bluuebunny/crossref_metadata_2025 huggingface dataset:
The fractal brain: scale-invariance in structure and dynamics
Authors: Grosu George F , Hopp Alexander V , Moca Vasile V , Bârzan Harald , Ciuparu Andrei , Ercsey-Ravasz Maria , Winkel Mathias , Linde Helmut , Mureșan Raul C
Published: September 2022

The past 40 years have witnessed extensive research on fractal structure and scale-free dynamics in the brain. Although considerable progress has been made, a comprehensive picture has yet to emerge, and needs further linking to a mechanistic account of brain function. Here, we review these concepts, connecting observations across different levels of organization, from both a structural and functional perspective. We argue that, paradoxically, the level of cortical circuits is the least understood from a structural point of view and perhaps the best studied from a dynamical one. We further link observations about scale-freeness and fractality with evidence that the environment provides constraints that may explain the usefulness of fractal structure and scale-free dynamics in the brain. Moreover, we discuss evidence that behavior exhibits scale-free properties, likely emerging from similarly organized brain dynamics, enabling an organism to thrive in an environment that shares the same organizational principles. Finally, we review the sparse evidence for and try to speculate on the functional consequences of fractality and scale-freeness for brain computation. These properties may endow the brain with computational capabilities that transcend current models of neural computation and could hold the key to unraveling how the brain constructs percepts and generates behavior.
Evaluation of an Opt-Out Protocol for Antibiotic De-Escalation in Patients With Suspected Sepsis: A Multicenter, Randomized, Controlled Trial
Authors: Moehring Rebekah W , Yarrington Michael E , Warren Bobby G , Lokhnygina Yuliya , Atkinson Erica , Bankston Allison , Collucio Julia , David Michael Z , Davis Angelina E , Davis Janice , Dionne Brandon , Dyer April P , Jones Travis M , Klompas Michael , Kubiak David W , Marsalis John , Omorogbe Jacqueline , Orajaka Patricia , Parish Alice , Parker Todd , Pearson Jeffrey C , Pearson Tonya , Sarubbi Christina , Shaw Christian , Spivey Justin , Wolf Robert , Wrenn Rebekah H , Dodds Ashley Elizabeth S , Anderson Deverick J ,   the Centers for Disease Control and Prevention’s Prevention Epicenters Program
Published: September 2022

Background

Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis.

Methods

We evaluated non–intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics.

Results

Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47–.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88–1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar.

Conclusions

An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm.

Clinical Trials Registration

NCT03517007.
The role of interleukin-33 in organ fibrosis
Authors: Di Carmine Samuele , Scott Molly M , McLean Mairi H , McSorley Henry J
Published: September 2022

Interleukin (IL)-33 is highly expressed in the nucleus of cells present at barrier sites and signals via the ST2 receptor. IL-33 signalling via ST2 is essential for return to tissue homeostasis after acute inflammation, promoting fibrinogenesis and wound healing at injury sites. However, this wound-healing response becomes aberrant during chronic or sustained inflammation, leading to transforming growth factor beta (TGF-β) release, excessive extracellular matrix deposition, and fibrosis. This review addresses the role of the IL-33 pathway in fibrotic diseases of the lung, liver, gastrointestinal tract, skin, kidney and heart. In the lung and liver, IL-33 release leads to the activation of pro-fibrotic TGF-β, and in these sites, IL-33 has clear pro-fibrotic roles. In the gastrointestinal tract, skin, and kidney, the role of IL-33 is more complex, being both pro-fibrotic and tissue protective. Finally, in the heart, IL-33 serves cardioprotective functions by favouring tissue healing and preventing cardiomyocyte death. Altogether, this review indicates the presence of an unclear and delicate balance between resolving and pro-fibrotic capabilities of IL-33, which has a central role in the modulation of type 2 inflammation and fibrosis in response to tissue injury.
333. THE EGIDIUS PROJECT: A NETWORK APPROACH TOWARDS EXCELLENT MULTIDISCIPLINARY QUALITY OF CARE FOR PATIENTS WITH ESOPHAGEAL AND GASTRIC CANCER
Authors: Geerts Julie , Wijnhoven Bas , Rosman Camiel , Verhoeven Rob , Nieuwenhuijzen Grard ,   Egidius Expert Collaborator Group
Published: September 2022

Diagnosis and treatment of esophageal and gastric cancer is complex and requires a multidisciplinary network approach involving multiple hospitals in the Netherlands. Recent studies have shown that there is still substantial practice variation and variation in outcomes. The aim of this project is to improve quality of care in oncological networks for patients with esophageal or gastric cancer for every disease stage and to minimize undesirable practice variation and improve outcomes.

To achieve excellent quality of care of all participants in an oncological network, a multidisciplinary improvement process has been initiated involving all participating hospitals. The pilot project has started in three networks comprising 20 hospitals. First, physicians from different specialties (surgery, oncology, radiotherapy and gastro-enterology), patient advocates and health insurance representatives determined the most important quality-of-care indicators to be measured prospectively. Second, Plan-Do-Check-ACT (PDCA) cycles will be established to evaluate process and outcome indicators with both professionals and patients, leading to improvement processes to be initiated. These will be evaluated quarterly.

Specialists and patient representatives have defined a list of quality-of-care indicators for all hospitals within this project: four indicators on gastroenterology, three for radiotherapy, four surgical indicators, six on medical oncology and six on the overarching care pathway. See table 1 for the full list of indicators. The prospective measurements will start May 2022. The first results and PDCA-cycles are expected to take place in June 2022. It is expected to lead to new insights in hospital variation in the Netherlands and to start an improvement process which will be agreed upon in the upcoming discussions.

A unique network multidisciplinary project involving physicians as well as patient and health insurance representatives has been initiated. Novel and existing specialty-specific and general quality-of-care indicators haven been defined. The quarterly evaluations of this specific set of indicators to assess practice performance and variation is expected to lead to new insights, improve outcomes and reduce undesirable practice variation within the Netherlands.
359. INTRATUMORAL MICROBIOME IMPACTS IMMUNE INFILTRATES IN TUMOR MICROENVIRONMENT AND PREDICTS PROGNOSIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS
Authors: Xie Xuan , Xie Xuan , Zhang Shuishen , Ma Xiaofan , Zhan Jing , Pan Chuqing , Zhang Huizhong , Xie Xiuying , Wen Jing
Published: September 2022

Emerging evidence suggests different intratumoral microbiome exists in different tumors and plays a crucial function in carcinogenesis. However, whether intratumoral microbiome in esophageal squamous cell carcinoma (ESCC) impacts clinical outcomes and its mechanism remains unclear.

16S rDNA amplicon sequencing was performed on surgical resected samples from 106 ESCC patients including 25 paired tumorous and non-tumorous tissues (NTs) to analyze intratumoral microbiome abundance and its composition. Multiplex fluorescent immunohistochemistry (mfIHC) staining was used to profile the phenotypes of immune infiltrates in tumor microenvironment (TME).

Both Shannon index and operational taxonomic units (OTUs), representing alpha-diversity of microbiome, were found significantly lower in tumors comparing to the corresponding NTs. Multivariate analysis revealed that the intratumoral Shannon index, the relative abundance of Lactobacillus and the pTNM stage were independently associated with patients’ overall survival. Furthermore, the relative abundance of Lactobacillus and Shannon index were both positively correlated with the proportions of PD-L1+ epithelial cells (ECs) and tumor-associated macrophages (TAMs, and Shannon index was negatively correlated with the proportions of natural killer cells (NKs) and activated cytotoxic T cells (aCTLs) in TME, indicating an immunosuppressive microenvironment.

These findings underscored for the first time that the high abundance of intratumoral Lactobacillus and microbiome alpha-diversity were associated with poor long-term survival of ESCC patients, which might be achieved by increasing PD-L1 + ECs and PD-L1 + TAMs and decreasing aCTLs and NKs in TME.
362. CLINICAL VALUE AND EFFICACY INDEX OF LYMPHADENECTOMY FOR THORACIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Li Kexun , Leng Xue Feng , Du Kunyi , Liu Kun , He Wenwu , Wang Qifeng , Luo Xi , Wang Chenghao , Wang Kangning , Liu Guangyuan , Wei Xing , Li Haojun , Zhou Qiang , Li Zhiyu , Zheng Kai , Li Changding , Li KunZhi , Mao Tianqin , Deng Xuyang , Luo Qiyu , Nie Xin , Fang Qiang , Xiao WenGuang , Han Yongtao , Peng Lin
Published: September 2022

Esophageal squamous cell carcinoma (ESCC) has high mortality in China. The cornerstone of treatment for resectable esophageal cancer is still surgery. It is vital to find the regularity of lymph node metastasis and the value of dissection for thoracic ESCC in China, to provide a basis for accurate staging and the relationship between overall survival (OS) and lymph node dissection.

Cases were collected from 2957 patients in Sichuan Cancer Hospital & Institute Esophageal Cancer Case Management Database (SCH-ECCM Database) from January 2010 to August 2017. The stations of lymph node were referenced according to CSCO diagnosis and treatment guidelines and JES, 11th Ed. According to the frequency and patient’s survival of metastases to each station of investigated tumor location were used to calculate the Efficacy Index (EI). EI was calculated by multiplying the frequency (%) and 5-year survival rate of metastases (%) in patients, and then dividing by the number of 100.

The median follow-up time was 59.5 months. The EI was high in supraclavicular and mediastinal zones in patients with upper esophageal tumors, and the EI of 106recR was 13.72, which was the highest among lymph node stations. The EI was high in mediastinal zone followed by celiac and supraclavicular zones in patients with middle esophageal tumors, 104R with EI of 15.54 was the highest among lymph node stations. As for patients with lower esophageal tumors, the EI was high in celiac zone followed by mediastinal zones, the EI of left gastric artery was 10.86, over every lymph node stations.

The EI of right recurrent nerve lymph nodes is the highest in upper esophageal cancer, as for middle esophageal cancer right supraclavicular lymph nodes had high metastasis rate and EI, but the left gastric lymph nodes had high metastasis rate and EI in the lower esophageal cancer. Although the lymph node metastasis rate of ESCC is still high, the more efficient lymphadenectomy should be considered based on further studies.
623. A NEW PROGNOSTIC EVALUATION OF POSTOPERATIVE ESOPHAGEAL CANCER: LONG-TERM FLAIL INVESTIGATION
Authors: Tanaka Tatsuya , Ogawa Ryo , Saito Masaki , Ito Sunao , Ueno Shuhei , Okubo Tomotaka , Sagawa Hiroyuki , Tanaka Tatsuya , Takahashi Hiroki , Matsuo Yoichi , MItsui Akira , Kimura Masahiro , Takiguchi Shuji
Published: September 2022

Recurrence-free survival and 5-year survival rates are still commonly used as prognostic indicators for gastrointestinal cancer. We believe that there is a need to find an appropriate index to evaluate changes in health status over time in postoperative patients.

We evaluated changes in "frailty" after esophageal cancer surgery using the Kihon Checklist (KCL) developed by the Japanese Ministry of Health, Labour and Welfare, and examined risk factors for worsening health status after surgery.

Twenty-four patients (21 thoracoscopic sub-total esophagectomy, 1 mediastinoscopic sub-total esophagectomy, and 2 total laryngopharyngoesophagectomy) who underwent esophageal cancer surgery in our department from December 2019 to April 2021 were included. Patients were asked to write down their KCL before surgery and one year after surgery at an outpatient clinic, and changes over time were checked. We compared the background factors in the "maintain" group (M group) and the "worsened" group (W group), and investigated the risk factors for pre-frail and frail states one year after the surgery.

8 patients worsened from robust to pre-frail to frail and pre-frail to frail, and 16 patients maintained their condition, with 33% of them worsening. Age (M/W: 70/72, p=0.296), male (M/W: 0.88/1.0, p=0.536), BMI (M/W: 22.4/19.6, p=0.142), pStage≥3 (M/W: 0.38/0.38, p=1.0), preoperative chemotherapy (M/W: 0.69/0.63, p=1.0), operative time (M/W: 566/610 minutes, p=0.327), blood loss (M/W: 103/151 ml, p=0.342), postoperative pneumonia (M/W: 0.25/0.25, p=1.0), and cancer recurrence (M/W: 0.19/0.50, p=0.167). The preoperative blood samples were Alb (M/W: 4.3/3.8 g/dl, p=0.046), Hb (M/W: 14.2/12.8 g/dl, p=0.015) and Cre (M/W: 0.85/0.79 mg/dl, p=0.713).

At 1 year after esophageal cancer surgery, health worsened and 33% of patients were in a pre-frail or frail state. Risk factors for worsening health were low Alb and low Hb, which were not related to stage or actual age. Further study is needed to clarify risk factors for frailty.
World War I: A Phoenix Moment in the History of International Criminal Tribunals
Authors: Bohrer Ziv , Pirker Benedikt
Published: September 2022

The post-World War II International Military Tribunal at Nuremberg is commonly considered the first-ever international criminal tribunal. It is also often argued that the very idea of an international criminal tribunal emerged after World War I, when the first plans for such a tribunal were drawn up. This article, however, presents a very different account. It shows that international criminal tribunals did not have to wait for their conception until after World War I; nor did they come into being after World War II – they already operated during World War I and the preceding century. The article also demonstrates that the existence of such tribunals did influence the participants of the Paris Peace Conference, even though they portrayed them as novel.
Effect of repeat catheter ablation vs. antiarrhythmic drug therapy among patients with recurrent atrial tachycardia/atrial fibrillation after atrial fibrillation catheter ablation: data from CHINA-AF registry
Authors: Zhou Lu , He Liu , Wang Wei , Li Changyi , Li Songnan , Tang Ribo , Sang Caihua , Liu Nian , Jiang Chenxi , Yu Ronghui , Long Deyong , Du Xin , Dong Jianzeng , Ma Changsheng
Published: September 2022

Aims

Although several studies have proved that repeat catheter ablation is beneficial to recurrent atrial tachycardia (AT)/atrial fibrillation (AF) after AF catheter ablation, the hard endpoints of the effect of catheter ablation on recurrent AT/AF patients after AF catheter ablation remains unclear. Our study aims to compare the effect of catheter ablation and drug therapy on recurrent AT/AF patients after AF catheter ablation.

Methods and results

Four thousand nine hundred and thirteen consecutive patients with recurrent AT/AF after catheter ablation from the China-AF registry were enrolled. The patients were divided into two study groups: the repeat catheter ablation group and the medical therapy group. The primary endpoint is a composite of cardiovascular mortality or ischaemic stroke or major bleeding events. Secondary endpoints were each component of the primary endpoints and AF recurrence rate. Landmark analysis and Cox regression were used in the statistical analysis. We chose landmark 36 months as the primary landmark date. Over a median follow-up period of 40 ± 24 months, 4913 patients were divided into either the repeat ablation group or the medical therapy group. The cumulative incidence of the composite primary outcome was significantly lower in the repeat ablation group than the medical therapy group (adjusted hazard ratio = 0.56; 95% confidence interval: 0.35–0.89; P = 0.015) of landmark 36 months (2359 patients were included in medical therapy group and 704 patients were included in repeat ablation group at landmark 36 months). However, all secondary endpoints were not statistically different in the two groups, including cardiovascular mortality, ischaemic stroke, major bleeding events, and AF recurrence rate.

Conclusion

Based on this research, in recurrent AT/AF patients after a catheter ablation procedure, compared with medical therapy, repeat catheter ablation may significantly reduce the risk of the endpoint of composite cardiovascular mortality, ischaemic stroke, and major bleeding events.
Multiple Horizontal Acquisitions of Plant Genes in the Whitefly Bemisia tabaci
Authors: Gilbert Clément , Maumus Florian
Published: September 2022

The extent to which horizontal gene transfer (HGT) has shaped eukaryote evolution remains an open question. Two recent studies reported four plant-like genes acquired through two HGT events by the whitefly Bemisia tabaci, a major agricultural pest (Lapadula WJ, Mascotti ML, Juri Ayub M. 2020. Whitefly genomes contain ribotoxin coding genes acquired from plants. Sci Rep. 10(1):15503; Xia J, et al. 2021. Whitefly hijacks a plant detoxification gene that neutralizes plant toxins. Cell 184(7):1693–1705 e1617.). Here, we uncovered a total of 49 plant-like genes deriving from at least 24 independent HGT events in the genome of the Middle East Asia Minor 1 (MEAM1) whitefly. Orthologs of these genes are present in three cryptic B. tabaci species, they are phylogenetically nested within plant sequences, they are expressed and have evolved under purifying selection. The predicted functions of these genes suggest that most of them are involved in plant–insect interactions. Thus, substantial plant-to-insect HGT may have facilitated the evolution of B. tabaci toward adaptation to a large host spectrum. Our study shows that eukaryote-to-eukaryote HGT may be relatively common in some lineages and it provides new candidate genes that may be targeted to improve current control strategies against whiteflies.
The Riemann problem for a traffic flow model on a road with variable widths
Authors: Sheng Wancheng , Zhang Qinglong
Published: September 2022

We propose and investigate a model describing the traffic flow on a road with variable widths in this paper. The model, which is modified on the Aw–Rascle model, is not conservative because of the source term generated from the real traffic scenarios. The model also takes the stationary wave into considerations in the traffic flow based on the balance laws. We obtain the elementary waves of the new traffic flow model, including rarefaction waves, shock waves, contact discontinuities and particularly stationary waves. The Riemann problems to the system for the traffic flows are solved constructively, which can be further used to design numerical schemes and applied to more complex traffic flows in the future study. Some real traffic flow simulations are given, which verify the effectiveness and versatility of the model.
Pointwisea posteriorierror analysis of a discontinuous Galerkin method for the elliptic obstacle problem
Authors: Ayuso de Dios Blanca , Gudi Thirupathi , Porwal Kamana
Published: September 2022

We present a posteriori error analysis in the supremum norm for the symmetric interior penalty discontinuous Galerkin method for the elliptic obstacle problem. We construct discrete barrier functions based on appropriate corrections of the conforming part of the solution obtained via a constrained averaging operator. The corrector function accounts properly for the nonconformity of the approximation and it is estimated by direct use of the Green’s function of the unconstrained elliptic problem. The use of the continuous maximum principle guarantees the validity of the analysis without mesh restrictions but with shape regularity. The proposed residual-type estimators are shown to be reliable and efficient. Numerical results in two dimensions are included to verify the theory and validate the performance of the error estimator.
Oral gamma-cyclodextrin-encapsulated tributyrin supplementation in young pigs with experimentally induced colitis
Authors: Sommer Kaitlyn M , Jespersen Julianna C , Sutkus Loretta T , Lee Youngsoo , Donovan Sharon M , Dilger Ryan N
Published: September 2022

Disruption of intestinal integrity and barrier function due to tissue inflammation has negative implications on overall growth and well-being in young pigs. In this study, we investigated the effects of oral gamma-cyclodextrin-encapsulated tributyrin (TBCD) in young pigs experiencing dextran sodium sulfate (DSS)-induced colitis. Pigs (n = 32 boars) were weaned from the sow at postnatal day (PND) 2, allotted to treatment based on the litter of origin and body weight (BW), and reared artificially over a 26-d feeding period. Treatment groups included: 1) nutritionally adequate (control) milk replacer, no DSS (Control n = 8), 2) control milk replacer plus oral DSS (DSS, n = 7), and 3) control diet supplemented with 8.3 g of TBCD per kg of reconstituted milk replacer plus oral DSS (TBCD + DSS, n = 8). Colitis was induced by administering DSS at 1.25 g of DSS/kg BW daily in a reconstituted milk replacer from PND 14–18. Milk replacer and water were provided ad libitum throughout the 26-d study. All the data were analyzed using a one-way ANOVA using the MIXED procedure of SAS. Control and DSS pigs had similar BW throughout the study, while TBCD + DSS pigs exhibited decreased (P < 0.05) BW starting at approximately PND 15. Additionally, average daily gain (ADG) before and after initiation of DSS dosing, along with over the total study duration, was decreased (P < 0.05) in pigs receiving TBCD + DSS compared with the Control. Milk disappearance was decreased (P < 0.05) in TBCD + DSS pigs when compared with Control and DSS groups. Both the concentration and molar ratio of cecal butyrate concentrations were increased (P < 0.05) in TBCD + DSS pigs compared with the Control group. The DSS and TBCD + DSS treatments also increased (P < 0.05) butyrate concentrations in the luminal contents with the proximal colon compared with Control. TBCD + DSS and DSS pigs had increased (P < 0.05) mucosal width in the distal colon compared with Control, thereby indicating heightened intestinal inflammation. Overall, oral supplementation of encapsulated tributyrin increased the concentration of butyrate in the colon, but was unable to mitigate the negative effects of DSS-induced colitis.
A Single-Institution Experience About 10 Years With Children Undergoing Fractional Ablative Carbon Dioxide Laser Treatment After Burns: Measurement of Air Pressure-Induced Skin Elevation and Retraction Time (Dermalab) Including Standardized Subjective and Objective Scar Evaluation
Authors: Staubach Raphael , Glosse Helen , Fennell Sarah , Loff Steffan
Published: September 2022

Laser treatment has gained more and more importance in the therapy of scars during the last years. Scientific work, especially in children, is scarce on this topic and mostly with an insufficient number of cases or only subjective descriptions. Our study included 77 children from 2012 to 2022 with scars after thermal injury. These were treated at least three times or more by CO2 laser or in combination with pulsed dyed laser (PDL). Beforehand, scar texture and elasticity were determined by a skin elasticity analysis system. Regarding the subjective evaluation, a questionnaire was given to the patients or their parents. Further criteria were the Patient and Observer Scar Assessment Scale (POSAS) and Vancouver Scar Scale (VSS). A statistically significant improvement in elasticity was demonstrated in all scars of any age after each laser treatment. In addition, a significant correlation was found between the number of laser treatments and an increase in elasticity. The assessments of scars after one or more laser sessions by the observer as well as the patient showed a decreasing score in all categories with an increase in the number of laser therapies. The VSS score also improved significantly after each laser session. The mean score before treatment was about 7, after the first laser session, the mean score was already below 6 with a statistical significance. Ninety-six percent of the patients or their parents were satisfied with the laser therapy, and 90% wished to repeat the procedure. This work confirms, by means of the objectification by the scar measurement, the previous scientific works concerning a scar therapy by laser and emphasizes particularly that this can also be used without problems with children with symptomatic scars, contractures, or with cosmetically relevant scars.
Genocide
Authors: Ambos Kai
Published: September 2022

This chapter focuses on genocide, which developed from a category of crimes against humanity to an autonomous crime after World War II. It considers the codification as a response to the German Holocaust, the archetypal genocide. The term was coined in 1944 by Raphael Lemkin, from the Greek word γένος and the combining form ‘cide’ from the Latin word caedere, in order to de-note an old practice to its modern development. The chapter mentions the US military tribunals sitting at Nuremberg that demonstrated the emerging acceptance of the concept by explicitly using the term genocide in both the indictment and the judgment in the Einsatzgruppen trial in order to characterize the activities of the German troops in Poland and the Soviet Union. Those who devise and implement genocide seek to deprive humanity of the manifold richness its nationalities, races, ethnicities, and religions provide.
Crimes against Humanity
Authors: Ambos Kai
Published: September 2022

This chapter explores the concept of crimes against humanity that goes back to the Declaration of 28 May 1915 by the governments of France, Great Britain, and Russia, relating to the massacres of the Armenian population in Turkey. It analyzes the declaration that described the atrocities as crimes against humanity for which all members of the Turkish Government will be held responsible together with its agents implicated in the massacres. Similarly, in the Nuremberg trials crimes against humanity were dealt with as crimes committed by Germans against fellow Germans. The chapter discusses crimes against humanity that provides penal protection against the transgression of the most basic laws protecting the individuality as political beings and social entity as members of political communities. The transgressor becomes an enemy and legitimate target of all humankind, who may bring to justice.
War Crimes
Authors: Ambos Kai
Published: September 2022

This chapter examines the concept of war crime that may be understood in both a broad and a narrow sense. In a broad sense, it encompasses all criminal acts committed in a war or an armed conflict, notwithstanding their character as war crimes in a narrow sense or other international crimes, in particular crimes against humanity. It deals with war crimes stricto sensu, specifically the ones codified in Article 8 of the International Criminal Court (ICC) Statute. The chapter talks about the crimes of armed conflict that belong to the ‘ius in bello’ and must be distinguished from punishable acts based on violations of the ‘ius ad bellum’, which may amount to a crime of aggression to be dealt with in Chapter 4.
Austria
Authors: Mock Sebastian
Published: September 2022

Generally, the Austrian legal system provides an explicit and comprehensive set of rules governing state liability. However, in the context of financial supervisors and resolution authorities Austrian state liability law limits the liability to damages that have been directly caused to the legal entity subject to supervision. Consequently, investors can usually not claim and damages from the Austrian financial supervisors or the Republic of Austria since these damages are not directly caused by the supervisors. However, it remains unsettled whether this limitation constitutes a violation of the Austrian constitution and European law.
Greece
Authors: Gortsos Christos V , Anastopoulou Elli K
Published: September 2022

The Greek financial supervisors (Bank of Greece and Hellenic Capital Market Commission) are subject to a statutory no-fault liability standard, whereby their liability is established in cases of illegality in their actions; proving fault in their behaviour (negligence or intention) is not required. However, Greek case law has limited their liability by holding them liable only in cases of grave illegality. Equally, case law has limited the right to compensation of aggrieved parties to reasonable compensation, while in certain instances it has granted the supervisors compensatory immunity. When the Bank of Greece acts in its capacity as a resolution authority, the statutory liability standard is that of gross negligence and bad faith. This chapter discusses the liability of Greek financial supervisors and resolution authorities and evaluates the limitations introduced thereto in light of the EU law requirements.
The Republic of South Africa
Authors: Schlemmer Engela Catharina
Published: September 2022

An overview and discussion of the private law liability of financial supervisors in the Republic of South Africa are provided. The supervision of the South African financial system is in the process of change. The supervisory liability historically was limited and currently, since the introduction of a twin peaks model of regulation in 2018, potential supervisory liability is again limited and now only to instances where one can prove the absence of good faith. If a supervisor has acted in bad faith, there is no immunity from liability. In such an instance, the determination of wrongfulness in the light of public and legal policy considerations and constitutional principles may point in the direction of holding the supervisory authority liable. However, supervisory liability has not been tested in the South African courts and the proving of such will not be an easy task. In the absence of a deposit insurance and banking resolution scheme (both of which have been tabled in Parliament) the position of depositors is not secure and indeed precarious. Public law remedies exist to potentially alleviate and correct the impact of wrong decisions made by supervisors, but very little protection exist as yet to depositors, and they have to rely on the goodwill of the government to step in when a financial institution has to be resolved.
Comparative Law Evaluation
Authors: Busch Danny , Gortsos Christos V , McMeel Gerard
Published: September 2022

In this chapter, we place the liability of financial supervisors and resolution authorities in a comparative law perspective. There is constant tension between those in favour and those against granting financial supervisors and resolution authorities some form of protection against liability claims. At first sight, those advocating a limitation of liability seem to be gaining the upper hand, since there is a growing tendency to limit the liability of financial supervisors and resolution authorities in one way or another. The extent to which financial supervisors and resolution authorities are protected against liability claims, and the exact shape that this takes, is however not uniform across the jurisdictions studied. At the same time, a counter-movement is emerging, as limitations of liability are by no means undisputed and are under attack on various grounds. We also discuss the question of whether the conditions for liability of financial supervisors and resolution authorities should be harmonised in the European Banking Union.
Damages
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter expounds on the concept, causation, foreseeability, and compensation of damages. The purpose of damages for breach of contract is traditionally understood to compensate losses. In some countries, the law of damages also serves a preventive function is reinforced by legal systems. However, true punishment is still found in private law. The chapter explains the methods of calculating and mitigating the extent of damages. Agreed sums payable upon breach of an obligation are a frequent feature in sales contracts and codifications in civil law systems. The three functions of agreed sums are deterrent to breach, compensation, facilitating the recovery of losses.
Revealing the late-time transition of H0: relieve the Hubble crisis
Authors: Hu J P , Wang F Y
Published: September 2022

The discrepancy between the value of the Hubble constant H0 measured from the local distance ladder and from the cosmic microwave background is the most serious challenge to the standard ΛCDM model. Various models have been proposed to solve or relieve it, but no satisfactory solution has been given until now. Here, we report a late-time transition of H0, i.e. H0 changes from a low value to a high one from early to late cosmic time, by investigating the Hubble parameter H($\mathit{ z}$) data based on the Gaussian process (GP) method. This finding effectively reduces the Hubble crisis by 70 per cent. Our results are also consistent with the descending trend of H0 measured using time-delay cosmography of lensed quasars at 1 σ confidence level, and support the idea that the Hubble crisis arises from new physics beyond the standard ΛCDM model. In addition, in the ΛCDM model and $w$CDM model, there is no transition behaviour of H0.
Comptonization by reconnection plasmoids in black hole coronae II: Electron-ion plasma
Authors: Sridhar Navin , Sironi Lorenzo , Beloborodov Andrei M
Published: September 2022

We perform 2D particle-in-cell simulations of magnetic reconnection in electron-ion plasmas subject to strong Compton cooling and calculate the X-ray spectra produced by this process. The simulations are performed for trans-relativistic reconnection with magnetization 1 ≤ σ ≤ 3 (defined as the ratio of magnetic tension to plasma rest-mass energy density), which is expected in the coronae of accretion discs around black holes. We find that magnetic dissipation proceeds with inefficient energy exchange between the heated ions and the Compton-cooled electrons. As a result, most electrons are kept at a low temperature in Compton equilibrium with radiation, and so thermal Comptonization cannot reach photon energies $\sim 100\,$ keV observed from accreting black holes. Nevertheless, magnetic reconnection efficiently generates $\sim 100\,$ keV photons because of mildly relativistic bulk motions of the plasmoid chain formed in the reconnection layer. Comptonization by the plasmoid motions dominates the radiative output and controls the peak of the radiation spectrum Epk. We find Epk ∼ 40 keV for σ = 1 and Epk ∼ 100 keV for σ = 3. In addition to the X-ray peak around 100 keV, the simulations show a non-thermal MeV tail emitted by a non-thermal electron population generated near X-points of the reconnection layer. The results are consistent with the typical hard state of accreting black holes. In particular, we find that the spectrum of Cygnus X-1 is well explained by electron-ion reconnection with σ ∼ 3.
Period change rates of Large Magellanic Cloud Cepheids using mesa
Authors: Espinoza-Arancibia F , Catelan M , Hajdu G , Rodríguez-Segovia N , Boggiano G , Joachimi K , Muñoz-López C , Ordenes-Huanca C , Orquera-Rojas C , Torres P , Valenzuela-Navarro Á
Published: September 2022

Pulsating stars, such as Cepheids and RR Lyrae, offer us a window to measure and study changes due to stellar evolution. In this work, we study the former by calculating a set of evolutionary tracks of stars with an initial mass of 4 to 7 M⊙, varying the initial rotation rate and metallicity, using the stellar evolution code modules for experiments in stellar astrophysics (mesa). Using Radial Stellar Pulsations (rsp), a recently added functionality of mesa, we obtained theoretical instability strip (IS) edges and linear periods for the radial fundamental mode. Period–age, period–age–temperature, period–luminosity, and period–luminosity–temperature relationships were derived for three rotation rates and metallicities, showing a dependence on crossing number, position in the IS, rotation, and metallicity. We calculated period change rates (PCRs) based on the linear periods from rsp. We compared our models with literature results using the geneva code, and found large differences, as expected due to the different implementations of rotation between codes. In addition, we compared our theoretical PCRs with those measured in our recent work for Large Magellanic Cloud Cepheids. We found good overall agreement, even though our models do not reach the short-period regime exhibited by the empirical data. Implementations of physical processes not yet included in our models, such as pulsation-driven mass-loss, an improved treatment of convection that may lead to a better description of the IS edges, as well as consideration of a wider initial mass range, could all help improve the agreement with the observed PCRs.
Strong C iv emission from star-forming galaxies: a case for high Lyman continuum photon escape
Authors: Saxena A , Cryer E , Ellis R S , Pentericci L , Calabrò A , Mascia S , Saldana-Lopez A , Schaerer D , Katz H , Llerena M , Amorín R
Published: September 2022

Finding reliable indicators of Lyman continuum (Ly C) photon leakage from galaxies is essential in order to infer their escape fraction in the epoch of reionization, where direct measurements of Ly C flux are impossible. To this end, here we investigate whether strong C iv λλ1548, 1550 emission in the rest-frame UV spectra of galaxies traces conditions ripe for ample production and escape of Ly C photons. We compile a sample of 19 star-forming galaxies in the redshift range $z$ = 3.1–4.6 from the VANDELS survey that exhibit strong C iv emission, producing a stacked spectrum where all major rest-UV emission lines are clearly detected. Best-fitting spectral energy distribution models containing both stellar and nebular emission suggest the need for low stellar metallicities ($Z=0.1--0.2\, Z_\odot$), young stellar ages ($\log (\rm {age\,yr^{-1}}) = 6.1--6.5$), a high ionization parameter (log U = −2) and little to no dust attenuation (E(B − V) = 0.00–0.01). However, these models are unable to fully reproduce the observed C iv and He ii line strengths. We find that the Ly α line in the stacked spectrum is strong and peaks close to the systemic velocity, features that are indicative of significant Ly C photon leakage along the line of sight. The covering fractions of low-ionization interstellar absorption lines are also low, implying Ly C escape fraction in the range ≈0.05–0.30, with signatures of outflowing gas. Finally, C iv/C iii] ratios of >0.75 for a subset of individual galaxies with reliable detections of both lines are also consistent with physical conditions that enable significant Ly C leakage. Overall, we report that multiple spectroscopic indicators of Ly C leakage are present in the stacked spectrum of strong C iv emitting galaxies, potentially making C iv an important tracer of Ly C photon escape at $z$ > 6.
Low-albedo asteroids: analogues with a high polarization at large phase angles
Authors: Hadamcik E , Renard J-B , Lasue J , Levasseur-Regourd A C , Ishiguro M
Published: September 2022

While remote observations of the linear polarization of five low-albedo near-Earth asteroids are available at large phase angles, space missions have collected materials from the surface of two of them and one of them is already back to Earth. The structure of the regolith on the surface may be different from that encountered on larger objects, because of their low gravity and thermal stress cycling. Dust particles crushed from low-albedo meteorites (i.e. Orgueil and Allende) are tentatively used as analogues to provide a better approach of such regoliths. The PROGRA2 experiment studies the light-scattering properties of dust particles of various size distributions under Earth’s gravity either deposited or with clouds lifted by an air-draught, as well as under μ-gravity conditions. Similar maximum in polarization (i.e. Pmax) values are obtained experimentally for dark particles deposited or in levitation, showing that multiple scattering is negligible. The increased sensitivity of PROGRA2 instruments, together with imaging techniques, makes it possible to study Pmax with increasing sizes of the lifted particles, up to mm-sizes and above. Our results confirm that particles constituting the regolith are mm-sized and may reach polarization values up to 50 per cent in good agreement with remote observations. Some materials are also suggested to be present on the surface of the particles. Also, huge agglomerates made by random ballistic deposition may be considered as relevant analogues e.g. for pebbles and boulders.
Histone protein surface accessibility dictates direction of RSC-dependent nucleosome mobilization
Authors: Bhat Javeed Ahmad , Balliano Angela J , Hayes Jeffrey J
Published: September 2022

Chromatin remodeling enzymes use energy derived from ATP hydrolysis to mobilize nucleosomes and alter their structure to facilitate DNA access. The Remodels the Structure of Chromatin (RSC) complex has been extensively studied, yet aspects of how this complex functionally interacts with nucleosomes remain unclear. We introduce a steric mapping approach to determine how RSC activity depends on interaction with specific surfaces within the nucleosome. We find that blocking SHL + 4.5/–4.5 via streptavidin binding to the H2A N-terminal tail domains results in inhibition of RSC nucleosome mobilization. However, restriction enzyme assays indicate that remodeling-dependent exposure of an internal DNA site near the nucleosome dyad is not affected. In contrast, occlusion of both protein faces of the nucleosome by streptavidin attachment near the acidic patch completely blocks both remodeling-dependent nucleosome mobilization and internal DNA site exposure. However, we observed partial inhibition when only one protein surface is occluded, consistent with abrogation of one of two productive RSC binding orientations. Our results indicate that nucleosome mobilization requires RSC access to the trailing but not the leading protein surface, and reveals a mechanism by which RSC and related complexes may drive unidirectional movement of nucleosomes to regulate cis-acting DNA sequences in vivo.
PRC2-independent actions of H3.3K27M in embryonic stem cell differentiation
Authors: Cohen Lea R Z , Kaffe Binyamin , Deri Eden , Leibson Chen , Nissim-Rafinia Malka , Maman Moria , Harpaz Nofar , Ron Guy , Shema Efrat , Meshorer Eran
Published: September 2022

The histone H3 variant, H3.3, is localized at specific regions in the genome, especially promoters and active enhancers, and has been shown to play important roles in development. A lysine to methionine substitution in position 27 (H3.3K27M) is a main cause of Diffuse Intrinsic Pontine Glioma (specifically Diffuse Midline Glioma, K27M-mutant), a lethal type of pediatric cancer. H3.3K27M has a dominant-negative effect by inhibiting the Polycomb Repressor Complex 2 (PRC2) activity. Here, we studied the immediate, genome-wide, consequences of the H3.3K27M mutation independent of PRC2 activity. We developed Doxycycline (Dox)-inducible mouse embryonic stem cells (ESCs) carrying a single extra copy of WT-H3.3, H3.3K27M and H3.3K27L, all fused to HA. We performed RNA-Seq and ChIP-Seq at different times following Dox induction in undifferentiated and differentiated ESCs. We find increased binding of H3.3 around transcription start sites in cells expressing both H3.3K27M and H3.3K27L compared with WT, but not in cells treated with PRC2 inhibitors. Differentiated cells carrying either H3.3K27M or H3.3K27L retain expression of ESC-active genes, in expense of expression of genes related to neuronal differentiation. Taken together, our data suggest that a modifiable H3.3K27 is required for proper histone incorporation and cellular maturation, independent of PRC2 activity.
SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination
Authors: Jeong Seo-Yeon , Hariharasudhan Gurusamy , Kim Min-Ji , Lim Ji-Yeon , Jung Sung Mi , Choi Eun-Ji , Chang In-Youb , Kee Younghoon , You Ho Jin , Lee Jung-Hee
Published: September 2022

Human CtIP maintains genomic integrity primarily by promoting 5′ DNA end resection, an initial step of the homologous recombination (HR). A few mechanisms have been suggested as to how CtIP recruitment to damage sites is controlled, but it is likely that we do not yet have full understanding of the process. Here, we provide evidence that CtIP recruitment and functioning are controlled by the SIAH2 E3 ubiquitin ligase. We found that SIAH2 interacts and ubiquitinates CtIP at its N-terminal lysine residues. Mutating the key CtIP lysine residues impaired CtIP recruitment to DSBs and stalled replication forks, DSB end resection, overall HR repair capacity of cells, and recovery of stalled replication forks, suggesting that the SIAH2-induced ubiquitination is important for relocating CtIP to sites of damage. Depleting SIAH2 consistently phenocopied these results. Overall, our work suggests that SIAH2 is a new regulator of CtIP and HR repair, and emphasizes that SIAH2-mediated recruitment of the CtIP is an important step for CtIP’s function during HR repair.