Circular Scan Research Articles

Lung Perfused Blood Volume Calculated From Dynamic Contrast Enhanced DECT for Radiation Treatment Planning of Lung Cancer

<h3>Purpose/Objective(s)</h3> In radiation therapy planning for lung cancer, it is desirable to minimize irradiation of functional lung tissue which may be mapped by the spatial distribution of perfused blood volume (PBV). In this exploratory study, we investigate the feasibility of generating PBV distribution based on equilibrium contrast enhanced dual-energy CT (DECT) routinely acquired at the time of CT simulation for lung cancer patients. <h3>Materials/Methods</h3> DECT data with iodine-based intravenous (IV) contrast enhancement along with 4DCT acquired using a Dual Source DECT scanner (Drive, Siemens Healthcare, Germany) for 5 lung cancer patients during routine CT simulation were analyzed. The delay of the IV contrast injection was calculated for each patient via a circular scan monitoring a region of interest (ROI) in the pulmonary trunk for a CT number increase of 150 HU. This increase triggers a further 7 second delay after which the scanner rapidly performs two simultaneous acquisitions, the first at a tubevoltage of 80 kV and the second at a tube voltage of 140 kV with Sn filtration. For each patient the PBV was automatically calculated via post-processing at the console. The obtained PBV maps were compared to ventilation maps calculated in a programming environment using a HU-based method from the 4DCT, which was sorted into 10 bins based on respiratory phase. The image set of the end of the inhale phase was warped to the image set of the end of the exhale phase (target images) in MIM software using an intensity-based deformable image registration algorithm. The HU values of the warped and target images in each associated voxel pair inside lung contours were used to calculate local lung volume changes. <h3>Results</h3> The obtained lung PBV maps demonstrated heterogeneity in lung function for all patients. The average PBV in arbitrary units was 52.3 ± 16.7. The PBV distribution for 4 patients had a single peak, while therewas a bifurcation for one case. For one of the patients, the image quality was degraded by high Z materials in the patient's shoulders. For one of the patients there was a correlation between the PBV map and the ventilation map. The tidal volumes calculated using the ventilation images agree within 5% with those measured through volume difference of lung contours on end of exhale and end of inhale images, indicating the accuracy of the ventilation images. <h3>Conclusion</h3> Lung PBV maps derived from equilibrium contrast enhanced DECT acquired for radiation therapy planning may provide a valuable new tool to assess the spatial distribution of normal lung function, alternative to the lung ventilation map. With additional study the PBV maps may be used to guide radiation treatment planning for lung cancer patients.

Modular deep neural networks for automatic quality control of retinal optical coherence tomography scans

Retinal optical coherence tomography (OCT) with intraretinal layer segmentation is increasingly used not only in ophthalmology but also for neurological diseases such as multiple sclerosis (MS). Signal quality influences segmentation results, and high-quality OCT images are needed for accurate segmentation and quantification of subtle intraretinal layer changes. Among others, OCT image quality depends on the ability to focus, patient compliance and operator skills. Current criteria for OCT quality define acceptable image quality, but depend on manual rating by experienced graders and are time consuming and subjective. In this paper, we propose and validate a standardized, grader-independent, real-time feedback system for automatic quality assessment of retinal OCT images. We defined image quality criteria for scan centering, signal quality and image completeness based on published quality criteria and typical artifacts identified by experienced graders when inspecting OCT images. We then trained modular neural networks on OCT data with manual quality grading to analyze image quality features. Quality analysis by a combination of these trained networks generates a comprehensive quality report containing quantitative results. We validated the approach against quality assessment according to the OSCAR-IB criteria by an experienced grader. Here, 100 OCT files with volume, circular and radial scans, centered on optic nerve head and macula, were analyzed and classified. A specificity of 0.96, a sensitivity of 0.97 and an accuracy of 0.97 as well as a Matthews correlation coefficient of 0.93 indicate a high rate of correct classification. Our method shows promising results in comparison to manual OCT grading and may be useful for real-time image quality analysis or analysis of large data sets, supporting standardized application of image quality criteria.

Clustering of childhood cancer in Colombia: a nationwide study

BACKGROUND AND AIM: Childhood cancer is considered as one the most important causes of death in children and adolescents, despite having a low incidence in this population. Spatial analysis has been previously used for the study of childhood cancer to study the geographical distribution of leukemias. This study aimed to identify the presence of space-time clusters of childhood of cancer excluding leukemia in Colombia between 2014 and 2017. METHODS: All incident cancer cases excluding leukemia in children under the age of 15 years that have confirmed by the National Surveillance System of Childhood Cancer between 2014 and 2017 were included. Kulldorf’s circular scan test was used to identify clusters using the municipality of residence as the spatial unit of analysis and the year of diagnosis as the temporal unit of analysis. A sensitivity analysis was conducted with different upper limit parameters for the at-risk population. RESULTS:A total of 2006 cases of non-leukemia childhood cancer were analyzed, distributed in 432 municipalities with a mean annual incidence rate of 44 cases per million children under the age of 15. Central nervous system (CNS) tumors were the most frequent type. Four spatial clusters and two space-time clusters were identified in the central and southwest regions of the country. In the analysis for CNS tumors, a spatial cluster was identified in the central region of the country. CONCLUSIONS:The distribution of non-leukemia childhood cancer seems to have a clustered distribution in some Colombian regions that may suggest infectious or environmental factors associated with its incidence. KEYWORDS: Outcomes, Children's environmental health, Spatial statistics

Circular RNA circ-RNF121 contributes to cisplatin (DDP) resistance of non-small-cell lung cancer cells by regulating the miR-646/SOX4 axis.

Chemo-resistance is considered a major obstacle in the clinical treatment of non-small-cell lung cancer (NSCLC). Circular RNA (circRNA) circ-RNF121 (hsa_circ_0023404) has been identified to be related to the cisplatin (DDP) resistance. However, the role and mechanism of circ-RNF121 in the DDP resistance in NSCLC are still unknown. Real-time quantitative PCR (RT-qPCR) was applied to detect the levels of circ-RNF121, microRNA-646 (miR-646) and SRY-related HMG box transcription factor 4 (SOX4). Cell viability, proliferation, apoptosis, migration, invasion and cell cycle progression were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, flow cytometry, wound-healing, transwell and flow cytometry assays, severally. The binding relationship between miR-646 and circ-RNF121 or SOX4 was predicted by the circular RNA interactome or Target Scan Human7.2 and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. SOX4 protein level was measured by western blot assay. The biological role of circ-RNF121 on NSCLC tumor growth and drug resistance was examined by the xenograft tumor model in vivo. Circ-RNF121 and SOX4 were increased, and miR-646 was declined in DDP-resistant NSCLC tissues and cells. Furthermore, the circ-RNF121 deficiency could enhance DDP sensitivity by inhibiting cell proliferation, migration, invasion, cell cycle progression and promoting apoptosis in DDP-resistant NSCLC cells in vitro. Mechanically, circ-RNF121 served as a sponge of miR-646 to increase SOX4 expression. Circ-RNF121 knockdown improved the drug sensitivity of NSCLC in vivo. Circ-RNF121 silencing could reduce the DDP resistance of NSCLC cells by regulating SOX4 expression via miR-646. These findings hinted at a promising therapeutic target for NSCLC treatment.

CMB polarization analysis on circular scans

Most cosmic microwave background experiments observe the sky along circular or near-circular scans on the celestial sphere. For such experiments, we show that simple linear systems connect the Fourier spectra of temperature and polarization time-ordered data to the harmonic spectra of T, E and B on the sphere. We also show how this can be used to estimate those spectra directly from data streams by inversion of a linear system that connects Fourier spectra to angular power spectra, offering an easy way to down-weight those modes of observation most contaminated by low-frequency noise, ground pickup, or fluctuations of atmospheric emission on large angular scale. This direct connection between Fourier spectra and harmonic spectra on the sphere can be of interest for the analysis of future CMB data sets, in complement to other approaches that involve map-making as a first analysis step.

Multimodal Machine Learning Using Visual Fields and Peripapillary Circular OCT Scans in Detection of Glaucomatous Optic Neuropathy

To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON). Cross-sectional study. Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients. FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects. Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input). FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucoma specialists (glaucoma specialist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucoma specialist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucoma specialists and FusionNet in the internal and external test sets, except for glaucoma specialist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set. FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON.

Estimating the optimal population upper bound for scan methods in retrospective disease surveillance.

Correctly and quickly identifying disease patterns and clusters is a vital aspect of public health and epidemiology so that disease outbreaks can be mitigated as effectively as possible. The circular scan method is one of the most commonly used methods for detecting disease outbreaks and clusters in retrospective and prospective disease surveillance. The circular scan method requires a population upper bound in order to construct the set of candidate zones to be scanned, which is usually set to 50% of the total population. The performance of the circular scan method is affected by the choice of the population upper bound, and choosing an upper bound different from the default value can improve the method's performance. Recently, the Gini coefficient based on the Lorenz curve, which was originally used in economics, was proposed to determine a better population upper bound. We present the elbow method, a new method for choosing the population upper bound, which seeks to address some of the limitations of the Gini-based method while improving the performance of the circular scan method over the default value. To evaluate the performance of the proposed approach, we evaluate the sensitivity and positive predictive value of the circular scan method for publicly-available benchmark data for the default value, the Gini coefficient method, and the elbowmethod.

Complex 3D scan trajectories for industrial cone-beam computed tomography using a hexapod

Industrial x-ray computed tomography (CT) represents an established measurement technique in the field of nondestructive testing and dimensional metrology. However, the measurement accuracy is sometimes limited by measurement artifacts that cannot be avoided using a standard circular scan trajectory. This problem can be addressed with the aid of flexible 3D trajectories, but up to date, the application of these is mainly restricted to special CT devices using robot arms. In this paper, we present results using a hexapod as an additional positioning system in a commercial industrial CT scanner. In addition to the 360∘ rotation, task-specific tilting of the part during the scan is possible in this way. We used and adapted geometry calibration procedures based on a multi-sphere reference object to enable reconstruction with high accuracy. Using a demonstrator test fixture with high absorbing elements, we show that severe metal and truncation artifacts can be avoided for a region-of-interest scan. Furthermore, cone-beam artifacts, which are inherent to circular scan trajectories, can be reduced significantly. Using measurement objects that can be measured well with a circular trajectory, we found that applying a 3D trajectory leads to dimensional measurement deviations in the same range or even lower than those of a circular trajectory. This suggests that the pose repeatability of the hexapod is sufficient to perform complex scan paths without general loss of accuracy. The obtained results could be relevant for end users of conventional CT scanners, as upgrading existing devices is in principle possible. The presented investigations form the basis for the application of trajectory optimization algorithms.

Clustering of non-leukemia childhood cancer in Colombia: a nationwide study

Background: Childhood cancer is considered one the most important causes of death in children and adolescents, despite having a low incidence in this population. Spatial analysis has been previously used for the study of childhood cancer to study the geographical distribution of leukemias. This study aimed to identify the presence of space-time clusters of childhood of cancer excluding leukemia in Colombia between 2014 and 2017. Methods: All incident cancer cases (excluding leukemia) in children under the age of 15 years that had been confirmed by the National Surveillance System of Childhood Cancer between 2014 and 2017 were included. Kulldorf’s circular scan test was used to identify clusters using the municipality of residence as the spatial unit of analysis and the year of diagnosis as the temporal unit of analysis. A sensitivity analysis was conducted with different upper limit parameters for the at-risk population in the clusters. Results: A total of 2006 cases of non-leukemia childhood cancer were analyzed, distributed in 432 out of 1,122 municipalities with a mean annual incidence rate of 44 cases per million children under the age of 15. Central nervous system (CNS) tumors were the most frequent type. Two space-time clusters were identified in the central and southwest regions of the country. In the analysis for CNS tumors, a spatial cluster was identified in the central region of the country. Conclusions: The distribution of non-leukemia childhood cancer seems to have a clustered distribution in some Colombian regions that may suggest infectious or environmental factors associated with its incidence although heterogeneity in access to diagnosis cannot be discarded.

Comparison of Two Spectral-domain Optical Coherence Tomography Scan Modes for Measuring Retinal Vessel Diameter

ABSTRACT Purpose: To assess the agreement between Line 3–5 raster scan mode and circular scan mode for measuring retinal vessel diameter, and to analyze the influence of scanning distance on retinal vessel diameter and agreement. Methods: 79 healthy participants (79 eyes) were scanned with two modes. The scanning distance was defined as the distance from the center of the optic disc to the intersection of the blood vessel and the scan line on the raster image. The large superior temporal vessel was measured, with the distance between vascular wall hyperreflectivities measured to obtain vessel diameters. The degree of agreement between the line 3–5 raster scan and circular scan modes, and the effect of scanning distance on agreement and vascular diameter were assessed. Results: There was good agreement between line 3 subgroup and the circular scan for measuring venous and arterial diameter (venous: intraclass correlation coefficients (ICCs) = 0.87, p < .001; arterial: ICCs = 0.84, p < .001). Unexpectedly, diameters from the fourth raster scan were only comparable to the circular scan in measuring venous diameter (ICCs = 0.86, p < .001), despite the same scanning distance between the fourth raster line and circular scan. Vessels with a scanning distance between 1400 μm – 1799 μm showed good agreement with the circular scan (venous and arterial: all ICCs ≥ 0.84, p < .001). In addition, venous diameter and arterial diameter decreased with increasing distance from the optic disc center, with venous and arterial diameter decreasing by 0.02 μm/μm (p < .001) and 0.007 μm/μm (p = .02), respectively. Conclusion: Arterial and venous diameter measured by the circular mode was comparable to only one scan line and two scan lines of the raster scan mode, respectively. Our study identified a difference between the two scan modes, with the difference not fully attributable to differences in scanning distance. Prospective studies reporting vascular diameter as a primary outcome should report the scan mode used.

Clustering of non-leukemia childhood cancer in Colombia: a nationwide study

Background: Childhood cancer is considered one the most important causes of death in children and adolescents, despite having a low incidence in this population. Spatial analysis has been previously used for the study of childhood cancer to study the geographical distribution of leukemias. This study aimed to identify the presence of space-time clusters of childhood of cancer excluding leukemia in Colombia between 2014 and 2017. Methods: All incident cancer cases (excluding leukemia) in children under the age of 15 years that had been confirmed by the National Surveillance System of Childhood Cancer between 2014 and 2017 were included. Kulldorf’s circular scan test was used to identify clusters using the municipality of residence as the spatial unit of analysis and the year of diagnosis as the temporal unit of analysis. A sensitivity analysis was conducted with different upper limit parameters for the at-risk population in the clusters. Results: A total of 2006 cases of non-leukemia childhood cancer were analyzed, distributed in 432 out of 1,122 municipalities with a mean annual incidence rate of 44 cases per million children under the age of 15. Central nervous system (CNS) tumors were the most frequent type. Two space-time clusters were identified in the central and southwest regions of the country. In the analysis for CNS tumors, a spatial cluster was identified in the central region of the country. Conclusions: The distribution of non-leukemia childhood cancer seems to have a clustered distribution in some Colombian regions that may suggest infectious or environmental factors associated with its incidence although heterogeneity in access to diagnosis cannot be discarded.

Segregation of neuronal-vascular components in a retinal nerve fiber layer for thickness measurement using OCT and OCT angiography.

Assessment of the circumpapillary retinal nerve fiber layer (RNFL) provides crucial knowledge on the status of the optic nerve. Current circumpapillary RNFL measurements consider only thickness, but an accurate evaluation should also consider blood vessel contribution. Previous studies considered the presence of major vessels in RNFL thickness measurements from optical coherence tomography (OCT). However, such quantitative measurements do not account for smaller vessels, which could also affect circumpapillary RNFL measurements. We present an approach to automatically segregate the neuronal and vascular components in circumpapillary RNFL by combining vascular information from OCT angiography (OCTA) and structural data from OCT. Automated segmentation of the circumpapillary RNFL using a state-of-the-art deep learning network is first performed and followed by the lateral and depth-resolved localization of the vascular component by vertically projecting the vessels along the circular scan from OCTA vessels map onto the segmented RNFL. Using this proposed approach, we compare the correlations of circumpapillary RNFL thicknesses with age at different levels of vessel exclusion (exclusion of major vessels only vs both major- and micro-vessels) and also evaluate the thickness variability in 75 healthy eyes. Our results show that the ratio of major- and micro-vessels to circumpapillary RNFL achieved a stronger correlation with aging (r = 0.478, P < .001) than the ratio with only major vessels to circumpapillary RNFL (r = 0.027, P = .820). Exclusion of blood vessels from circumpapillary RNFL thickness using OCTA imaging provides a better measure of the neuronal components and could potentially improve the diagnostic performance for disease detection.

Early Identification of Retinal Neuropathy in Subclinical Diabetic Eyes by Reduced Birefringence of the Peripapillary Retinal Nerve Fiber Layer.

PurposeTo study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT).MethodsIn this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC).ResultsOut of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients (P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors (P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group.ConclusionsWe identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.

Tuneable in-situ nanoCT workflow using FIB/SEM

Inspired by the standard computed tomography, a new method of 3D X-ray imaging embedded in FIB-SEM microscope is proposed. The unique combination of TEM-like specimen stage enabling in lens STEM detection (referred to as CompuStage), nanomanipulator (referred to as EasyLift) facilitating in-situ sample transfer from bulk sample to TEM-like stage and pixelated in-situ Timepix X-ray detector in Helios G4 FX FIB-SEM system offers an unprecedented workflow. Motivated by common circular CT scan known from microCT world, the object under study is placed on CompuStage rod which enables two possible rotation (in TEM/SEM terminology called tilt) movements – α-tilt – rotation of the CompuStage rod around its axis, and β-tilt – rotation around axis perpendicular to CompuStage rod. β-tilt rotation enables a circular movement of the sample while α-tilt sets the correct position of sample with respect to target and detector. Thin metal lamella of suitable material welded to EasyLift manipulator needle is used as an X-ray target. The final target-sample geometry – position, distance – can be fine-tuned using position control of CompuStage and EasyLift and in-situ monitored by SEM. Both sample and target can also be easily prepared in-situ. Radiographs are recorded by Timepix detector with inherent noise-free operation and energy filtration. For the 3D reconstruction standard microCT reconstruction algorithm is used with the procedure adjusted for the format and quality of nanoCT images.The experiments were carried out on Helios G4 FX DualBeam using titanium and tungsten targets and various semiconductor samples. The ultimate resolution of the proposed method in orders of tens of nanometers was achieved both by the possibility of close target to sample positioning and of adjustment of primary beam energy down to low energies reducing the interaction volume in the target. Since the lower energy radiation is well suited for life-science, the method was also tested on several bio-samples using silver target. The silver target, thanks to its massive low energy Lα line, allowed to distinguish subtle structures in the resin embedded stained mouse brain and also to observe and reconstruct canaliculi in the mouse bone (earlier reported by Dierolf et al. 2010, Nature 467 436).

A Comparative Analysis of Disk Scheduling Algorithms

In an operating system, disk scheduling is the process of managing the I/O request to the secondary storage devices such as hard disk. The speed of the processor and primary memory has increased in a rapid way than the secondary storage. Seek time is the important factor in an operating system to get the best access time. For the better performance, speedy servicing of I/O request for secondary memory is very important. The goal of the disk-scheduling algorithm is to minimize the response time and maximize throughput of the system.&#x0D; This work analyzed and compared various basic disk scheduling techniques like First Come First Serve (FCFS), Shortest Seek Time First (SSTF), SCAN, LOOK, Circular SCAN (C-SCAN) and Circular LOOK (C-LOOK) along with the corresponding seek time. From the comparative analysis, the result show that C-LOOK algorithm give the least head movement and seek time in different cases as compared to other algorithm. Therefore, it maximizes the throughput for the storage devices.

Automatic radar antenna scan type recognition based onlimited penetrable visibility graph

To address the problem of the weak anti-noise and macro-trend extraction abilities of the current methods for identifying radar antenna scan type, a recognition method for radar antenna scan types based on limited penetrable visibility graph(LPVG) is proposed. Firstly, seven types of radar antenna scans are analyzed, which include the circular scan, sector scan, helical scan, raster scan, conical scan, electromechanical hybrid scan and two-dimensional electronic scan. Then, the time series of the pulse amplitude in the radar reconnaissance receiver is converted into an LPVG network, and the feature parameters are extracted. Finally, the recognition result is obtained by using a support vector machine (SVM) classifier. The experimental results show that the recognition accuracy and noise resistance of this new method are improved, where the average recognition accuracy for radar antenna type is at least 90% when the signal-to-noise ratio (SNR) is 5 dB and above.

Confidence intervals for spatial scan statistic

The spatial scan statistic is a popular statistical tool to detect geographical clusters of diseases. The basic problem of constructing confidence intervals for the relative risk of the most likely cluster has remained an open question. To cover this lack, a Monte Carlo based interval estimator for the relative risk of the primary cluster is derived. The method works for the circular spatial scan statistic applied to binomial data, and it ensures, by construction, an analytical control of the coverage probability under the nominal confidence coefficient. In addition, its performance is illustrated on simulated and real data of birth defects in New York State.

Clustering of childhood cancer in Colombia: a nationwide study.

Background: Childhood cancer is considered one the most important causes of death in children and adolescents, despite having a low incidence in this population. Spatial analysis has been previously used for the study of childhood cancer to study the geographical distribution of leukemias. This study aimed to identify the presence of space-time clusters of childhood of cancer excluding leukemia in Colombia between 2014 and 2017. Methods: All incident cancer cases (excluding leukemia) in children under the age of 15 years that had been confirmed by the National Surveillance System of Childhood Cancer between 2014 and 2017 were included. Kulldorf's circular scan test was used to identify clusters using the municipality of residence as the spatial unit of analysis and the year of diagnosis as the temporal unit of analysis. A sensitivity analysis was conducted with different upper limit parameters for the at-risk population. Results: A total of 2006 cases of non-leukemia childhood cancer were analyzed, distributed in 432 municipalities with a mean annual incidence rate of 44 cases per million children under the age of 15. Central nervous system (CNS) tumors were the most frequent type. Four spatial clusters and two space-time clusters were identified in the central and southwest regions of the country. In the analysis for CNS tumors, a spatial cluster was identified in the central region of the country. Conclusions: The distribution of non-leukemia childhood cancer seems to have a clustered distribution in some Colombian regions that may suggest infectious or environmental factors associated with its incidence.

Biochemical and biophysical characterisation of a small purified lipase from Rhizopus oryzae ZAC3

The characteristics of a purified lipase from Rhizopus oryzae ZAC3 (RoL-ZAC3) were investigated. RoL-ZAC3, a 15.8 kDa protein, which was optimally active at pH 8 and 55 °C had a half-life of 126 min at 60 °C. The kinetic parameters using p-nitrophenylbutyrate as substrate were 0.19 ± 0.02 mM, 126 ± 5.6 U/ml and 122 s−1 for Km , V max and k cat respectively. RoL-ZAC3 showed stability in methanol and isopropanol with Na+ enhancing the activity. p-nitrophenyloleate and castor oil were the best preferred substrates among the p-nitrophenyl esters and vegetable oils tested respectively. About 43% residual activity was observed after incubation for 30 min at 75 °C. Circular dichroism thermal scan showed that the lipase displayed intense negative ellipticities even at high temperature. Perturbation of the tertiary structure with increasing temperature caused the exposure of hydrophobic side chains to the aqueous environment as revealed by tryptophan fluorescence, with a t−Tm of 50 °C. Differential scanning calorimetry analysis showed melting temperature and calorimetric enthalpy of 55.5 °C and 444 kJ/mol respectively. Dynamic light scattering analysis indicated that the lipase was prone to aggregation upon unfolding at high temperature. It can be concluded that RoL-ZAC3 possesses promising potential for numerous biotechnological applications.

Spatial scan statistics can be dangerous.

Spatial scan statistics are widely used tools for the detection of disease clusters. Especially, the circular spatial scan statistic proposed by Kulldorff along with SaTScan software has been used in a wide variety of epidemiological studies and disease surveillance. However, as it cannot detect non-circular, irregularly shaped clusters, many authors have proposed non-circular spatial scan statistics. Above all, the flexible spatial scan statistic proposed by Tango and Takahashi along with FleXScan software has also been used. However, it does not seem to be well recognized that these spatial scan statistics, especially SaTScan, tend to detect the most likely cluster, much larger than the true cluster by absorbing neighboring regions with nonelevated risk of disease occurrence. Therefore, if researchers reported the detected most likely cluster as they are, it might lead to a criticism to them due to the fact that some regions with nonelevated risk are included in the detected most likely cluster. In this paper, to avoid detecting such undesirable and misleading clusters which might cause a social concern, we shall propose the use of the restricted likelihood ratio proposed by Tango and illustrate the procedure with two kinds of mortality data in Japan.