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This paper presents an analytical investigation of the direct method of measurement of the source impedance of a linear time-variant source. The direct method yields a frequency-dependent effective source impedance which is routinely used in a time-invariant analysis to determine the insertion loss of two different acoustic loads applied to the same source. In such an analysis the strength of the source is assumed to be invariant with load. It is shown here that there is generally no precise correspondence between the effective source impedance as given by the direct method and the characteristics of the actual source. Furthermore, it is shown that the effective source impedance values given by the direct method are functions of the acoustic load and the location of the injected signal as used in the measurement. However, the effective source resistance is always found to be positive, in accordance with experimental measurements. In this regard the direct method is an improvement on the indirect method, where physically implausible negative resistance values are often found. Finally, it is shown that the effective impedance values as given by the direct method when used with a time-invariant analysis give rise to very accurate predictions of insertion loss, even when the strength of the actual time-variant source is allowed to vary with the acoustic load. [Copyright &y& Elsevier]

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma., Significance: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275., (©2023 The Authors; Published by the American Association for Cancer Research.)

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic., (© 2021. The Author(s).)

The UK Climate Change Act requires the Environment Agency to report the risks it faces from climate change and actions taken to address these. Derived information from projections is critical to understanding likely impacts in water management. In 2019, the UK published an ensemble of high-resolution model simulations. The UKCP Local (2.2 km) projections can resolve smaller scale physical processes that determine rainfall and other variables at subdaily time-scales with the potential to provide new insights into extreme events, storm runoff and drainage management. However, simulations also need to inform adaptation. The challenge ahead is to identify and provide derived products without the need for further analysis by decision-makers. These include a wider evaluation of uncertainty, narratives about rainfall change across the projections and bias-corrected datasets. Future flood maps, peak rainfall estimates, uplift factors and future design storm profiles also need detailed guidance to support their use. Central government support is justified in the provision of up-to-date impacts information to inform flood risk management, given the large risks and exposure of all sectors. The further development of projections would benefit from greater focus and earlier scoping with industry representatives, operational tool developers and end users. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

Objective: To determine changes in the nutritional content of children's menu items at U.S. restaurant chains between 2010 and 2014., Methods: The sample consisted of 13 sit down and 16 fast-food restaurant chains ranked within the top 50 US chains in 2009. Nutritional information was accessed in June-July 2010 and 2014. Descriptive statistics were calculated for nutrient content of main dishes and side dishes, as well as for those items that were added, removed, or unchanged during the study period., Results: Nutrient content of main dishes did not change significantly between 2010 and 2014. Approximately one-third of main dishes at fast-food restaurant chains and half of main dishes at sit down restaurant chains exceeded the 2010 Dietary Guidelines for Americans recommended levels for sodium, fat, and saturated fat in 2014. Improvements in nutrient content were observed for side dishes. At sit down restaurant chains, added side dishes contained over 50% less calories, fat, saturated fat, and sodium, and were more likely to contain fruits/vegetables compared to removed sides (p < 0.05 for all comparisons). Added side dishes at fast-food restaurant chains contained less saturated fat (p < 0.05)., Conclusions: The majority of menu items, especially main dishes, available to children still contain high amounts of calories, fat, saturated fat, and sodium. Efforts must be made by the restaurant industry and policy makers to improve the nutritional content of children's menu items at restaurant chains to align with the Dietary Guidelines for Americans. Additional efforts are necessary to help parents and children make informed choices when ordering at restaurant chains.

The surgical approach to the morbidly obese patient has been changing over the years because of complications of the procedure. Evolution of gastric surgical techniques has resulted in a decrease in the radiologically evident complications such as anastomotic leaks, abscess, and marginal ulceration. Knowledge of the pertinent surgical and radiographic anatomy is important to the radiologist in evaluating the patient who has undergone a gastric bypass or gastroplasty for morbid obesity.