Measuring rainfall from above and below the sea surface

Satellites play a major role in the determination of the rainfall at sea. Researchers at Southampton Oceanography Centre (SOC) have been involved in two projects addressing this task. First they have been instrumental in developing techniques to retrieve rain rate information from the 10+ years of dual-frequency altimeter data. The TOPEX radar measures rainfall via the attenuation it causes, producing a climatology that is independent of those derived from passive microwave (PM) and infrared (IR) sensors. Because TOPEX is an active microwave sensor, it can have a much smaller footprint than PM sensors. Therefore it can be used to estimate the size of rain cells, showing that the ITCZ and mid-latitude storm tracks are characterized by larger rain systems than elsewhere. TOPEX’s simultaneous recording of wind and wave data reveal that, for mid-latitude systems, rain is most likely in association with developing seas.All satellite-based datasets require validation, and SOC's work on the development and testing of acoustic rain gauges is the second aspect of this paper. By listening at a range of frequencies, an underwater hydrophone may distinguish the spectra of wind, rain, shipping etc., and estimate the wind speed or rain rate according to the magnitude of the signals. All our campaigns have shown a good acoustic response to changes in wind speed. However the quantitative inversion for recent trials has given values that are too high, possibly because of significant acoustic reflection from the sea bottom. The changes in spectral slope often agree with other observations of rain, although validation experiments in coastal regions are hampered by the extraneous sources present. Acoustic rain gauges would eventually see service not only for routine satellite validation, but also for real-time monitoring of locations of interest

Asymmetric transfer of CO2 across a broken sea surface

Most estimates of the climatically-important transfer of atmospheric gases into, and out of, the ocean assume that the ocean surface is unbroken by breaking waves. However the trapping of bubbles of atmospheric gases in the ocean by breaking waves introduces an asymmetry in this flux. This asymmetry occurs as a bias towards injecting gas into the ocean where it dissolves, and against the evasion/exsolution of previously-dissolved gas coming out of solution from the oceans and eventually reaching the atmosphere. Here we use at-sea measurements and modelling of the bubble clouds beneath the ocean surface to show that the numbers of large bubbles found metres below the sea surface in high winds are sufficient to drive a large and asymmetric flux of carbon dioxide. Our results imply a much larger asymmetry for carbon dioxide than previously proposed. This asymmetry contradicts an assumption inherent in most existing estimates of ocean-atmosphere gas transfer. The geochemical and climate implications include an enhanced invasion of carbon dioxide into the stormy temperate and polar seas

Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.

Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1–3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS. Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles. The primary endpoint was 4-month progression-free survival (PFS). Secondary endpoints were overall survival, response rate, and disease control rate. Results: Twenty-five patients were enrolled. The median age was 49 years (range, 22–77 years) and 52% were male. Median PFS was 2.27 months [95% confidence interval (CI), 1.9–3.9], and the 4-month PFS rate was 21.1% (95% CI, 9.7–45.9), which was not an improvement over the hypothesized null 4-month PFS rate of 28.3% (P ¼ 0.79). Median overall survival was 9.0 months (95% CI, 5.7–17.7). A partial response occurred in 2 (8%) of the evaluable patients (95% CI, 1.0–26.0), one with PIK3CA E542K-mutant embryonal rhabdomyosarcoma and another with spindle cell sarcoma. The disease control rate was 14/25 (56%; 95% CI, 34.9–75.6). The most common adverse events were diarrhea (84%), nausea (64%), and fatigue (56%). Conclusions: The combination of pazopanib and trametinib was tolerable without indication of added activity of the combination in STS. Further study may be warranted in RAS/RAF aberrant sarcomas. ©2017 AACR

BRAF V600E mutations in urine and plasma cell-free DNA from patients with Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare histiocytosis with a high prevalence of BRAF V600E mutation (>50% of patients). Patients with BRAF-mutant ECD can respond to BRAF inhibitors. Unfortunately, the lack of adequate archival tissue often precludes BRAF testing. We hypothesized that cell-free DNA (cfDNA) from plasma or urine can offer an alternative source of biologic material for testing. We tested for BRAF V600E mutation in cfDNA from the plasma and urine of 6 ECD patients. In patients with available archival tissue, the result of BRAF mutation analysis was concordant with plasma and urine cfDNA results in all 3 patients (100% agreement, kappa 1.00). In all 6 patients, BRAF mutation analysis of plasma and urine cfDNA was concordant in 5 of 6 patients (83% agreement, kappa 0.67). Testing for BRAF V600E mutation in plasma and urine cfDNA should be further investigated as an alternative to archival tissue mutation analysis

MET nucleotide variations and amplification in advanced ovarian cancer: characteristics and outcomes with c-Met inhibitors.

PurposeMET alterations including amplifications and nucleotide variations have been associated with resistance to therapy and aggressive clinical behavior.Experimental designThe medical records of patients presenting to the University of Texas MD Anderson Cancer Center Phase I Clinic with relapsed or metastatic ovarian cancers and known MET nucleotide variation or amplification status were reviewed retrospectively (n=178). Categorical and continuous clinical and molecular characteristics were compared using Fisher's exact and Wilcoxon rank-sum tests, respectively. Univariate and multivariate survival were assessed via Kaplan-Meier and Cox regression analysis, respectively.ResultsMET amplification occurred in 4 (3.5%) of 113 patients, whereas nonsynonomous nucleotide variations were present in 9 (7.4%) of 122 patients. No patients exhibited concomitant amplification and variation. MET variations were observed only in white women with high-grade ovarian tumors, whereas amplifications were observed in both black and white women with high-grade serous ovarian primary tumors. No patients (n=4) exhibiting a MET alteration achieved an objective response when treated on a c-Met inhibitor phase I trial. In addition, ovarian cancer patients treated with a c-Met inhibitor with multikinase activity trended towards a longer time-to-failure compared with those treated with a c-Met-specific inhibitor (median: 1.5 vs. 4.5 months, p=0.07).ConclusionsMET alterations occur in a minority of patients with ovarian cancer. c-Met inhibitors with multikinase activity may exhibit less activity in ovarian cancer than c-Met specific drugs. These findings warrant further investigation

Extending ballistic graphene FET lumped element models to diffusive devices

In this work, a modified, lumped element graphene field effect device model is presented. The model is based on the "Top-of-the-barrier" approach which is usually valid only for ballistic graphene nanotransistors. Proper modifications are introduced to extend the model's validity so that it accurately describes both ballistic and diffusive graphene devices. The model is compared to data already presented in the literature. It is shown that a good agreement is obtained for both nano-sized and large area graphene based channels. Accurate prediction of drain current and transconductance for both cases is obtained

Antimicrobial Effectiveness of Innovative Photocatalysts: A Review

Waterborne pathogens represent one of the most widespread environmental concerns. Conventional disinfection methods, including chlorination and UV, pose several operational and environmental problems; namely, formation of potentially hazardous disinfection by-products (DBPs) and high energy consumption. Therefore, there is high demand for effective, low-cost disinfection treatments. Among advanced oxidation processes, the photocatalytic process, a form of green technology, is becoming increasingly attractive. A systematic review was carried out on the synthesis, characterization, toxicity, and antimicrobial performance of innovative engineered photocatalysts. In recent decades, various engineered photocatalysts have been developed to overcome the limits of conventional photocatalysts using different synthesis methods, and these are discussed together with the main parameters influencing the process behaviors. The potential environmental risks of engineered photocatalysts are also addressed, considering the toxicity effects presented in the literature

Is the United States Claims Court Constitutional?

This article will deal with two major constitutional problems that have resulted from the creation of the Claims Court. The first issue is the constitutionality of the appointment of existing Court of Claims Commissioners to be judges on the Claims Court during a four-year transition period. By legislatively designating the persons who are to serve as judges on the new court, Congress has usurped the presidential appointment power. The second issue relates to the constitutional status of the Claims Court. The Court of Claims which it replaces was created under article III of the Constitution, and the judges on it were therefore entitled to life tenure and salaries that could not be reduced during their terms in office. The new Claims Court, on the other hand, is designated by Congress as an article I court; the judges are to be appointed for only fifteen year terms, and their salaries are subject to control by Congress. The new court exercises full judicial authority, however, and has jurisdiction over cases of national importance in which the government of the United States has a great financial stake. Although the analysis of this issue is far from simple, this author concludes that Congress has exceeded its constitutional authority by failing to comply with the requirements of article III of the Constitution in establishing the Claims Court

Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy.

Preclinical models suggest that histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors have synergistic anticancer activity. We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of combined mTOR inhibitor sirolimus (1 mg-5 mg PO daily) and HDAC inhibitor vorinostat (100 mg-400 mg PO daily) in patients with advanced cancer. Seventy patients were enrolled and 46 (66%) were evaluable for DLT assessment since they completed cycle 1 without dose modification unless they had DLT. DLTs comprised grade 4 thrombocytopenia (n = 6) and grade 3 mucositis (n = 1). Sirolimus 4 mg and vorinostat 300 mg was declared RP2D because MTD with sirolimus 5 mg caused significant thrombocytopenia. The grade 3 and 4 drug-related toxic effects (including DLTs) were thrombocytopenia (31%), neutropenia (8%), anemia (7%), fatigue (3%), mucositis (1%), diarrhea (1%), and hyperglycemia (1%). Of the 70 patients, 35 (50%) required dose interruption or modification and 61 were evaluable for response. Partial responses were observed in refractory Hodgkin lymphoma (-78%) and perivascular epithelioid tumor (-54%), and stable disease in hepatocellular carcinoma and fibromyxoid sarcoma. In conclusion, the combination of sirolimus and vorinostat was feasible, with thrombocytopenia as the main DLT. Preliminary anticancer activity was observed in patients with refractory Hodgkin lymphoma, perivascular epithelioid tumor, and hepatocellular carcinoma