Over the past decade, various liquid biopsy techniques have emerged as viable alternatives to the analysis of traditional tissue biopsy samples. Such surrogate ‘biopsies’ offer numerous advantages, including the relative ease of obtaining serial samples and overcoming the issues of interpreting one or more small tissue samples that might not reflect the entire tumour burden. To date, the majority of research in the area of liquid biopsies has focused on blood-based biomarkers, predominantly using plasma-derived circulating tumour DNA (ctDNA). However, ctDNA can also be obtained from various non-blood sources and these might offer unique advantages over plasma ctDNA. In this Review, we discuss advances in the analysis of ctDNA from non-blood sources, focusing on urine, cerebrospinal fluid, and pleural or peritoneal fluid, but also consider other sources of ctDNA. We discuss how these alternative sources can have a distinct yet complementary role to that of blood ctDNA analysis and consider various technical aspects of non-blood ctDNA assay development. We also reflect on the settings in which non-blood ctDNA can offer distinct advantages over plasma ctDNA and explore some of the challenges associated with translating these alternative assays from academia into clinical use.

Objectives-To determine whether a single high dose ofvitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme.Design-Opportunistic controlled trial. Setting-Jumla district, Nepal. Subjects-All children aged under 5 years; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation.Main outcome measures-Mortality and cause of death in the five months after supplementation.Results-Risk of death for children aged 1-59 months in supplemented communities was 26% lower (relative risk 0*74, 95% confidence interval 0-55 to 0.99) than in unsupplemented communities.The reduction in mortality was greatest among children aged 6-11 months: death rate (deaths/1000 child years at risk) was 133-8 in supplemented children and 260*8 in unsupplemented children (relative risk 0.51, 0*30 to 0.89). The death rate from diarrhoea was also reduced (63.5 supplemented v 97.5 unsupplemented; relative risk 0-65, 0 44 to 0.95). The extra cost per death averted was about $11.Conclusion-The results support a role for Vitamin A in increasing child survival. The supplementation programme was readily integrated with the ongoing community health programme at little extra cost.

Real-world data in the era of immune checkpoint inhibitors (ICIs): Cetuximab-containing first-line therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

This paper describes the modeling work by Makai Ocean Engineering, Inc. to simulate the biochemical effects of of the nutrient-enhanced seawater plumes that are discharged by one or several 100 megawatt OTEC plants. The modeling is needed to properly design OTEC plants that can operate sustainably with acceptably low biological impact.Ocean Thermal Energy Conversion (OTEC) uses large flows of warm tropical seawater and cold deep seawater to generate non-polluting electric power. The magnitude of the global OTEC resource dwarfs that of other other marine renewable energy technologies, and OTEC power is non-intermittent, making it suitable for utilities and manufacturing. Small demonstration OTEC plants using commercially-available equipment have generated 50 -270 kilowatts of electricity. Recent advances in offshore design and cold water pipe technologies have renewed interest in developing large 100 megawatt plants that would be cost-competive with local island utilities. Such plants would have several seawater pumps, each equivalent to tugboat engines, that would guide 750 tonnes per second of seawater thorugh the OTEC system.At most potential OTEC sites, the tropical ocean is thermally stratified into a well-mixed warm upper layer overlying cooler and denser seawater. This stratification hinders the supply of nutrients upwelled into the photic zone, which results in a nutrient-limited "oligotrophic" phytoplankton community having low biological productivity. Discharging deep seawater nutrients (primarily nitrates) into the upper waters from the OTEC plant could potentially enhance phytoplankton growth, shift community species composition, or cause algal blooms. It is desirable to discharge the seawater flows deep enough so that the discharged nutrients are diluted and remain below the photic zone. Thus, the size and depth of the large seawater ducts affect both the overall architecture of an OTEC plant as well as the extent of the perturbation to the ambient phytoplankton populations.In order to quantify the effect of discharge configuration and phytoplankton response, Makai Ocean Engineering implemented a biological and physical model for the waters surrounding O`ahu, Hawai`i, using the EPA-approved Environmental Fluid Dynamics Code (EFDC). Each EFDC grid cell was approximately 1 square kilometer by 20 meters deep, and used a time step of three hours. The biological model was set up to simulate the biochemical response for three classes of organisms: Picoplankton (< 2 um) such as prochlorococccus, nanoplankton (2-20 um), and microplankton (> 20 um) e.g., diatoms. The dynamic biological phytoplankton model was calibrated using chemical and biological data collected for the Hawaii Ocean Time Series (HOTS) project. Peer review of the biological modeling was performed by Dr. John Hamrick, the author of EFDC, and by Dr. Matt Church of the University of Hawai'i, a leading marine microbiologist.The physical oceanography model uses boundary conditions from a surrounding Hawai'i Regional Ocean Model, (ROM) operated by...

Small cell lung cancer (SCLC) has a particularly poor prognosis despite the high initial response to first-line systemic therapy, and there is a well-recognised lack of meaningful treatments beyond the second line. A number of reasons have been put forward to explain this, including a lack of common, easily-druggable genetic mutations in SCLC and rarity of high-quality tissue samples due to late presentation. Liquid biopsies, including circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) are increasingly used as surrogates for tumour tissue and have the advantage of being easily obtained serially to inform on the biology of disease progression and acquired chemoresistance, and may provide a pathway to improve care in this notoriously refractory disease. Here we discuss the current evidence behind these liquid biopsy methods in SCLC, and how they could be employed in future clinical care.