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How far do marine larvae disperse in the ocean? Decades of population genetic studies have revealed generally low levels of genetic structure at large spatial scales (hundreds of kilometres). Yet this result, typically based on discrete sampling designs, does not necessarily imply extensive dispersal. Here, we adopt a continuous sampling strategy along 950 km of coast in the northwestern Mediterranean Sea to address this question in four species. In line with expectations, we observe weak genetic structure at a large spatial scale. Nevertheless, our continuous sampling strategy uncovers a pattern of isolation by distance at small spatial scales (few tens of kilometres) in two species. Individual-based simulations indicate that this signal is an expected signature of restricted dispersal. At the other extreme of the connectivity spectrum, two pairs of individuals that are closely related genetically were found more than 290 km apart, indicating long-distance dispersal. Such a combination of restricted dispersal with rare long-distance dispersal events is supported by a high-resolution biophysical model of larval dispersal in the study area, and we posit that it may be common in marine species. Our results bridge population genetic studies with direct dispersal studies and have implications for the design of marine reserve networks.

Colorectal cancer is the second leading cause of cancer deaths worldwide, with a 5-year relative survival of 14% in patients with metastatic colorectal cancer (mCRC). Patients with BRAF V600E mutations, which occur in ∼10%-15% of patients with mCRC, have a poorer prognosis compared with those with wild-type BRAF tumours. The combination of the BRAF inhibitor encorafenib with the epidermal growth factor receptor inhibitor cetuximab currently represents the only chemotherapy-free targeted therapy approved in the USA and Europe for previously treated patients with BRAF V600E-mutated mCRC. As a class, BRAF inhibitors are associated with dermatologic, gastrointestinal, and renal events, as well as pyrexia and secondary skin malignancies. Adverse event (AE) profiles of specific BRAF inhibitors vary, however, and are affected by the specific agents given in combination. In patients with mCRC, commonly reported AEs of cetuximab monotherapy include infusion reactions and dermatologic toxicities. Data from the phase III BEACON CRC study indicate that the combination of encorafenib with cetuximab has a distinct safety profile. Here we review the most frequently reported AEs that occurred with this combination in BEACON CRC and best practices for managing and mitigating AEs that require more than standard supportive care.

Quantifying fish species diversity in rich tropical marine environments remains challenging. Environmental DNA (eDNA) metabarcoding is a promising tool to face this challenge through the filtering, amplification, and sequencing of DNA traces from water samples. However, because eDNA concentration is low in marine environments, the reliability of eDNA to detect species diversity can be limited. Using an eDNA metabarcoding approach to identify fish Molecular Taxonomic Units (MOTUs) with a single 12S marker, we aimed to assess how the number of sampling replicates and filtered water volume affect biodiversity estimates. We used a paired sampling design of 30 L per replicate on 68 reef transects from 8 sites in 3 tropical regions. We quantified local and regional sampling variability by comparing MOTU richness, compositional turnover, and compositional nestedness. We found strong turnover of MOTUs between replicated pairs of samples undertaken in the same location, time, and conditions. Paired samples contained non-overlapping assemblages rather than subsets of one another. As a result, non-saturated localized diversity accumulation curves suggest that even 6 replicates (180 L) in the same location can underestimate local diversity (for an area <1 km). However, sampling regional diversity using ~25 replicates in variable locations (often covering 10 s of km) often saturated biodiversity accumulation curves. Our results demonstrate variability of diversity estimates possibly arising from heterogeneous distribution of eDNA in seawater, highly skewed frequencies of eDNA traces per MOTU, in addition to variability in eDNA processing. This high compositional variability has consequences for using eDNA to monitor temporal and spatial biodiversity changes in local assemblages. Avoiding false-negative detections in future biomonitoring efforts requires increasing replicates or sampled water volume to better inform management of marine biodiversity using eDNA.

Many islands are biodiversity hotspots but also extinction epicenters. In addition to strong cultural connections to nature, islanders derive a significant part of their economy and broader wellbeing from this biodiversity. Islands are thus considered as the socio-ecosystems most vulnerable to species and habitat loss. Yet, the extent and key correlates of protected area coverage on islands is still unknown. Here we assess the relative influence of climate, geography, habitat diversity, culture, resource capacity, and human footprint on terrestrial and marine protected area coverage across 2323 inhabited islands globally. We show that, on average, 22% of terrestrial and 13% of marine island areas are under protection status, but that half of all islands have no protected areas. Climate, diversity of languages, human population density and development are strongly associated with differences observed in protected area coverage among islands. Our study suggests that economic development and population growth may critically limit the amount of protection on islands. © 2020, The Author(s).

Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malaria's Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality.

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This paper describes reasons for and importance of verifying that a computer correctly implements MIL-STD-1750A architectural speciications. It includes a brief summary of verification history. It describes present methodology for verification testing including test procedures, results analysis, and test reporting. finally, a future approach for verification testing is discussed. (Author), This article is from 'Proceedings Papers of the AFSC (Air Force Systems Command) Avionics Standardization Conference (2nd) Held at Dayton, Ohio on 30 November-2 December 1982. Volume 1', AD-A142 776, p493-499.