TaikOz – Performing Australian Taiko

TaikOz have for twenty years pioneered taiko and shakuhachi music in Australia to international acclaim. Taiko, the Japanese word for drum, is also the name of a multifaceted collection of Japanese-looking drumming cultures popular worldwide since the 1960s. As taiko players bolster the legitimacy of their activities with tangential histories of older, even imagined, Japanese art forms, Australian musicians TaikOz spend considerable effort trying to match their practice to this discourse while also challenging its validity. Stuck fitting in as outsiders, TaikOz head taiko proficiency globally and collaborate with the pioneers of the staged genre. By assessing several TaikOz compositions and collaborative projects, and through compilation of all print media mentions of TaikOz, this thesis demonstrates that the stories told about taiko and TaikOz are skewed. Through interviews and fieldwork, TaikOz revealed the ways they work, but how their processes are often unrecognised or misinterpreted. This thesis investigates where communicative errors are occurring and promotes that using a template of performativity might yield more honest renderings of this inter-cultural artistic exercise into text

Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations.

Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85α/p55α/p50α subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis. In 3 of these 4, plasma adiponectin was preserved, as in insulin receptor dysfunction. The fourth patient and her healthy mother had low plasma adiponectin associated with a potentially novel mutation, p.Asp231Ala, in adiponectin itself. Cells studied from one patient with the p.Tyr657X PIK3R1 mutation expressed abundant truncated PIK3R1 products and showed severely reduced insulin-stimulated association of mutant but not WT p85α with IRS1, but normal downstream signaling. In 3T3-L1 preadipocytes, mutant p85α overexpression attenuated insulin-induced AKT phosphorylation and adipocyte differentiation. Thus, PIK3R1 C-terminal mutations impair insulin signaling only in some cellular contexts and produce a subphenotype of insulin resistance resembling INSR dysfunction but unlike AKT2 dysfunction, implicating PI3K in the pathogenesis of key components of the metabolic syndrome.IHD was supported by the Raymond and Beverly Sackler Foundation via the University of Cambridge MB/PhD programme; RKS, IB, DBS, and SO were supported by the Wellcome Trust (grants WT098498, WT098051, WT107064, and WT095515, respectively and Strategic Award 100574/Z/12/Z), the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/5), and the United Kingdom National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The work was also supported by the Innovative Medicines Initiative Joint Undertaking under European Medical Information Framework (EMIF) grant agreement number 115372. UK10K was funded by the Wellcome Trust under award WT091310.This is the final version of the article. It first appeared from the American Society for Clinical Investigation via https://doi.org/10.1172/jci.insight.8876

Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study.

Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10(-6) > P > 5 × 10(-8)). The most strongly associated SNP (rs111513399, P = 5.38 × 10(-7)) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling

Elevated Humidity Impairs Evaporative Heat Loss and Self-Paced Exercise Performance in the Heat

This study investigated the effects of absolute humidity on heat dissipation and subsequent thermal, cardiovascular, and performance responses during self-paced exercise in the heat. Twelve trained male cyclists performed a 700-kJ time trial in four different humidity conditions (Low: 1.6 kPa, Moderate: 2.5 kPa, High: 3.5 kPa, and Very high: 4.5 kPa) in 33°C. The gradient in partial water vapor pressure at the saturated skin surface and in air, which determines sweat evaporation, decreased significantly with increasing humidity (Low: 3.53 ± 0.30 kPa, Moderate: 2.74 ± 0.24 kPa, High: 1.99 ± 0.20 kPa, Very high: 1.19 ± 0.16 kPa; p &lt; 0.001). The maximum evaporative capacity of the environment (E max) also decreased with greater humidity (Low: 309 ± 26 W m -2, Moderate: 240 ± 21 W m -2, High: 175 ± 18 W m -2, Very high: 104 ± 14 W m -2; p &lt; 0.001), as did sweating efficiency (S eff) (Low: 0.50 ± 0.13, Moderate: 0.39 ± 0.10, High: 0.28 ± 0.09, Very high: 0.16 ± 0.04; p ≤ 0.003). Power output was similar between Low (260 ± 33 W) and Moderate humidity (257 ± 27 W; p = 0.999), but lower in Very high (222 ± 37 W) than in all other conditions (p &lt; 0.001) and lower in High (246 ± 31 W) than in the Low and Moderate humidity (p &lt; 0.001). Peak core temperature was higher in Very high (39.49°C ± 0.56°C) than in Low (38.97°C ± 0.44°C; p &lt; 0.001), Moderate (39.04°C ± 0.39°C; p = 0.002) and High humidity (39.12°C ± 0.47°C; p = 0.010). Mean skin temperature was higher with elevated humidity (p &lt; 0.001) and mean heart rate was not significantly different between conditions (p ≥ 0.056). These data indicate that reductions in evaporative potential and efficiency with elevated humidity exacerbate thermal and cardiovascular strain during self-paced cycling in the heat, resulting in marked performance impairments. </p

'We're kind of like genetic nomads' : parents' experiences of biographical disruption and uncertainty following in/conclusive results from newborn cystic fibrosis screening

As whole genome sequencing is being considered as a tool to deliver expanded newborn screening (NBS) globally, the range of equivocal results it could produce are gaining increased attention. For cystic fibrosis (CF) screening, the use of next generation sequencing within existing UK NBS programmes would increase the number of uncertain designations returned within results, including that of Cystic Fibrosis Screen Positive Inconclusive Diagnosis (CFSPID). However, the experiences of families already living with this designation have been under-explored. This study uses in-depth interviews to explore the perspectives of sixteen parents who received positive results from CF NBS, with varying degrees of prognostic un/certainty; parents with a child diagnosed with CF (n = 6), CF carrier status (n = 3) and those with the CFSPID designation (n = 7). The biographically disruptive nature of positive NBS results-regardless of immediate relevance to the child-dominated early experiences of positive results across all groups. For those with CF, biographical reparation involved becoming ‘a CF family’, underscoring biological kinship bonds and reinforcing familial identity. For those with uncertain results, biographical re-calibration was more complex. Diagnostic and prognostic uncertainty posed a barrier to entry for both the ‘CF world’ and the ‘healthy kid’ world, leading parents to attempt to minimise its role, either through rejection, or re-interpretation of their child's result. Other parents, however, experienced biographical reparation more dynamically. The concept of ‘genetic nomadism’ captures accounts of oscillation between the two worlds; movements that were responsive to evolving health experiences, as well as social, environmental and temporal factors. Through the concept of genetic nomadism, this paper delineates both the productive, as well as divisive, nature of uncertainty for biographical reparation in the aftermath of NBS, as well as the strategies parents use to harness it, in order to successfully navigate the world with a child with an ambiguous genetic future

Impairment experiences, identity and attitudes towards genetic screening : the views of people with Spinal Muscular Atrophy

Developments in genetics are rapidly changing the capacity and scope of screening practices. However, people with genetic conditions have been under-represented in the literature exploring their implications. This mixed methods study explores the attitudes of people with Spinal Muscular Atrophy (SMA) towards three different population-level genetic screening programmes for SMA: pre-conception, prenatal and newborn. Drawing on qualitative interviews (n= 15) and a survey (n=82), this study demonstrates that more severely affected individuals with early-onset symptoms (Type II SMA), are less likely to support screening and more likely to view SMA positively than those with milder, later onset and/or fluctuating symptoms (Types III/ IV SMA). Indeed, this clinically milder group were more likely to support all forms of screening and view SMA negatively. This paper highlights that screening is a complex issue for people with genetic conditions, and the nature of impairment experiences plays a critical role in shaping attitudes

Expanding the notion of ‘benefit’ : comparing public, parent, and professional attitudes towards whole genome sequencing in newborns

Whole genome sequencing (WGS) is being considered as a tool to deliver newborn screening (NBS) internationally. Its use would dramatically increase the number of genetic variants identified, presenting a host of ethical, social, and practical considerations. A scoping review was conducted to examine the acceptability of WGS-NBS among parents, the public, and health professionals. Parent/public groups were enthusiastic about WGS-NBS, holding panoramic views of current/future benefits, incorporating family and wider society. While actionable early-onset findings were prioritised, non-actionable and uncertain results were still viewed as empowering. Conversely, professionals preferred selective results disclosure, prioritised by clinical need. They emphasised the need for meaningful consent and protection of the child’s autonomy. All groups outlined the importance of properly considered implementation (e.g. resources, governance) to minimise harms and prevent a reduction in NBS participation. As genomic medicine integrates into healthcare, divergent conceptualisations of ‘harms’ and ‘benefits’ across social groups must be considered

What is a 'serious' genetic condition? The perceptions of people living with genetic conditions

Despite no consensus on the definition of ‘seriousness’, the concept is regularly used in policy and practice contexts to categorise conditions, determine access to genetic technologies and uses of selective pregnancy termination. Whilst attempts have been made to create taxonomies of genetic condition seriousness to inform clinical and policy decision-making, these have often relied on condition appraisals made by health and genetics professionals. The views of people with genetic conditions have been largely under-represented. This study explores the concept of seriousness through the perspectives of people with a range of ‘clinically serious’ conditions (fragile X conditions, spinal muscular atrophy, cystic fibrosis, haemophilia, thalassaemia). Attitudes towards suffering, quality of life (QoL) and selective pregnancy termination were elucidated from 45 in-depth qualitative interviews and 469 postal/online surveys. The majority of participants reported good health/wellbeing, and the capacity for good QoL, despite experiencing suffering with their condition. Notably, participants with later-onset conditions held more negative views of their health and QoL, and were more likely to view their condition as an illness, than those with early-onset conditions. These participants were more likely to see their condition as part of their identity. Whilst most participants supported prenatal screening, there was little support for selective termination. Moreover, social environment emerged as a critical mediator of the experience of the condition. The complex and rich insights of people living with genetic conditions might usefully be incorporated into future genetic taxonomies of ‘seriousness’ to ensure they more accurately reflect the lived reality of those with genetic conditions

Qualitative Remote Data Collection Guidance 2024

In 2020, the sudden onset of the COVID-19 pandemic forced qualitative health and social care researchers to rapidly convert to remote methods of data collection (i.e. methods of collecting research data when the researcher and participant are not together in the same space). In a post-COVID-19 research landscape, use of remote qualitative methods is now a choice not a necessity. This guidance was developed to support researchers who are making decisions between the use of remote or face-to-face methods. MethodsThe guidance was developed by a team of experienced health and social care researchers through two literature reviews (a scoping review and a realist review), interviews with 25 researchers and research participants and a consensus conference (attended by 27 research stakeholders) where the guidance was ratified. A diverse public reference group (PRG) with eight members informed all stages of the research process and guidance production. ConclusionsThe literature broadly demonstrates the equivalence of remotely collected qualitative data vis-à-vis face-toface, both in terms of data quality and data depth (Boardman et al, 2022). Additionally, the use of remote methods can make qualitative research less resource intensive, with reduced environmental harms (travel). It can also be more convenient for participants and researchers alike and can facilitate access to more diverse groups of geographically dispersed participants, increasing diversity and inclusivity in health and social care research. Care must be taken, however, to ensure that remote methods are not exclusionary and to explore, before data collection commences, which voices are silenced by their use. Identifying participants’ needs, typical communication channels, abilities and technology access in ways that take account of their socioeconomic and cultural backgrounds and local contexts are pivotal to this endeavour. Researchers should support participants to harness the autonomy that remote methods can bring, so that they may directly shape the research encounter/s to suit their circumstances and needs. However, it is important to note that this might include the decision to defer entirely to face-to-face methods, or to offer face-to-face as an adjunct method within a hybrid remote/face-to-face design. More information on the Team and the Project can be found on the Project Webpages

Parents’ and children's views of wider genomic testing when used as part of newborn screening to identify cystic fibrosis

Newborn bloodspot screening (NBS) is currently undergoing a ‘revolution’ (Spiekerkoetter et al., 2023). The development of new therapies (Vockley et al., 2023) and the piloting of whole genome sequencing in healthy newborns (e.g. Newborn Genomes Programme, UK, BabySeq USA) are challenging NBS practice and policy, as well as the Wilson &amp; Jungner criteria (Wilson &amp; Jungner, 1968) that underpin them (Andermann et al., 2008; Rahimzadeh et al., 2022; Vears et al., 2023). The capacity to screen for large numbers of variants simultaneously and generate data with potential relevance across the life course, and for family members beyond the screened infant, has prompted widespread discussion of the benefits (e.g., early identification and treatment of screened conditions) and harms (e.g., identification of variants of unknown clinical significance) that such high throughput screening programmes bring (Bick et al., 2022; Remec et al., 2021; Spiekerkoetter et al., 2023; Tluczek et al., 2022)