bluuebunny/crossref_metadata_2025 huggingface dataset:
DEfiNING SPATIAL HETEROGENEITY OF A NOVEL LIVING BIOBANK OF POST-SURGICAL RESIDUAL GLIOBLASTOMA TO DEVELOP STRATEGIES FOR TARGETED THERAPY
Authors: McGarrity-Cottrell Connor , Myers Katie , Dunning Mark , Bagga Veejay , Sinna Saurabh , Al-Tamimi Yahia , Rominiyi Ola , Collis Spencer
Published: September 2023

AIMS

Glioblastoma is the most common cancer arising within the brain accounting for >2,000 deaths/year in the UK. Current standard-of-care therapy consists of maximal safe surgical resection followed by radiochemotherapy which activates the cellular DNA damage response (DDR). However, disease prognosis remains poor (median OS ~12-15 months). This stagnation in the development and clinical translation of novel therapeutics is largely attributed to extensive inter- and intra-tumoral heterogeneity and resistant glioma stem cell (GSC) niches. Traditionally, primary ex vivo and in vivo models of glioblastoma have been generated from the resected tumour mass potentially omitting the post-surgical residual tumour cells that give rise to disease recurrence and morbidity.

METHOD

Multiple parallel primary ex vivo GSC cell models were generated from anatomically discrete regions of en-bloc partial lobectomy glioblastoma specimens to produce 3D models of resected (tumour “core”) and typically residual (distal invasive tumour “edge”) GSC niches. These models were characterised using an array of biomolecular techniques and 3D based assays.

RESULTS

Preliminary RNA-seq analyses revealed largely divergent transcriptional landscapes for resected vs residual GSCs and protein expression/immunofluorescence analyses also identified key differences in GSC and DDR ex- pression, and subsequent cellular responses to current standard-of-care radio-chemotherapy regimens.

CONCLUSIONS

These data reveal phenotypic relationships between GSC “stemness” and DDR activity, therefore highlighting the potential clinical relevance of our novel parallel resected and residual ex vivo glioblastoma models. Characterisation of further models from within our 3D GSC biobank will also aid evaluation of novel therapeutics capable of targeting post-surgical GSC subpopulations leading to improved disease outcomes.
SIMVASTATIN INHIBITS MEDULLOBLASTOMA CELL MIGRATION VIA TARGETING THE MEVALONATE PATHWAY
Authors: Comer Charley , Michod David , Niklison-Chirou Maria Victoria
Published: September 2023

AIMS

Medulloblastoma (MB) is the most common malignant paediatric brain tumour. Arising in the cerebellum, MBs consist of four subgroups: Wingless (WNT), Sonic Hedgehog (SHH), Group 3 (G3) and Group 4 (G4), each with unique molecular and genetic features and clinical outcomes. G3 and G4 are the most aggressive, with a high tendency to metastasise, but are the least characterized. Current treatment for MB is surgical resection, radiation and chemotherapy, associated with high morbidity and adverse side effects. Therefore, more targeted and less toxic therapies are needed to improve quality of life for survivors. Cancer cells can enhance lipid metabolism through upregulation of the mevalonate pathway (MVP). Aberrant activity of MVP in tumour cells has been widely reported. Previous studies have shown statins can decrease mortality in colorectal, breast and lung cancer patients, and even decrease metastasis of osteosarcoma. Notably, simvastatin can penetrate the blood-brain barrier. This study aims to utilise statins as a potential novel therapy for MB metastasis.

METHOD

In silico gene expression analysis was performed to evaluate expression of enzymes involved in MVP in MB, validated through immunocytochemistry and RT-PCR in SHH, G3 and G4 cell lines. Further study analysed the anti-cancer and anti-metastatic potential of simvastatin using both 2D and 3D cell culture methods.

RESULTS

Results show that in 2D and 3D cell culture, simvastatin is capable of decreasing migration of MB cells in vitro.

CONCLUSIONS

Our work demonstrates that simvastatin has the capacity to decrease MB cell invasion, therefore making it an appealing novel therapy option for MB tumours.
AUTOMATIC DETECTION OF FACIAL LOCATIONS TO MEASURE FACIAL ASYMMETRY AFTER PAEDIATRIC RADIOTHERAPY
Authors: Dronne Clea , Durrant Helena , Davey Angela , Henderson Edward , Osorio Eliana Vasquez , Aznar Marianne
Published: September 2023

AIMS

Children receiving radiotherapy for head and neck tumours, such as Head and Neck Rhabdomyosarcoma (HN- RMS), often experience facial asymmetry later in life. Here, we present a convolutional neural network (CNN) that will enable the automatic detection of facial anatomical landmarks on MR images taken during follow-up examinations. This model will facilitate quantitative tracking of facial asymmetry, thus revealing the centres of growth that are most affected by radiation, with the ultimate goal of defining precise dose tolerance levels.

METHOD

A dataset of 61 paediatric MRI images was used to train separate models that infer the locations of four facial landmarks. These locations had previously been manually labelled by two independent observers. Before training, the images were normalised and registered to optimise model performance. The model was judged to be of acceptable accuracy if the distances between the observed landmark (gold-standard location) and the location predicted by the trained models were smaller than the inter-observer distances of each facial landmark.

RESULTS

The model predicted landmarks which were closer to the gold-standard location than the inter-observer locations. In detail:

• Optic chiasm: 0.81 ± 0.45 mm (inter-observer 1.49 mm).

• Nasion: 0.70 ± 0.62 mm (inter-observer 3.24 mm).

• Left Ectoconchion: 1.22 ± 0.44 mm (inter-observer 3.58 mm).

• Right Ectoconchion: 0.80 ± 0.82 mm (inter-observer 4.04 mm).

CONCLUSIONS

This research shows promising potential for a CNN to accurately locate head and neck landmarks in paediatric MRI images. This tool can label craniofacial landmarks in large clinical datasets quicker and more accurately than can be achieved through manual techniques.
IDENTIFYING ROLE OF YB1 AND NPM1 AS PART OF HISTONE 3 MUTANT PROTEIN INTERACTOME, IN H3 MUTATED PHGG
Authors: Cambampaty Tarak , Barrow Lucy , Layfield Robert , Haque Farhana
Published: September 2023

AIMS

Paediatric high-grade gliomas (pHGG) are the leading cause of childhood cancer deaths, accounting for over 40% of deaths in the UK. pHGG tumours harbour histone H3 mutations, defining 50% of pHGG cases. Studies show prominent mutations as being H3.3K27M and H3.3G34R/V.

Our previous research has identified unique and common interacting binding partners of H3-G34R and H3-G34V mutant proteins. Among these we have focused on YB-1 and Nucleophosmin (NPM1). YB-1 is multifunctional transcription factor and a well-known oncogenic protein. NPM1 is a molecular chaperone and frequently over- expressed in cancer as well. Our aim is to analyse the role of YB-1 and NPM1 in H3 mutated pHGG, in order to identify targeted therapeutic option for these diffcult to treat tumours.

METHOD

Further data analyses of mass spectrometric proteomic data were performed. Subsequently, H3 mutated glioma cell lines, and control H3 wild type pHGG cells were cultured and then subjected to proteomic analyses. A comparative immunofluorescence and microscopy, and western blot analyses were performed to investigate the role of YB-1 and NPM-1.

RESULTS

Results verified the proteomic data and further showed altered protein expression of YB-1 and altered localization of protein NPM1 in H3 mutated pHGG.

CONCLUSIONS

Results of the study support that YB-1 and NPM1 are important interacting proteins in H3G34-mutated pHGGs and can be explored as therapeutic targets in H3 mutated pHGG.
RECOVER REALITY FEASIBILITY TRIAL: INVESTIGATING THE FEASIBILITY OF IMMERSIVE TECHNOLOGIES TO ENHANCE NEUROREHABILITATION EDUCATION AFTER NEUROSURGERY FOR BRAIN CANCER
Authors: Bolton William , Sinha Rohit , Adebola Oluwaseyi , Stephenson Elisa , Cooper Sara , Ewan Seonaid , Mathew Ryan
Published: September 2023

AIMS

Neurorehabilitation is fundamental to better outcomes for those recovering from neurosurgery for brain cancer. Access to this essential therapy is limited by resource shortages and unfulfilled therapy needs lead to longer hospital stays. Immersive technologies such as virtual reality (VR) could be used to augment neurorehabilitation in a self-directed, safe, virtual environment. The aim of this study is to demonstrate the feasibility of a VR rehabilitation programme in an acute neurosurgical inpatient environment to augment neurorehabilitation.

METHOD

A single group, feasibility study was conducted in a tertiary UK neurosurgical department. Patients aged 16 and over who had undergone a neurosurgical intervention for brain tumours were eligible. Participants were offered a VR session at least once per day for the first 14 days post-surgery/injury or until discharge, whichever comes first, with reasons for non-engagement collected. Primary outcomes were feasibility outcomes, and secondary outcomes included rehabilitation engagement and length of stay.

RESULTS

Data collection is ongoing. At submission we have n=6 participants who used the VR. A seventh participant who was screened for inclusion declined, citing anxiety over causing headaches as the reason. All six participants used the VR on either post operative day 2 or day 3. Although offered VR on the immediate day after surgery, participants declined due to nausea or pain.

CONCLUSIONS

If this present study demonstrates feasibility of using VR in patients after neurosurgery for brain cancer, a randomised clinical effectiveness study with health-economics analysis will follow to inform widespread adoption into practice.
FISH-BASED INVESTIGATION OF CDKN2A AND IFNA14 IN GLIOBLASTOMA
Authors: Shboul Sofian Al , Boyle Shelagh , Singh Ashita , Saleh Tareq , AlRjoub Moath , Karsaneh Ola Abu Al , Mryyian Amel , Dawoud Rand , Gul Sinem , baker Shaden Abu , Ball Kathryn , Hupp Ted , Brennan Paul
Published: September 2023

AIMS

Glioblastoma (GBM) tumours have a dismal prognosis despite aggressive anticancer therapy. Deletion of CDKN2A is among the most common genetic changes in GBM (~50%) and has been strongly associated with worse prognosis. Next generation DNA sequencing had shown that deletion of IFNA genes (located proximal to CDKN2A) is also a major genetic event in GBM (~25%). Clinical Identification of in vivo state of these two genes might facilitate improved individualized therapeutics.

METHOD

Glioma tissue microarray consisting of 45 samples was used to assess the co-deletion of CDKN2A and IFNA14 genes simultaneously, using a novel three-color fluorescence in situ hybridization (FISH) probe. We examined the correlation between CDKN2A and p16INK4a protein expression detected using immunohistochemistry (IHC).

RESULTS

FISH analysis showed that 44% of the primary GBMs harboured homozygous deletions of both CDKN2a and INFA14. By contrast, all grade II and III gliomas, had either wild-type or amplified CDKN2A and INFA14. All samples that showed CDKN2A homozygous deletion (n=11) were negative for p16INK4a staining, while 20 cores that were positive for p16INK4a expression did not harbour CDKN2A deletion. Survival curves of primary GBMs suggested that both the co-deletion of CDKN2A/INFA14 and negative p16INK4a expression were associated with shorter survival time.

CONCLUSIONS

Our FISH/IHC analyses indicate a strong correlation between CDKN2A and p16INK4a protein expression in grade III/II glioma, suggesting that amplification of CDKN2A might act as a gatekeeper to reduce the incidence of grade

IV. Our data also highlight the high frequency of CDKN2A/INFA14 co-deletion in GBM tumours that might together impact on survival time.
FOCAL MANAGEMENT OF BRAIN METASTASES IN SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW
Authors: Wong Claudia Dols , Chandy Edward , Critchley Giles , Robinson Stephen David
Published: September 2023

AIMS

Small cell lung cancer (SCLC) brain metastases (BM) are common at both presentation and relapse. Historically, BM are managed with whole brain radiotherapy (WBRT) +/- chemotherapy. However, WBRT is associated with significant cognitive impairment, and so interest in the focal management of BM (encompassing stereotactic radiosurgery (SRS) and surgery) is increasing. We systematically reviewed the current literature regarding focal BM management.

METHOD

A systematic literature search of PubMed, Embase, and CENTRAL databases and clinicaltrials.gov was conducted to obtain published articles, abstracts, and ongoing studies regarding focal management of SCLC BM. Exclusion criteria included publication before 2005 and publication in a non-English language. Additional papers were added by reviewing citations of relevant papers.

RESULTS

Following initial review of 15,420 records, we identified 67 articles eligible for inclusion. 24 were published before 2015 and 44 published 2015-2023. 8 related to surgical BM treatment: case studies (n=6), retrospective cohort studies (n=2). 60 articles were identified regarding SRS: abstracts (n=13), case studies (n=5), retrospective cohort studies (n=14), retrospective case series (n=20), prospective trials (n=8). These papers have been further divided by topic: upfront SRS (n=23), salvage SRS (n=19) and WBRT with SRS boost (n=3). There are several ongoing trials (n=8) investigating outcomes in SRS for SCLC BM, both alone and when compared with WBRT.

CONCLUSIONS

Focal treatments for SCLC BM are being used more frequently. However, randomised trial evidence for their safety and effectiveness are still pending.
Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial
Authors: Johnson Theodore S , MacDonald Tobey J , Pacholczyk Rafal , Aguilera Dolly , Al-Basheer Ahmad , Bajaj Manish , Bandopadhayay Pratiti , Berrong Zuzana , Bouffet Eric , Castellino Robert C , Dorris Kathleen , Eaton Bree R , Esiashvili Natia , Fangusaro Jason R , Foreman Nicholas , Fridlyand Diana , Giller Cole , Heger Ian M , Huang Chenbin , Kadom Nadja , Kennedy Eugene P , Manoharan Neevika , Martin William , McDonough Colleen , Parker Rebecca S , Ramaswamy Vijay , Ring Eric , Rojiani Amyn , Sadek Ramses F , Satpathy Sarthak , Schniederjan Matthew , Smith Amy , Smith Christopher , Thomas Beena E , Vaizer Rachel , Yeo Kee Kiat , Bhasin Manoj K , Munn David H
Published: September 2023

Background

Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy.

Methods

We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing.

Results

Eighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39–77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2–62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7–29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4–61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2–62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype.

Conclusions

Indoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors.
Using Developmental Evaluation to Support Adaptive Strategies
Authors: Coffman Julia , Beer Tanya , Stid Daniel , Armstrong Kathy
Published: September 2023

Developmental evaluation is well suited for emergent strategies that are tackling problems rooted in complex systems. This chapter describes the use of developmental evaluation during the initial years of a complex philanthropic initiative focused on strengthening US democracy and its institutions—especially Congress—in a time of political polarization. Because the initiative reflected a different way of thinking about foundation strategy that was emergent and systems-focused, an innovative evaluation and learning approach was used to support ongoing decision-making and adaptation. The chapter, authored by and written from the perspective of both strategists and evaluators, describes the methods used, how the evaluation informed strategy, and reflections and lessons on the developmental evaluation experience and approach.
Process and Implementation Evaluation Methods
Authors: Rogers Patricia J. , Woolcock Michael
Published: September 2023

Beyond assessing whether or not interventions have achieved their stated goals, evaluations can also provide greater understanding—in real time and at completion—about how, where, for whom, over what time frame, and which aspects of an intervention may (or may not) have succeeded, and where improvements might be sought. Implementation evaluations help identify where breakdowns in the delivery system may have occurred and spaces wherein frontline implementers were able to find innovative solutions to local (“binding constraint”) problems. Process and implementation evaluations serve the vital purpose of jointly promoting accountability and learning, and provide discipline to internal procedures for promoting partnerships, innovation, and improvement. In this chapter, the authors describe six different types of process and implementation evaluations and describe their respective strengths and weaknesses in various contexts. As part of collective efforts to enhance the effectiveness of all classes of interventions, impact and process evaluations should be regarded as necessary complements.
Data Sources and Best Practices for Data Collection
Authors: Lee Helen , Strassberger Marissa , Naeve Katie
Published: September 2023

A sound and robust program design or evaluation is dependent on having good data. Having good data, in turn, means that the researcher has carefully and thoughtfully considered which data sources are needed to answer the fundamental questions of interest, makes plans for collecting high-quality data, puts in place processes and procedures to monitor data collection, and uses appropriate methods for analyzing data and interpreting results. This chapter describes the various types of quantitative and qualitative data commonly used in program design and evaluation, when they can be used, and their strengths and weaknesses. This chapter also describes important principles for ensuring the collection of high-quality data, including best practices to employ before, during, and after data collection.
Performance Evaluation of the Community Action for Reading and Security Program in Nicaragua
Authors: Blair Randall , Murray Nancy
Published: September 2023

The Community Action for Reading and Security (CARS) program was a collection of investments in early reading and community safety funded by the United States Agency for International Development (USAID) that were implemented in Nicaragua’s Caribbean coast from 2013 to 2020. CARS introduced in-school and out-of-school reading programs for primary school-age students in over 100 communities across the coastal region. The program also featured various community and parent engagement activities, as well as small grants for school improvements. This chapter describes the performance evaluation of CARS conducted in 2015 and 2016. Featuring visits to participating communities, interviews with educators, and an extensive analysis of administrative and survey data, the evaluation used a robust mixed-methods design to assess program implementation, outcomes, and sustainability. USAID and program implementers used the lessons from the evaluation findings in 2017 before CARS was scaled to other regions of Nicaragua.
Using Evidence to Scale Up India’s Most Promising Education Intervention
Authors: Banerji Rukmini , Venkatachalam Bala
Published: September 2023

This chapter outlines how Pratham, one of India’s best-known organizations working in primary education, went from designing methods to understand the contours of the “learning crisis” to developing solutions that were then used at scale across the country for raising children’s ability to read and do arithmetic. Evidence has played a significant role in this journey. First, the Annual Status of Education Report (ASER) highlighted the “invisible problem” of children’s learning across the country. Second, Pratham’s own internal measurement systems, along with a series of randomized controlled trials, evaluated Pratham’s evolving solution for raising children’s reading and arithmetic scores. Additionally, the chapter highlights the critical role of partnerships at various levels of government, as well as community engagement, including parents and volunteers. Essential elements to Pratham’s success have been the focus on raising awareness of the problem and demonstrating simple and actionable solutions.
The Changing World of Program Design, Implementation, and Evaluation in the Age of Big Data
Authors: Bamberger Michael , York Peter
Published: September 2023

This chapter reviews the present and potential contribution of big data and data science to strengthening the evaluation of social programs. The authors identify and define three main types of big data: (1) personal data generated by individuals and groups, (2) organizational and systems data, and (3) geospatial data. Each of these data sources has different applications for development programs, and the authors discuss the role of these data in program design, delivery, sustainability, and evaluation. The authors discuss how big data is transforming the nature of evaluation, and provide examples of current applications of such data, including the ability to evaluate complex programs and the application of artificial intelligence to construct “natural experiments.” The challenges of the transition to the world of big data are discussed, including the transition from the familiar evaluation ecosystem to the significantly different data science ecosystem.
Important Concepts Affecting Program Design, Management, and Evaluation, but That Are Frequently Ignored
Authors: Bamberger Michael
Published: September 2023

This chapter discusses some important concepts in program design, management, and evaluation that are frequently ignored or are not adequately addressed. These concepts include the lack of complexity-responsive evaluation methodologies and the failure to recognize and address the challenges of emergence, the inability of many widely used evaluation designs to identify unintended program outcomes, differential impacts of many program outcomes for women and men, and social exclusion and the need to give voice to vulnerable groups. Failure to address these issues can have serious consequences, particularly with regard to equity, gender equality, and the guiding principle of “do no harm.” The chapter concludes with recommendations on how these cross-cutting concepts can be addressed. The chapter draws on experience related to the evaluation of projects, programs, and policies in developing countries, but most of the lessons and issues are also relevant for industrialized nations.
Using the Consolidated Framework for Implementation Research to Identify Barriers and Facilitators to Primary Care Practices’ Implementation of a Diabetes Registry
Authors: Crosson Jesse C. , Keith Rosalind E. , Gonzalez Martha M. , Sabo Roy T. , Etz Rebecca S.
Published: September 2023

Diabetes registries are an evidence-based approach to tracking and monitoring the care needs of patients with diabetes in order to intensify treatment when needed. The authors of this chapter conducted a randomized trial of a low-cost approach to supporting diabetes registry implementation in primary care practices, the Supporting Practices to Adopt Registry-Based Care (SPARC) study. While the approach effectively supported registry implementation when compared to a control condition, success varied across the 16 intervention practices. The authors conducted a multi-method implementation study to identify reasons for this variation. They coded qualitative data using constructs from the Consolidated Framework for Implementation Research (CFIR) and then used analytic matrices for cross-case and individual case study analyses of successful and unsuccessful implementers. Use of CFIR supported identification of important barriers and facilitators to implementation as well as relationships between these factors. This approach can inform others using implementation science methods to evaluate evidence-based organizational change initiatives.
The American Assumption
Authors: Hunter Marcus Anthony
Published: September 2023

While the power of the American Dream persists, in Black Reconstruction in America 1860–1880, W. E. B. Du Bois challenges the historicity of the concept by detailing a profoundly different origin story. Du Bois details an alternative history placing the American Dream as a mid-twentieth-century invention and outgrowth of the Great Depression. Rather than a founding premise, in Du Bois’s rendering of the American Dream, it is nothing more than a derivative of what he terms the “American Assumption.” With great historical specificity, Du Bois proves that the American Dream is intentionally devoid of the context of enslavement, land dispossession, and the events preceding and following the Civil War and Reconstruction. This essay combines key passages in Black Reconstruction with sociobiographical context to excavate key Du Boisian contributions to the sociology of knowledge, poverty, mobility, and inequality through the dissection of the American Dream mythology.
Ardent Moral Realism and the Value-Laden World
Authors: FitzPatrick William J.
Published: September 2023

This chapter aims to shed light on what is ultimately at stake in debates over moral realism by examining a particularly ambitious form of it, which we’ll call “ardent moral realism.” On this view, the world is robustly value-laden such that it objectively favors certain ways of valuing and acting over others, where this favoring involves categorical moral normativity. An interesting recent challenge seeks to cast doubt on the very coherence of such a view. In exploring that challenge and how it might be answered we can gain insight into the motivation behind ardent moral realism, the reasons why it needs to take on (what are usually considered to be) non-naturalistic commitments, and what exactly those commitments amount to. At the heart of the view, setting it apart from most rival forms of realism, is a commitment to the irreducibly evaluative or normative nature of certain elements of the world.
Moral Realism and Objectivity
Authors: Svavarsdóttir Sigrún
Published: September 2023

The chapter argues that to do justice to questions of objectivity that arise within and about moral discourse, we must take into account that this discourse is embedded within a somewhat conventionally regimented practice that comprises attempts to guide attitude and action by way of justifying, criticizing, validating, or excusing them. The appropriate condition of objectivity rules out a specific narrow kind of response-dependence that would run counter to this kind of guiding role for moral verdicts. The relevant condition is identified (the discourse- and practice-independence condition or, for short, the DP-independence condition). This condition goes beyond the so-called minimal realist theses: (i) that moral sentences are truth-evaluable and (ii) that some of them are true, thanks to how reality is. If it is to be a viable metaethical position, moral realism needs to commit also to the DP-independence of the facts within the domain of moral discourse.
Deflationary Metaethics
Authors: Horwich Paul
Published: September 2023

This chapter will sympathetically explore a Wittgenstein-inspired view of morality—one that combines recognition of the non-natural character of basic moral concepts (such as OUGHT), the existence of moral facts, and the dim prospects for moral knowledge. This perspective will derive from applying, to ethical (= moral) discourse, his deflationism about TRUTH and FACT, his conception of meaning as “use,” his conservative, antitheoretical, “quietist” metaphilosophy, his pragmatist view of language as a useful multipurpose instrument, and his pluralistic appreciation of the variety of functions, types of concept, and norms of belief that this instrument needs to encompass.
Moral Anti-Exceptionalism
Authors: Williamson Timothy
Published: September 2023

This chapter defends an anti-exceptionalist realist approach to the normative, on which it requires no special treatment in metaphysics, epistemology, or semantics. It works within a standard intensional framework, where necessarily coextensive predicates express the same property. Thus a normative predicate and a non-normative one may express the same property, independently of any reductive naturalism. In particular, it explains how the antirealist arguments of Sharon Street’s “A Darwinian Dilemma for Realist Theories of Value” and Jonas Olson’s Moral Error Theory fail in this framework. The final part discusses various properties expressible by “good,” why treating some of them as parochial does not imply antirealism, and how the isolating a property of more universal interest creates no special problems for realism.
Can a Moral Judgment Be Moorean?
Authors: Lycan William G.
Published: September 2023

G. E. Moore claimed to refute versions of idealism and skepticism by citing plain truths of “common sense,” such as that he had his breakfast before he had lunch, or that he has hands. Assuming arguendo that he succeeded against at least some of his opponents, are there moral judgments that can similarly overturn one or more varieties of moral antirealism? This chapter argues that if Moore did ever succeed, parallel appeals to commonsense moral judgments would refute moral “error” theories such as those of Mackie and Garner, and “revisionary” moral fictionalisms that are based on error theories. But they would have no power vs. emotivist, prescriptivist, or “quasi-realist” metaethics.
The Explanatory Roles of Moral Facts and the Case for Moral Realism
Authors: Audi Robert
Published: September 2023

The fact that a fan is running can explain why there is a draft. Explanatory power of this kind is generally taken to support realism regarding the facts and properties in question. Mathematical objects and properties, however, unlike fans, are neither in the causal order nor explanatory in the way a fan’s running is. Nonetheless, it is commonly thought that mathematical facts, such as theorems in arithmetic and geometry, play essential roles in scientific explanations and that this wider explanatory power supports realism regarding mathematical objects and properties. Do purported moral facts have comparable explanatory power (if any)? This chapter explores several kinds of explanatory roles that mathematical facts and (purported) moral facts may play. In the light of what emerges from analysis of some important cases, the chapter shows how moral realism, both about moral properties and about particular moral facts, is supportable in ways that draw on an analogy between the explanatory roles of moral facts and counterpart roles played by both certain mathematical facts and certain natural facts in the physical realm.
Nuclear Security
Authors: Hobbs Christopher , Tzinieris Sarah
Published: September 2023

This chapter introduces what is an important but relatively new area of international security: the protection of nuclear weapons, nuclear and radioactive materials in civil use, and their associated infrastructure and assets. It traces the development of the concept of nuclear security since the beginning of the atomic age and discusses key events and changes in nuclear threat perceptions and political priorities over the subsequent decades that spurred the development of new physical, organizational, regulatory, and international measures to address them. The purpose of the chapter is to set the scene for the overall volume, highlighting key initiatives and aspects of nuclear security explored in later chapters and setting out the book’s constituent sections. It also outlines the approach and objectives of The Oxford Handbook of Nuclear Security, which is primarily a resource designed to provide a comprehensive examination of nuclear security—achieved by taking a multidisciplinary approach to exploring its different dimensions and through inviting a multitude of international perspectives.
Island Tourism and Archaeology
Authors: Baldacchino Godfrey , Vella Nicholas C.
Published: September 2023

Tourists may be especially drawn to islands because of factors like physical separation, cultural differences, attractive climate and environment, and political autonomy. Archaeology adds depth to these. The chapter reviews the contribution of archaeology to island tourism, while warning against some of the incorrect but enduring idiosyncrasies of islands (and islanders), such as their presumed tropical location, isolation and distinct personality. Even though tourism has been an economic boon for many islands, the scorecard also points to various disturbing trends, like the overzealous reconstruction of monuments, environmental degradation, and the consequences of climate change and sea-level rise.
Introduction
Authors: Lloyd-Richardson Elizabeth E. , Baetens Imke , Whitlock Janis L.
Published: September 2023

This chapter introduces the notion of nonsuicidal self-injury (NSSI). NSSI encompasses a wide variety of behaviors including but not limited to carving or cutting of the skin and subdermal tissue, scratching, and burning. NSSI became an indelible part of the mental health landscape in populations of all types. Moreover, NSSI occurs across cultures, geography, and population which eventually became a leading signal for suicide risk. The chapter looks into Bronfenbrenner’s ecological systems theory and a transdiagnostic perspective at the levels of conceptualization, therapeutic assessment, intervention, and treatment as per the Research Domain Criteria. It considers case vignettes and summaries of implications for research, clinical practice, and intervention.
NSSI in the DSM-5
Authors: Lengel Greg , Ammerman Brooke A. , Washburn Jason
Published: September 2023

Since the proposal for an NSSI disorder (NSSI-D) in DSM-5, there has been an expanding literature exploring the reliability, validity, and utility of NSSI-D and its proposed criteria. This chapter aims to identify NSSI features that may advance the construct from a behavior subordinated within other mental disorders to an independent diagnosis, and examines historical conceptualizations of NSSI as a clinical behavior and discrete syndrome, the initial proposal to include NSSI-D in DSM-5 and recent and future directions for NSSI-D. The chapter also identifies NSSI features that differentiate the construct from related diagnoses and behaviors (e.g., borderline personality disorder), explores challenges with the current NSSI-D criteria and its categorization in the diagnostic manual, and summarizes arguments for and against NSSI-D.
Language-Processing Experiments in the Field
Authors: Wagers Matthew , Chung Sandra
Published: September 2023

This chapter discusses some of the circumstances and opportunities that arise when doing language processing experiments in the field. We focus on how resource and cultural challenges can shape the design of experiments. Because of the diversity of small-language communities, we avoid generalizing very broadly and instead draw principally on our own experiences working with the Chamorro community in the Northern Marianas Islands.
The Future of Experimental Syntax
Authors: Almeida Diogo , Breen Mara , Brennan Jonathan R. , Carlson Katy , Chung Sandra , Culbertson Jennifer , Cunnings Ian , Dillon Brian , Foraker Stephani , Hunter Tim , Kaiser Elsi , Kush Dave , Lidz Jeffrey L. , Matchin William , Pearl Lisa S. , Perkins Laurel , Polinsky Maria , Rogalsky Corianne , Runner Jeffrey , Sprouse Jon , Syrett Kristen , Szendrői Kriszta Eszter , Wagers Matthew , Yoshida Masaya
Published: September 2023

In this concluding chapter of the handbook, each contributor has written a 500 word mini-essay presenting their view of the future of experimental syntax, from the important theoretical questions on the horizon, to the methodological challenges that experimental syntacticians need to solve to answer those questions. The hope is that this final chapter will serve both as concrete inspiration for future studies in experimental syntax and as a benchmark for measuring the success of the field in the years to come.
Modeling syntactic acquisition
Authors: Pearl Lisa S.
Published: September 2023

Informative computational modeling can be an invaluable tool for understanding syntactic acquisition. In this chapter, I describe how modeling can be used to both formalize specific proposals about syntactic acquisition and empirically evaluate those proposals. I then review several approaches to a key aspect of a model’s inference process: how the modeled learner updates the underlying representations, based on the data encountered. I survey several syntactic acquisition models (both parametric and non-parametric), highlighting the importance of the modeled learner’s assumptions in each case, and conclude with exciting future possibilities in syntactic acquisition modeling.
Scribes, Compositors, Correctors
Authors: Atkin Tamara
Published: September 2023

This chapter explores the roles of scribes, compositors, and correctors, as discussed in the prefatory materials produced by authors and publishers across the Short Title Catalogue (STC) period. Taking each of these roles in turn, it shows how the errors and mistakes recorded in such preliminaries correct the ideal but unrealistic accounts of the process of print production in early printing manuals like Joseph Moxon’s Mechanick exercises (London, 1683) and Hieronymous Hornschuch’s Orthotypographia (Leipzig, 1608) and in so doing emphasizes the inconstant, highly variable nature of the printed book. Far from offering what Elizabeth Eisenstein famously described as ‘typographical fixity’, printed books often draw attention to their typographical instability in ways that somehow also recuperate the ‘work’, the immaterial text, from the material circumstances of its transmission.
Publishing Virginia (1608–1615)
Authors: Melnikoff Kirk
Published: September 2023

This chapter considers the various ways in which England’s colonization of Virginia in the first decades of the seventeenth century was in part energized by the London book trade. Distributed across the country by booksellers of all sorts, first-hand accounts piqued interest, pamphlet edicts flouted apprehensions, and printed sermons recast the endeavour along religious and nationalist lines. Printed ephemera such as bills of adventure, lottery receipts, and position advertisements streamlined the Virginia Company’s administrative work and fundraising efforts. The process by which this material was acquired, printed, and disseminated was in almost every case collaborative, and it was prompted as much by writers, compilers, and translators as by book-trade publishers.
‘A Gifte of good Moment’
Authors: Lyons Tara L.
Published: September 2023

This essay offers a new assessment of the London Stationers’ Company and their 1610 agreement with the Bodleian Library. Manuscript documents in Bodleian Library Records show that London publishers were a vital part of building the Oxford library’s holdings through their many ‘gifts’ of books and services to the library. While earlier scholars have studied the agreement for evidence of why it failed in the seventeenth century, this essay considers to what extent it succeeded. A fresh look at the evidence challenges received wisdom that pits the ‘averse’, ‘parsimonious’, and ‘recalcitrant’ Stationers against the noble Sir Thomas Bodley and his library’s commitment to educational advancement. By highlighting the Stationers’ acts of generosity, this essay reveals the significance of gift-exchange in forging bonds between company and library, two burgeoning institutions of the book in the seventeenth century.
Translingual and Multilingual Print
Authors: Coldiron A. E. B.
Published: September 2023

Translingual and multilingual printing not only registered but also cultivated early modern English readers’ encounters with alterity. Significant, variable multilingual printing in England began with William Caxton, England’s first printer, and flourished through the early print period; it was necessarily connected with a flourishing translation praxis. Multilingual printing, like translation, often served certain larger cultural agendas (such as improving English literary culture; claiming ancient heritage; celebrating key political moments in a pseudo-universalizing way). While many printers in England imitated Continental conventions of multilingual printing, some also developed particular modes suited to special English contexts, including John Day and ‘cultural amphibians’ like Caxton, John Wolfe, and Richard Field. Strategies of mise-en-page and typography, such as type distinction and type assignment, guided readers’ encounters with foreign materials, as the chapter demonstrates in a gallery of ten wide-ranging examples and a broader survey of multilingual genres and kinds.
From Duck Lane to Lazarus Seaman
Authors: Woudhuysen H. R.
Published: September 2023

This chapter constitutes the first published outline of the trade in second-hand books and manuscripts in England during the sixteenth and seventeenth centuries. It gives an overview of the subject and is organized around three key events: the Dissolution of the Monasteries, the work of the Parliamentary Sequestration Committee, and the first known auction sale in the country—that of Lazarus Seaman in 1676. It goes slightly beyond that event and looks at the spread of auctions in the country before 1700. Particular attention is paid to the language used to describe the trade and to the locations in which it took place. Some consideration is given to booksellers’ warranties and to the significance of codes used to price second-hand books. In the course of the chapter, evidence from the collections of some notable figures—Ben Jonson, John Donne, James Ussher, Samuel Pepys among them—is cited.
Provenance Narratives in the Twenty-First Century
Authors: James Kathryn
Published: September 2023

This chapter examines the provenance narrative as a form of ontological mediation, a mechanism by which the text-object is framed as the focus of study. It argues that, as a narrative, the provenance history indelibly influences the categories by which the object is or isn’t presented to its observers. Taking the work of John Leland, Thomas Hearne, M. R. James, and others as its focus, the chapter argues that the Dissolution of the Monasteries and the consequent destruction of their libraries acted as an originating provenance for the study of the book in the early modern period. It examines the long consequences of this for the field of English Studies and the categories by which that field was defined and understood by practitioners from the sixteenth century onwards. One consequence can be seen in the prioritization of ideals of intactness, completeness, or textual recovery in English bibliographical work, and in the ways in which the text-object is defined through its relationship with the imagined plenum and prelapsarian state of a pre-dissolution world.
Conversations about Time and Space
Authors: Iyengar Sujata
Published: September 2023

This chapter defines and describes ‘bookness’, the phenomenology of codices and material texts as they encounter human bodies in time and space, through a sustained comparison between contemporary artists’ books and early modern books about counting, calculating, and identifying objects in the real world (field guides, including abecedaries), and imagining the universe (astronomical books). It foregrounds the functions of bookness in space, both private and public, historically and in the present by contrasting early modern, flexible uses of the codex form with contemporary artists’ books—limited edition, artisanal, or fine art print objects that, in Johanna Drucker’s phrase, consider the codex as ‘a form to interrogate’ rather than as ‘a vehicle for reproduction’. It concludes by suggesting that the deliberately archaic form of the printed book and the arguably elitist and certainly rarefied commodity of the artists’ or fine-press book highlights the beauty, fragility, and human-inflicted damage of the natural world.
Paediatric obesity and Crohn’s disease: a descriptive review of disease phenotype and clinical course
Authors: McCoy Jacob , Miller Michael R , Watson Melanie , Crowley Eileen , Woolfson Jessica P
Published: September 2023

Objectives

In an era of increasing paediatric obesity and inflammatory bowel disease (IBD), this study evaluates the disease phenotype and clinical course of Crohn’s disease (CD) in paediatric patients who are obese or overweight.

Methods

This is a retrospective, single-center, descriptive observational study from January 2010 to May 2020. Participants were included if they were: aged 2 to 18 years at the time of diagnosis, had a confirmed diagnosis of CD, and met WHO criteria for overweight or obesity at the time of diagnosis or within one year before diagnosis.

Results

A total of 345 patient charts with CD were screened during the study period, with 16 patients meeting inclusion criteria. Median age of patients was 15.5 years (IQR = 13.6, 16.1). Of the 15 patients over 10 years of age, median anthropometrics at diagnosis included body mass index (BMI) of 27.2 (IQR = 24.9, 29.4) and BMI for age z-score of 1.82 (IQR = 1.58, 2.19). Presenting symptoms included abdominal pain (80.0%), diarrhea (66.7%), hematochezia (66.7%), and weight loss (26.7%). Five patients (33.3%) had obesity-related complications. Median time from symptom onset to diagnosis was 146 days (IQR = 31, 367), and median time from diagnosis to remission was 229 days (IQR = 101.8, 496.3).

Conclusions

Patients with elevated BMI and CD present with typical symptoms of IBD, although weight loss was a less common presenting symptom. Time to disease remission is delayed, and obesity-related complications are common. Primary care providers must have a high degree of clinical suspicion in patients to prevent delays to gastroenterology referral and to improve time to disease remission.