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This study of West Nile virus (WNV) examined the possibility of avian transmission to explain synchronicity in the year‐to‐year variability of WNV case numbers from Texas northward to the Dakotas, and reasons for the large case numbers on the northern Great Plains. We determined correlation coefficients between annual disease incidence per 100,000 people among states within the Great Plains Region, as well as the Central Flyway. There was spatial and temporal synchronicity, as evidenced by Pearson "r," with values along the core of the Central Flyway (Oklahoma, Kansas, Nebraska, and South Dakota) varying between 0.69 and 0.79. Correlations for North Dakota (r = 0.6), however, were affected by local conditions. The concept of relative amplification is helpful in explaining why northerly states along the Central Flyway have larger annual case numbers per 100,000 than Texas but preserve the temporal signal. States differed in their capacity for amplifying the temporal signal in case numbers. For example, Nebraska, South Dakota, and North Dakota case numbers were commonly amplified relative to Texas, with Oklahoma and Kansas deamplified. Relative amplification factors for all states increased as a function of increasing case numbers in Texas. Thus, increased numbers of initially infected birds in Texas likely led to the rapid intensification of the zoonotic cycle as compared to more typical years. The study also confirmed the importance of winter weather in locally modulating disease cases. North Dakota appeared most impacted by these factors to the extent of reducing WNV case numbers in colder years and years with deep snow. Plain Language Summary: This study examined factors controlling broad patterns of transmission of West Nile virus (WNV) on the Great Plains of the United States. We found that yearly human case numbers are correlated both temporally and spatially from Texas northward. These findings support the idea that each year migratory birds were important in retransmitting WNV along the Central Flyway with Texas as the source of WNV and North Dakota and South Dakota as sinks. However, states differed in their capacity to enhance the temporal signal. In Oklahoma and Kansas, deamplification in case numbers relative to Texas was common except for the worst WNV years in Texas. For Nebraska, South Dakota, and North Dakota case numbers were commonly amplified relative to Texas. Relative amplification factors for all states increased as a function of increasing case numbers per 100,000 in Texas. These patterns are likely controlled by virulence of the dominant Culex species and local habitat. In North Dakota, the winter climate may also affect human case numbers. Cold conditions reduce populations of over‐wintering mosquitoes and large snow accumulations modulate the springtime return of migratory birds. Such correlations between the local WNV disease cases and these factors may provide a robust, early screening tool for WNV. Key Points: Spatial and temporal synchronicity in human West Nile virus cases was observed along the Central FlywayA consistent pattern of amplification and deamplifications in human case numbers is evident along the Central Flyway as compared to TexasKey factors controlling trends include avian spread, vector competence, and local winter conditions, especially in North Dakota [ABSTRACT FROM AUTHOR]

Objective: A modified version of row-action maximum likelihood algorithm (RAMLA) using a 'subset-dependent' relaxation parameter for noise suppression, or dynamic RAMLA (DRAMA), has been proposed. The aim of this study was to assess the capability of DRAMA reconstruction for quantitative (15)O brain positron emission tomography (PET). Methods: Seventeen healthy volunteers were studied using a 3D PET scanner. The PET study included 3 sequential PET scans for C(15)O, (15)O(2) and H (2) (15) O. First, the number of main iterations (N (it)) in DRAMA was optimized in relation to image convergence and statistical image noise. To estimate the statistical variance of reconstructed images on a pixel-by-pixel basis, a sinogram bootstrap method was applied using list-mode PET data. Once the optimal N (it) was determined, statistical image noise and quantitative parameters, i.e., cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)) and oxygen extraction fraction (OEF) were compared between DRAMA and conventional FBP. DRAMA images were post-filtered so that their spatial resolutions were matched with FBP images with a 6-mm FWHM Gaussian filter. Results: Based on the count recovery data, N (it) = 3 was determined as an optimal parameter for (15)O PET data. The sinogram bootstrap analysis revealed that DRAMA reconstruction resulted in less statistical noise, especially in a low-activity region compared to FBP. Agreement of quantitative values between FBP and DRAMA was excellent. For DRAMA images, average gray matter values of CBF, CBV, CMRO(2) and OEF were 46.1 +/- 4.5 (mL/100 mL/min), 3.35 +/- 0.40 (mL/100 mL), 3.42 +/- 0.35 (mL/100 mL/min) and 42.1 +/- 3.8 (%), respectively. These values were comparable to corresponding values with FBP images: 46.6 +/- 4.6 (mL/100 mL/min), 3.34 +/- 0.39 (mL/100 mL), 3.48 +/- 0.34 (mL/100 mL/min) and 42.4 +/- 3.8 (%), respectively. Conclusion: DRAMA reconstruction is applicable to quantitative (15)O PET study and is superior to conventional FBP in terms of image quality. [ABSTRACT FROM AUTHOR]

Aim: Inter-individual variations in normal human cerebral blood flow (CBF) at rest condition have been reported. Inter-individual variation of cerebral vascular tone is considered to contribute to this, and several determinants of cerebral vascular tone have been proposed. In the present study, the relationship between CBF and cerebral vascular tone to inter-individual variation at rest condition was investigated using positron emission tomography (PET). Methods: CBF was measured using PET with H215O in each of 20 healthy subjects (20–28 years) under three conditions: at rest (baseline), during hypercapnia and during hypocapnia. The vascular response to change in PaCO2 was calculated as the percentage changes in CBF per absolute change in PaCO2 in response to hypercapnia and hypocapnia. Results: A significant negative correlation between baseline CBF and the vascular response to hypocapnia was observed in the thalamus, temporal cortex, parietal cortex, occipital cortex and cerebral cortex ( P < 0.05). A trend towards negative correlation between baseline CBF and the vascular response to hypocapnia was observed in the cerebellum and putamen ( P < 0.1). A significant negative correlation between baseline CBF and the vascular response to hypercapnia was observed in the occipital cortex ( P < 0.05). No significant correlation was observed between baseline CBF and haemoglobin concentration, and PaCO2. Conclusion: These findings support the assumption that cerebral vascular tone might incline towards vasoconstriction and vasodilatation when baseline CBF is low and high between individuals respectively. Although several determinants of cerebral vascular tone have been proposed, the mechanism of such inter-individual differences in cerebral vascular tone is unknown. [ABSTRACT FROM AUTHOR]

Cerebral blood flow (CBF) and mean transit time (MTT) can be determined by dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) and deconvolution with an arterial input function (AIF). However, deconvolution with a singular value decomposition (SVD) method is sensitive to the tracer delay that often occurs in patients with cerebrovascular disease. We developed a delay correction method that determines tracer delay by means of least-squares fitting pixel-by-pixel. The corrected CBF was determined by SVD deconvolution after time-shifting of the measured concentration curve. The simulations showed that the corrected CBF was insensitive to tracer delay irrespective of the vascular model, although CBF fluctuation increased slightly. We applied the delay correction to the CBF and MTT images acquired for a patient with hyperacute stroke and unilateral occlusion of the middle cerebral artery. The delay correction modulated the contrast of perfusion images. For hyperacute stroke patients, tracer delay correction is essential to obtain reliable CBF and MTT images when SVD deconvolution is used. [Copyright &y& Elsevier]

A two-dimensional numerical model is developed that incorporates the mechanism of colloid-facilitated transport in discretely fractured porous media. The numerical model accounts for aqueous phase contaminant transport in the fractures and the porous matrix, colloid transport in the fractures, and sorption of the solute. Deep-bed filtration of the colloids is accounted for, and the solute is allowed to sorb on both the mobile and filtered colloids. The numerical formulation allows for either equilibrium or kinetic sorption reactions onto the fracture walls, the matrix solids, and the mobile and filtered colloids according to either a Langmuir or a Freundlich isotherm. The results of a series of simulations involving a system of parallel fractures explore the importance of mobile colloids on contaminant migration and indicate that if sorption onto the colloids is a slow kinetic process, then the mobile colloids may lead to significantly enhanced contaminant migration. [ABSTRACT FROM AUTHOR]

Numerical simulations of colloid-facilitated contaminant transport in fractured porous media were performed to examine the influence of mobile colloids on contaminant migration through a network of fractures. Simulations involving transport through fracture networks in a clay and a sandstone rock indicate that colloid-facilitated contaminant transport can be an important factor leading to the rapid exceedance of water quality standards at large distances from the contaminant source. If the colloids are highly mobile in open fractures and there is a strong affinity for a reactive contaminant to remain adsorbed onto them, then low but environmentally significant contaminant concentration levels can quickly propagate through an interconnected network of fractures. The total concentration plumes that are produced are highly irregular in regions in advance of the zone of bulk aqueous phase contaminant transport. Because of this feature, colloid-enhanced solute transport is likely to increase prediction uncertainty compared to the case when colloids are absent because field data on fracture network interconnectivity, aperture values, and values of parameters such as colloid filtration coefficients in the fractures are typically lacking. [ABSTRACT FROM AUTHOR]

Presents a reply to the criticism by Cass T. Miller and William G. Gray on the article on the state of hydrogeological research. Usefulness of the citation analysis for the evaluation of the impact of scientific work; Evolution of activity in research areas and topics.

Objective: To verify the visibility of physiological 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake in nuclei in and around the brainstem by a whole-body (WB) silicon photomultiplier positron emission tomography (SiPM-PET) scanner with point-spread function (PSF) reconstruction using various iteration numbers., Methods: Ten healthy subjects (5 men, 5 women; mean age, 56.0 ± 5.0 years) who underwent 18 F-FDG PET/CT using a WB SiPM-PET scanner and magnetic resonance imaging (MRI) of the brain including a spin-echo three-dimensional sampling perfection with application-optimized contrasts using different flip angle evolutions fluid-attenuated inversion recovery (3D-FLAIR) and a 3D-T1 magnetization-prepared rapid gradient-echo (T1-MPRAGE) images were enrolled. Each acquired PET image was reconstructed using ordered-subset expectation maximization (OSEM) with iteration numbers of 4, 16, 64, and 256 (subset 5 fixed) + time-of-flight (TOF) + PSF. The reconstructed PET images and 3D-FLAIR images for each subject were registered to individual T1-MPRAGE volumes using normalized mutual information criteria. For each MR-coregistered individual PET image, the pattern of FDG uptake in the inferior olivary nuclei (ION), dentate nuclei (DN), midbrain raphe nuclei (MRN), inferior colliculi (IC), mammillary bodies (MB), red nuclei (RN), subthalamic nuclei (STN), lateral geniculate nuclei (LGN), medial geniculate nuclei (MGN), and superior colliculi (SC) was visually classified into the following three categories: good, clearly distinguishable FDG accumulation; fair, obscure contour of FDG accumulation; poor, FDG accumulation indistinguishable from surrounding uptake., Results: Among individual 18 F-FDG PET images with OSEM iterations of 4, 16, 64, and 256 + TOF + PSF, the iteration numbers that showed the best visibility in each structure were as follows: ION, MRN, LGN, MGN, and SC, iteration 64; DN, iteration 16; IC, iterations 16, 64, and 256; MB, iterations 64 and 256; and RN and STN, iterations 16 and 64, respectively. Of the four iterations, the 18 F-FDG PET image of iteration 64 visualized FDG accumulation in small structures in and around the brainstem most clearly (good, 98 structures; fair, 2 structures)., Conclusions: A clinically available WB SiPM-PET scanner is useful for visualizing physiological FDG uptake in small brain nuclei, using a sufficiently high number of iterations for OSEM with TOF and PSF reconstructions., (© 2023. The Author(s).)

Purpose: X-map is a non-contrast dual-energy CT (DECT) application to identify acute ischemic stroke (AIS). Our aim was to verify region-specific characteristics of early ischemic changes (EIC) on X-map compared with simulated 120-kVp mixed-CT image and DWI., Methods: Fifty AIS patients who underwent DECT and DWI were enrolled (mean age, 76 years; 34 men, 16 women). All datasets including mixed-CT image, X-map, and DWI were transformed into a standard brain atlas with 11 × 2 ROIs based on the ASPECTS + W system. ROIs with EIC on DWI, mixed-CT image, and X-map were defined as DWI-positive, mixed-CT-positive, and X-map-positive, and those with normal finding were DWI-negative, mixed-CT-negative, and X-map-negative respectively, in visual assessment by two neuroradiologists in consensus., Results: EIC on X-maps were visually relevant to those on the other images: of 221 ROIs with mixed-CT-positive and X-map-positive, 198 (89.6%) were DWI-positive. X-map revealed moderate diagnostic accuracy for AIS compared with DWI in ROC curve analysis (AUC = 0.732). X-map identified EIC in deep white matter more sensitively than mixed-CT image: of 15 ROIs with mixed-CT-negative and X-map-positive in W segments, 14 (93.3%) were DWI-positive. X-map often showed EIC in cortical regions that were not detected on the other images: of 67 ROIs with mixed-CT-negative and X-map-positive in I and M1-M6 segments, 47 (70.1%) were DWI-negative., Conclusions: X-map is useful to detect EIC, especially in deep white matter, and may also provide additional information in acute ischemic lesions where DWI cannot be detected., (© 2023. The Author(s).)

The regional differences in cerebral oxygen extraction fraction (OEF) in brain were investigated using positron emission tomography (PET) in detail with consideration of systemic errors in PET measurement estimated by simulation studies. The cerebral blood flow (CBF), cerebral blood volume (CBV), OEF, and cerebral metabolic rate of oxygen (CMRO 2 ) were measured on healthy men by PET with 15 O-labeled gases. The OEF values in the pons and the parahippocampal gyrus were significantly smaller than in the other brain regions. The OEF value in the lateral side of the occipital cortex was largest among the cerebral cortical regions. Simulation studies have revealed that errors in OEF caused by regional differences in the distribution volume of 15 O-labeled water, as well as errors in OEF caused by a mixture of gray and white matter, must be negligible. The regional differences in OEF in brain must exist which might be related to physiological meanings.Article title: Kindly check and confirm the edit made in the article title.I have checked the article title and it is OK as is. Trial registration: The UMIN clinical trial number: UMIN000033382, https://www.umin.ac.jp/ctr/index.htm., (© 2023. The Physiological Society of Japan.)

Objective: In quantitative positron emission tomography (PET) of the brain, partial volume effect due mainly to the finite spatial resolution of the PET scanner (> 3 mm full width at half maximum [FWHM]) is a primary source of error in the measurement of tracer uptake, especially in small structures such as the cerebral cortex (typically < 3 mm thickness). The aim of this study was to evaluate the partial volume correction (PVC) performance of point spread function-incorporated reconstruction (PSF reconstruction) in combination with the latest digital PET scanner. This evaluation was performed through direct comparisons with magnetic resonance imaging (MR)-based PVC (used as a reference method) in a human brain study., Methods: Ten healthy subjects underwent brain 18 F-FDG PET (30-min acquisition) on a digital PET/CT system (Siemens Biograph Vision, 3.5-mm FWHM scanner resolution at the center of the field of view) and anatomical T1-weighted MR imaging for MR-based PVC. PSF reconstruction was applied with a wide range of iterations (4 to 256; 5 subsets). FDG uptake in the cerebral cortex was evaluated using the standardized uptake value ratio (SUVR) and compared between PSF reconstruction and MR-based PVC., Results: Cortical structures were visualized by PSF reconstruction with several tens of iterations and were anatomically well matched with the MR-derived cortical segments. Higher numbers of iterations resulted in higher cortical SUVRs, which approached those of MR-based PVC (1.76), although even with the maximum number of iterations they were still smaller by 16% (1.47), corresponding to approximately 1.5-mm FWHM of the effective spatial resolution., Conclusion: With the latest digital PET scanner, PSF reconstruction can be used as a PVC technique in brain PET, albeit with suboptimal resolution recovery. A relative advantage of PSF reconstruction is that it can be applied not only to cerebral cortical regions, but also to various small structures such as small brain nuclei that are hardly visualized on anatomical T1-weighted imaging, and thus hardly recovered by MR-based PVC., (© 2022. The Author(s).)

Background: Partial volume correction with anatomical magnetic resonance (MR) images (MR-PVC) is useful for accurately quantifying tracer uptake on brain positron emission tomography (PET) images. However, MR segmentation processes for MR-PVC are time-consuming and prevent the widespread clinical use of MR-PVC. Here, we aimed to develop a deep learning model to directly predict PV-corrected maps from PET and MR images, ultimately improving the MR-PVC throughput., Methods: We used MR T1-weighted and [ 11 C]PiB PET images as input data from 192 participants from the Alzheimer's Disease Neuroimaging Initiative database. We calculated PV-corrected maps as the training target using the region-based voxel-wise PVC method. Two-dimensional U-Net model was trained and validated by sixfold cross-validation with the dataset from the 156 participants, and then tested using MR T1-weighted and [ 11 C]PiB PET images from 36 participants acquired at sites other than the training dataset. We calculated the structural similarity index (SSIM) of the PV-corrected maps and intraclass correlation (ICC) of the PV-corrected standardized uptake value between the region-based voxel-wise (RBV) PVC and deepPVC as indicators for validation and testing., Results: A high SSIM (0.884 ± 0.021) and ICC (0.921 ± 0.042) were observed in the validation and test data (SSIM, 0.876 ± 0.028; ICC, 0.894 ± 0.051). The computation time required to predict a PV-corrected map for a participant (48 s without a graphics processing unit) was much shorter than that for the RBV PVC and MR segmentation processes., Conclusion: These results suggest that the deepPVC model directly predicts PV-corrected maps from MR and PET images and improves the throughput of MR-PVC by skipping the MR segmentation processes., (© 2022. The Author(s).)

As COVID-19 continues to spread globally, monitoring the disease at different scales is critical to support public health decision making. Surveillance for SARS-CoV-2 RNA in wastewater can supplement surveillance based on diagnostic testing. In this paper, we report the results of wastewater-based COVID-19 surveillance on Emory University campus that included routine sampling of sewage from a hospital building, an isolation/quarantine building, and 21 student residence halls between July 13th, 2020 and March 14th, 2021. We examined the sensitivity of wastewater surveillance for detecting COVID-19 cases at building level and the relation between Ct values from RT-qPCR results of wastewater samples and the number of COVID-19 patients residing in the building. Our results show that weekly wastewater surveillance using Moore swab samples was not sensitive enough (6 of 63 times) to reliably detect one or two sporadic cases in a residence building. The Ct values of the wastewater samples over time from the same sampling location reflected the temporal trend in the number of COVID-19 patients in the isolation/quarantine building and hospital (Pearson's r < -0.8), but there is too much uncertainty to directly estimate the number of COVID-19 cases using Ct values. After students returned for the spring 2021 semester, SARS-CoV-2 RNA was detected in the wastewater samples from most of the student residence hall monitoring sites one to two weeks before COVID-19 cases surged on campus. This finding suggests that wastewater-based surveillance can be used to provide early warning of COVID-19 outbreaks at institutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

SARS-CoV-2 is a respiratory virus, but it is also detected in a significant proportion of fecal samples from COVID-19 cases. Recent studies have shown that wastewater surveillance can be a low-cost tool compared to massive diagnostic testing for tracking COVID-19 outbreaks in communities, but most studies have focused on sampling from wastewater treatment plants. Institutional level wastewater surveillance may serve well for early warning purposes because specific geographic areas/populations with emerging cases can be tracked and immediate action can be executed in the event of a positive wastewater signal. In this study, a novel Moore swab method was developed and used for wastewater surveillance of COVID-19 at an institutional level. Of the 442 swab samples tested, 148 (33.5%) swabs collected from the three campuses and two buildings were positive for SARS-CoV-2 RNA. Further study of the quarantine building with a known number of cases indicated that this method was sensitive enough to detect few cases in the building. In addition, comparison between grab samples and Moore swab samples from the hospital sewage line indicated that Moore swabs were more sensitive than grab samples and offer a simple, inexpensive method for obtaining a composite sample of virus in wastewater over a 24-48 h period. These results suggest that collection and analyses of Moore swabs for SARS-CoV-2 RNA detection is a sensitive, low-cost, and easy to use tool for COVID-19 surveillance that is useful for institutional settings and could be deployed in low-resource settings to identify emerging COVID-19 clusters in communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Artificial intelligence (AI) has been applied to various medical imaging tasks, such as computer-aided diagnosis. Specifically, deep learning techniques such as convolutional neural network (CNN) and generative adversarial network (GAN) have been extensively used for medical image generation. Image generation with deep learning has been investigated in studies using positron emission tomography (PET). This article reviews studies that applied deep learning techniques for image generation on PET. We categorized the studies for PET image generation with deep learning into three themes as follows: (1) recovering full PET data from noisy data by denoising with deep learning, (2) PET image reconstruction and attenuation correction with deep learning and (3) PET image translation and synthesis with deep learning. We introduce recent studies based on these three categories. Finally, we mention the limitations of applying deep learning techniques to PET image generation and future prospects for PET image generation., (© 2021. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Introduction: In cerebral blood flow (CBF) quantification with pseudo-continuous arterial spin labeling (pCASL) MRI, arterial blood T1 (T1a) is usually fixed to a typical value (e.g., 1650 ms). However, individual T1a depends strongly on hematocrit (Hct) level. To investigate the utility of Hct-based T1a as an alternative to the fixed T1a method, we performed a comparative study with 15 O-water positron emission tomography (PET)., Methods: For patients with unilateral occlusion or stenosis of major arteries, hemispheric CBF on the healthy side was measured using pCASL and 15 O-water PET. The pCASL CBFs were calculated with both (a) fixed T1a (1650 ms) and (b) individual T1a estimated from blood-sampled Hct (Hct-based T1a). Correlation coefficients of Hct-CBF were calculated and compared between pCASL and PET., Results: In pCASL, CBF with fixed T1a showed a strong negative correlation with Hct (r = -0.568), which was reduced with individual Hct-based T1a (r = -0.341 to -0.190), consistent with the Hct-CBF relation measured with PET (r = -0.349)., Discussion and Conclusion: We demonstrated that Hct-based T1a resulted in smaller inter-individual variations in pCASL CBF and an inverse Hct-CBF relationship more similar to that of PET. Care must be taken in the interpretation of pCASL CBF imaging in relation to Hct level even in subjects without anemia. Further comparative studies are needed to investigate whether advanced techniques improve pCASL CBF quantification at the individual level., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The χMD matrix solver package is incorporated into USGS groundwater modeling software, such as MODFLOW-NWT, MODFLOW-USG, and MT3D. The solver is used to solve matrices assembled through numerical discretization of the groundwater flow equation, and solute transport equations. χMD has demonstrated its higher robustness, faster execution speed, and more efficient memory usage compared to the existing solvers for many types of groundwater flow problems. χMD uses preconditioned iterative Krylov-subspace methods and consists of preconditioning and acceleration modules. Because the solver package uses a variety of preconditioning features including level-based incomplete lower-upper (ILU) factorization method with a drop tolerance scheme, users must choose optimal preconditioning parameters to improve execution speed and robustness. In order to examine how the preconditioning parameters, ILU factorization level, and drop tolerance values affect the overall performance of the matrix solver, we evaluated five different groundwater model applications using MODFLOW-USG that include different numerical complexities. For those five cases, the number of discretization nodes varied from 10,000 cells to 730,300 cells. From the analysis, we found that the preconditioning parameters greatly affect execution times and memory usage of the preconditioning and acceleration procedures. In addition, a combination of the ILU level between five to seven and the drop tolerance value between 10 -2 and 10 -3 usually resulted in shorter overall execution time. Our study suggests that the users can elicit higher performance and robustness of the χMD matrix solver using this combination of the parameters and enhance computational efficiency of solving groundwater and solute transport problems., (© 2021 National Ground Water Association.)

Purpose: Oxygen extraction fraction (OEF) is a biomarker for the viability of brain tissue in ischemic stroke. However, acquisition of the OEF map using positron emission tomography (PET) with oxygen-15 gas is uncomfortable for patients because of the long fixation time, invasive arterial sampling, and radiation exposure. We aimed to predict the OEF map from magnetic resonance (MR) and PET images using a deep convolutional neural network (CNN) and to demonstrate which PET and MR images are optimal as inputs for the prediction of OEF maps., Methods: Cerebral blood flow at rest (CBF) and during stress (sCBF), cerebral blood volume (CBV) maps acquired from oxygen-15 PET, and routine MR images (T1-, T2-, and T2*-weighted images) for 113 patients with steno-occlusive disease were learned with U-Net. MR and PET images acquired from the other 25 patients were used as test data. We compared the predicted OEF maps and intraclass correlation (ICC) with the real OEF values among combinations of MRI, CBF, CBV, and sCBF., Results: Among the combinations of input images, OEF maps predicted by the model learned with MRI, CBF, CBV, and sCBF maps were the most similar to the real OEF maps (ICC: 0.597 ± 0.082). However, the contrast of predicted OEF maps was lower than that of real OEF maps., Conclusion: These results suggest that the deep CNN learned useful features from CBF, sCBF, CBV, and MR images and predict qualitatively realistic OEF maps. These findings suggest that the deep CNN model can shorten the fixation time for 15 O PET by skipping 15 O 2 scans. Further training with a larger data set is required to predict accurate OEF maps quantitatively., (© 2021. The Author(s).)

Enteric fever is a severe systemic infection caused by Salmonella enterica serovar Typhi (ST) and Salmonella enterica serovar Paratyphi A (SPA). Detection of ST and SPA in wastewater can be used as a surveillance strategy to determine burden of infection and identify priority areas for water, sanitation, and hygiene interventions and vaccination campaigns. However, sensitive and specific detection of ST and SPA in environmental samples has been challenging. In this study, we developed and validated two methods for concentrating and detecting ST/SPA from wastewater: the Moore swab trap method for qualitative results, and ultrafiltration (UF) for sensitive quantitative detection, coupled with qPCR. We then applied these methods for ST and SPA wastewater surveillance in Kolkata, India and Dhaka, Bangladesh, two enteric fever endemic areas. The qPCR assays had a limit of detection of 17 equivalent genome copies (EGC) for ST and 25 EGC for SPA with good reproducibility. In seeded trials, the Moore swab method had a limit of detection of approximately 0.05-0.005 cfu/mL for both ST and SPA. In 53 Moore swab samples collected from three Kolkata pumping stations between September 2019 and March 2020, ST was detected in 69.8% and SPA was detected in 20.8%. Analysis of sewage samples seeded with known amount of ST and SPA and concentrated via the UF method, followed by polyethylene glycol precipitation and qPCR detection demonstrated that UF can effectively recover approximately 8, 5, and 3 log 10 cfu of seeded ST and SPA in 5, 10, and 20 L of wastewater. Using the UF method in Dhaka, ST was detected in 26.7% (8/30) of 20 L drain samples with a range of 0.11-2.10 log 10 EGC per 100 mL and 100% (4/4) of 20 L canal samples with a range of 1.02-2.02 log 10 EGC per 100 mL. These results indicate that the Moore swab and UF methods provide sensitive presence/absence and quantitative detection of ST/SPA in wastewater samples., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Ibaraki, Kapoor, Amin, Das, Miah, Mukhopadhyay, Rahman, Dutta and Moe.)

Objectives: Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) by PET with oxygen-15 labeled gases is useful for diagnosis and treatment planning in cases of chronic occlusive cerebrovascular disease. In the present study, CBF, CBV, OEF and CMRO 2 were measured using the integrated design of PET/MRI scanner system. This is a first attempt to measure cerebral perfusion and oxygen metabolism using PET/MRI with oxygen-15 labeled gases., Methods: PET/MRI measurements with the steady-state method of oxygen-15 labeled gases, carbon monoxide (C 15 O), oxygen ( 15 O 2 ), and carbon dioxide (C 15 O 2 ) were performed on nine healthy men. Two kinds of attenuation correction for PET were performed using MRI with Dixon sequence (DIXON) and Dixon sequence with model-based bone segmentation (DIXONbone). A real-time motion correction of PET images was also performed using simultaneously measured MR images to detect head motion., Results: Mean and SD values of CBF, CBV, OEF, and CMRO 2 in the cerebral cortices with attenuation correction by DIXON were 31 ± 4 mL/100 mL/min, 2.7 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.5 ± 0.3 mL/100 mL/min without real-time motion correction, and 33 ± 4 mL/100 mL/min, 2.7 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.6 ± 0.3 mL/100 mL/min with real-time motion correction, respectively. Values with of CBF, CBV, OEF, and CMRO 2 with attenuation correction by DIXONbone were 35 ± 5 mL/100 mL/min, 2.8 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.8 ± 0.3 mL/100 mL/min without real-time motion correction, and 38 ± 5 mL/100 mL/min, 2.8 ± 0.2 mL/mL, 0.40 ± 0.07, and 3.0 ± 0.4 mL/100 mL/min with real-time motion correction, respectively., Conclusions: Using PET/MRI with oxygen-15 labeled gases, CBF, CBV, OEF, and CMRO 2 could be measured. Values of CBF, CBV, and CMRO 2 measured with attenuation correction by DIXON were significantly lower than those measured with correction by DIXONbone. One of the reasons for this is that attenuation correction of DIXON does not take into consideration of the photon absorption by bone. OEF values, corresponding to ratios of CMRO 2 to CBF, were not affected by attenuation correction methods. Values of CBF and CMRO 2 with a real-time motion correction were significantly higher than those without correction. Using PET/MRI with adequate corrections, similar values of CBF, CBV, OEF, and CMRO 2 as PET alone scanner system reported previously were obtained., Trail Registration: The UMIN clinical trial number: UMIN000033382.

Imprecise registration between positron emission tomography (PET) and anatomical magnetic resonance (MR) images is a critical source of error in MR imaging-guided partial volume correction (MR-PVC). Here, we propose a novel framework for image registration and partial volume correction, which we term PVC-optimized registration (PoR), to address imprecise registration. The PoR framework iterates PVC and registration between uncorrected PET and smoothed PV-corrected images to obtain precise registration. We applied PoR to the [ 11 C]PiB PET data of 92 participants obtained from the Alzheimer's Disease Neuroimaging Initiative database and compared the registration results, PV-corrected standardized uptake value (SUV) and its ratio to the cerebellum (SUVR), and intra-region coefficient of variation (CoV) between PoR and conventional registration. Significant differences in registration of as much as 2.74 mm and 3.02° were observed between the two methods (effect size <  - 0.8 or > 0.8), which resulted in considerable SUVR differences throughout the brain, reaching a maximal difference of 62.3% in the sensory motor cortex. Intra-region CoV was significantly reduced using the PoR throughout the brain. These results suggest that PoR reduces error as a result of imprecise registration in PVC and is a useful method for accurately quantifying the amyloid burden in PET.

Background: Novel partial volume correction (PVC) algorithms have been validated by assuming ideal conditions of image processing; however, in real clinical PET studies, the input datasets include error sources which cause error propagation to the corrected outcome., Methods: We aimed to evaluate error propagations of seven PVCs algorithms for brain PET imaging with [ 18 F]THK-5351 and to discuss the reliability of those algorithms for clinical applications. In order to mimic brain PET imaging of [ 18 F]THK-5351, pseudo-observed SUVR images for one healthy adult and one adult with Alzheimer's disease were simulated from individual PET and MR images. The partial volume effect of pseudo-observed PET images were corrected by using Müller-Gärtner (MG), the geometric transfer matrix (GTM), Labbé (LABBE), regional voxel-based (RBV), iterative Yang (IY), structural functional synergy for resolution recovery (SFS-RR), and modified SFS-RR algorithms with incorporation of error sources in the datasets for PVC processing. Assumed error sources were mismatched FWHM, inaccurate image-registration, and incorrectly segmented anatomical volume. The degree of error propagations in ROI values was evaluated by percent differences (%diff) of PV-corrected SUVR against true SUVR., Results: Uncorrected SUVRs were underestimated against true SUVRs (- 15.7 and - 53.7% in hippocampus for HC and AD conditions), and application of each PVC algorithm reduced the %diff. Larger FWHM mismatch led to larger %diff of PVC-SUVRs against true SUVRs for all algorithms. Inaccurate image registration showed systematic propagation for most algorithms except for SFS-RR and modified SFS-RR. Incorrect segmentation of the anatomical volume only resulted in error propagations in limited local regions., Conclusions: We demonstrated error propagation by numerical simulation of THK-PET imaging. Error propagations of 7 PVC algorithms for brain PET imaging with [ 18 F]THK-5351 were significant. Robust algorithms for clinical applications must be carefully selected according to the study design of clinical PET data.

Background: Around the world in tropical areas, certain vector-borne diseases have become endemic and hyperendemic. Among the developing nations, there are common difficulties in establishing the incidences of various diseases, especially vector-borne diseases with complex etiologies and a broad spectrum of presentations. One alternative approach to characterization of the disease outbreaks examines the possibilities of developing proxy information from online news articles. Such sources are being evaluated for applications to disease surveillance, early outbreak detection, and epidemiology research. Our study here looks to examine the potential of news articles in elucidating outbreaks of dengue in India and zika disease in Brazil., Objective: This study is designed to assess the potential usefulness of news articles in tracking case numbers of dengue and zika through an improved understanding of how news outlets report on disease. We specifically examine the possibilities of providing near real-time reporting on the development of outbreaks of dengue and zika., Methods: Newspaper articles related to dengue fever and zika disease in India and Brazil, respectively were extracted from the LexisNexis database. We targeted news articles available from five popular international news sources and two local newspapers in each country. The news articles were processed to provide yearly and weekly time series in the number of articles concerned with dengue and zika to test their potential suitability as proxies for disease prevalence. The collections of articles were analyzed using a text mining tool-kit that subdivides a collections of news articles into smaller clusters to study the topical focus of articles and their relevance to tracking diseases., Results: For dengue fever in India, the local newspapers provide a better source of information than international newspapers. The multi-year analysis (2010-2016) suggests that the numbers of dengue cases are strongly correlated with the numbers of news reports, with an R 2 value of 0.88. For zika disease in Brazil, the news reports provided useful information on the timing of the zika outbreak. Reporting increase sharply at the beginning of 2016, peaked in weeks 5 to 8, and decreased sharply. The numbers of articles remained low for the remainder of 2016 and 2017. Comparisons with reported case again show article numbers to be a useful proxy of prevalence of zika in Brazil., Conclusions: The paper describes a strategy that applies newspaper as proxies to monitor outbreaks of infectious diseases and to study the epidemiology. It has potential applicability in some developing countries and regions with relatively poor medical infrastructures and records. Clearly, large national newspapers in India provide a better source of information on diseases than international outlets. This approach has potential with selected diseases in a few selected countries. Article numbers internationally appear to vary in proportion to the perceived health impact., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: The study demonstrates the potential in using newspaper information as a proxy for monitoring dengue fever outbreaks in India. Online newspapers are being considered as sources of information on disease surveillance, early outbreak detection, and epidemiology research. Our objective is to understand the complex dengue epidemiology and discover inter-relationships between dengue fever and local social-environmental factors by mining information from local Indian news articles., Results: We search and extract articles from the newspaper database, LexisNexis. News articles related to dengue fever in India are analyzed together with local environmental, climate, and population data in both temporally and spatially to study disease epidemiology. We also examine the influence of newsworthiness for constructing a disease surveillance system. In terms of temporal aspects, dengue outbreaks follow consistent patterns every year. However, for many areas, this application is frustrated by the relatively small numbers of news articles., Conclusions: The study has advanced capabilities in producing approaches that provide for richer interpretations of textual information provided in newspaper articles. Such approaches appear particularly well suited for developing countries with relatively poor medical infrastructures and records., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Rare sugars are defined as monosaccharides that exist in nature but are only present in limited quantities. d-Allose is a rare sugar that has been reported to have some unique physiological effects. The present study describes suitable synthetic procedures for novel rare sugars of d-allose that are 18 F-labeled at the C-3 and C-6 positions and the preparation of the appropriate labeling precursors. The goal is to facilitate in vivo, noninvasive positron emission tomography (PET) investigation of the behavior of rare sugar analogs of d-allose in organs. We found five precursors that were practical for labeling, three for 3-deoxy-3-[ 18 F]fluoro-d-allose ([ 18 F]3FDA) and two for 6-deoxy-6-[ 18 F]fluoro-d-allose ([ 18 F]6FDA). With manual operation synthesis, the highest radiochemical conversion rates were 75% for [ 18 F]3FDA with a precursor of 1,2,4,6-tetra-O-acetyl-3-O-trifluoromethanesulfonyl-β-d-glucopyranose and 69% for [ 18 F]6FDA with a precursor of 1,2,3,4-tetra-O-acetyl-6-O-trifluoromethanesulfonyl-β-d-allopyranose. Furthermore, the practical yields of [ 18 F]3FDA and [ 18 F]6FDA using an automated synthesizer were also investigated. Radiochemical yields of 67% and 49% were obtained for [ 18 F]3FDA and [ 18 F]6FDA, respectively, in an automated synthesizer. As basic assessment of stability for use in PET scanning, high performance liquid chromatography analysis showed no decomposition of [ 18 F]3FDA and [ 18 F]6FDA after up to 6 h in rabbit blood plasma., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Fibronectin-binding protein A (FnBPA), a protein displayed on the outer surface of Staphylococcus aureus, has a structured A-domain that binds fibrinogen (Fg) and a disordered repeat-region that binds fibronectin (Fn). Amino acid substitutions in Fn-binding repeats (FnBRs) have previously been linked to cardiovascular infection in humans. Here we used microtiter and atomic force microscopy (AFM) to investigate adhesion by variants of full-length FnBPA covalently anchored in the outer cell wall of Lactococcus lactis, a Gram-positive surrogate that otherwise lacks adhesins to mammalian ligands. Fn adhesion increased in five of seven FnBPA variants under static conditions. The bond targeting Fn increased its strength with load under mechanical dissociation. Substitutions extended bond lifetime (1/k off ) up to 2.1 times for FnBPA-Fn. Weaker adhesion was observed for Fg in all FnBPA variants tested with microtiter. However, mechanical dissociation with AFM showed significantly increased tensile strength for Fg interacting with the E652D/H782Q variant. This is consistent with a force-induced mechanism and suggests that the dock, lock, and latch (DLL) mechanism is favored for Fg-binding under mechanical stress. Collectively, these experiments reveal that FnBPA exhibits bimodal, ligand-dependent adhesive behavior. Amino acid substitutions in the repeat-region of FnBPA impact binding to both ligands. This was unexpected for Fg since all variants have the same A-domain sequence, and the Fg-binding site is distant from the repeat region. This indicates that FnBRs may fold back on the A-domain in a way that impacts the DLL binding mechanism for Fg.

This paper shows how important the historical contaminant boom, 1975 to 2005, has been to hydrogeology. Its role in this respect has never been well documented or appreciated. We use text mining and machine learning to extract information describing research trends in subsurface hydrology (SH), groundwater plus the vadose zone. The analysis, using articles from Water Resources Research (WRR) and Environmental Science and Technology, shows how SH grew from a small niche area within broader hydrologic sciences in the 1960s to become the dominant area of research by 1995. Subsequently, the performance of SH has declined, as other areas of hydrologic sciences have emerged. These patterns reflect the growth and decline of research related to contaminant topics in SH. Thus, the decline is economic-less money leads to less research. The boom in contaminant hydrogeology was effectively a 1000-year flood of money for SH. It let us outcompete the non-SH areas for a while. From 1991 to 2000, SH research in WRR was dominated by papers on contaminant-related themes. More recently, these themes and all other areas of SH except one have declined significantly in WRR. All major topics related to non-SH areas are growing except one. This evidence points to a continuing decline in competitiveness of basic research in SH. The fact that critical problems or social needs for research still exist has not changed this basic trend. The focus of research has clearly shifted away from SH to areas of hydrology associated with climate change, water cycle modeling and similar themes., (© 2018, National Ground Water Association.)

Pseudo-continuous arterial spin labeling (pCASL) is a completely non-invasive method of cerebral perfusion measurement. However, cerebral blood flow (CBF) quantification is hampered by arterial transit artifacts characterized by bright vascular signals surrounded by decreased signals in tissue regions, which commonly appear in patients with reduced cerebral perfusion pressure. The spatial coefficient of variation (CoV) of pCASL CBF images has been proposed as an alternative region-of-interest (ROI)-based hemodynamic measure to predict prolonged arterial transit time (ATT). This retrospective study investigates the utility of spatial CoV by comparison with 15 O positron emission tomography (PET). For patients with cerebrovascular steno-occlusive disease ( n = 17), spatial CoV was positively correlated with ATT independently measured by pulsed arterial spin labeling ( r = 0.597, p < 0.001), confirming its role as an ATT-like hemodynamic measure. Comparisons with 15 O PET demonstrated that spatial CoV was positively correlated with vascular mean transit time ( r = 0.587, p < 0.001) and negatively correlated with both resting CBF ( r = -0.541, p = 0.001) and CBF response to hypercapnia ( r = -0.373, p = 0.030). ROI-based spatial CoV calculated from single time-point pCASL can potentially detect subtle perfusion abnormalities in clinical settings.

The academic world is driven by scholarly research and publications. Yet, for many fields, the volume of published research and the associated knowledge base have been expanding exponentially for decades. The result is that scientists are literally drowning in data and information. There are strategies and approaches that could help with this problem. The goal of this paper is to demonstrate the power of computer-based approaches such as data mining and machine learning to evaluate large collections of papers. The objective is to conduct a systematic analysis of research related to the emerging area of groundwater-related diseases. More specifically, the analysis of information from the database of papers will examine systematics in the research topics, the inter-relationships among multiple diseases, contaminants, and groundwater, and discover styles of research associated with groundwater and disease. The analysis uses 426 papers (1971 to 2017) retrieved from a MEDLINE bibliographic database, PubMed, given the search terms "groundwater" and "disease." We developed tools that take care of necessary text processing steps, which lead naturally to clustering and visualization techniques that demonstrate published research. The resulting 2D article map shows how the collection of papers is subdivided into 11 article clusters. The cluster topics were determined by analyzing keywords or common words contained in the articles' titles, abstracts, and key words. We found that research on water-related disease in groundwater primarily focuses on two types of contaminants-chemical compounds and pathogens. Cancer and diarrhea are two major diseases associated with groundwater contamination. According to the systematic analysis, the study of this area is still growing., (© 2018, National Ground Water Association.)

The city of Bismarck, North Dakota has one of the highest numbers of West Nile Virus (WNV) cases per population in the U.S. Although the city conducts extensive mosquito surveillance, the mosquito abundance alone may not fully explain the occurrence of WNV. Here, we developed models to predict mosquito abundance and the number of WNV cases, independently, by statistically analyzing the most important climate and virus transmission factors. An analysis with the mosquito model indicated that the mosquito numbers increase during a warm and humid summer or after a severely cold winter. In addition, river flooding decreased the mosquito numbers. The number of WNV cases was best predicted by including the virus transmission rate, the mosquito numbers, and the mosquito feeding pattern. This virus transmission rate is a function of temperature and increases significantly above 20 °C. The correlation coefficients ( r ) were 0.910 with the mosquito-population model and 0.620 with the disease case model. Our findings confirmed the conclusions of other work on the importance of climatic variables in controlling the mosquito numbers and contributed new insights into disease dynamics, especially in relation to extreme flooding. It also suggested a new prevention strategy of initiating insecticides not only based on mosquito numbers but also 10-day forecasts of unusually hot weather.

Purpose: To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study., Methods: We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [ 18 F]THK5351 and [ 11 C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data., Results: In regions of high uptake of [ 18 F]THK5351 and [ 11 C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition., Conclusion: Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.

The relation between cerebral blood flow (CBF) and cerebral oxygen extraction fraction (OEF) can be expressed using the effective diffusivity for oxygen in the capillary bed (D) as OEF = 1 - exp(-D/CBF). The D value is proportional to the microvessel blood volume. In this study, changes in D during neural activation and deactivation were estimated from changes in capillary and arteriole diameter measured by two-photon microscopy in awake mice. Capillary and arteriole vessel diameter in the somatosensory cortex and cerebellum were measured under neural activation (sensory stimulation) and neural deactivation [crossed cerebellar diaschisis (CCD)], respectively. Percentage changes in D during sensory stimulation and CCD were 10.3 ± 7.3 and -17.5 ± 5.3 % for capillary diameter of <6 μm, respectively. These values were closest to the percentage changes in D calculated from previously reported human positron emission tomography data. This may indicate that thinner capillaries might play the greatest role in oxygen transport from blood to brain tissue.

High non-specific uptake of [ 11 C]Pittsburgh compound B ([ 11 C]PiB) in white matter and signal spillover from white matter, due to partial volume effects, confound radioactivity measured in positron emission tomography (PET) with [ 11 C]PiB. We aimed to reveal the partial volume effect in absolute values of kinetic parameters for [ 11 C]PiB, in terms of spillover from white matter. Dynamic data acquired in [ 11 C]PiB PET scans with five healthy volunteers and eight patients with Alzheimer's disease were corrected with region-based and voxel-based partial volume corrections. Binding potential (BP ND ) was estimated using the two-tissue compartment model analysis with a plasma input function. Partial volume corrections significantly decreased cortical BP ND values. The degree of decrease in healthy volunteers (-52.7±5.8%) was larger than that in Alzheimer's disease patients (-11.9±4.2%). The simulation demonstrated that white matter spillover signals due to the partial volume effect resulted in an overestimation of cortical BP ND , with a greater degree of overestimation for lower BP ND values. Thus, an overestimation due to partial volume effects is more severe in healthy volunteers than in Alzheimer's disease patients. Partial volume corrections may be useful for accurately quantifying Aβ deposition in cortical regions., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Positron emission tomography (PET) enables quantitative measurements of various biological functions. Accuracy in data acquisition and processing schemes is a prerequisite for this. The correction of scatter is especially important when a 3D PET scanner is used. The aim of this study was to validate the use of a simplified calculation-based scatter correction method for 15 O studies in the brain., Methods: We applied two scatter correction methods to the same 15 O PET data acquired from patients with cerebrovascular disease (n = 10): a hybrid dual-energy-window scatter correction (reference method), and a deconvolution scatter correction (simplified method). The PET study included three sequential scans for 15 O-CO, 15 O-O 2 , and 15 O-H 2 O, from which the following quantitative parameters were calculated, cerebral blood flow, cerebral blood volume, cerebral metabolic rate of oxygen, and oxygen extraction fraction., Results: Both scatter correction methods provided similar reconstruction images with almost identical image noise, although there were slightly greater differences in white-matter regions compared with gray matter regions. These differences were also greater for 15 O-CO than for 15 O-H 2 O and 15 O-O 2 . Region of interest analysis of the quantitative parameters demonstrated that the differences were less than 10 % (except for cerebral blood volume in white-matter regions), and the agreement between the methods was excellent, with intraclass correlation coefficients above 0.95 for all the parameters., Conclusions: The deconvolution scatter correction despite its simplified implementation provided similar results to the hybrid dual-energy-window scatter correction. We consider it suitable for application in a clinical 15 O brain study using a 3D PET scanner., Competing Interests: Compliance with ethical standads Conflict of interest M. Ibaraki, K. Matsubara, K. Sato, and T. Kinoshita declare that they have no conflict of interest.

Background: The outcome of anti-tuberculosis treatment varies according to patient factors., Objective: To retrospectively identify risks related to the extension of time to negative sputum culture (Tn) and to determine their clinical significance., Design: Patients with bacilli susceptible to isoniazid and rifampicin who received initial standard treatment without cessation were recruited into the study. A total of 630 consecutive in-patients were included in the risk development analysis (development cohort) and another 611 consecutive in-patients in the risk validation analysis (validation cohort)., Results: Univariate analysis showed that Tn was related to sex, body mass index (BMI), white blood cell count (WBC), serum albumin, fasting blood sugar, haemoglobin A1c, C-reactive protein and total cholesterol levels and sputum smear positivity (SSP). Multivariate analysis showed that BMI, WBC and SSP were significant risk factors related to extended Tn. Optimal cut-offs of BMI and WBC for predicting good (Tn < 46 days) and poor responders (Tn ⩾ 46 days) according to each risk were determined by receiver operating characteristics analysis. Risks were verified with the validation cohort. Tn increased according to the number of risks; the median Tn for patients with three risks was 21 days longer than that of patients with none., Conclusion: The nutritional state of a TB patient can be used to predict Tn.