Quantitative Assessment of 3D Dose Rate for Proton Pencil Beam Scanning FLASH Radiotherapy and Its Application for Lung Hypofractionation Treatment Planning

To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton therapy (IMPT) treatment planning using transmission beams. An in-house FLASH planning platform was developed to optimize transmission (shoot-through) plans for nine consecutive lung cancer patients previously planned with proton SBRT. Dose and dose rate calculation codes were developed to quantify three types of dose rate calculation methods (dose-averaged dose rate (DADR), average dose rate (ADR), and dose-threshold dose rate (DTDR)) based on both phantom and patient treatment plans. Two different minimum MU/spot settings were used to optimize two different dose regimes, 34-Gy in one fraction and 45-Gy in three fractions. The OAR sparing and target coverage can be optimized with good uniformity (hotspot < 110% of prescription dose). ADR, accounting for the spot dwelling and scanning time, gives the lowest dose rate; DTDR, not considering this time but a dose-threshold, gives an intermediate dose rate, whereas DADR gives the highest dose rate without considering any time or dose-threshold. All three dose rates attenuate along the beam direction, and the highest dose rate regions often occur on the field edge for ADR and DTDR, whereas DADR has a better dose rate uniformity. The differences in dose rate metrics have led a large variation for OARs dose rate assessment, posing challenges to FLASH clinical implementation. This is the first attempt to study the impact of the dose rate models, and more investigations and evidence for the details of proton PBS FLASH parameters are needed to explore the correlation between FLASH efficacy and the dose rate metrics.

The effect of varying alkalinity in Mediterranean seawater on lightning flash intensity – An experimental approach

&lt;p&gt;The atmospheric phenomenon of lightning has been the focus of many studies in atmospheric physics and chemistry. In our laboratory investigations we have shown that the intensity of electrical sparks discharged into natural and artificial saline solutions are strongly influenced by their salinity and pH. We consider the radiative intensity of the laboratory generated electrical spark to be a scaled down replication of natural lightning and therefore define it as Lightning Flash Intensity (LFI). Based on the pH experiments it was suggested that a decrease in ocean pH due to ocean acidification corresponding to the predicted increase in atmospheric CO&lt;sub&gt;2&lt;/sub&gt; according to the IPCC RCP 8.5 worst case emission scenario, may increase the LFI by approximately 30&amp;#177;7% by the end of the 21&lt;sup&gt;st&lt;/sup&gt; century relative to 2000. In that study, it was also shown that the acidification of seawater with a strong acid resulted also in a positive but weaker effect on LFI, suggesting that the alkalinity of seawater may also have an effect on it. Where, alkalinity is defined as the ability of seawater to resist a change in pH by addition of an acid (buffering capacity). In this study we tested the effect of changes in the alkalinity of Mediterranean seawater on its LFI by addition of concentrated HCl (alkalinity decrease) and NaOH (alkalinity increase). These treatments varied the alkalinity from its naturally occurring value of ca. 2600 to as little as 2100 and as much as 3000 &amp;#181;mole/kg. The additions of HCl decreased the pH of the seawater from its naturally occurring value of ca. 8.2 to a minimum value of 7.4 after equilibration with atmospheric CO&lt;sub&gt;2&lt;/sub&gt;. While, the additions of NaOH increased the pH to a maximum value of 8.5. It should be noted that within the experimental range, the addition of HCl and NaOH did not have a measurable effect on the electrical conductivity/salinity of the seawater solutions. The results of these experiments showed that the LFI was strongly and positively correlated with alkalinity and was higher by ca. 40% at 3000 &amp;#181;mole/kg relative to its value at 2100 &amp;#181;mole/kg. These results imply that the alkalinity of natural waters may also be a strong predictor of LFI, especially in regions where there is a significant alkalinity input from external sources such as rivers and groundwater inputs or upwelling of alkalinity and CO&lt;sub&gt;2&lt;/sub&gt; enriched deep waters. Such regions could include the Mediterranean and North Seas as well as the intense upwelling regions off the west coasts of Africa and South America as well as South Africa. It is interesting to note that these regions also coincide with high densities of super-bolt events as previously shown.&lt;/p&gt;

Use of a novel camera trapping approach to measure small mammal responses to peatland restoration

Small mammals, such as small rodents (Rodentia: Muroidea) and shrews (Insectivora: Soricidae), present particular challenges in camera trap surveys. Their size is often insufficient to trigger infra-red sensors, whilst resultant images may be of inadequate quality for species identification. The conventional survey method for small mammals, live-trapping, can be both labour-intensive and detrimental to animal welfare. Here, we describe a method for using camera traps for monitoring small mammals. We show that by attaching the camera trap to a baited tunnel, fixing a close-focus lens over the camera trap lens, and reducing the flash intensity, pictures or videos can be obtained of sufficient quality for identifying species. We demonstrate the use of the method by comparing occurrences of small mammals in a peatland landscape containing (i) plantation forestry (planted on drained former blanket bog), (ii) ex-forestry areas undergoing bog restoration, and (iii) unmodified blanket bog habitat. Rodents were detected only in forestry and restoration areas, whilst shrews were detected across all habitat. The odds of detecting small mammals were 7.6 times higher on camera traps set in plantation forestry than in unmodified bog, and 3.7 times higher on camera traps in restoration areas than in bog. When absolute abundance estimates are not required, and camera traps are available, this technique provides a low-cost survey method that is labour-efficient and has minimal animal welfare implications.

EFFECT OF PLAN TEXTRACTS ON THE LEVEL OF FREE-RADICAL PROCESSES IN HUMAN CELLS

We evaluated the effects of extracts from the pomegranate (Punica granatum), vine (Vitis vinifera) seeds and garlic (Allium sativum) on free-radical reactions in human cells in relation to SNPs in the SOD2and СAT genes. The object was human peripheral leukocytes cultured in the presence of extracts from pomegranate (1.2; 2.4 %), garlic (0.5; 1.2 %) and vine seeds (1.2; 2.4 %). Intensity of free-radical reactions was assessed by a fast flash and flashlight sum of the luminol-dependent chemiluminescence (LDCL). Alleles of SOD2and СAT were analyzed using allele-specific PCR. The results showed that the pomegranate extract decreases LDCL intensity reliably in comparison with the control. Extracts of the garlic (1.2 %) and vine seeds (1.2 %) increase LDCL intensity. Correlation was established between the genotype determined by polymorphism of SOD2 gene Ala16Val (rs4880) and fast flash intensity during human cell cultivation with the extract of vine seeds (1.2 %).

Ocean acidification may be increasing the intensity of lightning over the oceans

The anthropogenic increase in atmospheric CO2 is not only considered to drive global warming, but also ocean acidification. Previous studies have shown that acidification will affect many aspects of biogenic carbon uptake and release in the surface water of the oceans. In this report we present a potential novel impact of acidification on the flash intensity of lightning discharged into the oceans. Our experimental results show that a decrease in ocean pH corresponding to the predicted increase in atmospheric CO2 according to the IPCC RCP 8.5 worst case emission scenario, may increase the intensity of lightning discharged into seawater by approximately 30 ± 7% by the end of the twenty-first century relative to 2000.

Ocean acidification may be increasing the intensity of lightning over the oceans

&lt;p&gt;The anthropogenic increase in atmospheric CO&lt;sub&gt;2&lt;/sub&gt; is not only considered to drive global warming, but also ocean acidification. Previous studies have shown that acidification will affect many aspects of carbon uptake and release in the surface water of the ocean through increased primary productivity and decreased biogenic calcification and CaCO&lt;sub&gt;3&lt;/sub&gt; dissolution. In this report we present a potential novel impact of acidification on the flash intensity of lightning discharged into the oceans. Our experimental results show that a decrease in ocean pH corresponding to the predicted increase in atmospheric CO&lt;sub&gt;2&lt;/sub&gt; according to the IPCC RCP 8.5 worst case emission scenario will increase the Lightning Flash Intensity (LFI) by ca. 30% by the end of the 21&lt;sup&gt;st&lt;/sup&gt; century relative to 2000. This increase in LFI may have broader implications for the atmospheric NO&lt;sub&gt;x&lt;/sub&gt; production and precipitation as well as the atmospheric ozone budget (O&lt;sub&gt;3&lt;/sub&gt; and N&lt;sub&gt;2&lt;/sub&gt;O production). In turn, these feedback processes may impact both marine and terrestrial biological uptake of carbon that should be considered in global carbon and climate models.&lt;/p&gt;

A quantitative account of mammalian rod phototransduction with PDE6 dimeric activation: responses to bright flashes

We develop an improved quantitative model of mammalian rod phototransduction, and we apply it to the prediction of responses to bright flashes of light. We take account of the recently characterized dimeric nature of PDE6 activation, where the configuration of primary importance has two transducin molecules bound. We simulate the stochastic nature of the activation and shut-off reactions to generate the predicted kinetics of the active molecular species on the disc membrane surfaces, and then we integrate the differential equations for the downstream cytoplasmic reactions to obtain the predicted electrical responses. The simulated responses recover the qualitative form of bright-flash response families recorded from mammalian rod photoreceptors. Furthermore, they provide an accurate description of the relationship between the time spent in saturation and flash intensity, predicting the transition between first and second ‘dominant time constants’ to occur at an intensity around 5000 isomerizations per flash, when the rate of transducin activation is taken to be 1250 transducins s −1 per activated rhodopsin. This rate is consistent with estimates from light-scattering experiments, but is around fourfold higher than has typically been assumed in other studies. We conclude that our model and parameters provide a compelling description of rod photoreceptor bright-flash responses.

Ophthalmic findings in sheep treated with closantel in Curitiba, Brazil

Background and Aim: Closantel is a widely used anti-parasitic drug that is known to cause ophthalmic problems that lead to blindness. The aim of this study was to investigate the possible electroretinographic changes in sheep that received closantel. Materials and Methods: Twenty-four 30-day-old Suffolk sheep were split into control group (12 animals) and closantel group (12 animals). The latter group received 15 mg/kg of closantel subcutaneously immediately after the first electroretinography (ERG). The ISCEV protocol was used to perform the ERGs pre-dose (0), 7, and 30 days after treatment. Statistical analyses to compare ERG responses using t-test and analysis of variance were performed (p<0.05). Three months later, the animals were euthanized and the eyes and a part of optic nerve were collected for histopathology. Photography of the retina and optic nerve was taken, and measures of the retinal layers were made and analyzed by paired t-test. Results: Closantel group showed a significant increase of the mean scotopic a-wave amplitude from 0 to 7 days after closantel administration, using a stimulus of 10,000 mcd.s/m2 and a decrease of the mean scotopic and photopic a-wave amplitude (from 7 to 30 days) using the same flash intensity, as well as a decrease in mean photopic b-wave amplitude (from 7 to 30 days) within the group. Control group showed a significant increase of the mean scotopic b-wave implicit time from pre to 30 days after treatment and an increase of the mean scotopic a-wave implicit time from pre to 7 days after treatment, with the stimulus of 10,000 mcd.s/m2. This group also showed a decrease in mean photopic b-wave implicit time (from pre to 30 days after treatment), using a stimulus of 10,000 mcd.s/m2 and a decrease in mean photopic a-wave implicit time from pre to 30 days after treatment, using a stimulus of 3000 mcd.s/m2. The no difference was found in images neither in the measurements of the retina layers. Conclusion: As observed by ERG responses and the histopathology, a dose of 15 mg/kg of closantel does not significantly affect retinal and optic nerve structures in sheep but the electroretinographic results, however, showed alterations on the phototransduction.