Treatment data and technical process challenges for practical big data efforts in radiation oncology.

The term Big Data has come to encompass a number of concepts and uses within medicine. This paper lays out the relevance and application of large collections of data in the radiation oncology community. We describe the potential importance and uses in clinical practice. The important concepts are then described and how they have been or could be implemented are discussed. Impediments to progress in the collection and use of sufficient quantities of data are also described. Finally, recommendations for how the community can move forward to achieve the potential of big data in radiation oncology are provided.

Technical Report: Evaluation of peripheral dose for flattening filter free photon beams.

PURPOSE: To develop a comprehensive peripheral dose (PD) dataset for the two unflattened beams of nominal energy 6 and 10 MV for use in clinical care. METHODS: Measurements were made in a 40 × 120 × 20 cm(3) (width × length × depth) stack of solid water using an ionization chamber at varying depths (dmax, 5, and 10 cm), field sizes (3 × 3 to 30 × 30 cm(2)), and distances from the field edge (5-40 cm). The effects of the multileaf collimator (MLC) and collimator rotation were also evaluated for a 10 × 10 cm(2) field. Using the same phantom geometry, the accuracy of the analytic anisotropic algorithm (AAA) and Acuros dose calculation algorithm was assessed and compared to the measured values. RESULTS: The PDs for both the 6 flattening filter free (FFF) and 10 FFF photon beams were found to decrease with increasing distance from the radiation field edge and the decreasing field size. The measured PD was observed to be higher for the 6 FFF than for the 10 FFF for all field sizes and depths. The impact of collimator rotation was not found to be clinically significant when used in conjunction with MLCs. AAA and Acuros algorithms both underestimated the PD with average errors of -13.6% and -7.8%, respectively, for all field sizes and depths at distances of 5 and 10 cm from the field edge, but the average error was found to increase to nearly -69% at greater distances. CONCLUSIONS: Given the known inaccuracies of peripheral dose calculations, this comprehensive dataset can be used to estimate the out-of-field dose to regions of interest such as organs at risk, electronic implantable devices, and a fetus. While the impact of collimator rotation was not found to significantly decrease PD when used in conjunction with MLCs, results are expected to be machine model and beam energy dependent. It is not recommended to use a treatment planning system to estimate PD due to the underestimation of the out-of-field dose and the inability to calculate dose at extended distances due to the limits of the dose calculation matrix.

Intention to prescribe self-injectable epinephrine: Are there differences depending on who assesses the patient post-reaction?

INTRODUCTION: Anaphylaxis is the most severe of all allergic reactions and can even prove fatal. There is limited evidence of a difference in prescribing patterns for self-injectable epinephrine (SIE) between general paediatricians and paediatricians with greater knowledge of allergology. OBJECTIVES: Assess knowledge about prescribing SIE of a sample of primary care/hospital paediatricians and paediatricians with specialised knowledge of allergology through a questionnaire asking them about clinical cases of anaphylaxis in their daily paediatric practice. MATERIALS AND METHODS: Participants were primary care and hospital paediatricians practicing in different regions of the province of Barcelona and paediatricians with specialised knowledge in the field of allergology from Spain. RESULTS: A total of 183 paediatricians responded. Of that 59.6% were paediatricians with specialised knowledge of allergology. General paediatricians in most cases correctly prescribed SIE device (more than 70% answered correctly in five of the eight clinical cases). In the case of drug anaphylaxis, which is an avoidable allergen for which SIE is not indicated, 67.5% of general paediatricians would prescribe it. In the case of exercise-induced anaphylaxis there were also differences in the prescription of epinephrine by general paediatricians, with only 40% prescribing it. CONCLUSIONS: In this study the percentage of SIE prescriptions would be higher than expected by general paediatricians, with no differences in the cases proposed between them and the paediatricians with better knowledge of allergology. Despite these results, it is important to insist on conducting education programmes and disseminating them to facilitate physicians' recognition and treatment of anaphylactic reactions.

The protective effect of calcium on bone mass in postmenopausal women with high selenium intake.

OBJECTIVE: Nutritional factors, especially the two essential nutrients calcium and vitamin D, have been shown to play an important role in bone health. We wanted to determine the possible protective effect of calcium intake in adequate amounts on bone mass as assessed by quantitative ultrasound in postmenopausal women who also have a high intake of selenium. SETTING: Health district of Cáceres, Spain. PARTICIPANTS AND STUDY DESIGN: 335 postmenopausal women aged 60.9 (SD = 8.1) years. Women were stratified based on the vitamin D, vitamin E, calcium intake and the calcium/protein and calcium/phosphorous index. MEASUREMENTS: Bone status (Ad-SoS measured at the phalanges) was assessed with an ultrasound device model DBM Sonic 1200R. Food intake was quantified using dietetic scales, measuring cups, and spoons based on 7 days of diet records. Urine samples were collected the morning of testing after an overnight fast. Venous blood samples for the hematological and biochemical studies were also obtained in the fasting state. RESULTS: In the group of women with Ca intake < 800 mg / d we found a significant and negative relationship between Ad-SoS with age (ß= -4.020, F = 23.327) and selenium intake (ß = -0.419, F = 10.067), as well as a positive relationship with Ca intake (ß= 0.104 and F = 7.084) (p <0.0001 in all). In the group of women with Ca intake > 800 mg / d, age has a significant and negative relationship (ß = -4.829 and F = 106.745), whereas folic acid intake has a significant and positive relationship (ß = 0.047 and F = 5.858) (p <0.0001 in both). CONCLUSION: Elevated selenium intake negatively affects bone mass measurements in postmenopausal women over the age of 51 but only if calcium intake is also less than 800 mg / day. When calcium intake is greater than 800 mg/day, selenium did not appear to affect bone mass.

[Changes in the fat composition and histomorphology of the liver in TPN, with and without ultra-short bowel]. / Cambios en la composición de la grasa y en la histomorfología hepáticas tras NPT, con y sin intestino ultra-corto.

BACKGROUND & AIMS: Short Bowel syndrome is a serious intestinal insufficiency. The most common etiology in adults nowadays is intestinal ischemia and inflammatory disease, while in children the most common are congenital anomalies, volvolus and necrotizing enterocolaitis, which makes the TPN obligatory. However the intestine is intimately related to the liver through the entero-hepatic circulation and different endocrinological entero-hepatic systems. Massive intestinal resections and TPN would alter this relationship, and could change the hepatic tissue composition and its histomorphology. The aim of this work is to know these changes in more detail. MATERIALS AND METHODS: We used 3 experimental groups: Group A (10 guinea pigs), which was given anesthetic and a simple laparotomy and fed for 10 days with NPT. Group B (10 guinea pigs), underwent total thin intestine resection and were fed for 10 days with NTP. The control group (6 guinea pigs) underwent anesthetic and a simple sham laparotomy and were fed orally. After this period blood and hepatic tissue samples were taken in order to study the liver fat (total fat, proportion of neutral and polar lipids, proportion of phospholipids and fatty acids). Liver biopsies were taken and studied under an optical microscope. RESULTS: The animals from group A and B, underwent NPT, showed a significant increase in glycemie and serum triglycerides, decreasing the cholesterol in GB. There was a significant decrease in weight and in the proportion of fat per g of the liver tissue, at a maximum level in GB, and an even higher decrease in the LP/LN ratio in GA and GB. There was also a change in the proportion of phospholipids, decreasing the Phosphatidilinositol and increasing the Phosphatidiletanolamine. There was also a decrease in the AG w6/w3 ratio. Histologically appear a steatohepatitys, with a striking decrease in the mitochondrial density, being more intensive in GB. CONCLUSIONS: NPT alters the composition of the hepatic fat and the hystomorphology of the liver. The short bowel syndrome have more lesional mechanisms, favouring the hepatic damage caused by NPT.

Nitric oxide induces caspase activity in boar spermatozoa.

Nitric oxide (NO) is a highly reactive free radical that plays a key role in intra- and intercellular signaling. Production of radical oxygen species and an apoptotic-like phenomenon have recently been implicated in cryodamage during sperm cryopreservation. The objective of the present study was to evaluate the effect of sodium nitroprusside (SNP), an NO donor, on boar sperm viability. Semen samples were pooled from four boars that were routinely used for artificial insemination. Flow cytometry was used to compare semen incubated with SNP to control semen. Specifically, NO production was measured using the NO indicator dye diaminofluorescein diacetate, and caspase activity was determined using the permeable pan-caspase inhibitor Z-VAD linked to FITC. SNP induced a significant increase in the percentage of sperm cells showing caspase activity, from 9.3% in control samples to 76.2% in SNP-incubated samples (P<0.01). This study suggests that NO is a major free radical involved in boar sperm damage.

Identification of sperm morphometric subpopulations in the canine ejaculate: do they reflect different subpopulations in sperm chromatin integrity?

A statistical approach using sequentially principal component analysis (PCA) clustering and discriminant analysis was developed to disclose morphometric sperm subpopulations. In addition, we used a similar approach to disclose subpopulations of spermatozoa with different degrees of DNA fragmentation. It is widely accepted that sperm morphology is a strong indicator of semen quality and since the sperm head mainly comprises the sperm DNA, it has been proposed that subtle changes in sperm head morphology may be related to abnormal DNA content. Semen from four mongrel dogs (five replicates per dog) were used to investigate DNA quality by means of the sperm chromatin structure assay (SCSA), and for computerized sperm morphometry (ASMA). Each sperm head was measured for nine primary parameters: head area (A), head perimeter (P), head length (L), head width (W), acrosome area (%), midpiece width (w), midpiece area (a), distance (d) between the major axes of the head and midpiece, angle (theta) of divergence of the midpiece from the head axis; and four parameters of head shape: FUN1 (L/W), FUN2 (4pi A/P2), FUN3 ((L - W)/(L + W)) and FUN 4 (pi LW/4A). The data matrix consisted of 2361 observations, (morphometric analysis on individual spermatozoa) and 63,815 observations for the DNA integrity. The PCA analysis revealed five variables with Eigen values over 1, representing more than 79% of the cumulative variance. The morphometric data revealed five sperm subpopulations, while the DNA data gave six subpopulations of spermatozoa with different DNA integrity. Significant differences were found in the percentage of spermatozoa falling in each cluster among dogs (p < 0.05). Linear regression models including sperm head shape factors 2, 3 and 4 predicted the amount of denatured DNA within each individual spermatozoon (p < 0.001). We conclude that the ASMA analysis can be considered a powerful tool to improve the spermiogram.

Differences in boar sperm head shape and dimensions recorded by computer-assisted sperm morphometry are not related to chromatin integrity.

Although sperm head shape and relative dimensions are considered reliable indicators of sperm quality, their quantification is most often operator-driven, e.g., subjective. Artificial insemination semen doses from 35 mature stud boars of known fertility and belonging to three breeds and two hybrid breeds (Duroc, Large White, Landrace, respectively, Yorker and Risco) were used in this study. Sperm samples were extended to 100x10(6) cells per mL and 10microL of the sperm suspension used to made smears which, stained, were examined using phase contrast microscopy interfaced with an automated sperm morphology analyzer (ASMA, ISAS). Each sperm head was measured for four primary parameters [area (A) microm(2), perimeter (P) mum, length (L) microm, width (W) microm], and four derived parameters of head shape [(L/W), (4piA/P(2)), ((L-W)/(L+W)), (piLW/4A)]. Definition of head size was statistically performed. The threshold for each class was established on the basis of the area values, considering the 25th percentile as small and the 75th percentile as large spermatozoa. In a second step, sperm head shape was determined as normal, elliptic, abnormal (rugose) contour, long or irregular and percentiles set as above to define spermatozoa with normal values for each shape parameter. Significant differences were found among breeds in the size of morphologically normal spermatozoa, which were significantly larger and more elliptic (P<0.001) in the Duroc breed. Sperm chromatin integrity was studied using the SCSA-assay, with significant differences observed in the degree of fragmentation intensity (DFI) although this value was consistently low in all animals studied. The hereby-validated ASMA was able to determine significant differences in sperm shape and dimensions among breeds, which were not accompanied by deviations in chromatin structure neither within nor between fertile AI-boars.

Sperm indexes obtained using computer-assisted morphometry provide a forecast of the freezability of canine sperm.

Sperm morphometric indexes obtained after principal component analysis were used to investigate its value as diagnostic tests for freezability. Semen from six dogs was frozen-thawed following a standard protocol. Before freezing, computer-assisted analysis of sperm morphometry (CASMA) was performed. The principal component analysis (a statistical technique for simplifying a dataset, by reducing multidimensional datasets to lower dimensions for analysis) performed in the data obtained after the CASMA analysis gave four morphometric indexes. After thawing, ejaculates were evaluated for early changes in sperm membranes using the combination of two fluorescent probes, YO-PRO-1 and ethidium homodimer and flow cytometry. Significant differences in the percentages of intact membranes post-thaw were observed among dogs (p < 0.01). Significant non-parametric correlations were found between index 3 and the percentage of intact membranes after thawing (R = 0.432 p < 0.05). Receiving operating system curves demonstrate a good diagnostic value for indexes 2 and 3 in the prediction of freezability, with areas under the curve of 0.798 and 0.786, respectively.

A three-step statistical procedure to identify sperm kinematic subpopulations in canine ejaculates: changes after cryopreservation.

Strong evidences suggest that many different sperm subpopulations co-exist within the mammalian ejaculate. These subpopulations have been identified in a number of species; however, to the best of our knowledge, no data exist regarding the existence of sperm subpopulations within the canine ejaculate. Ejaculates were obtained by masturbation from four mongrels and processed using a standard freezing protocol. Motility data were analysed before and after cryopreservation using a computer assisted sperm analysis (CASA) system ISAS. On raw data, a principal component analysis (PCA) was performed to reduce the number of motility descriptors to a few informative variables, and then a K-means cluster procedure was performed and then a regression analysis to validate the clusters obtained in the second analysis. ANOVAs and chi-squared analyses were used to compare clusters and males. PCA revealed that two principal components represented more that the 88% of the variance with eigenvalues of 3.25 and 3.02, respectively. The clustering and discriminant analysis using curvilinear velocity and linear velocity as variables revealed the existence of 11 sperm subpopulations--four of them characterized by high velocities, two by medium values and five by low velocities. After freezing-thawing, nine subpopulations were found--four of high velocities, two of medium and three of low velocities. It is concluded that freezing-thawing not only impairs sperm motility but also produces changes in the sperm subpopulation structure in the canine ejaculate, that the evaluation of the sperm structure subpopulations is a better indicator of semen quality and freezeability than the use of mean values, and that two sperm motility quality indexes can be used to resume of the variables obtained from the CASA analysis.

Semen technologies in dog breeding: an update.

Pure dog breeding is experiencing growing interest. Assisted reproductive technologies are each time demanded more by the small animal practitioner. In this paper different semen technologies are briefly reviewed under the perspective of the authors. In addition, new trends in the evaluation of canine ejaculates, developed in the laboratory of the authors are discussed. The existence of sperm subpopulations defined based both on kinematics and morphometric characteristics of the spermatozoa is now widely accepted by the scientific community. In the laboratory of the authors new, simpler and more straightforward statistical tools have been used to disclose the sperm subpopulation structure in the canine ejaculate. The study of the sperm subpopulation structure and its changes after cryopreservation has allowed us to gain an insight into the differences in freezeability among dogs, and also predict to a great extent the outcome of a cryopreservation procedure of a given semen sample. New techniques to evaluate early membrane changes have also been recently developed in our laboratory.