Variation between general practices in the rate of consultations for musculoskeletal pain conditions may signal important differences in access to primary care, perceived usefulness, or available alternative sources of care; however, it might also just reflect differences in underlying ‘need’ between practices’ registered populations. In a study of 30 general practices in Staffordshire, we calculated the proportion of adults consulting for a musculoskeletal pain condition, then examined this in relation to selected practice and population characteristics, including the estimated prevalence of self-reported musculoskeletal problems and chronic pain in each practices’ registered population. Between September 2021 and July 2022, 18,388 adults were consulted for a musculoskeletal pain condition. After controlling for length of recruitment, time of year, and age-sex structure, the proportion consulting varied up to two-fold between practices but was not strongly associated with the prevalence of self-reported long-term musculoskeletal problems, chronic pain, and high-impact chronic pain.

Objectives/Goals: Osteosarcoma (OS) is the most common primary bone malignancy in humans and dogs. >40% of children and >90% of dogs succumb to metastatic disease. We hypothesize MYC overexpression in metastatic canine and human OS contributes to an immunosuppressive tumor environment by driving tumor-associated macrophage influx and T lymphocyte exclusion. Methods/Study Population: To characterize the role of oncogenic MYC signaling in the canine metastatic tumor immune microenvironment (TIME), 42 archived FFPE lung metastatic canine OS samples were evaluated for MYC copy number variation (CNV), mRNA, and protein expression via ddPCR, nanostring analysis, and immunohistochemistry (IHC). Seven samples also underwent GeoMX spatial profiling to more specifically evaluate T cell and macrophage transcriptional profiles based on MYC status. To determine the role of MYC target modulation as a potential therapeutic option, canine and human OS cell lines were treated with a novel MYC inhibitor (MYCi975) and assessed for effects on survival, proliferation, and cytokine profiles. Results/Anticipated Results: We demonstrate that copy number gains are not a key driver of MYC hyperactivity in canine metastatic OS. However, stratification based on MYC protein expression demonstrates that “MYC-high” tumors are associated with downregulation of cytotoxic effector T-cell associated transcripts and upregulation of tumor-associated macrophage (TAM) and extracellular matrix remodeling transcripts. We also report that MYCi975 treatment of canine and human OS cell lines results in significant inhibition of OS cell survival and proliferation at concentrations that are pharmacologically achievable in mice. Furthermore, we demonstrate MYC inhibition by MYCi975 is associated with reduced pro-inflammatory cytokine secretion in OS cell culture models. Discussion/Significance of Impact: While MYC overactivity in metastatic canine OS may not be genomically driven, other mechanisms that lead to increased MYC protein expression are associated with transcriptomic profiles supportive of local immunosuppression. Pharmacologic targeting of MYC may serve as a strategy to bolster immunotherapeutic options in metastatic OS treatment.

A biographic summary of the research of Dr Graham Charles George Argent (born 15 May 1941, died 24 April 2019) is presented, summarising his research career. Expedition information, including dates, collection number series and the names of collaborators, is given, as is a list of his publications, annotated with taxonomic decisions and the names of new species described within them.

Six new species of Vaccinium, identified as new to science by the late George Argent while compiling a revision of Vaccinium sect. Orianthe for New Guinea, are described and illustrations provided.

The species of the tree genus Pterospermum Schreb. (Malvaceae: Dombeyoideae) in Malesia are revised. Twenty-six species of Pterospermum are recognised, six of which are new (P. aureum S.K.Ganesan, P. borneense S.K.Ganesan, P. glabrum S.K.Ganesan, P. havilandii S.K.Ganesan, P. merrillianum S.K.Ganesan and P. zollingerianum S.K.Ganesan) and one (P. grewiifolium Pierre) that is a new distributional record for Malesia. Identification keys are provided. All names are typified, and detailed descriptions of all species recognised are provided. Information on habitat, uses and conservation status is given for all species.

A new species, Diplycosia kalimantanensis P.Wilkie & Argent (Ericaceae), collected on an expedition to Gunung Besar in the Meratus mountains, South Kalimantan, is described and illustrated, and a conservation assessment provided.

This report, which was sponsored by the Life Board of the Faculty and Institute of Actuaries, was originally published in November 1997.

Because it is referred to several times in the paper ‘Reserving, Pricing and Hedging for Policies with Guaranteed Annuity Options’, and in the discussions of the paper, and because it is not easily accessible elsewhere, it is printed here as a background paper for reference.

In this paper we present many investigations into the results of simulating the process of hedging a vanilla option at discrete times. We consider mainly a ‘maxi’ option (paying Max(A, B)), though calls, puts and ‘minis’ are also considered. We show the sensitivity of the variability of the hedging error to the actual investment strategy adopted, and to the many ways in which the simulated real world can diverge from the assumed option pricing model. We show how prudential reserves can be calculated, using conditional tail expectations, and how net premiums or fair values (which we present as the same) can be calculated, allowing for the necessary prudential reserves. We use two bond models, the very simple Black-Scholes one and a less unrealistic one. We also use the Wilkie model as an even more realistic real-world model, allowing for many complications in it to make it more realistic. We make observations on the important difference between real-world models and option pricing models, and emphasise the latter as the way of getting hedging quantities, and not just option prices.

Species delimitation in Scaphium (Sterculioideae, Malvaceae/Sterculiaceae) has been problematic and has led to confusion in identification of species. The genus was last revised in 1953 and at that time comprised four species. Since then five new species have been published. This revision of Scaphium recognises eight species, with other names being accounted for in synonymy or by exclusion from the genus.

Scaphium parviflorum P.Wilkie sp. nov. (Sterculioideae, Malvaceae/Sterculiaceae) is described and illustrated. The flowers are intermediate between the tubular flowers of Scaphium macropodum and the deeply lobed ones of Scaphium affine. However, Scaphium parviflorum differs from these species by its smooth to fissured or dippled and brown to grey-brown bark, small narrowly ovate to narrowly elliptic leaves and the presence of sparse minute flattened stellate hairs (resembling scales) on the midrib of the lower surface of the lamina.

Pterospermum mengii P.Wilkie (Dombeyoideae, Malvaceae/Sterculiaceae) from Cambodia and Vietnam is described as new to science and illustrated. It is most similar to Pterospermum pecteniforme Kosterm., sharing a distinctive wavy ridge at the margin of each locule of the capsular fruit, but differing by its larger leaves, oblong to obovate leaf shape, deeply cordate leaf base, and stellate indumentum on the undersurface of the leaves and fruit.

In AIDS Bulletins Nos. 1 to 4 the Institute of Actuaries AIDS Working Party presented projections of HIV infection and AIDS based on a model developed by Wilkie. This paper explores the sensitivity of those projections to the various different assumptions which have to be made and presents results on a number of alternative sets of assumptions.

1.1 In March 1987 the Futures Committee of the Institute considered a preliminary report (Daykin, 1987) on the possible impact of AIDS in the United Kingdom and the consequences for life insurance. The Committee recommended the setting up of a Working Party to study the problem. The Working Party on AIDS was accordingly established, under the auspices of the Research Committee. The authors of this paper formed the membership of the Working Party, under the chairmanship of C. D. Daykin.