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Purpose Recent reports personalizing the administered activity (AA) of each cycle of peptide receptor radionuclide therapy based on the predicted absorbed dose (AD) to the kidneys (dose-limiting organ) have been promising. Assuming identical renal pharmacokinetics for each cycle is pragmatic, however it may lead to over- or under-estimation of the optimal AA. Here, we investigate the influence that earlier cycles of [177Lu]Lu-DOTATATE had on the biokinetics and AD of subsequent cycles in a recent clinical trial that evaluated the safety and activity of [177Lu]Lu-DOTATATE in pediatric neuroblastoma (NBL). We investigated whether predictions based on an assumption of unchanging AD per unit AA (Gy/GBq) prove robust to cyclical changes in biokinetics. Methods A simulation study, based on dosimetry data from six children with NBL who received four-cycles of [177Lu]Lu-DOTATATE in the LuDO trial (ISRCTN98918118), was performed to explore the effect of variable biokinetics on AD. In the LuDO trial, AA was adapted to the patient’s weight and SPECT/CT-based dosimetry was performed for the kidneys and tumour after each cycle. The largest tumour mass was selected for dosimetric analysis in each case. Results The median tumour AD per cycle was found to decrease from 15.6 Gy (range 8.12–26.4) in cycle 1 to 11.4 Gy (range 9.67–28.8), 11.3 Gy (range 2.73–32.9) and 4.3 Gy (range 0.72–20.1) in cycles 2, 3 and 4, respectively. By the fourth cycle, the median of the ratios of the delivered AD (ADD) and the predicted (or “expected”) AD (ADE) (which was based on an assumption of stable biokinetics from the first cycle onwards) were 0.16 (range 0.02–0.92, p = 0.013) for the tumour and 1.08 (range 0.84–1.76, p > 0.05) for kidney. None of the patients had an objective response at 1 month follow up. Conclusion This study demonstrates variability in Gy/GBq and tumour AD per cycle in children receiving four administrations of [177Lu]Lu-DOTATATE treatment for NBL. NBL is deemed a radiation sensitive tumour; therefore, dose-adaptive treatment planning schemes may be appropriate for some patients to compensate for decreasing tumour uptake as treatment progresses. Trial registration ISRCTN ISRCTN98918118. Registered 20 December 2013 (retrospectively registered).

We consider nonadaptive group testing with Bernoulli tests, where each item is placed in each test independently with some fixed probability. We give a tight threshold on the maximum number of tests required to find the defective set under optimal Bernoulli testing. Achievability is given by a result of Scarlett and Cevher; here we give a converse bound showing that this result is best possible. Our new converse requires three parts: a typicality bound generalising the trivial counting bound, a converse on the COMP algorithm of Chan et al, and a bound on the SSS algorithm similar to that given by Aldridge, Baldassini, and Johnson. Our result has a number of important corollaries, in particular that, in denser cases, Bernoulli nonadaptive group testing is strictly worse than the best adaptive strategies., Comment: 7 pages, 1 figure

The article focuses on the revitalization of the Welsh language in Wales. The article discusses the reasons for the revival of Welsh, including efforts by the Welsh Language Board and the Welsh Assembly Government, Welsh-medium schools being considered as elite and the positive view of being Welsh in popular culture. The article discusses the prevalence of bilingualism and the legislative self-determination in Wales. The article also addresses the theme of reports within the issue, including the use of English and Welsh by students in north Wales, the discourse of social inclusiveness in language policy and anti-colonial discourse by pressure groups.