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Abstract. Anthropogenic warming and nutrient over-enrichment of our oceans have resulted in significant, and often catastrophic, reductions in dissolved oxygen (deoxygenation). Stress on water-breathing animals from this deoxygenation has been shown to occur at all levels of biological organization: cellular; organ; individual; species; population; community; and ecosystem. Most climate forecasts predict increases in ocean deoxygenation, thus it is essential to develop reliable biological indicators of oxygen stress that can be used by regional and global oxygen monitoring efforts to detect and assess the impacts of deoxygenation on ocean life. This review focuses on indicators of low-oxygen stress that are manifest at different levels of biological organization and at a variety of spatial and temporal scales. We compare particular attributes of these indicators to the dissolved oxygen threshold of response, time-scales of response, sensitive life stages and taxa, and the ability to scale the response to oxygen stress across levels of organization. Where there is available evidence, we discuss the interactions of other biological and abiotic stressors on the biological indicators of oxygen stress. We address the utility, confounding effects, and implementation of the biological indicators of oxygen stress for both research and societal applications. Our hope is that further refinement and dissemination of these oxygen stress indicators will provide more direct support for environmental managers, fisheries and mariculture scientists, conservation professionals, and policy makers to confront the challenges of ocean deoxygenation. An improved understanding of the sensitivity of different ocean species, communities and ecosystems to low oxygen stress will empower efforts to design monitoring programs, assess ecosystem health, develop management guidelines, track conditions, and detect low-oxygen events.

Background: In responding to the global problems facing humankind, there is great value in equipping science and engineering students with skills to function well in multidisciplinary teams. Little attention has been paid into the factors that influence multidisciplinary collaboration and teamwork of science and engineering students. Purpose: This research describes multidisciplinary teamwork of applied physics and mechanical engineering students in a challenge-based learning (CBL) course. The study aimed to: a) identify the facilitators and barriers to multidisciplinary teamwork and b) explore learning outcomes connected to working in multidisciplinary teams. Sample: 30 students registered to the course, two teachers, and three tutors participated in this research. Design and Methods: An instrumental case study was conducted in the context of a pilot CBL course. Data included interviews, reflection reports, observations, and design posters. Transcribed video recordings were searched in an attempt to demonstrate the codes revealed with the qualitative content analysis of interview transcripts and reflection reports. Results: The results indicated knowledge acquisition, application, and an awareness of other disciplinary approaches as the learning outcomes with some differences for engineering and physics students. The findings also yielded individual (e.g. knowledge of control theory), team (e.g. disciplinary perspectives), and course factors (e.g. disciplinary connections to the challenge) that influenced multidisciplinary teamwork. Conclusion: Multidisciplinary teamwork is supported by the unique ways of thinking and approaching problems of the two disciplines. Implications contribute to future research and thinking for similar learning environments while improving student learning in multidisciplinary teams.

Higher engineering education programmes increasingly include courses characterised by real-world problems and student collaboration in multidisciplinary teams. Research findings demonstrate that students remain limited in perceiving and meaningfully bridging disciplinary differences in these course contexts. Drawing on the literature on boundaries and boundary interactions, this study sought to investigate how applied physics and mechanical engineering students managed their disciplinary differences in a challenge-based learning course. Using a qualitative, case study methodology, data from two multidisciplinary student teams (n = 12) were collected through reflective journals, individual interviews, and observations of team meetings. The findings confirm the value of disciplinary boundaries in creating new learning opportunities. The students coordinated their disciplinary differences during discussions in team meetings, preparations for the project plan and the stakeholder pitch, and test sessions in the lab. Results provide insights for designing similar courses and for future research.

Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings.Prevention relevanceUnderstanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

In this paper, we outline the need for a coordinated international effort toward the building of an open-access Global Ocean Oxygen Database and ATlas (GO2DAT) complying with the FAIR principles (Findable, Accessible, Interoperable, and Reusable). GO2DAT will combine data from the coastal and open ocean, as measured by the chemical Winkler titration method or by sensors (e.g., optodes, electrodes) from Eulerian and Lagrangian platforms (e.g., ships, moorings, profiling floats, gliders, ships of opportunities, marine mammals, cabled observatories). GO2DAT will further adopt a community-agreed, fully documented metadata format and a consistent quality control (QC) procedure and quality flagging (QF) system. GO2DAT will serve to support the development of advanced data analysis and biogeochemical models for improving our mapping, understanding and forecasting capabilities for ocean O2 changes and deoxygenation trends. It will offer the opportunity to develop quality-controlled data synthesis products with unprecedented spatial (vertical and horizontal) and temporal (sub-seasonal to multi-decadal) resolution. These products will support model assessment, improvement and evaluation as well as the development of climate and ocean health indicators. They will further support the decision-making processes associated with the emerging blue economy, the conservation of marine resources and their associated ecosystem services and the development of management tools required by a diverse community of users (e.g., environmental agencies, aquaculture, and fishing sectors). A better knowledge base of the spatial and temporal variations of marine O2 will improve our understanding of the ocean O2 budget, and allow better quantification of the Earth’s carbon and heat budgets. With the ever-increasing need to protect and sustainably manage ocean services, GO2DAT will allow scientists to fully harness the increasing volumes of O2 data already delivered by the expanding global ocean observing system and enable smooth incorporation of much higher quantities of data from autonomous platforms in the open ocean and coastal areas into comprehensive data products in the years to come. This paper aims at engaging the community (e.g., scientists, data managers, policy makers, service users) toward the development of GO2DAT within the framework of the UN Global Ocean Oxygen Decade (GOOD) program recently endorsed by IOC-UNESCO. A roadmap toward GO2DAT is proposed highlighting the efforts needed (e.g., in terms of human resources).

Marine omega-3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Multivariable hazard ratios and 95% confidence intervals (CIs) were calculated for the association between MO3PUFA and disease-free survival (DFS) and overall survival according to KRAS and BRAFV600E mutations and DNA mismatch repair (MMR) status. Higher MO3PUFA intake was associated with improved 3-year DFS for KRAS wild-type tumors (77% vs. 73%; HR: 0.84; 95% CI: 0.67-1.05) but not KRAS-mutant tumors (64% vs. 70%; HR: 1.30; 95% CI: 0.97-1.73; Pinteraction = 0.02). Similar heterogeneity was found by MMR (Pinteraction = 0.14): higher MO3PUFA was associated with better 3-year DFS for tumors with deficient MMR (72% vs. 67%) but not proficient MMR (72% vs. 72%). No heterogeneity was found by BRAFV600E mutation. Similar findings were obtained for overall survival. In conclusion, we found a suggestive beneficial association between higher MO3PUFA intake and improved survival among stage III colon cancer patients with wild-type KRAS and deficient MMR. Given the relatively small number of cases with tumor molecular assessments, further studies, preferably through pooled analyses of multiples cohorts, are needed to validate our findings.

The recent pace, extent, and impact of paradigm-changing cancer prevention science has been remarkable. The American Association for Cancer Research (AACR) convened a 3-day summit, aligned with five research priorities: (i) Precancer Atlas (PCA). (ii) Cancer interception. (iii) Obesity-cancer linkage, a global epidemic of chronic low-grade inflammation. (iv) Implementation science. (v) Cancer disparities. Aligned with these priorities, AACR co-led the Lancet Commission to formally endorse and accelerate the NCI Cancer Moonshot program, facilitating new global collaborative efforts in cancer control. The expanding scope of creative impact is perhaps most startling-from NCI-funded built environments to AACR Team Science Awarded studies of Asian cancer genomes informing global primary prevention policies; cell-free epigenetic marks identifying incipient neoplastic site; practice-changing genomic subclasses in myeloproliferative neoplasia (including germline variant tightly linked to JAK2 V617F haplotype); universal germline genetic testing for pancreatic cancer; and repurposing drugs targeting immune- and stem-cell signals (e.g., IL-1β, PD-1, RANK-L) to cancer interception. Microbiota-driven IL-17 can induce stemness and transformation in pancreatic precursors (identifying another repurposing opportunity). Notable progress also includes hosting an obesity special conference (connecting epidemiologic and molecular perspectives to inform cancer research and prevention strategies), co-leading concerted national implementation efforts in HPV vaccination, and charting the future elimination of cancer disparities by integrating new science tools, discoveries and perspectives into community-engaged research, including targeted counter attacks on e-cigarette ad exploitation of children, Hispanics and Blacks. Following this summit, two unprecedented funding initiatives were catalyzed to drive cancer prevention research: the NCI Cancer Moonshot (e.g., PCA and disparities); and the AACR-Stand Up To Cancer bold "Cancer Interception" initiative.

IntroductionCurrent tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages.Materials and methodsWe compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry.ResultsEngineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not undergo endochondral ossification in vivo.ConclusionshOA chondrocytes can adopt an endochondral phenotype after passaging and TGF-β superfamily treatment. Engineered endochondral cartilage grafts can integrate with host bone, undergo ossification, and heal critical-size long-bone defects in a mouse model. However, additional methods to further enhance ossification of these grafts are required before the clinical translation of this approach.

Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury.