Feasibility of removable balloon implant for simultaneous magnetic nanoparticle heating and HDR brachytherapy of brain tumor resection cavities.

AIM: Hyperthermia (HT) has been shown to improve clinical response to radiation therapy (RT) for cancer. Synergism is dramatically enhanced if HT and RT are combined simultaneously, but appropriate technology to apply treatments together does not exist. This study investigates the feasibility of delivering HT with RT to a 5-10mm annular rim of at-risk tissue around a tumor resection cavity using a temporary thermobrachytherapy (TBT) balloon implant. METHODS: A balloon catheter was designed to deliver radiation from High Dose Rate (HDR) brachytherapy concurrent with HT delivered by filling the balloon with magnetic nanoparticles (MNP) and immersing it in a radiofrequency magnetic field. Temperature distributions in brain around the TBT balloon were simulated with temperature dependent brain blood perfusion using numerical modeling. A magnetic induction system was constructed and used to produce rapid heating (\u3e0.2°C/s) of MNP-filled balloons in brain tissue-equivalent phantoms by absorbing 0.5 W/ml from a 5.7 kA/m field at 133 kHz. RESULTS: Simulated treatment plans demonstrate the ability to heat at-risk tissue around a brain tumor resection cavity between 40-48°C for 2-5cm diameter balloons. Experimental thermal dosimetry verifies the expected rapid and spherically symmetric heating of brain phantom around the MNP-filled balloon at a magnetic field strength that has proven safe in previous clinical studies. CONCLUSIONS: These preclinical results demonstrate the feasibility of using a TBT balloon to deliver heat simultaneously with HDR brachytherapy to tumor bed around a brain tumor resection cavity, with significantly improved uniformity of heating over previous multi-catheter interstitial approaches. Considered along with results of previous clinical thermobrachytherapy trials, this new capability is expected to improve both survival and quality of life in patients with glioblastoma multiforme

The porphyrin TmPyP4 unfolds the extremely stable G-quadruplex in MT3-MMP mRNA and alleviates its repressive effect to enhance translation in eukaryotic cells

We report that the cationic porphyrin TmPyP4, which is known mainly as a DNA G-quadruplex stabilizer, unfolds an unusually stable all purine RNA G-quadruplex (M3Q) that is located in the 5′-UTR of MT3-MMP mRNA. When the interaction between TmPyP4 and M3Q was monitored by UV spectroscopy a 22-nm bathochromic shift and 75% hypochromicity of the porphin major Soret band was observed indicating direct binding of the two molecules. TmPyP4 disrupts folded M3Q in a concentration-dependent fashion as was observed by circular dichroism (CD), 1D 1H NMR and native gel electrophoresis. Additionally, when TmPyP4 is present during the folding process it inhibits the M3Q RNA from adopting a G-quadruplex structure. Using a dual reporter gene construct that contained the M3Q sequence alone or the entire 5′-UTR of MT3-MMP mRNA, we report here that TmPyP4 can relieve the inhibitory effect of the M3Q G-quadruplex. However, the same concentrations of TmPyP4 failed to affect translation of a mutated construct. Thus, TmPyP4 has the ability to unfold an RNA G-quadruplex of extreme stability and modulate activity of a reporter gene presumably via the disruption of the G-quadruplex

Bioavailability of Macro and Micronutrients Across Global Topsoils: Main Drivers and Global Change Impacts

Understanding the chemical composition of our planet\u27s crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro- and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome-dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling-atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world

How Much is the Public Willing to Pay to be Protected from Identity Theft?

Identity theft has become one of the most ubiquitous crimes in the USA with estimates of the number of households being victimized annually ranging between 5% and 25%, resulting in direct losses totaling hundreds of billions of dollars over the past few years. Government efforts to combat identity theft have included legislation criminalizing and increasing penalties as well as regulatory efforts designed to protect individual identifying information held by financial and other business organizations. At the same time, individuals are taking their own preventive actions and purchasing private protection such as credit monitoring and identity theft insurance services. We use data from a large sample of residents from four states (Illinois, Louisiana, Pennsylvania, and Washington) in order to assess the public's willingness to pay (WTP) for a government program designed to reduce identify theft under two separate conditions, one promising a 25% reduction in identity theft and the other promising a 75% reduction in identity theft. Results indicate that: (1) between 40% and 66% of the public is willing to pay an additional tax for identity theft prevention, more so when the promise of a reduction is highest (75% compared to 25%) with an average WTP of $87, and (2) WTP is highest among individuals who carry many credit cards, who subscribe to an identity theft protection service, and who take active steps in preventing fraud by shredding bills and paying with cash, but is lowest among individuals who believe that taxes are too high. Converted into a "per crime" cost and combined with the portion of identity theft costs that are borne directly by business, we estimate the average cost per identity theft to range from approximately$2,800 to $5,100

Radium-226 accumulation in Florida freshwater mussels.

Selected lakes in Hillsborough County, Florida have been hydrologically augmented with groundwater to offset stage declines caused by excessive pumping of the Floridan Aquifer. Augmentation water can be relatively rich in 226Ra (\u3e5 decays per minute [dpm] L-1). We measured 226Ra activities in shells and soft tissues of adult bivalve molluscs (Elliptio cf. buckleyi) from groundwater-augmented and nonaugmented lakes to assess bioaccumulation of 226Ra by mussels. Mussels from augmented lakes displayed higher 226Ra in both shells and tissues than did mussels from nonaugmented lakes. Within a sample, 226Ra activity in Elliptio tissues was higher than the value measured in shells. Highest activities were found in a composite mussel sample (n = 6) from an augmented lake; soft tissue activity was 619 ± 33 dpm g-1 dry weight and shell activity was 147 ± 7 dpm g-1 g dry weight. Large mussels displayed greater activities in soft tissues and shells than did small mussels. We transplanted animals from a nonaugmented lake into a groundwater-augmented water body. 226Ra activity in dry tissue rose from 32 ± 1 to 196 ± 2 dpm g-1 within 2 months. When 226Ra -rich mussels (232 ± 2 dpm g-1) from the augmented lake were transferred to the nonaugmented lake, they showed no significant 226Ra loss over the 69-d experiment. Large Elliptio mussels concentrated 226Ra in their soft tissues to levels about 1,000 to 25,000 times concentrations in lake water. Pumping of groundwater in Florida for residential, agricultural, and industrial use contributes dissolved 226Ra to some surface water bodies, where it can be bioaccumulated by bivalve molluscs

Biological accumulation of 226Ra in a groundwater-augmented Florida lake.

Round Lake, Hillsborough County, Florida (U.S.A.) has been augmented with 226Ra-rich (6.2 dpm L-1) groundwater from the Floridan aquifer for more than 30 years. Water column 226Ra activity in Round Lake is 3.4 dpm L-1, about one third of the U.S. drinking water standard value. Radionuclide measurements in biota and sediment cores from the lake indicate high 226Ra activities in plants, mollusc shells and tissues, fish bones, and recent sediments. Unionid mussels bioaccumulate 226Ra and display very high activities in soft tissues (219.9-454.8 dpm g-1 dry). Throughout Florida, groundwaters are increasingly pumped for agricultural irrigation, as well as residential and industrial use. Biological accumulation of 226Ra by filter-feeding pelecypods in aquatic ecosystems is an important pathway for transfer of the radionuclide to higher trophic levels of both aquatic and terrestrial food webs. Radionuclide analysis of soft tissues from aquatic bivalves provides a rapid means of identifying waterbodies that receive substantial inputs of dissolved 226Ra