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Abstract Objectives Bispecific antibodies targeting CD47 and PD‐L1 (CD47 × PD‐L1 BisAb) demonstrate efficacy against a range of solid cancers. While dual blockade negates anti‐CD47‐mediated toxicity, the effect of combined innate and adaptive immune activation on protective tumor‐resident CD8+ T cells has yet to be fully elucidated. Methods CD8+ T cell populations were tracked upon CD47 × PD‐L1 BisAb treatment in an orthotopic model of murine breast cancer where anti‐tumor immunity is mediated by CD8+ T cells. Immune responses were also compared with anti‐PD‐L1 monotherapy to assess the advantage of dual checkpoint targeting. Results We found that CD47 × PD‐L1 BisAb treatment augmented CD8+ T cell responses in tumors, which resulted in enhanced tumor control. Compared with anti‐PD‐L1 treatment, dual CD47 and PD‐L1 blockade promoted greater numbers of antigen‐specific tumor‐resident CD8+ T cells that exhibited increased cytokine production. Conclusions Engagement of innate and adaptive immune checkpoint molecules via CD47 × PD‐L1 BisAb treatment resulted in robust CD8+ T cell responses, including the induction of tumor‐resident CD8+ T cells that exhibited functionally superior anti‐tumor immunity. These results demonstrate that innate immune activation potentiates anti‐tumor adaptive responses, highlighting the use of dual checkpoint blockade as an optimal strategy for promoting CD8+ T cell‐mediated protection.

Abstract Environmental research often occurs in short bursts with the duration of fieldwork often governed by the time constraints of a funding body. Collaborations between academic researchers and Indigenous People have occurred for many years and the exchange of information can create value and knowledge for both participants in the collaboration. Indigenous People play a vital role as knowledge keepers in environmental science and can, in some instances, provide a more secure repository of local knowledge and conservation practice than digital archives. In this essay, Indigenous Rangers on Larrakia country in Darwin, Australia, and a non‐Indigenous academic researcher describe how value‐creation was increased for both parties involved in a collaborative project on the migratory shorebird far eastern curlew (Numenius madagascariensis). We share our experiences of expectations, the development of methods, the codeveloped goals and complementary ways of thinking to manage threatened species at a local scale, the scale at which the local Larrakia People operate. Through our collaboration, we show that both parties within the collaboration can benefit and create value for a species of conservation concern that has not typically been considered culturally important.

Abstract Objectives Metastasis is the principal cause of breast cancer mortality. Vaccines targeting breast cancer antigens have yet to demonstrate clinical efficacy, and there remains an unmet need for safe and effective treatment to reduce the risk of metastasis, particularly for people with triple‐negative breast cancer (TNBC). Certain glycolipids can act as vaccine adjuvants by specifically stimulating natural killer T (NKT) cells to provide a universal form of T‐cell help. Methods We designed and made a series of conjugate vaccines comprising a prodrug of the NKT cell‐activating glycolipid α‐galactosylceramide covalently linked to tumor‐expressed peptides, and assessed these using E0771‐ and 4T1‐based breast cancer models in vivo. We employed peptides from the model antigen ovalbumin and from clinically relevant breast cancer antigens HER2 and NY‐ESO‐1. Results Glycolipid‐peptide conjugate vaccines that activate NKT cells led to antigen‐presenting cell activation, induced inflammatory cytokines, and, compared with peptide alone or admixed peptide and α‐galactosylceramide, specifically enhanced CD8+ T‐cell responses against tumor‐associated peptides. Primary tumor growth was delayed by vaccination in all tumor models. Using 4T1‐based cell lines expressing HER2 or NY‐ESO‐1, a single administration of the relevant conjugate vaccine prevented tumor colonisation of the lung following intravenous inoculation of tumor cells or spontaneous metastasis from breast, respectively. Conclusion Glycolipid‐peptide conjugate vaccines that activate NKT cells prevent lung metastasis in breast cancer models and warrant investigation as adjuvant therapies for high‐risk breast cancer.

Abstract Investigation of exophthalmos and blood‐colored discharge from the left ventral punctum in a dog was consistent with a conjunctival cyst in the orbit. 3‐D prints of the cyst and surrounding facial bones identified a successful transconjunctival approach without an orbitotomy and patency of the left lacrimal duct was reestablished.

Abstract Background Accurate measurements of knee and hip motion are required for management of musculoskeletal pathology. The purpose of this investigation was to compare three techniques for measuring motion at the hip and knee. The authors hypothesized that digital photography would be equivalent in accuracy and show higher precision compared to the other two techniques. Methods Using infrared motion capture analysis as the reference standard, hip flexion/abduction/internal rotation/external rotation and knee flexion/extension were measured using visual estimation, goniometry, and photography on 10 fresh frozen cadavers. These measurements were performed by three physical therapists and three orthopaedic surgeons. Accuracy was defined by the difference from the reference standard, while precision was defined by the proportion of measurements within either 5° or 10°. Analysis of variance (ANOVA), t-tests, and chi-squared tests were used. Results Although two statistically significant differences were found in measurement accuracy between the three techniques, neither of these differences met clinical significance (difference of 1.4° for hip abduction and 1.7° for the knee extension). Precision of measurements was significantly higher for digital photography than: (i) visual estimation for hip abduction and knee extension, and (ii) goniometry for knee extension only. Conclusions There was no clinically significant difference in measurement accuracy between the three techniques for hip and knee motion. Digital photography only showed higher precision for two joint motions (hip abduction and knee extension). Overall digital photography shows equivalent accuracy and near-equivalent precision to visual estimation and goniometry.

Spheroidal Carbonaceous Particle distribution is a robust peat cohort dating tool. Charcoal impacts on carbon accumulation are context specific (i.e., controlled burns on UK blanket bog). Carbon sequestration rates need to consider topography (i.e., slope) and runoff (i.e., erosion).

Peatlands are globally important carbon stores, yet both natural and human impacts can influence peatland carbon accumulation. While changes in climate can alter peatland water tables leading to changes in peat decomposition, managed burning of vegetation has also been claimed to reduce peat accumulation. Particularly in the UK, blanket bog peatlands are rotationally burned to encourage heather re‐growth on grouse shooting estates. However, the evidence of burning impacts on peat carbon stocks is very limited and contradictory. We assessed peat carbon accumulation over the last few hundred years in peat cores from three UK blanket bog sites under rotational grouse moor burn management. High resolution (0.5 cm) peat core analysis included dating based on spheroidal carbonaceous particles, determining fire frequency based on macro‐charcoal counts and assessing peat properties such as carbon content and bulk density. All sites showed considerable net carbon accumulation during active grouse moor management periods. Averaged over the three sites, burns were more frequent, and carbon accumulation rates were also higher, over the period since 1950 than in the period 1700–1950. Carbon accumulation rates during the periods 1950–2015 and 1700–1850 were greater on the most frequently burnt site, which was linked to bulk density and carbon accumulation rates showing a positive relationship with charcoal abundance. Charcoal input from burning was identified as a potentially crucial component in explaining reported differences in burning impacts on peat carbon accumulation, as assessed by carbon fluxes or stocks. Both direct and indirect charcoal impacts on decomposition processes are discussed to be important factors, namely charcoal production converting otherwise decomposable carbon into an inert carbon pool, increasing peat bulk density, altering peat moisture and possibly negative impacts on soil microbial activity. This study highlights the value of peat core records in understanding management impacts on peat accumulation and carbon storage in peatlands.

Activation of resting T lymphocytes through the T cell antigen receptor complex is initiated by critical phosphorylation and dephosphorylation events that regulate the function and interaction of a number of signaling molecules. Key elements in these reactions are members of the Src, Syk and Csk families of protein tyrosine kinases (PTKs) and the phosphotyrosine phosphatases (PTPases) that regulate and/or counteract them, such as CD45. The PTKs can autophosphorylate and phosphorylate each other at multiple sites and, as the result of these interactions, they are induced to phosphorylate other cellular proteins. These phosphorylation events lead to modulation of enzymatic activities and/or serve as binding sites for other signaling molecules having phosphotyrosine-binding Src homology 2 (SH2) domains. As a result, these proteins translocate to the receptor complexes and are juxtaposed to the kinases that phosphorylate them. Some of the SH2-domain-containing polypeptides lack enzymatic activities and, instead, serve as adapter molecules that couple the signal to downstream effectors, such as regulators of the Ras proteins, and further into serine/threonine-specific protein kinase cascades. Through largely unknown steps these reactions lead to the transcription of previously silent genes, activation of lymphocyte effector functions, progression through the cell cycle and cell proliferation.