Detailed analysis of the cell-inactivation mechanism by accelerated protons and light ions

Published survival data for V79 cells irradiated by monoenergetic protons, helium-3, carbon, and oxygen ions and for CHO cells irradiated by carbon ions have been analyzed using the probabilistic two-stage model of cell inactivation. Three different classes of DNA damages formed by traversing particles have been distinguished, namely severe single-track damages which might lead to cell inactivation directly, less severe damages where cell inactivation is caused by their combinations, and damages of negligible severity that can be repaired easily. Probabilities of single ions to form these damages have been assessed in dependence on their linear energy transfer (LET) values. Damage induction probabilities increase with atomic number and LET. While combined damages play crucial role at lower LET values, single-track damages dominate in high-LET regions. The yields of single-track lethal damages for protons have been compared with the Monte Carlo estimates of complex DNA lesions, indicating that lethal events correlate well with complex DNA double-strand breaks. The decrease in the single-track damage probability for protons of LET above approx. 30 keV/$\mu$m, suggested by limited experimental evidence, is discussed, together with the consequent differences in the mechanisms of biological effects between protons and heavier ions. Applications of the results in hadrontherapy treatment planning are outlined.Comment: submitted to Physics in Medicine and Biolog

Anisotropic Magnetoconductance in Quench-Condensed Ultrathin Beryllium Films

Near the superconductor-insulator (S-I) transition, quench-condensed ultrathin Be films show a large magnetoconductance which is highly anisotropic in the direction of the applied field. Film conductance can drop as much as seven orders of magnitude in a weak perpendicular field (< 1 T), but is insensitive to a parallel field in the same field range. We believe that this negative magnetoconductance is due to the field de-phasing of the superconducting pair wavefunction. This idea enables us to extract the finite superconducting phase coherence length in nearly superconducting films. Our data indicate that this local phase coherence persists even in highly insulating films in the vicinity of the S-I transition.Comment: 4 pages, 4 figure RevTex, Typos Correcte

An Expanded Multi-scale Monte Carlo Simulation Method for Personalized Radiobiological Effect Estimation in Radiotherapy: a feasibility study

A novel and versatile “bottom-up� approach is developed to estimate the radiobiological effect of clinic radiotherapy. The model consists of multi-scale Monte Carlo simulations from organ to cell levels. At cellular level, accumulated damages are computed using a spectrum-based accumulation algorithm and predefined cellular damage database. The damage repair mechanism is modeled by an expanded reaction-rate two-lesion kinetic model, which were calibrated through replicating a radiobiological experiment. Multi-scale modeling is then performed on a lung cancer patient under conventional fractionated irradiation. The cell killing effects of two representative voxels (isocenter and peripheral voxel of the tumor) are computed and compared. At microscopic level, the nucleus dose and damage yields vary among all nucleuses within the voxels. Slightly larger percentage of cDSB yield is observed for the peripheral voxel (55.0%) compared to the isocenter one (52.5%). For isocenter voxel, survival fraction increase monotonically at reduced oxygen environment. Under an extreme anoxic condition (0.001%), survival fraction is calculated to be 80% and the hypoxia reduction factor reaches a maximum value of 2.24. In conclusion, with biological-related variations, the proposed multi-scale approach is more versatile than the existing approaches for evaluating personalized radiobiological effects in radiotherapy

Reactive Molecular Dynamics study on the first steps of DNA-damage by free hydroxyl radicals

We employ a large scale molecular simulation based on bond-order ReaxFF to simulate the chemical reaction and study the damage to a large fragment of DNA-molecule in the solution by ionizing radiation. We illustrate that the randomly distributed clusters of diatomic OH-radicals that are primary products of megavoltage ionizing radiation in water-based systems are the main source of hydrogen-abstraction as well as formation of carbonyl- and hydroxyl-groups in the sugar-moiety that create holes in the sugar-rings. These holes grow up slowly between DNA-bases and DNA-backbone and the damage collectively propagate to DNA single and double strand break.Comment: 6 pages and 8 figures. movies and simulations are available at: http://qmsimulator.wordpress.com

ГЕПАТИТ Е: НОВАЯ ПРОБЛЕМА ТРАНСПЛАНТОЛОГИИ?

Hepatitis E is enterically transmitted infection and is the cause of outbreaks and sporadic cases. Disease was originally registered only in the developing subtropical and tropical countries and has been connected with I or II genotypes of hepatitis E virus (HEV). Later sporadic hepatitis E has been registered in a number of the deve- loped countries of Western Europe, North America, South East Asia and Ocenia. These cases have been caused, as a rule, by III or IV genotypes of HEV. Until recently it was considered, that the disease is usually self-limited except pregnant women in which HEV infection is more severe, often leading to fulminant liver failure and death in a significant proportion of patients. The current review represents the analysis of publications of the last years reflecting the facts that HEV infection may develop in immunosuppressed patients, in particular in liver transplant recipients, who may then serve as long-term carriers of the virus with progression to cirrhosis. The information on the first attempts of antiviral therapy in these patients is presented. Гепатит Е относится к группе энтеральных гепатитов и может иметь характер как эпидемической, так и спорадической инфекции. Заболевание первоначально регистрировалось только в развивающихся суб- тропических и тропических странах и было связано с заражением I или II генотипами вируса. Позже спо- радический гепатит Е был зарегистрирован в ряде развитых стран Западной Европы, Северной Америки, Юго-Восточной Азии и Океании. Эти случаи были обусловлены инфицированием, как правило, III или IV генотипами вируса гепатита Е (HEV). До недавнего времени считалось, что течение болезни имеет об- ратимый характер и обычно завершается выздоровлением за исключением случаев заражения женщин на поздних сроках беременности, у которых была описана возможность развития фульминантного гепатита. Настоящий обзор посвящен анализу публикаций последних лет, отражающих течение HEV-инфекции у больных с иммунодефицитом, в частности у реципиентов трансплантатов солидных органов, для кото- рых совсем недавно была показана возможность хронизации болезни и трансформации ее в цирроз пече- ни. Представлена информация о первых попытках противовирусной терапии у этих больных.

Cervical Screening within HIV Care: Findings from an HIV-Positive Cohort in Ukraine

HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe

Treatment and disease progression in a birth cohort of vertically HIV-1 infected children in Ukraine

Background: Ukraine has the highest HIV prevalence (1.6%) and is facing the fastest growing epidemic in Europe. Our objective was to describe the clinical, immunological and virological characteristics, treatment and response in vertically HIV-infected children living in Ukraine and followed from birth.Methods: The European Collaborative Study (ECS) is an ongoing cohort study, in which HIV-1 infected pregnant women are enrolled and followed in pregnancy, and their children prospectively followed from birth. ECS enrolment in Ukraine started in 2000 initially with three sites, increasing to seven sites by 2009.Results: A total of 245 infected children were included in the cohort by April 2009, with a median age of 23 months at most recent follow-up; 33% (n = 77) had injecting drug using mothers and 85% (n = 209) were infected despite some use of antiretroviral prophylaxis for prevention of mother-to-child transmission. Fifty-five (22%) children had developed AIDS, at a median age of 10 months (IQR = 6-19). The most prevalent AIDS indicator disease was Pneumocystis jiroveci pneumonia (PCP). Twenty-seven (11%) children had died (median age, 6.2 months). Overall, 108 (44%) children had started highly active antiretroviral treatment (HAART), at a median 18 months of age; median HAART duration was 6.6 months to date. No child discontinued HAART and 92% (100/108) remained on their first-line HAART regimen to date. Among children with moderate/severe immunosuppression, 36% had not yet started HAART. Among children on HAART, 71% (69/97) had no evidence of immunosuppression at their most recent visit; the median reduction in HIV RNA was 4.69 log10 copies/mL over a median of 10 months treatment. From survival analysis, an estimated 94%, 84% and 81% of children will be alive and AIDS-free at 6, 12 and 18 months of age, respectively. However, survival increased significantly over time: estimated survival rates to 12 months of age were 87% for children born in 2000/03 versus 96% for those born in 2004/08.Conclusion: One in five children had AIDS and one in ten had died. The half of children who received HAART has responded well and survival has significantly improved over time. Earlier diagnosis and prompt initiation of HAART remain key challenges

Localisation of C-nociceptor-activated spinal cord neurones that project to the ventrolateral periaqueductal grey in the rat

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Nociceptor activation of descending pathways from the hypothalamus that relay in the periaqueductal grey

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Activation of spinal dorsal horn neurones that project to depressor sites in the ventrolateral periaqueductal grey

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