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Age, Gender, and Agency in Juvenile Migration from England to Canada, 1850–1900
Get PDFThis article makes two important contributions. Firstly, it provides valuable insights into the motivations of working-class migrants in the second half of the nineteenth century, adding a new dimension to a scholarship focused on studies of forced migration or middle-class empire building. Its analysis of a rich body of published and unpublished letters from former institutionalized children reveals the primacy of financial gain in the migration decision and shows that working-class Britons saw the world beyond the British Isles as a space of opportunity, where they could leverage their mobility in pursuit of profit. Secondly, by arguing that juvenile emigrants need to be viewed as a heterogeneous body where age and gender made a difference in terms of experience, the article provides an important new perspective on institutional migration that has implications for wider literatures on childhood and youth. The average age of the boys studied for this article was sixteen and the research shows that they were active participants in the emigration process, shaping their own futures through their diverse decisions. Recognizing this significantly undermines the modern discourses of blame and victimhood that dominate the historiography and encourages us to re-evaluate our approach to nineteenth-century juvenile migration
Modelling and optimising turbulence in 3D magnetic geometries for enhanced microstability
Get PDFThis thesis investigates microturbulence in three-dimensional magnetised plasma geometries, with a specific focus on the impact of turbulence to plasma stability. Microturbulence is the small-scale turbulent fluctuations in a plasma caused by instabilities at or near the ion and electron gyroradius scales. Microturbulence remains a critical challenge within the field of plasma physics, and in order to control the effects of turbulence, we first need to accurately model it. This task is particularly complex in non-axisymmetric geometries, where mode-coupling occurs across nonidentical field lines, leading to potential inconsistencies in the common representation of zonal flows.
The first part of the thesis focuses on the development and validation of a novel δf-gyrokinetic code, designed to model microturbulence across a full flux-annulus in non-axisymmetric magnetic configurations. This is especially important when considering turbulent dynamics in stellarators and tokamaks with 3D magnetic perturbations, as capturing the coupling of modes across different field lines is necessary to accurately resolve ‘zonal’ modes, that are constant across a flux surface. The code is benchmarked against the current flux-tube implementation of the stella code, along with other existing gyrokinetic codes. Novel results incorporating kinetic electrons are also presented.
The second part of the thesis addresses microstability, which poses unique optimisation challenges due to the large number of tunable parameters in magnetic confinement devices. To tackle this problem, an efficient method for calculating the derivative of the linear growth rate with respect to multiple externally-controllable parameters, has been developed using an adjoint method. The theoretical framework is derived in the limit of no field-line coupling, including electromagnetic effects and collisions. Numerical simulations then demonstrate the efficacy of the approach in the electrostatic, collisionless regime
Tiny LiDARs for manipulator self-awareness: sensor characterization and initial localization experiments
Get PDFFor several tasks, ranging from manipulation to inspection, it is beneficial for robots to localize a target object in their surroundings. In this paper, we propose an approach that utilizes coarse point clouds obtained from miniaturized VL53L5CX Time-of-Flight (ToF) sensors (tiny LiDARs) to localize a target object in the robot's workspace. We first conduct an experimental campaign to calibrate the dependency of sensor readings on relative range and orientation to targets. We then propose a probabilistic sensor model, which we validate in an object pose estimation task using a Particle Filter (PF). The results show that the proposed sensor model improves the performance of the localization of the target object with respect to two baselines: one that assumes measurements are free from uncertainty and one in which the confidence is provided by the sensor datasheet
The moderating and mediating role of resilience in the relationship between adverse childhood experiences and depression, PTSD, and suicidality in Kenyan youth
Get PDFAdverse childhood experiences (ACEs) are widely associated with mental health disorders, such as depression, post-traumatic stress disorder (PTSD), and suicidality. Resilience plays a role in mediation and moderation of these associations, yet there is limited data from Kenya on this. This cross-sectional study examined the role of resilience in the relationship between ACEs and mental health outcomes among 1,972 participants aged 14–25 years in the Nairobi Metropolitan area. Participants completed the Trauma and Distress Scale (ACEs), Patient Health Questionnaire-9 (depression), Columbia-Suicide Severity Rating Scale (suicidality), Harvard Trauma Questionnaire (PTSD), and Adult Resilience Measure-Revised (resilience). Analyses of moderation and mediation using Hayes Process Macro indicated that resilience moderated the association between ACEs with PTSD and depression, with minimal effect on suicidality. It also moderated specific associations, including emotional/physical neglect on ideation, physical abuse on lifetime behavior (p = 0.0479), and total ACEs on recent behavior (p = 0.0514). Resilience also partially mediated the effects of ACEs on PTSD and depression, and fully mediated suicidality for specific ACE domains (emotional neglect, physical neglect, and physical abuse on suicidal ideation and all ACEs on recent suicidal behaviors). Building resilience mitigates the effects of ACEs on depression, PTSD, and suicidality among Kenyan youth
Comparative performance of a commercial and in-house Mp1p antigen-detecting enzyme immunoassay for the rapid diagnosis of talaromycosis
Get PDFBackground: Several antigen-detection assays have been developed for the rapid diagnosis of talaromycosis, but their utility has been limited by a lack of commercial options. The aim of this study was to perform a head-to-head comparison of the performance of our in-house monoclonal antibody-based Mp1p antigen-detecting enzyme immunoassay (EIA) with its recently-developed commercial platform. Methods: In this diagnostic accuracy, retrospective, case-cohort study, we compared the sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of the commercial Wantai Mp1p EIA versus our in-house Mp1p EIA on paired plasma and urine samples from 424 hospitalized adults with advanced HIV disease, including 224 cases of proven talaromycosis, where Talaromyces marneffei was isolated in culture of blood or other clinical specimens, and 200 controls diagnosed with a range of other opportunistic infections. All participants were randomly selected from prospective cohorts recruited between 2011 and 2019 from five centers in Vietnam. Results: The sensitivity of the Wantai and in-house Mp1p EIAs were comparable in plasma (95.1% vs 92.4%, P = 0.11), in urine (91.5% vs 87.1% P = 0.07), and in combined testing of plasma and urine (96.4% vs 96.0%, P = 1.00), where talaromycosis was diagnosed based on the positivity of either specimen. The specificity of the Wantai and in-house Mp1p EIAs were consistently high in plasma, in urine, and in combined testing (93 – 97%). The Wantai and in-house Mp1p EIAs provided substantially higher sensitivity than blood culture detection (96.4% and 96.0% vs 78.6%, P < 0.001). For both EIAs, LR+ were greater than 10 and LR- were less than 0.1, which increases the confidence to rule in or rule out talaromycosis. Conclusions: The diagnostic performance of the Wantai Mp1p EIA was comparable to our validated in-house Mp1p EIA, and significantly more sensitive than blood culture, offering a standardized tool for the rapid diagnosis of talaromycosis
Targeting MHC-E as a new strategy for vaccines and immunotherapeutics
No full textMHC-E is a highly conserved, non-polymorphic MHC protein that engages inhibitory and activating receptors on natural killer (NK) cells and T cells and can also present antigens to T cell receptors. NK cell responses driven by activating receptor interactions with MHC-E are implicated in controlling chronic viral infections and cancer. Immunotherapeutic targeting of interactions between MHC-E and inhibitory receptors to increase the activation of NK cells and T cells shows promise in improving antitumour immune responses. Furthermore, MHC-E-restricted CD8+ T cells elicited by cytomegalovirus-based vaccines might, for certain infections and cancers, be more effective than CD8+ T cells restricted by classical MHC class I or class II molecules. The ability of MHC-E to regulate or mediate both innate and adaptive immune responses independently of an individual’s MHC haplotype raises the possibility of new, universally effective vaccines and immunotherapies for infectious disease and cancer. Although the therapeutic exploitation of MHCE is still in its infancy, recent advances in the understanding of MHC-E biology show enormous potential, as described in this Review
The dynamic interplay between mental health difficulties and the family environment in early adolescence
Get PDFBackground: Adolescents experiencing mental health problems have an elevated risk of persisting difficulties as they transition into adulthood, stressing the importance of identifying modifiable factors impacting mental health during adolescence. The family environment is recognised as a key influence on adolescent mental health in theory and interventions. Notably, few studies have disentangled within‐person and between‐person effects in relating adolescent mental health and the family environment. Methods: We analysed data from 1067 adolescents across three waves using panel graphical vector autoregressive modelling, separating contemporaneous and temporal within‐person and between‐person associations in relationships between mental health difficulties (i.e., emotional, hyperactivity/inattention, conduct problems) and family‐related factors (i.e., aspects of the general family environment, parent‐child relationships, and sibling dynamics). We also assessed how the different mental health difficulties and family environment factors were themselves interrelated over time. The mean age (in years) was 10.51 at Wave 1, 12.49 at Wave 2, and 14.49 at Wave 3. Results: Emotional symptoms predicted increases in hyperactivity/inattention and more sibling problems over time. Lack of family support and negative feelings towards family were reciprocally related, indicative of a reinforcing loop. Both mental health difficulties and family environment factors exhibited considerable stability. In contemporaneous within‐person associations, mental health difficulties were strongly interrelated, as were aspects of the family environment. Furthermore, conduct problems were linked to externalising behaviours (e.g., fighting with parents, bothering siblings) and emotional symptoms to internalising experiences of family dynamics (e.g., feeling negative towards family, being bothered by siblings). Negative feelings towards family and hyperactivity/inattention were strongly predicted by included variables, while emotional symptoms, fighting with parents, and lacking family support were predictive of other variables. Conclusions: Our findings point to the importance of emotional problems in adolescence, which may contribute to worsened hyperactivity/inattention and more problems with siblings over time, and the interrelatedness of mental health and the family environment. Alleviating internalising problems in affected adolescents may help mitigate development of other mental health difficulties and negative sibling dynamics
Single-cell profiling of blood and cerebrospinal fluid in tuberculous meningitis
Get PDFTuberculous meningitis (TBM) is the most severe form of tuberculosis, with a fatality rate of 20% to 50% in treated individuals. Although corticosteroid therapy can increase survival in HIV-negative people with TBM, better antimicrobial and host-directed therapies are required to improve outcome. There is, therefore, a need to better understand local immunopathologic pathways. Despite its power in identifying disease-specific cellular profiles, single-cell RNA sequencing (scRNA-seq) has been underutilized in cerebral samples in brain infection. We employed scRNA-seq to analyze fresh pretreatment cerebrospinal fluid (CSF) from 4 TBM patients, along with paired PBMCs. While 29 cell subtypes were present in both tissues, their relative abundance varied significantly. In particular, CSF was enriched with highly inflammatory microglia-like macrophages, GZMK+CD8+ effector-memory T (TEM) cells, and CD56bright NK cells. The latter 2 subsets exhibited reduced cytotoxicity compared with their blood-enriched counterparts, namely cytotoxic GNLY+CD8+ TEM and CD56dim NK cells, respectively. Across multiple cell types, inflammatory signaling pathways were increased and oxidative phosphorylation was decreased in CSF compared to PBMCs. This study highlights the value of scRNA-seq for exploring CSF immunopathogenesis in TBM patients and offers a resource for future studies investigating the pathophysiology of TBM and other brain infections, including potentially targetable cell populations linked with immune-mediated pathology
High Propensity for Multidrug-Resistant Pneumococcal Shedding Among Adults Living With HIV on Stable Antiretroviral Therapy in Malawi
Get PDFBackground: People living with human immunodeficiency virus (HIV; PLHIV) on antiretroviral therapy (ART) are still at risk of pneumococcal disease and have over 2-fold higher pneumococcal carriage prevalence than HIV-uninfected (HIV−) adults). Carriage is a risk factor for pneumococcal disease, antimicrobial resistance (AMR) emergence, and transmission. Therefore, we tested whether the high prevalence of pneumococcal carriage in PLHIV on ART is associated with increased bacterial density, shedding, and AMR. Methods: We recruited asymptomatic PLHIV on ART for >1 year (PLHIV-ART>1y) and HIV− adults. Nasopharyngeal swab samples were collected on days 3, 7, 14, 21, and 28, followed by monthly collections for 12 months, while shedding samples were collected on days 3, 21, and 28. Peripheral blood samples were collected on day 3 to measure CD4 cell count and HIV viral load. Pneumococcal carriage density and shedding were assessed using standard bacterial culture, multiple carriage was detected using whole-plate sweep sequencing, and AMR profiling was conducted using disk diffusion and Etest. Results: PLHIV-ART>1y had a higher propensity for high-density carriage (adjusted odds ratio, 1.67 [95% confidence interval (CI), 1.07–2.60]; P = .02). Moreover, PLHIV-ART>1y are more likely to shed pneumococci than HIV− adults (adjusted odds ratio, 2.52 [95% CI, 1.06–6.00]; P = .04), with carriage density identified as an important risk factor for shedding (3.35 [1.55–7.24]; P = .002). Aerosol shed isolates from PLHIV-ART>1y were mostly multidrug resistant (18 of 29 [ 62%; 95% CI, 48%–77%]). Conclusions: These findings indicate that PLHIV-ART>1y remain at high risk of pneumococcal disease and could also be an important reservoir for shedding multidrug-resistant pneumococci