The movement for the abolition of child labor in the mines of England. |c Boston University Graduate School dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, 1954.

Thesis (Ph.D.)--Boston UniversityIn the early part of the nineteenth century many children were employed in the coal mines of England and Scotland. By the early twentieth century this was no longer true. Between 1842 and 1920 several acts were passed by Parliament which regulated the work of children in mines. Before examining this legislation is is necessary to inquire how the children happened to be working in the mines in the first place. During the seventeenth and eighteenth centuries the use of coal for various purposes greatly increased. This demand for coal increased the demand for workers in the mines. Since there was little movement of population to the mining centers this demand was met partly by the employment of children. In the early nineteenth century this employment of children was taken for granted, just as it had been for centuries. [TRUNCATED

Modulation of host intestinal epithelium by gastrointestinal nematode secreted extracellular vesicles

Helminths have co-evolved alongside their hosts for millions of years and haveadapted eloquent mechanisms that allow them to reside in the host withoutcausing significant pathology, or elimination. The ability of these parasites tomanipulate their specialised host is reflected by their continued persistence asa global health concern, with ~1 billion people infected with soil transmittedhelminths (STHs). Helminth infections have long been associated with reducedallergic and autoimmune diseases leading to the hypothesis that helminthsuppress the host immune system, and this has been confirmed in both animalmodels and controlled human infection studies. Many studies have shown thatmany suppressive effects of infection on the host immune system can beattributed to helminth excreted/secreted products (ES). A small but growing listof individual molecules from helminth ES have been characterised, and themechanism of action elucidated. For example, multiple helminth species havebeen identified to secrete TGFβ mimic proteins that can bind host TGFβreceptor and induce T-regulatory (Treg) immunosuppressive cells. However,the full repertoire of helminth secreted molecules that modulate the host ishypothesised to be far from complete. Our lab discovered the presence of extracellular vesicles (EVs) within ES fromthe mouse infective helminth Heligmosomoides polygyrus bakeri (H. bakeri).EVs are lipid bilayer enclosed nanoparticles that carry proteins, lipids andnucleic acids and are released ubiquitously by all cells and organisms studiedto date. In mammalian systems EVs provide a mechanism of communicationbetween near or distal cells. In the context of host-pathogen dynamics it isproposed that EVs could play a role in enabling parasites to condition theirenvironment during infection. There is mounting evidence of host-parasite EVmediated modulation occurrence between plants and colonising fungal cells,bacteria and mammalian host cells, and several parasites and theirmammalian hosts including several helminth species. During H. bakeri infection host immune suppression is thought to primarilyoccur during the adult stage of infection when the parasite resides in the lumenof the duodenum in close proximity to the intestinal epithelium. The intestinalepithelium plays an integral role both in helminth detection, and in mediatingparasite clearance. Therefore, I hypothesised that adult H. bakeri EVs targetthe intestinal epithelium and directly modulate this tissue. The goal of thisthesis was to determine the role of helminth EVs in infection dynamics andhost modulation in the intestinal epithelium. I aimed to address whether H.bakeri EVs enter the intestinal epithelium, whether uptake is targeted to aspecific cell type and how these effects the function of this tissue usingintestinal organoid models. To address these aims development and refinement of methods for high purityEV preparations and EV labelling was required in order to directly implicate H.bakeri EVs as the causative agent in host responses. In Chapter 3, I comparedvarious combinational approaches to EV isolation and improved the purity ofour EV and EV depleted HES preparations. I then assessed EV preparationsusing cryoEM which furthered our understanding of the morphology anddiversity of H bakeri secreted EVs. I trialled multiple labelling methodologiesand found a low-background labelling method that allowed high confidenceidentification of uptake for subsequent chapters. However, I later discoveredthat the majority of labelling techniques trialled had variable labelling efficiencywith low proportions of EVs labelled; this is a caveat to consider wheninterpreting results using labelled EVs. To understand how H. bakeri EVs interact with the intestinal epithelium Ideveloped methods to grow small intestinal 2-D organoids (enteroids) whichare in vitro cultures that reconstitute the intestinal epithelium (Chapter 4). 2-Denteroids have greater cellular complexity as compared to a homogenous cellline and allow us to address the question of cell type specificity for uptake. 2-D enteroid cultures maintained cellular polarisation and differentiated into 6-7major cell types of the intestinal epithelium. In Chapter 5, I demonstrated by using fluorescently labelled EVs that H. bakeriEVs enter organoid cells, however at a lower proportion than I see side-by-side for our cell line cultures. This led to the hypothesis that H. bakeri EVscould target specific cellular populations within the intestinal epithelium. Toidentify whether uptake of H. bakeri EVs occurs in a targeted fashion byspecific cell types I performed microscopy experiments aiming to co-localiseEVs with certain cell types. Microscopy approaches did not provide a definitiveanswer to the question of whether uptake is cell type specific. Next, I modifiedthe cellular proportion of our 2-D enteroids to identify whether this altered theproportion of EV uptake. Goblet and tuft cells are specialised cells of theepithelium that are strongly induced during helminth infection and mediatehelminth clearance; I reasoned that H. bakeri EVs may specifically enter andmodulate these cell types. Organoid cultures that were enriched in goblet andtuft cells showed no enhanced ability to take up EVs, suggesting that neithergoblet nor tuft cells are specifically targeted over other cell types; however, thisdata does not rule out that H. bakeri EVs can enter these cell types andmodulate them. Whether cell type specificity exists for the uptake of H. bakeriEVs within the intestinal epithelium remains unclear and is still an active areaof investigation. To understand how EV treatment of 2-D enteroids altered host geneexpression in Chapter 6, I performed RNA sequencing (RNA seq) andcharacterised the transcriptional changes within 2-D enteroids to H. bakeri EVsor EV depleted ES after 24 h. Genes critical for maintenance of stem cells, cellcycle and antimicrobial defence were downregulated by H. bakeri EVs. Withinthe intestinal epithelium only a proportion of the cells are mitotic, thereforechanges in cell cycle suggest a modulation of either stem cells of Transit-amplifying (TA) cells. I also identified several changes in cell type restricted genes expressed specifically by stem cells, Paneth cells, TA cells orEnteroendocrine cells (EECs). I now hypothesise EVs specifically modify thesecell types. To define the cell type specific responses after EV or EV depletedES treatment I performed single cell RNA seq, unfortunately the quality of ourcontrol sample made interpreting these results difficult. However, these dataserve as conformation of the cellular composition of our 2-D enteroids model. In addition, I also utilised our 2-D organoid model to perform novel co-culturedexperiments with live adult or larval stage 4 (L4) H. bakeri and performedtranscriptional analysis of the host epithelium under these conditions. Thesedata allow us to uncouple the impact of infection with whole parasites on theintestinal epithelium from any immune driven changes in the epithelium thatoccur in vivo. These data also serve as a comparison between host effectsattributed specifically to H. bakeri EVs, and changes induced by the wholeparasite. In summary, this thesis contributes new knowledge to our understanding of H.bakeri interactions with the intestinal epithelium in the absence of host immunedriven responses and distinguishes the role of secreted H. bakeri EVs inmodulating this tissue. I determined that H. bakeri EVs enter host epithelialcells in 2-D enteroids, but whether this is specifically targeted to certainsubpopulations remains elusive. I characterised the host gene expressionchanges upon H. bakeri EV treatment in 2-D enteroids, these findings furtherour understanding as a field of which host genes and pathways are targetedby H. bakeri. In the future, this thesis along with continued research, couldhave important implications for helminth eradication. Conversely, where H.bakeri EVs suppress specific genes or pathways involved in diseases of theintestinal epithelium such as ulcerative colitis, Crohn's disease, oradenocarcinoma, they could provide novel strategies for therapeutics

Understanding the varieties of self-generated thought

Although self-generated thought (SGT i.e. cognition unrelated to the here and now) has traditionally been considered as a homogeneous phenomenon, recent findings challenge this assumption by showing that SGT can have both costs and benefits, and that SGT can be linked to both executive control and executive failure. To gain insight into these discrepancies, this PhD tested the hypothesis that SGT is a heterogeneous phenomenon and examined whether the content of the thoughts is one factor underlying the heterogeneities observed. By taking into account the temporal, social and emotional dimensions of SGT content, we were able to systematically identify distinct types of thoughts. In addition, we observed that these different SGT types can have heterogeneous functional outcomes (for example, in terms of their relation to task performance or to measures of self-concept). We also found that these SGT types can have different phenomenological properties, suggesting that heterogeneous cognitive correlates are recruited during the generation of distinct types of thoughts. Finally, we demonstrated that the neural substrates of SGT (as assessed using resting state fMRI) varied according to individual differences in thought content. Altogether, the empirical findings described in the current thesis strongly support the hypothesis that SGT is a heterogeneous phenomenon and highlight that taking into account SGT content allows a better understanding of the neurocognitive underpinnings supporting this subjective experience

Representing Representation : Integration between the Temporal Lobe and the Posterior Cingulate Influences the Content and Form of Spontaneous Thought

When not engaged in the moment, we often spontaneously represent people, places and events that are not present in the environment. Although this capacity has been linked to the default mode network (DMN), it remains unclear how interactions between the nodes of this network give rise to particular mental experiences during spontaneous thought. One hypothesis is that the core of the DMN integrates information from medial and lateral temporal lobe memory systems, which represent different aspects of knowledge. Individual differences in the connectivity between temporal lobe regions and the default mode network core would then predict differences in the content and form of people's spontaneous thoughts. This study tested this hypothesis by examining the relationship between seed-based functional connectivity and the contents of spontaneous thought recorded in a laboratory study several days later. Variations in connectivity from both medial and lateral temporal lobe regions was associated with different patterns of spontaneous thought and these effects converged on an overlapping region in the posterior cingulate cortex. We propose that the posterior core of the DMN acts as a representational hub that integrates information represented in medial and lateral temporal lobe and this process is important in determining the content and form of spontaneous thought

Children and young people's mental health outcome measures in paediatrics

Paediatricians are increasingly likely to encounter children and young people with mental health difficulties, either as primary presentations or as comorbidities linked with chronic illnesses. However, paediatricians may have limited training or experience regarding the tools available to identify mental health needs and how to use these tools. The current paper aims to provide a go-to guide for paediatricians when considering the use of mental health and well-being outcome measures, including how to select, administer and interpret measures effectively. It also provides practical guidance on the most common mental health outcome measures used in children and young people's mental health services across the UK and elsewhere, which paediatricians are likely to encounter in their practice. Paediatricians may also find these measures useful in their own practice to screen for potential mental health difficulties, monitor the impact of chronic health conditions on a young person's mental health and well-being, or to provide evidence when referring young people to mental health services

The Iowa Homemaker vol.20, no.2

Your College Home, Editor, page 1 Home Economics Cabinet, Florence Byrnes, page 2 Study on a Budget, Dorothy Lee Conquest, page 4 Forward March with Confidence, Eleanor White, page 6 Home Economist from Far Away, Ruby Jackson, page 7 It’s a Man’s World, Gaynold Carroll, page 8 Art, Music, and Literature Mingle, Nancy Mason, page 10 Who’s Who on Campus, Dorothy Anne Roost, page 11 What’s New in Home Economics, page 12 Women’s Athletics Will Enter New Home, Jeanette Foster, page 14 Personalize Your Letter Writing, Virginia Kirkpatrick, page 15 Behind Bright Jackets, Marjorie Thomas, page 16 Coed Concoctions, Marian Dougan, page 18 Alums in the News, Bette Simpson, page 20 Give Beauty a Chance, Ida Halpin, page 22 Journalistic Spindles, Ruth Jensen, page 2

Examining concurrent validity and item selection of the Session Wants and Needs Outcome Measure (SWAN-OM) in a children and young people web-based therapy service

Background: Single-session mental health interventions are frequently attended by children and young people (CYP) in both web-based and face-to-face therapy settings. The Session “Wants” and “Needs” Outcome Measure (SWAN-OM) is an instrument developed in a web-based therapy service to overcome the challenges of collecting outcomes and experiences of single-session therapies (SSTs). It provides pre-defined goals for the session, selected by the young person prior to the intervention, on which progress toward achievement is scored at the end of the session. Objective: The objective of this study was to evaluate the instrument's psychometric properties, including concurrent validity against three other frequently used outcome and experience measures, at a web-based and text-based mental health service. Methods: The SWAN-OM was administered for a period of 6 months to 1,401 CYP (aged 10–32 years; 79.3% white; 77.59% female) accessing SST on a web-based service. Item correlations with comparator measures and hierarchical logistic regressions to predict item selection were calculated for concurrent validity and psychometric exploration. Results: The most frequently selected items were “Feel better” (N = 431; 11.61%) and “Find ways I can help myself” (N = 411; 11.07%); unpopular items were “Feel safe in my relationships” (N = 53; 1.43%) and “Learn the steps to achieve something I want” (N = 58; 1.56%). The SWAN-OM was significantly correlated with the Experience of Service Questionnaire, particularly the item “Feel better” [rs(109) = 0.48, p < 0.001], the Youth Counseling Impact Scale, particularly the item “Learn the steps to achieve something I want” [rs(22) = 0.76, p < 0.001], and the Positive and Negative Affect Schedule, particularly the items “Learn how to feel better” [rs(22) = 0.72, p < 0.001] and “Explore how I feel” [rs(70) = −0.44, p < 0.001]. Conclusion: The SWAN-OM demonstrates good concurrent validity with common measures of outcome and experience. Analysis suggests that lesser-endorsed items may be removed in future iterations of the measure to improve functionality. Future research is required to explore SWAN-OM's potential to measure meaningful change in a range of therapeutic settings

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

Pearson's correlations between t₀ Affect Component and mood measures.

<p>Pearson's correlations between t₀ Affect Component and mood measures.</p