Comparative Analysis of Sea Scallop Escapement/Retention and Resulting Economic Impacts

During the months of June and September 1988, gear experiments were conducted aboard the F/V Carolina Dawn and Carolina Capes. The primary objective of the experiments was to assess the technical efficiency and size selectivity of 3.5-inch ring dredges relative to the current commercially-used 3.0-inch ring dredges. Secondary objectives were to analyze the economic and regulatory ramifications of using 3.5-inch ring dredges to control the age-at-capture and enhance the yield-per- recruit

The burden of proof: the current state of atrial fibrillation prevention and treatment trials

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015

Amplification of Microsatellites in the Persian Sturgeon (Acipenser Persicus)

Persian sturgeon (Acipenser persicus) is a benthic species occurring primarily on sandy bottoms in the mid and southern Caspian Sea, especially along the shores of Iran (Berg, 1948; Holcik, 1989). The Persian sturgeon in the Caspian Sea is anadromous, with at least eighteen groups that segregate spatially and temporally for spawning. These populations are supported by some spawners, each of which considered to be of two seasonal races and divided into two or four biological groups (Perevaryukha, 2001)

Population structure, connectivity, and demographic history of an apex marine predator, the bull shark <i>Carcharhinus leucas</i>

Knowledge of population structure, connectivity, and effective population size remains limited for many marine apex predators, including the bull shark Carcharhinus leucas. This large‐bodied coastal shark is distributed worldwide in warm temperate and tropical waters, and uses estuaries and rivers as nurseries. As an apex predator, the bull shark likely plays a vital ecological role within marine food webs, but is at risk due to inshore habitat degradation and various fishing pressures. We investigated the bull shark\u27s global population structure and demographic history by analyzing the genetic diversity of 370 individuals from 11 different locations using 25 microsatellite loci and three mitochondrial genes (CR, nd4, and cytb). Both types of markers revealed clustering between sharks from the Western Atlantic and those from the Western Pacific and the Western Indian Ocean, with no contemporary gene flow. Microsatellite data suggested low differentiation between the Western Indian Ocean and the Western Pacific, but substantial differentiation was found using mitochondrial DNA. Integrating information from both types of markers and using Bayesian computation with a random forest procedure (ABC‐RF), this discordance was found to be due to a complete lack of contemporary gene flow. High genetic connectivity was found both within the Western Indian Ocean and within the Western Pacific. In conclusion, these results suggest important structuring of bull shark populations globally with important gene flow occurring along coastlines, highlighting the need for management and conservation plans on regional scales rather than oceanic basin scale

Serum vitamin D levels and survival of patients with colorectal cancer: Post-hoc analysis of a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Recently, serum 25-hydroxyvitamin D (25OHD) levels were shown to be associated with the survival of patients with colorectal cancer. However, 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels. In this study, we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer.</p> <p>Methods</p> <p>We started a prospective cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum samples and clinical data. As part of a post-hoc analysis, serum 25OHD levels were measured by radioimmunoassay. Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis, gender, cancer stage, residual tumor after surgery, time period of surgery, location of tumor, adjuvant chemotherapy and number of lymph nodes with metastasis at surgery. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were determined.</p> <p>Results</p> <p>Serum 25OHD levels were measured in 257 patients. Only 3% had sufficient levels (30 ng/ml and greater). Based on month of blood sampling, an annual oscillation of 25OHD levels was seen, with levels being lower in spring and higher in late summer. Higher 25OHD levels were associated with better overall survival under multi-variate analysis (HR, 0.91: 95% CI, 0.84 to 0.99, <it>P </it>= 0.027).</p> <p>Conclusions</p> <p>These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer.</p

Acquired Resistance to KRAS (G12C) Inhibition in Cancer

BACKGROUND: Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS(G12C)). The mechanisms of acquired resistance to these therapies are currently unknown. METHODS: Among patients with KRAS(G12C) -mutant cancers treated with adagrasib monotherapy, we performed genomic and histologic analyses that compared pretreatment samples with those obtained after the development of resistance. Cell-based experiments were conducted to study mutations that confer resistance to KRAS(G12C) inhibitors. RESULTS: A total of 38 patients were included in this study: 27 with non-small-cell lung cancer, 10 with colorectal cancer, and 1 with appendiceal cancer. Putative mechanisms of resistance to adagrasib were detected in 17 patients (45% of the cohort), of whom 7 (18% of the cohort) had multiple coincident mechanisms. Acquired KRAS alterations included G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and high-level amplification of the KRAS(G12C) allele. Acquired bypass mechanisms of resistance included MET amplification; activating mutations in NRAS, BRAF, MAP2K1, and RET; oncogenic fusions involving ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN. In two of nine patients with lung adenocarcinoma for whom paired tissue-biopsy samples were available, histologic transformation to squamous-cell carcinoma was observed without identification of any other resistance mechanisms. Using an in vitro deep mutational scanning screen, we systematically defined the landscape of KRAS mutations that confer resistance to KRAS(G12C) inhibitors. CONCLUSIONS: Diverse genomic and histologic mechanisms impart resistance to covalent KRAS(G12C) inhibitors, and new therapeutic strategies are required to delay and overcome this drug resistance in patients with cancer. (Funded by Mirati Therapeutics and others; ClinicalTrials.gov number, NCT03785249.)

Prognostic Significance of Vitamin D Receptor Polymorphisms in Head and Neck Squamous Cell Carcinoma

BACKGROUND:In patients with advanced non-small-cell lung cancer, vitamin D receptor (VDR) polymorphisms and haplotypes are reported to be associated with survival. We hypothesized that a similar association would be observed in patients with head and neck squamous-cell carcinoma (HNSCC). METHODS:In a post-hoc analysis of our previous prospective cohort study, VDR polymorphisms including Cdx2 G/A (rs11568820), FokI C/T (rs10735810), BsmI A/G (rs1544410), ApaI G/T (rs7976091), and TaqI T/C (rs731236) were genotyped by sequencing in 204 consecutive patients with HNSCC who underwent tumor resection. Progression-free survival was compared between VDR polymorphisms using Kaplan-Meier survival curves with log-rank tests and Cox proportional hazard models adjusting for age, gender, smoking status, primary tumor sites, postoperative stages, existence of residual tumor, and postoperative treatment with chemotherapy or radiotherapy. RESULTS:During a median follow-up of 1,047 days, tumor progression and death occurred in 76 (37.3%) and 27 (13.2%) patients, respectively. The FokI T/T genotype was associated with poor progression-free survival: median survival for T/T was 265 days compared with 1,127 days for C/C or C/T (log-rank test: P = 0.0004; adjusted hazard ratio, 3.03; 95% confidence interval, 1.62 to 5.67; P = 0.001). In contrast, the other polymorphisms (Cdx2, BsmI, ApaI, TaqI) showed no significant association with progression-free survival. The A-T-G (Cdx2-FokI-ApaI) haplotype demonstrated a significant association with a higher progression rate (P = 0.02). CONCLUSION:These results suggest that VDR polymorphisms and haplotypes may be associated with prognosis in patients with HNSCC, although the sample size is not large enough to draw definitive conclusions

The impact of polymorphic variations in the 5p15, 6p12, 6p21 and 15q25 loci on the risk and prognosis of Portuguese patients with non-small cell lung cancer

Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. MATERIALS AND METHODS: Blood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF -460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p?=?0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p?=?0.042; rs3025010 (VEGF intron 5 C/T), p?=?0.047; rs401681 C/T at 5p15, p?=?0.046; and rs31489 C/A at 5p15, p?=?0.029. CONCLUSIONS: Our study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well.This project was supported by Programa Doutoral em Medicina e Oncologia Molecular, University of Porto, Porto, Portugal and University of Minho, Braga, Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript