Pulse parameter optimizer: an efficient tool for achieving prescribed dose and dose rate with electron FLASH platforms.

Purpose. Commercial electron FLASH platforms deliver ultra-high dose rate doses at discrete combinations of pulse parameters including pulse width (PW), pulse repetition frequency (PRF) and number of pulses (N), which dictate unique combinations of dose and dose rates. Additionally, collimation, source to surface distance, and airgaps also vary the dose per pulse (DPP). Currently, obtaining pulse parameters for the desired dose and dose rate is a cumbersome manual process involving creating, updating, and looking up values in large spreadsheets for every treatment configuration. This work presents a pulse parameter optimizer application to match intended dose and dose rate precisely and efficiently.Methods. Dose and dose rate calculation methods have been described for a commercial electron FLASH platform. A constrained optimization for the dose and dose rate cost function was modelled as a mixed integer problem in MATLAB (The MathWorks Inc., Version9.13.0 R2022b, Natick, Massachusetts). The beam and machine data required for the application were acquired using GafChromic film and alternating current current transformers (ACCTs). Variables for optimization included DPP for every collimator, PW and PRF measured using ACCT and airgap factors.Results. Using PW, PRF,Nand airgap factors as parameters, a software was created to optimize dose and dose rate, reaching the closest match if exact dose and dose rates are not achievable. Optimization took 20 s or less to converge to results. This software was validated for accuracy of dose calculation and precision in matching prescribed dose and dose rate.Conclusion. A pulse parameter optimization application was built for a commercial electron FLASH platform to increase efficiency in dose, dose rate, and pulse parameter prescription process. Automating this process reduces safety concerns associated with manual look up and calculation of these parameters, especially when many subjects at different doses and dose rates are to be safely managed.

Reduced contamination of pig carcasses using an alternative pluck set removal procedure during slaughter.

This study compared the current pig slaughter procedure where the pluck set is completely removed with a procedure where the pluck set is partially removed, leaving the highly contaminated oral cavity, tonsils and tongue untouched. The effect on carcass contamination was investigated by enumerating hygiene indicator bacteria (total aerobic count, Enterobacteriaceae and E. coli) and cefotaxime-resistant E. coli (CREC) as well as assessing Salmonella and Yersinia enterocolitica presence on the sternum, elbow and throat of pig carcasses. Using the alternative pluck set removal, significantly lower mean numbers of hygiene indicator bacteria on throat samples and E. coli on elbow samples were found. Less pig carcasses were highly contaminated and a lower presence and level of CREC was observed. No difference in Salmonella or Yersinia enterocolitica presence was seen. The data in this study can help to assess the effect of this alternative procedure on the safety of pork and subsequently public health.

SU-E-T-436: Feasibility of Using the 'Irregular Surface Compensator' Planning Feature of the Eclipse TPS for Total Body Irradiation (TBI) Treatment Planning.

PURPOSE: To investigate the feasibility of using the Irregular Surface Compensator (ISC) planning feature of the Eclipse treatment planning system (TPS) for Total Body Irradiation (TBI). METHODS: TBI treatments require that the whole body receives within +-10% of the prescribed dose. Different body parts with different thicknesses compared to the umbilicus separation may receive higher or lower doses compared to the prescribed dose. Another challenge is to keep the lung dose below 10Gy to avoid complications. To mitigate this problem, physical compensators and blocks are used during the treatment for different body parts and lungs. This method presents a challenge during the treatment delivery and prolongs the treatment time due to patient setup, in-vivo on-line dosimetric monitoring and the adjustment of the compensators frequently during the treatment. We investigated the use of ISC planning feature of Eclipse TPS which is an electronic compensation method that calculates a fluence map based on the body contour from the CT image. The fluence map is delivered with dynamic MLCs . This TBI treatment technique was tested using a Rando phantom in Head First Supine position with lateral beams at SSD=250cm.The calculated fluence were edited so that the lung received <∼10Gy for 12Gy prescription. A single fraction of 2Gy was delivered and the in-vivo measurements were performed in the neck, lung and the umbilicus by using OSLDs. RESULTS: OSLD measurements and the Eclipse TPS predictionswere 200.4/195.0, 162.2/168.9, and 196.1/208.9 cGy for the neck, lung and the umbilicus respectively. CONCLUSIONS: The feasibility of using the 'Irregular Surface Compensator' feature of Eclipse TPS for TBI treatment planning was demonstrated. Good agreement (<6%) between the predicted and measured doses was obtained. The proposed planning and delivery simplifies the compensation and blocking to achieve uniform dose distributions and reduces the treatment time.

A mouse model of autosomal recessive polycystic kidney disease with biliary duct and proximal tubule dilatation.

Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the polycystic kidney and hepatic disease (PKHD1) gene encoding the protein fibrocystin/polyductin. The aim of our study was to produce a mouse model of ARPKD in which there was no functional fibrocystin/polyductin to study the pathophysiology of cystic and fibrocystic disease in renal and non-renal tissues. Exon 2 of the gene was deleted and replaced with a neomycin resistance cassette flanked by loxP sites, which could be subsequently removed by Cre-lox recombinase. Homozygous Pkhd1(del2/del2) mice were viable, fertile and exhibited hepatic, pancreatic, and renal abnormalities. The biliary phenotype displayed progressive bile duct dilatation, resulting in grossly cystic and fibrotic livers in all animals. The primary cilia in the bile ducts of these mutant mice had structural abnormalities and were significantly shorter than those of wild-type (WT) animals. The Pkhd1(del2/del2) mice often developed pancreatic cysts and some exhibited gross pancreatic enlargement. In the kidneys of affected female mice, there was tubular dilatation of the S3 segment of the proximal tubule (PT) starting at about 9 months of age, whereas male mice had normal kidneys up to 18 months of age. Inbreeding the mutation onto BALBc/J or C57BL/6J background mice resulted in females developing PT dilatation by 3 months of age. These inbred mice will be useful resources for studying the mechanisms underlying the pathogenesis of ARPKD.

A shielding design for an accelerator-based neutron source for boron neutron capture therapy.

Research in boron neutron capture therapy (BNCT) at The Ohio State University Nuclear Engineering Department has been primarily focused on delivering a high quality neutron field for use in BNCT using an accelerator-based neutron source (ABNS). An ABNS for BNCT is composed of a proton accelerator, a high-energy beam transport system, a (7)Li target, a target heat removal system (HRS), a moderator assembly, and a treatment room. The intent of this paper is to demonstrate the advantages of a shielded moderator assembly design, in terms of material requirements necessary to adequately protect radiation personnel located outside a treatment room for BNCT, over an unshielded moderator assembly design.

Effects of general practice-based nurse-counselling on ambulatory blood pressure and antihypertensive drug prescription in patients at increased risk of cardiovascular disease.

Lifestyle programmes delivered by academic nurse-counsellors in a primary care setting lowered blood pressure (BP) among at-risk patients. We examined whether the programmes could be successfully implemented by nurses employed in Australian general practices. In a randomised controlled trial, 212 of 591 eligible 20-75-year olds with hypertension, Type II diabetes or coronary disease from seven practices volunteered. Patients were randomised to: a 'Low' group with one face-to-face individual counselling session, then monthly telephone contacts for 1 year (n=69); a 'High' group with individual face-to-face counselling up to 1 h monthly for 1 year (n=74) or a control group receiving usual care only (n=69), and were evaluated at baseline and 12 and 18 months later; 164 individuals completed the study. Patients' usual doctors continued to prescribe in all groups. Changes in 24 h ambulatory BP did not differ significantly between groups at 12 months (Low, -2+/-2/1+/-1 mmHg; High, +4+/-2/1+/- 1 mmHg; usual care, +1+/-2/1+/-1 mmHg) or 18 months (-2+/-2/2+/-1 mmHg; -4+/-2/3+/-2 mmHg; -1+/-2/2+/- 1 mmHg, respectively). Antihypertensive drugs prescribed decreased by 12 months in 33% of the High, 5% of the Low and 13% of the control groups (P=0.008) and by 36, 7 and 16% at 18 months (P=0.018). After 18 months, targets for BP control were not met in about 60% of patients and almost 50% had clinic BP above 140/90 mmHg. Year-long interaction with nurse-counsellors may influence longer-term antihypertensive drug prescription, possibly by improving compliance. Suboptimal BP control suggests that continuing physician education on BP targets is needed.

Evidence for new alleles in the protein kinase adenosine monophosphate-activated gamma(3)-subunit gene associated with low glycogen content in pig skeletal muscle and improved meat quality.

Several quantitative trait loci (QTL) affecting muscle glycogen content and related traits were mapped to pig chromosome 15 using a three-generation intercross between Berkshire x Yorkshire pigs. On the basis of the QTL location the PRKAG3 (protein kinase, AMP-activated, gamma(3)-subunit) gene was considered to be a good candidate for the observed effects. Differences in the PRKAG3 gene sequences of the founder animals of the intercross were analyzed. The RN(-) mutation previously reported was not present in the cross but three missense substitutions and a polymorphic short interspersed element (SINE) were identified. To confirm the hypothesis that at least one of these mutations was associated with differences in meat quality, >1800 animals from several unrelated commercial lines were genotyped for the candidate substitutions and an association study was performed. The results demonstrate the presence of new economically important alleles of the PRKAG3 gene affecting the glycogen content in the muscle and the resulting meat quality. Haplotype analysis was shown to resolve the effects of PRKAG3 more clearly than analysis of individual polymorphisms. Because of their prevalence in the more common commercial breeds, the potential implications for the pig industry and consumers are considerably greater than the original discovery of the RN(-) mutation. Furthermore, these results illustrate that additional alleles of genes involved in major mutations may play a significant role in quantitative trait variation.

Development and calculation of an energy dependent normal brain tissue neutron RBE for evaluating neutron fields for BNCT.

In Boron Neutron Capture Therapy (BNCT) of malignant brain tumors, the energy dependence of a clinically relevant Relative Biological Effectiveness (RBE) for epithermal neutrons, RBE(En), is important in neutron field design. In the first half of this paper, we present the development of an expression for the energy dependent normal-tissue RBE, RBE(En). We then calculate a reasonable estimate for RBE(En) for adult brain tissue. In the second half of the paper, two separate RBE expressions are developed, one for the RBE of the neutrons that interact in tissue via the 14N(n,p)14C reaction, denoted RBE(N), and one for the RBE of the neutrons which interact in tissue via the 1H(n,n')1H reaction, denoted RBE(H). The absorbed-dose-averaged values of these expressions are calculated for the neutron flux spectrum in phantom for the Brookhaven Medical Research Reactor (BMRR) epithermal neutron beam. The calculated values, [RBE(norm)N] = 3.4 and [RBE(norm)H] = 3.2, are within 6% of being equal, and support the use of equal values for RBEN and RBE(H) by researchers at Brookhaven National Laboratory (BNL). Finally, values of [RBE(norm)N] and [RBE(norm)H], along with the absorbed-dose-averaged RBE for brain, [RBE(norm)b], were calculated as a function of depth along the centerline of an ellipsoidal head phantom using flux spectra calculated for our Accelerator-Based Neutron Source (ABNS). These values remained essentially constant with depth, supporting the use of constant values for RBE, as is done at BNL.

A comparison of neutron beams for BNCT based on in-phantom neutron field assessment parameters.

In this paper our in-phantom neutron field assessment parameters, T and DTumor, were used to evaluate several neutron sources for use in BNCT. Specifically, neutron fields from The Ohio State University (OSU) Accelerator-Based Neutron Source (ABNS) design, two alternative ABNS designs from the literature (the Al/AIF3-Al2O3 ABNS and the 7LiF-AI2O3 ABNS), a fission-convertor plate concept based on the 500-kW OSU Research Reactor (OSURR), and the Brookhaven Medical Research Reactor (BMRR) facility were evaluated. In order to facilitate a comparison of the various neutron fields, values of T and DTumor were calculated in a 14 cm x 14 cm x 14 cm lucite cube phantom located in the treatment port of each neutron source. All of the other relevant factors, such as phantom materials, kerma factors, and treatment parameters, were kept the same. The treatment times for the OSURR, the 7LiF-Al2O3 ABNS operating at a beam current of 10 mA, and the BMRR were calculated to be comparable and acceptable, with a treatment time per fraction of approximately 25 min for a four fraction treatment scheme. The treatment time per fraction for the OSU ABNS and the Al/AlF3-Al2O3 ABNS can be reduced to below 30 min per fraction for four fractions, if the proton beam current is made greater than approximately 20 mA. DTumor was calculated along the bean centerline for tumor depths in the phantom ranging from 0 to 14 cm. For tumor depths ranging from 0 to approximately 1.5 cm, the value of DTumor for the OSURR is largest, while for tumor depths ranging from 1.5 to approximately 14 cm, the value of DTumor for the OSU-ABNS is the largest.

Predictions of a stochastic model of bone marrow cell survival in high dose rate radiation fields with arbitrary neutron to gamma-ray absorbed dose rate ratios.

In this paper, a stochastic model of cell survival, which was developed by Cotlet and Blue, based on the work of Jones, is extended to describe bone marrow cell survival in high dose rate radiation fields with arbitrary neutron to gamma-ray absorbed dose rate ratios. Mathematical formulas are obtained that describe the interaction of the neutron and gamma-ray components of the absorbed dose, for radiation fields with arbitrary neutron to gamma-ray dose rate ratios, for exposures of cells to various absorbed doses, at various high dose rates.

Synthesis of 5-(carboranylalkylmercapto)-2'-deoxyuridines and 3-(carboranylalkyl)thymidines and their evaluation as substrates for human thymidine kinases 1 and 2.

Derivatives of thymidine containing o-carboranylalkyl groups at the N-3 position and derivatives of 2'-deoxyuridine containing o-carboranylalkylmercapto groups at the C-5 position were synthesized. The alkyl spacers consist of 4-8 methylene units. The synthesis of the former compounds required 3-4 reaction steps in up to 75% overall yield and that of the latter 9-10 reaction steps with significantly lower overall yield. Derivatives of thymidine substituted with carboranylalkyl substituents at the N-3 position and short spacers were phosphorylated by both recombinant and purified cytosolic thymidine kinase (TK1) to a relatively high degree. None of the tested 2'-deoxyuridine derivatives possessing carboranyl substituents at the C-5 position were phosphorylated by either recombinant or purified TK1. The amounts of phosphorylation product detected for some of the C-5-substituted nucleosides with recombinant mitochondrial thymidine kinase (TK2) were low but significant and decreased with increasing lengths of the alkyl spacer. The data obtained in this study do not seem to support the tether concept applied in the synthesis of the new C-5- and N-3-substituted carboranyl nucleosides intended to reduce possible steric interference in the binding of carboranyl nucleosides with deoxynucleoside kinases. Instead, it appeared that a closer proximity of the bulky carborane moiety to the nucleoside scaffold resulted in better substrate characteristics.

A controlled trial of nurse counselling on lifestyle change for hypertensives treated in general practice: preliminary results.

1. We assessed whether a lifestyle modification programme implemented by nurse counsellors in a general practice setting would improve blood pressure (BP) control in treated hypertensive patients. 2. Patients were randomized into a control group or one of two intervention groups who received either a high or low level of counselling. 3. Patients in the intervention groups had appointments every 4th week for 18 weeks. The low intervention group had one practice appointment and five telephone counselling appointments while the high intervention group had six appointments in their general practice. The patients were counselled using a stage of change behavioural model and motivational interviewing to: reduce alcohol consumption, dietary fat and salt intake and weight; cease smoking; and increase leisure time physical activity. 4. Compared with controls the low intervention group showed significant decreases in alcohol and salt intake while the high intervention resulted in significant decreases in both weight and BP. 5. We conclude that nurse counselling targeted to specific aspects of lifestyle can improve BP control and weight in treated hypertensive patients over 18 weeks. Its longer term effectiveness in the management of hypertension warrants further evaluation.

An expression for the RBE of neutrons as a function of neutron energy.

The goal of this paper is to develop a relationship between a neutron RBE and neutron energy, En, which can be used to design neutron sources for BNCT. In an earlier calculation of a neutron RBE as a function of En, we approximated the contribution to a total neutron RBE, RBEt (En), arising from 14N(n,p)14C reactions. In this paper, we recalculate RBEt (En), accounting more exactly for the contribution to RBEt (En) from 14N(n,p)14C reactions.

Primary immunisations in Liverpool. II: Is there a gap between consent and completion?

The association between completion of primary dipht eria, tetanus and pertussis, measles, mumps, and rubella and polio immunisation courses in Liverpool and five sociodemographic factors, namely the child's sex, position in the family, family type, migration into Liverpool since birth, and local deprivation was examined. Only 68% of children were fully immunised by their second birthday. The immunisation rate for pertussis was 74%, compared with 85-89% for the other antigens. Children who had older siblings, were recorded as living with one parent, had moved into Liverpool or who lived in areas of high deprivation were less likely to complete the full set of antigens and individual courses. Boys were significantly less likely than girls to be fully immunised against pertussis. Differences in the completion of pertussis immunisation associated with the child's sex and with local deprivation were a direct reflection of differences in rates of parental consent. Parental consent did not wholly account for significantly lower rates among children with older siblings, those living with a lone parent, and those who had moved into Liverpool, however. This may reflect the practical difficulties of attending immunisation clinics. To achieve immunisation targets, a more flexible and targeted approach is required of health professionals. This may include the careful targeting of efforts to increase consent and the improvement of access to immunisations by providing domiciliary services or by opportunistic immunisation of infants when they are in contact with primary and community health care services.

Primary immunisations in Liverpool. I: Who withholds consent?

The association between parents in Liverpool consenting to their children being invited for primary immunisations and five sociodemographic factors, namely sex, position of child in the family, family type, migration into Liverpool since birth, and local deprivation was examined. Rates of consent to invitation were over 97% for each antigen except pertussis, which had a consent rate of 83%. Consent to invitation for pertussis vaccine was least likely to have been given for boys, children with older siblings, those recorded as living with a single parent, and those in the most deprived areas. Local deprivation also had an effect on consent to the measles, mumps, and rubella vaccine. Migration into Liverpool had a significant effect on consent to invitation for all antigens except pertussis. The child's sex, family type, and local deprivation had no effect on consent to diphtheria, tetanus, and polio immunisations. Maximising pertussis vaccine uptake will require more attention to be paid to those parents who have been identified as being less likely to give consent. It is particularly important that consistent and clear advice about immunisations is made available to parents with two or more children, lone parents, and those living in materially deprived areas. Our findings challenge some of the assumptions underlying the principles of 'first parent visiting', at least so far as pertussis is concerned.