Simulation and experimental verification of ambient neutron doses in a pencil beam scanning proton therapy room as a function of treatment plan parameters.

Out-of-field patient doses in proton therapy are dominated by neutrons. Currently, they are not taken into account by treatment planning systems. There is an increasing need to include out-of-field doses in the dose calculation, especially when treating children, pregnant patients, and patients with implants. In response to this demand, this work presents the first steps towards a tool for the prediction of out-of-field neutron doses in pencil beam scanning proton therapy facilities. As a first step, a general Monte Carlo radiation transport model for simulation of out-of-field neutron doses was set up and successfully verified by comparison of simulated and measured ambient neutron dose equivalent and neutron fluence energy spectra around a solid water phantom irradiated with a variation of different treatment plan parameters. Simulations with the verified model enabled a detailed study of the variation of the neutron ambient dose equivalent with field size, range, modulation width, use of a range shifter, and position inside the treatment room. For future work, it is planned to use this verified model to simulate out-of-field neutron doses inside the phantom and to verify the simulation results by comparison with previous in-phantom measurement campaigns. Eventually, these verified simulations will be used to build a library and a corresponding tool to allow assessment of out-of-field neutron doses at pencil beam scanning proton therapy facilities.

Range-shifter effects on the stray field in proton therapy measured with the variance-covariance method.

Measurements in the stray radiation field from a proton therapy pencil beam at energies 70 and 146 MeV were performed using microdosimetric tissue-equivalent proportional counters (TEPCs). The detector volumes were filled with a propane-based tissue-equivalent gas at low pressure simulating a mean chord length of 2 µm in tissue. Investigations were performed with and without a beam range shifter, and with different air gaps between the range shifter and a solid water phantom. The absorbed dose, the dose-mean lineal energy, and the dose equivalent were determined for different detector positions using the variance-covariance method. The influence from beam energy, detector- and range-shifter positions on absorbed dose, LET, and dose equivalent were investigated. Monte Carlo simulations of the fluence, detector response, and absorbed dose contribution from different particles were performed with MCNP 6.2. The simulated dose response for protons, neutrons, and photons were compared with, and showed good agreement with, previously published experimental data. The simulations also showed that the TEPC absorbed dose agrees well with the ambient absorbed dose for neutron energies above 20 MeV. The results illustrate that changes in both dose and LET variations in the stray radiation field can be identified from TEPC measurements using the variance-covariance method. The results are in line with the changes seen in the simulated relative dose contributions from different particles associated with different proton energies and range-shifter settings. It is shown that the proton contribution scattered directly from the range shifter dominates in some situations, and although the LET of the radiation is decreased, the ambient dose equivalent is increased up to a factor of 3.

Immunogenicity properties of authentic and heterologously synthesized structural protein VP2 of infectious pancreatic necrosis virus.

The sole coat protein VP2 of infectious pancreatic necrosis virus (IPNV) was isolated and purified from intact virions, propagated in CHSE-214 cells. Likewise was the full-length VP2 protein isolated and purified upon cloning and expression of the corresponding complete gene in E. coli. The two purified proteins of different synthetic origins carrying identical primary structures were utilized in an immunization program using a rabbit model. Sera obtained against both immunogens react equally well with authentic and recombinant VP2 in Western blots and ELISAs. Also, the total net binding forces as determined by avidity index (AI) calculations were high and of similar stature, exceeding 80. An IPNV infection of susceptible and permissive CHSE-214 cells could only be neutralized by IgG preparations obtained from rabbits immunized with authentic VP2. Only such antibodies were able to aggregate and sediment radiolabeled virions in glycerol gradients upon rate zonal centrifugations. The presence of sugar moieties on the authentic protein is suggested to be of pivotal importance in eliciting an immune response capable of preventing infection in cell cultures in vitro.

Characterization of two novel cutaneous human papillomaviruses, HPV93 and HPV96.

Two novel human papillomaviruses (HPVs), HPV93 and HPV96, with genomes of 7450 and 7438 bp, respectively, are described. The L1 open reading frame of HPV93 showed highest identity to HPV24 (79%) and that of HPV96 had highest identity to HPV92 (71%). Real-time PCR for HPV92, 93 and 96 on stripped biopsies from tumours and healthy skin from 269 immunocompetent patients found HPV DNA in 2.6% of tumours and in 0.4% of healthy skin samples. Double infections were observed in two tumours. HPV92 was detected in four, HPV93 in two and HPV96 in three tumours. The range of viral loads spanned from one copy per 45 cells to one copy per 10,000 cells. The E7 proteins of HPV92, 93 and 96 were found to bind the retinoblastoma protein (pRb). These results suggest a possible role for these HPV types in skin carcinogenesis that deserves further study.

Subtype HPV38b[FA125] demonstrates heterogeneity of human papillomavirus type 38.

The human papillomaviruses (HPVs) exist as more than 100 distinct types. While variants of HPV are common, only few HPV subtypes have been reported. HPV type 38 has been proposed to be associated with nonmelanoma skin cancer (NMSC), with reported prevalences of up to 55%. A subtype of HPV38 was cloned, completely sequenced and found to have a 96% sequence similarity to prototype HPV38 in the L1 open reading frame. The presence of prototype HPV38 and HPV38b[FA125] was examined in paired biopsies of tape-stripped skin lesions and healthy skin from 269 immunocompetent patients by real-time PCR. Prototype HPV38 and HPV38b[FA125] were present in seven (3%) and five (2%) lesions, respectively, in viral loads ranging from one copy per 150 cells to one copy per 70,000 cells. In summary, we found that HPV38 is heterogeneous and is one of so far only few HPVs that contain subtypes. The heterogeneity needs to be considered in studies of the biology of this virus.

Prevalence and stability of human serum antibodies to simian virus 40 VP1 virus-like particles.

Possible human infection with simian virus 40 (SV40) has been of great concern ever since SV40 was discovered in polio vaccines. Human populations are SV40-seropositive, but because of serological cross-reactivity between SV40 and the human polyomaviruses BK virus (BKV) and JC virus (JCV), it is debatable whether these antibodies are specific. An SV40-specific serological assay was established, based on purified virus-like particles (VLPs), where the SV40 VLPs were blocked with hyperimmune sera to BKV and JCV. Competition with SV40 hyperimmune sera was used as a confirmatory test. Among 288 Swedish children of between 1 and 13 years of age, 7.6 % had SV40-specific antibodies. SV40 seroprevalence reached a peak of 14 % at 7-9 years of age. Among 100 control patients with benign tumours, 9 % were SV40-seropositive. However, SV40 DNA was not detectable in corresponding buffy-coat samples. In serial samples taken up to 5 years apart from 141 Finnish women participating in the population-based serological screening for congenital infections, only two of 141 women were SV40-seropositive in both samples. Six women seroconverted and eight women had a loss of antibodies over time. None of the SV40-seropositive samples contained detectable SV40 DNA. In conclusion, there is a low prevalence of SV40-specific antibodies in the Nordic population. The SV40 antibodies appear to have a low stability over time and their origin is not clear.

Capturing ion exchanger-bound infectious pancreatic necrosis virus--design and application for large volume water samples.

A method was designed for rapid and reliable demonstration of the presence of infectious pancreatic necrosis virus retrieved from 5 l water samples. Viruses together with an added carrier protein were adsorbed to a resin of an added anion exchanger. Then the resin was collected rapidly and quantitatively through a specific device which we designed. The resin was transferred to a column from which the viruses were eluted, and subsequently further concentrated by acid precipitation, followed by SDS-polyacrylamide gel electrophoresis and Western blot analysis. Serological results were obtained within 24 h after the water sample was introduced into the laboratory. Proteins were recovered at an efficiency between 70 and 80% and the total concentration factor ranged between 150000 and 250000 times, depending on the requirements and the methods of choice.