Indirect costs in the Australian for-purpose sector: Paying what it takes for Australian for-purpose organisations to create long-term impact

Indirect costs (or overhead) are a fraught topic in the not-for-profit world. Many people across philanthropy, government, the public and the media all expect them to be minimised, or not to pay for them at all. Yet they are essential to running a functioning, effective organisation. In the context of a struggling NFP sector, this is a crucial issue to ensure the long-term effectiveness of Australia’s charities. US research has shown that one of the key drivers of NFP vulnerability is insufficient funding of charity indirect costs. This is called the “non-profit starvation cycle”, in which funders having inaccurate expectations of how much overhead is needed to run a not-for-profit means that charities under report their costs to funders. This leads to a sector starved of the necessary core funding required to create resilient charities delivering long-term impact on complex social issues

Field-based high-throughput plant phenotyping reveals the temporal patterns of quantitative trait loci associated with stress-responsive traits in cotton

The application of high-throughput plant phenotyping (HTPP) to continuously study plant populations under relevant growing conditions creates the possibility to more efficiently dissect the genetic basis of dynamic adaptive traits. Towards this end, we employed a field-based HTPP system that deployed sets of sensors to simultaneously measure canopy temperature, reflectance, and height on a cotton (Gossypium hirsutum L.) recombinant inbred line mapping population. The evaluation trials were conducted under well-watered and water-limited conditions in a replicated field experiment at a hot, arid location in central Arizona, with trait measurements taken at different times on multiple days across three years. Canopy temperature, normalized difference vegetation index (NDVI), height, and leaf area index (LAI) displayed moderate to high broad-sense heritabilities as well as varied interactions among genotypes with water regime and time of day. Distinct temporal patterns of quantitative trait loci (QTL) expression were mostly observed for the more dynamic HTPP canopy traits, canopy temperature and NDVI, and varied across plant developmental stages. In addition, the strength of correlation between HTPP canopy and agronomic traits such as lint yield displayed a time-dependent relationship. We also found that the position of some QTL controlling HTPP canopy traits were shared with agronomic and physiological traits. This work demonstrates the novel use of a field-based, HTPP system to study the genetic basis of stress-adaptive traits in cotton, and these results have the potential to facilitate the development of stress-resilient cotton cultivars

The DEHVILS Survey Overview and Initial Data Release: High-Quality Near-Infrared Type Ia Supernova Light Curves at Low Redshift

While the sample of optical Type Ia Supernova (SN Ia) light curves (LCs) usable for cosmological parameter measurements surpasses 2000, the sample of published, cosmologically viable near-infrared (NIR) SN Ia LCs, which have been shown to be good "standard candles," is still $\lesssim$ 200. Here, we present high-quality NIR LCs for 83 SNe Ia ranging from $0.002 < z < 0.09$ as a part of the Dark Energy, H$_0$, and peculiar Velocities using Infrared Light from Supernovae (DEHVILS) survey. Observations are taken using UKIRT's WFCAM, where the median depth of the images is 20.7, 20.1, and 19.3 mag (Vega) for $Y$, $J$, and $H$-bands, respectively. The median number of epochs per SN Ia is 18 for all three bands ($YJH$) combined and 6 for each band individually. We fit 47 SN Ia LCs that pass strict quality cuts using three LC models, SALT3, SNooPy, and BayeSN and find scatter on the Hubble diagram to be comparable to or better than scatter from optical-only fits in the literature. Fitting NIR-only LCs, we obtain standard deviations ranging from 0.128-0.135 mag. Additionally, we present a refined calibration method for transforming 2MASS magnitudes to WFCAM magnitudes using HST CALSPEC stars that results in a 0.03 mag shift in the WFCAM $Y$-band magnitudes.Comment: 24 pages, 9 figures. Accepted by MNRA

SN 2021hpr and its two siblings in the Cepheid calibrator galaxy NGC 3147: A hierarchical BayeSN analysis of a Type Ia supernova trio, and a Hubble constant constraint

To improve Type Ia supernova (SN Ia) standardisability, the consistency of distance estimates to siblings -- SNe in the same host galaxy -- should be investigated. We present Young Supernova Experiment Pan-STARRS-1 $grizy$ photometry of SN 2021hpr, the third spectroscopically confirmed SN Ia in the high-stellar-mass Cepheid-calibrator galaxy NGC 3147. We analyse NGC 3147's trio of SN Ia siblings: SNe 1997bq, 2008fv and 2021hpr, using a new version of the BayeSN model of SN Ia spectral-energy distributions, retrained simultaneously using optical-NIR $BgVrizYJH$ (0.35--1.8 $\mu$m) data. The distance estimates to each sibling are consistent, with a sample standard deviation $\lesssim$0.01 mag, much smaller than the total intrinsic scatter in the training sample: $\sigma_0\approx0.09$ mag. Fitting normal SN Ia siblings in three additional galaxies, we estimate a $\approx$90% probability that the siblings' intrinsic scatter is smaller than $\sigma_0$. We build a new hierarchical model that fits light curves of siblings in a single galaxy simultaneously; this yields more precise estimates of the common distance and the dust parameters. Fitting the trio for a common dust law shape yields $R_V=2.69\pm0.52$. Our work motivates future hierarchical modelling of more siblings, to tightly constrain their intrinsic scatter, and better understand SN-host correlations. Finally, we estimate the Hubble constant, using a Cepheid distance to NGC 3147, the siblings trio, and 109 Hubble flow ($0.01 < z_{\rm{CMB}} < 0.08$) SNe Ia; marginalising over the siblings' and population's intrinsic scatters, and the peculiar velocity dispersion, yields $H_0=77.9\pm6.5 \text{ km s}^{-1}\text{Mpc}^{-1}$.Comment: Submitted to MNRAS; 30 pages, 22 figure

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Evaluation of sit-stand workstations in an office setting: A randomised controlled trial

Background: Excessive sitting time is a risk factor for cardiovascular disease mortality and morbidity independent of physical activity. This aim of this study was to evaluate the impact of a sit-stand workstation on sitting time, and vascular, metabolic and musculoskeletal outcomes in office workers, and to investigate workstation acceptability and feasibility. Methods: A two-arm, parallel-group, individually randomised controlled trial was conducted in one organisation. Participants were asymptomatic full-time office workers aged ≥18 years. Each participant in the intervention arm had a sit-stand workstation installed on their workplace desk for 8 weeks. Participants in the control arm received no intervention. The primary outcome was workplace sitting time, assessed at 0, 4 and 8 weeks by an ecological momentary assessment diary. Secondary behavioural, cardiometabolic and musculoskeletal outcomes were assessed. Acceptability and feasibility were assessed via questionnaire and interview. ANCOVA and magnitude-based inferences examined intervention effects relative to controls at 4 and 8 weeks. Participants and researchers were not blind to group allocation. Results: Forty-seven participants were randomised (intervention n = 26; control n = 21). Relative to the control group at 8 weeks, the intervention group had a beneficial decrease in sitting time (-80.2 min/8-h workday (95 % CI = -129.0, -31.4); p = 0.002), increase in standing time (72.9 min/8-h workday (21.2, 124.6); p = 0.007) and decrease in total cholesterol (-0.40 mmol/L (-0.79, -0.003); p = 0.049). No harmful changes in musculoskeletal discomfort/pain were observed relative to controls, and beneficial changes in flow-mediated dilation and diastolic blood pressure were observed. Most participants self-reported that the workstation was easy to use and their work-related productivity did not decrease when using the device. Factors that negatively influenced workstation use were workstation design, the social environment, work tasks and habits. Conclusion: Short-term use of a feasible sit-stand workstation reduced daily sitting time and led to beneficial improvements in cardiometabolic risk parameters in asymptomatic office workers. These findings imply that if the observed use of the sit-stand workstations continued over a longer duration, sit-stand workstations may have important ramifications for the prevention and reduction of cardiometabolic risk in a large proportion of the working population. Trial registration: ClinicalTrials.gov NCT02496507