Normal Probability Curve Research Articles

A study of pre- and post-treatment hematologic markers of immune response in patients undergoing radiotherapy for soft tissue sarcoma.

This study investigates the impact of pre- and post-treatment hematologic markers, specifically neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on treatment outcomes in soft tissue sarcoma (STS) patients undergoing radiation therapy (RT). Data from 64 patients who underwent RT for curative management of STS were reviewed. Pre-RT and post-RT hematologic measures were evaluated for associations with survival outcomes. A normal tissue complication probability (NTCP) curve for predicting ΔPLR ≥ 75 was modeled using a probit function. Elevated baseline NLR was associated with worse overall survival (OS) and disease-free survival (DFS), while elevated PLR was associated with worse DFS. Post-RT, elevated PLR was linked to worse OS and DFS. Increasing PLR change post-RT was associated with worse OS and DFS. Receiver operating characteristics analysis determined ΔPLR ≥ 75 to be a robust cutoff associated with worse DFS. Bone V10Gy ≥362 cc corresponded to a 50% risk of developing ΔPLR ≥ 75. These results suggest that hematologic markers could serve as prognostic biomarkers in both pre- and post-treatment settings for STS patients undergoing RT. Future studies can consider using bone V10Gy < 362 cc as a potential cutoff to reduce the risk of increased PLR after RT.

Biomedical advances and future prospects of high-precision three-dimensional radiotherapy and four-dimensional radiotherapy.

Biomedical advances of external-beam radiotherapy (EBRT) with improvements in physical accuracy are reviewed. High-precision (±1 mm) three-dimensional radiotherapy (3DRT) can utilize respective therapeutic open doors in the tumor control probability curve and in the normal tissue complication probability curve instead of the one single therapeutic window in two-dimensional EBRT. High-precision 3DRT achieved higher tumor control and probable survival rates for patients with small peripheral lung and liver cancers. Four-dimensional radiotherapy (4DRT), which can reduce uncertainties in 3DRT due to organ motion by real-time (every 0.1-1 s) tumor-tracking and immediate (0.1-1 s) irradiation, have achieved reduced adverse effects for prostate and pancreatic tumors near the digestive tract and with similar or better tumor control. Particle beam therapy improved tumor control and probable survival for patients with large liver tumors. The clinical outcomes of locally advanced or multiple tumors located near serial-type organs can theoretically be improved further by integrating the 4DRT concept with particle beams.

A Diagnostic Study on English Spelling Errors Among the Elementary School Children in India

Learning the four skills of the English language is a requirement for pupils to utilize the language effectively, given the importance of learning it for both school and profession. Spelling – an important part of writing skill – is considered to be fundamental for written texts. The real meaning of a piece of writing can be changed by spelling mistakes, making it more challenging to understand. In India, teaching spelling is frequently overlooked while teaching English as a second language. The research attempts to determine the current level of spelling proficiency among Indian primary school students as well as the gaps and issues they encounter when spelling English words. The research approach used for this investigation was a form of descriptive survey. Children attending Jalpaiguri Municipal Corporation's elementary school in West Bengal, India, served as the study's sample. Normal probability curves and Ogive were created to analyze the frequency distribution of the English Diagnostic Test results. Central tendencies of the sample and sub-samples were studied. According to the study, spelling proficiency among elementary school students differs significantly depending on whether they attend government or non-government schools, even though there is no statistically significant difference between them based on gender and the medium of instruction they receive.

Connectedness and spillover between African equity, commodity, foreign exchange and cryptocurrency markets during the COVID-19 and Russia-Ukraine conflict

Since the onset of the COVID-19 pandemic, financial and commodity markets have exhibited significant volatility and displayed fat tail properties, deviating from the normal probability curve. The recent Russia-Ukraine war has further disrupted these markets, attracting considerable attention from both researchers and practitioners due to the occurrence of consecutive black swan events within a short timeframe. In this study, we utilized the Quantile-VAR technique to examine the interconnectedness and spillover effects between African equity markets and international financial/commodity assets. Daily data spanning from January 3, 2020, to September 6, 2022, was analyzed to capture tail risks. Our main findings can be summarized as follows. Firstly, the level of connectedness in returns is more pronounced in the lower and upper tails compared to the median. Secondly, during times of crisis, African equity markets primarily serve as recipients of systemic shocks. Lastly, assets such as Silver, Gold, and Natural Gas exhibit greater resilience to systemic shocks, validating their suitability as hedging instruments for African equities, in contrast to cryptocurrencies and international exchange rates. These findings carry significant implications for policymakers and investors in Africa equities.

Toxicity Analysis of a Modified Prostate Bed CTV Based on PSMA-PET Patterns of Failure.

After radical prostatectomy (RP), about 20-50% of prostate cancer patients experience biochemical failure, and many can be cured with salvage radiotherapy (sRT). Adding androgen deprivation and pelvic lymph node (PLN) RT to sRT decreases risk of disease progression at the cost of increased toxicity. PSMA PET patterns of local failure after RP show failures outside the RTOG prostate bed CTV (RTOG_CTV) occurring postero-laterally and inferiorly, while in much of the covered bladder local failures are not seen. A modified CTV (m_CTV) encompassing all sites of observed local failures and less of the bladder would potentially reduce dose to the bladder but increase dose to rectum. Herein, we compared sRT plans using RTOG_CTV vs. m_CTV and assessed predicted genitourinary (GU) and gastrointestinal adverse events (AEs). Volumes for RTOG_CTV, m_CTV, PLN CTV, and OARs were retrospectively contoured on planning CT scans of 28 post-RP patients. Plans were generated for each RTOG_CTV and m_CTV. Doses to prostate bed PTV (CTV + 8mm expansion, 6mm posteriorly) and PLN CTV were 68 Gy and 52.7 Gy, respectively, all in in 34 fractions. Dose-volume histogram (DVH) data for bladder, rectum, and bowel of each plan were extracted. Normal Tissue Complication Probability (NTCP) curves were generated using Lyman-Kutcher-Burman model to predict risk of late G≥3 GU AEs, early GU urgency, leakage, frequency, nocturia, late GI bleed, and late G≥3 GI AEs. Data were compared using 2 sample t-test and Wilcox signed rank test. Correlation of bladder volume and differences in DVH and NTCP data between plans was assessed using Pearson coefficient. The m_CTV and RTOG_CTV had a median volume of 70.56cc (IQR 59.72-82.17cc) and 132.14cc (IQR 109.33-155.84cc), respectively. Use of m_CTVs resulted in mean absolute decrease of 20.22% and 17.94% in bladder V65 Gy and V40 Gy, respectively (p<0.01 for both), without differences in rectum V65 Gy (p = 0.44), rectum V40 Gy (p = 0.11), or bowel V45 Gy (p = 0.29). Per NTCP curves, m_CTV plans had mean absolute decrease of 24.89% in predicted late G≥3 GU AEs (p<0.01). For predicted early GU AEs, there were mean absolute decreases ranging from 4.85 to 10.21% (p<0.01 for all). Predicted late GI bleed (p = 0.98) and late G≥3 GI AEs (p = 0.99) were not significantly different between plans. When assessed as a continuous variable, smaller bladder volumes had strong correlation with more benefit from m_CTV in bladder V65 Gy (r = -0.71, p<0.01) and moderate correlation with less early GU AEs (r -0.59 to -0.56, p<0.01 for all). There was no correlation with bladder V40 Gy (p = 0.27) or late G≥3 GU AEs (p = 0.14). The m_CTV plans had significantly less dose to the bladder, no increased dose to the rectum and significantly lower predicted rates of early and late GU toxicity. Using a m_CTV encompassing observed local failures from PSMA PET could improve the therapeutic ratio for patients undergoing sRT. Further clinical validation is warranted.

Normality of teaching aptitude of high school teachers

A study is being conducted to determine the normality of high school teachers' teaching aptitude in the Tamilnadu districts of Salem and Namakkal. Two hundred and fifty teachers were randomly chosen from thirty six Community Developmental (CD) educational blocks for a brief survey. Battery of Teaching Aptitude Test, standardized by Shamim Karim &amp; Ashok Kumar Dixit (1986) has been employed to assess teaching aptitude. The data were subjected to descriptive analysis in order to determine the normality of the high school teachers' teaching aptitude scores. The results demonstrated that high school teachers' normal distribution scores deviated slightly from normality. The sample's general teaching aptitude was average in character, and 60.80% of teachers scoring lies within the Mean±1σ boundary limit of the normal probability curve. 22.0 percent of high school teachers have a low level of teaching aptitude in the range of less than Mean-1σ range limit. According to the Mean+1σ mentioned range limitations, 17.20% of school teachers have excellent teaching aptitude. The pre-service teacher education training programmes for prospective student teachers are strengthened with training strategies to promote and enhance required teaching aptitude.

An approach to exploring patterns of imbalance and potential missingness in reports of the randomized baseline values for primary outcomes measurable at baseline in randomized controlled trials for meta-analyses

BackgroundThis study evaluated the adequacy of randomization in randomized controlled trials by investigating baseline differences in the primary outcome when a meta-analysis employed an outcome whose baseline level was measurable.MethodsWe retrieved Cochrane reviews published during one year. We calculated the proportion of studies that reported randomized baseline values for the primary outcome. The standardized mean difference (SMD) was used to assess baseline imbalance and heterogeneity. We explored ranking-ordered forest plots using a normal cumulative probability curve as a guideline representing well-performed randomized trials. When skewness was suggested, a funnel plot was drawn to assess whether there was a significant linear trend.ResultsIn 10 of 18 meta-analyses, more than 25% of trials did not report randomized baseline values of the primary outcomes. Three meta-analyses indicated baseline imbalance (P < 0.1) and three showed substantial heterogeneity (I2 > 60%). Four meta-analyses with forest plots suggesting a skewed SMD distribution also showed a linear trend on their standard errors on the funnel plot.ConclusionsIf the primary outcome is measured at baseline, it is essential to explore the full scope of baseline imbalance among the trials. This could help understand patterns of bias, including missingness, for designing adjustment.

MENTAL HEALTH AND SOCIAL MEDIA ADDICTION OF SECONDARY SCHOOL STUDENTS IN RELATION TO LOCALE DURING PANDEMIC COVID-19

The present study was conducted with the main objectives to study the mental health and social media addiction among secondary students with respect to certain variable like gender locale (rural, urban) and also to find out the relationship between mental health and social media addiction. The data was collected by selecting randomly 156 secondary school students by using a self made questionnaire “Social Media Addiction questionnaire Student Form”- developed by Researcher and “Mental Health Battery” by A. K. Singh &amp; Alpana Sengupta. The sample consisted of 53% students from rural schools and 47% students from urban schools. Descriptive research method was employed to carry out this quantitative research work. Normalization of data was done by using Histogram with normal probability curve. Descriptive Statistical technique like mean and standard deviation and inferential statistics like‘t’-test and correlation were used to analyze and interpret the data. All hypotheses were checked at the 0.05 level of significance. Result showed that significant differences of mental health exist rural and urban students (t=4.60, p=0.00) and significance differences of social media addiction exist between rural and urban students (t=2.62, p=0.009). Moreover, there exist a significant negative relationship (r= -0.769) between mental health and social media addiction. These finding will be helpful to aware about the use of social media and the better way to use social media for mentally healthy students. Present study offers to make insight in the social media user to eliminate the effect of addiction. Social media directly or indirectly affects the mental health of younger generation. These findings suggest that helping school students to gain a better understanding of the adverse effects of social media addiction.

Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) in Mono and Dual-isocentric Techniques of Breast Cancer Radiation Therapy

Background: Nowadays, radiation therapy plays an important role in the treatment of breast cancer. The important point is the optimal control of the tumor along with the protection of organs at risk. This study aims to investigate and compare the radiobiological factors of the tumor and organs at risk in two different radiation therapy techniques of breast cancer.Methods: Ten left-sided breast cancer patients with breast-conservative surgery were selected for this study. Three-dimensional treatment planning was performed using CT scan images of the patients using PCRT 3D software. Two different tangential external beam techniques were compared: first, dual-isocentric technique (DIT) with two isocentre, one on the breast tissue, and the other one on the supraclavicular lymph nodes and second, a mono-isocentric technique (MIT) with one isocentre at the intersection of the tangential and the supraclavicular field. The total prescribed dose was 5000 cGy per 25 fractions. Dose-volume histograms (DVHs), Tumor control probability (TCP), and normal tissue complication probability (NTCP) curves were used to compare the dosimetric and radiobiological parameters of the tissues in the prementioned techniques. Results: The results showed that the maximum doses in planning target volume (PTV) with mean values of 109% and 110% in the SI and DIT were not significantly different in both techniques and that they were indeed at the optimum level based on the RTOG 1005 protocol. The dose homogeneity index in MMIT was more than that in DIT, while the conformity index and the mean TCP did not show a significant difference in the two techniques. Furthermore, minimum, mean, and maximum dose in the lung and the probability of pneumonitis decreased in MIT. On the other hand, the maximum dose, the dose of 33%, 66%, and 100% of the heart, and the probability of pericarditis in MIT were lower than the figure in DIT. Conclusion: Due to the absence of hot spots at the intersection of tangential and supraclavicular fields and the reduction of mechanical movements of the coach and collimator in MIT, the superiority of this method was confirmed.

Integration of various scales for measurement of insomnia

Background Scales for evaluating insomnia differ in number of items, response format, and result in different scores distributions and score ranges and may not facilitate meaningful comparisons. Objectives Transform ordinal item-scores of three scales of insomnia to continuous, equidistant, monotonic, normally distributed scores, avoiding limitations of summative scoring of Likert scales. Methods Equidistant item-scores by weighted sum using data-driven weights to different levels of different items, considering cell frequencies of Item-Levels matrix, followed by normalization and conversion to [1, 10]. Equivalent test-scores (as sum of transformed item- scores) for a pair of scales were found by Normal Probability curves. Empirical illustration given. Results Transformed test-scores are continuous, monotonic and followed Normal distribution with no outliers and tied scores. Such test-scores facilitate ranking, better classification and meaningful comparison of scales of different lengths and formats and finding equivalent score combinations of two scales. For a given value of transformed test-score of a scale, easy alternate method avoiding integration proposed to find equivalent scores of another scales. Equivalent scores of scales help to relate various cut-off scores of different scales and uniformity in interpretations. Integration of various scales of insomnia is achieved by finding one-to-one correspondence among the equivalent score of various scales with correlation over 0.99 Conclusion Resultant test-scores facilitated undertaking analysis in parametric set up. Considering the theoretical advantages including meaningfulness of operations, better comparison, use of such method of transforming scores of Likert items/test is recommended test and items, Future studies were suggested.

Radioembolization of hepatocarcinoma with 90Y glass microspheres: treatment optimization using the dose-toxicity relationship.

Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50Gy/90Gy for bilirubin >/< 1.1mg/dL. These results are valid for a 90Y glass microsphere administration 4days after the reference time. Given the low predictive accuracy of 99mTc-MAA on lesion absorbed dose reported by several authors, an optimized TARE with 90Y glass microspheres with lobar injection 4days after reference time should aim at an absorbed dose averaged over the whole non-tumoural liver of 50Gy/90Gy for basal bilirubin higher/lower than 1.1mg/dL, respectively.

Efficacy of Integrated Intervention Program on Mental Health of Cancer Patients

Introduction Copious researchers have made notable findings on the mental health of cancer patients and effect of various discrete therapies, but still there exist a significant paucity on integrated therapeutic interventions over their mental health. The objectives of this study were to find the prevalence of mental health morbidity and the efficacy of an integrated intervention program comprised of Aaron Beck’s Cognitive Behavior Therapy (CBT), Jacobson Progressive Muscle Relaxation Therapy (JPMRT) and self- imagery training on the mental health of cancer patients.&#x0D; MethodsIn this cross-sectional study, data was collected from 20 patients diagnosed with cancer aged between 40-55 years from an outpatient department of Cancer Institute, India. General Health Questionnaire by Goldberg &amp; Hiller, 1979 (GHQ-28) was administrated to assess the mental health in four domains viz: somatic complaints, anxiety and insomnia, social dysfunction and severe depression. Integrated intervention program was conducted for four days per week for one month. Data was analyzed statistically by using normal probability curve (NPC) and paired t-test.&#x0D; ResultsAn overall prevalence of negative mental health and significant positive effect by the integrated intervention on the mental health among cancer patients have been statistically corroborated in this pre-post research.&#x0D; ConclusionIntegrated intervention program is efficacious in improving mental health in cancer patients.

Efficacy of Integrated Intervention Program on Mental Health of Cancer Patients

Introduction: Copious researchers have made notable findings on the mental health of cancer patients and effect of various discrete therapies, but still there exist a significant paucity on integrated therapeutic interventions over their mental health. The objectives of this study were to find the prevalence of mental health morbidity and the efficacy of an integrated intervention program comprised of Aaron Beck’s Cognitive Behavior Therapy (CBT), Jacobson Progressive Muscle Relaxation Therapy (JPMRT) and self- imagery training on the mental health of cancer patients. Methods: In this cross-sectional study, data was collected from 20 patients diagnosed with cancer aged between 40-55 years from an outpatient department of Cancer Institute, India. General Health Questionnaire by Goldberg &amp; Hiller, 1979 (GHQ-28) was administrated to assess the mental health in four domains viz: somatic complaints, anxiety and insomnia, social dysfunction and severe depression. Integrated intervention program was conducted for four days per week for one month. Data was analyzed statistically by using normal probability curve (NPC) and paired t-test. Results: An overall prevalence of negative mental health and significant positive effect by the integrated intervention on the mental health among cancer patients have been statistically corroborated in this pre-post research. Conclusion: Integrated intervention program is efficacious in improving mental health in cancer patients.

Mining-induced ground movements and displacements using transparent soil model test

Surface subsidence induced by mining subsidence affects the overlying buildings and nearby utilities. Therefore, an investigation of the internal displacement and surface settlement is very important. A small-scale transparent soil model was developed to study the surface settlement profile and displacement field induced by mining subsidence. An analysis of the continuous change of the displacement field inside the transparent soil models indicates that the subsurface settlement at different subsidence stages can be approximated by a normal probability curve. Additionally, the observed surface settlements are consistent with settlement predictions of both the probability integral method and the Gaussian distribution method. The results indicate that it is a good way to study further the underground structure–soil interaction.

INFLUENCE OF CHEMICAL SURFACE MODIFICATION ON MICRO-WEAR CHARACTERISTICS OF SUGARCANE NANOCELLULOSE EPOXY NANOCOMPOSITES

The waste sugarcane bagasse is the primary agricultural biomass of sugarcane industry and its main constituents is cellulose. These waste sugarcane bagasse can also be applied as reinforcement material in polymer matrix composites. In this present work, the nanocellulose fibers extracted from sugarcane bagasse using salt solution and alkaline treatment process. Sugarcane nanocellulose fiber reinforced epoxy nanocomposites were manufactured by wet layup method. This investigation has been conducted to exhibit the utilization of plant cellulose fiber as the potential reinforcement of synthetic fibers in tribo-composites. The dry sliding wear experiments designed and carried out as per central composite design to determine influence of 3 variable factors such as sliding velocity, sliding distance and load on the wear characteristics of epoxy nanocomposites. From ANOVA (Analysis of variance), it is observed that all three independent parameters plays an important role in the wear characteristics of epoxy nanocomposites, as proven from scanning electron microscope. Simultaneously minimize these tribological characteristics, desirable values of the parameters were depicted to be 5.94 m/s, 5 km and 5 N for sliding velocity, distance and load respectively. From normal probability curves, it is signified that there is a good agreement within the RSM models and experimental results.

Normal Tissue Complication Probability (NTCP) modeling and validation of quantitative analysis of normal tissue effects in the clinic (QUANTEC) guideline using quality of life questionnaire for parotid gland during head and neck radiotherapy

Introduction: Radiation therapy is the main treatment method for head and neck cancers, which comprise 3–5% of all cancers. A major side effect of this treatment is complication of the parotid glands, i.e. xerostomia, which occurs at relatively low doses. This complication leads to mouth dryness which is the most common problem for head and neck cancer survivors. There are different grades of xerostomia and severe xerostomia is defined as a long-term reduction in the function of salivary gland to less than 25% relative to the pre-radiotherapy baseline value. The grading of xerostomia is usually assessed by patient self-reports carried out by the quality of life questionnaire (QoL), designed based on indigenous criteria and internationally recognized protocols. In recent years several studies have focused on normal tissue complication probability (NTCP) modeling of xerostomia using quality of life questionnaires with or without functional analysis based on various standard model parameters. Lyman (LKB) model is commonly used to predict the normal tissue complication probability (NTCP). This model uses the patient’s calculated dose volume histogram of (DVH) of an organ at risk (OAR) and the dose response curve parameters. The quantitative analysis of normal tissue effects in the clinic (QUANTEC) effort is to refine the guidelines based on 3D dose/volume and outcome data. According to QUANTEC guideline to limit the severity of xerostomia, maximum dose received by one or both of parotid glands should be 20 Gy and 25 Gy (20/25 Gy), respectively. The aim of this study was to evaluate the NTCP model parameters for all grades of acute parotid complications using the LKB model during head and neck conformal radiotherapy treatment and using a QoL questionnaire. Materials and Methods: 50 patients with head and neck cancer who have been referred for radiotherapy to Milad Hospital in Isfahan, Iran, were selected. QoL questionnaire datasets of patients with squamous cell carcinoma and lymph node cancers beside the parotids were within the radiation field were analyzed. The European organization for research and treatment of cancer (EORTC) QLQ HN35 was used in three stages (before, during and at the end of treatment). Prescribed dose per fraction was modified to 2 Gy/fraction equivalent dose for each patients. The LKB model with DVH reduction to form the equivalent uniform dose (EUD), known as LEUD was used. The model parameters of TD50 (Tolerance Dose 50%) and m was assessed by fitting the patient reported complication data to the normal tissue complication probability (NTCP) curve. Results: One patient (2%) at stage 2 and 5 patients (10%) at stage 3 experienced grade 3 xerostomia. The dose-response curves (LKB model) for occurrence of xerostomia was fitted to the QoL data which were collected at stages 2 and 3. These parameters were TD50 =23.3Gy, m =1 and TD50 =21.6 Gy, m =1 at stage 2 and stage 3, respectively. Conclusion: The agreement between the NTCP modeling based on QoL questionnaire data and the QUANTEC guidelines, confirms the cutoff values of 20/25 Gy to spare the parotid gland.

OA187] Transfer of minibeam radiation therapy into a cost-effective equipment: A proof of concept

Introduction Minibeam radiation therapy (MBRT) is an innovative synchrotron radiotherapy technique able to shift the normal tissue complication probability curves to very high doses [1] . MBRT seem to involve different biological mechanisms (not well understood yet) different from those in standard RT. However, its exploration was hindered due to the limited and expensive beamtime at synchrotrons. The aim of this work was to evaluate the feasibility of the implementation of MBRT into cost-effective equipment. Materials and methods A series of modifications of a small animal irradiator were performed to make it suitable for MBRT experiments. In particular, an adapted collimator was designed by means of Monte Carlo simulations (Geant4). Peak to valley dose ratio values and full width half at maximum similar to those obtained at the European synchrotron radiation facility (ESRF) [2] were used as figure of merit. As a proof of concept, the whole brain of two groups were irradiated: a first group received conventional (broad beam) irradiations, the second series was irradiated with MBRT. The same average dose was deposited in both cases, 20 ± 1 Gy, which corresponds to 58 Gy peak dose in the MBRT case. The animals were followed-up for 6.5 months. At the end of the study a magnetic resonance imaging (MRI) evaluation and histological analysis were performed. Results The dosimetric features of our system were shown to be similar to the synchrotron ones [2] . Concerning the in vivo experiment, rats treated with conventional irradiation exhibited very important brain damage, including radionecrosis. In contrast, no substantial brain damage was observed in the animals of the MBRT group. Conclusions This work proves the feasibility of the transfer of MBRT outside synchrotron sources towards a small animal irradiator [3] . This is the first time that such an evaluation is done with millimetre-sized minibeams in the brain, which opens the door for future implementations with less technically demanding and very compact systems.

Model Based Radiation Therapy: Submandibular Dose-Response NTCP-Curve Based on Objective Measurements

Submandibular gland (SMG) normal tissue complication probability (NTCP) curves will be part of model-based indication for proton therapy in the Netherlands. Subjective measurements of xerostomia and sticky saliva reflect whole saliva, and are not suitable for the determination of the SMG NTCP curve. Therefore, we performed direct measurements of salivary flow, including the SMG flow. Based on a large database with a broad mean SMG dose distribution we obtained NTCP curves 6 weeks and 1 year after therapy. We utilized dose-response data of 200 head-and-neck patients, obtained from prospective salivary gland function studies. SMG flow was measured before, 6 weeks, and 1 year after therapy. Thirty patients were treated after unilateral neck dissection. Patients with N2c or N3 nodes were excluded. Tumors were localized in the oropharynx (69%), larynx (14%), nasopharynx (9%), oral cavity (4%), and hypopharynx (3%), 38% were N0, 32% T3-4. Treatment consisted of conventional RT, non-SMG sparing IMRT, SMG sparing IMRT, in 34, 84, and 82 patients, respectively. The mean dose to the ipsilateral submandibular gland was 62Gy, for the contralateral submandibular gland 47 Gy (range 0-72 Gy). Flow rates were converted to the baseline unilateral SMG flow rate, and compared with the contralateral SMG mean dose. Data were fitted to logistic regression (LR) and the Lyman-Kutcher-Burman (LKB) model, with a complication defined as a flow 6 weeks/ 1 year after therapy <25% of the flow before therapy [1]. There was a highly significant correlation between increasing mean SMG dose and decreasing absolute and relative SMG flow 6 weeks and 1 year after therapy. Mean contralateral SMG dose could be divided in five groups: ≤30 Gy (n=30), 30-40 Gy (28) 40-50 Gy (32), 50-60 Gy (57), > 60 Gy (53), the complication rate at 6 weeks was 22%, 50%, 73%, 76% and 86%, respectively; at 1 year 30%, 31%, 75%, 86% and 94%, respectively (P<.001). The D50 after 6 weeks was 31 Gy (95% CI 24-37), and 28 Gy (95% CI 21-34) after 1 year after analysis with the LKB model; 33 Gy (26-40) and 34 Gy (28-40), respectively, using the LR model. This NTCP-curve for submandibular gland function is based on the largest database of objective measurements in the literature. For planning purposes, usually a mean SMG-dose constraint of 40 Gy is chosen. We recommend a mean SMG dose of less than 30 Gy. [1] Dijkema et al. Int J Radiat Oncol Biol Phys. 2010:78;449-453.

Transfer of Minibeam Radiation Therapy into a cost-effective equipment for radiobiological studies: a proof of concept

Minibeam radiation therapy (MBRT) is an innovative synchrotron radiotherapy technique able to shift the normal tissue complication probability curves to significantly higher doses. However, its exploration was hindered due to the limited and expensive beamtime at synchrotrons. The aim of this work was to develop a cost-effective equipment to perform systematic radiobiological studies in view of MBRT. Tumor control for various tumor entities will be addressable as well as studies to unravel the distinct biological mechanisms involved in normal and tumor tissues responses when applying MBRT. With that aim, a series of modifications of a small animal irradiator were performed to make it suitable for MBRT experiments. In addition, the brains of two groups of rats were irradiated. Half of the animals received a standard irradiation, the other half, MBRT. The animals were followed-up for 6.5 months. Substantial brain damage was observed in the group receiving standard RT, in contrast to the MBRT group, where no significant lesions were observed. This work proves the feasibility of the transfer of MBRT outside synchrotron sources towards a small animal irradiator.

Optimization of Microbial Leaching of Base Metals from a South African Sulfidic Nickel Ore Concentrate by Acidithiobacillus ferrooxidans

ABSTRACTX-ray diffraction analysis revealed that pentlandite and chalcopyrite were the prominent mineral phases in a South African sulfidic nickel ore concentrate that hosted nickel and copper. Cobalt was found to be closely associated with the nickel-bearing pentlandite phase of the ore sample. Microbial batch leaching experiments designed according to a central composite design model were run for 15 days in a shaking incubator (150 rpm) at a constant temperature (30°C) with variations in experimental parameters like ore pulp density, particle size, bacterial inoculum, pH of the culture medium, and residence time. Quadratic mathematical models were developed to predict the rate of metal extractions. The suitability of the model of the microbial leaching process was confirmed from normal probability curves. An analysis of variance indicated that the residence time, pulp density of the ore, and particle size were the most significant factors. Bacterial inoculum size hardly showed any effect on the total metal extractions. Maximum nickel (82%), cobalt (76%) and copper (25.6%) extractions were achieved under optimum conditions, operated for 15 days at pulp density of 2% and particle size of −75 µm at pH 1.5.