bluuebunny/crossref_metadata_2025 huggingface dataset:
Berlioz’s Requiem
Authors: Walker Jennifer
Published: January 2025

Hector Berlioz’s Requiem (Grande Messe des morts, 1837) remains a fixture in the repertoire of choirs and orchestras today. Since 2003, it has been performed in its entirety over one hundred times and has appeared on concert programs spanning the globe: from Russia to the United Kingdom, Finland to the United States, and many locations in between. These performances have, for the most part, been received positively—but critics have not always been this kind to Berlioz and his Requiem. Romantic grandiosity, empty dramatic effect, religious insincerity: such are the descriptors that undergird modern understandings of Berlioz’s canonic work. Nineteenth-century critics and audiences, however, heard the Requiem in different and compelling ways. This book allows for a new hearing of the Requiem by presenting a broad new musical and social context for understanding the work as Berlioz conceived it and his contemporaries heard it. I ask what, if anything, did nineteenth-century listeners find to be notable, and why? The answers to these questions lie in detailed explorations of Berlioz’s relationship to the aesthetics of French sacred music, the theological sublime, and aural architecture. Theatrical as they may have appeared, Berlioz’s innovative orchestrations and colossal choral configurations in the Requiem might now be heard as an embrace of the aural possibilities offered by the sounding of the sacred sublime, the physical architecture of French churches, and the interplay between the sacred and the secular.
Meaning and language
Authors: Borg Emma , Fisher Sarah A.
Published: January 2025

This chapter introduces meaning and why it matters. It shows how fundamental questions about meaning arise particularly clearly with respect to language, suggesting that a focus on word, sentence, and utterance meaning will be helpful in trying to understand what meaning is. The chapter explores the similarities and differences between natural human languages (like English, French, and Mandarin) and artificial languages (such as computer codes and the processing behind Large Language Models like ChatGPT). It then looks at non-human animal languages, seeing what these tell us about meaning in language. Finally, it investigates the relationship between meaning and practice, introducing the idea that what people do with words, and the contexts in which utterances are made, can fundamentally affect meaning.
Meaning and practical problems
Authors: Borg Emma , Fisher Sarah A.
Published: January 2025

Meaning is a complex, fascinating, and important phenomenon, one which is worth exploring just for its own sake. Beyond this, however, having an account of meaning might also help us solve certain puzzles or practical problems. This chapter explores a number of these practical concerns, including how to draw the distinction between lying and misleading, how to think about the meaning of slurs and other offensive expressions, and how these expressions should be regulated, for example by ‘hate speech’ laws. By looking at some of the practical issues which have exercised theorists in this area, the chapter shows how abstract questions about meaning are fundamentally connected with pressing topics in contemporary life.
Meaning and objects
Authors: Borg Emma , Fisher Sarah A.
Published: January 2025

To make progress on understanding meaning we need to resolve a fundamental theoretical question: ‘What makes any linguistic sign meaningful?’ (or, in more general terms, not restricted to words and utterances, ‘Where does meaning come from?’). This chapter introduces a first answer to that fundamental question: the referential approach to meaning. The referential approach holds that the meaning of a sign is given by the thing(s) in the world which it picks out. The chapter explores how this idea might be applied to the meaning of certain categories of words, or to signs in general. The benefits of the approach are discussed (e.g. a referential account shows how the complex notion of meaning can be analysed in terms of more basic notions), but the chapter closes by outlining some of the serious problems faced by a referential approach.
Meaning and use
Authors: Borg Emma , Fisher Sarah A.
Published: January 2025

The final chapter explores the idea that meaning is inextricably linked to the norms and institutions that characterize a society and shape the activities of its members. The chapter begins by introducing Ludwig Wittgenstein’s slogan that ‘meaning is use’. It considers his analogy of words as tools, used to fulfil a range of different functions, and utterances as moves in a ‘language game’. The chapter considers what kinds of rules could govern a language game—how determinate or indeterminate they might be—and who judges whether or not they have been followed. The discussion concludes by considering a view that ties meaning to settled conventions, as opposed to speakers’ intentions or the open-ended ways in which they use words. Having surveyed different approaches to meaning, the book ends by reminding the reader of the implications of pursuing one approach or another—and predicts that the deep philosophical debates will continue, since how we understand meaning matters.
Technological and economic interventions for a sustainable society
Authors: Ali Saleem H.
Published: January 2025

This chapter examines the technological and economic interventions for a sustainable society. It explains that technology is a key mediating mechanism for managing human needs for well-being in both biological and social terms. However, technology can have an ecological impact on planetary support systems. The chapter considers the ultimate goal of human development to improve quality of life in correlation with sustainability. It then provides an overview of the goal of a sustainable economy to find ways of decoupling localized growth from ecological harm before discussing the key concern revolving around the dominance of private profit-driven corporations in shepherding sustainability.
The relationship between psychology and linguistics
Authors: Ferreira Fernanda
Published: January 2025

This chapter provides an overview of the relationship between psychology and linguistics. It notes that psycholinguistics refers to the study of the processing routines that underlie our ability to produce and understand language. Essentially, psycholinguistics connects linguistic concepts such as verb, phrase, and clause not only to psychological concepts such as action, object, and event, but also to cognitive processes including perception, attention, memory, and decision-making. The chapter discusses the Derivational Theory of Complexity (DTC) for psycholinguistic testing. It also explains that today’s theories of processing are informed by a broader range of disciplines, including memory, statistical reasoning, and decision-making.
Conversation and dialogue
Authors: Ferreira Fernanda
Published: January 2025

This chapter elaborates on the key concepts of conversation and dialogue. It discusses the maxims of conversation presented by language philosopher Paul Grice. The core idea behind the Gricean maxims of conversation is that a cooperative interlocutor will say things they believe to be true and that are relevant to the ongoing conversation. Grice’s maxims are important because they motivate a central observation about language use. The chapter then provides an overview of theories of dialogue and alignment. It also looks into Maryellen MacDonald’s Production–Distribution–Comprehension or PDC model with the core idea that speakers choose linguistic forms to make it easier to speak fluently.
Introducing toleration
Authors: Murphy Andrew R.
Published: January 2025

This chapter provides an introduction to toleration. Toleration involves a complex blend of objection and acceptance, a willingness to guarantee rights to those holding beliefs or engaging in practices that many consider wrong or misguided. Although its modern roots lie in early modern European religious disputes, efforts to secure peaceful coexistence are not limited to those times and places. Nor has toleration been limited to the religious; it has been invoked in disputes over civil liberties, human rights, race, gender, and sexuality. The chapter distinguishes between toleration and the related notion of tolerance, and explores the relationship between toleration and the notion of a modus vivendi, a “way of living together” that seeks minimal civil peace and eschews more robust notions of community.
Early modern foundations
Authors: Murphy Andrew R.
Published: January 2025

This chapter explores the roles played by Luther, Erasmus, Christian humanists, and a range of early modern thinkers and activists in the sixteenth- and seventeenth-century emergence of religious toleration. Although Locke’s Letter Concerning Toleration is the best-known account, a broad tolerationist coalition advanced a range of sophisticated scriptural, psychological-epistemological, pragmatic-political, and historical arguments. Tolerationists, however, faced powerful opponents, and the chapter also investigates antitolerationist arguments. In addition, it illustrates the powerful role played by anti-Catholicism in the development of early modern toleration. The chapter concludes by considering the ways in which thinkers tied religious toleration to a cluster of related rights at the core of a free society, including speech, press, and assembly.
Colonial and imperial complications
Authors: Murphy Andrew R.
Published: January 2025

This chapter considers the role played by toleration in colonial and imperial contexts, and the ways that it functioned as a tool of power and control. It opens with the anti-Catholic “Black Legend,” accusing the Spanish of intolerant savagery in their treatment of indigenous peoples. It explores the East India Company’s attempt to define Hinduism as a religion worthy of toleration, and the related controversies over allowing missionaries into India, which illustrated the conflict between evangelical claims of freedom to preach and another understanding of religious freedom as guaranteeing communities the liberty to live unmolested. The chapter closes by considering the intersection between enslavement, toleration, and proselytization in the Americas.
Contesting and defending toleration
Authors: Murphy Andrew R.
Published: January 2025

This chapter brings the story down to the present day. It opens with disputes between those who view toleration as key to the modern liberal democratic tradition and those who take a dimmer view of its interconnections with colonial and imperial projects, as well as its minimal nature. It also considers toleration’s relevance to controversies over LGBTQ rights, as well as the tradition of research on political tolerance. The chapter concludes by exploring rhetoric about a “tolerant” West and “intolerant” non-Western traditions like Islam that reverberate in global affairs; and emphasizes toleration’s status within the “negative liberty” tradition in which freedom is understood as the absence of restraint.
The future of toleration?
Authors: Murphy Andrew R.
Published: January 2025

This chapter considers the future of the tolerationist legacy. It argues that Karl Popper’s “paradox of tolerance,” which justified intolerance directed toward intolerant parties in society, offers an oversimplified answer to the dynamics of toleration in contemporary societies. The chapter considers toleration and related terms in human rights charters and in efforts to improve the condition of marginalized religious, ethnic, and cultural groups. Despite toleration’s minimal nature, it retains a role to play in guaranteeing basic protections to those facing hostility from their neighbors or governments. The chapter returns to the notion of a “way of living together” that seeks minimal civil peace and eschews more robust notions of community.
BHSeP5 Implementing a pre-optimisation pathway in a tertiary hernia centre
Authors: Birch Alice , Cocciolo Federica
Published: January 2025

Incisional hernias can affect up to 20% of patients after midline laparotomy. Those at higher risk include patients with obesity, a smoking history, and poor glycaemic control. These individuals often experience poorer outcomes in elective hernia repair. Pre-optimizing these patients can decrease the risk of post-operative complications and hernia recurrence.

This paper examines the benefits of a pre-optimization pathway for patients with complex abdominal wall hernias requiring repair.

Recognizing the importance of pre-optimization, each patient was assessed for modifiable risk factors at their initial consultation, focusing on diabetes, smoking, and weight. Targets were established collaboratively between patient and clinician, aiming for weight loss, good diabetic control, smoking cessation, or a combination of these. Patients were then enrolled in a pre-optimization program, which included tri-monthly telephone clinics with an advanced clinical practitioner. Resources were provided to support goal achievement, such as healthy lifestyle advice, exercise and diet guidance, and referrals to specialists like weight management services or diabetic teams.

Over the past year, 49 patients were enrolled in the pre-optimization program: 8 for smoking cessation, 45 for weight loss, and 13 for diabetes control, with some patients needing multiple interventions. During the same period, 42 patients underwent surgery; 22 required pre-optimization—19 for weight loss, 2 for diabetes control, and 6 for smoking cessation, some needing a combination of interventions.

The majority of patients undergoing incisional hernia repair will need some form of pre-optimisation. Close follow-up increases the likelihood of patients achieving pre-surgery goals, thus reducing the risk of post-operative complications.
BHSeP6 Cumulative sum analysis of the robotic inguinal hernia repair learning curve
Authors: Hayward Romilly K , Smellie W James B , Sanchez-Thompson Natalia , Warren Oliver J
Published: January 2025

Background

The use of robotics in hernia surgery is increasing and is associated with a significant learning curve. Continuous, real-time outcome analysis is vital to inform and protect patients, and enable cost-benefit decisions.

Methods

Prospective data capture of patients undergoing robotic hernia repair during one surgeon’s introduction of robotics into their high-volume practice. Learning curve analysis was conducted using the cumulative sum (CUSUM) method.

Results

31 unilateral inguinal repairs were performed between February 2023 and May 2024. Median age was 68 years. 78% had a history of previous abdominopelvic surgery. There was one conversion to open. Median blood loss was 0 ml with no requirement for blood transfusion. 84% of patients achieved complication free recovery; all complications were Clavien-Dindo Grade I. There were no returns to theatre and 1 readmission within 30 days.

Median console time was 36 min (IQR 26–52); median time to dock and undock the robot was 13 min, making average operative time 49 min. CUSUM learning curve analysis of console time established three phases: initial training (case 1–5), improvement (case 6–15), and mastery (case 16 onwards). Perioperative outcomes were similar across phases, though console time decreased significantly.

Conclusions

Perioperative outcomes including length of stay, complications, readmissions, and return to theatre were acceptable in a relatively comorbid patient cohort, supporting the feasibility of introducing robotic hernia surgery into practice. CUSUM analysis established a clear learning curve for robotic inguinal hernia repair with rapid and significant improvement in console time over the first 31 cases.
BHSeP18 Complete abdominal wall reconstruction in a patient with chronically infected mesh
Authors: Taddeo Ghani Omar Sayed , De Brito Ana Paula Coutinho Barros , Fernandes Murakami Abel Hiroshi , Vianna Birolini Claudio Augusto
Published: January 2025

A 53-year-old male presented to the HCFMUSP’s Abdominal Wall Clinic with a history of four surgeries in 2012 due to acute appendicitis complications: he developed a subphrenic abscess, necessitating multiple laparotomies and mesh placement, resulting in a 64-day hospitalization. He is a half-pack-a-day smoker with a BMI of 29.3 kg/m². Examination in June 2023 revealed a scarified wound, exposed mesh, and a contained eventration on one-third of the anterior abdominal wall. He experienced limiting pain and purulent discharge from the exposed mesh.

A CT scan showed a 16 cm × 13 cm abdominal wall discontinuity, lateralized rectus abdominis muscles, and mesh restraining the left hepatic lobe and intestines. In March 2024, he underwent total abdominal wall reconstruction. The surgery involved removing the infected mesh and scarified skin, treating intense adhesions, and performing an opportunistic cholecystectomy. Primary abdominal wall closure was achieved using extensive bilateral Gibson's incisions and an onlay polypropylene mesh.

Postoperatively, the patient did not require ICU care. He resumed ambulation and diet on the first day. Empirical oxacillin was given for 7 days until cultures identified Proteus mirabilis and Pseudomonas aeruginosa, switching to oral ciprofloxacin upon discharge. Follow-up showed no infection, hernia recurrence, or mesh exposure.

Literature suggests complete excision of infected mesh. Shubinets et al. advocate for a single-stage approach with retromuscular biological meshes, while Devin, C.L. supports polypropylene meshes in infected sites. This case reinforces that synthetic onlay mesh offers good infection control, non-recurrence of hernias, and low complication rates, aligning with Birolini et al.'s findings.
BHSeP26 Abdominal wall reconstruction outcomes of the first 50 cases in a district general hospital
Authors: Gungadin Pallavi , Bhandari Mayank , Cheetham Mark , Chakravartty Saurav , Mccloud Joe , Parampalli Umesh
Published: January 2025

Background

The purpose of this study was to evaluate the short-term clinical outcomes of patients undergoing reconstruction of abdominal wall following repair of complex hernias at a recently established unit.

Methods

This retrospective study included all patients who underwent abdominal wall reconstruction for complex incisional hernias between January 2022 and March 2024. Clinical data encompassing patient demographics, operative parameters, post-operative complications, length of hospital stay and 30-day mortality was analysed.

Results

50 patients were included with a male to female ratio of 1:1. The median age of the participants was 62 (26–82). 25% of participants had a BMI of 35. The majority of hernias were approached with a vertical elliptical incision; Fleur de Lys incision was used in 1 case and abdominoplasty incision in 3 cases. The following reconstruction techniques were used: 27 patients underwent Rives Stoppa repair and 16 patients underwent Transversus Abdominis Muscle Release. 30% patients had Botulinum toxin injection pre-operatively. The types of mesh used included: Ultrapro 80 %, Phasix 16 % and Parietex 4 %.

Complications included: Surgical site occurrence 6%, cardiorespiratory complications 10%, vascular complications 2% and bowel obstruction 4%. ICU admission included 3 out of 50 patients. Length of hospital stay in 90% patients was 5 days. 60% patients had a 6-monthly follow up where 1 recurrence was noted.

Conclusion

The early outcomes in our patients demonstrates the feasibility to achieve acceptable outcomes in a district general hospital, by following a multidisciplinary approach and optimising modifiable risk factors preoperatively.
A novel microsatellite instability test of sebaceous tumours to facilitate low cost universal screening for Lynch syndrome
Authors: Gallon Richard , Holt Georgie , Alfailakawi Waleed , Husain Akhtar , Jones Claire , Sowter Peter , Santibanez-Koref Mauro , Jackson Michael S , Burn John , Cook Sam , Rajan Neil
Published: January 2025

Background

One in five sebaceous tumour (ST) patients may have Lynch syndrome (LS), a hereditary cancer predisposition. LS patients benefit from cancer surveillance and prevention programmes and immunotherapy. Whilst universal tumour mismatch repair (MMR) deficiency testing is recommended in colorectal and endometrial cancers to screen for LS, there is no consensus screening strategy for ST, leading to low testing rates and inequity of care.

Objectives

To assess a low cost and scalable, sequencing-based, microsatellite instability (MSI) assay, previously shown to enhance LS screening of colorectal cancers, for MMR deficiency detection in ST against the current clinical standard of immunohistochemistry (IHC).

Methods

One-hundred-and-seven consecutive ST cases were identified from a single pathology department. MMR protein IHC staining was interpreted by a consultant histopathologist. MSI analysis used amplicon-sequencing of 14 microsatellites and a naïve Bayesian classifier to calculate sample MSI score.

Results

Loss of MMR protein expression was observed in 49/104 ST with interpretable IHC (47.1%; 95% CI: 37.3-57.2%). MMR deficiency was less frequent in carcinoma than adenoma and sebaceoma (P = 4.74x10-3). The majority of MMR deficient ST had concurrent loss of MSH2 and MSH6 expression. The MSI score achieved a receiver operator characteristic area under curve of 0.944 relative to IHC. Lower MSI scores were associated with MSH6 deficiency.

Conclusions

These data support MSI testing as an adjunct or alternative to MMR IHC in ST. Integration of ST into established LS screening pathways using this high throughput methodology could increase testing and reduce costs.
Perioperative extracorporeal membrane oxygenation in neonates with transposition of the great arteries: 15 years of experience
Authors: Weeda Jesse A , Van Der Palen Roel L F , Bunker-Wiersma Heleen E , Koers Lena , Van Es Eelco , Hazekamp Mark G , Te Pas Arjan B , Roeleveld Peter Paul
Published: January 2025

OBJECTIVES

Extracorporeal membrane oxygenation (ECMO) can act as a bridge to recovery in both pre- and postoperative patients with transposition of the great arteries (TGA). However, literature on its use in these patients is scarce.

METHODS

Retrospective single-centre cohort study encompassing all TGA patients who received ECMO between January 2009 and March 2024.

RESULTS

Twenty-two neonates received ECMO during the study period, with an overall median age and weight at time of ECMO cannulation of 6.5 (1.8–10) days and 3.7 (3.3–4.0) kg, respectively. Twelve neonates received ECMO prior to the arterial switch operation because of severe persistent pulmonary hypertension (83%), respiratory failure due to severe pulmonary atelectasis (8%) or hypoxia after pulmonary arterial banding procedure (8%). Postoperative ECMO was used in 11 patients; of these, 1 (9%) had also received ECMO preoperatively. Postoperative indications for the remaining patients included failure to wean from cardiopulmonary bypass (50%), low cardiac output in Intensive Care Unit (20%), or after cardiopulmonary arrest (30%). Overall, median ECMO duration for all TGA patients was 75 (45–171) h, with a survival rate of 59% to hospital discharge. Among the preoperative ECMO patients, 5 patients (42%) died (4 preoperatively, 1 postoperatively performed while on ECMO). In the postoperative ECMO group, survival rate was 60%.

CONCLUSIONS

In this single-centre retrospective study, TGA neonates received ECMO preoperatively primarily for severe pulmonary hypertension and postoperatively for failure to wean from cardiopulmonary bypass. This study showed a 58% and 60% survival to hospital discharge in ECMO patients supported preoperatively and those supported postoperatively, respectively.
Atmospheric polycyclic aromatic hydrocarbon concentrations in a semi-urban site: temporal variation, risk assessment, source identification, and estimation of levels in diverse environments
Authors: Caliskan Burak , Celik Semra , Sakin Ahmet Egemen , Tasdemir Yücel
Published: January 2025

This study evaluates atmospheric polycyclic aromatic hydrocarbon (PAH) concentrations in a semi-urban area, Görükle, Turkey, from June 2021 to February 2022. The average concentration of ∑16 PAHs was 24.85 ± 19.16 ng/m3, ranging from 6.70 to 59.11 ng/m3. Seasonal variations were observed, with winter concentrations approximately five times higher than those in summer, driven by increased residential heating emissions and adverse meteorological effects. The results were compared to literature values, revealing lower PAH levels than those found in other urban and industrial areas. Meteorological factors were statistically analyzed. Polycyclic aromatic hydrocarbon concentrations exhibited an inverse relationship with temperature and mixing height, while relative humidity showed a positive linear correlation. The study also estimated PAH concentrations in various environmental media using gas-particle partitioning and equilibrium models. The concentrations of PAHs in the particulate phase were minimal, suggesting that most PAHs were present in the gas phase. Additionally, the equilibrium concentrations of PAHs in soil, leaves, bark, and water were modeled, emphasizing the accumulation of heavier PAHs in these media yet 2- and 3-ring PAHs were predominant in the ambient air samples. Source apportionment and principal component analysis studies identified vehicle emissions and combustion for heating purposes as the primary sources of pollution. However, air mass trajectory analysis indicated contributions from Kocaeli, an area with significant industrial activity. The cancer risk assessment yielded low risks for both adults and children.
Depletion of fenbendazole sulfone residues in Northern Bobwhite (Colinus virginianus) liver following medicated feed treatment
Authors: Henry Brett J , Henry Cassandra , Patel Dhaval , Brym Matthew Z , Kalyanasundaram Aravindan , Leach Jeremiah , Kendall Ronald J
Published: January 2025

Northern bobwhite quail (Colinus virginianus) are an important game bird that generates substantial revenue for rural communities and is also an important grassland conservation species. Unfortunately, Northern bobwhite populations have been declining across their range for over 50 years. In the southwest bobwhite range, parasites are suspected to contribute substantially to the decline. To test the relationship of parasites and wild Northern bobwhite populations, an anthelmintic medicated feed was developed. The medicated feed was then tested as part of the U.S. Food and Drug Administration registration process. Because Northern bobwhite are a game species and harvested birds are ingested by people, it was necessary to estimate the tissue clearance rate of the drug. This study examined how quickly the conjugated metabolite fenbendazole sulphone was cleared from quail liver. A validated LC/MS-MS method was used to determine clearance rate from pen-reared northern bobwhite fed the anthelmintic at 110 ppm in feed. Results of the tissue clearance study found the drug never exceeded the maximum allowable concentration of 6 ppm and was cleared from the liver in 9.38 hours. Based on the Center for Veterinary Medicine guidance for industry #3, a 0-day withdrawal period was assigned to the recently registered medicated feed in wild northern bobwhite. Thus, the anthelmintic fenbendazole was shown to be rapidly cleared from Northern bobwhite and represents a viable option for treating wild populations for parasite infections while treated game birds remain safe for human consumption.
The State of Repair: The International Norm of Reparations between Aspirations and Expectations
Authors: Ben-Josef Hirsch Michal , Dixon Jennifer M
Published: January 2025

ABSTRACT∞

Transitional justice has long been established as a rich field of scholarship and policy. An enduring concern has been the mix of advocacy and scholarship and its effects on empirical assessments. A more recent concern is that the international consensus supporting transitional justice is eroding. This article engages these concerns through the lens of international norms. Systematically analyzing international discourse within the United Nations and Amnesty International, the article maps the content of, and changes since 1945 in, the international norm of reparations, which is a core element of transitional justice. The analysis reveals that the strength of the international norm of reparations is not eroding, and that there is broad consensus about its core content. The analysis also highlights claims about reparations that – as assessed in international discourse – are more aspirational than empirical, including that nonstate actors are responsible for reparations and that reparations should be both concrete and symbolic.
Development of a technique to optimize micro-hydro turbine location and capacity for optimal pressure control and energy recovery in water systems
Authors: Kwon Hui Geon , Choi Young Hwan
Published: January 2025

In the water supply system, for stable operation and management, pressure control, and energy consumption are important factors. However, gravity flow water supply systems can cause leaks and pipe damage when high pressure from upstream moves downstream. Therefore, the only popular way to control pressure within an acceptable range is to use a pressure reduction valve to control pressure within an appropriate range. However, using only the pressure reduction valve causes indiscriminate energy waste in operating and managing the water supply system. Accordingly, a micro-hydro turbine was proposed to replace the pressure reduction valve to provide appropriate pressure control and energy recovery. In addition, existing micro-hydro turbine designs were designed with only energy recovery in mind, but for sustainable operation, various design factors must be considered for optimal design. However, in design, EPANET2.2, the model simulation program in this study, does not have a model that can calculate the size of the turbine, so it is replaced with the pressure reduction valve and designed using the corresponding pressure and flow rate. Therefore, in this study, the range that satisfies the appropriate pressure condition is determined by using the pressure reduction valve (if a micro-hydro turbine is used with a surplus pressure head considering appropriate pressure control, the potential energy recovery amount can be determined). Therefore, a multi-objective optimal design technique was proposed that can optimize objective functions such as energy recovery and installation cost. The optimization technique is a multi-objective harmony search, and benchmark networks were applied to verify the proposed methodology. Through this study, it is expected that it can be effectively used in the sustainable operation of the water supply system by considering various design factors through adjustment of the set pressure.
Inherited obstruction: the complaint procedure under the Biological Weapons Convention and the UN Charter rule on obligatory abstention in the Security Council
Authors: Hoffberger-Pippan Elisabeth , Pippan Christian
Published: January 2025

In November 2022, the UN Security Council rejected a draft resolution, tabled by Russia, which sought to initiate an investigation into allegations of purported non-compliance by the US and Ukraine with their obligations under the Biological Weapons Convention (BWC). Using this episode as a point of departure, the present article takes a closer look at the BWC’s complaint procedure and the role allocated therein to the Security Council. The piece commences with a detailed account of Russia’s first-ever invocation of Article VI BWC, followed by an examination of the normative interplay between the Convention’s complaint mechanism and Chapter VI of the UN Charter. The article then turns to the ‘obligatory abstention rule’ enshrined in Article 27(3) of the UN Charter and its potential to address the concern that the BWC’s complaint procedure is de facto a dead-end for complaints against a permanent member of the Security Council. The analysis suggests that while greater adherence to the obligatory abstention rule by the Council could potentially enhance the fairness and effectiveness of the BWC’s complaint mechanism (particularly at the fact-finding stage), too much hope should not be placed in a possible reactivation of the rule. The inherent limitations of the rule, coupled with ambiguous procedures for determining its application in a particular case, ultimately leave ample room for the P5 to keep their sacrosanct veto power intact.
Outpatient palliative care and end-of-life care intensity: linking Massachusetts Cancer Registry with All-Payer Claims Database
Authors: Keating Nancy L , Weissman Joel S , Wright Alexi A , Wolf Robert , Gershman Susan , Knowlton Richard , Ayanian John Z
Published: January 2025

Background

Early palliative care is associated with better outcomes for patients with advanced-stage cancers. Using a novel data linkage, we assessed outpatient palliative care use before death and its association with end-of-life care intensity and variation across 8 provider networks in Massachusetts.

Methods

We linked Massachusetts Cancer Registry and the All-Payer Claims Database for individuals with commercial insurance, Medicaid, or Medicare Advantage diagnosed with colorectal, lung, prostate, and breast cancers from 2010 to 2013 who died by December 31, 2014. We characterized outpatient palliative care visits in the 6 months before death and identified end-of-life hospitalizations, emergency department visits, intensive care unit admissions, chemotherapy, no/late hospice enrollment, and in-hospital deaths. We used logistic regression to assess factors associated with outpatient palliative care and ordinal logistic regression with provider network fixed effects to assess the association of palliative care with a composite measure summing individual end-of-life intensity measures.

Results

Among 6279 decedents, 11.3% had at least 1 outpatient palliative care visit. Palliative care use varied across provider networks from 6.0% to 19.3%. In adjusted analyses, younger age, longer duration from diagnosis to death, death in 2012-2014 vs 2010, and provider network were associated with palliative care visits (all P values less than .05). End-of-life care intensity varied across provider networks. Patients with palliative care visits had lower adjusted odds of receiving intensive end-of-life care (adjusted odds ratio = 0.62 per additional measure of end-of-life intensity, 95% CI = 0.53 to 0.72).

Conclusions

Outpatient palliative care use varied substantially among regional provider networks and was associated with less intensive end-of-life care.
Reflecting on the interpretation and application of the international convention for the suppression of the financing of terrorism in light of the Ukraine v Russia case
Authors: Musmeci Daniele
Published: January 2025

The present article intends to provide an assessment of the International Court of Justice’s judgment on the merits in the case concerning Application of the International Convention for the Suppression of the Financing of Terrorism and of the International Convention on the Elimination of All Forms of Racial Discrimination (Ukraine v Russian Federation). The assessment is confined to the International Convention for the Suppression of the Financing of Terrorism (ICSFT) and addresses critical issues, including the international responsibility stemming from the breach of the ICSFT, the interpretation of the key term ‘fund’, and the mental element ‘in the knowledge’. Afterwards, it delves into the Court’s findings vis-à-vis the Applicant’s allegations and concludes by illustrating the results of the analysis.
Semiparametric posterior corrections
Authors: Yiu Andrew , Fong Edwin , Holmes Chris , Rousseau Judith
Published: January 2025

We present a new approach to semiparametric inference using corrected posterior distributions. The method allows us to leverage the adaptivity, regularization, and predictive power of nonparametric Bayesian procedures to estimate low-dimensional functionals of interest without being restricted by the holistic Bayesian formalism. Starting from a conventional posterior on the whole data-generating distribution, we correct the marginal posterior for each functional of interest with the help of the Bayesian bootstrap. We provide conditions for the resulting one-step posterior to possess calibrated frequentist properties and specialize the results for several canonical examples: the integrated squared density, the mean of a missing-at-random outcome, and the average causal treatment effect on the treated. The procedure is computationally attractive, requiring only a simple, efficient postprocessing step that can be attached onto any arbitrary posterior sampling algorithm. Using the ACIC 2016 causal data analysis competition, we illustrate that our approach can outperform the existing state-of-the-art through the propagation of Bayesian uncertainty.
Alkylated DNA repair by a novel HhH-GPD family protein from Crenarchaea
Authors: Zhang Likui , Gao Tian , Li Zheng , Chen Cai , Jiang Donghao , Yin Youcheng , Zheng Yaqi , Cao Peng , Gong Yong , Yang Zhihui
Published: January 2025

HhH-GPD (helix–hairpin–helix-glycine/proline/aspartate) family proteins are involved in DNA damage repair. Currently, mechanism of alkylated DNA repair in Crenarchaea has not been fully clarified. The hyperthermophilic model crenarchaeon Saccharolobus islandicus REY15A possesses a novel HhH-GPD family protein (Sis-HhH-GPD), where its Ser152 corresponds to a conserved catalytic Asp in other HhH-GPD homologs. Herein, we report that Sis-HhH-GPD is a novel bi-functional glycosylase, capable of removing both 1-methyladenine (1-meA) from DNA and alkylated bases from DNA created by methyl methanesulfonate (MMS). Mutational analyses show that E134 is essential for catalysis, whereas S152 is not essential. Sis-HhH-GPD might utilize aromatic rings of Y154 and W57 to stack against 1-meA base for flipping-out and then be removed by E134. Additionally, R157, R161 and R200 participate in catalysis. Among four cysteine residues that potentially coordinate with the Fe-S cluster loop, C203, C210 and C219 are involved in catalysis. Importantly, Sis-HhH-GPD is responsible for repair of alkylated DNA created by MMS in vivo. Interestingly, genetic complementary data have confirmed physiological function of Sis-HhH-GPD in alkylated DNA repair and clarified functional roles of its four cysteine residues in vivo. Overall, we provide first evidence that HhH-GPD family protein from Crenarchaea functions in alkylated DNA repair.
A phosphorylation signal activates genome-wide transcriptional control by BfmR, the global regulator of Acinetobacter resistance and virulence
Authors: Raustad Nicole , Dai Yunfei , Iinishi Akira , Mohapatra Arpita , Soo Mark W , Hay Everett , Hernandez Gabrielle M , Geisinger Edward
Published: January 2025

The nosocomial pathogen Acinetobacter baumannii is a major threat to human health. The sensor kinase-response regulator system, BfmS-BfmR, is essential to multidrug resistance and virulence in the bacterium and represents a potential antimicrobial target. Important questions remain about how the system controls resistance and pathogenesis. Although BfmR knockout alters expression of >1000 genes, its direct regulon is undefined. Moreover, how phosphorylation controls the regulator is unclear. Here, we address these problems by combining mutagenesis, ChIP-seq, and in vitro phosphorylation to study the functions of phospho-BfmR. We show that phosphorylation is required for BfmR-mediated gene regulation, antibiotic resistance, and sepsis development in vivo. Consistent with activating the protein, phosphorylation induces dimerization and target DNA affinity. Integrated analysis of genome-wide binding and transcriptional profiles of BfmR led to additional key findings: (1) Phosphorylation dramatically expands the number of genomic sites BfmR binds; (2) DNA recognition involves a direct repeat motif widespread across promoters; (3) BfmR directly regulates 303 genes as activator (e.g., capsule, peptidoglycan, and outer membrane biogenesis) or repressor (pilus biogenesis); (4) BfmR controls several non-coding sRNAs. These studies reveal the centrality of a phosphorylation signal in driving A. baumannii disease and disentangle the extensive pathogenic gene-regulatory network under its control.
Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer
Authors: Skoulidis Ferdinandos , Li Bob T , Hochmair Maximilian , Govindan Ramaswamy , Vincent Mark , van der Wekken Anthonie J , Reguart Aransay Noemi , O’Byrne Kenneth J , Girard Nicolas , Griesinger Frank , Nishio Makoto , Häfliger Simon , Lindsay Colin , Reinmuth Niels , Paulus Astrid , Papakotoulas Pavlos , Kim Sang-We , Ferreira Carlos Gil , Pasello Giulia , Duruisseaux Michael , Gennatas Spyridon , Dimou Anastasios , Mehta Bhakti , Kormany William , Nduka Chidozie , Sylvester Brooke E , Ardito-Abraham Christine , Wang Yang , de Langen Adrianus Johannes
Published: January 2025

Introduction

We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods

Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment.

Results

In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT; 68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of >90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy <3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause.

Conclusions

Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.
Is it time to retire preoperative radiation for localized esophageal and gastro-esophageal adenocarcinoma?
Authors: Pabon Cindy M , Spieler Benjamin , Li Jenny J , Ajani Jaffer , Hosein Peter J , Blum Murphy Mariela
Published: January 2025

Whether preoperative chemoradiotherapy (CRT) or perioperative chemotherapy is superior for localized esophageal or gastro-esophageal junction (GEJ) cancers has been a topic of long-standing debate. For years, standard of care in the United States for localized esophageal or GEJ adenocarcinoma (EAC) has been physician’s choice between the 2 strategies. More recently, adjuvant immunotherapy has also been introduced into the treatment approach for those who received neoadjuvant CRT. While preoperative radiation remains an important option for patients with esophageal squamous cell carcinomas, the ESOPEC trial presented in 2024 suggested that perioperative chemotherapy is superior to preoperative CRT in EAC. In addition, the results of the TOPGEAR trial presented in 2024 showed that adding CRT to perioperative chemotherapy did not lead to improved outcomes. This has led to a shift in practice among oncologists. However, there are various complexities and factors to consider when interpreting these studies. In this review, we outline both trials and what their findings may mean for the future of preoperative CRT in EAC. Ultimately, until more data are available that incorporate novel agents such as immunotherapy, these studies indicate that we should defer the routine inclusion of radiation in preoperative treatment for EAC.
Levels of Description and Levels of Reality
Authors: List Christian
Published: January 2025

This expository chapter presents a general framework for representing levels and inter-level relations. The framework is intended to capture both epistemic and ontological notions of levels and to clarify the sense in which levels of explanation might or might not be related to a levelled ontology. The framework also allows us to study and compare different kinds of inter-level relations, especially supervenience and reduction but also grounding and mereological constitution. This, in turn, enables us to explore questions such as whether supervenience implies explanatory reducibility and whether there can be irreducible higher-level explanations or even “emergent” higher-level properties. The chapter finally discusses some further philosophical applications: to the free-will debate, the determinism-indeterminism distinction, indexicality and consciousness, and the relationship between positive and normative facts.
Antireductionism Has Outgrown Levels
Authors: Potochnik Angela
Published: January 2025

Positing levels of explanation has played an important role in philosophy of science. This facilitated the advocacy of antireductionism of explanations, which, at its most basic, is the idea that scientific explanations citing large (i.e., non-microphysical) entities will persist. The idea that explanations come in levels captures important features of explanatory practices, and it also does well at helping to define different positions one might take regarding explanatory reductionism or antireductionism. Yet the idea that explanations come in levels has also led philosophers astray. This systematically misconstrues the relationship different explanations bear to one another, suggests candidate explanations are less numerous than they in fact are, and occludes recognition of how the selection of explanations can vary across research projects. Antireductionists about explanation should move on from talk of levels. Or so this chapter will argue.
Messy but Real Levels in the Social Sciences
Authors: Kincaid Harold
Published: January 2025

This chapter surveys some issues about levels in the sciences as they surface in the social and behavioral sciences. However, it is hard to discuss issues in the social sciences without also discussing the issues about levels in science in general. Thus, the chapter proposes a general take on debates about levels that it calls naturalist and contextualist: naturalist in that conceptual metaphysics cannot trump science and contextualist in that the use and usefulness of level concepts means different things with different plausibility according to scientific context. The chapter argues that the levels concept is neither incoherent or always useful, that many objections to levels such as doubts about downward causation are anti-naturalist conceptual metaphysical approaches that should be rejected, and that levels cannot be replaced with concepts of mechanisms or scale. All this is tied down and expanded with discussions of some empirical social methodological and research areas. Section 1 sets up the general naturalist and contextualist framework, Section 2 applies these to general debates about levels, and Section 3 discusses in detail some social science research.