Tinnitus groups – a model of social support and social connectedness from peer interaction

Tinnitus is a chronic condition for which there is no medical treatment. Tinnitus groups are a widely available resource for people with tinnitus. Objectives: Our objectives were to explore the active ingredients of tinnitus support groups in terms of their mechanisms for providing support, the contextual factors that elicit such mechanisms, and the outcomes in terms of coping enhancement. Design: We adopted a pluralist and iterative approach informed by the realist evaluation method. Methods: We conducted ethnographic data generation at tinnitus support groups involving observations (n = 160), focus groups (n = 130), and individual interviews (n = 20). Inductive analyses were conducted following the constant comparison method of grounded theory. We then interrogated the inductive themes to identify evidence of Contexts, Mechanisms, and Outcomes. We then produced a model which was tested in a survey of tinnitus group members (n = 65) in effect providing large-scale respondent validation of the data-driven model created through our inductive analysis. Results: We identified that tinnitus groups can facilitate social connectedness between group members. This experience appeared to build resilience among those experiencing tinnitus-related distress. Groups also played a role in building a sense of control related to knowledge and information sharing. Additionally, we identified risks associated with not accessing social support in a group environment. Conclusions: Our findings contribute to the growing understanding of the power of social connectedness as building shared social identity when living with tinnitus. Statement of contribution What is already known on this subject? Tinnitus is a prevalent condition with approximately 10–15% of the population experiencing a spontaneous sound without obvious source. Tinnitus is an invisible health and chronic condition. People with tinnitus experience high levels of distress, anxiety, and depression. Group support is beneficial to people with many health problems. What does this study add? This study describes the mechanisms by which tinnitus support groups can support coping in tinnitus. This is the first study to comprehensively explore the views of those who attend tinnitus groups. The study identifies the key features of support groups that facilitate social connectedness among group members. The most valued features of groups are the knowledge and information provided, the sense of belonging communicated to group members, and the creation and maintenance of a sense of hope towards the tinnitus. This study contributes new insights to both the tinnitus field and adds to the literature on support groups in health

Predicting the Availability of Hematopoietic Stem Cell Donors Using Machine Learning

Hematopoietic stem cell transplantation (HSCT) is firmly established as an important curative therapy for patients with hematologic malignancies and other blood disorders. Apart from finding HLA-matched donors during the HSCT process, donor availability remains a key consideration as the time taken from diagnosis to transplant is recognized to adversely affect patient outcome. In this study, we aimed to develop and validate a machine learning approach to predict the availability of stem cell donors. We retrospectively collected a data set containing 10,258 verification typing requests made during the HSCT process in the British Bone Marrow Registry (BBMR) between January 1, 2013, and December 31, 2018. Three machine learning algorithms were implemented and compared, including boosted decision trees (BDTs), logistic regression, and support vector machines. Area under the receiver operating characteristic curve (AUC) was primarily used to assess the algorithms. The experimental results showed that BDTs performed better in predicting the availability of BBMR donors. The overall predictive power of the model, using AUC on the test cohort of 2052 records, was found to be 0.826. Our findings show that machine learning can predict the availability of donors with a high degree of accuracy. We propose the use of the BDT machine learning approach to predict the availability of BBMR donors and use the predictive scores during the HSCT process to ensure patients with blood cancers or disorders receive a transplant at the optimum time

Australia’s COVID-19 pandemic housing policy responses

This research reviewed Australia’s COVID-19 housing policy responses to better understand their intervention approach, underlying logic, short and long term goals, target groups and level of success. It considered literature and policy from Australia and a small number of international comparator policies; conducted online surveys of landlords and of economists; and consulted key stake holders. Given Australia’s federated system of government, considerable differences quickly emerged between intervention approaches across states and territories. This was also driven by the extent to which different jurisdictions were impacted by the spread of the virus, the extent and frequency of lockdowns, and damage to state/local economies. The national and state policy measures implemented to support home ownership achieved the desired goal of providing short-term stimulus to the residential building sector and support to the broader economy. However, a range of anticipated and unforeseen consequences have precipitated as a result of concentrated demand-side subsidies, low interest rates and flexible lending conditions. The establishment of an agile infrastructure to support information sharing will support more effective and innovative housing policy development in the future. The state-to-state infrastructure and approaches that were developed rapidly and which supported jurisdictional responses to COVID-19 provide a template for a shelf-ready policy-sharing practice that warrants supported development across governments. This could usefully include local government as well as state and territory and national tiers of governance

Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene

G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH β-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH(2)-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH β-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH(2)-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH β-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression

Demand-side assistance in Australia’s rental housing market: exploring reform options

By international comparison, Australia’s Commonwealth RentAssistance (CRA) regime is distinctive in terms of being (a) restrictedto income-support recipients; (b) paid to renters, not landlords;(c) capped at modest maximum rates; (d) regionally invariant; and(e) not rationed.• In severely disadvantaged areas, 32.4 per cent of a modelledincrease in CRA is shifted into higher rents. CRA is more likely becaptured in higher rents in disadvantaged rental markets becauseof relatively inelastic housing supply in low-value market segments.Out of 1.41 million low-income private renter income units, nearlytwo-thirds or 933,000 are assisted by CRA. Meanwhile, CRA is alsopaid to 419,000 private renter income units with moderate incomes,partly due to targeting error.Over one-third of low-income CRA recipients still carry a net housingcost burden of more than 30 per cent after CRA is deducted fromrents.Around 246,000 or 18 per cent of low-income private renter incomeunits pay rents that exceed 30 per cent of their income but areineligible for CRA. Another 330,000 or 23 per cent receive CRAdespite paying rents below 30 per cent of their income. CRA’s overalltarget error rate is 41 per cent.Raising the CRA maximum rate would improve affordabilityoutcomes for 623,800 income units or 44 per cent of low-incomeprivate renters. However, it is the costliest of the three modelledreforms, requiring additional annual expenditure of $1 billion toamount to a total cost of$5.6 billion.• Reforming the CRA eligibility rules to reflect housing need wouldachieve the greatest housing affordability improvements among thethree modelled reforms, and at the lowest cost. The reform wouldreduce the CRA target error rate to zero and cut the population oflow-income private renter income units in housing stress by 371,200or 44 per cent. At the same time, it would generate an annual costsaving of $1.2 billion.• Because it would involve severing the existing link with other socialsecurity entitlements, constitutional barriers would need to beovercome to change the CRA eligibility rules to reflect housingneed. However, it is possible that this issue could be addressedwithin existing constitutional limitations

SHCA PHOSPHOTYROSINE DERIVED SIGNALING IS REQUIRED FOR THE MAINTENANCE OF CARDIAC FUNCTION

Background: ShcA, a scaffolding protein, generates signalspecificity by docking to activated tyrosine kinases through distinct phosphotyrosine recognition motifs, while mediating signal complexity through formation of diverse downstream phosphotyrosine complexes. Mammalian ShcA encodes 3 isoforms having a modular architecture of a PTB domain and SH2 domain, separated by a CH1 region containing tyrosine phosphorylation sites important in Ras-MAPK activation. Objective and Methods: ShcA has a necessary role in cardiovascular development^1,2. However, the role of ShcA in the adult myocardium is largely unknown, also unclear, is how ShcA uses its signaling modules to mediate downstream signaling. To this end, cre/loxP technology was employed to generate a conditional ShcA allele series. The myocardial specific ShcA KO (ShcA CKO) and myocardial restricted domain mutant KI mice were generated using cre expressed from the mlc2v locus^3 coupled with the ShcA floxed allele and in combination with the individual ShcA domain mutant KI alleles^2. Results: ShcACKO mice develop a dilated cardiomyopathy phenotype by 3 months of life, typified by depressed cardiac function and enlarged chamber dimensions. Isolated cardiomyocytes from ShcA CKO mice have preserved contractility indicating an uncoupling between global heart function and single myocyte contractile mechanics. Force-length experiments suggest that the loss of shcAmediates the uncoupling through deregulation of extracellular matrix interactions. Subsequent, analysis of the ShcA myocardial restricted domain mutant KImice suggests that ShcA requires PTB domain docking to upstream tyrosine kinases and subsequent phosphorylation of the CH1 tyrosines important for downstream signaling. Conclusion: ShcA is required for proper maintenance of cardiac function, possibly regulation of extracellular matrix interactions. References: 1. Lai KV, Pawson AJ. The ShcA phosphotyrosine docking protein sensitizescardiovascular signaling in the mouse embryo. Genes and Dev 2000;14:1132-45. 2. Hardy WR. et al. Combinatorial ShcA docking interactions supportdiversity in tissue morphogenesis. Science2007;317:251-6. 3.Minamisawa, s. et al. A post-transcriptional compensatory pathway inheterozygous ventricular myosin light chain 2-deficient mice results in lack ofgene dosage effect during normal cardiac growth or hypertrophy. J Biol Chem 1999;274:10066-70