The LGBT+ Pupil as the Abject: An Ethnographic Exploration of Subjectivity and Discourse in UK Secondary Schools

According to many scholars, schools are the last bastion of permitted homophobia (Beadle, 2009; Grew, 2008; as cited in Formby, 2013). Primarily using the theories of Foucault, Kristeva and Butler, the thesis uses critical theory as a means to both understand and critically analyse the construction of subjectivity within and throughout discourse in the hetero-/cis-normative institution, and how this related to the potential abjection of LGBT+ pupils. Whilst it is agreed in this thesis that LGBT+phobia is still widespread in both schools and wider society, it was found in this research that the impact of direct LGBT+phobic discrimination was less evident. Instead, the discursive spaces where LGBT+phobia had been silenced were filled with hetero-/cis-normative discourse. Concomitantly, the impact of LGBT+ invisibility, the silencing of positive discourse surrounding sexuality and the institutional rejection of performative LGBT+phobia without cultural or organisational change meant there remained a negative impact on LGBT+ young people, despite a reduction in visible LGBT+phobia (DePalma and Atkinson, 2006/2010). Through the use of short vignettes taken from a period of ethnographic research, I have used discursive reflexivity to offer an alternative discourse surrounding the LGBT+ pupil in the school. In a thesis preoccupied with language, the institutional denial of appropriate language, the lack of positive space for LGBT+ young people to construct their identity and the potential risk of abjection from the hetero-/cis-normative institution are all highlighted as points for discussion. Viewed through a critical theory lens, the exemplars used to illustrate these complex theories are chosen from 72 workshops undertaken in schools with Year Nine pupils over a the 2015 to 2016 academic year in the Merseyside region, and also from self-identified LGBT+ young people (also in Year Nine during the academic year 2015 to 2016), who were part of discussions in an LGBT+ Youth drop in based in Liverpool city centre. Intertwining academic analysis and philosophical reflection, the research finds that not only is the LGBT+ pupil abject in the school, but this abjection is threefold. It is enacted by the institution, the peer group and by the internalised LGBT+phobia of the abjected pupil. In the conclusion, it is reflected upon how the impact abjection from school continues to affect LGBT+ people into adulthood

Euthanasia-related strain and coping strategies in animal shelter employees

Objective—To identify and evaluate coping strategies advocated by experienced animal shelter workers who directly engaged in euthanizing animals. Design—Cross-sectional study. Sample Population—Animal shelters across the United States in which euthanasia was conducted (5 to 100 employees/shelter). Procedures—With the assistance of experts associated with the Humane Society of the United States, the authors identified 88 animal shelters throughout the United States in which animal euthanasia was actively conducted and for which contact information regarding the shelter director was available. Staff at 62 animal shelters agreed to participate in the survey. Survey packets were mailed to the 62 shelter directors, who then distributed them to employees. The survey included questions regarding respondent age, level of education, and role and asked those directly involved in the euthanasia of animals to provide advice on strategies for new euthanasia technicians to deal with the related stress. Employees completed the survey and returned it by mail. Content analysis techniques were used to summarize survey responses. Results—Coping strategies suggested by 242 euthanasia technicians were summarized into 26 distinct coping recommendations in 8 categories: competence or skills strategies, euthanasia behavioral strategies, cognitive or self-talk strategies, emotional regulation strategies, separation strategies, get-help strategies, seek long-term solution strategies, and withdrawal strategies. Conclusions and Clinical Relevance—Euthanizing animals is a major stressor for many animal shelter workers. Information regarding the coping strategies identified in this study may be useful for training new euthanasia technicians

A Fully Non-Metallic Gas Turbine Engine Enabled by Additive Manufacturing Part I: System Analysis, Component Identification, Additive Manufacturing, and Testing of Polymer Composites

The research and development activities reported in this publication were carried out under NASA Aeronautics Research Institute (NARI) funded project entitled "A Fully Nonmetallic Gas Turbine Engine Enabled by Additive Manufacturing." The objective of the project was to conduct evaluation of emerging materials and manufacturing technologies that will enable fully nonmetallic gas turbine engines. The results of the activities are described in three part report. The first part of the report contains the data and analysis of engine system trade studies, which were carried out to estimate reduction in engine emissions and fuel burn enabled due to advanced materials and manufacturing processes. A number of key engine components were identified in which advanced materials and additive manufacturing processes would provide the most significant benefits to engine operation. The technical scope of activities included an assessment of the feasibility of using additive manufacturing technologies to fabricate gas turbine engine components from polymer and ceramic matrix composites, which were accomplished by fabricating prototype engine components and testing them in simulated engine operating conditions. The manufacturing process parameters were developed and optimized for polymer and ceramic composites (described in detail in the second and third part of the report). A number of prototype components (inlet guide vane (IGV), acoustic liners, engine access door) were additively manufactured using high temperature polymer materials. Ceramic matrix composite components included turbine nozzle components. In addition, IGVs and acoustic liners were tested in simulated engine conditions in test rigs. The test results are reported and discussed in detail

Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-infected Patients

BackgroundEarly diagnosis of reactivated Chagas disease in HIV patients could be lifesaving. In Latin America, the diagnosis is made by microscopical detection of the T. cruzi parasite in the blood; a diagnostic test that lacks sensitivity. This study evaluates if levels of T. cruzi antigens in urine, determined by Chunap (Chagas urine nanoparticle test), are correlated with parasitemia levels in T. cruzi/HIV co-infected patients.Methodology/Principal FindingsT. cruzi antigens in urine of HIV patients (N = 55: 31 T. cruzi infected and 24 T. cruzi serology negative) were concentrated using hydrogel particles and quantified by Western Blot and a calibration curve. Reactivation of Chagas disease was defined by the observation of parasites in blood by microscopy. Parasitemia levels in patients with serology positive for Chagas disease were classified as follows: High parasitemia or reactivation of Chagas disease (detectable parasitemia by microscopy), moderate parasitemia (undetectable by microscopy but detectable by qPCR), and negative parasitemia (undetectable by microscopy and qPCR). The percentage of positive results detected by Chunap was: 100% (7/7) in cases of reactivation, 91.7% (11/12) in cases of moderate parasitemia, and 41.7% (5/12) in cases of negative parasitemia. Chunap specificity was found to be 91.7%. Linear regression analysis demonstrated a direct relationship between parasitemia levels and urine T. cruzi antigen concentrations (p 105 pg was chosen to determine patients with reactivation of Chagas disease (7/7). Antigenuria levels were 36.08 times (95% CI: 7.28 to 64.88) higher in patients with CD4+ lymphocyte counts below 200/mL (p = 0.016). No significant differences were found in HIV loads and CD8+ lymphocyte counts.ConclusionChunap shows potential for early detection of Chagas reactivation. With appropriate adaptation, this diagnostic test can be used to monitor Chagas disease status in T. cruzi/HIV co-infected patients.Author SummaryReactivation of Chagas disease in people living with HIV is a serious clinical condition that is associated with high mortality. Hence, early diagnosis and treatment can be lifesaving. Although there are not well accepted criteria to identify patients at risk of reactivation, parasitemia levels are usually considered as the best predictor. Microscopy is used in Latin America for detection of parasitemia levels. However, this has low sensitivity, which usually leads to a delay in diagnosis and treatment. Quantitative PCR is used only for research proposes in endemic areas. Antigens in urine (antigenuria) are correlated with parasitemia levels in animal models, as well as in cases of congenital Chagas disease. We believe that antigenuria can also be used for prediction of parasitemia levels in T. cruzi/HIV co-infected patients. In this study, Chunap (Chagas urine nanoparticle test) was used for concentration and quantification of T. cruzi antigens in urine of T. cruzi/HIV co-infected patients. Values of more than 105 pg of T. cruzi antigens in urine were observed only in patients with reactivation of Chagas disease. This study shows that antigenuria levels are highly correlated to levels of parasitemia and can be used as a non-invasive technique for monitoring parasitemia levels in T. cruzi/HIV co-infected patients

Direct and indirect costs of acute diarrhea in children under five years of age in Indonesia: Health facilities and community survey

Background: Diarrhea remains a major cause of child morbidity and mortality in low- and middle-income countries. Reliable data on the economic burden of diarrhea is required to support the selection of appropriate health intervention programs. This study aimed to estimate the costs of acute diarrhea in children under five years of age in Indonesia, a large middle-income country with a substantial diarrheal burden. Methods: Direct medical cost data were extracted retrospectively for 1050 children under five years of age with acute diarrhea receiving inpatient care across 45 health facilities in seven Indonesian provinces during 2017–2020. Direct medical costs for children treated in outpatient settings were estimated by collecting unit costs associated with standard diarrhea case management in children. A structured interview of 240 caregivers of inpatients was also conducted retrospectively to estimate direct non-medical costs as well as indirect costs from caregiver income loss. Results: The weighted average direct medical cost for treatment of acute diarrhea as an inpatient and outpatient across health facility types was US$99.8 (SD±$56.8)(35% room costs, 29% professional fees, 26% medication costs, 10% diagnostic costs) and US$7.6 (SD±$4.3) (34% diagnostic costs, 28% medication costs, 27% professional fees, 10% registration fees), respectively. The average direct non-medical household cost for an acute diarrheal admission was US$4.90 and the indirect cost was US$9.90. Conclusion: There is a significant economic burden associated with acute diarrhea in children in Indonesia. This study, based on a wide variety of health care settings and geographical regions, provides data to inform the economic evaluation of rotavirus vaccines and other diarrheal prevention programs. Funding: This work was supported by a research grant from the Murdoch Children's Research Institute (MCRI) and PATH; and the Indonesian Technical Advisory Group on Immunization (ITAGI)

microRNA-seq of cartilage reveals an over-abundance of miR-140-3p which contains functional isomiRs

miR-140 is selectively expressed in cartilage. Deletion of the entire Mir140 locus in mice results in growth retardation and early-onset osteoarthritis-like pathology; however, the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified miR-140-3p as significantly more abundant (>10-fold) than miR-140-5p in human cartilage. Analysis of these data identified multiple miR-140-3p isomiRs differing from the miRBase annotation at both the 5' and 3' end, with >99% having one of two seed sequences (5' bases 2-8). Canonical (miR-140-3p.2) and shifted (miR-140-3p.1) seed isomiRs were overexpressed in chondrocytes and transcriptomics performed to identify targets. miR-140-3p.1 and miR-140-3p.2 significantly down-regulated 694 and 238 genes, respectively, of which only 162 genes were commonly down-regulated. IsomiR targets were validated using 3'UTR luciferase assays. miR-140-3p.1 targets were enriched within up-regulated genes in rib chondrocytes of Mir140- null mice and within down-regulated genes during human chondrogenesis. Finally, through imputing the expression of miR-140 from the expression of the host gene WWP2 in 124 previously published data sets, an inverse correlation with miR-140-3p.1 predicted targets was identified. Together these data suggest the novel seed containing isomiR miR-140- 3p.1 is more functional than original consensus miR-140-3p seed containing isomiR

The microRNA-29 family in cartilage homeostasis and osteoarthritis

MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways

Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins

The clustering of platelet glycoprotein receptors with cytosolic YxxL and YxxM motifs, including GPVI, CLEC-2 and PEAR1, triggers activation via phosphorylation of the conserved tyrosine residues and recruitment of the tandem SH2 (Src homology 2) domain effector proteins, Syk and PI 3-kinase. We have modelled the clustering of these receptors with monovalent, divalent and tetravalent soluble ligands and with transmembrane ligands based on the law of mass action using ordinary differential equations and agent-based modelling. The models were experimentally evaluated in platelets and transfected cell lines using monovalent and multivalent ligands, including novel nanobody-based divalent and tetravalent ligands, by fluorescence correlation spectroscopy. Ligand valency, receptor number, receptor dimerisation, receptor phosphorylation and a cytosolic tandem SH2 domain protein act in synergy to drive receptor clustering. Threshold concentrations of a CLEC-2-blocking antibody and Syk inhibitor act in synergy to block platelet aggregation. This offers a strategy for countering the effect of avidity of multivalent ligands and in limiting off-target effects

Strategies to self-manage side-effects of adjuvant endocrine therapy among breast cancer survivors : an umbrella review of empirical evidence and clinical guidelines

Purpose: Side-effects of adjuvant endocrine therapy (AET) are common in breast cancer survivors, and can affect adherence to treatment. We synthesised the evidence for strategies to self-manage these side-effects. Methods: We searched for systematic reviews and clinical guidelines on self-management strategies for AET side-effects (arthralgia, fatigue, hot flashes, gastrointestinal discomfort, nausea, vulvovaginal symptoms, and sleep disturbance). We searched oncology organisation’s websites and eight databases (Inception-November 2020). Screening, data extraction and quality assessment were completed independently in duplicate. PROSPERO: 2019CRD4201914001. Results: We identified 33 systematic reviews and 18 clinical guidelines. 21% of reviews were high quality, and the average quality score for guidelines was 44%. Evidence for most strategies was absent or weak. There was consensus from a low-quality review and multiple guidelines to recommend moisturisers, gels and lubricants for vulvovaginal symptoms. Evidence was weak for physical activity for self-managing most symptoms, although two high-quality reviews indicated yoga and aerobic exercise could reduce fatigue. Primary research was often biased by weak and underpowered study designs. Eleven reviews did not report information on adverse events. Conclusions: Most self-management strategies for breast cancer survivors experiencing side-effects from AET lack evidence. Primary research is needed using high-quality well-powered designs focusing on implementable strategies. Implications for Cancer Survivors: Patients and clinicians should be aware that although the risk of harm is low for these self-management strategies, the likelihood of benefit is often unclear. Women should consider moisturisers, gels or lubricants for self-managing vulvovaginal symptoms, and yoga or aerobic exercise for alleviating fatigue

Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE