Search

Narrow-leafed lupin (NLL; Lupinus angustifolius) is a key rotational crop for sustainable farming systems, whose grain is high in protein content. It is a gluten-free, non-genetically modified, alternative protein source to soybean (Glycine max) and as such has gained interest as a human food ingredient. Here, we present a chromosome-length reference genome for the species and a pan-genome assembly comprising 55 NLL lines, including Australian and European cultivars, breeding lines and wild accessions. We present the core and variable genes for the species and report on the absence of essential mycorrhizal associated genes. The genome and pan-genomes of NLL and its close relative white lupin (Lupinus albus) are compared. Furthermore, we provide additional evidence supporting LaRAP2-7 as the key alkaloid regulatory gene for NLL and demonstrate the NLL genome is underrepresented in classical NLR disease resistance genes compared to other sequenced legume species. The NLL genomic resources generated here coupled with previously generated RNA sequencing datasets provide new opportunities to fast-track lupin crop improvement.

Genetic studies place Tbx5 at the apex of the sinoatrial node (SAN) transcriptional program. To understand its role in SAN differentiation, clonal embryonic stem (ES) cell lines were made that conditionally overexpress Tbx5, Tbx3, Tbx18, Shox2, Islet-1, and MAP3k7/TAK1. Cardiac cells differentiated using embryoid bodies (EBs). EBs overexpressing Tbx5, Islet1, and TAK1 beat faster than cardiac cells differentiated from control ES cell lines suggesting possible roles in SAN differentiation. Tbx5 overexpressing EBs showed increased expression of TAK1, but cardiomyocytes did not differentiate as SAN cells. EBs showed no change in the expression of the SAN transcription factors Shox2 and Islet1 and decreased expression of the SAN channel protein HCN4. EBs constitutively overexpressing TAK1 direct cardiac differentiation to the SAN fate but have reduced phosphorylation of its targets, p38 and Jnk. This opens the possibility that blocking the phosphorylation of TAK1 targets may have the same impact as forced overexpression. To test this, we treated EBs with 5z-7-Oxozeanol (OXO), an inhibitor of TAK1 phosphorylation. Like TAK1 overexpressing cardiac cells, cardiomyocytes differentiated in the presence of OXO beat faster and showed increased expression of SAN genes (Shox2, HCN4, and Islet1). This suggests that activation of the SAN transcriptional network can be accomplished by blocking the phosphorylation of TAK1.

Introduction Interleukin-6 (IL-6) and Interleukin-10 (IL-10) are members of the cytokine family demonstrating pro-inflammatory and anti-inflammatory properties respectively. Disruption in the balance of inflammation postoperatively leads to wound complications and cancer recurrence. Surgical adjuvants including 1,4,5-oxathiazinane-4,4-dioxide (OTD) can reduce inflammation while also demonstrating cytotoxic effects on cancer cells. Thus, we evaluated the effect of OTD on Human Dermal Fibroblasts (HDFs) and subsequent IL-6 and IL-10 levels. Methods Five concentrations of OTD were applied to HDF cells over time to assess migration and wound closure. Leica Las X software and a light microscope were used to obtain photographs at nine timepoints. After 30 hours cell media was removed and levels of IL-6 and IL-10 were measured. Migration and wound closure were assessed using percentage area of the wound gap, determined using ImageJ. Results OTD application demonstrated a dose-dependent arrest in fibroblast migration, greatest at 3-6 hours. This is represented by greater percentage area relative to control (15%Area – 6hrs) for concentrations 0.75mM (19%Area – 6hrs), 1mM (25%Area – 6hrs) and 1.25mM (30.5%Area - 6hrs). Percentage area was greater for 1mM and 1.25mM at 3hrs relative to 0hrs indicating gap widening, however for 0.75mM %Area was reduced. This correlated with IL-6 and IL-10 levels which were raised at 30hrs for 1mM and 1.25mM but not 0.75mM. Conclusion Lower concentrations of OTD do not demonstrate a negative effect on fibroblast migration, IL-6 and IL-10 levels despite previously demonstrated cytotoxic effects on cancer cells. Thus, OTD is a potential surgical adjuvant in cancer treatment.

Introduction Surgical-related immunity dysfunction in normal adjacent tumour (NAT) tissue of breast cancer (BC) patients is associated with BC recurrence. Characterising inflammation and immunosuppression in NAT tissue at the time of surgical excision of the tumour, using transcriptomics, may reveal a tissue phenotype more vulnerable to surgical-related immunity dysfunction. Methods RNA-Seq read counts from matched BC patient tumour and NAT tissues from the cancer genome atlas (TCGA) (n=54) and from University College Cork (UCC) & Cork University Hospital (CUH) biobank (n=10) were used. Differential gene expression was analysed using EdgeR and pathway analysis by Gene Set Enrichment Analysis using Hallmark gene sets. Immune cell subsets were deconvoluted using CIBERSORTx using the LM22 signature matrix. Genes were significantly different with a False Discovery Rate (FDR) Results Adipogenesis and IL6 JAK STAT3 signalling pathways were enriched in NAT and not in tumour tissue (FDR Conclusion Surgical-related immunity dysfunction in NAT breast tissue, may worsen postoperative immune-adipose-residual breast cancer cell interactions, contributing to poorer patient outcome.

Vouchers that reduce the cost of sport and active recreation participation have been shown to increase children’s and adolescent’s physical activity levels. Yet, the influence of government-led voucher programs on the capacity of sport and active recreation organisations is unclear. This qualitative study explored the experiences of stakeholders in the sport and recreation sector that were engaged in implementing the New South Wales (NSW) Government’s Active Kids voucher program in Australia. Semi-structured interviews were conducted with 29 sport and active recreation providers. Interview transcriptions were analysed by a multidisciplinary team using the Framework method. Overall, participants reported that the Active Kids voucher program was an acceptable intervention to address the cost barrier to participation for children and adolescents. Three main steps influenced the capacity of organisations to deliver their sport and recreation programs and the voucher program: (1) Implementation priming—alignment of the intervention aims with stakeholder priorities and early information sharing, (2) Administrative ease—enhanced technology use and establishment of simple procedures, and (3) Innovation impacts—enablement of staff and volunteers to address barriers to participation for their participants. Future voucher programs should include strategies to enhance the capacity of sport and active recreation organisations to meet program guidelines and increase innovation.

Introduction Physical activity can improve academic performance; however, much less is known about the specific association between sport participation and academic performance, and this evidence has not been synthesized. Our aim was to systematically review and combine via meta-analyses evidence of the association between sport participation and academic performance in children and adolescents. Methods We conducted searches of five electronic databases using sport and academic performance related terms. We combined evidence from eligible studies using a structural equation modeling approach to multilevel meta-analysis. Results From 115 eligible studies, most of which had a high risk of bias (k = 87), we meta-analyzed 298 effect sizes. Overall, sport participation had a small positive effect on academic performance (d = 0.26, 95% confidence interval = 0.09, 0.42). Moderator analyses indicated that sports participation was most beneficial for academic performance when it was at a moderate dose (i.e., 1–2 h·wk−1), compared with no sport or a high dose of sport (3+ h·wk−1). Conclusions Sports participation during school hours was more beneficial for academic performance compared with sport participation outside school hours. Based on mostly low-quality studies, we found some evidence that sport could positively affect academic performance in children and adolescents. It appears that sport participation of a moderate dose and at school could be used to promote academic performance. However, if this field were to inform policy, high-quality studies are needed that provide insight into the effect of dose and sport characteristics on academic performance.

Introduction The COVID-19 pandemic has greatly impacted healthcare service delivery. This study explored patient experiences of hospital care during the COVID-19 pandemic in Ireland, using National Inpatient Experience Survey (NIES) 2021 data. Methods NIES is a repeat cross-sectional survey of inpatient experiences in all public acute hospitals in Ireland. Patients who spent 24+ hours in hospital and were discharged in September 2021 were eligible to participate. 7 questions addressed experiences specific to the pandemic. Comparisons between 2019 and 2021 were conducted using t-tests. Effect sizes (d) are reported. Qualitative data were thematically analysed. Results 10,743 patients participated (42% response rate). While 68% did not feel at risk of catching COVID-19, 9% felt at risk. 35% reported that staff always helped them to keep in touch with family. There were small, statistically significant differences between 2019 and 2021 ratings, with questions on opportunity for family to talk to a doctor (d=-.328), provision of information to family (d=-.136), and being able to find staff to talk to about worries and fears (d=-.167) recording the biggest decreases. Scores for cleanliness of wards (d = 0.063) and bathrooms (d=.075), and privacy during examination or treatment in the ED (d = 0.085) improved significantly. Patients commented on their appreciation of staff, but missed having visitors, with restrictions posing challenges for those with sensory or physical impairments. Conclusions Given the unique challenges experienced by acute healthcare services during the COVID-19 pandemic, comparisons with pre-pandemic patient experiences should be interpreted with caution. Continuing to gather patient feedback during a pandemic presents a unique opportunity to understand the resilience of healthcare systems as they continue to operate under unprecedented pressure, with the potential to inform responses and delivery of care during future pandemics or other emergencies. Key messages • Visiting restrictions posed many challenges for patients and affected communication both between patients and their family members, as well as between healthcare staff and patients’ family. • Gathering patient feedback during a pandemic presents a unique opportunity to inform responses and delivery of care during future pandemics or other emergencies.

Background Throughout the ecosystem of sport, women have been and continue to be underrepresented at all levels compared to men. The capacity of community-level sport is heavily reliant on the many non-player roles including governance, as well as administration, coaching and officiating. Recently there has been increased attention to improving the gender balance in sport. The aim of this study is to investigate the proportions of women engaged in non-playing roles in sport (2016–2018). Methods This study involved secondary analysis of the AusPlay survey, a national population survey, funded by Sport Australia. This study utilised data from people aged 15-years or older about their involvement in non-playing roles in sport, and their demographic data. Survey respondents were asked “During the last 12 months, have you been involved with any sports in a nonplaying role, such as official, coach, referee, administrator, etc?” Analysis of non-player role responses focussed specifically on the top four non-player role categories; coach, official, administrator and manager. Frequency analysis concentrated on the distribution of men and women involvement in a non-player capacity for the three years, with detailed analysis of the most recent year (2018). Results In this study of 61,578 Australians there was a higher proportion of men in non-player roles in sport compared to women, across each of the three years (2018: men 55 %, women 46 %). Involvement of women in coaching increased significantly from 38 % to 2016 to 44 % in 2018 (p p Conclusions Aligned with strategic policy and investment strategies, there are gradual increased representation of women in non-playing sport, coaching roles. Women are still underrepresented in terms of coaches, officials and administrators, but are more likely to be managers. It is recommended that there is continued mentoring, identification and emphasising of female role models, and further strategies to increase female presence in non-playing roles. We recommend that future research, in line with appropriate gender and cultural-change theories, investigates and discusses the progress of gender equality throughout playing and non-playing role in sport.

Introduction The Active Kids voucher is a universal, state-wide voucher program, provided by the New South Wales (NSW) Government, Office of Sport. All school-aged children in NSW are eligible to receive a voucher to reduce registration costs of structured physical activity programs. This study explores reasons behind lower uptake among children who are overweight or obese, from cultural and linguistically diverse families and those living in low socio-economic areas. Methods Participants were recruited through a convenience sample of parent/carers who participated in the NSW Health Go4Fun program. Qualitative data was collected using focus groups. The Framework method was adapted for the analysis, taking an interpretive phenomenological approach. Results Study participants (n= 54) were all parents of children who were overweight or obese from both low and high socio-economic status (SES). Most reported speaking a primary language other than English at home (65%). Parents were mostly aware of the Active Kids program (91%) and reported that the voucher had a positive impact on their children's participation in structured physical activity. A range of socio-ecological factors, in addition to activity cost, influenced whether parents were able to use an Active Kids voucher and participate in structured physical activity. Conclusions The Active Kids voucher does not alleviate all barriers, particularly for families living in low socioeconomic areas. Engagement of this population in structured physical activities using the Active Kids vouchers could be strengthened through the implementation of effective interventions which comprehensively address the remaining barriers, such as access and flexibility of programs with local stakeholders and activity providers.

Aim Urodynamic assessment is an invasive outpatient diagnostic modality that is performed in most urological centres. What is the patient experience of our service, in regard to levels of anxiety, embarrassment and overall satisfaction? Method Patients undergoing urodynamic investigation, between August and November 2021, were asked to complete a questionnaire, with a visual analogue scale (VAS), where 1 was ‘not at all’, 2 ‘a little’, 3 ‘moderate’, 4 ‘a lot’ and 5 ‘extremely’. Levels of anxiety (pre- and peri-procedure), embarrassment, pain and overall satisfaction were assessed. Basic patient demographic data were obtained, in addition to the type of lower urinary tract symptoms (LUTS) under investigation. Results Questionnaires from 26 patients were obtained. The majority were male (80.8%) with a myriad of symptoms: 30.8% storage, 23% voiding and 46.2% mixed LUTS. The mean overall satisfaction, via the VAS, was 4.35. Anxiety was 3.38 pre-procedure, and 2.23 peri-procedure. Both pain and embarrassment scores were 1.81 and 2.08 respectively. All patients received a urodynamics information leaflet prior to their appointment. Furthermore, all patients would have been willing to undergo the procedure again in the future, if necessary, and recommended the unit to a friend or colleague. Conclusions On review of our local urodynamics service overall patient satisfaction is excellent, with low levels of peri-procedural anxiety, pain and embarrassment. Prior to their appointment, patients are understandably anxious and additional adjuncts to mitigate this, such as an informative telephone call in advance or urodynamics information video, are currently being explored.

National strategies are needed to continue to promote the broader benefits of participating in sport and organised physical activity to reduce physical inactivity and related disease burden. This paper employs the RE-AIM framework to evaluate the impact of the federally funded $150 million Move it AUS program in engaging inactive people in sport and physical activity through the Participation (all ages) and Better Ageing (over 65 years) funding streams. A pragmatic, mixed-methods evaluation was conducted to understand the impact of the grant on both the participants, and the funded organisations. This included participant surveys, case studies, and qualitative interviews with funded program leaders. A total of 75% of participants in the Participation stream, and 65% in the Better Ageing stream, were classified as inactive. The largest changes in overall physical activity behaviour were seen among socioeconomically disadvantaged participants and culturally and linguistically diverse participants. Seven key insights were gained from the qualitative interviews: Clarity of who, Partnerships, Communication, Program delivery, Environmental impacts, Governance, and that Physical inactivity must be a priority. The Move It AUS program successfully engaged physically inactive participants. Additional work is needed to better engage inactive people that identify as culturally and linguistically diverse, Aboriginal and/or Torres Strait Islander and those that live in disadvantaged communities in sport and physical activities. Tangible actions from the seven key insights should be adopted into workforce capability planning for the sport sector to effectively engage physically inactive communities.

Here, we review the management of peripheral T-cell lymphoma, particularly focusing on the role of autologous and allogeneic stem cell transplant.Peripheral T-cell lymphomas are a rare subset of non-Hodgkin's lymphomas that are treated with curative intent. While therapy has been based on other aggressive lymphoid malignancies, outcomes are generally poorer than B-cell lymphomas with 5-year overall and progression-free survival of 30-40% and 20-30%, respectively. In effort to improve outcomes, transplant has been used in both the frontline and salvage settings. Although not studied in randomized studies, consolidation with autologous stem cell transplant in first remission has been associated with an approximate 5-year overall survival of 50-60% and 5-year progression-free survival of 40-45%. Unfortunately, most patients relapse, and, in this setting, allogeneic transplant remains the only curative option for those who are transplant-eligible. Multiple series have now shown that 3-year overall survival with allogeneic transplant is approximately 60%. However, outcomes with transplant are associated with disease control at the time of transplant. In contrast to B-cell malignancies, treatment decisions for peripheral T-cell lymphomas are supported mostly by phase II studies, retrospective series, and expert opinion. For patients with peripheral T-cell lymphoma able to achieve sufficient disease control, autologous stem cell transplantation in first remission and allogeneic stem cell transplantation in relapsed disease offer modest benefit over chemotherapy alone.

Background There is an urgent need for scaled-up effective interventions which overcome barriers to health-enhancing physical activity for children and adolescents. In New South Wales (NSW), Australia, the state government implemented a universal voucher program, ‘Active Kids’ to support the cost of structured physical activity registration for school-enrolled children aged 4.5–18 years old. The objective of this study was to understand the effects a financial incentive intervention delivered in a real-world setting has on children and adolescent’s physical activity participation. Method In 2018, all children and adolescents registered for an Active Kids voucher provided sociodemographic characteristics, physical activity and research consent. This prospective cohort study used an online survey with validated items to measure physical activity and other personal and social factors in children and adolescents who used an Active Kids voucher. Generalized linear mixed models were used to examine changes from registration to after voucher use at ≤8 weeks, 9–26 weeks and ≥ 6 months. Results Study participants reported increasing their days achieving physical activity guidelines from 4.0 days per week (95%CI 3.8, 4.2) at registration (n = 37,626 children) to 4.9 days per week (95%CI 4.7, 5.1) after 6 months (n = 14,118 children). Increased physical activity was observed for all sociodemographic population groups. The voucher-specific activity contributed 42.4% (95%CI 39.3, 45.5) to the total time children participated in structured physical activities outside of school. Children and adolescents who increased to, or maintained, high levels of activity were socially supported to be active, had active parent/caregivers, had better concentration and were overall happier than their low-active counterparts. Conclusion The Active Kids program significantly increased children’s physical activity levels and these increases continued over a six-month period. The Active Kids voucher program shows promise as a scaled-up intervention to increase children and adolescents’ physical activity participation. Trial registration Australian New Zealand Clinical Trial Registry ACTRN12618000897268, approved May 29th, 2018 - Retrospectively registered.

A central hypothesis in research on executive function is that controlled information processing is costly and is allocated according to the behavioral benefits it brings. However, while computational theories predict that the benefits of new information depend on prior uncertainty, the cellular effects of uncertainty on the executive network are incompletely understood. Using simultaneous recordings in monkeys, we describe several mechanisms by which the fronto-parietal network reacts to uncertainty. We show that the variance of expected rewards, independently of the value of the rewards, was encoded in single neuron and population spiking activity and local field potential (LFP) oscillations, and, importantly, asymmetrically affected fronto-parietal information transmission (measured through the coherence between spikes and LFPs). Higher uncertainty selectively enhanced information transmission from the parietal to the frontal lobe and suppressed it in the opposite direction, consistent with Bayesian principles that prioritize sensory information according to a decision maker’s prior uncertainty., Bahareh Taghizadeh and Nicholas Foley et al. show that individual neuronal responses, population spiking activity, and local field potential oscillations encode the variance of expected rewards independent of their value. They also demonstrate that reward uncertainty asymmetrically affects neuronal transmission within the monkey fronto-parietal network.

Purpose. This study investigated the effect of different sit–stand workstations on lumbar spine kinematics, lumbar muscle activity and musculoskeletal pain. Methods. Thirty-two office workers were ...

Objectives In 2018, the New South Wales (NSW) Government implemented a State-wide program to reduce the cost barrier to organised sport and physical activity participation. We explored parent/carer’s awareness and children’s engagement in the Active Kids program across socioeconomic groups and used the NSW Population Health Survey (PHS) to validate engagement in the program. Design Cross-sectional. Methods Data were obtained from the 2018 NSW PHS and the Active Kids program registration database. We compared demographic characteristics of children who had registered for the program in the registration database with children in the weighted NSW PHS. Multinomial regression models were used to determine whether socioeconomic status was associated with parent/carer awareness and children’s engagement in the program. Results Parent/carer’s in the most disadvantaged quartile were twice as likely to have never heard of the Active Kids program (OR: 2.04, 95% CIs 1.31, 3.16) or to have heard or the program but not registered (OR: 1.94, 95% CIs 1.26, 3.00), and more than twice as likely to have registered for a voucher, but not followed through and redeemed the voucher (OR: 2.68, 95% CIs 1.27, 5.63) compared with the least disadvantaged quartile. Conclusions The Active Kids program has provided financial support for organised sport and physical activity to a large number of children. However, there are still a substantial proportion of socially disadvantaged groups who are unaware or have not engaged in the program. Further targeted work is required to increase the awareness and engagement in the program for socially disadvantaged groups.

Significance Deposition of some aggregated and misfolded polypeptides (amyloids) is the hallmark of many degenerative diseases. Amyloid assembly is slow, unfavorable, and still poorly understood. Here, we show that liquid–liquid demixing (like oil forming droplets in water) of type II diabetes IAPP amyloid precursors is not dependent on the human amyloidogenic sequence and leads to the formation of a water-filled gel within phase-separated droplets. Both processes then trigger pathological aggregation at the droplet surface, which is modulated by insulin. This localized aggregation propagates to interconnect droplets, leading to a macroscopic meshwork formation with increased local viscosity, eventually percolating the whole system. These processes may be at the heart of the pathology of type II diabetes., Amyloidoses (misfolded polypeptide accumulation) are among the most debilitating diseases our aging societies face. Amyloidogenesis can be catalyzed by hydrophobic–hydrophilic interfaces (e.g., air–water interface in vitro [AWI]). We recently demonstrated hydrogelation of the amyloidogenic type II diabetes-associated islet amyloid polypeptide (IAPP), a hydrophobic–hydrophilic interface-dependent process with complex kinetics. We demonstrate that human IAPP undergoes AWI-catalyzed liquid–liquid phase separation (LLPS), which initiates hydrogelation and aggregation. Insulin modulates these processes but does not prevent them. Using nonamyloidogenic rat IAPP, we show that, whereas LLPS does not require the amyloidogenic sequence, hydrogelation and aggregation do. Interestingly, both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology. By developing an experimental setup and analysis tools, we show that, within the whole system (beyond the droplet stage), macroscopic interconnected aggregate clusters form, grow, fuse, and evolve via internal rearrangement, leading to overall hydrogelation. As the AWI-adsorbed gelled layer matures, its microviscosity increases. LLPS-driven aggregation may be a common amyloid feature and integral to pathology.

National strategies are needed to continue to promote the broader benefits of participating in sport and organised physical activity to reduce physical inactivity and related disease burden. This paper employs the RE-AIM framework to evaluate the impact of the federally funded $150 million Move it AUS program in engaging inactive people in sport and physical activity through the Participation (all ages) and Better Ageing (over 65 years) funding streams. A pragmatic, mixed-methods evaluation was conducted to understand the impact of the grant on both the participants, and the funded organisations. This included participant surveys, case studies, and qualitative interviews with funded program leaders. A total of 75% of participants in the Participation stream, and 65% in the Better Ageing stream, were classified as inactive. The largest changes in overall physical activity behaviour were seen among socioeconomically disadvantaged participants and culturally and linguistically diverse participants. Seven key insights were gained from the qualitative interviews: Clarity of who, Partnerships, Communication, Program delivery, Environmental impacts, Governance, and that Physical inactivity must be a priority. The Move It AUS program successfully engaged physically inactive participants. Additional work is needed to better engage inactive people that identify as culturally and linguistically diverse, Aboriginal and/or Torres Strait Islander and those that live in disadvantaged communities in sport and physical activities. Tangible actions from the seven key insights should be adopted into workforce capability planning for the sport sector to effectively engage physically inactive communities.