Linguistics

Contains table of contents, an introduction and abstracts for two doctoral dissertations

Climate Action In Megacities 3.0

"Climate Action in Megacities 3.0" (CAM 3.0) presents major new insights into the current status, latest trends and future potential for climate action at the city level. Documenting the volume of action being taken by cities, CAM 3.0 marks a new chapter in the C40-Arup research partnership, supported by the City Leadership Initiative at University College London. It provides compelling evidence about cities' commitment to tackling climate change and their critical role in the fight to achieve global emissions reductions

Testing causality violation on spacetimes with closed timelike curves

Generalized quantum mechanics is used to examine a simple two-particle scattering experiment in which there is a bounded region of closed timelike curves (CTCs) in the experiment's future. The transitional probability is shown to depend on the existence and distribution of the CTCs. The effect is therefore acausal, since the CTCs are in the experiment's causal future. The effect is due to the non-unitary evolution of the pre- and post-scattering particles as they pass through the region of CTCs. We use the time-machine spacetime developed by Politzer [1], in which CTCs are formed due to the identification of a single spatial region at one time with the same region at another time. For certain initial data, the total cross-section of a scattering experiment is shown to deviate from the standard value (the value predicted if no CTCs existed). It is shown that if the time machines are small, sparsely distributed, or far away, then the deviation in the total cross-section may be negligible as compared to the experimental error of even the most accurate measurements of cross-sections. For a spacetime with CTCs at all points, or one where microscopic time machines pervade the spacetime in the final moments before the big crunch, the total cross-section is shown to agree with the standard result (no CTCs) due to a cancellation effect.Comment: 28 pages, 8 figures, late

Relinquishing and Governing the Volatile: The Many Afghanistans and Critical Research Agendas of NATO's Governance

This article invites academics and policy analysts to examine the mechanisms and legacy of NATO's security and development governance of Afghan social spaces by using critical theory concepts. It argues that such scholarly endeavors are growing in importance as the United States and NATO gradually pull their troops out of Afghanistan. Thus, the article suggests a broad twofold research agenda. First, it points out that researching social spaces such as towns, villages, marketplaces, and neighborhoods beyond the realm of intergovernmental politics can lead to thick descriptions of how such places have been governed from within by agents external to them. Second, the study argues for a multifaceted examination of instruments, strategies, and institutions of security governance, its conduct and social effects by deploying critical and Foucauldian concepts such as the rationality and apparatuses of power relations. Thereby, it proposes an inquiry into Provincial Reconstruction Teams and Afghan National Security Forces as spatially and temporally specific apparatuses of surveillance and security

Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings from a Randomized Trial

Background. Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant. Methods. Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose. Results. One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses. Conclusions. GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates

Audit of medical (non-targeted) liver biopsy specimen quality, pathology reporting and effect on patient management

Aims: To evaluate our medical liver pathology practice and its influence on patient management, using audit templates published by the UK Royal College of Pathologists (RCPath). Methods: We audited medical liver biopsies reported in our centre in 2019 using RCPath proformas. Data were collected from pathology reports and corresponding electronic patient record. Results: 60 cases were selected for audit from 135 eligible biopsies reported in 2019. 58/60 cases were core biopsies and 2/60 were laparoscopic wedge biopsies. 53/57 (93%) core biopsies with available data met RCPath adequacy criteria (length &gt;15 mm and/or ≥6 portal tracts). Most reports (57/60; 95%) were judged to have helped patient management. 25/60 (42%) biopsy reports helped to clarify the clinical diagnosis and 48/60 (80%) led to altered management. Conclusions: We demonstrate the utility of the RCPath audit templates, highlighting the clinical value of medical liver biopsies in the diagnostic work-up and management of patients with liver disease

Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.

Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9. The production of ultra-low endotoxin Cas9 protein manufactured at scale further improved innate immunity. We conclude that injection-based delivery of minimally immunogenic CRISPR genome editing RNPs into the CNS provides a valuable alternative to virus-mediated genome editing

'It's small steps, but that leads to bigger changes': evaluation of a nurture group intervention

This article presents the results of a small-scale research project that aimed to evaluate the effectiveness of a part-time nurture group recently established in one primary school. Qualitative interviews were used to gather staff, pupil and parental perceptions about the nurture group. These focused on what difference the nurture group was making to the pupils concerned but also on views about what factors contributed to noted changes. All stakeholder groups identified areas of development for nurture group pupils. These included improved social skills, growth in personal confidence, greater engagement with academic tasks, and fewer incidences of undesirable behaviour. The evidence gathered so far suggests that the nurture group offered an effective way of supporting the social, emotional and behavioural skills of a group of 'at-risk' pupils. A range of factors thought to be important in achieving these outcomes are highlighted. These align broadly with the theoretical underpinnings of nurture groups

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution