A SANS and APT study of precipitate evolution and strengthening in a maraging steel

In this work a combination of the characterisation techniques small angle neutron scattering (SANS) and atom probe tomography (APT) are used to study the precipitation in a maraging steel. Three similar maraging steel alloys were aged at different temperatures and ageing times, and then characterised using SANS, APT and microhardness. The alloys consist of two types of precipitates, namely Laves phase and β-NiAl, the precipitates have different composition and hence precipitate ageing, which makes it complicated to model. The SANS experimental set-up was relatively simple and allowed the precipitate size and fraction of a large number of samples to be measured in a single experiment. The APT results were used for constraining the SANS modelling, particularly the composition, shape and distribution of phases. The characterisation led to the following description of precipitation: NiAl phase reaches coarsening at early stages of ageing and shifts its strength mechanisms from shearing to Orowan looping, which cause the characteristic peak strength; the Laves phase is in growth throughout and its strength contribution increases with ageing time. These observations were shown to be consistent with precipitate evolution and strengthening models, and the work of others. Although, there are some issues with the combination of SANS and APT approach, which are discussed, the methodology provides a valuable tool to understand complex precipitation behaviours

Pathological response and tumour bed histopathological features correlate with survival following neoadjuvant immunotherapy in stage III melanoma

Background: Guidelines for pathological evaluation of neoadjuvant specimens and pathological response categories have been developed by the International Neoadjuvant Melanoma Consortium (INMC). As part of the Optimal Neo-adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo) clinical trial of neoadjuvant combination anti-programmed cell death protein 1/anti-cytotoxic T-Iymphocyte-associated protein 4 immunotherapy for stage III melanoma, we sought to determine interobserver reproducibility of INMC histopathological assessment principles, identify specific tumour bed histopathological features of immunotherapeutic response that correlated with recurrence and relapse-free survival (RFS) and evaluate proposed INMC pathological response categories for predicting recurrence and RFS.Patients and methods: Clinicopathological characteristics of lymph node dissection specimens of 83 patients enrolled in the OpACIN-neo clinical trial were evaluated. Two methods of assessing histological features of immunotherapeutic response were evaluated: the previously described immune-related pathologic response (irPR) score and our novel immunotherapeutic response score (ITRS). For a subset of cases (n = 29), cellular composition of the tumour bed was analysed by flow cytometry.Results: There was strong interobserver reproducibility in assessment of pathological response (kappa = 0.879) and percentage residual viable melanoma (intraclass correlation coefficient = 0.965). The immunotherapeutic response subtype with high fibrosis had the strongest association with lack of recurrence (P = 0.008) and prolonged RFS (P = 0.019). Amongst patients with criteria for pathological non-response (pNR, >50% viable tumour), all who recurred had >= 70% viable melanoma. Higher ITRS and irPR scores correlated with lack of recurrence in the entire cohort (P = 0.002 and P = 70% viable melanoma and incorporating additional criteria of <10% fibrosis subtype of response may identify those at highest risk of recurrence, but requires validation.Analysis and support of clinical decision makin

The Subcutaneous Air-Pouch Model of Synovium and the Inflammatory Response to Heat Aggregated Gammaglobulin

Subcutaneous injection of sterile air in rodents results in the formation of an air pouch with a lining morphologically similar to synovium (Edwards et al., 1981). We extended the comparison between pouch and synovial tissue and confirmed broad similarities in structure and function but also noted important differences. The air pouch was used to study the time course of the acute inflammatory response to heat aggregated human IgG. Saline washout of the pouch allowed simultaneous measurement of cellular and mediator components of the inflammatory exudate. The aggregates were rapidly phagocytosed by the pouch lining cells, resulting in acute inflammation characterised by polymorphonuclear leucocyte infiltration with peak numbers in the exudate at 12 hours, temporally dissociated from the earlier peak of PGE2 at 3 hours