Autosomal dominant STAT6 Gain of function causes severe atopy associated with lymphoma

The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator of Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified a novel heterozygous germline mutation STAT6 c.1255G > C, p.D419H leading to overactivity of IL-4 JAK/STAT signalling pathway, in a kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis and follicular lymphoma. STAT6 D419H expression and functional activity were compared with wild type STAT6 in transduced HEK293T cells and to healthy control primary skin fibroblasts and peripheral blood mononuclear cells (PBMC). We observed consistently higher STAT6 levels at baseline and higher STAT6 and phosphorylated STAT6 following IL-4 stimulation in D419H cell lines and primary cells compared to wild type controls. The pSTAT6/STAT6 ratios were unchanged between D419H and control cells suggesting that elevated pSTAT6 levels resulted from higher total basal STAT6 expression. The selective JAK1/JAK2 inhibitor ruxolitinib reduced pSTAT6 levels in D419H HEK293T cells and patient PBMC. Nuclear staining demonstrated increased STAT6 in patient fibroblasts at baseline and both STAT6 and pSTAT6 after IL-4 stimulation. We also observed higher transcriptional upregulation of downstream genes (XBP1 and EPAS1) in patient PBMC. Our study confirms STAT6 gain of function (GOF) as a novel monogenetic cause of early onset atopic disease. The clinical association of lymphoma in our kindred, along with previous data linking somatic STAT6 D419H mutations to follicular lymphoma suggest that patients with STAT6 GOF disease may be at higher risk of lymphomagenesis

Exploring Knowledge Management and Knowledge Sharing in a Non-Profit Human Service Organisation

Non-profit, human service organisations are continuing to struggle for limited money and are being held accountable more than ever before to prove an increase in quality and efficacy of services. Agency administrators have to think creatively in order to help their agencies stand out. Efforts include tapping not only into the knowledge of their employees but also knowledge of their consumers. Utilising qualitative methods, with a highly successful non-profit agency, this document investigates the information sharing activities and the knowledge gained from consumers when knowledge transfer backflow was allowed. Shared are findings on how public service agencies, often dealing with those individuals in need, can use knowledge management processes to inform and improve future service delivery. The thick descriptions provided in this document give context to the multi-layered knowledge dimensions involved. Highlighted is the importance of the embedded knowledge their participants come in with and the need for agencies to consider the intricacies of this knowledge. Noticeably, this study also delineates how the historical and current oppression experienced contributes to this complexity. The data reported in this study is the first step in understanding the individual and organisation factors contributing to the collaboration efforts of non-profit agencies.Non-profit organisations, human service organisations, knowledge management, knowledge sharing, organisational culture

Bridging Two Worlds: Using Knowledge Management Theory to Understand the Merging of Two Non-Profit Organisations

In today's economic climate, knowledge management is very important to the non-profit sector as these organisations experience the effects of a global recession. Financial instability may lead to downsising that creates a loss of important information. For non-profit organisations, a creative solution to the financial crisis has been re-structuring through multi-agency collaborations and mergers. These restructuring processes are complex and disruptive, making effective knowledge management processes even more important for organisational success. This study employs a qualitative interview design to explore the merger of two non-profit cancer support agencies through the lens of knowledge management theory. Participants of the original agencies shared their views of previous knowledge processes, how the processes changed as a result of the merger and strategies used by the newly formed agency to address merger complexities. Results reflect that one of the original organisations began as a non-profit medical provider with formal culture and communication patterns; the other a grass-roots social service agency with informal structure and communication patterns. These differences contributed to differing views about how the merger was implemented and perceived by various employees and board members. Knowledge gains were generally explicit knowledge processes while knowledge losses were implicit processes. Some important strategies and lessons learned included the need for good documentation of all work processes, an external facilitator, and the need for transparency and collaboration between all constituents.Non-profit, knowledge management, mergers, lessons learned, merger strategies

Parent-Child Communication Related to Sexual Health: The Contextual Experiences of Rural Latino Parents and Youth

Understanding how parent-child communication occurs within the cultural context is an important consideration in sexual health given that culture plays a major role in the development of various beliefs and attitudes. This qualitative study explores the perceived experiences of first-generation, immigrant rural Latino parents and youths (N = 19) about parent-child communication related to sexual health. Specifically, the article explores their perceptions on (a) the process of such communication when and if it occurs; (b) the content of such discussions when they occur; and (c) whether the content of these discussions is based on gender or familial context. Results suggest that cultural norms are followed in regards to gender of both the parent and the youth, but often going against religious and father’s expectations, with the mothers discussing birth control facts in greater frequency. We discuss implications for Latino teen pregnancy prevention efforts

Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)

An amendment to this paper has been published and can be accessed via a link at the top of the paper