Multi-institutional evaluation using the end-to-end test for implementation of dynamic techniques of radiation therapy in Thailand

AimIn this study, an accuracy survey of intensity-modulated radiation therapy (IMRT) and volumetric arc radiation therapy (VMAT) implementation in radiotherapy centers in Thailand was conducted.BackgroundIt is well recognized that there is a need for radiotherapy centers to evaluate the accuracy levels of their current practices, and use the related information to identify opportunities for future development.Materials and methodsAn end-to-end test using a CIRS thorax phantom was carried out at 8 participating centers. Based on each center's protocol for simulation and planning, linac-based IMRT or VMAT plans were generated following the IAEA (CRP E24017) guidelines. Point doses in the region of PTVs and OARs were obtained from 5 ionization chamber readings and the dose distribution from the radiochromic films. The global gamma indices of the measurement doses and the treatment planning system calculation doses were compared.ResultsThe large majority of the RT centers (6/8) fulfilled the dosimetric goals, with the measured and calculated doses at the specification points agreeing within ±3% for PTV and ±5% for OARS. At 2 centers, TPS underestimated the lung doses by about 6% and spinal cord doses by 8%. The mean percentage gamma pass rates for the 8 centers were 98.29 ± 0.67% (for the 3%/3 mm criterion) and 96.72 ± 0.84% (for the 2%/2 mm criterion).ConclusionsThe 8 participating RT centers achieved a satisfactory quality level of IMRT/VMAT clinical implementation.     

A regression-based method for estimating mean treatment cost in the presence of right-censoring

In many clinical trials and evaluations using medical care administrative databases it is of interest to estimate not only the survival time of a given treatment modality but also the total associated cost. The most widely used estimator for data subject to censoring is the Kaplan-Meier (KM) or product-limit (PL) estimator. The optimality properties of this estimator applied to time-to-event data (consistency, etc.) under the assumptions of random censorship have been established. However, whenever the relationship between cost and survival time includes an error term to account for random differences among patients' costs, the dependency between cumulative treatment cost at the time of censoring and at the survival time results in KM giving biased estimates. A similar phenomenon has previously been noted in the context of estimating quality-adjusted survival time. We propose an estimator for mean cost which exploits the underlying relationship between total treatment cost and survival time. The proposed method utilizes either parametric or nonparametric regression to estimate this relationship and is consistent when this relationship is consistently estimated. We then present simulation results which illustrate the gain in finite-sample efficiency when compared with another recently proposed estimator. The methods are then applied to the estimation of mean cost for two studies where right-censoring was present. The first is the heart failure clinical trial Studies of Left Ventricular Dysfunction (SOLVD). The second is a Health Maintenance Organization (HMO) database study of the cost of ulcer treatment.     

A new analytical formula for neutron capture gamma dose calculations in double-bend mazes in radiation therapy

BackgroundPhotoneutrons are produced in radiation therapy with high energy photons. Also, capture gamma rays are the byproduct of neutrons interactions with wall material of radiotherapy rooms.AimIn the current study an analytical formula was proposed for capture gamma dose calculations in double bend mazes in radiation therapy rooms.Materials and methodsA total of 40 different layouts with double-bend mazes and a 18 MeV photon beam of Varian 2100 Clinac were simulated using MCNPX Monte Carlo (MC) code. Neutron capture gamma ray dose equivalent was calculated by the MC method along the maze and at the maze entrance door of all the simulated rooms. Then, all MC resulted data were fitted to an empirical formula for capture gamma dose calculations. Wu–McGinley analytical formula for capture gamma dose equivalent at the maze entrance door in single-bend mazes was also used for comparison purposes.ResultsFor capture gamma dose equivalents at the maze entrance door, the difference of 2–11% was seen between MC and the derived equation, while the difference of 36–87% was found between MC and the Wu–McGinley methods.ConclusionOur results showed that the derived formula results were consistent with the MC results for all of 40 different geometries. However, as a new formula, further evaluations are required to validate its use in practical situations. Finally, its application is recommend for capture gamma dose calculations in double-bend mazes to improve shielding calculations.     

Validation of the theoretical domains framework for use in behaviour change and implementation research

Background

An integrative theoretical framework, developed for cross-disciplinary implementation and other behaviour change research, has been applied across a wide range of clinical situations. This study tests the validity of this framework.

Methods

Validity was investigated by behavioural experts sorting 112 unique theoretical constructs using closed and open sort tasks. The extent of replication was tested by Discriminant Content Validation and Fuzzy Cluster Analysis.

Results

There was good support for a refinement of the framework comprising 14 domains of theoretical constructs (average silhouette value 0.29): ??Knowledge??, ??Skills??, ??Social/Professional Role and Identity??, ??Beliefs about Capabilities??, ??Optimism??, ??Beliefs about Consequences??, ??Reinforcement??, ??Intentions??, ??Goals??, ??Memory, Attention and Decision Processes??, ??Environmental Context and Resources??, ??Social Influences??, ??Emotions??, and ??Behavioural Regulation??.

Conclusions

The refined Theoretical Domains Framework has a strengthened empirical base and provides a method for theoretically assessing implementation problems, as well as professional and other health-related behaviours as a basis for intervention development.     

Use of current radiation techniques in the diagnosis and treatment of juvenile angiofibromas of the nasopharynx

In 1992-2001 seventeen patients with juvenile nasopharyngeal angiofibromas (JNAs) were treated at Krasnoyarsk Territorial Clinical Hospital. The patients underwent a comprehensive diagnosis involving computed tomography (CT), magnetic resonance imaging (MRI), and angiography, followed by tumor vascular embolization. Later on JNAs were surgically removed in 14 patients, a course of radiation therapy was performed. In suspected JNA, the authors consider it necessary to concomitantly use CT, MRI, and angiography, which provides the most complete diagnostic picture of a pathological focus. X-ray endovascular occlusion considerably lowers blood loss, facilitates a complete angiofibroma removal, and affects the tolerability of radiation therapy in inoperable cases.     

A framework for providing scientific advice for the management of new and developing invertebrate fisheries

A framework is developed for the provision of scientific advice to support the management of new and developing marine invertebrate fisheries. These fisheries often occur on species for which little biological or exploitation information is available. The framework explicitly endorses the precautionary approach to fisheries management and research. Three general management strategies (size/sex limits, regulation by total allowable catch, control of the exploitation rate) and their needs for supporting scientific information are identified. The significance of spatial pattern, and of recognizing the need for different approaches to obtain scientific information and to manage sedentary benthic and mobile pelagic species, is a central theme. Three 'phases' are proposed to obtain the necessary scientific information: (a) Phase 0, 'collecting existing information', consisting of syntheses of available biological and fisheries information on the target (and similar) species, leading to formulation of potential management strategies; (b) Phase 1, 'collecting new information', to obtain the essential information that is lacking or insufficient from the Phase 0 analysis, and to evaluate alternative management strategies and propose regulatory actions; and (c) Phase 2, 'fishing for commerce', to implement the chosen management actions and to monitor fishing operations, so as to increase the information base available to refine the results from previous phases. Phase 1 activities may consist of surveys, site-specific depletion experiments and studies to obtain biological information, and development of experimental management areas to test different exploitation rates. A strategy that includes establishing reserve areas recognises the inherent uncertainties associated with developing fisheries and provides a buffer against mistakes or 'surprises'; it also provides control areas to compare stock productivity in fished and unfished locations. The application of this framework to a developing sea cucumber fishery in British Columbia is presented as an example. Throughout, strong interaction and collaboration among science, management, and stakeholders is crucial to the provision of scientific advice for precautionary management of new invertebrate fisheries.     

Cost and Efficiency of Large Mammal Census Techniques: Comparison of Methods for a Participatory Approach in a Communal Area, Zimbabwe

The comparison of precision is often advocated for the selection of an appropriate census and/or monitoring method for wildlife, but little attention is generally paid to their cost effectiveness, a crucial criterion given budgetary and logistical constraints. We present six direct count methods conducted in a communal area of the Zambezi Valley, Zimbabwe, and compare them in terms of (1) effort and cost to survey an area (sampling efficiency), and (2) efficiency in data collection (detection efficiency). Methods ranged from c.US$0.2 to over US$6.0/km² and needed from 0.1 to 5.0 human-h/km². The comparison of efficiencies showed the advantages of simple ground methods: foot counts and particularly bicycle counts appear well adapted to the ecological and human context of our study. The relative benefits and constraints of the different methods are discussed in the context of a community-based wildlife management programme.     

Comparative life cycle assessment of two landfill technologies for the treatment of municipal solid waste

Goal and Scope  The potential environmental impacts associated with two landfill technologies for the treatment of municipal solid waste (MSW), the engineered landfill and the bioreactor landfill, were assessed using the life cycle assessment (LCA) tool. The system boundaries were expanded to include an external energy production function since the landfill gas collected from the bioreactor landfill can be energetically valorized into either electricity or heat; the functional unit was then defined as the stabilization of 600 000 tonnes of MSW and the production of 2.56x10⁸ MJ of electricity and 7.81x10⁸ MJ of heat. Methods  Only the life cycle stages that presented differences between the two compared options were considered in the study. The four life cycle stages considered in the study cover the landfill cell construction, the daily and closure operations, the leachate and landfill gas associated emissions and the external energy production. The temporal boundary corresponded to the stabilization of the waste and was represented by the time to produce 95% of the calculated landfill gas volume. The potential impacts were evaluated using the EDIP97 method, stopping after the characterization step. Results and Discussion  The inventory phase of the LCA showed that the engineered landfill uses 26% more natural resources and generates 81% more solid wastes throughout its life cycle than the bioreactor landfill. The evaluated impacts, essentially associated with the external energy production and the landfill gas related emissions, are on average 91% higher for the engineered landfill, since for this option 1) no energy is recovered from the landfill gas and 2) more landfill gas is released untreated after the end of the post-closure monitoring period. The valorization of the landfill gas to electricity or heat showed similar environmental profiles (1% more raw materials and 7% more solid waste for the heat option but 13% more impacts for the electricity option). Conclusion and Recommendations  The methodological choices made during this study, e.g. simplification of the systems by the exclusion of the identical life cycle stages, limit the use of the results to the comparison of the two considered options. The validity of this comparison could however be improved if the systems were placed in the larger context of municipal solid waste management and include activities such as recycling, composting and incineration.     

Overview of the ability of different treatment methods for liquid and solid manure to inactivate pathogens

The use of manure as a fertilizer in agriculture includes the risk of spreading pathogenic infectious agents to the environment, to animals and humans. The treatment of manure can help avoid or reduce these risks. Even if the treatment is dominated by economic considerations such as biogas production, ammonia stripping or phosphorous precipitation, the hygienic aspect should be kept in mind. Otherwise, new infection chains may be established by the use of insufficiently treated manure by-products such as fertilizers still containing infective pathogens. Treatment plants should use a concept according to HACCP principles that includes hazard analysis, risk assessment, the determination of process relevant CCPs and the validation of the process by determining the hygienizing efficiency using representative test organisms as well as microbial end product supervision. Treatment methods can be divided into physical, chemical and microbiological treatment, sometimes used in combination. For economical reasons, only composting or anaerobic treatment (biogas) or, to a minor extent, aerobic thermophilic stabilization (ATS) are used as routine preventive measures on a farm level. In cases of outbreaks of notifiable diseases both physical and chemical treatment of manure can lead to reliable disinfected/pasteurised end products which can be used in agriculture without long-lasting risks for soil fertility or the environment.     

Adjuvant gamma knife surgery and image-guided,intensity-modulated radiation therapy for the treatment of sacral chordomas

AimThe aim of this study was to confirm whether patients with sacral chordoma benefit from adjuvant radiotherapy and to determine the optimal photon radiotherapy module for comprehensive treatment.BackgroundChordoma is a rare slow-growing neoplasm arisen from cellular remnants of the notochord. About 50% occur in the sacrococcygeal region. Surgical resection and adjuvant radiation therapy are recommended treatment due to the improving local control rate.Materials and methods118 patients treated by surgery and adjuvant radiotherapy from August 2003 to May 2015 were retrospectively analyzed. All patients received surgical resection after diagnosis. Among these patients, 44 were treated by exclusive surgery, and 48 were treated with adjuvant image-guided, intensity-modulated radiation therapy (IG-IMRT). In addition, 26 patients were treated with gamma knife surgery (GKS) after surgical resection. The median follow-up was 54 months for all patients. Kaplan–Meier analysis was used to calculate recurrence-free survival (RFS) overall survival (OS).ResultsPatients treated with adjuvant radiotherapy had better RFS (p = 0.014) than those treated exclusively by surgery. The patients in the IG-IMRT group exhibited better recurrence-free survival (p = 0.01) than the GKS group. Moreover, in the IG-IMRT group, patients treated by higher dose were associated with better RFS (p = 0.04). No significant difference in OS was found. No grade 3 late toxicity was found.ConclusionsWe confirmed that adjuvant radiotherapy improved RFS but not OS in sacral chordoma patients after surgery. Furthermore, favorable RFS and low adverse event rates were observed following IG-IMRT. Our results suggest that high dose IG-IMRT is an appropriate module of adjuvant radiotherapy for sacral chordoma patients.     

Structure-activity relationships of adenosine A3 receptor ligands: new potential therapy for the treatment of glaucoma

Structure-activity relationships (SAR) of fused 1,2,4-triazolo[1,5-c ]pyrimidine were performed. Various substituents were introduced into the heterocyclic ring to improve the potency of adenosine A(3) receptor binding affinity and A(3)-selectivity against other subtypes. Potent and selective A(3) receptor antagonists were identified and were evaluated in a monkey model of intraocular pressure by eye-drop administration. As a result, compound 1c (OT-7999) was found to significantly decrease intraocular pressure in the animal model.     

A thermomechanical framework for reconciling the effects of ultraviolet radiation exposure time and wavelength on connective tissue elasticity

Augmentation of the mechanical properties of connective tissue using ultraviolet (UV) radiation—by targeting collagen cross-linking in the tissue at predetermined UV exposure time \((t)\) and wavelength \((\lambda )\) —has been proposed as a therapeutic method for supporting the treatment for structural-related injuries and pathologies. However, the effects of \(\lambda \) and \(t\) on the tissue elasticity, namely elastic modulus \((E)\) and modulus of resilience \((u_\mathrm{Y})\) , are not entirely clear. We present a thermomechanical framework to reconcile the \(t\) - and \(\lambda \) -related effects on \(E\) and \(u_\mathrm{Y}\) . The framework addresses (1) an energy transfer model to describe the dependence of the absorbed UV photon energy, \(\xi \) , per unit mass of the tissue on \(t\) and \(\lambda \) , (2) an intervening thermodynamic shear-related parameter, \(G\) , to quantify the extent of UV-induced cross-linking in the tissue, (3) a threshold model for the \(G\) versus \(\xi \) relationship, characterized by   \(t_\mathrm{C}\) —the critical \(t\) underpinning the association of \(\xi \) with \(G\) —and (4) the role of \(G\) in the tissue elasticity. We hypothesized that \(G\) regulates \(E\) (UV-stiffening hypothesis) and \(u_\mathrm{Y}\) (UV-resilience hypothesis). The framework was evaluated with the support from data derived from tensile testing on isolated ligament fascicles, treated with two levels of \(\lambda \) (365 and 254 nm) and three levels of \(t\) (15, 30 and 60 min). Predictions from the energy transfer model corroborated the findings from a two-factor analysis of variance of the effects of \(t\) and \(\lambda \) treatments. Student’s t test revealed positive change in \(E\) and \(u_\mathrm{Y}\) with increases in \(G\) —the findings lend support to the hypotheses, implicating the implicit dependence of UV-induced cross-links on \(t\) and \(\lambda \) for directing tissue stiffness and resilience. From a practical perspective, the study is a step in the direction to establish a UV irradiation treatment protocol for effective control of exogenous cross-linking in connective tissues.     

A new chronostratigraphic framework for the Upper Palaeolithic of Riparo Mochi (Italy)

The rockshelter of Mochi, on the Ligurian coast of Italy, is often used as a reference point in the formation of hypotheses concerning the arrival of the Aurigancian in Mediterranean Europe. Yet, the site is poorly known. Here, we describe the stratigraphic sequence based on new field observations and present 15 radiocarbon determinations from the Middle Palaeolithic (late Mousterian) and Early Upper Palaeolithic (Aurignacian and Gravettian) levels. The majority of dates were produced on humanly modified material, specifically marine shell beads, which comprise some of the oldest directly-dated personal ornaments in Europe. The radiocarbon results are incorporated into a Bayesian statistical model to build a new chronological framework for this key Palaeolithic site. A tentative correlation of the stratigraphy to palaeoclimatic records is also attempted.     

A new, enigmatic family for new genus and species of Polyneoptera from the Upper Permian of Russia

Alexarasniidaefam. n. and Alexarasnia rossicagen. et sp. n. are described from the Upper Permian of European Russia. Systematic position of this enigmatic family within the infraclass Polyneoptera is unclear.     

A new system for understanding the biodiversity in different nature reserves:capacity,connectivity and quality of biodiversity

In this paper,we propose a new system for understanding the biodiversity in different conservation areas.It includes three aspects:the capacity,the connectivity and the quality.The capacity refers to the numbers of biodiversity,including absolute and relative richness of the vegetation types Nv and Dv = (Nv-1)/lnA,species numbers S and richness of species dGI = (S- 1)/lnA,and germ plasm resources within a nature reserve,and also the potential biological living space offered by the natural resource.It comprises the total biological resources in a nature reserve.The connectivity refers to the flux of biodiversity,including similarity and connected status of the vegetation types SILi = 2z/(x + y) and species numbers SIc = 2z/(x + y) among different nature reserves.The quality refers to the stability of biodiversity,including relative species richness index RSLi = d/dmax,relative vegetation richness index RVLi =Dv/Dmaxv,fastness to invasion species fLi = 1-Si/St,weighted values,representativeness and vulnerability of special vegetations,special species,CITES species and rare species as the protected targets.     

A new system for understanding the biodiversity in different nature reserves: capacity, connectivity and quality of biodiversity

In this paper, we propose a new system for understanding the biodiversity in different conservation areas. It includes three aspects: the capacity, the connectivity and the quality. The capacity refers to the numbers of biodiversity, including absolute and relative richness of the vegetation types N _v and D _v =(N _v −1)/lnA, species numbers S and richness of species d _Gl =(S − 1)/lnA, and germ plasm resources within a nature reserve, and also the potential biological living space offered by the natural resource. It comprises the total biological resources in a nature reserve. The connectivity refers to the flux of biodiversity, including similarity and connected status of the vegetation types SI _Li =2z/(x + y) and species numbers SI _C =2z/(x + y) among different nature reserves. The quality refers to the stability of biodiversity, including relative species richness index RS _Li =d/d _max, relative vegetation richness index RV _Li =D _v /D _maxv , fastness to invasion species ƒ _Li =1−S _i /S _t , weighted values, representativeness and vulnerability of special vegetations, special species, CITES species and rare species as the protected targets.     

A mathematical model of the treatment and survival of patients with high-grade brain tumours

More years of life per patient are lost as the result of primary brain tumours than any other form of cancer. The most aggressive of these is known as glioblastoma (GBM). The median survival time of patients with GBM is under 10 months and the outlook has hardly improved over the past 20 years. Generally, these tumours are remarkably resistant to radiotherapy and yet about 2-3% of all GBMs appear to be cured.The objectives of this study were to formulate a mathematical and phenomenological model of tumour growth in a population of patients with GBM to predict survival, and to use the model to extract biological information from clinical data.The model describes the growth of the tumour and the resulting damage to the normal brain using simple concepts borrowed from chemical reaction engineering. Death is assumed to result when the amount of surviving normal brain falls to a critical level. Radiotherapy is assumed to destroy tumour but not healthy brain. Simple rules are included to represent approximately the clinician's decisions about what type of treatment to offer each patient. A population of patients is constructed by assuming that key parameters can be sampled from statistical distributions. Following Monte Carlo simulation, the model can be fitted to data from clinical trials.The model reproduces clinical data extremely accurately. This suggests that the long-term survivors are not a separate sub-population but are the ‘lucky tail’ of a unimodal distribution. The estimated values of radiation sensitivity (represented as SF2, the survival fraction after 2 Gy) suggest the presence of severe hypoxia, which renders cells less sensitive to radiation. The model can predict the probable age distribution of tumours at presentation. The model shows the complicated effects of waiting times for treatment on the survival outcomes, and is used to predict the effects of escalation of radiotherapy dose.The model may aid the design of clinical trials using radiotherapy for patients with GBM, especially in helping to estimate the size of trial required. It is also designed in a generic form, and might be applicable to other tumour types.