bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrolyzable microplastics in soil—low biodegradation but formation of a specific microbial habitat?
Authors: Schöpfer Lion , Schnepf Uwe , Marhan Sven , Brümmer Franz , Kandeler Ellen , Pagel Holger
Published: March 2022

Microplastics (MP, plastic particles between 0.1 and 5000 μm) contaminate agricultural soils through the application of organic fertilizers, sewage sludge, and plastic mulch. MP surfaces and the MP-soil interface provide specific habitats for soil microorganisms—the plastisphere. Microorganisms in the plastisphere may benefit from utilizing MP as a carbon (C) source. Hydrolyzable MP with ester bonds are susceptible to enzymatic depolymerization by hydrolysis. In a microcosm experiment, we investigated MP biodegradation of small and large (< 0.5 mm and 0.5–2 mm respectively), hydrolyzable (a poly(lactic acid)/poly(butylene co-adipate terephthalate) blend, PLA/PBAT) and non-hydrolyzable (low-density polyethylene, LDPE) polymers, and the effects of these MP on microorganisms in dry and wet MP-amended soil. MP affected neither abundance and composition of the main soil microbial groups (fungi, Gram-negative, and Gram-positive bacteria), specific activities of ß-glucosidase, ß-xylosidase, lipase, and phenoloxidase, nor respiration in MP-amended soil. Only large PLA/PBAT particles in dry soil were significantly mineralized (15.4% of initial PLA/PBAT-C after 230 days). PLA/PBAT mineralization coincided with enhanced lipase and ß-glucosidase activities on the surfaces of individual PLA/PBAT particles extracted from the soil after incubation (compared to LDPE and non-incubated PLA/PBAT particles). We detected cracks on the surfaces of PLA/PBAT particles using scanning electron microscopy, indicating initiation of MP biodegradation, presumably due to depolymerization by lipases. Results suggest that the PLA/PBAT plastisphere is a polymer-specific habitat for lipase-producing soil microorganisms. Our study demonstrates that analyzing biogeochemical interactions within polymer-specific plastispheres is essential to assess MP fate and their impacts on microbially driven soil processes.
The importance of the Peritoneal Cancer Index (PCI) to predict surgical outcome after neoadjuvant chemotherapy in advanced ovarian cancer
Authors: Rawert Friederike Luise , Luengas-Würzinger Veronica , Claßen-Gräfin von Spee Sabrina , Baransi Saher , Schuler Esther , Carrizo Katharina , Dizdar Anca , Mallmann Peter , Lampe Björn
Published: March 2022

Purpose

Achieving complete cytoreduction (CCR) is crucial for a patient’s prognosis with advanced epithelial ovarian cancer (EOC). So far, prognostic predictors have failed to predict surgical outcome after neoadjuvant chemotherapy (NACT). In clinical trials, scores were used to predict operability in recurrent ovarian cancer (Harter et al. in N Engl J Med 385(23):2123–2131, 2021) but there is no known prediction score for CCR after NACT. The Peritoneal Cancer Index (PCI) is an established tool to predict surgical outcome in primary setting (Lampe et al. in 25:135–144, 2015). We now examined the predictive power of the PCI to achieve CCR after NACT.

Methods

In this single-center study, the data of patients with advanced stage EOC (FIGO > IIIb) treated between 01/2015 and 12/2020 were analyzed retrospectively. Inclusion criteria were a mandatory staging laparoscopy, a PCI score > 25, and NACT. CT scans were analyzed in blinded fashion according to RECIST criteria (Borgani et al. in 237; 93–99, 2019) Reaction of PCI after NACT was compared with the analysis of radiologic imaging and CA-125 levels.

Results

Three hundred and sixteen patients were screened, 62 were treated with NACT, and 23 were included in our analysis. 87% of cases presented with an FIGO IIIc stadium. The reduction of PCI itself after NACT showed to be the most powerful predictor for achieving CCR. The reduction of the initial PCI score by minimum of 8.5 points was a better predictor for CCR than reaching a PCI < 25. In contrast to data deriving from patients undergoing primary debulking surgery (PDS), we found a PCI of 17, rather than 25, to be a more valuable cut-off for CCR in neoadjuvant-treated patients.

Conclusion

The extend of PCI reduction after NACT is a better predictor for achieving CCR compared with CA125 levels and radiologic imaging. The PCI must be assessed differently in neoadjuvant setting than in a primary situation. CCR was most likely for a post-NACT PCI < 17.
Metastasis in the gallbladder: does literature reflect reality?
Authors: de Bitter Tessa J. J. , Trapman Daan M. , Simmer Femke , Hugen Niek , de Savornin Lohman Elise A. J. , de Reuver Philip R. , Verheij Joanne , Nagtegaal Iris D. , van der Post Rachel S.
Published: March 2022

Background

Metastases to the gallbladder (GBm) are rare and pose a unique diagnostic challenge because they can mimic a second primary tumor. This study aimed to gain insight into the clinicopathological and epidemiological characteristics of GBm.

Methods

A comprehensive literature review was performed (literature cohort) and compared with a nationwide cohort of GBm patients diagnosed between 1999 and 2015 in the Netherlands, collected via two linked registries (population cohort). Overall survival (OS) was estimated by Kaplan–Meier. Hazard ratios were determined by a Cox proportional hazard model.

Results

The literature cohort and population cohort consisted of 225 and 291 patients, respectively. In the literature cohort, melanoma was the most frequent origin (33.8%), while colorectal cancer was the most frequent origin in the population cohort (23.7%). Prognosis was poor with median OS ranging from 6.0 to 22.5 months in the literature and population cohorts, respectively. Age, timing of GBm (synchronous/metachronous) and primary tumor origin were independent prognostic factors for OS.

Discussion

Metastases to the gallbladder are rare and carry a poor prognosis. Differences between both cohorts can be attributable to the biased reporting of tumor types that are more easily recognized as GBm because of distinct histological features.
Human-stool-associated tusavirus (Parvoviridae) in domestic goats and sheep
Authors: Reuter Gábor , Pankovics Péter , László Zoltán , Gáspár Gábor , Hui Alvin , Delwart Eric , Boros Ákos
Published: March 2022

In this study, genetic counterparts of the human-stool-associated tusavirus (subfamily Parvovirinae, family Parvoviridae) with >97% and 95-100% amino acid sequence identity in the parvoviral NS1 and VP1 protein were identified in faecal specimens from domestic goats (Capra hircus) and sheep (Ovis aries) in Hungary. Eleven (17.8%) of the 62 faecal specimens from goats and 12 (25.5%) of the 47 from sheep both from less than 12 months old animals were positive for tusavirus DNA by PCR, while none of the specimens collected from cattle and swine were positive. Thus, it cannot be ruled out that tusavirus infection in humans is of zoonotic origin.
HIV Pre-exposure Prophylaxis Implant Stated Preferences and Priorities: Results of a Discrete Choice Experiment Among Women and Adolescent Girls in Gauteng Province, South Africa
Authors: Little Kristen M. , Flomen Lola , Hanif Homaira , Anderson Sharon M. , Thurman Andrea R. , Clark Meredith R. , Doncel Gustavo F.
Published: March 2022

For adolescent girls (AG) and young women (YW), adherence barriers may limit the effectiveness of daily oral HIV pre-exposure prophylaxis (PrEP). Due to its low-burden and long-lasting product attributes, PrEP implants could remove some of the critical adherence barriers of oral PrEP products for individuals at risk of HIV. To explore stated preferences for a long-acting PrEP implant, we conducted a quantitative survey and discrete choice experiment with AG (ages 15–17), YW (18–34), and female sex workers (FSW; ≥ 18) in Gauteng Province, South Africa. We completed 600 quantitative surveys across the three subgroups of women. Respondents stated preference for an implant that provided longer HIV protection (24 months versus 6 months) and required a single insertion. They stated that they preferred a biodegradable implant that could be removed within 1 month of insertion. Respondents had no preference for a particular insertion location. Overall, 78% of respondents said they would be likely (33%) or very likely (45%) to use a PrEP implant were one available, with the majority (82%) stating preference for a product that would provide dual protection against HIV and unintended pregnancies. To reduce their risk of HIV, AG, YW, and FSW in our survey reported a strong willingness to use long-acting, highly-effective, dissolvable PrEP implants.
Targeting Transporters for Drug Delivery to the Brain: Can We Do Better?
Authors: Puris Elena , Fricker Gert , Gynther Mikko
Published: March 2022

Limited drug delivery to the brain is one of the major reasons for high failure rates of central nervous system (CNS) drug candidates. The blood–brain barrier (BBB) with its tight junctions, membrane transporters, receptors and metabolizing enzymes is a main player in drug delivery to the brain, restricting the entrance of the drugs and other xenobiotics. Current knowledge about the uptake transporters expressed at the BBB and brain parenchymal cells has been used for delivery of CNS drugs to the brain via targeting transporters. Although many transporter-utilizing (pro)drugs and nanocarriers have been developed to improve the uptake of drugs to the brain, their success rate of translation from preclinical development to humans is negligible. In the present review, we provide a systematic summary of the current progress in development of transporter-utilizing (pro)drugs and nanocarriers for delivery of drugs to the brain. In addition, we applied CNS pharmacokinetic concepts for evaluation of the limitations and gaps in investigation of the developed transporter-utilizing (pro)drugs and nanocarriers. Finally, we give recommendations for a rational development of transporter-utilizing drug delivery systems targeting the brain based on CNS pharmacokinetic principles.
Local trade-off between information and disturbance in quantum measurements
Authors: Terashima Hiroaki
Published: March 2022

This study confirms a local trade-off between information and disturbance in quantum measurements. It is represented by the correlation between the changes in these two quantities when the measurement is slightly modified. The correlation indicates that when the measurement is modified to increase the obtained information, the disturbance also increases in most cases. However, the information can be increased while decreasing the disturbance because the correlation is not necessarily perfect. For measurements having imperfect correlations, this paper discusses a general scheme that raises the amount of information while decreasing the disturbance.
Mental health conditions and academic burnout among medical and non-medical undergraduates during the mitigation of COVID-19 pandemic in China
Authors: Yang Qian , Liu Yueheng , Yang Winson Fuzun , Peng Pu , Chen Shubao , Wang Yunfei , Wang Xin , Li Manyun , Wang Yingying , Hao Yuzhu , He Li , Wang Qianjin , Zhang Junhong , Ma Yuejiao , He Haoyu , Zhou Yanan , Long Jiang , Qi Chang , Tang Yi-Yuan , Liao Yanhui , Tang Jinsong , Wu Qiuxia , Liu Tieqiao
Published: March 2022

The outbreak of the novel coronavirus disease 2019 (COVID-19) has posed a great impact on people’s mental health, especially for undergraduate students. This study aimed to compare the mental health conditions and academic burnout between medical and non-medical undergraduates in China when the COVID-19 pandemic is mitigating. A cross-sectional online survey was conducted among 4,972 undergraduates between October 2020 and April 2021, when the pandemic was basically under control. The survey included basic demographics information and standardized scales to evaluate depression, anxiety, perceived stress, daytime sleepiness, alcohol abuse/dependence, quality of life, fatigue, and academic burnout. Compared with medical undergraduates, non-medical undergraduates had higher rates of moderate to severe depression symptoms (29.1% vs. 17.9%, P < 0.001), moderate to severe anxiety symptoms (19.7% vs. 8.9%, P < 0.001), alcohol abuse/dependence (16.3% vs.10.3%, P < 0.001), excessive daytime sleepiness (47.4% vs. 43.4%, P = 0.018), high perceived stress (34.7% vs. 22.2%, P < 0.001), high level of fatigue (51.8% vs. 42.2%, P < 0.001), low QOL (35.8% vs. 21.4%, P < 0.001), and higher academic burnout score (59.4 vs. 57.5, P < 0.001). Being non-medical undergraduates, depression, alcohol abuse/dependence, excessive daytime sleepiness, and high perceived stress were positively associated with academic burnout, while high QOL was negatively associated with the burnout (all P < 0.001). Excessive daytime sleepiness was the strongest predictor for academic burnout.
Automated 3D thorax model generation using handheld video-footage
Authors: Dussel Nadine , Fuchs Reinhard , Reske Andreas W. , Neumuth Thomas
Published: March 2022

Purpose

For the visualization of pulmonary ventilation with Electrical Impedance Tomography (EIT) most devices use standard reconstruction models, featuring common thorax dimensions and predetermined electrode locations. Any discrepancies between the available model and the patient in terms of body shape and electrode position lead to incorrectly displayed impedance distributions. This work addresses that problem by presenting and evaluating a method for 3D model generation of the thorax and any affixed electrodes based on handheld video-footage.

Methods

Therefore, a process was developed, providing users with the ability to capture a patient's chest and the attached electrodes via smartphone. Once data is collected, extracted images are used to generate a 3D model with a structure from motion approach and locate electrodes with ArUco markers. For the evaluation of the developed method, multiple tests were performed in laboratory environments, which were compared with manually created reference models and differences quantified based on mean distance, standard deviation, and maximum distance.

Results

The implemented workflow allows for automated model reconstruction based on videos or selected images captured with a handheld device. It generates sparse point clouds from which a surface mesh is reconstructed and returns relative coordinates of any identified ArUco marker. The average value for the mean distance error of two model generations was 5.4 mm while the mean standard deviation was 6.0 mm. The average runtime of twelve reconstructions was 5:17 min, with a minimal runtime of 3:22 min and a maximal runtime of 7:29 min.

Conclusion

The presented methods and results show that model reconstruction of a patient’s thorax and applied electrodes at an emergency site is feasible with already available devices. This is a first step toward the automated generation of patient-specific reconstruction models for Electrical Impedance Tomography based on images recorded with handheld devices.
Multiphysics Simulation of Seebeck Coefficient Measurement
Authors: Huang K. , Edler F.
Published: March 2022

Using the finite element method (FEM), we developed a simulation model based on our actual apparatus, which is used for measuring the Seebeck coefficient and the electrical conductivity of thermoelectric materials. In terms of geometry, materials, and physics, our simulation model corresponds to the essential details of the experimental device. This article describes the model in detail and highlights key technical characteristics. By comparing it with actual measurement results, the accuracy of the model has been verified. Based on this accurate model, a simulation comparison study on the changes of certain parameters was carried out. Finally, the results of these comparisons are discussed to gain a deeper understanding of the actual experimental process and to improve the accuracy of the measurement.
Dissolved methane in anaerobic effluent: Emission or recovery?
Authors: Zhang Xiaoyuan , Gu Jun , Meng Shujuan , Liu Yu
Published: March 2022

Various anaerobic processes have been explored for the energy-efficient treatment of municipal wastewater. However, dissolved methane in anaerobic effluent appears to be a barrier towards the energy and carbon neutrality of wastewater treatment. Although several dissolved methane recovery methods have been developed, their engineering feasibility and economic viability have not yet been assessed in a holistic manner. In this perspective, we thus intend to offer additional insights into the cost-benefit of dissolved methane recovery against its emission.
Language of Religion, Religions as Languages. Introduction to the Special Issue ‘Religions and Languages: A Polyphony of Faiths’
Authors: Vestrucci Andrea
Published: March 2022

Religions use linguistic and non-linguistic codes of meaning to express their contents: natural tongues, music, sculpture, poetry, rituals, practices... Also, religions provide the semantic context and the rules to produce, validate, and interpret their expressions: as such, religions can be considered languages. TheSophiaSpecial Issue ‘Religions and Languages: A Polyphony of Faiths’ explores the multifaceted relationships of world religions with languages broadly construed, intended as other religious codes, natural tongues, artistic forms, digital media, and even science. Do natural languages modify themselves in order to convey a divine message? How do artistic means of expression accommodate religious contents? What are the aspects of interaction between religions, technological advances, and scientific methods? The five contributions in this issue offer innovative, compelling, and engaging perspectives regarding this complex and fascinating issue.
Activation and Stabilization of Lipase B from Candida antarctica by Immobilization on Polymer Brushes with Optimized Surface Structure
Authors: Wunschik Dennis Sebastian , Lorenz André , Ingenbosch Kim Nadine , Gutmann Jochen Stefan , Hoffmann-Jacobsen Kerstin
Published: March 2022

A reusable support system for the immobilization of lipases is developed using hybrid polymer-inorganic core shell nanoparticles. The biocatalyst core consists of a silica nanoparticle. PMMA is grafted from the nanoparticle as polymer brush via ARGET ATRP (activator regenerated by electron transfer atom transfer radical polymerization), which allows defining the surface properties by chemical synthesis conditions. Lipase B from Candida antarctica is immobilized on the hybrid particles. The activity and stability of the biocatalyst are analyzed by spectroscopic activity analysis. It is shown that the hydrophobic PMMA brushes provide an activating surface for the lipase giving a higher specific activity than the enzyme in solution. Varying the surface structure from disordered to ordered polymer brushes reveals that the reusability of the biocatalyst is more effectively optimized by the surface structure than by the introduction of crosslinking with glutaraldehyde (GDA). The developed immobilization system is highly suitable for biocatalysis in non-native media which is shown by a transesterification assay in isopropyl alcohol and an esterification reaction in n-heptane.
GLP-1R Agonist Exendin-4 Protects Against Hemorrhagic Transformation Induced by rtPA After Ischemic Stroke via the Wnt/β-Catenin Signaling Pathway
Authors: Liu Chengli , Sun Shanshan , Xie Jie , Li Hui , Li Tianyu , Wu Qiqi , Zhang Yongsheng , Bai Xiangjun , Wang Jian , Wang Xin , Li Zhanfei , Wang Wei
Published: March 2022

Tissue plasminogen activator (tPA) is recommended by the FDA to dissolve intravascular clots after acute ischemic stroke (AIS). However, it may contribute to hemorrhagic transformation (HT). The Wnt/β-catenin signaling pathway plays an important role in regulating the blood–brain barrier (BBB) formation in the central nervous system. We explored whether glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (EX-4) reduces the risk of HT after rtPA treatment via the Wnt/β-catenin pathway by using a rat transient middle cerebral artery occlusion (MCAO) modelin vivoand an oxygen–glucose deprivation plus reoxygenation (OGD/R) model in vitro. Our results showed that EX-4 attenuated neurological deficits, brain edema, infarct volume, BBB disruption, and rtPA-induced HT in ischemic stroke. EX-4 suppressed the production of ROS and the activation of MMP-9 to protect the integrity of the BBB by activating the Wnt/β-catenin signaling pathway. PRI-724, a selective inhibitor of β-catenin, was able to reverse the therapeutic effect of EX-4 in vivo and in vitro. Therefore, our results indicate that the GLP-1R agonist may be a potential therapeutic agent to decrease the risk of rtPA-induced HT after ischemic stroke via the Wnt/β-catenin signaling pathway.
Optimized Identification of Triacylglycerols in Milk by HPLC-HRMS
Authors: Imperiale Sebastian , Morozova Ksenia , Ferrentino Giovanna , Scampicchio Matteo
Published: March 2022

This work has developed an optimized workflow for the targeted analysis of triacylglycerols (TAGs) in milk by liquid chromatography coupled with a Q-Exactive Orbitrap mass spectrometer. First, the effects of resolution (17,500; 35,000; 70,000; 140,000) and automatic gain control target (AGC, from 2×104, 2×105, 1×106, and 3×106) have been optimized with the goal to minimize the injection time, maximize the number of scans, and minimize the mass error. Then, the flow rate of the liquid chromatography system was also optimized by maximizing the number of theoretical plates. The resulting optimized parameters consisted of a flow rate of 200 μL/min, mass resolution of 35,000, and AGC target of 2×105. Such optimal conditions were applied for targeted TAG analysis of milk fat extracts. Up to 14 target triglycerides in milk fat were identified performing a data-dependent HPLC-HRMS-MS2 experiment (t-SIM-ddMS2). The findings reported here can be helpful for MS-based lipidomic workflows and targeted milk lipid analysis.
Serial Homology
Authors: Fusco Giuseppe
Published: March 2022

Serial homology, i.e., homology between repetitive structures in the same individual organism, is a debated concept in evolutionary developmental biology. The central question is the evolutionary interpretation of “sameness” in the context of the same body. This essay provides a synthetic analysis of the main issues involved in the debate, connecting conceptual problems with current experimental research. It is argued that a concept of serial homology that is not of the all-or-nothing kind can smooth several theoretical inconsistencies, while being more in line with what we know about evolutionary change and the way we investigate it.
Quality of cost evaluations of physician continuous professional development: Systematic review of reporting and methods
Authors: Cook David A. , Wilkinson John M. , Foo Jonathan
Published: March 2022

Introduction We sought to evaluate the reporting and methodological quality of cost evaluations of physician continuing professional development (CPD).

Methods We conducted a systematic review, searching MEDLINE, Embase, PsycInfo, and the Cochrane Database for studies comparing the cost of physician CPD (last update 23 April 2020). Two reviewers, working independently, screened all articles for inclusion. Two reviewers extracted information on reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), and on methodological quality using the Medical Education Research Study Quality Instrument (MERSQI) and a published reference case.

Results Of 3338 potentially eligible studies, 62 were included. Operational definitions of methodological and reporting quality elements were iteratively revised. Articles reported mean (SD) 43% (20%) of CHEERS elements for the Title/Abstract, 56% (34%) for Introduction, 66% (19%) for Methods, 61% (17%) for Results, and 66% (30%) for Discussion, with overall reporting index 292 (83) (maximum 500). Valuation methods were reported infrequently (resource selection 10 of 62 [16%], resource quantitation 10 [16%], pricing 26 [42%]), as were descriptions/discussion of the physicians trained (42 [68%]), training setting (42 [68%]), training intervention (40 [65%]), sensitivity analyses of uncertainty (9 [15%]), and generalizability (30 [48%]). MERSQI scores ranged from 6.0 to 16.0 (mean 11.2 [2.4]). Changes over time in reporting index (initial 241 [105], final 321 [52]) and MERSQI scores (initial 9.8 [2.7], final 11.9 [1.9]) were not statistically significant (p ≥ 0.08).
Nutzungsverhalten von Lehrkräften bei der Implementierung einer physikdidaktisch innovativen Unterrichtskonzeption
Authors: Breuer Judith , Vogelsang Christoph , Reinhold Peter
Published: March 2022

Eine zentrale Aufgabe fachdidaktischer Forschung stellt die Verbesserung schulischen Unterrichts dar. Die freie Bereitstellung wirksamer Unterrichtskonzeptionen zur Unterstützung des Selbststudiums von Lehrkräften bildet eine Strategie für eine flächendeckende Implementierung fachdidaktischer Innovationen. Allerdings etablieren sich zahlreiche, empirisch erfolgreich evaluierte Unterrichtskonzeptionen nicht nachhaltig an Schulen. Daher untersucht das vorliegende Forschungsvorhaben den Implementationsprozess solcher Materialien unter authentischen Bedingungen. Dazu wurde kriteriengeleitet eine evidenzbasierte, fachdidaktisch innovative Unterrichtskonzeption ausgewählt: das Münchener Unterrichtskonzept zur Quantenmechanik (MILQ). Diese wurde den teilnehmenden Lehrkräften fakultativ zur Verfügung gestellt. Mittels Fallstudien wurde die Implementierung von MILQ von elf Lehrkräften durch halbstandardisierte Interviews zu Beginn und am Ende einer Unterrichtsreihe zur Quantenmechanik sowie zwei Unterrichtsbeobachtungen mit je einem anschließendenstimulated recallexplorativ erfasst. Die Probanden setzten sich überwiegend heuristisch mit MILQ auseinander und implementierten vor allem Elemente auf Sichtstrukturebene im Unterricht, die konform zu ihren bisherigen Vorstellungen waren. Dadurch wurde das fachdidaktische Innovationspotential nicht ausgeschöpft. Bezeichnend ist, dass der empirische Wirksamkeitsnachweis von MILQ für die Beurteilung der Lehrkräfte nicht relevant war, was aus theoretischer Sicht bislang als ein zentrales Argument der Bereitstellungsstrategie zur Implementierung fachdidaktischer Innovation angenommen wurde.
Are there country-specific differences in the use of pegvisomant for acromegaly in clinical practice? An analysis from ACROSTUDY
Authors: Grottoli S. , Bianchi A. , Bogazzi F. , Bona C. , Carlsson M. O. , Colao A. , Dassie F. , Giampietro A. , Gomez R. , Granato S. , Maffei P. , Pivonello R. , Prencipe N. , Ragonese M. , Urbani C. , Cannavò S.
Published: March 2022

Objective

A comprehensive picture of pegvisomant use for treating acromegaly in routine clinical practice in different countries is lacking. We aimed, therefore, to document country-specific behaviors in real-life pegvisomant use, and the main safety and effectiveness outcomes in the ACROSTUDY.

Design

ACROSTUDY is an open-label, non-interventional, post-marketing safety surveillance study.

Methods

A descriptive analysis was performed using data from the six top-recruiter ACROSTUDY countries, i.e., Germany (n = 548 patients), Italy (n = 466), France (n = 312), USA (n = 207), Spain (n = 200) and the Netherlands (n = 175). These nations accounted for > 85% of the ACROSTUDY cases.

Results

The mean pegvisomant dose at treatment start was lowest in the Netherlands (9.4 mg/day), whereas it ranged between 10.9 and 12.6 mg/day in the other countries. At year 5, the mean pegvisomant dose was around 15 mg/day in all countries, except France (18.1 mg/day). At starting pegvisomant, patients treated with monotherapy ranged between 15% in the Netherlands and 72% in Spain. Monotherapy remained lowest over time in the Netherlands. In all countries, the percentage of patients with normal IGF-1 increased steeply from < 20% at baseline to 43–58% at month 6 and 51–67% at year 1. After that, we observed minor changes in the rate of acromegaly control in all countries. The Netherlands peaked in disease control at year 2 (72%). The proportion of patients reporting changes in pituitary tumor size was generally low. Serious treatment-related adverse events were < 5% in all countries.

Conclusions

Our study provided a detailed summary of real-life use of pegvisomant in the six top-recruiter ACROSTUDY nations.
Large-Scale Fatigue Testing Based on the Rotating Beam Method
Authors: Isakov M. , Rantalainen O. , Saarinen T. , Lehtovaara A.
Published: March 2022

A large-scale fatigue testing machine based on the rotating beam method in a four-point bending configuration was designed and built. With the device, high-strength metal specimens with a 32-mm gauge diameter and a 100-mm gauge length can be tested at a cyclic frequency of up to 48 Hz. In this work, particular attention was paid to evaluating the spatial and temporal uniformity of the loading within the large specimen; methods for quantitative evaluation of these effects were developed. The developed test methodology allows for the fatigue testing of specimens with size, microstructure, and surface conditions that are similar to actual machine parts.
The crisis of nuclear arms control
Authors: Kühn Ulrich
Published: March 2022

The politics of nuclear arms control between the United States and Russia are in a protracted state of crisis, which is in need of explanation. This article provides an overview of bilateral contractual milestones from 1972 to 2001 and analyzes instances of cooperation through the lens of three key factors that have influenced the process. It then considers the changes that these factors have undergone over twenty years of crisis in bilateral arms control from 2001 to 2021 and gauges the possible consequences of a continuation of the current situation. It concludes that during the first period, a shared willingness to shield the bilateral process from political disruption, U.S. bipartisan support, and cooperatively addressing the vertical diffusion of offensive and defensive missile capabilities were both possible and necessary for ensuring success. During the second period, these key factors underwent significant changes and ultimately had a negative effect on the bilateral process, which makes the current crisis unique compared to earlier episodes of regression. Most importantly, both sides were no longer willing to shield the bilateral process in its entirety during this period, including defensive and sub-strategic offensive elements. With a view to future consequences, these findings point to reduced arms race stability, weaker negotiated outcomes, and an erosion of the global nonproliferation regime.
Using and Abusing the Arts with ‘At-Risk’ Youth
Authors: Howard Frances
Published: March 2022

Arts programmes are frequently provided for youth who are deemed unfortunate or unruly. Globally, arts programmes for at-risk youth have been widely recognised as beneficial; however, there has been a lack of criticality on how arts experiences can have an adverse impact. Research into a UK-based programme—the Arts Award—is presented to highlight the different, and lower quality, offer for at-risk youth. Multi-sited ethnography captured the experiences of participants accessing the programme through five diverse youth settings. My research demonstrated that often the most disadvantaged young people receive the weakest arts programmes, that are deficit-oriented, mechanistic and instrumentalised. This article offers a unique perspective on the ways in which the arts can fail at-risk youth.
Extension and Evaluation of the PROMIS Sexual Function and Satisfaction Measures for Use in Adults Living with Multiple Sclerosis
Authors: Amtmann Dagmar , Bamer Alyssa M. , Salem Rana , McMullen Kara , Beier Meghan , Flynn Kathryn E. , Foley Frederick W. , Weinfurt Kevin P. , Wilkie Dana , Alschuler Kevin N.
Published: March 2022

Background

Sexual dysfunction is a common symptom of multiple sclerosis (MS). Clinically meaningful and psychometrically sound measures of sexual function validated in people with MS are necessary to identify people with MS who experience problems with sexual function.

Aim

To evaluate the Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (SexFS) v2.0 measure in people with MS and to extend the PROMIS SexFS Brief and Full Profiles to include additional aspects of sexual function relevant to people living with MS.

Methods

A convenience sample of MS clinicians and sexually active individuals with MS ranked relevance of 26 items that listed specific factors that interfere with sexual function. Rankings were used to select items to include in the modified SexFS for Multiple Sclerosis (SexFS-MS) profiles. Sex-FS Brief and Full profiles along with the top 22 ranked interfering factor items underwent cognitive interviews (CI) to assess whether the items were understandable and meaningful.

Outcomes

The SexFS as originally published functioned well in people with MS after minor modifications.

Results

Twelve MS clinicians and 26 people with MS ranked items. The 10 highest ranked questions about factors that interfere with sexual function most relevant to people with MS were added to the SexFS-MS Brief profiles and 18 to the Full profiles. Ten men and 12 women with MS participated in CIs and found most items to be clear and meaningful. However, important changes were made to the profile instructions, some response sets, and to some items to improve clarity and function. New items to assess numbness and reasons why sexually active people choose at times not to engage in sexual activity were added.

Clinical Implications

Brief and Full profiles are freely available and are recommended for research and clinical practice that include people with MS.

Strengths & Limitations

This study is the first to provide validity evidence for the PROMIS SexFS in people living with MS. Though the PROMIS SexFS was tested in people who identify as lesbian, gay, or bisexual, only individuals who identified as heterosexual participated in this study. Results may not represent views of people with MS who identify as other sexual orientations who may have different concerns and priorities related to sexual function.

Conclusion

This study extended the PROMIS SexFS Brief and Full profiles to create the SexFS-MS by adding items that measure most relevant issues related to sexual function in individuals living with MS.
Gender Identity and Non-Binary Presentations in Adolescents Attending Two Specialized Services in Italy
Authors: Mirabella Marta , Piras Irene , Fortunato Alexandro , Fisher Alessandra D. , Lingiardi Vittorio , Mosconi Maddalena , Ristori Jiska , Speranza Anna Maria , Giovanardi Guido
Published: March 2022

Background

Recently, the variability and heterogeneity of gender presentations in transgender youths have gained significant attention worldwide. Alongside this, specialized gender services have reported an increase in referrals of youths reporting non-binary identities. In Italy, studies investigating gender identity and expression in gender non-conforming youths are lacking, as are data regarding the non-binary population.

Aim

The present study aimed at dimensionally exploring how transgender and non-binary Italian adolescents identify and express their gender.

Outcomes

Gender expression in trans binary youths and non-binary youths.

Methods

The Gender Diversity Questionnaire (GDQ; Twist & de Graaf, 2019) was used to investigate gender identity, gender fluidity, and gender expression in a sample of 125 adolescent patients from the Gender Identity Development Service (SAIFIP) in Rome and the Gender Incongruence Unit of the Careggi Hospital in Florence, between April 2019–June 2021.

Results

The majority of participants (74.4%) identified as trans* binary and the remaining (25.6%) participants identified as non-binary. Trans binary participants reported a stable gender identity, whereas non-binary participants reported a more fluid gender identity across time and contexts. Almost all participants rated external appearance as important to their gender expression, yet trans binary participants attributed more importance to the body in this respect. Body discomfort and pubertal stage emerged as the most influential factors in participants’ experiences of gender. Participants who were assigned male at birth expressed significantly more desire for puberty blockers, whereas those who were assigned female at birth had a stronger desire to engage in breast/chest surgery. Non-binary participants sought different medical interventions relative to trans binary participants.

Clinical Implications

These results may be useful for clinicians working with transgender youths as they provide awareness regarding the features of young people who identify within and outside of binary constructions of gender.

Strengths & Limitations

This study provides useful data in gaining insight into understanding the variety of experiences and challenges of gender non-conforming youths. However as the sample was recruited from specialized services, it may not represent the entire gender non-conforming population in Italy.

Conclusion

The results describe the range of gender identities and expressions among gender non-conforming youths attending gender specialized services in Italy, thereby improving our understanding of the variety of identities experienced and the specific medical needs of both trans binary and non-binary adolescents.
Travel-Associated Venous Thromboembolism
Authors: McKerrow Johnson Isla , Shatzel Joseph , Olson Sven , Kohl Tovah , Hamilton Andrew , DeLoughery Thomas G.
Published: March 2022

Introduction

Long-distance travel is assumed to be a risk factor for venous thromboembolism (VTE). However, the available data have not clearly demonstrated the strength of this relationship, nor have they shown evidence for the role of thromboprophylaxis.

Methods

We performed a systematic review of the literature. We also summarized available guidelines from 5 groups.

Results

We found 18 studies that addressed this question. Based on the data presented in the review, we conclude that there is an association between VTE and length of travel, but this association is mild to moderate in effect size with odds ratios between 1.1 and 4. A dose-response relationship between VTE and travel time was identified, with a 26% higher risk for every 2 h of air travel ( P=0.005) starting after 4 h. The quality of evidence for both travel length and thromboprophylaxis was low. However, low-risk prophylactic measures such as graduated compression stockings were shown to be effective in VTE prevention. There is heterogeneity among the different practice guidelines. The guidelines generally concur that no prophylaxis is necessary in travelers without known thrombosis risk factors and advocate for conservative treatment such as compression stockings over pharmacologic prophylaxis.

Conclusions

We conclude air travel is a risk factor for VTE and that there is a dose relationship starting at 4 h. For patients with risk factors, graduated compression stockings are effective prophylaxis.
Temperament Based Therapy with Support for Anorexia Nervosa
Authors: Hill Laura L. , Knatz Peck Stephanie , Wierenga Christina E.
Published: March 2022

Anorexia nervosa has one of the highest death rates of all mental illnesses and one of the poorest treatment outcomes. However, one novel treatment, the neurobiologically-based treatment Temperament Based Therapy with Support (TBT-S), works with clients' temperament and traits to motivate change, ultimately managing and reducing symptoms. This practical and accessible book is the first guide to delivering TBT-S that addresses the underlying traits leading to symptoms of anorexia nervosa and helps people to manage symptoms long-term. It offers background information on the role of temperament in anorexia nervosa, the development of the TBT-S protocol and the evidence gathered. Chapters also cover how to use this therapy to augment existing treatment. A valuable resource for clinicians involved in the treatment of anorexia nervosa, including psychologists, psychiatrists, psychotherapists, specialist nurses, dieticians, and educators.
Reading Medieval Ruins
Authors: Pitelka Morgan
Published: March 2022

The Japanese provincial city of Ichijōdani was destroyed in the civil wars of the late sixteenth century but never rebuilt. Archaeological excavations have since uncovered the most detailed late medieval urban site in the country. Drawing on analysis of specific excavated objects and decades of archaeological evidence to study daily life in Ichijōdani, Reading Medieval Ruins in Sixteenth-Century Japan illuminates the city's layout, the possessions and houses of its residents, its politics and experience of war, and religious and cultural networks. Morgan Pitelka demonstrates how provincial centers could be dynamic and vibrant nodes of industrial, cultural, economic, and political entrepreneurship and sophistication. In this study a new and vital understanding of late medieval society is revealed, one in which Ichijôdani played a central role in the vibrant age of Japan's sixteenth century.
Becoming Young Men in a New India
Authors: Philip Shannon
Published: March 2022

Becoming Young Men in a New India tells the gendered story of a changing India through the lives of its young middle class men. Through time spent ethnographically 'hanging-out' with young men in gyms, bars, clubs, trains and gay cruising grounds in India, this book critically reveals Indian men's violence towards women in various city spaces and also shows the many classed and masculine entitlements and challenges that they experience. The book lays bare the often secretive and hidden social worlds of young Indian men and critically analyses the impact young men's actions and identities have not just for themselves, but for the many women they encounter. In this way, it puts forward a critical queer-feminist perspective of men and masculinities in postcolonial India where the politics of class, gender, sexuality, violence and urban spaces come together.
Optimal Distinctiveness
Authors: Zhao Eric Yanfei
Published: March 2022

Optimal distinctiveness – being both 'similar to' and 'different from' peers – is an important imperative of organizational life and represents a common research question of organizational scholars across various disciplinary domains such as strategy, organization theory, entrepreneurship, and international business. This Element reviews the historical grounding and recent development of optimal distinctiveness scholarship, based on which an orienting framework is proposed to stress the highly contextualized and dynamic nature of optimal distinctiveness. The orienting framework provides several powerful and unique angles for understanding organizations' competitive positioning in various types of markets, for applying optimal distinctiveness research to different levels of analysis, and for nurturing a more cross-disciplinary and mutually generative conversation on optimal distinctiveness theory.
THEOREMS OF HYPERARITHMETIC ANALYSIS AND ALMOST THEOREMS OF HYPERARITHMETIC ANALYSIS
Authors: BARNES JAMES S. , GOH JUN LE , SHORE RICHARD A.
Published: March 2022

Theorems of hyperarithmetic analysis (THAs) occupy an unusual neighborhood in the realms of reverse mathematics and recursion-theoretic complexity. They lie above all the fixed (recursive) iterations of the Turing jump but below ATR
$_{0}$
(and so
$\Pi _{1}^{1}$
-CA
$_{0}$
or the hyperjump). There is a long history of proof-theoretic principles which are THAs. Until the papers reported on in this communication, there was only one mathematical example. Barnes, Goh, and Shore [1] analyze an array of ubiquity theorems in graph theory descended from Halin’s [9] work on rays in graphs. They seem to be typical applications of ACA
$_{0}$
but are actually THAs. These results answer Question 30 of Montalbán’s Open Questions in Reverse Mathematics [19] and supply several other natural principles of different and unusual levels of complexity.

This work led in [25] to a new neighborhood of the reverse mathematical zoo: almost theorems of hyperarithmetic analysis (ATHAs). When combined with ACA
$_{0}$
they are THAs but on their own are very weak. Denizens both mathematical and logical are provided. Generalizations of several conservativity classes (
$\Pi _{1}^{1}$
, r-
$\Pi _{1}^{1}$
, and Tanaka) are defined and these ATHAs as well as many other principles are shown to be conservative over RCA
$_{0}$
in all these senses and weak in other recursion-theoretic ways as well. These results answer a question raised by Hirschfeldt and reported in [19] by providing a long list of pairs of principles one of which is very weak over RCA
$_{0}$
but over ACA
$_{0}$
is equivalent to the other which may be strong (THA) or very strong going up a standard hierarchy and at the end being stronger than full second-order arithmetic.
An exploration of staff experience and participation in a perinatal and infant mental health network group
Authors: O’Leary N. , Wynne F. , Moore P.
Published: March 2022

Objectives

Infant mental health (IMH), an area which focuses on the social and emotional development of infants in the context of the parent-infant relationship, has become an increasingly prominent field of both research and clinical practice worldwide. IMH network groups are initiatives which aim to facilitate continuous learning in the IMH approach, provide an opportunity for case discussion and encourage reflective practice. This study aimed to explore the experiences of staff working within an adult mental health (AMH) service and their participation in a perinatal IMH network group (PIMH-NG).

Methods

This study had a qualitative research design and the data were collected using a focus group methodology. Participants were recruited from a PIMH-NG which aimed to provide staff working within an AMH setting with the opportunity for continuous development of IMH knowledge. The data were analysed using thematic analysis.

Results

The data gathered from the focus group indicated that staff participating in a PIMH-NG enhanced their clinical skill, reflective practice and supported the dissemination of IMH knowledge throughout their respective teams. The PIMH-NG facilitated this work by providing the opportunity for continuous learning, reflective group discussion and ongoing peer support.

Conclusions

The findings of this study indicate that incorporating elements of an IMH model into AMH services can be beneficial for staff, service users and overall service delivery and development. These findings may be used to develop the structure and content of future network groups of this nature.
Injunctions, land and the cynical breach
Authors: Sawtell David
Published: March 2022

An injunction is typically characterised as the primary remedy to prevent a continuing interference with a claimant's property rights. It can be easier to obtain such a remedy against a cynical defendant who knowingly interfered with those rights, as opposed to a naïve or unwitting party who was unaware of them. It is not obvious, however, why the defendant's state of mind should affect what remedy the claimant is afforded in vindicating their property rights. This paper examines the role played by the defendant's state of mind when considering whether to grant an injunction. It argues that a defendant who knowingly infringes a property right in respect of land for material gain assumes the risk that an injunction will be granted to stop that infringement. As a consequence, the question of whether such an order will create hardship or oppression is either diminished or eliminated as a factor. This approach also vindicates the proprietary nature of such rights, which may be difficult to assess in financial terms.