Assessment and monitoring of marine debris in Gray's Reef National Marine Sanctuary

Gray’s Reef National Marine Sanctuary (GRNMS) is located 32.4 km offshore of Sapelo Island, Georgia. The ecological importance of this area is related to the transition between tropical and temperate waters, and the existence of a topographically complex system of ledges. Due to its central location, GRNMS can be used as a focal site to study the accumulation and impacts of marine debris on the Atlantic continental shelf offshore of the Southeast United States. Previously, researchers characterized marine debris in GRNMS and reported that incidence of the debris at the limited densely colonized ledge sites was significantly greater than at sand or sparsely colonized live bottom, and is further influenced by the level of boating activity and physiographic characteristics (e.g., ledge height). Information gleaned from the initial marine debris characterization was used to devise a strategy for prioritizing cleanup and monitoring efforts. However, a significant gap in knowledge was the rate of debris accumulation. The primary objective of this study was to select, mark, and perform initial marine debris surveys at permanent monitoring sites within GRNMS to quantify long-term trends in types, abundance, impacts, and accumulation rates of debris. Ledge sites were selected to compare types, abundance, and accumulation rates of marine debris between a) areas of high and low use and b) short and tall ledges. Nine permanent monitoring sites were marked and initially surveyed in 2007/2008. Surveys were conducted within a 50 x 4 m transect for a total survey area of 200 square meters. All debris was removed and detailed information was taken on the types of debris, quantity, and associations with benthic fauna. Information on associations with benthic fauna included degree of entanglement, type of organism with which it is entangled or resting on, degree of fouling, and visible impacts such as tissue abrasions. Sites were re-surveyed approximately one year later to quantify new accumulation. During the initial survey, a total of ten debris items, totaling 16.3 kg in weight, were removed from two monitoring stations, both “tall” sites within the area of high boat use. Year-one accumulation totaled five items and approximately 7 kg in weight. Similar to the initial survey, all debris was found at sites in the area of high boat use. However, in contrast to the initial survey, two of these items were found on medium-height ledges. Removed items included fishing line, leaders, rope, plastic, and fabric. Although items were often encrusted in benthic biota or entangled on the ledge, impacts such as abrasions or other injuries were not observed. During the 2009 monitoring efforts, volunteer divers were trained to conduct the survey. Monitoring protocols were documented for GRNMS staff and included as an appendix of this report to enable long-term monitoring of sites. Additionally, national reconnaissance data (e.g. satellite, radar, aerial surveys) and other information on known fishing locations were examined for patterns of resource use and correlations with debris occurrence patterns. A previous model predicting the density of marine debris based on ledge features and boat use was refined and the results were used to generate a map of predicted debris density for all ledges

Data Exploration, Quality Control and Testing in Single-Cell qPCR-Based Gene Expression Experiments

Cell populations are never truly homogeneous; individual cells exist in biochemical states that define functional differences between them. New technology based on microfluidic arrays combined with multiplexed quantitative polymerase chain reactions (qPCR) now enables high-throughput single-cell gene expression measurement, allowing assessment of cellular heterogeneity. However very little analytic tools have been developed specifically for the statistical and analytical challenges of single-cell qPCR data. We present a statistical framework for the exploration, quality control, and analysis of single-cell gene expression data from microfluidic arrays. We assess accuracy and within-sample heterogeneity of single-cell expression and develop quality control criteria to filter unreliable cell measurements. We propose a statistical model accounting for the fact that genes at the single-cell level can be on (and for which a continuous expression measure is recorded) or dichotomously off (and the recorded expression is zero). Based on this model, we derive a combined likelihood-ratio test for differential expression that incorporates both the discrete and continuous components. Using an experiment that examines treatment-specific changes in expression, we show that this combined test is more powerful than either the continuous or dichotomous component in isolation, or a t-test on the zero-inflated data. While developed for measurements from a specific platform (Fluidigm), these tools are generalizable to other multi-parametric measures over large numbers of events.Comment: 9 pages, 5 figure

Diskless Image Management (DIM) for Cluster Administration

Large computing systems have large administration needs. But just as technologies have evolved to take advantage of certain parallelisms of large scale computing, administrating these technologies must evolve to take advantage of the associated operational efficiencies. Using a straightforward push technology, and scalable to thousands of blades, Diskless Image Management (DIM) allows system administrators to boot, patch, or modify one, several or all distributed images in minutes from a single management console. DIM was prototyped on the MareNostrum cluster with 2406 blades, but is scalable to 7000 blades. Using IBM JS20 blade technology MareNostrum consists of 172 BladeCenters

Carbon Monoxide: A Rare Cause of Myocardial Ischemia

In an acute care setting, chemical asphyxiants (CA) are a vice which cause debilitating injury. Carbon monoxide (CO) is one well known CA which causes hypoxic injury to cardiovascular and neurological tissue. CO poisoning is one of the leading causes of death in USA. As many as 6% of patients who get admitted with CO poisoning in the USA have acute myocardial infarction. A strong positive correlation of CO Hb concentration has been established with increased incidence of MIs. We present a case of a 75-year-old male with complaints of chest discomfort, dyspnea, diaphoresis that was attributed to CO poisoning. Over the course of his stay he had two sets of positive serial troponins and was diagnosed with a non-ST elevation MI. Most of the recent literature focuses on ST elevation and T wave inversions in patients with CO poisoning. Contrary to this, our patient did not exhibit any EKG changes at any point during his hospital course. CO poisoning can cause fatal complications including an MI

Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection

In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 – 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 – 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 – 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist

Genetic and environmental susceptibility to food allergy in a registry of twins

Non peer reviewe

"Happy to Close?": The relationship between surgical experience and incisional hernia rates following abdominal wall closure in colorectal surgery

Aim Incisional hernia (IH) is a common complication of colorectal surgery, affecting up to 30% of patients at 2 years. Given the associated morbidity and high recurrence rates after attempted repair of IH, emphasis should be placed on prevention. There is an association between surgeon volume and outcomes in hernia surgery, yet there is little evidence regarding impact of the seniority of the surgeon performing abdominal wall closure on IH rate. The aim of our study was to assess the rates of IH at 1 year following abdominal wall closure between junior and senior surgeons in patients undergoing elective colorectal surgery. Methods This was an exploratory analysis of patients who underwent elective surgery for colorectal cancer between 2014–2018 as part of the Hughes Abdominal Repair Trial (HART), a prospective, multicentre randomised control trial comparing abdominal wall closure methods. Grade of surgeon performing abdominal closure was categorised into “trainee” and “consultant” and compared to IH rate at one year. Results A total of 663 patients were included in this retrospective analysis of patients in the HART trial. The rate of IH in patients closed by trainees was 20%, compared to 12% in those closed by consultants (p = <0.001). When comparing closure methods, IH rates were significantly higher in the Hughes closure arm between trainees and consultants (20% vs. 12%, p = 0.032), but not high enough in the mass closure arm to reach statistical significance (21% vs. 13%, p = 0.058). On multivariate analysis, age (p = 0.036, OR: 1.02, 95% CI: 1.00–1.04), Male sex (p = 0.049, OR: 1.61, 95% CI: 1.00–2.59) and closure by a trainee (p = 0.006, OR: 1.85, 95% CI: 1.20–2.85) were identified as risk factors for developing IH. Conclusion Patients who undergo abdominal wall closure by a surgeon in training have an increased risk of developing IH when compared to those closed by a consultant. Further work is needed to determine the impact of supervised and unsupervised trainees on IH rates, but abdominal wall closure should be regarded as a training opportunity in its own righ

Molecular Signatures of Hemagglutinin Stem-Directed Heterosubtypic Human Neutralizing Antibodies against Influenza A Viruses

Recent studies have shown high usage of the IGHV1-69 germline immunoglobulin gene for influenza hemagglutinin stem-directed broadly-neutralizing antibodies (HV1-69-sBnAbs). Here we show that a major structural solution for these HV1-69-sBnAbs is achieved through a critical triad comprising two CDR-H2 loop anchor residues (a hydrophobic residue at position 53 (Ile or Met) and Phe54), and CDR-H3-Tyr at positions 98±1; together with distinctive V-segment CDR amino acid substitutions that occur in positions sparse in AID/polymerase-η recognition motifs. A semi-synthetic IGHV1-69 phage-display library screen designed to investigate AID/polη restrictions resulted in the isolation of HV1-69-sBnAbs that featured a distinctive Ile52Ser mutation in the CDR-H2 loop, a universal CDR-H3 Tyr at position 98 or 99, and required as little as two additional substitutions for heterosubtypic neutralizing activity. The functional importance of the Ile52Ser mutation was confirmed by mutagenesis and by BCR studies. Structural modeling suggests that substitution of a small amino acid at position 52 (or 52a) facilitates the insertion of CDR-H2 Phe54 and CDR-H3-Tyr into adjacent pockets on the stem. These results support the concept that activation and expansion of a defined subset of IGHV1-69-encoded B cells to produce potent HV1-69-sBnAbs does not necessarily require a heavily diversified V-segment acquired through recycling/reentry into the germinal center; rather, the incorporation of distinctive amino acid substitutions by Phase 2 long-patch error-prone repair of AID-induced mutations or by random non-AID SHM events may be sufficient. We propose that these routes of B cell maturation should be further investigated and exploited as a pathway for HV1-69-sBnAb elicitation by vaccination

Linkage Disequilibrium in Wild Mice

Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD) in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1) Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2) they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3) LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits