Evolution and Dynamics of Tropical River Plumes in the Great Barrier Reef: An Integrated Remote Sensing and In Situ Study

[1] The short-lived but intense discharge of freshwater from tropical rivers into the Great Barrier Reef (GBR) Lagoon and the associated salinity reductions are a critical consideration in marine research and management of the ecologically sensitive GBR World Heritage Area. Salinity provides a unique tracer that gives clues to the origin of river-borne contaminants and allows the influences of storm-induced resuspension and river discharge on turbidity to be clearly distinguished. We describe a field investigation of the evolution and dynamics of the Herbert River plume in the central GBR. Its primary goals were to use an airborne salinity mapper and in situ instruments to study the three-dimensional structure and evolution of the plume and to lay a foundation for numerical modeling studies of its dynamics. The aircraft surveys provided a rapid assessment of the plumes spatial extent, while the in situ data revealed details of its subsurface structure. The Herbert River plume was produced by heavy rainfall associated with tropical storms during the La Nina-dominated 1999/2000 monsoon season. In the near field, the surface expression of the plume boundaries was indicated by sharp color and salinity fronts that were clearly visible from the air and sea surface. In the far field and middle Lagoon, the plume was more dispersed and ultimately merged with the larger-scale salinity gradients and with the remnant plume of the more distant, and larger, Burdekin River. The plume location and structure evolved in response to changing river flows, tidal and subtidal circulation, and wind. Using Garvine\u27s Kelvin number-based scheme, the plume was classified as intermediate in dynamical character and thus is subject to a variety of forcings. The plume evolved in response to changes in the relative intensity of tidal currents and low-frequency circulation due to wind and western boundary current forcing. It also displayed a characteristic hook-shaped\u27\u27 structure, which has been identified previously in numerical plume model studies. This structure appeared in the presence of accelerating along-shelf current flow and horizontal shear and it indicates that the plume circulation had a strongly three-dimensional character. The approach demonstrates the efficacy of combining airborne and in situ methods to observe rapidly evolving coastal salinity structure and dynamics and sets the stage for future satellite-borne studies of larger-scale features showing contrasting salinity distributions

Evolution and dynamics of tropical river plumes in the Great Barrier Reef: an integrated remote sensing and in situ study

The short-lived but intense discharge of freshwater from tropical rivers into the Great Barrier Reef (GBR) Lagoon and the associated salinity reductions are a critical consideration in marine research and management of the ecologically sensitive GBR World Heritage Area. Salinity provides a unique tracer that gives clues to the origin of river-borne contaminants and allows the influences of storm-induced resuspension and river discharge on turbidity to be clearly distinguished. We describe a field investigation of the evolution and dynamics of the Herbert River plume in the central GBR. Its primary goals were to use an airborne salinity mapper and in situ instruments to study the three-dimensional structure and evolution of the plume and to lay a foundation for numerical modeling studies of its dynamics. The aircraft surveys provided a rapid assessment of the plumes spatial extent, while the in situ data revealed details of its subsurface structure. The Herbert River plume was produced by heavy rainfall associated with tropical storms during the La Nina-dominated 1999/2000 monsoon season. In the near field, the surface expression of the plume boundaries was indicated by sharp color and salinity fronts that were clearly visible from the air and sea surface. In the far field and middle Lagoon, the plume was more dispersed and ultimately merged with the larger-scale salinity gradients and with the remnant plume of the more distant, and larger, Burdekin River. The plume location and structure evolved in response to changing river flows, tidal and subtidal circulation, and wind. Using Garvine’s Kelvin number-based scheme, the plume was classified as intermediate in dynamical character and thus is subject to a variety of forcings. The plume evolved in response to changes in the relative intensity of tidal currents and low-frequency circulation due to wind and western boundary current forcing. It also displayed a characteristic ‘‘hook-shaped’’ structure, which has been identified previously in numerical plume model studies. This structure appeared in the presence of accelerating along-shelf current flow and horizontal shear and it indicates that the plume circulation had a strongly three-dimensional character. The approach demonstrates the efficacy of combining airborne and in situ methods to observe rapidly evolving coastal salinity structure and dynamics and sets the stage for future satellite-borne studies of larger-scale features showing contrasting salinity distributions

Building and Improving Reference Genome Assemblies: This paper reviews the problems and algorithms of assembling a complete genome from millions of short DNA sequencing reads

A genome sequence assembly provides the foundation for studies of genotypic and phenotypic variation, genome structure, and evolution of the target organism. In the past four decades, there has been a surge of new sequencing technologies, and with these developments, computational scientists have developed new algorithms to improve genome assembly. Here we discuss the relationship between sequencing technology improvements and assembly algorithm development and how these are applied to extend and improve human and nonhuman genome assemblies. © 1963-2012 IEEE

Quantum entanglement with acousto-optic modulators: 2-photon beatings and Bell experiments with moving beamsplitters

We present an experiment testing quantum correlations with frequency shifted photons. We test Bell inequality with 2-photon interferometry where we replace the beamsplitters by acousto-optic modulators, which are equivalent to moving beamsplitters. We measure the 2-photon beatings induced by the frequency shifts, and we propose a cryptographic scheme in relation. Finally, setting the experiment in a relativistic configuration, we demonstrate that the quantum correlations are not only independent of the distance but also of the time ordering between the two single-photon measurements.Comment: 14 pages, 16 figure

Inflammatory breast cancer: dynamic contrast-enhanced MR in patients receiving bevacizumab. Initial experience

To retrospectively compare three dynamic contrast material-enhanced magnetic resonance (MR) imaging (dynamic MR imaging) analytic methods to determine the parameter or combination of parameters most strongly associated with changes in tumor microvasculature during treatment with bevacizumab alone and bevacizumab plus chemotherapy in patients with inflammatory or locally advanced breast cancer. MATERIALS AND METHODS: This study was conducted in accordance with the institutional review board of the National Cancer Institute and was compliant with the Privacy Act of 1974. Informed consent was obtained from all patients. Patients with inflammatory or locally advanced breast cancer were treated with one cycle of bevacizumab alone (cycle 1) followed by six cycles of combination bevacizumab and chemotherapy (cycles 2-7). Serial dynamic MR images were obtained, and the kinetic parameters measured by using three dynamic analytic MR methods (heuristic, Brix, and general kinetic models) and two region-of-interest strategies were compared by using two-sided statistical tests. A P value of .01 was required for significance. RESULTS: In 19 patients, with use of a whole-tumor region of interest, the authors observed a significant decrease in the median values of three parameters measured from baseline to cycle 1: forward transfer rate constant (Ktrans) (-34% relative change, P=.003), backflow compartmental rate constant extravascular and extracellular to plasma (Kep) (-15% relative change, P<.001), and integrated area under the gadolinium concentration curve (IAUGC) at 180 seconds (-23% relative change, P=.009). A trend toward differences in the heuristic slope of the washout curve between responders and nonresponders to therapy was observed after cycle 1 (bevacizumab alone, P=.02). The median relative change in slope of the wash-in curve from baseline to cycle 4 was significantly different between responders and nonresponders (P=.009). CONCLUSION: The dynamic contrast-enhanced MR parameters Ktrans, Kep, and IAUGC at 180 seconds appear to have the strongest association with early physiologic response to bevacizumab. Clinical trial registration no. NCT0001654

Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.

IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. INTERVENTIONS: Treatment with TTFields was delivered continuously (&gt;18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409

Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial.

Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles). Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P &lt; .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P &lt; .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis. clinicaltrials.gov Identifier: NCT00916409

Monkey-based Research on Human Disease: The Implications of Genetic Differences

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology — there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists

A historical perspective on the discovery of statins

Cholesterol is essential for the functioning of all human organs, but it is nevertheless the cause of coronary heart disease. Over the course of nearly a century of investigation, scientists have developed several lines of evidence that establish the causal connection between blood cholesterol, atherosclerosis, and coronary heart disease. Building on that knowledge, scientists and the pharmaceutical industry have successfully developed a remarkably effective class of drugs—the statins—that lower cholesterol levels in blood and reduce the frequency of heart attacks

VERTIGO (VERtical Transport In the Global Ocean) : a study of particle sources and flux attenuation in the North Pacific

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 55 (2008): 1522-1539, doi:10.1016/j.dsr2.2008.04.024.The VERtical Transport In the Global Ocean (VERTIGO) study examined particle sources and fluxes through the ocean’s “twilight zone” (defined here as depths below the euphotic zone to 1000 m). Interdisciplinary process studies were conducted at contrasting sites off Hawaii (ALOHA) and in the NW Pacific (K2) during 3 week occupations in 2004 and 2005, respectively. We examine in this overview paper the contrasting physical, chemical and biological settings and how these conditions impact the source characteristics of the sinking material and the transport efficiency through the twilight zone. A major finding in VERTIGO is the considerably lower transfer efficiency (Teff) of particulate organic carbon (POC), POC flux 500 / 150 m, at ALOHA (20%) vs. K2 (50%). This efficiency is higher in the diatom-dominated setting at K2 where silica-rich particles dominate the flux at the end of a diatom bloom, and where zooplankton and their pellets are larger. At K2, the drawdown of macronutrients is used to assess export and suggests that shallow remineralization above our 150 m trap is significant, especially for N relative to Si. We explore here also surface export ratios (POC flux/primary production) and possible reasons why this ratio is higher at K2, especially during the first trap deployment. When we compare the 500 m fluxes to deep moored traps, both sites lose about half of the sinking POC by >4000 m, but this comparison is limited in that fluxes at depth may have both a local and distant component. Certainly, the greatest difference in particle flux attenuation is in the mesopelagic, and we highlight other VERTIGO papers that provide a more detailed examination of the particle sources, flux and processes that attenuate the flux of sinking particles. Ultimately, we contend that at least three types of processes need to be considered: heterotrophic degradation of sinking particles, zooplankton migration and surface feeding, and lateral sources of suspended and sinking materials. We have evidence that all of these processes impacted the net attenuation of particle flux vs. depth measured in VERTIGO and would therefore need to be considered and quantified in order to understand the magnitude and efficiency of the ocean’s biological pump.Funding for VERTIGO was provided primarily by research grants from the US National Science Foundation Programs in Chemical and Biological Oceanography (KOB, CHL, MWS, DKS, DAS). Additional US and non-US grants included: US Department of Energy, Office of Science, Biological and Environmental Research Program (JKBB); the Gordon and Betty Moore Foundation (DMK); the Australian Cooperative Research Centre program and Australian Antarctic Division (TWT); Chinese NSFC and MOST programs (NZJ); Research Foundation Flanders and Vrije Universiteit Brussel (FD, ME); JAMSTEC (MCH); New Zealand Public Good Science Foundation (PWB); and internal WHOI sources and a contribution from the John Aure and Cathryn Ann Hansen Buesseler Foundation (KOB)