bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutische Injektion und Manuelle Medizin beim tiefen Rückenschmerz
Authors: Schütz Uwe H. W.
Published: March 2022

Hintergrund

Angelehnt an die zielorientierte Therapieplanung und -führung in der Versorgung chronisch Rheumakranker, plädiert der Autor bei Patienten mit (chronischem) degenerativem tiefem Rückenschmerz (TRS), orientiert an den differenzialtherapeutischen Grundsätzen der Manuellen Medizin (MM), und unter Kenntnis von Techniken und Evidenzen therapeutischer Lokalinfiltrationen (TLI), für die Etablierung eines strukturierten mechanismenbasierten Therapiekonzeptes im Sinne des „treat to target“ (T2T) im ambulanten schmerztherapeutischen Versorgungsbereich.

Diagnostik

Dies setzt eine konsequente (Primär‑)Diagnostik mit Schmerzanalyse unter der Prämisse, dass TRS, wenn strukturell-funktionell bedingt, immer spezifisch ist, voraus. Eine breite biopsychosoziale Anamnese und strukturbezogene klinisch-bildgebende (Ausschluss‑)Diagnostik mit funktioneller Differenzierung nach MM-Grundsätzen und ggf. interventionelle Blocks, sollten am Ende zur Formulierung einer 3‑Ebenen-Diagnose als Voraussetzung zu einer mechanismenbasiert-zielorientiert-hierarchischen Stufentherapie bei TRS führen. Diese wird in diesem Artikel pragmatisch fallorientiert, unter Implementierung von Techniken und Evidenzen der TLI und MM, vorgestellt.
Effects of elevated temperature on the performance and survival of pacific crown-of-thorns starfish (Acanthaster cf. solaris)
Authors: Lang Bethan J. , Donelson Jennifer M. , Caballes Ciemon F. , Uthicke Sven , Doll Peter C. , Pratchett Morgan S.
Published: March 2022

Population irruptions of Pacific crown-of-thorns starfish (Acanthaster cf. solaris) have caused substantial damage to coral reefs, but it is largely unknown how this asteroid will fare in a warmer ocean. We exposed these starfish to one of four thermal treatments, with final temperatures of 26 °C (control, annual average), 28 °C (summer average), 30 °C (summer maximum) and 32 °C (predicted summer maximum by 2100). We measured the righting time, movement rate, standard metabolic rate and probability of survival of the crown-of-thorns starfish at various timepoints over ~ 60 days. We found that while temperature did not affect righting time, it did significantly affect movement rate. The movement rate of starfish increased across the 26 to 30 °C range, with those at 28 °C and 30 °C moving 18 and 27% faster than those at the control temperature. Similarly, the standard metabolic rate of starfish increased from 26 to 30 °C, with metabolism 100% and 260% faster at 28 °C and 30 °C compared to those at the 26 °C control. At 32 °C, individual starfish exhibited a 14% slower movement rate, a 33% slower metabolic rate, and also exhibited a fourfold lower probability of survival than those at 30 °C. These results indicate that 32 °C is above the thermal optimum of crown-of-thorns starfish, suggesting that prolonged exposure to temperatures that are expected to be regularly exceeded under near-future climate change may be detrimental to this species.
Clinical comparative study assessing the effect of ivabradine on neopterin and NT-Pro BNP against standard treatment in chronic heart failure patients
Authors: Dogheim Gaidaa M. , Khairat Ibtsam , Omran Gamal A. , El-Haggar Sahar M. , Amrawy Ahmed M. El , Werida Rehab H.
Published: March 2022

Purpose

Heart rate reduction (HR) is a cornerstone in heart failure therapy as it improves patient outcomes. The aim of this study is to evaluate short-term effect of ivabradine on NT-Pro BNP and neopterin in heart failure patients and assess the association between HR and these biomarkers.

Methods

Sixty patients on standard heart failure therapy were randomly allocated into ivabradine group (n = 30) and non-ivabradine group (n = 30). Ivabradine 5 mg twice daily was given for 3 months. Lipid profile and kidney functions were performed and blood samples for NT-Pro BNP and neopterin were analysed at baseline and after 3 months of intervention in both groups.

Results

There was a significant improvement in NYHA class in ivabradine group (p < 0.001). Ejection fraction was improved in ivabradine and non-ivabradine groups after intervention (p < 0.001), with a greater improvement in ivabradine group (p = 0.026). Heart rate was reduced in ivabradine group (p < 0.001) and non-ivabradine group (p < 0.001) yet greater reduction was seen in ivabradine group (p < 0.001). Serum creatinine and blood urea nitrogen were reduced in ivabradine group (Scr: p = 0.001, BUN: p = 0.001). NT-Pro BNP and neopterin levels significantly decreased in ivabradine group (NT-Pro BNP: p < 0.001, neopterin p < 0.001). Significant positive correlation was found between HR and biomarker levels after intervention (NT-Pro BNP: r = 0.475, p < 0.001, neopterin: r = 0.384, p = 0.002).

Conclusion

Ivabradine therapy reduced levels of both biomarkers which correlated well with HR. Biomarker levels might provide a tool for assessing ivabradine effectiveness in HF.

Trial registration

Date: June 26, 2020. Identifier: NCT04448899. Link: Ivabradine in Patients with Congestive Heart Failure—Full Text View—ClinicalTrials.gov.
Fc-independent functions of anti-CTLA-4 antibodies contribute to anti-tumor efficacy
Authors: Sato Yosuke , Casson Cierra N. , Matsuda Atsushi , Kim James I. , Shi Judy Qiuju , Iwasaki Shinji , Chen Susan , Modrell Brett , Chan Chingkit , Tavares Daniel , Austen Douglas , Ida Koh , Tayber Olga , Hein Pyae , Comeau Robert , Lin Yafang , Shaw Michael H.
Published: March 2022

Ipilimumab, a monoclonal antibody that recognizes cytotoxic T-lymphocyte associated protein 4 (CTLA-4), was the first immune checkpoint inhibitor approved by the FDA to treat metastatic melanoma patients. Multiple preclinical studies have proposed that Fc effector functions of anti-CTLA-4 therapy are required for anti-tumor efficacy, in part, through the depletion of intratumoral regulatory T cells (Tregs). However, the contribution of the Fc-independent functions of anti-CTLA-4 antibodies to the observed efficacy is not fully understood. H11, a non-Fc-containing single-domain antibody (VHH) against CTLA-4, has previously been demonstrated to block CTLA-4-ligand interaction. However, in vivo studies demonstrated lack of anti-tumor efficacy with H11 treatment. Here, we show that a half-life extended H11 (H11-HLE), despite the lack of Fc effector functions, induced potent anti-tumor efficacy in mouse syngeneic tumor models. In addition, a non-Fc receptor binding version of ipilimumab (Ipi-LALAPG) also demonstrated anti-tumor activity in the absence of Treg depletion. Thus, we demonstrate that Fc-independent functions of anti-CTLA-4 antibodies contributed to anti-tumor efficacy, which may indicate that non-Treg depleting activity of anti-CTLA-4 therapy could benefit cancer patients in the clinic.
Esophageal Achalasia: Pros and Cons of the Treatment Options
Authors: Costantini Mario , Salvador Renato , Costantini Andrea
Published: March 2022

Achalasia is a primary esophageal motility disorder of unknown origin. The goal of treatment is to reduce the resistance caused by a lower esophageal sphincter that fails to relax and is frequently hypertensive. Many treatment options are available to achieve this goal. In this review, we discuss the pros and cons of each therapeutic approach.
Influence of oral contrast type and volume on patient experience and quality of luminal distension at MR Enterography in Crohn’s disease: an observational study of patients recruited to the METRIC trial
Authors: Bhatnagar Gauraang , Mallett Sue , Quinn Laura , Ilangovan Rajapandian , Patel Uday , Jaffer Asif , Pawley Christopher , Gupta Arun , Higginson Anthony , Slater Andrew , Tolan Damian , Zealley Ian , Halligan Steve , Taylor Stuart A ,   on behalf of the METRIC study investigators
Published: March 2022

Objectives

To compare the distention quality and patient experience of oral mannitol and polyethylene glycol (PEG) for MRE.

Methods

This study is a retrospective, observational study of a subset of patients enrolled in a multicentre, prospective trial evaluating the diagnostic accuracy of MRE for small bowel Crohn’s. Overall and segmental MRE small bowel distention, from 105 patients (64 F, mean age 37) was scored from 0 = poor to 4 = excellent by two experienced observers (68 [65%] mannitol and 37 [35%] PEG). Additionally, 130 patients (77 F, mean age 34) completed a questionnaire rating tolerability of various symptoms immediately and 2 days after MRE (85 [65%] receiving mannitol 45 [35%] receiving PEG). Distension was compared between agents and between those ingesting ≤ 1 L or > 1 L of mannitol using the test of proportions. Tolerability grades were collapsed into “very tolerable,” “moderately tolerable,” and “not tolerable.”

Results

Per patient distension quality was similar between agents (“excellent” or “good” in 54% [37/68] versus 46% [17/37]) with mannitol and PEG respectively. Jejunal distension was significantly better with mannitol compared to PEG (40% [27/68] versus 14% [5/37] rated as excellent or good respectively). There was no significant difference according to the volume of mannitol ingested. Symptom tolerability was comparable between agents, although fullness following MRE was graded as “very tolerable” in 27% (12/45) of patients ingesting PEG, verses 44% (37/84) ingesting mannitol, difference 17% (95% CI 0.6 to 34%).

Conclusion

Mannitol-based solutions and PEG generally achieve comparable distension quality and side effect profiles, although jejunal distension is better quality with mannitol. Neither distension quality nor side-effect profile is altered by ingestion of more than 1 L of mannitol.

Key Points

• Mannitol-based and PEG-based oral preparation agents generally achieve comparable distension quality for MRE with the exception of the jejunum which is better distended with mannitol.

• Mannitol-based and PEG-based oral preparation agents used for MRE have similar side effect profiles.

• Neither distension quality nor side-effect profile is altered by ingestion of more than 1 L of mannitol.
Vitreous cytokine levels following the administration of a single 0.19 mg fluocinolone acetonide (ILUVIEN®) implant in patients with refractory diabetic macular edema (DME)—results from the ILUVIT study
Authors: Deuchler Svenja K. , Schubert Ralf , Singh Pankaj , Chedid Adonis , Kenikstul Ninel , Scott Julia , Kohnen Thomas , Ackermann Hanns , Koch Frank
Published: March 2022

Purpose

To investigate the changes in vitreous inflammatory and angiogenic cytokine levels, primarily interleukin-(IL)-6, following intravitreal injection of the 0.19 mg fluocinolone acetonide (FAc, ILUVIEN®) implant in patients with diabetic macular edema.

Methods

A single-center phase IV study involving 12 patients’ eyes with diabetic macular edema. Vitreous fluid samples were obtained prior to intravitreal injection of the fluocinolone acetonide implant and then again over a 6-month period. Vitreous samples were examined using a cytometric bead array to measure IL-6, IL-8, IP-10, MCP-1, VEGF, and CD54. PIGF and PEDF were measured using an enzyme-linked immunosorbent assay. Changes in the cytokine and chemokine expression patterns were analyzed. Clinical parameters such as BCVA and center point thickness (CPT) were also examined.

Results

There were mean reductions in all parameters between baseline and month 6. Significant changes (p < 0.05 versus baseline) were observed in the expression of IL-6, IP-10, MCP-1, and CD54 following the administration of fluocinolone acetonide implant. VEGF and PIGF increased at month 1 before declining at month 6, though this trend was not significant. CPT decreased rapidly between screening and the first follow-up visit, and this decrease was sustained. BCVA remained relatively stable throughout.

Conclusion

This study demonstrated changes in vitreous inflammatory and angiogenic cytokine levels following intravitreal injection of the FAc implant in patients with diabetic macular edema. Data show that the fluocinolone acetonide implant led to rapid and sustained reductions of some inflammatory cytokines with improvement of the overall clinical picture.
A co-alteration parceling of the cingulate cortex
Authors: Manuello Jordi , Mancuso Lorenzo , Liloia Donato , Cauda Franco , Duca Sergio , Costa Tommaso
Published: March 2022

The cingulate cortex is known to be a complex structure, involved in several cognitive and emotional functions, as well as being altered by a variety of brain disorders. This heterogeneity is reflected in the multiple parceling models proposed in the literature. At the present, sub-regions of the cingulate cortex had been identified taking into account functional and structural connectivity, as well as cytological and electrochemical properties. In the present work, we propose an innovative node-wise parceling approach based on meta-analytic Bayesian co-alteration. To this aim, 193 case–control voxel-based morphometry experiments were analyzed, and the Patel’sκindex was used to assess probability of morphometric co-alteration between nodes placed in the cingulate cortex and in the rest of the brain. Hierarchical clustering was then applied to identify nodes in the cingulate cortex exhibiting a similar pattern of whole-brain co-alteration. The obtained dendrogram highlighted a robust fronto-parietal cluster compatible with the default mode network, and being supported by the interplay between the retrosplenial cortex and the anterior and posterior cingulate cortex, rarely described in the literature. This ensemble was further confirmed by the analysis of functional patterns. Leveraging on co-alteration to investigate cortical organization could, therefore, allow to combine multimodal information, resolving conflicting results sometimes coming from the separate use of singular modalities. Crucially, this provides a valuable way to understand the pathological brain using data driven, whole-brain informed and context-specific evidence in a way not yet explored in the field.
Cognitive and academic outcomes in children with chronic kidney disease
Authors: Kim Siah , Van Zwieten Anita , Lorenzo Jennifer , Khalid Rabia , Lah Suncica , Chen Kerry , Didsbury Madeleine , Francis Anna , Mctaggart Steven , Walker Amanda , Mackie Fiona E. , Prestidge Chanel , Teixeira-Pinto Armando , Tong Allison , Blazek Katrina , Barton Belinda , Craig Jonathan C. , Wong Germaine
Published: March 2022

Background

Few data exist on the cognitive and academic functioning of children with chronic kidney disease (CKD) over the trajectory of their illness. We aimed to determine the association between CKD stages and cognitive and academic performance in children over time.

Methods

We included 53 participants (aged 6–18 years) with CKD stages 1–5 (n = 37), on dialysis (n = 3), or with functioning kidney transplant (n = 22) from three units in Australia from 2015 to 2019. Participants undertook a series of psychometric tests and were invited for repeated assessments annually. We used linear regression and linear mixed models to investigate the effect of CKD stage, adjusted for socioeconomic status.

Results

At baseline, full-scale intelligence quotient (FSIQ) (95%CI) of children on kidney replacement therapy (KRT) was in the low average range (87: 78, 96) and average (101: 95, 108) for children with CKD 1–5. Mean (95%CI) FSIQ, word reading, numerical operations, and spelling scores for children on KRT were 14.3 (− 25.3, − 3.3), 11 (− 18.5, − 3.6), 8.5 (− 17.6, 0.76), and 10 (− 18.6, − 1.3) points lower than children with CKD Stages 1–5. Spelling and numerical operations scores declined by 0.7 (− 1.4, − 0.1) and 1.0 (− 2.0, 0.2) units per year increase in age, regardless of CKD stage.

Conclusions

Children treated with KRT have low average cognitive abilities and lower academic performance for numeracy and literacy compared to both children with CKD 1–5 and to the general population. However, the rate of decline in academic performance over time is similar for children across the full spectrum of CKD.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information.
Health-related quality of life in long-term survivors of childhood brain tumors: a population-based cohort study
Authors: Ljungman Lisa , Remes Tiina , Westin Elisabeth , Huittinen Alina , Lönnqvist Tuula , Sirkiä Kirsti , Rantala Heikki , Ojaniemi Marja , Harila Marika , Lähteenmäki Päivi , Arikoski Pekka , Wikman Anna , Harila-Saari Arja
Published: March 2022

Purpose

Survivors of childhood brain tumors (BT) are at high risk for long-term physical and psychological sequelae. Still, knowledge about health-related quality of life (HRQL) and associated factors in this population is sparse. This study investigated HRQL and its predictors in long-term survivors of childhood BT.

Methods

Survivors of childhood BT (mean age = 28.1 years, SD = 6.8, n = 60) underwent clinical examination and neurocognitive examination, and completed self-rating questionnaires assessing HRQL (RAND-36) and depressive symptoms (Beck Depression Inventory-II). Socio-demographic information was gathered via a questionnaire. Tumor- and treatment-related information was collected from medical records. Control group data were collected from age-matched controls (n = 146) without a history of cancer, randomly selected from the local population registry. Multiple linear regression models were used to investigate predictors of HRQL; separate models were fitted for each domain of the RAND-36.

Results

Male survivors (mean age = 27.0, SD = 6.0, n = 39) reported significantly lower HRQL than male controls in the domains of physical functioning, general health, vitality, social functioning, and role limitations-emotional. Female survivors (mean age = 30.2 years, SD = 7.6, n = 21) reported comparable levels as female controls in all domains except physical functioning. A higher burden of late effects, not working/studying, being diagnosed with BT during adolescence, and reporting current depressive symptoms were significant predictors of lower HRQL.

Conclusion

Our results highlight that male survivors of childhood BT are at particular risk of impaired HRQL. Also, results point to the close relation between symptoms of depression and impaired HRQL in survivors of childhood BT which should be acknowledged by long-term follow-up care.
Effect of intraoperative needle biopsy on the survival of nonsmall cell lung cancer patients: a propensity score matching analysis
Authors: Morota Mizuki , Nagano Masaaki , Ijiri Naohiro , Yoshiyasu Nobuyuki , Shinohara Yoshikazu , Nobori Yuya , Yamaguchi Hirokazu , Kawashima Shun , Yanagiya Masahiro , Konoeda Chihiro , Kitano Kentaro , Sato Masaaki , Nakajima Jun
Published: March 2022

Purpose

It is unknown whether intraoperative needle biopsy (INB) predisposes to the postoperative recurrence of lung cancer and compromises the prognosis of these patients. We conducted this study to identify the effect of INB before lobectomy on the postoperative recurrence rate and prognosis of patients with nonsmall cell lung cancer (NSCLC).

Methods

The subjects of this retrospective study were 953 patients with pathological stage I–III NSCLC who underwent lobectomy between 2001 and 2016. The patients were divided into two groups: the INB group (n = 94) and the non-INB group (n = 859). After propensity score matching (PSM), we compared the postoperative cumulative recurrence rate, recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) between the two groups.

Results

After PSM, 94 patient pairs were matched. The cumulative recurrence rate was significantly higher in the INB group than in the non-INB group (P = 0.01). The 5-year RFS rate was significantly lower in the INB group than in non-INB group (48% vs 68%), as were the 5-year DSS (76% vs 92%) and 5-year OS rates (67% vs 84%) (all P < 0.05).

Conclusions

The findings of this analysis suggest that INB before lobectomy may increase the cumulative recurrence rate and worsen the prognosis of patients with resectable NSCLC. Thus, we believe that INB should be avoided unless a lung lesion cannot be diagnosed by another type of biopsy.
Influence of an active T-foil on motions and passenger comfort of a large high-speed wave-piercing catamaran based on sea trials
Authors: Lau Chun-Yu , Ali-Lavroff Jason , Holloway Damien S. , Shabani Babak , Mehr Javad A. , Thomas Giles
Published: March 2022

T-foil and stern tabs were installed on a wave-piercing catamaran (Incat Tasmania Hull 061) to improve ship motions and passenger comfort. More than 40 total effective hours of sea trials were conducted by the US Navy in 2004, encountering sea states 4–5 in the Atlantic Ocean near the United Kingdom. In this paper the influence of a ride-control system (RCS) on the heave and pitch response amplitude operator (RAO) of the full-scale high-speed catamaran was investigated using the sea trial data. The reduction in motion sickness incidence (MSI) was estimated in order to examine the effectiveness of the RCS in improving passenger comfort. With the existing control algorithm, the vertical accelerations were found to be best controlled by the active T-foil working together with the active stern tabs, while the pitch RAO was mainly mitigated by deploying only the stern tabs. About a 23% reduction was observed in the peak heave RAO with deployment of an active T-foil. The MSI can be reduced by up to 23% with respect to the cases with stern tabs only, depending on the encountered wave conditions, based on ISO recommendation for MSI calculation of a 2-h seaway passage.
Solution speciation and human serum protein binding of indium(III) complexes of 8-hydroxyquinoline, deferiprone and maltol
Authors: Dömötör Orsolya , Keppler Bernhard K. , Enyedy Éva A.
Published: March 2022

Solution speciation and serum protein binding of selected In(III) complexes bearingO,OandO,Ndonor sets were studied to provide comparative data for In(III) and analogous Ga(III) complexes. Aqueous stability of the In(III) complexes of maltol, deferiprone, 8-hydroxyquinoline (HQ) and 8-hydroxyquinoline-5-sulfonate (HQS) was characterized by a combined pH-potentiometric and UV–visible spectrophotometric approach. Formation ofmono,bisandtris-ligand complexes was observed. Thetris-ligand complexes of HQ (InQ3) and deferiprone (InD3) are present in solution inca. 90% at 10 µM concentration at pH = 7.4, while thetris-maltolato complex (InM3) displays insufficient stability under these conditions. Binding towards human serum albumin (HSA) and (apo)transferrin ((apo)Tf) of InQ3, InD3and InM3complexes and Ga(III) analogue of InQ3(GaQ3) together with InCl3was investigated by a panel of methods: steady-state and time-resolved spectrofluorometry, UV–visible spectrophotometry and membrane ultrafiltration. Moderate binding of InQ3to HSA was found (logK′ = 5.0–5.1). InD3binds to HSA to a much lower extent in comparison to InQ3. ApoTf is able to displace HQ, deferiprone and maltol effectively from their In(III) complexes. Protein binding of non-dissociated InQ3was also observed at high complex-to-apoTf ratios. Studies conducted with the InQ3/GaQ3– HSA – Tf ternary systems revealed the more pronounced Tf binding of In(III) via ligand release, while the original GaQ3scaffold is preferably retained upon protein interactions and significant albumin binding occurs. Significant dissociation of InQ3was detected in human blood serum as well.

Graphical abstract
Evaluation of responses to tomato brown rugose fruit virus (ToBRFV) and selection of resistant lines in Solanum habrochaites and Solanum peruvianum germplasm
Authors: Jewehan Ahmad , Salem Nida , Tóth Zoltán , Salamon Pál , Szabó Zoltán
Published: March 2022

Reactions of plants in 173 wild tomato accessions belonging to Solanum habrochaites and S. peruvianum were studied by inoculation with a tobamovirus, tomato brown rugose fruit virus (ToBRFV). Around 10–50% of plants in nine accessions of S. habrochaites and one of S. peruvianum were demonstrated to be highly resistant. Resistant plants showed no symptoms at 22–24 °C, and no virus could be detected in their inoculated and newly developed leaves using bioassays and RT-qPCR. ToBRFV-resistant plants were also resistant to tobacco mosaic virus and tomato mosaic virus. The susceptible wild tomatoes were infected systemically with ToBRFV showing different severity of symptoms. When resistant plants inoculated with ToBRFV were incubated in a plant growth chamber at a temperature of 33 °C, they expressed mosaic and deformation symptoms, indicating that the resistance was broken at elevated temperature. However, when these plants were transferred to the greenhouse at 24 °C, their newly emerged leaves showed no symptoms, and the virus could not be detected in the new leaves. Cleft grafting was done with scions from a resistant plant of S. habrochaites LA1739 into ToBRFV-infected susceptible tomato rootstock. The scions became infected and showed mosaic symptoms indicating that the resistance was ineffective after grafting. Sequences comparison of Solyc08g075630 loci of nine resistant accessions showed high heterogenity. Only one resistant plant of S. habrochaites carried an allele almost identical to the resistance gene reported previously. All other resistant plants may have probably unknown gene(s) of resistance to ToBRFV.
Population-based estimates of overtreatment with adjuvant systemic therapy in early breast cancer patients with data from the Netherlands and the USA
Authors: Ragusi M. A. A. , van der Velden B. H. M. , van Maaren M. C. , van der Wall E. , van Gils C. H. , Pijnappel R. M. , Gilhuijs K. G. A. , Elias S. G.
Published: March 2022

Purpose

Although adjuvant systemic therapy (AST) helps increase breast cancer-specific survival (BCSS), there is a growing concern for overtreatment. By estimating the expected BCSS of AST using PREDICT, this study aims to quantify the number of patients treated with AST without benefit to provide estimates of overtreatment.

Methods

Data of all non-metastatic unilateral breast cancer patients diagnosed in 2015 were retrieved from cancer registries from The Netherlands and the USA. The PREDICT tool was used to estimate AST survival benefit. Overtreatment was defined as the proportion of patients that would have survived regardless of or died despite AST within 10 years. Three scenarios were evaluated: actual treatment, and recommendations by the Dutch or USA guidelines.

Results

59.5% of Dutch patients were treated with AST. 6.4% (interquartile interval [IQI] = 2.5, 8.2%) was expected to survive at least 10 years due to AST, leaving 93.6% (IQI = 91.8, 97.5%) without AST benefit (overtreatment). The lowest expected amount of overtreatment was in the targeted and chemotherapy subgroup, with 86.5% (IQI = 83.4, 89.6%) overtreatment, and highest in the only endocrine treatment subgroup, with 96.7% (IQI = 96.0, 98.1%) overtreatment. Similar results were obtained using data from the USA, and guideline recommendations.

Conclusion

Based on PREDICT, AST prevents 10-year breast cancer death in 6.4% of the patients treated with AST. Consequently, AST yields no survival benefit to many treated patients. Especially improved personalization of endocrine therapy is relevant, as this therapy is widely used and is associated with the highest amount of overtreatment.
Deep learning-based simultaneous registration and unsupervised non-correspondence segmentation of medical images with pathologies
Authors: Andresen Julia , Kepp Timo , Ehrhardt Jan , Burchard Claus von der , Roider Johann , Handels Heinz
Published: March 2022

Purpose

The registration of medical images often suffers from missing correspondences due to inter-patient variations, pathologies and their progression leading to implausible deformations that cause misregistrations and might eliminate valuable information. Detecting non-corresponding regions simultaneously with the registration process helps generating better deformations and has been investigated thoroughly with classical iterative frameworks but rarely with deep learning-based methods.

Methods

We present the joint non-correspondence segmentation and image registration network (NCR-Net), a convolutional neural network (CNN) trained on a Mumford–Shah-like functional, transferring the classical approach to the field of deep learning. NCR-Net consists of one encoding and two decoding parts allowing the network to simultaneously generate diffeomorphic deformations and segment non-correspondences. The loss function is composed of a masked image distance measure and regularization of deformation field and segmentation output. Additionally, anatomical labels are used for weak supervision of the registration task. No manual segmentations of non-correspondences are required.

Results

The proposed network is evaluated on the publicly available LPBA40 dataset with artificially added stroke lesions and a longitudinal optical coherence tomography (OCT) dataset of patients with age-related macular degeneration. The LPBA40 data are used to quantitatively assess the segmentation performance of the network, and it is shown qualitatively that NCR-Net can be used for the unsupervised segmentation of pathologies in OCT images. Furthermore, NCR-Net is compared to a registration-only network and state-of-the-art registration algorithms showing that NCR-Net achieves competitive performance and superior robustness to non-correspondences.

Conclusion

NCR-Net, a CNN for simultaneous image registration and unsupervised non-correspondence segmentation, is presented. Experimental results show the network’s ability to segment non-correspondence regions in an unsupervised manner and its robust registration performance even in the presence of large pathologies.
Assessment of lung density in pediatric patients using three-dimensional ultrashort echo-time and four-dimensional zero echo-time sequences
Authors: Zeimpekis Konstantinos G. , Kellenberger Christian J. , Geiger Julia
Published: March 2022

Purpose

Lung magnetic resonance imaging (MRI) using conventional sequences is limited due to strong signal loss by susceptibility effects of aerated lung. Our aim is to assess lung signal intensity in children on ultrashort echo-time (UTE) and zero echo-time (ZTE) sequences. We hypothesize that lung signal intensity can be correlated to lung physical density.

Materials and methods

Lung MRI was performed in 17 children with morphologically normal lungs (median age: 4.7 years, range 15 days to 17 years). Both lungs were manually segmented in UTE and ZTE images and the average signal intensities were extracted. Lung-to-background signal ratios (LBR) were compared for both sequences and between both patient groups using non-parametric tests and correlation analysis. Anatomical region-of-interest (ROI) analysis was performed for the normal cohort for assessment of the anteroposterior lung gradient.

Results

There was no significant difference between LBR of normal lungs using UTE and ZTE (p < 0.05). Both sequences revealed a LBR age-dependency with a high negative correlation for UTE (Rs =  – 0.77; range 2.98–1.41) and ZTE (Rs =  – 0.82; range 2.66–1.38)). Signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were age-dependent for both sequences. SNR was higher for children up to 2 years old with 3D UTE Cones while for the rest it was higher with 4D ZTE. CNR was similar for both sequences. Posterior lung areas exhibited higher signal intensity compared to anterior ones (UTE 9.4% and ZTE 12% higher), both with high correlation coefficients (R2UTE = 0.94, R2ZTE = 0.97).

Conclusion

The ZTE sequence can measure signal intensity similarly to UTE in pediatric patients. Both sequences reveal an age- and gravity-dependency of LBR.
On a Minimax Principle in Spectral Gaps
Authors: Seelmann Albrecht
Published: March 2022

The minimax principle for eigenvalues in gaps of the essential spectrum in the form presented by Griesemer et al. (Doc Math 4:275–283, 1999) is adapted to cover certain abstract perturbative settings with bounded or unbounded perturbations, in particular ones that are off-diagonal with respect to the spectral gap under consideration. This in part builds upon and extends the considerations in the author’s appendix to Nakić et al. (J Spectr Theory 10:843–885, 2020). Several monotonicity and continuity properties of eigenvalues in gaps of the essential spectrum are deduced, and the Stokes operator is revisited as an example.
MOG-Specific T Cells Lead to Spontaneous EAE with Multilocular B Cell Infiltration in the GF-IL23 Model
Authors: Nitsch Louisa , Petzinna Simon , Zimmermann Julian , Getts Daniel R. , Becker Albert , Müller Marcus
Published: March 2022

Although IL-23 and downstream signal transduction play essential roles in neuroinflammation, the local impact of IL-23 in multiple sclerosis is still not fully understood. Our previous study revealed that the central nervous system (CNS)-restricted expression of IL-23 in a mouse model with astrocyte-specific expression of IL-23, called GF-IL23 mice, leads to spontaneous formation of infiltrates in the brain, especially in the cerebellum. To further investigate the impact of CNS-specific IL-23-expression on neuroinflammation, we studied the GF-IL23 model in mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell receptor (GF23-2D2 mice). The GF23-2D2 mice developed a chronic progressive experimental autoimmune encephalomyelitis with myelitis and ataxia without requiring additional immunization. CNS-production of IL-23 alone induced pronounced neuroinflammation in the transgenic MOG-specific T cell receptor model. The GF23-2D2 mice spontaneously developed multilocular infiltrates with a high number of B cells, demyelination and a proinflammatory cytokine milieu indicating that the interaction of encephalitogenic T cells and B cells via co-stimulatory factors seemed to be crucial.
First fossil tumbling flower beetle-type larva from 99 million-year-old amber
Authors: Zippel Ana , Haug Carolin , Müller Patrick , Haug Joachim T.
Published: March 2022

Beetle larvae often differ significantly in morphology from their adult counterparts. Therefore, it should be surprising that these immatures are often not considered to the same extent as the adult beetles. As an example, the fossil record of most beetle groups is largely represented by adult specimens. Representatives of Mordellidae, the group of tumbling flower beetles, have a cosmopolitan distribution with myriads of formally described species, based mostly on adult male specimens. Mordellidae is also well represented in the fossil record, but again only by adults; not a single fossil specimen of a larva has been reported until now. We report a new well-preserved beetle larva in 99 million-year-old Kachin amber. The larva possesses specialisations not known from the modern larvae of Mordellidae, but otherwise is clearly similar to them in many aspects. It appears possible that the fossil represents yet another holometabolan larva in Kachin amber that is associated with life within wood and/or fungi, and therefore, may have contributed to carbon cycling of the past.
Digestate Composition Affecting N Fertiliser Value and C Mineralisation
Authors: Häfner Franziska , Hartung Jens , Möller Kurt
Published: March 2022

A variety of organic feedstocks can be used for anaerobic digestion, resulting in digestates with different compositions, affecting the fertiliser value. Therefore, two experiments were conducted to assess (1) differences in the nitrogen (N) fertiliser value of seven digestates from different feedstocks in a 2-year field experiment with spring wheat, and (2) the degradability of organic matter (OM) in the digestates within an aerobic incubation experiment. In the field, mineral fertiliser equivalents were in a range of 18–60% (1st year) and 39–83% (2nd year). Fertiliser properties could describe 58.9–74.2% of the N offtake variance among digestates. In the incubation experiment, digestates produced 720–1900 mg CO2-C kg−1. After 56 days, 61% of organic C added by food waste digestate has been mineralised, compared to 16–22% for the other digestates. Digestate composition (C/N, Corg/Norg, carbonate, cellulose, lignin, and crude fibre) could explain 90.4% of the CO2 evolution. In both experiments, digested food waste stood out among digestates with the highest N offtake and highest OM mineralisation. In conclusion, differences in fertiliser value and OM degradability could be related to compositional variations. However, apart from food waste, the composition had only minor influence on digestate performance after soil application.

Graphical Abstract
A real options analysis of existing green energy facilities: maintain or replace?
Authors: Dønnestad E. M. , Fleten S.-E. , Kleiven A. , Lavrutich M. , Teige A. M.
Published: March 2022

We consider an operator of machinery with deteriorating efficiency, facing the problem of optimally timing of either a minor (maintenance) investment or a major (replacement) investment under price uncertainty. If a maintenance investment is chosen, the efficiency of the machinery will deteriorate more slowly, and replacing later is still possible. The optimal decision rule is expressed in the form of thresholds for long-run prices, indicating that it may be rational to wait to see which of the large and small investment is the better choice. We relate the setting to repowering of green energy facilities, such as hydropower plants and wind farms. Our analysis provides several managerial insights. We characterize the conditions that govern whether the smaller investment should be considered at all, and we quantify the effect of having a replacement option embedded in a maintenance option. Our analysis demonstrates that the large investment may get postponed significantly in expectation, which recognizes maintenance as a temporary alternative to replacement.
Secondary electron yield reduction of copper after 355 nm ultrashort pulse laser ablation
Authors: Lorenz Pierre , Himmerlich Marcel , Ehrhardt Martin , Bez Elena , Bogdanowicz Karolina , Taborelli Mauro , Zimmer Klaus
Published: March 2022

Nanostructured surfaces exhibit remarkable chemical, physical and microbiological properties and have therefore various technical and industrial applications. The ultrashort laser pulse irradiation (wavelength λ = 355 nm, pulse duration Δtp = 12 ps, repetition rate f = 100 kHz) of copper samples with appropriate laser parameters results in the formation of a micro- and nanostructured surfaces. The influence of these hierarchically textured surfaces on the secondary electron yield (SEY) was studied especially with regard to their morphological and geometrical properties. Specific SEY changes are caused by both, the shape and the depth of the microstructures, as well as the morphology of the formed nanostructures; that can be either compact flower head-like nanostructures, non-compact filament-shaped nanostructures, molten and resolidified spherical structures, or minor modified surfaces. The measured SEY as a function of the primary electron energy is correlated with the surface topography that forms upon laser irradiation. The SEY decreases with increasing accumulated laser fluence and ablated volume, respectively. Especially flower-head-like nanostructures can be produced at high laser power (P ≥ 400 mW) and low scanning velocity (v ≤ 10 mm/s) and represent a surface with strongly reduced SEY maximum as low as 0.7.
Money in the Dutch Republic
Authors: Felten Sebastian
Published: March 2022

The Dutch Republic was an important hub in the early modern world-economy, a place where hundreds of monies were used alongside each other. Sebastian Felten explores regional, European and global circuits of exchange by analysing everyday practices in Dutch cities and villages in the period 1600-1850. He reveals how for peasants and craftsmen, stewards and churchmen, merchants and metallurgists, money was an everyday social technology that helped them to carve out a livelihood. With vivid examples of accounting and assaying practices, Felten offers a key to understanding the internal logic of early modern money. This book uses new archival evidence and an approach informed by the history of technology to show how plural currencies gave early modern users considerable agency. It explores how the move to uniform national currency limited this agency in the nineteenth century and thus helps us make sense of the new plurality of payments systems today.
Disorder Contained
Authors: Cox Catherine , Marland Hilary
Published: March 2022

Disorder Contained is the first historical account of the complex relationship between prison discipline and mental breakdown in England and Ireland. Between 1840 and 1900 the expansion of the modern prison system coincided with increased rates of mental disorder among prisoners, exacerbated by the introduction of regimes of isolation, deprivation and hard labour. Drawing on a range of archival and printed sources, the authors explore the links between different prison regimes and mental distress, examining the challenges faced by prison medical officers dealing with mental disorder within a system that stressed discipline and punishment and prisoners' own experiences of mental illness. The book investigates medical officers' approaches to the identification, definition, management and categorisation of mental disorder in prisons, and varied, often gendered, responses to mental breakdown among inmates. The authors also reflect on the persistence of systems of punishment that often aggravate rather than alleviate mental illness in the criminal justice system up to the current day. This title is also available as Open Access.
Remarks by Geraldo Vidigal
Authors: Vidigal Geraldo
Published: March 2022

During the decade between 2007 and 2017, the World Trade Organization (WTO) became the almost exclusive forum for the settlement of interstate trade disputes. The previous 1995–2005 period had seen some signs that regional trade agreements (RTAs), such as the North American Free Trade Agreement (NAFTA), the Common Market of the South (MERCOSUR), and the Andean Community, could become alternative forums for dispute settlement in trade. Between 2007 and 2017, however, the only agreement under which (two) trade disputes were brought to adjudication was the Dominican Republic—Central America—United States Free Trade Agreement (CAFTA-DR).
Climate Lawyers as Movement Lawyers (and Vice Versa)
Authors: Gonzalez Carmen G.
Published: March 2022

The knowledge, skills, and expertise of lawyers in all practice areas are desperately needed to address the interrelated crises of climate change and racial injustice.
Remarks by Faisal Saeed Al Mutar
Authors: Al Mutar Faisal Saeed
Published: March 2022

We live in both the information and the misinformation age.
Remarks by Lucy Reed
Authors: Reed Lucy
Published: March 2022

Thank you, Catherine, for your kind welcome, and for your calm and inspirational leadership of the Society through troubled times. I thank all for attending this Lecture in two dimensions.
Introductory Remarks by Catherine Amirfar
Authors: Amirfar Catherine
Published: March 2022

Welcome everyone to the 2021 Hudson Medal Presentation. The Manley O. Hudson Medal, the Society's highest honor, has been awarded since 1959 to a distinguished person of American or other nationality for outstanding contributions to scholarship and achievement in international law. The medal has been conferred on many luminaries, including Rosalyn Higgins, Tom Franck, Michael Reisman, Eli Lauterpacht, John Jackson, Bruno Simma, Peter Trooboff, and Stephen Breyer.
Introductory Remarks by Marsha Echols
Authors: Echols Marsha
Published: March 2022

In introducing “International Aid in a Time of Global Crisis,” Professor Marsha Echols (moderator) urged a positive approach in spite of the many global crises, including this year's COVID-19 crisis and the longer term global environmental, migration, food security, governance, and others. The Panelists, who represented multinational, national, and civil society perspectives, emphasized their experiences and the purposes of their institutions to confirm the appropriateness of thinking positively about the aid being provided to address global crises. Multilateralism and cross-institutional collaborations and partnerships were highlighted in concepts, laws, and practical experiences.
Remarks by Katherine Meighan
Authors: Meighan Katherine
Published: March 2022

I am delighted to join this insightful ASIL event and want to begin by discussing the global context and multilateralism, fully supporting the remarks of the previous speaker, Mr. Jay Pozenel. I then turn to the role of International Fund for Agricultural Development (IFAD) lawyers in innovating international aid responses in this time of global crisis, and end with two specific examples of these legal innovations.
Remarks by Peter Danchin
Authors: Danchin Peter
Published: March 2022

The origins and implications of the current backlash to international legal norms and institutions are arguably the most pressing and perplexing issues in international law today. We appear to be at a moment when the modern internationalist vision of multilateral cooperation and global governance is widely understood to be under assault and unraveling, and when ideas of supranational organization and post-national sovereignty are increasingly resisted.
Remarks by Shruti Rana
Authors: Rana Shruti
Published: March 2022

We find ourselves today poised on the edge of a moment of transition. As the traditional structures and institutions of the post-World War II global legal order weaken or fall around us, international lawyers have been questioning whether what we are witnessing is merely a cyclical downturn in the strength and utility of the international legal order, that is, just another periodic adjustment or ebb from the high-water mark of the 1990s—or whether we are instead witnessing the messy and painful collapse of one order and the bloody birth of another.
Protecting People in the Context of Climate Change and Disasters: Setting the Scene
Authors: Hagon Kirsten
Published: March 2022

For the 2020 World Disasters Report, the International Federation of Red Cross and Red Crescent Societies (IFRC) compiled and analyzed disaster data since the 1960s, looking globally at the number and type of disasters, the number of people affected and how and where and reviewing how this has changed over time. When looking at the trends in disaster data, the impact of climate crisis is clear.
The Case of Ioane Teitiota v. New Zealand at the Human Rights Committee: A Common Sense approach
Authors: Laki Duncan Muhumuza
Published: March 2022

On October 24, 2019, The Human Rights Committee adopted a view in the case of Ioane Teitiota v. New Zealand; a case concerning the complaint of a national of Kiribati, seeking asylum in New Zealand, from the effects of climate change in Kiribati. With his claim being rejected by New Zealand, Mr. Teitiota was returned to his country; however, he insisted that by sending him back to Kiribati, New Zealand violated his right to life under the International Covenant on Civil and Political Rights (ICCPR) by exposing him to conditions that endanger his life. The conditions included the sea level rise in Kiribati due to climate change, resulting in the scarcity of habitable space, environmental degradation, and saltwater contamination of the freshwater supply.
Introductory Remarks by Jorge Viñuales
Authors: Viñuales Jorge
Published: March 2022

Good morning, afternoon, or evening to all and welcome to this session of ASIL's Annual Meeting on “Judging the Climate Crisis: the Role of the International Court of Justice in Addressing Environmental Harms,” which is held online this year due to the COVID-19 pandemic.