Devising a method for the study of the overt selfishness of nursery school children

Thesis (M.A.)--Boston University, 1936. This item was digitized by the Internet Archive

An evaluation of tuberculosis contact investigations against national standards.

BACKGROUND: Contact tracing is a key element in England's 2015 collaborative TB strategy, although proposed indicators of successful contact tracing remain undescribed. METHODS: We conducted descriptive and multivariable analyses of contact tracing of TB cases in London between 1 July 2012 and 31 December 2015 using cohort review data from London's TB Register, identifying characteristics associated with improved indicators and yield. RESULTS: Of the pulmonary TB cases notified, 60% (2716/4561) had sufficient information for inclusion. Of these, 91% (2481/2716) had at least 1 contact (median: 4/case (IQR: 2-6)) identified, with 86% (10 251/11 981) of these contacts evaluated. 4.1% (177/4328), 1.3% (45/3421) and 0.70% (51/7264) of evaluated contacts of pulmonary smear-positive, pulmonary smear-negative and non-pulmonary cases, respectively, had active disease. Cases who were former prisoners or male were less likely to have at least one contact identified than those never imprisoned or female, respectively. Cases diagnosed at clinics with more directly observed therapy or social workers were more likely to have one or more contacts identified. Contacts screened at a different clinic to their index case or of male index cases were less likely to be evaluated than those screened at the same clinic or of women, respectively; yield of active disease was similar by sex. 10% (490/4850) of evaluated child contacts had latent TB infection. CONCLUSIONS: These are the first London-wide estimates of TB contact tracing indicators which are important for monitoring the strategy's success and informing risk assessment of index cases. Understanding why differences in indicators occur between groups could improve contact tracing outcomes

Should NICE reconsider the 2016 UK guidelines on TB contact tracing? A cost-effectiveness analysis of contact investigations in London.

BACKGROUND: In January 2016, clinical TB guidance in the UK changed to no longer recommend screening contacts of non-pulmonary, non-laryngeal (ETB) index cases. However, no new evidence was cited for this change, and there is evidence that screening these contacts may be worthwhile. The objective of this study was to estimate the cost-effectiveness of screening contacts of adult ETB cases and adult pulmonary or laryngeal TB (PTB) cases in London, UK. METHODS: We carried out a cross-sectional analysis of data collected on TB index cases and contacts in the London TB register and an economic evaluation using a static model describing contact tracing outcomes. Incremental cost-effectiveness ratios (ICERs) were calculated using no screening as the baseline comparator. All adult TB cases (≥15 years old) in London from 2012 to 2015, and their contacts, were eligible (2465/5084 PTB and 2559/6090 ETB index cases were included). RESULTS: Assuming each contact with PTB infects one person/month, the ICER of screening contacts of ETB cases was £78 000/quality-adjusted life-years (QALY) (95% CI 39 000 to 140 000), and screening contacts of PTB cases was £30 000/QALY (95% CI 18 000 to 50 000). The ICER of screening contacts of ETB cases was £30 000/QALY if each contact with PTB infects 3.4 people/month. Limitations of this study include the use of self-reported symptomatic periods and lack of knowledge about onward transmission from PTB contacts. CONCLUSIONS: Screening contacts of ETB cases in London was almost certainly not cost-effective at any conventional willingness-to-pay threshold in England, supporting recent changes to National Institute for Health and Care Excellence national guidelines

A multi-site service evaluation of silver diamine fluoride use for children

Introduction: The use of silver diamine fluoride (SDF) is relatively new to the UK. It is unknown how it is being used and for what indications in UK paediatric dental services. // Aim To: 1) establish how SDF is being used across different paediatric dental settings in the UK; and 2) consider parental and patient views on the treatment experience and side effect of discolouration. // Method: A multi-site service evaluation was carried out across six paediatric dentistry units covering hospital and community services. Data were collected prospectively from 17/02/2020 to 02/03/2022. Simple descriptive statistics were used to analyse the data. // Results: Data were collected for 54 patients. The included patients had an age range of 2-13 years, with a mean of 4.9 years. The reason SDF was chosen was reported as: to avoid general anaesthetic (n = 25); to avoid extractions (n = 8); stabilisation (n = 25); acclimatisation (n = 24); and insufficient cooperation for other treatment (n = 17). In total, 42 cases had SDF applied to the primary dentition. This was in the anterior dentition for 18 patients and the posterior dentition for 15, with nine patients having SDF applied both anteriorly and posteriorly. The majority of children and parents were accepting of the technique and immediate aesthetic outcome. // Conclusion: In the services involved in this multi-site service evaluation, SDF is used for young patients in the primary dentition for the purpose of caries arrest. The technique was viewed positively by the majority of parents and children

Engaging Opportunities: Connecting young people with contemporary research and researchers

This is the final report for ‘Engaging Opportunities’, an RCUK-funded School-University Partnership between the Open University and the Denbigh Teaching School Alliance. Informed by action research, this four-year project was designed to create structured, strategic, sustainable and equitable mechanisms for effective school-university engagement with research. The report describes an evidence-based strategy designed to embed school-university engagement with research within the University’s strategic planning for research and the operational practices of researchers. Through the early stages of our partnership we noted a lack of suitable planning tools that work for researchers, teachers and students. We therefore introduced a flexible and adaptable framework of four types of activity—open lectures, open dialogues, open inquiry and open creativity—combined with an upstream approach to planning based on a set of six principles. A sub-set of these activities were evaluated through a combination of surveys, interviews and interventions. In conclusion, we argue that institutional and professional cultures can be resistant to the prospect of fully embedding school-university engagement with research in a structured, strategic and sustainable manner, and offer suggestions for how this context could and should be changed

Automated pathway and reaction prediction facilitates in silico identification of unknown metabolites in human cohort studies

Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Current approaches utilize chemical information, such as spectral details and fragmentation characteristics to determine components of unknown metabolites. Here, we propose a systems biology model exploiting the internal correlation structure of metabolite levels in combination with existing biochemical and genetic information to characterize properties of unknown molecules. Levels of 758 metabolites (439 known, 319 unknown) in human blood samples of 2279 subjects were measured using a non-targeted metabolomics platform (LC-MS and GC-MS). We reconstructed the structure of biochemical pathways that are imprinted in these metabolomics data by building an empirical network model based on 1040 significant partial correlations between metabolites. We further added associations of these metabolites to 134 genes from genome-wide association studies as well as reactions and functional relations to genes from the public database Recon 2 to the network model. From the local neighborhood in the network, we were able to predict the pathway annotation of 180 unknown metabolites. Furthermore, we classified 100 pairs of known and unknown and 45 pairs of unknown metabolites to 21 types of reactions based on their mass differences. As a proof of concept, we then looked further into the special case of predicted dehydrogenation reactions leading us to the selection of 39 candidate molecules for 5 unknown metabolites. Finally, we could verify 2 of those candidates by applying LC-MS analyses of commercially available candidate substances. The formerly unknown metabolites X-13891 and X-13069 were shown to be 2-dodecendioic acid and 9-tetradecenoic acid, respectively. Our data-driven approach based on measured metabolite levels and genetic associations as well as information from public resources can be used alone or together with methods utilizing spectral patterns as a complementary, automated and powerful method to characterize unknown metabolites

“It’s all about asking from those who have walked the path”: Patient and stakeholder perspectives on how peers may shift substance use stigma in HIV care in South Africa

South Africa has the highest number of people with HIV (PWH) globally and a significant burden of co-occurring substance use disorder (SUD). Health care worker (HCW) stigma towards SUD is a key barrier to HIV care engagement among PWH with SUD. Support from peers—individuals with lived experience of SUD—may be a promising solution for addressing SUD stigma, while also improving engagement in HIV care. We evaluated the perceived acceptability of integrating a peer role into community-based HIV care teams as a strategy to address SUD stigma at multiple levels and improve patient engagement in HIV care. Patients and stakeholders (N = 40) were recruited from publicly-funded HIV and SUD organizations in Cape Town, South Africa. We conducted a quantitative assessment of stigma among stakeholders using an adapted Social Distance Scale (SDS) and patient perceptions of working with a peer, as well as semi-structured interviews focused on experiences of SUD stigma, acceptability of a peer model integrated into community-based HIV care, and potential peer roles. On the SDS, 75% of stakeholders had high stigma towards a patient with SUD, yet 90% had low stigma when in recovery for at least 2 years. All patients endorsed feeling comfortable talking to someone in recovery and wanting them on their HIV care team. Three main themes emerged from the qualitative data: (1) patient-reported experiences of enacted SUD and HIV stigmas were common and impacted HIV care engagement; (2) both patients and stakeholders considered a peer model highly acceptable for integration into HIV care to support engagement and address SUD stigma; and (3) patients and stakeholders identified both individual-level and systems-level roles for peers, how peers could work alongside other providers to improve patient care, and key characteristics that peers would need to be successful in these roles. Findings from this formative work point to the promise of a peer model for reducing SUD stigma among patients and HCWs within community-based HIV care teams in SA.https://doi.org/10.1186/s13722-022-00330-

KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control

Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB zinc-finger proteins (KZNFs), but little is known about the regulation of ERVs in adult tissues. We observed that KAP1 repression of HERVK14C was conserved in differentiated human cells and performed KAP1 knockout to obtain an overview of KAP1 function. Our results show that KAP1 represses ERVs (including HERV-T and HERV-S) and ZNF genes, both of which overlap with KAP1 binding sites and H3K9me3 in multiple cell types. Furthermore, this pathway is functionally conserved in adult human peripheral blood mononuclear cells. Cytosine methylation that acts on KAP1 regulated loci is necessary to prevent an interferon response, and KAP1-depletion leads to activation of some interferon-stimulated genes. Finally, loss of KAP1 leads to a decrease in H3K9me3 enrichment at ERVs and ZNF genes and an RNA-sensing response mediated through MAVS signaling. These data indicate that the KAP1-KZNF pathway contributes to genome stability and innate immune control in adult human cells