expression. Yet, the relationship between 3′‐UTR length and protein expression remains a paradox in a majority of diseases. Here, we review occurrence of APA, mechanism of PA‐site selection, and consequences of transcript length variation in different diseases. Emerging evidence reveals coordinated involvement of core RNA processing factors including poly(A) polymerases in the PA‐site selection in diseases‐associated APAs. Targeting such APA regulators will be therapeutically significant in combating drug resistance in cancer and other complex diseases.

This article is categorized under:

RNA Processing > 3′ End Processing

RNA in Disease and Development > RNA in Disease

Translation > Regulation
The Multiple Potentials of Urban Brownfields
Authors: Rey Emmanuel , Laprise Martine , Lufkin Sophie
Published: September 2021

The phenomenon of urban brownfields is significant throughout European metropolitan areas. In this chapter, we assess, both in qualitative and quantitative terms, the inherent potential of urban brownfields to provide a relevant and substantial densification strategy for metropolitan areas. First, we explore the various opportunities for improvement of the built environment offered by urban brownfields in terms of environment, society, and economics, which are the core principles of sustainable development. This analysis is, inter alia, a juxtaposition between urban brownfields and the compact and polycentric city model, adapted to the metropolitan area. While brownfield regeneration appears to be a relevant densification strategy, it nevertheless implies that a sufficient reserve of land is available to engage policymakers. Thus, we attempt to estimate the urban brownfield stock in three countries: the United Kingdom, Switzerland, and France. The data subsequently serves as a basis for our calculation of the theoretical construction potential of brownfield sites.
Sustainability Monitoring: Principles, Challenges, and Approaches
Authors: Rey Emmanuel , Laprise Martine , Lufkin Sophie
Published: September 2021

Because of the inherent complexity of urban brownfield regeneration projects, achieving sustainability objectives is not easy. It requires approaches adapted to the specificities of this type of operation, that allow for structured and regular follow-up, and that are integrated into the project dynamics. In this chapter, we argue that sustainability monitoring can help address this challenge. We start by defining the principles of sustainability evaluation and monitoring. Then, we look deeper at the challenges of an operational monitoring tool from the brownfield regeneration perspective. On this basis, we plead for the necessity of tailor-made operational monitoring tools for this type of operation and define, to this end, three general requirements for said tools. Finally, we make a critical analysis of existing certifications at the neighbourhood scale and different approaches developed for brownfield regeneration projects.
An Operational Monitoring Tool
Authors: Rey Emmanuel , Laprise Martine , Lufkin Sophie
Published: September 2021

The transition from an urban brownfield to a sustainable neighbourhood is a complex operation. To help decision-makers reach sustainability objectives through measurement, follow-up, and communication about performance indicators, we introduce in this chapter a tailor-made operational monitoring tool. Such a tool should satisfy three general requirements: a search for overall quality, adequacy with the specificities of urban brownfield regeneration projects, and integration into the project dynamics. Accordingly, the multi-criteria evaluation system SIPRIUS and the quality management monitoring software OKpilot are hybridized to create SIPRIUS+. In the first section, we explain the functioning of the two existing methodologies and the adaptions we made to help meet the general requirements and to create the hybrid tool. Then, we present the resulting monitoring tool, SIPRIUS+, and its functionalities.
Bulk reconstruction and Bogoliubov transformations in AdS2
Authors: Dey Parijat , Kajuri Nirmalya
Published: September 2021

Abstract

In the bulk reconstruction program, one constructs boundary representations of bulk fields. We investigate the relation between the global/Poincare and AdS-Rindler representations for AdS2. We obtain the AdS-Rindler smearing function for massive and massless fields and show that the global and AdS-Rindler boundary representations are related by conformal transformations. We also use the boundary representations of creation and annihilation operators to compute the Bogoliubov transformation relating global modes to AdS-Rindler modes for both massive and massless particles.
Color confinement at the boundary of the conformally compactified AdS5
Authors: Kirchbach M. , Popov T. , Vallejo J. A.
Published: September 2021

Abstract

The topology of closed manifolds forces interacting charges to appear in pairs. We take advantage of this property in the setting of the conformal boundary of AdS5 spacetime, topologically equivalent to the closed manifold S1× S3, by considering the coupling of two massless opposite charges on it. Taking the interaction potential as the analog of Coulomb interaction (derived from a fundamental solution of the S3 Laplace-Beltrami operator), a conformal S1× S3 metric deformation is proposed, such that free motion on the deformed metric is equivalent to motion on the round metric in the presence of the interaction potential. We give explicit expressions for the generators of the conformal algebra in the representation induced by the metric deformation.

By identifying the charge as the color degree of freedom in QCD, and the two charges system as a quark-anti-quark system, we argue that the associated conformal wave operator equation could provide a realistic quantum mechanical description of the simplest QCD system, the mesons.

Finally, we discuss the possibility of employing the compactification radius, R, as an- other scale along ΛQCD, by means of which, upon reparametrizing Q2c2 as (Q2c2+ħ2c2/R2), a perturbative treatment of processes in the infrared could be approached.
MHV amplitudes and BCFW recursion for Yang-Mills theory in the de Sitter static patch
Authors: Albrychiewicz Emil , Neiman Yasha , Tsulaia Mirian
Published: September 2021

Abstract

We study the scattering problem in the static patch of de Sitter space, i.e. the problem of field evolution between the past and future horizons of a de Sitter observer. We formulate the problem in terms of off-shell fields in Poincare coordinates. This is especially convenient for conformal theories, where the static patch can be viewed as a flat causal diamond, with one tip at the origin and the other at timelike infinity. As an important example, we consider Yang-Mills theory at tree level. We find that static-patch scattering for Yang-Mills is subject to BCFW-like recursion relations. These can reduce any static-patch amplitude to one with N−1MHV helicity structure, dressed by ordinary Minkowski amplitudes. We derive all the N−1MHV static-patch amplitudes from self-dual Yang-Mills field solutions. Using the recursion relations, we then derive from these an infinite set of MHV amplitudes, with arbitrary number of external legs.
Innovation in the discovery of the HIV-1 attachment inhibitor temsavir and its phosphonooxymethyl prodrug fostemsavir
Authors: Wang Tao , Kadow John F. , Meanwell Nicholas A.
Published: September 2021

The discovery and development of fostemsavir (2), the tromethamine salt of the phosphonooxymethyl prodrug of temsavir (1), encountered significant challenges at many points in the preclinical and clinical development program that, in many cases, stimulated the implementation of innovative solutions in order to enable further progression. In the preclinical program, a range of novel chemistry methodologies were developed during the course of the discovery effort that enabled a thorough examination and definition of the HIV-1 attachment inhibitor (AI) pharmacophore. These discoveries helped to address the challenges associated with realizing a molecule with all of the properties necessary to successfully advance through development and this aspect of the program is the major focus of this retrospective. Although challenges and innovation are not unusual in drug discovery and development programs, the HIV-1 AI program is noteworthy not only because of the serial nature of the challenges encountered along the development path, but also because it resulted in a compound that remains the first and only example of a mechanistically novel class of HIV-1 inhibitor that is proving to be very beneficial for controlling virus levels in highly treatment-experienced HIV-1 infected patients.
18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum
Authors: Moscoso Alexis , Silva-Rodríguez Jesús , Aldrey Jose Manuel , Cortés Julia , Pías-Peleteiro Juan Manuel , Ruibal Álvaro , Aguiar Pablo ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2021

Purpose

Recent evidence suggests that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer’s disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored.

Methods

Participants with concurrent 18F-florbetapir (FBP) PET, MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aβ-positive cognitively impaired, and 207 Aβ-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n = 195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and fluid biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline.

Results

In AD-continuum individuals, FBP retention in NAWM was (1) higher compared with WMH regions, (2) associated with DTI-based measures of WM integrity, and (3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aβ, and WMH burden. Most of these associations were also observed in Aβ-negative cognitively impaired individuals.

Conclusion

These results support the hypothesis that FBP retention in the WM is myelin-related. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course.
The use of acetabular screws in total hip arthroplasty and its influence on wear and periacetabular osteolysis in the long-term follow-up
Authors: Brodt Steffen , Bischoff Kathleen , Schulze Marcel , Nowack Dimitri , Roth Andreas , Matziolis Georg
Published: September 2021

Purpose

The cementless implantation of hip replacement cups may be performed with and without the additional use of acetabular screws. If the surgeon uses screws or not depends on variable factors. In general, the use of screws is intended to increase the primary stability of the cup. Whether screws increase the initial stability of the cup construct, or even reduce it in part, is the subject of considerable debate in the literature. It is also unclear whether the additional screws lead to increased wear or increased periacetabular osteolysis over the long-term course.

Methods

Two hundred eleven patients from a previous study with a minimum follow-up of 10.7 years were included. Of these, 68 patients with 82 total hip arthroplasties (THA) were given clinical and radiological follow-up examinations. Of these, 52 had been fitted without screws and 30 with screws. On the basis of radiographs, annual wear and osteolysis were quantified. The clinical results were recorded by means of VAS, HHS, and WOMAC scores.

Results

Significantly more periacetabular osteolysis was found if additive acetabular screws had been used. No difference was found in relation to the volumetric wear per year. Likewise, no difference was found with regard to the clinical scores.

Conclusions

The use of additive acetabular screws leads to increased osteolysis in the periacetabular bone stock. Insofar as the primary stability of the cementless cup construct allows it, no additional acetabular screws should be used.
Comparison of Outcomes of Emergency Laparotomies Performed During Daytime Versus Nights and Weekends in Rwandan University Teaching Hospitals
Authors: Twahirwa Isaie , Niyonshuti Norbert , Uwase Clement , Rickard Jennifer
Published: September 2021

Background

Emergency laparotomy is a common procedure with high morbidity and mortality. The aim of this study was to assess if the time of surgery (day versus night and weekend) affects the morbidity and mortality in a low‐resource setting.

Methods

A retrospective study was conducted in 2 university teaching hospitals in Rwanda. Patient characteristics, time of laparotomy, operative details and postoperative outcomes were recorded. Chi‐square and Wilcoxon rank sum tests were used to determine factors and outcomes associated with time of surgery. Logistic regression was used to determine factors associated with mortality.

Results

In 309 patients, who underwent emergency laparotomy, 147 (48%) patients were operated during the daytime, 123 (40%) patients were operated during the night shift and 39 (12%) patients were operated on the weekend. Common diagnoses were intestinal obstruction (n = 141, 46%), peritonitis (n = 101, 33%) and abdominal trauma (n = 40, 13%). The overall mortality rate was 16% with 14% in patients operated during day and 17% in patients operated during night and weekends (p = 0.564). Overall, the morbidity rate was 30% with 27% in patients operated during the day compared with 32% in patients operated during night/weekends (p = 0.348). After controlling for confounding factors, there was no association between time of operation and mortality or morbidity.

Conclusion

Morbidity and mortality associated with emergency laparotomy are high but the time of day for emergency laparotomy did not affect outcome in Rwandan referral hospitals.
Comparison of a Lateral Flow Assay and a Latex Agglutination Test for the Diagnosis of Cryptococcus Neoformans Infection
Authors: Schub Thilo , Forster Johannes , Suerbaum Sebastian , Wagener Johannes , Dichtl Karl
Published: September 2021

Infections by the basidiomycete yeast Cryptococcus neoformans are life-threatening diseases claiming more than 600,000 lives every year. The most common manifestation is cryptococcal meningitis in AIDS patients. Diagnosis primarily relies on antigen testing from serum and cerebrospinal fluid (CSF). Current guidelines recommend rapid antigen testing with a focus on point-of-care assays. Over the recent years, a range of new lateral flow assays (LFAs) was launched. There is still a lack of data evaluating the CE-certified Biosynex RDT CryptoPS LFA. We compared the performance of this LFA with a latex agglutination assay (LAA; Latex-Cryptococcus Antigen Detection System, IMMY) from blood and CSF samples. Blood and/or CSF samples of 27 patients with proven cryptococcal infections caused by different species and blood–CSF pairs of 20 controls were tested applying LFA and LAA. Upon combined analysis of blood and CSF, both assays were able to identify all C. neoformans infections. Based on CSF analysis only, the LFA and the LAA had sensitivities of 100% and 93%. Neither test gave false-positive results nor was reactive in two cases of C. non-neoformans/non-gattii species infections. Both assays have high sensitivities and specificities for the diagnosis of C. neoformans infection. Contrarily to the IMMY LAA, the RDT CryptoPS LFA is suitable as a point-of-care test but is limited in the quantification of antigen reactivity.
Stochastic mixed model sequencing with multiple stations using reinforcement learning and probability quantiles
Authors: Brammer Janis , Lutz Bernhard , Neumann Dirk
Published: September 2021

In this study, we propose a reinforcement learning (RL) approach for minimizing the number of work overload situations in the mixed model sequencing (MMS) problem with stochastic processing times. The learning environment simulates stochastic processing times and penalizes work overloads with negative rewards. To account for the stochastic component of the problem, we implement a state representation that specifies whether work overloads will occur if the processing times are equal to their respective 25%, 50%, and 75% probability quantiles. Thereby, the RL agent is guided toward minimizing the number of overload situations while being provided with statistical information about how fluctuations in processing times affect the solution quality. To the best of our knowledge, this study is the first to consider the stochastic problem variation with a minimization of overload situations.
Sexual dysfunction and depression in Behçet’s disease in comparison to healthy controls
Authors: Saur Sebastian-Jonas , Schlögl Alexandra , Schmalen Torsten , Krittian Simon , Pecher Ann-Christin , Henes Melanie , Xenitidis Theodoros , Henes Jörg
Published: September 2021

Behçet’s disease (BD) can affect the genital system and is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) and depression in patients with BD compared to a healthy control group (HCG). In addition, differences with regard to depression and patients’ origin were evaluated. This prospective, monocentric study included 106 consecutive patients from our specialized BD outpatient clinic. Patients were asked to fill out the paper based standardized and validated questionnaires International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI). In addition, 206 healthy controls were asked to fill out the questionnaires. 106 patients with BD were evaluated and 206 participants in the HCG. The mean age in BD group was 40.5 years as compared to 44.4 years in the HCG. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of male patients showed signs of SD, while half of the women’s group was suffering from SD. The prevalence for SD was significantly higher in women with Middle Eastern ethnic origin compared to women with Caucasian origin (75 vs. 33.3%, p = 0.024). Erectile Dysfunction occurred in 55% of all male patients which was not statistical different from the HCG. Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects as compared to 6.25% in the HCG (p < 0.001). Both, SD and depression correlated positively in males (p = 0.017) and females (p = 0.013). SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. Depression especially is more prevalent compared to the healthy population.
Predictive value of gadoxetic acid–enhanced MRI for posthepatectomy liver failure: a systematic review
Authors: Wang Qiang , Wang Anrong , Sparrelid Ernesto , Zhang Jiaxing , Zhao Ying , Ma Kuansheng , Brismar Torkel B.
Published: September 2021

Objectives

Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy of gadoxetic acid–enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF.

Methods

A systematic literature search was performed in the databases of PubMed/Medline, Web of Science, Embase, and Cochrane Library up to 11 December 2020. Studies evaluating the incidence of PHLF on patients who underwent hepatectomy with preoperative liver function assessment using gadoxetic acid–enhanced MRI were included. Data was extracted using pre-designed tables. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias.

Results

A total of 15 studies were identified for qualitative synthesis and most studies were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%. The predictive sensitivity and specificity of gadoxetic acid–enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid–enhanced MRI parameter was a predictor for PHLF.

Conclusions

Gadoxetic acid–enhanced MRI showed a high predictive capacity for PHLF and represents a promising imaging biomarker in prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters.

Key Points

• There is an obvious heterogeneity of the published studies, not only in variance of MRI liver function parameters but also in indication and extent of the liver resection.

• Signal intensity (SI)–based parameters derived from gadoxetic acid–enhanced MRI are the commonly used method for PHLF prediction.

• Gadoxetic acid–enhanced MRI-derived parameters showed high predictive efficacy for PHLF and can potentially serve as a predictor for the incidence of PHLF.
Occult lymph node metastases in patients without residual muscle-invasive bladder cancer at radical cystectomy with or without neoadjuvant chemotherapy: a nationwide study of 5417 patients
Authors: van Hoogstraten L. M. C. , van Gennep E. J. , Kiemeney L. A. L. M. , Witjes J. A. , Voskuilen C. S. , Deelen M. , Mertens L. S. , Meijer R. P. , Boormans J. L. , Robbrecht D. G. J. , Beerepoot L. V. , Verhoeven R. H. A. , Ripping T. M. ,   BlaZIB Study Group, van Rhijn B. W. G. , Aben K. K. H. , Hermans T. J. N.
Published: September 2021

Purpose

Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS).

Methods

Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995–December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017–October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with <(y)pT2N0 vs. <(y)pT2N+ disease was estimated by the Kaplan–Meier method.

Results

In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to  <(y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of  <(y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with  <(y)pT2N+ and  <(y)pT2N0, median OS was 3.5 years (95% CI 2.5–8.9) versus 12.9 years (95% CI 11.7–14.0), respectively.

Conclusion

Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments.
Hip joint range of motion is restricted by pain rather than mechanical impingement in individuals with femoroacetabular impingement syndrome
Authors: Naili Josefine E. , Stålman Anders , Valentin Anders , Skorpil Mikael , Weidenhielm Lars
Published: September 2021

Introduction

Discerning whether range of motion (ROM) is restricted by morphology or other pain sources is challenging in patients with femoroacetabular impingement syndrome (FAIS). Computed tomography (CT) motion simulation provides a hypothetical ROM based on morphology. This study aimed to explore associations between ROM measured using CT motion simulation and maximum passive ROM measured clinically using three dimensional (3D) motion analysis in patients with FAIS, prior to and post arthroscopic hip surgery.

Materials and methods

Eight males with FAIS (in total 12 hip joints) were included in this explorative feasibility study. Participants were examined using CT according to a low-dose protocol prior to and 7-months post arthroscopic surgery. Software was used to simulate at which ROM the impingement would occur. With the hip in 90 degrees’ flexion, maximum passive range of internal hip rotation, and maximum passive internal hip rotation coupled with adduction was examined clinically using 3D motion analysis pre- and postoperatively. Spearman rank correlation coefficients and linear regressions examined associations between methods.

Results

Preoperatively, the correlation between maximum internal hip rotation measured using CT motion simulation and 3D motion analysis was strong (r = 0.71, p = 0.009). Linear regressions demonstrated that maximal internal rotation measured using CT motion simulation was predominantly larger than when measured using 3D motion analysis. Postoperatively, and when maximum internal rotation was coupled with adduction, no correlations were found between the two methods.

Conclusions

The hypothetical morphology restricted ROM is larger than clinically assessed pain restricted ROM, both prior to and post hip arthroscopy. These findings suggest that ROM is restricted by pain rather than mechanical, morphology-based impingement in individuals with FAIS.
Analyse realer 110-kV-Lastverläufe für die zeitreihenbasierte probabilistische Lastflussrechnung in der Netzplanung unter Berücksichtigung der neuen Kundengruppe Rechenzentren
Authors: Pfüller Tim , Hanson Jutta
Published: September 2021

Verteilnetzbetreiber sind in den vergangenen Jahren immer neuen Herausforderungen ausgesetzt worden. Zu nennen sind die Energiewende, die Mobilitätswende und die Digitalisierung. Einige Netzbetreiber erleben die Digitalisierung in Form von vermehrten Netzanschlussanfragen von Rechenzentren im Verteilnetz, deren Größenordnung sich jeweils zwischen 5 MVA und 300 MVA bewegt. Um eine erfolgreiche und schnelle Integration dieser neuen Kunden zu ermöglichen, reicht der konventionelle Ansatz zur Planung, Starklast ohne Einspeisung und Schwachlast mit maximaler Einspeisung gemäß VDE-AR-N 4121, nicht mehr aus bzw. hätte dieser Ansatz einen enormen Netzausbau für die Verteilnetze zur Folge. Probabilistische Ansätze können bei der Bewältigung dieser Herausforderung helfen und eine bedarfsorientierte Netzausbauplanung vorantreiben. Das setzt eine Auseinandersetzung mit den realen Lastverläufen im 110-kV-Verteilnetz voraus. Dieser Artikel gibt einen Überblick über die Analyse und Gruppierung realer Lastverläufe im 110-kV-Verteilnetz der Syna GmbH aus dem Jahr 2018. Die Besonderheiten der Lastverläufe von Rechenzentren und deren Auswirkungen auf die Netzplanung werden aufgezeigt. Hierdurch werden aufschlussreiche Erkenntnisse über den tagestyp- und jahreszeitabhängigen Lastverlauf gewonnen. Auch lässt sich eine sehr große Abweichung von ca. 25 % zwischen Starklast- und Höchstlastfall, bezogen auf die Netzlast, identifizieren. Insbesondere der Starklastfall ist bei einigen Verteilnetzbetreibern als „Worst-Case-Szenario“ in Gebrauch. Dies ist einer der Gründe, die es rechtfertigen, sich mit den zeitreihenbasierten probabilistischen Lastflussrechnungen auseinanderzusetzen, mit dem Ziel, Strategien zum Anschluss großer Leistungen zu entwickeln.
A post hoc analysis of the effect of viloxazine extended-release capsules on learning and school problems in children and adolescents with attention-deficit/hyperactivity disorder
Authors: Faraone Stephen V. , Gomeni Roberto , Hull Joseph T. , Busse Gregory D. , Melyan Zare , Rubin Jonathan , Nasser Azmi
Published: September 2021

Improvement in attention-deficit/hyperactivity disorder (ADHD) symptoms vs. placebo was reported in a series of pediatric clinical trials of viloxazine extended-release capsules (viloxazine ER; Qelbree™). This post hoc analysis of those studies evaluated the effect of viloxazine ER on learning and school problems (LSPs). We used data from four Phase 3 placebo-controlled trials of 100–600 mg/day viloxazine ER (N = 1354; 6–17 years of age). LSPs were evaluated using the School domain of the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P-S) and the Learning Problems content scale of the Conners 3rd Edition-Parent Short Form (C3PS-LP) at baseline and end of study (≥ Week 6). ADHD symptoms were assessed weekly using the ADHD Rating Scale 5th Edition. The analyses were performed using the general linear mixed model with participant as a random effect. The responder analyses were performed using the Chi-square test. Viloxazine ER demonstrated significantly greater improvements in WFIRS-P-S (p < 0.0001) and C3PS-LP (p = 0.0113) scores vs. placebo. The response rate for the WFIRS-P-S was significantly greater for viloxazine ER vs. placebo (p = 0.001), and the number needed to treat (NNT) was 10.3 (effect size 0.7). Conversely, response rates for C3PS-LP did not differ between groups (p = 0.9069). In addition to ADHD symptoms improvement demonstrated in previous studies, viloxazine ER significantly reduced LSPs in pediatric subjects with ADHD. The responder analyses and NNT estimates indicate that a substantial number of children and adolescents with ADHD treated with viloxazine ER improved in clinically assessed LSPs.
Prevalence and factors related to sleep apnoea in ankylosing spondylitis
Authors: Wiginder Adrian , Sahlin-Ingridsson Carin , Geijer Mats , Blomberg Anders , Franklin Karl A. , Forsblad-d’Elia Helena
Published: September 2021

An increased prevalence of obstructive sleep apnoea (OSA) has been suggested in patients with ankylosing spondylitis (AS) in a few controlled studies. We aimed to study the prevalence of OSA compared to controls and to investigate if disease-related and non-disease-related factors were determinants of OSA in AS patients. One hundred and fifty-five patients with AS were included in the Backbone study, a cross-sectional study that investigates severity and comorbidities in AS. Controls were recruited from the Swedish CArdioPulmonary bioImage Study. To evaluate OSA, the participants were asked to undergo home sleep-monitoring during one night’s sleep. For each AS patient 45–70 years old, four controls were matched for sex, age, weight, and height. OSA was defined as an apnoea-hypopnoea index (AHI) ≥ 5 events/hour. Sixty-three patients with AS were examined with home sleep-monitoring, and 179 controls were matched with 46 patients, 45–70 years. Twenty-two out of 46 (47.8%) patients with AS vs. 91/179 (50.8%) controls had OSA (AHI ≥ 5 events/hour), P = 0.72. No differences in the sleep measurements were noted in AS patients vs. controls. In logistic regression analysis adjusted for age and sex, higher age, higher BMI, and lesser chest expansion were associated with the presence of OSA in the 63 AS patients. In the current study, patients with AS did not have a higher prevalence of OSA compared to matched controls. AS patients with OSA had higher BMI, were older, and had lesser chest expansion because of more severe AS compared to patients without OSA.

Key points

• Patients with ankylosing spondylitis did not have a higher prevalence of obstructive sleep apnoea versus matched controls.

• Patients with ankylosing spondylitis and obstructive sleep apnoea were older and had higher body mass index versus patients without obstructive sleep apnoea.

• Patients with ankylosing spondylitis and obstructive sleep apnoea had lesser chest expansion versus patients without obstructive sleep apnoea.
Real-world safety and effectiveness of nivolumab in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction cancer that has progressed after chemotherapy: a postmarketing surveillance study
Authors: Yamaguchi Kensei , Boku Narikazu , Muro Kei , Yoshida Kazuhiro , Baba Hideo , Tanaka Shinji , Akamatsu Ayumi , Sano Takeshi
Published: September 2021

Background

This postmarketing surveillance study evaluated the real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer.

Methods

This multicenter, observational study was conducted at 158 centers in Japan. Patients with unresectable advanced or recurrent G/GEJ cancer were registered between Nov 1, 2017, and Oct 31, 2018, and observed for 6 months after treatment initiation with nivolumab. Correlation of background characteristics with treatment-related adverse events (TRAEs) and tumor response was explored.

Results

Overall, 654 patients were registered (safety analysis set, n = 650; effectiveness analysis set, n = 636; response evaluation set, n = 516). The incidences of all TRAEs and grade ≥ 3 TRAEs were 31.5 and 11.2%, respectively. TRAEs significantly correlated with the absence of peritoneal metastasis; C-reactive protein level < 1; prior G/GEJ cancer surgery; and past or concomitant pulmonary, thyroid, or renal disease (each p < 0.05). The incidence of TRAEs was significantly lower in patients with higher Glasgow prognostic scores (p < 0.05). No new safety signals were observed. Complete response, partial response, stable disease, and progressive disease were observed in 1.2, 10.1, 27.1, and 58.3% of the response evaluation set, respectively. Patients aged ≥ 65 years (13.9 vs 5.3%, p = 0.0083) and ≥ 75 years (18.8 vs 9.2%, p = 0.0036) showed a higher response rate than their younger counterparts.

Conclusions

The real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent G/GEJ cancer were consistent with those observed in the phase 3 ATTRACTION-2 study.
Comparison of inulin clearance with 2-h creatinine clearance in Japanese pediatric patients with renal disease: open-label phase 3 study of inulin
Authors: Uemura Osamu , Ishikura Kenji , Kamei Koichi , Hamada Riku , Yamamoto Masaki , Gotoh Yoshimitsu , Fujita Naoya , Sakai Tomoyuki , Sano Takafumi , Fushimi Masahiko , Iijima Kazumoto
Published: September 2021

Background

There is no approved dosage and administration of inulin for children. Therefore, we measured inulin clearance (Cin) in pediatric patients with renal disease using the pediatric dosage and administration formulated by the Japanese Society for Pediatric Nephrology, and compared Cin with creatinine clearance (Ccr) measured at the same time. We examined to what degree Ccr overestimates Cin, using the clearance ratio (Ccr/Cin), and confirmed the safety of inulin in pediatric patients.

Methods

Pediatric renal disease patients aged 18 years or younger were enrolled. Inulin (1.0 g/dL) was administered intravenously at a priming rate of 8 mL/kg/hr (max 300 mL/hr) for 30 min. Next, patients received inulin at a maintenance rate of 0.7 × eGFR mL/min/1.73 m2 × body surface area (max 100 mL/hr) for 120 min. With the time the maintenance rate was initiated as a starting point, blood was collected at 30 and 90 min, while urine was collected twice at 60-min intervals. The primary endpoint was the ratio of Ccr to Cin (Ccr/Cin).

Results

Inulin was administered to 60 pediatric patients with renal disease; 1 patient was discontinued and 59 completed. The primary endpoint, Ccr/Cin, was 1.78 ± 0.52 (mean ± standard deviation). Regarding safety, five adverse events were observed in four patients (6.7%); all were non-serious. No adverse reactions were observed in this study.

Conclusions

The results in this study on the dosage and administration of inulin showed that inulin can safely and accurately determine GFR in pediatric patients with renal disease.

ClinicalTrials.gov identifier

NCT03345316.
A Study of Gene Expression, Structure, and Contractility of iPSC-Derived Cardiac Myocytes from a Family with Heart Disease due to LMNA Mutation
Authors: Mehrabi Mehrsa , Morris Tessa A. , Cang Zixuan , Nguyen Cecilia H. H. , Sha Yutong , Asad Mira N. , Khachikyan Nyree , Greene Taylor L. , Becker Danielle M. , Nie Qing , Zaragoza Michael V. , Grosberg Anna
Published: September 2021

Genetic mutations to the Lamin A/C gene (LMNA) can cause heart disease, but the mechanisms making cardiac tissues uniquely vulnerable to the mutations remain largely unknown. Further, patients with LMNA mutations have highly variable presentation of heart disease progression and type. In vitro patient-specific experiments could provide a powerful platform for studying this phenomenon, but the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) introduces heterogeneity in maturity and function thus complicating the interpretation of the results of any single experiment. We hypothesized that integrating single cell RNA sequencing (scRNA-seq) with analysis of the tissue architecture and contractile function would elucidate some of the probable mechanisms. To test this, we investigated five iPSC-CM lines, three controls and two patients with a (c.357-2A>G) mutation. The patient iPSC-CM tissues had significantly weaker stress generation potential than control iPSC-CM tissues demonstrating the viability of our in vitro approach. Through scRNA-seq, differentially expressed genes between control and patient lines were identified. Some of these genes, linked to quantitative structural and functional changes, were cardiac specific, explaining the targeted nature of the disease progression seen in patients. The results of this work demonstrate the utility of combining in vitro tools in exploring heart disease mechanics.
Evaluation of the URGOnight Tele-neurofeedback Device: An Open-label Feasibility Study with Follow-up
Authors: Krepel Noralie , Egtberts Tommy , Touré-Cuq Emma , Bouny Pierre , Arns Martijn
Published: September 2021

SMR neurofeedback shows potential as a therapeutic tool for reducing sleep problems. It is hypothesized that SMR neurofeedback trains the reticulo-thalamocortical-cortical circuit involved in sleep-spindle generation. As such, strengthening this circuit is hypothesized to reduce sleep problems. The current study aims to investigate the effectiveness of a home-based device that uses SMR neurofeedback to help reduce sleep problems. Thirty-seven participants reporting sleep problems received the SMR neurofeedback-based program for 40 (n = 21) or 60 (n = 16) sessions. The Pittsburgh Sleep Quality Index (PSQI) and Holland Sleep Disorders Questionnaire (HSDQ) were assessed at baseline, session 20, outtake, and follow-up (FU). Actigraphy measurements were taken at baseline, session 20, and outtake. Significant improvements were observed in PSQI Total (d = 0.78), PSQI Sleep Duration (d = 0.52), HSDQ Total (d = 0.80), and HSDQ Insomnia (d = 0.79). Sleep duration (based on PSQI) increased from 5.3 h at baseline to 5.8 after treatment and 6.0 h. at FU. No effects of number of sessions were found. Participants qualified as successful SMR-learners demonstrated a significantly larger gain in sleep duration (d = 0.86 pre-post; average gain = 1.0 h.) compared to non-learners. The home-based SMR tele-neurofeedback device shows the potential to effectively reduce sleep problems, with SMR-learners demonstrating significantly better improvement. Although randomized controlled trials (RCTs) are needed to further elucidate the specific effect of this device on sleep problems, this is the first home-based SMR neurofeedback device using dry electrodes demonstrating effectiveness and feasibility.
Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study
Authors: Thein Kyaw Z. , Karp Daniel D. , Tsimberidou Apostolia , Gong Jing , Sulovic Selma , Shah Jatin , Milton Denái R. , Hong David S. , Janku Filip , McQuinn Lacey , Stephen Bettzy A. , Colen Rivka , Carter Brett W. , Yap Timothy A. , Piha-Paul Sarina A. , Fu Siqing , Meric-Bernstam Funda , Naing Aung
Published: September 2021

Background. Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies. Methods. This was a single-center, multi-arm phase Ib study utilizing a “basket type” expansion. CT and selinexor was employed as one of the 13 parallel arms. Advanced relapsed/refractory solid tumors following standard therapy or where the addition of selinexor to standard regimens deemed appropriate, were eligible. Results. Of 13 patients treated, 12 patients were evaluable for response. The most common cancers were breast (n = 4), esophageal (n = 2), ovarian (n = 2) and non-small cell lung cancers (n = 2). All 13 patients had at least one treatment-related adverse events (TRAEs) and the most common were neutropenia (85%), leukopenia (85%), thrombocytopenia (85%), anemia (69%), nausea (54%), vomiting (46%), and fatigue (46%). One patient at 60 mg QW experienced DLT with grade 3 nausea and vomiting lasting 3 days. Unconfirmed partial response (uPR) was observed in 3 patients; one patient each with esophageal, breast, and ovarian cancer. One patient with esophageal adenocarcinoma had confirmed PR, however, was discontinued from the study due to clinical progression. Five patients achieved stable disease (SD). Disease control rate was 8%. Majority of patients (77%), including two patients who had uPR, had prior exposure to carboplatin and/or paclitaxel. Time-to-treatment failure (TTF) ranged from 1 to 153 weeks. Conclusion. The RP2D of selinexor was 60 mg QW in combination with CT. The combination conferred viable clinical activity with durable objective responses which should further be explored in tumor types for which CT is used as standard of care. Trial information. ClinicalTrials.gov Identifier: NCT02419495. Sponsor(s): Karyopharm Therapeutics. (Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495).