Viability of Non-Coplanar VMAT for Liver SBRT as Compared to Coplanar VMAT and Beam Orientation Optimized 4π IMRT.

PurposeThe 4π static non-coplanar radiotherapy delivery technique has demonstrated better normal tissue sparing and dose conformity than the clinically used volumetric modulated arc therapy (VMAT). It is unclear whether this is a fundamental limitation of VMAT delivery or the coplanar nature of its typical clinical plans. The dosimetry and the limits of normal tissue toxicity constrained dose escalation of coplanar VMAT, non-coplanar VMAT and 4π radiotherapy are quantified in this study.Methods and materialsClinical stereotactic body radiation therapy plans for 20 liver patients receiving 30-60 Gy using coplanar VMAT (cVMAT) were re-planned using 3-4 partial non-coplanar arcs (nVMAT) and 4π with 20 intensity-modulated non-coplanar fields. The conformity number (CN), homogeneity index (HI), 50% dose spillage volume (R50), normal liver volume receiving >15 Gy (VL>15), dose to organs at risk (OARs), and tumor control probability (TCP) were compared for all three treatment plans. The maximum tolerable dose (MTD) yielding a normal liver normal tissue control probability (NTCP) below 1%, 5%, and 10% was calculated with the Lyman-Kutcher-Burman model for each plan, as well as the resulting survival fractions at one, two, three, and four years.ResultsCompared to cVMAT, the nVMAT and 4π plans reduced VL>15 by an average of 5 cm3 and 80 cm3, respectively. 4π reduced the 50% dose spillage volume by ~23% compared to both VMAT plans, and either significantly decreased or maintained OAR doses. The 4π MTDs and survival fractions were significantly higher than both cVMAT and nVMAT (p<0.05) for all normal liver NTCP limits used in this study.ConclusionsThe 4π technique provides significantly better OAR sparing than both cVMAT and vMAT and enables more clinically relevant dose escalation for tumor local control. Therefore, despite the current accessibility of nVMAT, it is not a viable alternative to 4π for liver SBRT

Optimization of interaction of agrarian entities as an imperative of ensuring food security of the state

The interaction of agricultural entities is based on modern market relations and the state agrarian policy. Managing the subjects of the agricultural sector of the economy is the primary task of the state, since the provision of food security of the state depends on this. The subject of the study is the establishment of relations of the agricultural sector of the country. In the grouping method, a direct relationship was established between the sum of agricultural production in farms of all categories in the constituent entities of the Russian Federation and the number of employees in the regional agro-industrial complex of the agricultural sector, as well as the number of departments in them. The purpose and objective of the study is to highlight the main functions of state administration of the agricultural sector at the regional level, to identify the lack of an effective mechanism for interaction of the subjects of the agricultural market with each other and with the regional authorities of the agricultural sector. The presented model of optimizing the relationships between the agrarian entities of the region will increase the efficiency of the agrarian sector of the region’s economy and ensure its food security. The necessity of planning and forecasting the volumes of production and use of agricultural products and raw materials is substantiated. The system of such forecasting includes such subsystems as agricultural enterprises, processing enterprises, and the population of the region. It is concluded that each subsystem works on a well-formed and well-founded functional model, which includes input and output information, controls that regulate functioning, as well as mechanisms that ensure such functioning. A special role in the forecasting process is assigned to the regional management bodies of the agro-industrial sector represented by the department for optimizing the interaction of agricultural entities in the region. The final forecast result should be a balance model of the degree of food security in the region's population

Patient-cost survey for tuberculosis in the context of patient-pathway modelling.

ETTING: Eight tuberculosis treatment sites in Cavite Province, the Philippines, including two sites specialising in management of multidrug-resistant tuberculosis (MDR-TB).OBJECTIVE: To evaluate costs incurred by TB patients and to determine the proportion of households that faced catastrophic costs, then to consider cost survey responses alongside results of detailed patient-pathway modelling.DESIGN: Clustered cross-sectional survey using a field testing version of the WHO TB patient-costing tool and protocol; face-to-face interviews with 194 patients conducted in May-August 2016. Costs included direct-medical, direct non-medical and indirect costs using the human capital approach. Patients were deemed to incur catastrophic expenditure if TB-related costs exceeded 20% of annual household income. Patient pathways were modelled following multiple health staff interviews.RESULTS: Estimated mean cost incurred by patients with drug-susceptible TB was US$321 vs.$2356 for MDR-TB patients. Catastrophic costs were suffered by 28% of drug-susceptible and 80% of MDR-TB patients, with lost income being the largest contributor. Patient-pathway modelling suggested most patients had under-reported health visits.CONCLUSION: Survey results indicate that patient costs are large for all patients in Cavite, particularly for MDR-TB patients. Patient-pathway modelling suggests these costs are an underestimate due to poor recollection of health visits, suggesting that the WHO instrument and protocol could be improved to better capture the diagnostic journey

Applying switchable Cas9 variants to in vivo gene editing for therapeutic applications

Progress in targeted gene editing by programmable endonucleases has paved the way for their use in gene therapy. Particularly, Cas9 is an endonuclease with high activity and flexibility, rendering it an attractive option for therapeutic applications in clinical settings. Many disease-causing mutations could potentially be corrected by this versatile new technology. In addition, recently developed switchable Cas9 variants, whose activity can be controlled by an external stimulus, provide an extra level of spatiotemporal control on gene editing and are particularly desirable for certain applications. Here, we discuss the considerations and difficulties for implementing Cas9 to in vivo gene therapy. We put particular emphasis on how switchable Cas9 variants may resolve some of these barriers and advance gene therapy in the clinical setting

Applying switchable Cas9 variants to in vivo gene editing for therapeutic applications

Progress in targeted gene editing by programmable endonucleases has paved the way for their use in gene therapy. Particularly, Cas9 is an endonuclease with high activity and flexibility, rendering it an attractive option for therapeutic applications in clinical settings. Many disease-causing mutations could potentially be corrected by this versatile new technology. In addition, recently developed switchable Cas9 variants, whose activity can be controlled by an external stimulus, provide an extra level of spatiotemporal control on gene editing and are particularly desirable for certain applications. Here, we discuss the considerations and difficulties for implementing Cas9 to in vivo gene therapy. We put particular emphasis on how switchable Cas9 variants may resolve some of these barriers and advance gene therapy in the clinical setting

A multi-institutional analysis of a general pelvis continuous Hounsfield unit synthetic CT software for radiotherapy

Purpose To validate a synthetic computed tomography (sCT) software with continuous HUs and large field-of-view (FOV) coverage for magnetic resonance imaging (MRI)-only workflow of general pelvis anatomy in radiotherapy (RT).Methods An sCT software for general pelvis anatomy (prostate, rectum, and female pelvis) has been developed by Philips Healthcare and includes continuous HUs assignment along with large FOV coverage. General pelvis sCTs were generated using a two-stack T1-weighted mDixon fast-field echo (FFE) sequence with a superior-inferior coverage of 36 cm. Seventy-seven prostate, 43 rectum, and 27 gynecological cases were scanned by three different institutions. mDixon image quality and sCTs were evaluated for soft tissue contrast by using a confidence level scale from 1 to 5 for bladder, prostate/rectum interface, mesorectum, and fiducial maker visibility. Dosimetric comparison was performed by recalculating the RT plans on the sCT after rigid registration. For 12 randomly selected cases, the mean absolute error (MAE) between sCT and CT was calculated to evaluate HU similarity, and the Pearson correlation coefficients (PCC) between the CT- and sCT-generated digitally reconstructed radiographs (DRRs) were obtained for quantitative comparison. To examine geometric accuracy of sCT as a reference for cone beam CT (CBCT), the difference between bone-based alignment of CBCT to CT and CBCT to sCT was obtained for 19 online-acquired CBCTs from three patients.Results Two-stack mDixon scans with large FOV did not show any image inhomogeneity or fat-water swap artifact. Fiducials, Foley catheter, and even rectal spacer were visible as dark signal on the sCT. Average visibility confidence level (average +/- standard deviation) on the sCT was 5.0 +/- 0.0, 4.6 +/- 0.5, 3.8 +/- 0.4, and 4.0 +/- 1.1 for bladder, prostate/rectum interface, mesorectum and fiducial markers. Dosimetric accuracy showed on average < 1% difference with the CT-based plans for target and normal structures. The MAE of bone and soft tissue between the sCT and CT are 120.9 +/- 15.4 HU, 33.4 +/- 4.1 HU, respectively. Average PCC of all evaluated DRR pairs was 0.975. The average offset between CT and sCT as reference was (LR, AP, SI) = (0.19 +/- 0.35, 0.14 +/- 0.60, 0.44 +/- 0.54) mm.Conclusions The continuous HU sCT software-generated realistic sCTs and DRRs to enable MRI-only planning for general pelvis anatomy

Typical food portion sizes consumed by Australian adults: results from the 2011–12 Australian National Nutrition and Physical Activity Survey

Considerable evidence has associated increasing portion sizes with elevated obesity prevalence. This study examines typical portion sizes of commonly consumed core and discretionary foods in Australian adults, and compares these data with the Australian Dietary Guidelines standard serves. Typical portion sizes are defined as the median amount of foods consumed per eating occasion. Sex- and age-specific median portion sizes of adults aged 19 years and over (n&thinsp;=&thinsp;9341) were analysed using one day 24&thinsp;hour recall data from the 2011&ndash;12 National Nutrition and Physical Activity Survey. A total of 152 food categories were examined. There were significant sex and age differences in typical portion sizes among a large proportion of food categories studied. Typical portion sizes of breads and cereals, meat and chicken cuts, and starchy vegetables were 30&ndash;160% larger than the standard serves, whereas, the portion sizes of dairy products, some fruits, and non-starchy vegetables were 30&ndash;90% smaller. Typical portion sizes for discretionary foods such as cakes, ice-cream, sausages, hamburgers, pizza, and alcoholic drinks exceeded the standard serves by 40&ndash;400%. The findings of the present study are particularly relevant for establishing Australian-specific reference portions for dietary assessment tools, refinement of nutrition labelling and public health policies

Towards the Composition of Services by End-Users: A Mobile-Based Solution

[EN] Nowadays, we live surrounded by heterogeneous and distributed services that are available to people anytime and anywhere. Even though these services can be used individually, it is through their synchronized and combined usage that end-users are provided with added value. However, existing solutions to service composition are not targeted at ordinary end-users. In fact, these solutions require technical knowledge to deal with the technological heterogeneity in which they are offered to the market. To this end, the paper presents a tool-supported platform that is aided by: (1) EUCalipTool, an end-user mobile tool that implements a Domain Specific Visual Language, which has been specifically designed to compose services on mobile devices; (2) a Faceted Service Registry, which plays the role of gateway between service implementations and end-users, hiding technological issues from the latter when including services in a composition; and (3) a Generation Module, which transforms end-user descriptions into BPMN specification that are interpreted by an execution infrastructure developed for that purpose.This work has been developed with the financial support of the Spanish State Research Agency under the project TIN2017-84094-R and co-financed with ERDF.Valderas, P.; Torres Bosch, MV.; Pelechano Ferragud, V. (2020). Towards the Composition of Services by End-Users: A Mobile-Based Solution. 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Detection of North American orthopoxviruses by real time-PCR

The prevalence of North American orthopoxviruses in nature is unknown and may be more difficult to ascertain due to wide spread use of vaccinia virus recombinant vaccines in the wild. A real time PCR assay was developed to allow for highly sensitive and specific detection of North American orthopoxvirus DNA in animal tissues and bodily fluids. This method is based on the amplification of a 156 bp sequence within a myristylated protein, highly conserved within the North American orthopoxviruses but distinct from orthologous genes present in other orthopoxviruses. The analytical sensitivity was 1.1 fg for Volepox virus DNA, 1.99 fg for Skunkpox virus DNA, and 6.4 fg for Raccoonpox virus DNA with a 95% confidence interval. Our assay did not cross-react with other orthopoxviruses or ten diverse representatives of the Chordopoxvirinae subfamily. This new assay showed more sensitivity than tissue culture tests, and was capable of differentiating North American orthopoxviruses from other members of Orthopoxvirus. Thus, our assay is a promising tool for highly sensitive and specific detection of North American orthopoxviruses in the United States and abroad

Present and Future CP Measurements

We review theoretical and experimental results on CP violation summarizing the discussions in the working group on CP violation at the UK phenomenology workshop 2000 in Durham.Comment: 104 pages, Latex, to appear in Journal of Physics