Outcomes That Matter Most to Young Adults Diagnosed with Cancer: A Qualitative Study.

Purpose: The purpose of this study is to provide insight for improvement in care for young adults diagnosed with cancer (YADC), by identifying underemphasized outcomes that strongly matter to YADC and the gaps in care that may limit achieving these outcomes for this unique and vulnerable population. Methods: Twenty-seven YADC, ages 25-39, participated in unstructured discussions focusing on topics relating to diagnosis, daily experiences living with cancer outside of the clinical setting, goals, concerns, and clinical care experience. Most participants engaged in group discussions using Experience Group methodology. Discussions were designed to collect information on three dimensions of health: capability, comfort, and calm (CCC). Data were coded using thematic analysis with NVivo software. Results: Several themes were identified within the CCC framework: capability in terms of confronting mortality at a young age, losing youthful identity and control over major life course decisions, especially fertility, and debilitating side effects, comfort in terms of the lack of understanding from peers and family and the fear of cancer recurrence, and calm was discussed as the difficulty of making complex medical decisions, financial toxicity, and loss of clinical support in survivorship. Conclusion: This research highlighted four care additions that are important for YADC: (1) concise and understandable education about their condition and treatment; (2) same-age support groups; (3) fertility support; and (4) better care transitions for life after cancer. These findings emphasize the importance of creating a collaborative, multidisciplinary care team and a holistic approach with care innovations that support clinicians to meet the unique needs of YADC.

Movement patterns and habitat use of tiger sharks (Galeocerdo cuvier) across ontogeny in the Gulf of Mexico.

The tiger shark (Galeocerdo cuvier) is globally distributed with established coastal and open-ocean movement patterns in many portions of its range. While all life stages of tiger sharks are known to occur in the Gulf of Mexico (GoM), variability in habitat use and movement patterns over ontogeny have never been quantified in this large marine ecosystem. To address this data gap we fitted 56 tiger sharks with Smart Position and Temperature transmitting tags between 2010 and 2018 and examined seasonal and spatial distribution patterns across the GoM. Additionally, we analyzed overlap of core habitats (i.e., 50% kernel density estimates) among individuals relative to large benthic features (oil and gas platforms, natural banks, bathymetric breaks). Our analyses revealed significant ontogenetic and seasonal differences in distribution patterns as well as across-shelf (i.e., regional) and sex-linked variability in movement rates. Presumably sub-adult and adult sharks achieved significantly higher movement rates and used off-shelf deeper habitats at greater proportions than juvenile sharks, particularly during the fall and winter seasons. Further, female maximum rate of movement was higher than males when accounting for size. Additionally, we found evidence of core regions encompassing the National Oceanographic and Atmospheric Administration designated Habitat Areas of Particular Concern (i.e., shelf-edge banks) during cooler months, particularly by females, as well as 2,504 oil and gas platforms. These data provide a baseline for future assessments of environmental impacts, such as climate variability or oil spills, on tiger shark movements and distribution in the region. Future research may benefit from combining alternative tracking tools, such as acoustic telemetry and genetic approaches, which can facilitate long-term assessment of the species' movement dynamics and better elucidate the ecological significance of the core habitats identified here.

Distinct mechanisms of mutagenic processing of alternative DNA structures by repair proteins.

Repetitive sequences can form a variety of alternative DNA structures (non-B DNA) that can modulate transcription, replication, and repair. However, non-B DNA-forming sequences can also stimulate mutagenesis, and are enriched at mutation hotspots in human cancer genomes. Interestingly, different types of non-B DNA stimulate mutagenesis via distinct repair processing mechanisms.

Distinct DNA repair pathways cause genomic instability at alternative DNA structures.

Alternative DNA structure-forming sequences can stimulate mutagenesis and are enriched at mutation hotspots in human cancer genomes, implicating them in disease etiology. However, the mechanisms involved are not well characterized. Here, we discover that Z-DNA is mutagenic in yeast as well as human cells, and that the nucleotide excision repair complex, Rad10-Rad1(ERCC1-XPF), and the mismatch repair complex, Msh2-Msh3, are required for Z-DNA-induced genetic instability in yeast and human cells. Both ERCC1-XPF and MSH2-MSH3 bind to Z-DNA-forming sequences, though ERCC1-XPF recruitment to Z-DNA is dependent on MSH2-MSH3. Moreover, ERCC1-XPF-dependent DNA strand-breaks occur near the Z-DNA-forming region in human cell extracts, and we model these interactions at the sub-molecular level. We propose a relationship in which these complexes recognize and process Z-DNA in eukaryotes, representing a mechanism of Z-DNA-induced genomic instability.

Population connectivity of pelagic megafauna in the Cuba-Mexico-United States triangle.

The timing and extent of international crossings by billfishes, tunas, and sharks in the Cuba-Mexico-United States (U.S.) triangle was investigated using electronic tagging data from eight species that resulted in >22,000 tracking days. Transnational movements of these highly mobile marine predators were pronounced with varying levels of bi- or tri-national population connectivity displayed by each species. Billfishes and tunas moved throughout the Gulf of Mexico and all species investigated (blue marlin, white marlin, Atlantic bluefin tuna, yellowfin tuna) frequently crossed international boundaries and entered the territorial waters of Cuba and/or Mexico. Certain sharks (tiger shark, scalloped hammerhead) displayed prolonged periods of residency in U.S. waters with more limited displacements, while whale sharks and to a lesser degree shortfin mako moved through multiple jurisdictions. The spatial extent of associated movements was generally associated with their differential use of coastal and open ocean pelagic ecosystems. Species with the majority of daily positions in oceanic waters off the continental shelf showed the greatest tendency for transnational movements and typically traveled farther from initial tagging locations. Several species converged on a common seasonal movement pattern between territorial waters of the U.S. (summer) and Mexico (winter).

Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes.

Sequences with the capacity to adopt alternative DNA structures have been implicated in cancer etiology; however, the mechanisms are unclear. For example, H-DNA-forming sequences within oncogenes have been shown to stimulate genetic instability in mammals. Here, we report that H-DNA-forming sequences are enriched at translocation breakpoints in human cancer genomes, further implicating them in cancer etiology. H-DNA-induced mutations were suppressed in human cells deficient in the nucleotide excision repair nucleases, ERCC1-XPF and XPG, but were stimulated in cells deficient in FEN1, a replication-related endonuclease. Further, we found that these nucleases cleaved H-DNA conformations, and the interactions of modeled H-DNA with ERCC1-XPF, XPG, and FEN1 proteins were explored at the sub-molecular level. The results suggest mechanisms of genetic instability triggered by H-DNA through distinct structure-specific, cleavage-based replication-independent and replication-dependent pathways, providing critical evidence for a role of the DNA structure itself in the etiology of cancer and other human diseases.

Long-term assessment of whale shark population demography and connectivity using photo-identification in the Western Atlantic Ocean.

The predictable occurrence of whale sharks, Rhincodon typus, has been well documented in several areas. However, information relating to their migratory patterns, residency times and connectivity across broad spatial scales is limited. In the present study photo-identification data is used to describe whale shark population structure and connectivity among known aggregation sites within the Western Central Atlantic Ocean (WCA). From 1999 to 2015, 1,361 individuals were identified from four distinct areas: the Yucatan Peninsula, Mexico (n = 1,115); Honduras (n = 146); northern Gulf of Mexico, United States (n = 112), and Belize (n = 49). Seasonal patterns in whale shark occurrence were evident with encounters occurring in the western Caribbean Sea earlier in the year than in the GOM. There was also a significant sex bias with 2.6 times more males present than females. Seventy sharks were observed in more than one area and the highest degree of connectivity occurred among three aggregation sites along the Mesoamerican Reef. Despite this, the majority of resightings occurred in the area where the respective sharks were first identified. This was true for the WCA as a whole, with the exception of Belize. Site fidelity was highest in Mexico. Maximum likelihood modelling resulted in a population estimate of 2,167 (95% c.i. 1585.21-2909.86) sharks throughout the entire region. This study is the first attempt to provide a broad, regional population estimate using photo-identification data from multiple whale shark aggregations. Our aim is to provide population metrics, along with the description of region-scale connectivity, that will help guide conservation action in the WCA. At a global level, rapidly growing photographic databases are allowing for researchers to look beyond the description of single aggregation sites and into the ocean-scale ecology of this pelagic species.