bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation and Application of a PET Tracer in Preclinical and Phase 1 Studies to Determine the Brain Biodistribution of Minzasolmin (UCB0599)
Authors: Mercier Joël , Bani Massimo , Colson Anny-Odile , Germani Massimiliano , Lalla Marianna , Plisson Christophe , Huiban Mickael , Searle Graham , Mathy François-Xavier , Nicholl Richard , Otoul Christian , Smit Johan Willem , van Asch Vanja , Wagneur Michel , Maguire Ralph Paul
Published: December 2023

Purpose

Minzasolmin (UCB0599) is an orally administered, small molecule inhibitor of ASYN misfolding in development as a potential disease-modifying therapy for Parkinson’s disease. Here we describe the preclinical development of a radiolabeled tracer and results from a phase 1 study using the tracer to investigate the brain distribution of minzasolmin.

Procedures

In the preclinical study, two radiolabeling positions were investigated on the S-enantiomer of minzasolmin (UCB2713): [11C]methylamine UCB2713 ([11C-N-CH3]UCB2713) and [11C]carbonyl UCB2713 ([11C-CO]UCB2713). Male C57 black 6 mice (N = 10) received intravenous [11C-N-CH3]UCB2713; brain homogenates were assessed for radioactivity and plasma samples analyzed by high-performance liquid chromatography. Positron emission tomography-computed tomography (PET-CT) was used to image brains in a subset of mice (n = 3). In the open-label, phase 1 study, healthy volunteers were scanned twice with PET-CT following injection with [11C]minzasolmin radiotracer (≤ 10 µg), first without, then with oral dosing with non-radiolabeled minzasolmin 360 mg. Primary objective: to determine biodistribution of minzasolmin in the human brain; secondary objectives included minzasolmin safety/tolerability.

Results

Preclinical data supported the use of [11C]minzasolmin in clinical studies. In the phase 1 study, PET data showed substantial drug signal in the brain of healthy volunteers (N = 4). The mean estimated whole brain total distribution volume (VT) at equilibrium across all regions of interest was 0.512 mL/cm3, no difference in VT was observed following administration of minzasolmin 360 mg. Treatment-emergent adverse events (TEAEs) were reported by 75% (n = 3) of participants. No drug-related TEAEs, deaths, serious adverse events, or discontinuations were reported.

Conclusion

Following positive preclinical results with the N-methyl labeled PET tracer, [11C]minzasolmin was used in the phase 1 study, which demonstrated that minzasolmin readily crossed the blood–brain barrier and was well distributed throughout the brain. Safety and pharmacokinetic findings were consistent with previous early-phase studies (such as UP0077, NCT04875962).
Numerical investigation of mixed physical barriers for saltwater removal in coastal heterogeneous aquifers
Authors: Emara Sobhy R. , Armanuos Asaad M. , Zeidan Bakenaz A. , Gado Tamer A.
Published: December 2023

Saltwater intrusion is a prevalent global environmental issue that detrimentally impacts coastal groundwater aquifers. This problem is exacerbated by climate change and increased groundwater abstraction. Employing physical barriers proves effective in mitigating saline water intrusion. In this study, a validated numerical simulation model is utilized to assess the impact of aquifer stratification on the effectiveness of mixed physical barriers (MPBs) and their response to structural variations. Additionally, the performance of MPBs was compared with that of single physical barriers in a laboratory-scale aquifer. Three different configurations were replicated, comprising two stratified aquifers (HLH and LHL) and a homogenous reference aquifer (H). The results demonstrate that MPBs are efficient in decreasing the saltwater penetration length in the investigated cases. The reductions in penetration length were up to 65% in all cases. The removal efficacy of residual saline water for MPBs exceeded that of the subsurface dam by 2.1–3.3 times for H, 2.1–3.6 times for HLH, and 8.3 times for LHL conditions, while outperforming the cutoff wall by 38–100% for H, 39–44% for HLH, and 2.7–75% for LHL. These findings are of importance for decision-makers in choosing the most appropriate technique for mitigating saline water intrusion in heterogeneous coastal aquifers.
How to Achieve a Healthy City: a Scoping Review with Ten City Examples
Authors: Ziafati Bafarasat Abbas , Sharifi Ayyoob
Published: December 2023

This scoping review of the literature explores the following question: what systematic measures are needed to achieve a healthy city? The World Health Organization (WHO) suggests 11 characteristics of a healthy city. Measures contributing to these characteristics are extracted and classified into 29 themes. Implementation of some of these measures is illustrated by examples from Freiburg, Greater Vancouver, Singapore, Seattle, New York City, London, Nantes, Exeter, Copenhagen, and Washington, DC. The identified measures and examples indicate that a healthy city is a system of healthy sectors. A discussion section suggests healthy directions for nine sectors in a healthy city. These sectors include transportation, housing, schools, city planning, local government, environmental management, retail, heritage, and healthcare. Future work is advised to put more focus on characteristic 5 (i.e., the meeting of basic needs for all the city's people) and characteristic 10 (i.e., public health and sick care services accessible to all) of a healthy city.
Schule als Ort der Cannabisprävention – Was wir von Kanada lernen können
Authors: Steimle Larissa , Stöver Heino
Published: December 2023

Hintergrund

Im Zuge der Diskussionen um die Legalisierung von Cannabis in Deutschland wird der Schutz von Kindern und Jugendlichen oft als Gegenargument verwendet. In der Tat sollten insbesondere Heranwachsende vor einem Substanzkonsum geschützt werden. Ziel dieses Beitrags ist es, zu diskutieren, wie dies gelingen kann.

Methoden

Kanada legalisierte bereits 2018 den Freizeit-Cannabiskonsum für Erwachsene. Ziel der Legalisierung war es u. a., junge Menschen besser vor einem Konsum zu schützen. In diesem Beitrag wird daher aufgezeigt, wie Kanada mit dem Thema Jugendschutz umgeht, wobei v. a. der Kontext Schule fokussiert wird und welche Schlussfolgerungen sich hieraus für Deutschland ableiten lassen.

Schlussfolgerungen

Am Beispiel Kanada zeigt sich, dass Schule ein Ort ist, der zum Schutz von Heranwachsenden aktiv genutzt werden sollte. Maßnahmen im Hinblick auf Cannabis sollten über ausschließlich abstinenzorientierte, wissensbasierte Aufklärungsprogramme hinausgehen. Entsprechend bedarf es eines ganzheitlichen, universellen und multimodalen Ansatzes bestehend aus Primärprävention, Schadensminimierung, Reduzierung von Stigmatisierung sowie Ansätzen zur Chancengleichheit, um Jugendliche bestmöglich schützen zu können.
Automated Trajectory Planning and Analytical Improvement for Automated Repair by Robot-Guided Cold Spray
Authors: Lewke Marcel , Wu Hongjian , List Alexander , Gärtner Frank , Klassen Thomas , Fay Alexander
Published: December 2023

Cold spraying has emerged as a promising technique for the repair of metallic components. Manipulating the cold spray gun by industrial robots, referred to as robot-guided cold spraying, enables flexible and controlled material deposition. This work proposes a concept for automated planning of robotic cold spray paths and trajectories, enabling effective and efficient material deposition at specified repair locations. The concept incorporates predefined cold spray parameterizations and boundary conditions to provide the best possible material deposition for the individual repair application. The concept begins with the extraction of the volume to be filled. This volume is then sliced into suitable adaptively curved layers and converted into point clouds for path planning. Subsequently, the cold spray path is converted into a trajectory by adding a calculated spray velocity profile to produce the required locally varying layer thicknesses. In addition, simulation of the material deposition and a kinematic analysis of the simulated trajectory are performed. These are utilized as performance indicators for assessing deposit quality and material efficiency, enabling the validation and improvement of the parameterized trajectory. Finally, the implementation of the entire concept is demonstrated by representative use cases. The results demonstrate successful automated path and trajectory planning by the proposed concept, contributing to the overall goal of automated repair of damaged components by cold spraying.
Analysis of Changes in Glucose and Lipid Metabolism in Patients with Clinically Severe Obesity and Type 2 Diabetes Mellitus Undergoing Laparoscopic Sleeve Gastrectomy—Prospective Observational Study
Authors: Wysocki Michał , Mizera Magdalena , Karpińska Izabela , Ptaszkiewicz Kuba , Małczak Piotr , Pisarska-Adamczyk Magdalena , Kania Michał , Major Piotr
Published: December 2023

Introduction

We still lack studies providing analysis of changes in glucose and lipid metabolism after laparoscopic sleeve gastrectomy (LSG) in patients with type 2 diabetes mellitus (DM2). We aimed to investigate postoperative changes in glucose and lipid metabolism after LSG in patients with DM2.

Material and Methods

Prospective, observational study included patients with BMI ≥ 35 kg/m2 and ≤ 50 kg/m2, DM2 < 10 years of duration, who were qualified for LSG. Perioperative 14-day continuous glucose monitoring (CGM) began after preoperative clinical assessment and OGTT, then reassessment 1 and 12 months after LSG. Thirty-three patients in mean age of 45 ± 10 years were included in study (23 females).

Results

EBMIL before LSG was 17 ± 11.7%, after 1 month—36.3 ± 12.8%, while after 12 months—66.1 ± 21.7%. Fifty-two percent of the patients had DM2 remission after 12 months. None required then insulin therapy. 16/33 patients initially on oral antidiabetics still required them after 12 months. Significant decrease in HbA1C was observed: 5.96 ± 0.73%; 5.71 ± 0.80; 5.54 ± 0.52%. Same with HOMA-IR: 5.34 ± 2.84; 4.62 ± 3.78; 3.20 ± 1.99. In OGTT, lower increase in blood glucose with lesser insulin concentrations needed to recover glucose homeostasis was observed during follow-ups. Overtime perioperative average glucose concentration in CGM of 5.03 ± 1.09 mmol/L significantly differed after 12 months, 4.60 ± 0.53 (p = 0.042). Significantly higher percentage of glucose concentrations above targeted compartment (3.9–6.7 mmol/L) was observed in perioperative period (7% ± 4%), than in follow-up (4 ± 6% and 2 ± 1%). HDL significantly rose, while triglyceride levels significantly decreased.

Conclusions

Significant improvement in glucose and lipid metabolism was observed 12 months after LSG and changes began 1 month after procedure.

Graphical Abstract
Die Behandlung persönlichkeitsgestörter Rechtsbrecher im schweizerischen Maßnahmensystem
Authors: Höfer Friederike
Published: December 2023

Die Behandlung persönlichkeitsgestörter Rechtsbrecher erweist sich im forensisch-psychiatrischen Kliniksettings häufig als unbefriedigend. Der vorliegende Beitrag skizziert dazu die Rahmenbedingungen für die Behandlung solcher Straftäterinnen und Straftäter in der Schweiz, wo diese vorwiegend vollzugsbegleitend, in spezialisierten Abteilungen des Vollzugs oder in sozialtherapeutisch ausgerichteten Maßnahmezentren behandelt werden.
Cesium removal from radioactive wastewater by adsorption and membrane technology
Authors: Zhuang Shuting , Wang Jianlong
Published: December 2023

Radiocesium is frequently present in radioactive wastewater, while its removal is still a challenge due to its small hydrated radius, high diffusion coefficient, and similar chemical behavior to other alkali metal elements with high background concentrations. This review summarized and analyzed the recent advances in the removal of Cs+ from aqueous solutions, with a particular focus on adsorption and membrane separation methods. Various inorganic, organic, and biological adsorbents have undergone assessments to determine their efficacy in the removal of cesium ions. Additionally, membrane-based separation techniques, including reverse osmosis, forward osmosis, and membrane distillation, have also shown promise in effectively separating cesium ions from radioactive wastewater. Additionally, this review summarized the main approaches, including Kurion/SARRY system + desalination system and advanced liquid processing system, implemented after the Fukushima Daiichi nuclear power plant accident in Japan to remove radionuclides from contaminated water. Adsorption technology and membrane separation technology play a vital role in treatment of contaminated water.
Kinderen van acht tot en met twaalf jaar hebben een duidelijke mening over Positieve Gezondheid
Authors: de Bot Cindy , Dierx John
Published: December 2023

Samenvatting

Inleiding

Positieve Gezondheid (PG) focust op het vermogen om regie over de eigen gezondheid te behouden, ook bij kinderen. In dit onderzoek wordt geëxploreerd hoe basisschoolkinderen in de leeftijd van acht tot en met twaalf jaar denken over het begrip ‘Positieve Gezondheid’ en de dimensies van PG zoals opgenomen in de kindtool.

Methode

Een kwalitatieve onderzoeksmethode is toegepast, waarbij 25 semigestructureerde interviews werden afgenomen, bestaande uit acht vragen.

Resultaat

Kinderen denken vooral aan voeding, bewegen en ‘je goed voelen’ wanneer ze gevraagd worden wat PG betekent. Meer specifiek denken ze bij de dimensie ‘Mijn lichaam’ vooral aan slapen, gezond eten en beweging. Bij ‘Mijn gevoelens en gedachten’ noemen ze vooral vrolijk, verdrietig of boos zijn en ze hebben het ook bij ‘Lekker in je vel’ vooral over emoties en zich goed voelen, waarbij uiterlijk belangrijk is. De dimensie ‘Nu en later’ gaat volgens de kinderen vooral over een beroep later. Vrienden en pesten zijn termen die genoemd worden bij de dimensie ‘Meedoen’. Kunnen doen waar ze zin in hebben, vinden ze het belangrijkste bij de dimensie ‘Dagelijks leven’. Voor kinderen zijn de dimensies ‘Lekker in je vel zitten’ en ‘Mijn gevoelens en gedachten’ het belangrijkst. Daarnaast is ‘Meedoen’ van belang, waarbij alle kinderen vooral plezier hebben met vrienden en vriendinnen noemen.

Conclusie

Kinderen in de leeftijd van acht tot en met twaalf jaar zien PG breder dan alleen als de fysieke component en er- en herkennen in hun eigen bewoordingen alle dimensies van PG. Voor kinderen van alle leeftijden zijn de dimensies ‘Lekker in je vel zitten’, ‘Mijn gevoelens en gedachten’ en ‘Meedoen’ belangrijk, maar die worden bij toenemende leeftijd steeds belangrijker. Dat betekent voor docenten, jeugdgezondheidsprofessionals en ouders/verzorgers ten eerste dat ze het concept PG kunnen gebruiken bij het praten over gezond zijn en blijven, en daarmee interventies beter kunnen laten aansluiten op de belevingswereld en taal van kinderen.
Understanding the vulnerability of surface–groundwater interactions to climate change: insights from a Bavarian Forest headwater catchment
Authors: Munir Muhammad Usman , Blaurock Katharina , Frei Sven
Published: December 2023

Headwaters play a crucial role in maintaining forest biodiversity by providing unique habitats and are important for the regulation of water temperature and oxygen levels for downstream river networks. Approximately 90% of the total length of streams globally originate from headwaters and these systems are discussed to be especially vulnerable to impacts of climate change. This study uses an integrated hydrological model (HydroGeoSphere) in combination with 23 downscaled ensemble members from representative concentration pathways (RCPs) 2.6, 4.5 and 8.5 to examine how climate change affects water availability in a headwater catchment under baseflow conditions. The simulations consistently predict increasing water deficits in summer and autumn for both the near (2021–2050) and far future (2071–2099). Annual mean water deficits were estimated to be 4 to 7 times higher than historical levels. This is mainly due to a projected reduction in precipitation inputs of up to – 22%, while AET rates remain similar to those observed during the historical reference period (1992–2018). The declining groundwater storage reserves within the catchment are expected to result in a significant decline in surface water availability during summer and autumn, with a reduction in mean annual stream discharge by up to 34% compared to the reference period. Due to declining groundwater levels, upstream reaches are predicted to become intermittent in summer leading to a reduction of the total stream flow length by up to 200 m. Findings from this study will enhance our understanding of future water availability in headwater systems and may aid in the development of effective management strategies for mitigating local impacts of climate change and preserving these vulnerable ecosystems.
Examining the Effect of Assessment Construct Characteristics on Machine Learning Scoring of Scientific Argumentation
Authors: Haudek Kevin C. , Zhai Xiaoming
Published: December 2023

Argumentation, a key scientific practice presented in the Framework for K-12 Science Education, requires students to construct and critique arguments, but timely evaluation of arguments in large-scale classrooms is challenging. Recent work has shown the potential of automated scoring systems for open response assessments, leveraging machine learning (ML) and artificial intelligence (AI) to aid the scoring of written arguments in complex assessments. Moreover, research has amplified that the features (i.e., complexity, diversity, and structure) of assessment construct are critical to ML scoring accuracy, yet how the assessment construct may be associated with machine scoring accuracy remains unknown. This study investigated how the features associated with the assessment construct of a scientific argumentation assessment item affected machine scoring performance. Specifically, we conceptualized the construct in three dimensions: complexity, diversity, and structure. We employed human experts to code characteristics of the assessment tasks and score middle school student responses to 17 argumentation tasks aligned to three levels of a validated learning progression of scientific argumentation. We randomly selected 361 responses to use as training sets to build machine-learning scoring models for each item. The scoring models yielded a range of agreements with human consensus scores, measured by Cohen’s kappa (mean = 0.60; range 0.38 − 0.89), indicating good to almost perfect performance. We found that higher levels of Complexity and Diversity of the assessment task were associated with decreased model performance, similarly the relationship between levels of Structure and model performance showed a somewhat negative linear trend. These findings highlight the importance of considering these construct characteristics when developing ML models for scoring assessments, particularly for higher complexity items and multidimensional assessments.
Politische Unterstützung im Dauerstresstest – Einstellungen zur Demokratie in Thüringen seit der Jahrtausendwende
Authors: Hebenstreit Jörg , Reiser Marion
Published: December 2023

Vor dem Hintergrund der aktuellen Vielfachkrise und der Langzeitfolgen des Systemumbruchs untersucht der Beitrag die regionale politische Kultur in Thüringen. Auf Basis der Daten des Thüringen-Monitors zeigt die Langzeitanalyse der demokratischen Einstellungen für die Jahre 2000 bis 2022 ein differenziertes Ergebnis. Trotz einer hohen Volatilität von Vertrauens- und Zufriedenheitswerten kann bis zum Jahr 2021 ein tendenziell linearer Anstieg der politischen Unterstützung für die Demokratie in Thüringen festgestellt werden. Der starke Rückgang der Werte für die Demokratiezufriedenheit und das Vertrauen in die parteienstaatlichen Institutionen im Jahr 2022 zeigt jedoch, dass lang aufgebaute Unterstützungswerte in Kürze verschleißen können. Mit Blick auf die Determinanten der politischen Unterstützung bestätigen sich für Thüringen, dass die Performanz- sowie Deprivations- und eingeschränkt auch die Sozialisationshypothese erklärungsstarke Ansätze zur Bestimmung politischer Unterstützung darstellen.
Detection, Monitoring, and Mitigation of Drug-Induced Nephrotoxicity: A Pragmatic Approach
Authors: Antognini Nicola , Portman Ronald , Dong Victor , Webb Nicholas J. , Chand Deepa H.
Published: December 2023

The kidneys play a pivotal role in elimination of most drugs; therefore, a comprehensive understanding of renal physiology and pathology is important for those involved in drug development. High filtration capacity and metabolic activity make the kidneys vulnerable to drug-induced nephrotoxicity (DIN). Acute DIN may manifest on a background of renal impairment that has resulted from underlying disease, previously administered nephrotoxic medications, congenital renal abnormalities, or the natural aging process. The ability of the kidneys to compensate for DIN depends on the degree of pre-insult renal function. Therefore, it can be difficult to identify. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately than current clinical measures and may be effective in detecting DIN. The goal of this manuscript is to provide a pragmatic and evidence-based supportive guidance for the early identification and management of DIN during the drug development process for clinical trial participants of all ages. The overall objective is to minimize the impact of DIN on kidney function and to collect renal safety data enabling risk analysis and mitigation.
Vibration response of a hybrid steel–timber building element with uncertain material and joint parameters
Authors: Chocholaty Bettina , Eser Martin , Hoppe Karl-Alexander , Wang Daotong , Marburg Steffen
Published: December 2023

The design of building elements is usually done conservatively by considering safety factors. However, more efficient designs are gaining interest for economic and sustainability reasons. Hence, an adequate prediction tool can improve the design of building elements. Probabilistic modeling, for example, Monte Carlo simulations, represents a remedy to this by examining uncertainties in a structure through uncertain input parameters. In this work, a Monte Carlo simulation is performed to quantify the uncertainty in the modal properties of a hybrid steel–timber building element. The material properties of the timber material and the stiffness of the structural joints are considered uncertain inputs. The probabilistic properties of the timber material are evaluated utilizing Bayesian inference instead of the usually applied empirical methods. Using these inferred timber material properties leads to a good match of simulated and measured natural frequencies of the timber components. These parameters are utilized together with the joints’ uncertain inputs in the Monte Carlo simulation of the hybrid steel–timber building element. The results show a significant span for the identified eigenfrequencies, which proves the relevance of probabilistic analyses for the vibration characteristics of building elements.
Beyond Desirable in North America: an examination of actual and ideal body preferences, and body attractiveness preferences in a heterosexual sample of men and women from the USA
Authors: Talbot Daniel
Published: December 2023

A recent Australian study demonstrated that both men and women want to have less body fat and more muscularity than they perceived that they had, and that men and women’s body ideals are more extreme than the opposite sex finds most attractive. The present study aimed to provide more evidence for the discrepancy between self-reported actual and ideal body fat and muscularity. Further, the present study aimed to explore the relationship between ideal bodies, and the bodies reported to be most attractive by the opposite sex by examining a sample of heterosexual North American men and women. Using data from 362 participants recruited through Amazon’s MTurk, this study employed figural rating scales to assess participants' actual and ideal body fat and muscularity, as well as their perceptions of the most attractive body for the opposite sex. Results showed that men wanted to have less body fat and more muscularity, and women wanted to have less body fat than they perceived themselves to have. Additionally, results showed that men’s ideal body was in-line with women’s preferences. However, analogous to prior research in an Australian sample, women wanted to be thinner than what men found most attractive. These findings underscore the importance of addressing body dissatisfaction and promoting healthy body image ideals. Future interventions should focus on challenging societal beauty standards and promoting body acceptance, taking into account the influence of media and social factors on body image perceptions and preferences.
Multidimensional intuitive–analytic thinking style and its relation to moral concerns, epistemically suspect beliefs, and ideology
Authors: Bayrak Fatih , Dogruyol Burak , Alper Sinan , Yilmaz Onurcan
Published: December 2023

Literature highlights the distinction between intuitive and analytic thinking as a prominent cognitive style distinction, leading to the proposal of various theories within the framework of the dual process model. However, it remains unclear whether individuals differ in their thinking styles along a single dimension, from intuitive to analytic, or if other dimensions are at play. Moreover, the presence of numerous thinking style measures, employing different terminology but conceptually overlapping, leads to confusion. To address these complexities, Newton et al. suggested the idea that individuals vary across multiple dimensions of intuitive–analytic thinking styles and distinguished thinking styles between 4 distinct types: Actively open-minded thinking, close-minded thinking, preference for effortful thinking, and preference for intuitive thinking. They proposed a new measure for this 4-factor disposition, The 4-Component Thinking Styles Questionnaire (4-CTSQ), to comprehensively capture the psychological outcomes related to thinking styles; however, no independent test exists. In the current pre-registered studies, we test the validity of 4-CTSQ for the first time beyond the original study and examine the association of the proposed measure with various factors, including morality, conspiracy beliefs, paranormal and religious beliefs, vaccine hesitancy, and ideology in an underrepresented culture, Türkiye. We found that the correlated 4-factor model of 4-CTSQ is an appropriate measure to capture individual differences based on cognitive style. The results endorse the notion that cognitive style differences are characterized by distinct structures rather than being confined to two ends of a single continuum.
Meteorological drivers of melt at two nearby glaciers in the McMurdo Dry Valleys of Antarctica
Authors: Hofsteenge Marte G. , Cullen Nicolas J. , Conway Jonathan P. , Reijmer Carleen H. , van den Broeke Michiel R. , Katurji Marwan
Published: December 2023

We study the meteorological drivers of melt at two glaciers in Taylor Valley, Antarctica, using 22 years of weather station observations and surface energy fluxes. The glaciers are located only 30 km apart, but have different local climates; Taylor Glacier is generally drier and windier than Commonwealth Glacier, which receives more snowfall due to its proximity to the coast. Commonwealth Glacier shows more inter-annual melt variability, explained by variable albedo due to summer snowfall events. A significant increase in surface melt at Commonwealth Glacier is associated with a decrease in summer minimum albedo. Inter-annual variability in melt at both glaciers is linked to degree-days above freezing during föhn events, occurring more frequently at Taylor Glacier. At Taylor Glacier melt occurs most often with positive air temperatures, but föhn conditions also favour sublimation, which cools the surface and prevents melt for the majority of the positive air temperatures. At Commonwealth Glacier, most of the melt instead occurs with sub-zero air temperatures, driven by strong solar radiative heating. Future melt at Taylor Glacier will likely be more sensitive to changes in föhn events, while Commonwealth Glacier will be impacted more by changes in near coastal weather, where moisture inputs can drive cloud cover, snowfall and change albedo.
Looking at Monarchy Askance: Royal Brand Names and Trademark Law in the German Empire
Authors: Giloi Eva
Published: December 2023

This article uses the example of Manoli Cigarettes and its product line, The Kaiser Cigarettes, to examine the concept of co-branding as applied to royal brand names in the German Empire. It reviews the broader networks of circulation that determined the production of royal brand names: commercial laws, business ties, advances in technology, advertising structures, tourism, and other sectors of the consumer economy. The article delves into how trademark law, the Imperial Patent Office's role in approving brand names, and case law contributed to the choice of royal brand names. The article also illuminates how manufacturers used royal brands to implement business strategies along a horizontal plane of market competition. The production of the monarchy as a cultural object was thus activated through a process of triangulation: not only through the bilateral relationship between monarch and subjects, but also lateral relations between producers who were concerned about their professional networks.
An investigation into the factors influencing teachers’ inclusion of improvisation in piano lessons
Authors: Cossey Catherine
Published: December 2023

Despite the evidence of the benefits of improvisation in instrumental teaching, research indicates that many piano teachers do not include it in their lessons. The purpose of this study was to investigate the influences on piano teachers’ pedagogy to determine what factors impacted the teaching of improvisation. A total of 117 UK-based piano teachers participated in the survey. The data obtained indicates that an understanding of how to teach improvisation is a significant influence on teachers’ pedagogy. The conclusion argues that there is a need for piano teachers to have greater access to instrumental teaching courses to encourage them to reflect on their teaching practice.
Real-world evidence: experiences and challenges for decision making in Latin America
Authors: García Martí Sebastián , Pichón-Riviere Andrés , Augustovski Federico , Espinoza Manuel
Published: December 2023

Objective

The Health Technology Assessment (HTA) process aims to optimize health system funding of technologies. In recent years there has been an increase in what is known as Real-World Evidence (RWE) as a complement to clinical trials. The objective of Health Technology Assessment International’s Latin American Policy Forum 2022 was to explore the utility of incorporating RWE into HTA and decision-making processes in the region.

Methods

This article is based on a background document, survey, and the deliberative work of the country representatives who participated in the Forum.

Results

There is a growing interest in the use of Real-World Data / Real-World Evidence in HTA processes in Latin America, although currently there are no specific local guidelines for RWE use by HTA agencies. At present, its use is limited to certain areas such as adding context to HTA reports, the evaluation of adverse events, or cost estimation.

Potential future uses of RWE were identified, including the creation of risk-sharing agreements, the assessment of technology performance in routine practice, providing information on outcomes that are not so easily evaluated in clinical trials (e.g., the identification of specific subpopulations or quality of life), and the estimation of input parameters for economic evaluations.

Conclusions

The participants agreed that there are several areas presenting significant potential to expand the application of RWD/RWE and that the development of normative frameworks for its use could be helpful.
High-Flow Nasal Cannula versus Bag Valve Mask for Preoxygenation during Rapid Sequence Intubation in the Emergency Department: A Single-Center, Prospective, Randomized Controlled Trial
Authors: Cırıl Muhammed Fatih , Akarca Mustafa , Unal Akoglu Ebru , Cimilli Ozturk Tuba , Onur Özge
Published: December 2023

Objective:

Hypoxia is a frequently reported complication during the intubation procedure in the emergency department (ED) and may cause bad outcomes. Therefore, oxygenation plays an important role in emergency airway management. The efficacy of oxygenation with high-flow nasal cannula (HFNC) in the ED has been studied, though the evidence is limited. The study aim was to compare two methods of preoxygenation in patients undergoing rapid sequence intubation (RSI) in the ED: (1) HFNC and (2) bag-valve mask (BVM) oxygenation.

Methods:

This is a single-center, prospective, randomized controlled trial (RCT) in adult ED patients requiring RSI. Patients were randomized to receive preoxygenation with either HFNC or BVM. While HFNC therapy was continued during the intubation procedure, BVM oxygenation was interrupted for laryngoscopy. The primary outcome was the lowest peripheral oxygen saturation (SpO2) level during intubation. Secondary outcomes were incidence of desaturation (SpO2<90%) and severe hypoxemia (SpO2<80%) throughout the procedure, intubation time, rate of failed intubation, and 30-day survival rates.

Results:

A total of 135 patients were randomized into two groups (HFNC n = 68; BVM n = 67). The median lowest SpO2 value measured during intubation was 96% (88.8%-99.0%) in the HFNC group and 92% (86.0%-97.5%) in the BVM group (P = .161). During the intubation procedure, severe hypoxemia occurred in 13.2% (n = 9) of patients in the HFNC group and 8.9% (n = 6) in the BVM group, while mild hypoxemia was observed in 35.8% (n = 24) of the BVM group and 26.5% (n = 18) of the HFNC group. However, there was no statistically significant difference between the groups in terms of hypoxemia development (P = .429 and P = .241, respectively). No significant difference was reported in the rate of failed intubation between the groups. Thirty-day mortality was observed in 73.1% of the BVM group and 57.4% of the HFNC group, with a borderline statistically significant difference (difference 15.7; 95% CI of the difference: −0.4 to 30.7; P = .054).

Conclusion:

The use of HFNC for preoxygenation, when compared to standard care with BVM oxygenation, did not improve the lowest SpO2 levels during intubation. Also, the use of HFNC during intubation did not provide benefits in reducing the incidence of severe hypoxemia. However, the 30-day survival rates were slightly better in the HFNC group compared to the BVM group.
NORMAL SUBMONOIDS AND CONGRUENCES ON A MONOID
Authors: ELGUETA JOSEP
Published: December 2023

A notion of normal submonoid of a monoid M is introduced that generalizes the normal subgroups of a group. When ordered by inclusion, the set
$\mathsf {NorSub}(M)$
of normal submonoids of M is a complete lattice. Joins are explicitly described and the lattice is computed for the finite full transformation monoids
$T_n$
,
$n\geq ~1$
. It is also shown that
$\mathsf {NorSub}(M)$
is modular for a specific family of commutative monoids, including all Krull monoids, and that it, as a join semilattice, embeds isomorphically onto a join subsemilattice of the lattice
$\mathsf {Cong}(M)$
of congruences on M. This leads to a new strategy for computing
$\mathsf {Cong}(M)$
consisting of computing
$\mathsf {NorSub}(M)$
and the so-called unital congruences on the quotients of M modulo its normal submonoids. This provides a new perspective on Malcev’s computation of the congruences on
$T_n$
.
Litigating Policy Drift: Frozen Categories and Thresholds in Court
Authors: Hackett Ursula
Published: December 2023

The combination of rigid policy rules with shifting political, economic, and social environments can produce drift: policy change without formal modification. We know much about the political origins and consequences of drift but little about the legal battles that accelerate or impede it. I identify two distinct forms of policy rigidity that generate drift: interval freezing and categorical freezing. Drawing from recent and historical cases encompassing voting rights, racial discrimination, religious conscience protections, and other hot-button issues, I argue that drifting policies possess several sources of legal resilience: injuries are difficult to identify; judges can be persuaded of the merits of restraint, textual formalism, and bright-line rules; and policy makers plausibly deny any intentional action in pursuit of controversial outcomes. Drift is not an automatic and unremarkable process of continual policy change but rather the outcome of high-stakes political and legal contestation over how rigid policy thresholds and categories should be adapted to meet shifting conditions.
Cost-effectiveness analysis of intravascular ultrasound-guided	peripheral vascular interventions in patients with femoropopliteal peripheral	artery disease
Authors: Lichtenberg Michael , Mustapha Jihad , Tan Yan Zhi , Stavroulakis Konstantinos , Meijer Catherina , Bavière Henri Vanden
Published: December 2023

Summary: Background: Intravascular ultrasound (IVUS)-guided percutaneous transluminal angioplasty (PTA) might offer clinical benefits compared to angiography-guided PTA in patients with peripheral artery disease (PAD). A cost-effectiveness model was developed to examine the benefits and costs of IVUS-guided PTA versus angiography-guided PTA in PAD patients with femoropopliteal (FP) occlusive disease. Methods: A two-step model (a one-year decision tree followed by a lifetime semi-Markov model) was developed from a German healthcare payer perspective to estimate the costs and outcomes over a one-year and lifetime horizon. Clinical events included target lesion revascularization (TLR), amputation, and death. Transition probabilities and utility values were derived from published literature. Healthcare costs were based on German Diagnosis Related Groups (DRG) codes. Costs and outcomes were discounted at a rate of 3% per year. The incremental cost-effectiveness ratio (ICER) was calculated, and sensitivity analyses were performed to assess the robustness of the results. Results: In the one-year horizon, IVUS-guided PTA resulted in incremental quality-adjusted life-years (QALY) and costs of 0.02 and €919 per patient respectively, with a corresponding ICER of €45,195/QALY gained versus angiography-guided PTA. In the lifetime horizon, IVUS-guided PTA outperforms angiography-guided PTA; it was associated with a cost saving of €46 per patient and incremental QALY of 0.22. Utility value for post-TLR, as well as probabilities of death and TLR had the greatest impact on the one-year ICER, while cost of TLR and probabilities of TLR and amputation influenced the lifetime ICER most. The probability of IVUS-guided PTA being cost-effective at a willingness-to-pay (WTP) threshold of €50,000/QALY was 50.4% in the one-year horizon and increased to 85.9% in the lifetime horizon. Conclusions: In this analysis IVUS-guided PTA among patients with symptomatic FP atherosclerosis was cost-saving in a lifetime horizon from the German healthcare payer perspective.
Albedo as a Competing Warming Effect of Urban Greening
Authors: Schlaerth Hannah L. , Silva Sam J. , Li Yun , Li Dan
Published: December 2023

Urban greening is often proposed for urban heat island (UHI) mitigation because vegetation provides shade and increases evapotranspiration. However, vegetation has lower albedo and higher emissivity than the bare soil it often replaces, which increases incoming energy fluxes. Here, we use the Weather Research and Forecasting model to quantify and compare the albedo and non‐albedo effects (i.e., changes in emissivity, surface roughness, and evaporative fluxes) of urban greening in the Los Angeles Basin under policy relevant urban greening scenarios. When albedo‐induced effects were included in the model, daytime surface temperatures in urban areas warmed by 0.70 ± 0.89°C with increases in the sensible heat flux outweighing increases in the latent heat flux from increased evapotranspiration. In contrast, daytime surface temperatures cooled by 0.27 ± 0.72°C when the albedo‐induced effects were ignored. At night, including albedo‐induced effects of urban greening resulted in only half the cooling modeled in the non‐albedo simulations. Near surface air temperatures also had contrasting model results, with nighttime cooling of 0.21 ± 0.47°C outweighing slight daytime warming of 0.04 ± 0.32°C in the non‐albedo simulations and daytime warming of 0.33 ± 0.41°C outweighing slight nighttime cooling of 0.05 ± 0.46°C in the albedo simulations. Our results reveal the critical role that albedo plays in determining the net surface climate effects of urban greening. Reductions in albedo from urban greening should be carefully considered by policy makers and urban planners, especially as high albedo roofs and pavements are simultaneously being deployed for UHI mitigation in many cities.
Clinical and Ethical Considerations of Maladaptive Social Media Use in Pediatric Patients With Disorders of Gut–Brain Interaction
Authors: David Jennie G. , Kroon Van Diest Ashley , Hatley-Cotter Allison , Sanchez Raul , McKillop Hannah N.
Published: December 2023

Objective:

Social media (SM) use among adolescents is commonplace and an extension of their daily lives, with emerging attention to how SM can impact healthcare behaviors. In particular, the clinical and ethical nuance of maladaptive SM use among adolescents with disorders of gut–brain interaction (DGBI) diagnoses remains unclear and pressing to consider.

Method:

This article presents case examples of maladaptive SM use in (a) a pediatric patient with DGBI and (b) a caregiver of a pediatric patient with a DGBI. We then contextualize these case examples in existing ethical frameworks (e.g., the American Psychological Association Ethics Code) and the extant literature.

Results:

SM use in pediatrics can negatively impact healthcare behaviors and can lead to consumption of medical misinformation; this impact is particularly significant in pediatric DGBI and merits clinical assessment of maladaptive SM use in this population.

Conclusions:

SM use can be adaptive or maladaptive for adolescents with DGBIs and caregivers, with maladaptive SM use presenting significant clinical and ethical considerations. In addition to discussing ethical considerations, recommendations, and resources, we also provide clinical questions and takeaways for healthcare professionals to implement in pediatric DGBI care.

Implications for Impact Statement

Adolescents commonly use social media (SM), with growing attention to how SM can negatively impact health. Adolescents with disorders of gut–brain interaction may be particularly sensitive to this, and healthcare professionals working with this population should consider the ethical and clinical implications of maladaptive SM use.
PAK inhibitor FRAX486 decreases the metastatic potential of triple-negative breast cancer cells by blocking autophagy
Authors: Lyu Liang , Li Haiyan , Lu Kefeng , Jiang Shu , Li Huihui
Published: December 2023

Background

Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with a high risk of metastasis and recurrence and a poor prognosis. Epithelial-mesenchymal transition (EMT) endows epithelial cells with the ability to move to distant sites, which is essential for the metastasis of TNBC to organs, including the lung. Autophagy, an intracellular degradation process that involves formation of double-layered lipid autophagosomes that transport cytosolic cargoes into lysosomes via autophagosome–lysosome fusion, is involved in various diseases, including cancer and neurodegenerative, metabolic, cardiovascular, and infectious diseases. The relationship between autophagy and cancer has become relatively clear. However, research on pharmacological drugs that block cancer EMT by targeting autophagy is still in the initial stages. Therefore, the re-evaluation of old drugs for their potential in blocking both autophagy and EMT was conducted.

Methods

More than 2000 small molecule chemicals were screened for dual autophagy/EMT inhibitors, and FRAX486 was identified as the best candidate inhibitor of autophagy/EMT. The functions of FRAX486 in TNBC metastasis were detected by CCK-8, migration and wound healing assays. The effects of FRAX486 on autophagy and its target PAK2 were determined by immunoblotting, immunofluorescence, immunoprecipitation analysis and transmission electron microscopy. The findings were validated in mouse models.

Results

Here, we report that FRAX486, a potent P21-activated kinase 2 (PAK2) inhibitor, facilitates TNBC suppression both in vitro and in vivo by blocking autophagy. Mechanistically, FRAX486 inhibits autophagy in TNBC cells by targeting PAK2, leading to the ubiquitination and proteasomal degradation of STX17, which mediates autophagosome–lysosome fusion. The inhibition of autophagy by FRAX486 causes upregulation of the epithelial marker protein E-cadherin and thus suppresses the migration and metastasis of TNBC cells.

Conclusions

The effects of FRAX486 on TNBC metastasis suppression were verified to be dependent on PAK2 and autophagy inhibition. Together, our results provide a molecular basis for the application of FRAX486 as a potential treatment for inhibiting the metastasis of TNBC.
Bacteroides is increased in an autism cohort and induces autism-relevant behavioral changes in mice in a sex-dependent manner
Authors: Carmel Julie , Ghanayem Nasreen , Mayouf Rasha , Saleev Natalia , Chaterjee Ipsita , Getselter Dmitriy , Tikhonov Evgeny , Turjeman Sondra , Shaalan Monia , Khateeb Saleh , Kuzminsky Alla , Kvetniy-Ferdman Netta , Kronos Tanya , Bretler-Zager Tali , Koren Omry , Elliott Evan
Published: December 2023

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition which is defined by decreased social communication and the presence of repetitive or stereotypic behaviors. Recent evidence has suggested that the gut-brain axis may be important in neurodevelopment in general and may play a role in ASD in particular. Here, we present a study of the gut microbiome in 96 individuals diagnosed with ASD in Israel, compared to 42 neurotypical individuals. We determined differences in alpha and beta diversity in the microbiome of individuals with ASD and demonstrated that the phylum Bacteroidetes and genus Bacteroides were the most significantly over-represented in individuals with ASD. To understand the possible functional significance of these changes, we treated newborn mice with Bacteroides fragilis at birth. B. fragilis-treated male mice displayed social behavior dysfunction, increased repetitive behaviors, and gene expression dysregulation in the prefrontal cortex, while female mice did not display behavioral deficits. These findings suggest that overabundance of Bacteroides, particularly in early life, may have functional consequences for individuals with ASD.