Complex patterns of genetic population structure in the mouthbrooding marine catfish, Bagre marinus, in the Gulf of Mexico and U.S. Atlantic.

Patterns of genetic variation reflect interactions among microevolutionary forces that vary in strength with changing demography. Here, patterns of variation within and among samples of the mouthbrooding gafftopsail catfish (Bagre marinus, Family Ariidae) captured in the U.S. Atlantic and throughout the Gulf of Mexico were analyzed using genomics to generate neutral and non-neutral SNP data sets. Because genomic resources are lacking for ariids, linkage disequilibrium network analysis was used to examine patterns of putatively adaptive variation. Finally, historical demographic parameters were estimated from site frequency spectra. The results show four differentiated groups, corresponding to the (1) U.S. Atlantic, and the (2) northeastern, (3) northwestern, and (4) southern Gulf of Mexico. The non-neutral data presented two contrasting signals of structure, one due to increases in diversity moving west to east and north to south, and another to increased heterozygosity in the Atlantic. Demographic analysis suggested that recently reduced long-term effective population size in the Atlantic is likely an important driver of patterns of genetic variation and is consistent with a known reduction in population size potentially due to an epizootic. Overall, patterns of genetic variation resemble that of other fishes that use the same estuarine habitats as nurseries, regardless of the presence/absence of a larval phase, supporting the idea that adult/juvenile behavior and habitat are important predictors of contemporary patterns of genetic structure.

Rosai-Dorfman disease of the cauda equina: illustrative case.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, nonmalignant histiocytosis. It typically occurs in lymph nodes, skin, and soft tissues, but numerous reports of central nervous system involvement exist in the literature. The peripheral nervous system has rarely been involved. In this study, the authors present a case of RDD isolated to the cauda equina. The presentation, management, surgical technique, and adjunctive treatment strategy are described. OBSERVATIONS: A 31-year-old female presented with 6 months of progressive left lower-extremity numbness involving the lateral aspect of the foot and weakness of the left toes. Magnetic resonance imaging of the lumbar spine demonstrated a homogeneously enhancing intradural lesion involving the cauda equina at the L2-3 levels. Histopathology after resection revealed a histiocytic infiltrate, positive for CD68 and S100, and emperipolesis consistent with RDD. No adjuvant therapy was administered, and the patient had full remission at the 1-year follow-up. Only five other cases of intradural RDD lesions of the cauda equina have been reported in the literature. LESSONS: RDD of the cauda equina is an especially rare and challenging diagnosis that can mimic other dura-based lesions, such as meningiomas. A definitive diagnosis of RDD relies on pathognomonic histopathological and immunohistochemical findings.

Interrelationships and biogeography of the New World pufferfish genus Sphoeroides (Tetraodontiformes: Tetraodontidae) inferred using ultra-conserved DNA elements.

Colonization of the New World by marine taxa has been hypothesized to have occurred through the Tethys Sea or by crossing the East Pacific Barrier. To better understand patterns and timing of diversification, geological events can be coupled with time calibrated phylogenetic hypotheses to infer major drivers of diversification. Phylogenetic relationships among members of Sphoeroides, a genus of four toothed pufferfishes (Tetraodontiformes: Tetraodontidae) which are found nearly exclusively in the New World (eastern Pacific and western Atlantic), were reconstructed using sequences from ultra-conserved DNA elements, nuclear markers with clear homology among many vertebrate taxa. Hypotheses derived from concatenated maximum-likelihood and species tree summary methods support a paraphyletic Sphoeroides, with Colomesus deeply nested within the genus. Analyses also revealed S. pachygaster, a pelagic species with a cosmopolitan distribution, as the sister taxon to the remainder of Sphoeroides and recovered distinct lineages within S. pachygaster, indicating that this cosmopolitan species may represent a species complex. Ancestral range reconstruction may suggest the genus colonized the New World through the eastern Pacific before diversifying in the western Atlantic, though date estimates for these events are uncertain due to the lack of reliable fossil record for the genus.

Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial.

In this randomized phase 2 trial, blockade of cytotoxic T-lymphocyte protein 4 (CTLA-4) with continuation of programmed death protein 1 (PD-1) blockade in patients with metastatic melanoma who had received front-line anti-PD-1 or therapy against programmed cell death 1 ligand 1 and whose tumors progressed was tested in comparison with CTLA-4 blockade alone. Ninety-two eligible patients were randomly assigned in a 3:1 ratio to receive the combination of ipilimumab and nivolumab, or ipilimumab alone. The primary endpoint was progression-free survival. Secondary endpoints included the difference in CD8 T cell infiltrate among responding and nonresponding tumors, objective response rate, overall survival and toxicity. The combination of nivolumab and ipilimumab resulted in a statistically significant improvement in progression-free survival over ipilimumab (hazard ratio = 0.63, 90% confidence interval (CI) = 0.41-0.97, one-sided P = 0.04). Objective response rates were 28% (90% CI = 19-38%) and 9% (90% CI = 2-25%), respectively (one-sided P = 0.05). Grade 3 or higher treatment-related adverse events occurred in 57% and 35% of patients, respectively, which is consistent with the known toxicity profile of these regimens. The change in intratumoral CD8 T cell density observed in the present analysis did not reach statistical significance to support the formal hypothesis tested as a secondary endpoint. In conclusion, primary resistance to PD-1 blockade therapy can be reversed in some patients with the combination of CTLA-4 and PD-1 blockade. Clinicaltrials.gov identifier: NCT03033576 .

Philopatry influences the genetic population structure of the blacktip shark (Carcharhinus limbatus) at multiple spatial scales.

Understanding how interactions among microevolutionary forces generate genetic population structure of exploited species is vital to the implementation of management policies that facilitate persistence. Philopatry displayed by many coastal shark species can impact gene flow and facilitate selection, and has direct implications for the spatial scales of management. Here, genetic structure of the blacktip shark (Carcharhinus limbatus) was examined using a mixed-marker approach employing mitochondrial control region sequences and 4339 SNP-containing loci generated using ddRAD-Seq. Genetic variation was assessed among young-of-the-year sampled in 11 sites in waters of the United States in the western North Atlantic Ocean, including the Gulf of Mexico. Spatial and environmental analyses detected 68 nuclear loci putatively under selection, enabling separate assessments of neutral and adaptive genetic structure. Both mitochondrial and neutral SNP data indicated three genetically distinct units-the Atlantic, eastern Gulf, and western Gulf-that align with regional stocks and suggest regional philopatry by males and females. Heterogeneity at loci putatively under selection, associated with temperature and salinity, was observed among sites within Gulf units, suggesting local adaptation. Furthermore, five pairs of siblings were identified in the same site across timescales corresponding with female reproductive cycles. This indicates that females re-used a site for parturition, which has the potential to facilitate the sorting of adaptive variation among neighbouring sites. The results demonstrate differential impacts of microevolutionary forces at varying spatial scales and highlight the importance of conserving essential habitats to maintain sources of adaptive variation that may buffer species against environmental change.

Haploid gynogens facilitate disomic marker development in paleotetraploid sturgeons.

Acipenseriformes (sturgeons and paddlefishes) are of substantial conservation concern, and development of genomic resources for these species is difficult due to past whole genome duplication. Development of disomic markers for polyploid organisms can be challenging due to difficulty in resolving alleles at a single locus from those among duplicated loci. In this study, we detail the development of disomic markers for the endangered pallid sturgeon (Scaphirhynchus albus) found in North America. One of the strategies for pallid sturgeon conservation is to stock U.S. rivers with offspring of pure pallid sturgeon, but introgression with the sympatric shovelnose sturgeon (S. platorynchus) threatens pallid sturgeon genetic integrity. Currently, 19 microsatellite loci are used to differentiate between both species and their hybrids, but the markers are insufficient to robustly identify backcrosses. We performed double digest restriction site-associated DNA sequencing (ddRADseq) on shovelnose sturgeon haploid gynogens to produce a reduced-representation genomic reference. Contiguous sequences that were heterozygous within a haploid individual were flagged as potentially encompassing multiple loci. Approximately 60 individuals of each species from two management units were sequenced, and reads were mapped to the haploid reference to identify single nucleotide polymorphisms (SNPs) at individual loci. The final data set contained 11,082 microhaplotyped loci which offer at least an order of magnitude greater resolution for species discrimination than the current panel of 19 microsatellites. These markers will be used to examine a larger sample of Scaphirhynchus individuals throughout their ranges to determine the extent and trajectory of hybridization.

Temperature-associated selection linked to putative chromosomal inversions in king scallop (Pecten maximus).

The genomic landscape of divergence-the distribution of differences among populations or species across the genome-is increasingly characterized to understand the role that microevolutionary forces such as natural selection and recombination play in causing and maintaining genetic divergence. This line of inquiry has also revealed chromosome structure variation to be an important factor shaping the landscape of adaptive genetic variation. Owing to a high prevalence of chromosome structure variation and the strong pressure for local adaptation necessitated by their sessile nature, bivalve molluscs are an ideal taxon for exploring the relationship between chromosome structure variation and local adaptation. Here, we report a population genomic survey of king scallop (Pecten maximus) across its natural range in the northeastern Atlantic Ocean, using a recent chromosome-level genome assembly. We report the presence of at least three large (12-22 Mb), putative chromosomal inversions associated with sea surface temperature and whose frequencies are in contrast to neutral population structure. These results highlight a potentially large role for recombination-suppressing chromosomal inversions in local adaptation and suggest a hypothesis to explain the maintenance of differences in reproductive timing found at relatively small spatial scales across king scallop populations.

Hexabothriidae and Monocotylidae (Monogenoidea) from the gills of neonate hammerhead sharks (Sphyrnidae) Sphyrna gilberti, Sphyrna lewini and their hybrids from the western North Atlantic Ocean.

Neonates of hammerhead sharks (Sphyrnidae), Sphyrna lewini (Griffith and Smith, 1834), the sympatric cryptic species, Sphyrna gilberti Quattro et al., 2013, and their hybrids were captured in the western North Atlantic, along the coast of South Carolina, USA, between 2018 and 2019 and examined for gill monogenoids. Parasites were identified and redescribed from the gills of 79 neonates, and DNA sequences from partial fragments of the nuclear 28S ribosomal RNA (rDNA) and cytochrome c oxidase I mitochondrial DNA (COI) genes were generated to confirm species identifications. Three species of monogenoids from Hexabothriidae Price, 1942 and Monocotylidae Taschenberg, 1879 were determined and redescribed. Two species of Hexabothriidae, Erpocotyle microstoma (Brooks, 1934) and Erpocotyle sphyrnae (MacCallum, 1931), infecting both species of Sphyrna and hybrids; and 1 species of Monocotylidae, Loimosina wilsoni Manter, 1944, infecting only S. lewini and hybrids. Loimosina wilsoni 28S rDNA sequences matched those of Loimosina sp. from the southern coast of Brazil. Based on limited morphological analysis, Loimosina parawilsoni is likely a junior synonym of L. wilsoni. This is the first taxonomic study of monogenoids infecting S. gilberti and hybrids of S. gilberti and S. lewini.

Visceral angiosarcoma: A nationwide analysis of treatment factors and outcomes.

BACKGROUND AND OBJECTIVES: Visceral angiosarcoma is rare and aggressive, accounting for 2% of soft tissue sarcomas. Using a national data set, we examine determinants of outcomes for patients presenting with this rare disease. METHODS: The 2004-2015 National Cancer Database was queried for patients with visceral angiosarcoma. Trends in treatment and outcomes were examined. Factors affecting overall survival (OS) were assessed with log-rank and Cox regression. RESULTS: Eight hundred and ninety-three patients with visceral angiosarcoma were identified (median age 65 years, male [63%], Charlson comorbidity index <1 [86%]). Tumor size was <5 cm in 20.7%, and 34.2% were moderate/high grade. Median OS was 3.8 months (95% CI: 3.4-4.4). By multivariate analysis, increased tumor grade and size, and liver/biliary origin demonstrated worse OS while surgery, radiation, and systemic chemotherapy demonstrated improved OS (all p < 0.001). Survival was similar between patients achieving R0 resection and those with R1/2 resection receiving chemotherapy by Kaplan-Meier analysis. CONCLUSIONS: Visceral angiosarcomas are rare tumors with poor outcomes. Liver/biliary origin, higher tumor grade, and larger tumor size demonstrate worse outcomes. While R0 resection remains the mainstay of treatment, patients with R1/R2 resection have improved survival with addition of chemotherapy. Consideration should be made for multimodal therapy in these patients.

Disentangling complex genomic signals to understand population structure of an exploited, estuarine-dependent flatfish.

Interpreting contemporary patterns of population structure requires an understanding of the interactions among microevolutionary forces and past demographic events. Here, 4,122 SNP-containing loci were used to assess structure in southern flounder (Paralichthys lethostigma) sampled across its range in the US Atlantic Ocean (Atlantic) and Gulf of Mexico (Gulf) and relationships among components of genomic variation and spatial and environmental variables were assessed across estuarine population samples in the Gulf. While hierarchical amova revealed significant heterogeneity within and between the Atlantic and Gulf, pairwise comparisons between samples within ocean basins demonstrated that all significant heterogeneity occurred within the Gulf. The distribution of Tajima's D estimated at a genome-wide scale differed significantly from equilibrium in all estuaries, with more negative values occurring in the Gulf. Components of genomic variation were significantly associated with environmental variables describing individual estuaries, and environment explained a larger component of variation than spatial proximity. Overall, results suggest that there is genetic spatial autocorrelation caused by shared larval sources for proximal nurseries (migration/drift), but that it is modified by environmentally driven differentiation (selection). This leads to conflicting signals in different parts of the genome and creates patterns of divergence that do not correspond to paradigms of strong local directional selection.

Map-like use of Earth's magnetic field in sharks.

Migration is common in marine animals,1-5 and use of the map-like information of Earth's magnetic field appears to play an important role.2,6-9 While sharks are iconic migrants10-12 and well known for their sensitivity to electromagnetic fields,13-20 whether this ability is used for navigation is unresolved.14,17,21,22 We conducted magnetic displacement experiments on wild-caught bonnetheads (Sphyrna tiburo) and show that magnetic map cues can elicit homeward orientation. We further show that use of a magnetic map to derive positional information may help explain aspects of the genetic structure of bonnethead populations in the northwest Atlantic.23-26 These results offer a compelling explanation for the puzzle of how migratory routes and population structure are maintained in marine environments, where few physical barriers limit movements of vagile species. VIDEO ABSTRACT.

Genetic diversity and structure of circumtropical almaco jack, Seriola rivoliana: tool for conservation and management.

The almaco jack, Seriola rivoliana, is a circumtropical pelagic fish of importance both in commercial fisheries and in aquaculture. To understand levels of genetic diversity within and among populations in the wild, population genetic structure and the relative magnitude of migration were assessed using mtDNA sequence data and single nucleotide polymorphisms (SNPs) from individuals sampled from locations in the Pacific and Atlantic Oceans. A total of 25 variable sites of cytochrome c oxidase subunit 1 and 3678 neutral SNPs were recovered. Three genetic groups were identified, with both marker types distributed in different oceanic regions: Pacific-1 in central Pacific, Pacific-2 in eastern Pacific and Atlantic in western Atlantic. Nonetheless, the analysis of SNP identified a fourth population in the Pacific coast of Baja California Sur, Mexico (Pacific-3), whereas that of mtDNA did not. This mito-nuclear discordance is likely explained by a recently diverged Pacific-3 population. In addition, two mtDNA haplogroups were found within the western Atlantic, likely indicating that the species came into the Atlantic from the Indian Ocean with historical gene flow from the eastern Pacific. Relative gene flow among ocean basins was low with r m < 0.2, whereas in the eastern Pacific it was asymmetric and higher from south to north (r m > 0.79). The results reflect the importance of assessing genetic structure and gene flow of natural populations for the purposes of sustainable management.

Influence of Warning Statements on Understanding of the Negative Health Consequences of Smoking.

INTRODUCTION: Pursuant to the Tobacco Control Act (TCA), the US Food and Drug Administration (FDA) is developing new cigarette health warnings to convey the negative health consequences of cigarette smoking. AIMS AND METHODS: This study assessed which of 15 revised warning statements (10 on topics similar to TCA statements and 5 on other topics) promoted greater understanding of cigarette smoking risks relative to TCA statements. In February 2018, adolescent and adult smokers and adolescents susceptible to smoking (n = 2505) completed an online experiment. Control condition participants viewed TCA statements; treatment condition participants viewed combinations of TCA and revised statements. Analyses compared revised statements to TCA statements on the same health topic or to randomly selected TCA statements if there were no statements on the same topic. RESULTS: Relative to TCA statements, 12 of 15 revised statements were more likely to be considered new information, and 12 resulted in more self-reported learning. Three revised statements made participants think more about health risks than TCA statements; the reverse was true for one revised statement. Participants rated most TCA and revised statements as moderately believable and informative. Seven revised statements were found to be less believable and factual, and one revised statement more believable and factual. Treatment condition participants correctly selected more smoking-related health conditions than control condition participants (13.79 versus 12.42 of 25). CONCLUSIONS: Findings suggest that revised statements can promote greater understanding of cigarette smoking risks. Results informed FDA's selection of warning text that was paired with images for testing in a follow-up study. IMPLICATIONS: The US FDA may adjust the text of the cigarette warning statements provided in the TCA if the revised statements promote greater public understanding of the negative health consequences of cigarette smoking. Most of the revised warning statements tested were more likely to be considered new information and resulted in more self-reported learning compared with paired TCA statements, providing support for using revised statements as part of cigarette health warnings. These results informed the development of pictorial cigarette warnings by FDA that were tested in a follow-up study and included in a proposed rule.

Impact of Pictorial Cigarette Warnings Compared With Surgeon General's Warnings on Understanding of the Negative Health Consequences of Smoking.

INTRODUCTION: The Family Smoking Prevention and Tobacco Control Act requires cigarette packages and advertisements to bear health warnings with "color graphics depicting the negative health consequences of smoking." AIMS AND METHODS: This study assessed whether new US Food and Drug Administration developed pictorial cigarette warnings (PCW) increased understanding of smoking-related risks relative to the current Surgeon General's (SG) warnings. In March-May 2019, adolescent and adult smokers and nonsmokers participated in an online experiment with three sessions completed over approximately 2 weeks. Participants viewed 1 of 16 PCW (treatment conditions) or an SG warning (control) on mock cigarette packages and advertisements. Measures assessed whether warnings provided new information, induced thinking about risks, changed smoking-related health beliefs, and were accurately recalled, among other outcomes. RESULTS: The majority of PCW (≥13 conditions) resulted in greater learning of new information, higher self-reported learning, and greater reports of thinking about smoking risks; they were viewed as more informative, understandable, and attention-drawing compared with the control condition. Most participants believed the warning were factual, although 8 PCW were perceived as less factual than the control. There were changes toward more agreement with health beliefs for 11 PCW between Sessions 1 and 2 and 7 PCW between Sessions 1 and 3. Participants in all treatment conditions were more likely than control condition participants to correctly recall the warning. Across outcomes, PCW related to addiction, death, and quitting did not perform as well as other PCW. CONCLUSIONS: Many of the PCW tested increased understanding of the risks associated with cigarette smoking relative to current SG warnings. IMPLICATIONS: The Tobacco Control Act requires cigarette packages and advertisements to bear PCW depicting the negative health consequences of smoking. This study tested whether any of 16 newly proposed PCW increased understanding of smoking-related risks relative to existing SG warnings. Results suggest that most PCW tested, particularly those related to less widely known health effects, resulted in greater learning of new information, higher self-reported learning, and greater reports of thinking about smoking risks compared with SG warnings. These results, along with other factors, informed the US Food and Drug Administration's selection of proposed PCW.

Adult Use of and Transitions From Nicotine and Non-nicotine-Containing E-cigarettes: Data From the Population Assessment of Tobacco and Health (PATH) Study, 2013-2016.

INTRODUCTION: Studies largely focus on nicotine-containing e-cigarettes (NiCE) though non-nicotine-containing e-cigarettes (NoCE) exist; NoCE prevalence and patterns of use are largely unknown. This study examines self-reported prevalence and patterns of NiCE/NoCE use. METHODS: We analyzed adult (18+ years) data from the Population Assessment of Tobacco and Health (PATH) study from Wave 1 (2013-2014, n = 32,320), Wave 2 (2014-2015, n = 28,632), and Wave 3 (2015-2016, n = 28,148). We test associations between Wave 1 self-reported current NoCE/NiCE use status and demographic characteristics and assess the proportion of self-reported current NoCE/NiCE users at Wave 1 or Wave 2 who continue to use NoCE or NiCE, switch to NiCE or NoCE, discontinue e-cigarette use, switch to use other nicotine products (ONP), or add ONP use 1 year later (i.e., at Wave 2 or 3). RESULTS: Maintaining the same self-reported NiCE/NoCE and ONP use status 1 year later was the most common use pattern between waves. However, 15.65% of exclusive NoCE users in Wave 2 transitioned to NoCE plus nicotine product use in Wave 3. Also, some exclusive NoCE users transitioned to exclusive NiCE use (17.77% Waves 1-2; 11.55% Waves 2-3). DISCUSSION: Some exclusive NoCE users transitioned to NiCE or added nicotine product use, suggesting there may be other factors (e.g., familiarity with using an aerosolizing device) in addition to the presence of nicotine in influencing initiation or sustained use of nicotine products. IMPLICATIONS: Studies largely focus on nicotine-containing e-cigarettes (NiCE) though non-nicotine-containing e-cigarettes (NoCE) exist; this study adds to the literature by describing demographic characteristics and tobacco use of adult self-reported NoCE users. In addition, the study examines transitions in self-reported NoCE/NiCE use, revealing that some exclusive NoCE users transition to other nicotine product use 1 year later.

Tobacco Product Use and Associated Factors Among Middle and High School Students - United States, 2019.

PROBLEM/CONDITION: Tobacco use is the leading cause of preventable disease, disability, and death in the United States. Most tobacco product use begins during adolescence. In recent years, tobacco products have evolved to include various smoked, smokeless, and electronic products. PERIOD COVERED: 2019. DESCRIPTION OF SYSTEM: The National Youth Tobacco Survey (NYTS) is an annual, cross-sectional, school-based, self-administered survey of U.S. middle school (grades 6-8) and high school (grades 9-12) students. A three-stage cluster sampling procedure is used to generate a nationally representative sample of U.S. students attending public and private schools. NYTS is the only nationally representative survey of U.S. middle and high school students that focuses exclusively on tobacco use patterns and associated factors. NYTS is designed to provide national data on tobacco product use and has been conducted periodically during 1999-2009 and annually since 2011. Data from NYTS are used to support the design, implementation, and evaluation of comprehensive tobacco use prevention and control programs and to inform tobacco regulatory activities. Since its inception in 1999 through 2018, NYTS had been conducted via paper and pencil questionnaires. In 2019, NYTS for the first time was administered in schools using electronic data collection methods. CDC's Office on Smoking and Health, in collaboration with the U.S. Food and Drug Administration's (FDA's) Center for Tobacco Products, analyzed data from the 2019 NYTS to assess tobacco product use patterns and associated factors among U.S. middle and high school students. Overall, 19,018 questionnaires were completed and weighted to represent approximately 27.0 million students. On the basis of self-reported grade level, this included 8,837 middle school questionnaires (11.9 million students) and 10,097 high school questionnaires (15.0 million students); 84 questionnaires with missing information on grade level were excluded from school-level analyses. RESULTS: In 2019, an estimated 53.3% of high school students (8.0 million) and 24.3% of middle school students (2.9 million) reported having ever tried a tobacco product. Current (past 30-day) use of a tobacco product (i.e., electronic cigarettes [e-cigarettes], cigarettes, cigars, smokeless tobacco, hookahs, pipe tobacco, and bidis [small brown cigarettes wrapped in a leaf]) was reported by 31.2% of high school students (4.7 million) and 12.5% of middle school students (1.5 million). E-cigarettes were the most commonly cited tobacco product currently used by 27.5% of high school students (4.1 million) and 10.5% of middle school students (1.2 million), followed in order by cigars, cigarettes, smokeless tobacco, hookahs, and pipe tobacco. Tobacco product use also varied by sex and race/ethnicity. Among current users of each tobacco product, the prevalence of frequent tobacco product use (on ≥20 days of the preceding 30 days) ranged from 16.8% of cigar smokers to 34.1% of smokeless tobacco product users. Among current users of each individual tobacco product, e-cigarettes were the most commonly used flavored tobacco product (68.8% of current e-cigarette users). Among students who reported ever having tried e-cigarettes, the three most commonly selected reasons for use were "I was curious about them" (55.3%), "friend or family member used them" (30.8%), and "they are available in flavors, such as mint, candy, fruit, or chocolate" (22.4%). Among never users of each individual tobacco product, curiosity and susceptibility (a construct that can help to identify future tobacco product experimentation or use) was highest for e-cigarettes (39.1% and 45.0%, respectively) and cigarettes (37.0% and 45.9%, respectively). Overall, 86.3% of students who reported contact with an assessed potential source of tobacco product advertisements or promotions (going to a convenience store, supermarket, or gas station; using the Internet; watching television or streaming services or going to the movies; or reading newspapers or magazines) reported exposure to marketing for any tobacco product; 69.3% reported exposure to e-cigarette marketing and 81.7% reported exposure to marketing for cigarettes or other tobacco products. Among all students, perceiving no harm or little harm from intermittent tobacco product use (use on some days but not every day) was 28.2% for e-cigarettes, 16.4% for hookahs, 11.5% for smokeless tobacco products, and 9.5% for cigarettes. Among current users of any tobacco product, 24.7% reported experiencing cravings to use tobacco products during the past 30 days and 13.7% reported wanting to use a tobacco product within 30 minutes of waking. Moreover, 57.8% of current tobacco product users reported they were seriously thinking about quitting the use of all tobacco products and 57.5% reported they had stopped using all tobacco products for ≥1 day because they were trying to quit. INTERPRETATION: In 2019, approximately one in four youths (23.0%) had used a tobacco product during the past 30 days. By school level, this represented approximately three in 10 high school students (31.2%) and approximately one in eight middle school students (12.5%). Since 2014, e-cigarettes have been the most commonly used tobacco product among youths. Importantly, more than half of current youth tobacco product users reported seriously thinking about quitting all tobacco products in 2019. However, established factors of use and initiation, including the availability of flavors, exposure to tobacco product marketing, curiosity and susceptibility, and misperceptions about harm from tobacco product use, remained prevalent in 2019 and continue to promote tobacco product use among youths. PUBLIC HEALTH ACTION: The continued monitoring of all forms of youth tobacco product use and associated factors through surveillance efforts including NYTS is important to the development of public health policy and action at national, state, and community levels. Everyone, including public health professionals, health care providers, policymakers, educators, parents, and others who influence youths, can help protect youths from the harms of all tobacco products. In addition, the comprehensive and sustained implementation of evidence-based tobacco control strategies, combined with FDA's regulation of tobacco products, is important for reducing all forms of tobacco product use among U.S. youths.

Adjuvant chemotherapy is associated with improved survival in patients with nodal metastases after neoadjuvant therapy and esophagectomy.

BACKGROUND: Studies supporting adjuvant chemotherapy after complete resection of esophageal cancer are scarce, and current clinical guidelines recommend either adjuvant chemotherapy or observation. We aimed to clarify the role of adjuvant chemotherapy in patients found to have persistent nodal metastases after neoadjuvant chemoradiation and complete resection of esophageal adenocarcinoma. METHODS: We queried the National Cancer Database (NCDB) for all patients from 2006 to 2012 with esophageal adenocarcinoma who received neoadjuvant chemoradiotherapy, underwent esophagectomy with complete resection, and were found to have lymph node metastases on final pathology. We compared patients who received adjuvant chemotherapy with patients followed by observation only. After performing propensity-score matching to create a well-balanced cohort, we compared survival using the Kaplan-Meier method. RESULTS: We identified 2,046 patients with lymph node metastases after neoadjuvant chemoradiotherapy and esophagectomy; 295 received adjuvant chemotherapy, and 1,751 did not. The median survival in the unmatched cohort was 2.6 years with adjuvant chemotherapy and 2.1 years with observation only (P=0.0185). Five-year survival was 27.9% with adjuvant chemotherapy and 21.5% with observation only. When we examined survival in a balanced cohort of 295 propensity-matched pairs, median survival was 2.6 years with adjuvant chemotherapy and 2.0 years with observation only (P=0.031). Five-year survival was 27.9% with adjuvant chemotherapy and 20.2% with observation only. CONCLUSIONS: In a large, propensity-matched cohort, adjuvant chemotherapy was associated with significantly improved survival for patients with node-positive esophageal adenocarcinoma after neoadjuvant therapy and complete resection. This finding supports the use of adjuvant therapy for patients with node-positive adenocarcinoma after neoadjuvant therapy and surgery.

Evolution of population structure in an estuarine-dependent marine fish.

Restriction site-associated DNA (RAD) sequencing was used to characterize neutral and adaptive genetic variation among geographic samples of red drum, Sciaenops ocellatus, an estuarine-dependent fish found in coastal waters along the southeastern coast of the United States (Atlantic) and the northern Gulf of Mexico (Gulf). Analyses of neutral and outlier loci revealed three genetically distinct regional clusters: one in the Atlantic and two in the northern Gulf. Divergence in neutral loci indicated gradual genetic change and followed a linear pattern of isolation by distance. Divergence in outlier loci was at least an order of magnitude greater than divergence in neutral loci, and divergence between the regions in the Gulf was twice that of divergence between other regions. Discordance in patterns of genetic divergence between outlier and neutral loci is consistent with the hypothesis that the former reflects adaptive responses to environmental factors that vary on regional scales, while the latter largely reflects drift processes. Differences in basic habitat, initiated by glacial retreat and perpetuated by contemporary oceanic and atmospheric forces interacting with the geomorphology of the northern Gulf, followed by selection, appear to have led to reduced gene flow among red drum across the northern Gulf, reinforcing differences accrued during isolation and resulting in continued divergence across the genome. This same dynamic also may pertain to other coastal or nearshore fishes (18 species in 14 families) where genetically or morphologically defined sister taxa occur in the three regions.

Hybridization between sympatric hammerhead sharks in the western North Atlantic Ocean.

Hybridization between closely related species has been documented across a wide range of taxa but has not been well studied in elasmobranchs. Hammerhead sharks have drawn global conservation concern because they experience some of the highest mortality rates among sharks when interacting with fisheries. Here we report on the detection of hybrids between the globally distributed scalloped hammerhead ( Sphyrna lewini) and recently described Carolina hammerhead ( S. gilberti) which are only known from the western Atlantic Ocean. Using a genomics approach, 10 first-generation hybrids and 15-17 backcrosses were detected from 554 individuals. The identification of backcrosses demonstrates hybrids are viable, and all backcrosses but one involved a scalloped hammerhead. All hybrids but one possessed Carolina hammerhead mtDNA, indicating sex-biased gene flow between species. Repeated hybridization and backcrossing with scalloped hammerheads could lead to the loss of endemic Carolina hammerheads.

Youth perception of harm and addictiveness of tobacco products: Findings from the Population Assessment of Tobacco and Health Study (Wave 1).

PURPOSE: We provide a US national assessment of youth perceptions of the harm and addictiveness of six separate tobacco products, identifying a continuum of perceived harm associated with a range of products in relation to patterns of current use, former use, and susceptibility to use tobacco products. METHODS: We evaluated youth respondents (N = 13,651) ages 12-17 from Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study. Analyses (2015-2016) focused on refining measures of perceived harm for each product and delineating youth characteristics (demographic, tobacco use status) associated with beliefs about the harmfulness and addictiveness of tobacco products. RESULTS: Cigars, hookah and e-cigarettes were each perceived as having significantly lower harm (p's < 0.05) than smokeless products, with the lowest ratings of harmfulness and addictiveness observed for hookah and e-cigarettes (p's < 0.001). Incrementally lower levels of harm and addictiveness perceptions were observed among youth at increasing risk for tobacco use (p's < 0.05). CONCLUSIONS: Among U.S. youth, lower perceptions of harm and addictiveness of tobacco products were associated with susceptibility to use tobacco and patterns of tobacco product use. Future longitudinal assessments from the PATH Study can provide key information on youth development of perceptions of harm and addictiveness and influences on patterns of tobacco use.