Attenuation correction for TOF-PET with a limited number of stationary coincidence line-sources

INTRODUCTION Accurate attenuation correction remains a major issue in combined PET/MRI. We have previously presented a method to derive the attenuation map by performing a transmission scan using an annulus-shaped source placed close to the edge of the FOV of the scanner. With this method, simultaneous transmission and emission data acquisition is possible as transmission data can be extracted using Time-of-Flight (TOF) information. As this method is strongly influenced by photon scatter and dead time effects, its performance depends on the accuracy of the correction techniques for these effects. In this work we present a new approach in which the annulus source is replaced with a limited number of line-sources positioned at 35 cm from the center of the FOV. By including the location of the line sources into the algorithm, the extraction of true transmission data can be improved. The setup was validated with simulations studies and evaluated with a phantom study acquired on the LaBr3-based TOF-PET scanner installed at UPENN. MATERIALS AND METHODS First we performed GATE simulations using the digital NCAT phantom. The phantom was segmented into bone, lung and soft-tissue and injected with 6.5 Mbq/kg 18F-FDG. Simultaneous transmission/emission scans of 3 minutes were simulated using 6, 12 and 24 18F-FDG line sources with a total activity of 0.5 mCi. To obtain the attenuation map, the transmission data is first extracted using TOF information. To reduce misclassification of prompt emission data as transmission data, only events on LORs, which pass within a radial distance of 1 cm from at least one line source, are accepted. The attenuation map is then reconstructed using an iterative gradient descent approach. As a proof of concept, the method was evaluated on the LaBr3-based TOF PET scanner using an anthropomorphic torso phantom injected with 2mCi of 18F-FDG. 24 line-sources of 20μCi each were fixed to a wooden template at the back of the scanner. Simultaneous transmission/emission scans were acquired using 24 line sources. RESULTS Simulation results demonstrate that the fraction of scattered emission events classified as transmission data was reduced from 4.32% with the annulus source to 2.29%, 1.25% and 0.63% for the 24, 12 and 6 line sources respectively. The fraction of misclassified true emission events was reduced from 1.10% to 0.42%, 0.24% and 0.13% respectively. Only in case of 6 line sources, the attenuation maps showed severe artifacts. Compared to the classification solely based on TOF-information, preliminary experimental results indicate an improvement in the accuracy of the attenuation coefficients of 10.44%, 0.12% and 5.09% for soft-tissue, lung and bone tissue respectively. CONCLUSION The proposed method can be used for attenuation correction in sequential or simultaneous TOF-PET/MRI systems. The PET transmission and emission data are acquired simultaneously so no acquisition time for attenuation correction is lost in PET or MRI. Attenuation maps with higher accuracy can be obtained by including information about the location of the line-sources. However, at least 12 line sources are needed to avoid severe artifacts

Étude de la diversité génomique de la levure d'intérêt fromager, Geotrichum candidum

Geotrichum candidum est une levure dimorphique utilisée en fromagerie pour l’affinage des fromages de spécialité. Elle s’implante à la surface des fromages et utilise les constituants de la matrice fromagère (protéines, lipides, acides organiques, etc.), ce qui confère aux fromages leurs propriétés sensorielles typiques. Ces capacités technologiques dépendent toutefois de la souche. Les études récentes basées sur l’analyse phylogénétique et transcriptomique de souches de G. candidum ont révélé une diversité génétique importante au sein de cette espèce, ce qui pourrait expliquer la variabilité des capacités technologiques. Cependant, peu d’informations sont disponibles quant aux caractéristiques génétiques des souches responsables de leurs propriétés aromatisantes et fonctionnelles lors de l’affinage des fromages. La compréhension fine des activités de G. candidum est prioritaire tant pour les artisans-fromagers que pour les grandes fromageries industrielles afin de sélectionner les souches les plus performantes pour leur produit. L’objectif principal de cette étude était de déterminer la diversité génétique entre les souches de la levure Geotrichum candidum par utilisation de la génomique comparative et de proposer une méthode moléculaire pour l’identification et la caractérisation rapide des souches. Les génomes de huit souches de G. candidum d’origine laitière ont été séquencés. Les génomes obtenus avaient une taille moyenne de 24,5 Mb et 5 230 gènes prédits. L’homologie des séquences de chaque souche a permis de les regrouper en trois groupes phylogénétiques distincts pour lesquels des gènes uniques ont pu être identifiés. Sur la base de l’analyse des séquences génomique, une méthode optimisée de génotypage par MLST a été développée et validée sur 41 souches de G. candidum. Cette méthode a permis de reproduire les résultats obtenus avec l’analyse génomique et permet une identification rapide des souches et de leurs groupements phylogénétiques. Les résultats générés dans ce projet permettront de développer des outils pour la sélection optimale des ferments d’affinages basés sur leurs capacités technologiques spécifiques. Ils serviront également à améliorer notre compréhension de la physiologie de cette levure et de décrire et optimiser l’utilisation des souches de G. candidum lors de l’affinage afin d’ultimement contrôler davantage la qualité des fromages.The yeast Geotrichum candidum is used in several specialty cheeses varieties, such as mold and smear-ripened cheeses, and plays several roles during cheese ripening. Its ability to metabolize proteins, lipids and organic acids enables its growth on the cheese surface and participate to the development of organoleptic properties. By alkalinizing the surface duringi ts growth, it also establishes suitable conditions for the growth of other ripening microorganisms. Yet, several technological abilities of G. candidum are strains dependent. However, little information is available related to the genetic characteristics that define the flavoring and functional properties of this yeast during the ripening of cheeses. A detailed understanding of G. candidum metabolic activities is a priority for both artisanal cheese makers and large industrial cheese factories in order to detect the most efficient strains for their product. The main objective of this study was to determine the genetic diversity within the G. candidum species by comparative genomic and to propose a rapid molecular method for the identification and characterization of the strains. Eight strains of G. candidum of dairy origin was sequenced. The genomes obtained had an average of 24.5 Mb and 5,230 putative genes. The sequence homologies show that the strains divide into three distinct groups for which each contains unique genes. On the basis of the genomic sequences, a MLST method was optimized and validated for 41 G. candidum strains. This method reproduces the results obtained for the genomic analysis and allows a rapid identification of the strains and their grouping.The results generated in this project will improve our understanding of the physiology and the utility of the G. candidum strains during the ripening of cheese to ultimately be able to better control it

Herbicide Options to Control Naturalised Infestations of Cereus uruguayanus in Rangeland Environments of Australia

While there are many high profile Opuntioid cactus species invading rangeland environments in Australia, Cereus uruguayanus Ritt. ex Kiesl. has also naturalised and formed large and dense infestations at several locations. With no herbicides registered for control of C. uruguayanus in Australia, the primary aim of this study was to identify effective herbicides to control it using a range of techniques. This involved a large screening trial of twelve herbicides and four techniques, followed by a rate refinement trial for cut stump applications and another to test residual herbicides. Despite most treatments (except monosodium methylarsonate (MSMA)) taking a long time to kill plants, at least one effective herbicide was identified for basal bark (triclopyr/picloram), cut stump (aminopyralid/metsulfuron-methyl, glyphosate, metsulfuron-methyl, triclopyr/picloram, triclopyr/picloram/aminopyralid), stem injection (glyphosate, MSMA, triclopyr/picloram/aminopyralid) and foliar applications (aminopyralid/metsulfuron-methyl, MSMA, triclopyr, triclopyr/picloram/aminopyralid) due to their ability to kill both small and large plants. Ground application of residual herbicides was less conclusive with neither hexazinone nor tebuthiuron causing adequate mortality at the rates applied. This study has identified effective herbicides for the control of C. uruguayanus using several techniques, but further research is needed to refine herbicide rates and develop integrated management strategies for a range of situations and infestation sizes and densities

Formation of cristae and crista junctions in mitochondria depends on antagonism between Fcj1 and Su e/g

Crista junctions (CJs) are important for mitochondrial organization and function, but the molecular basis of their formation and architecture is obscure. We have identified and characterized a mitochondrial membrane protein in yeast, Fcj1 (formation of CJ protein 1), which is specifically enriched in CJs. Cells lacking Fcj1 lack CJs, exhibit concentric stacks of inner membrane in the mitochondrial matrix, and show increased levels of F1FO–ATP synthase (F1FO) supercomplexes. Overexpression of Fcj1 leads to increased CJ formation, branching of cristae, enlargement of CJ diameter, and reduced levels of F1FO supercomplexes. Impairment of F1FO oligomer formation by deletion of its subunits e/g (Su e/g) causes CJ diameter enlargement and reduction of cristae tip numbers and promotes cristae branching. Fcj1 and Su e/g genetically interact. We propose a model in which the antagonism between Fcj1 and Su e/g locally modulates the F1FO oligomeric state, thereby controlling membrane curvature of cristae to generate CJs and cristae tips

Parasites of an Arctic scavenger; the wolverine (Gulo gulo)

Parasites are fundamental components within all ecosystems, shaping interaction webs, host population dynamics and behaviour. Despite this, baseline data is lacking to understand the parasite ecology of many Arctic species, including the wolverine (Gulo gulo), a top Arctic predator and scavenger. Here, we combined traditional count methods (i.e. adult helminth recovery, where taxonomy was confirmed by molecular identification) with 18S rRNA high-throughput sequencing to document the wolverine parasite community. Further, we investigated whether the abundance of parasites detected using traditional methods were associated with host metadata, latitude, and longitude (ranging from the northern limit of the boreal forest to the low Arctic and Arctic tundra in Nunavut, Canada). Adult parasites in intestinal contents were identified as Baylisascaris devosi in 72% (n = 39) of wolverines and Taenia spp. in 22% (n = 12), of which specimens from 2 wolverines were identified as T. twitchelli based on COX1 sequence. 18S rRNA high-throughput sequencing on DNA extracted from faeces detected additional parasites, including a pseudophyllid cestode (Diplogonoporus spp. or Diphyllobothrium spp.), two metastrongyloid lungworms (Angiostrongylus spp. or Aelurostrongylus spp., and Crenosoma spp.), an ascarid nematode (Ascaris spp. or Toxocara spp.), a Trichinella spp. nematode, and the protozoan Sarcocystis spp., though each at a prevalence less than 13% (n = 7). The abundance of B. devosi significantly decreased with latitude (slope = -0.68; R2 = 0.17; P = 0.004), suggesting a northerly limit in distribution. We describe B. devosi and T. twitchelli in Canadian wolverines for the first time since 1978, and extend the recorded geographic distribution of these parasites ca 2000 km to the East and into the tundra ecosystem. Our findings illustrate the value of molecular methods in support of traditional methods, encouraging additional work to improve the advancement of molecular screening for parasites

Social Network Correlates of Free and Purchased Insecticide-treated Bed Nets in Rural Uganda

Background Malaria is a major cause of mortality and morbidity in Uganda. Despite Uganda’s efforts to distribute bed nets, only half of households have achieved the World Health Organization (WHO) Universal Coverage Criteria (one bed net for every two household members). The role of peer influence on bed net ownership remains underexplored. Data on the complete social network of households were collected in a rural parish in southwestern Uganda to estimate the association between household bed net ownership and peer household bed net ownership. Methods Data on household sociodemographics, bed net ownership, and social networks were collected from all households across one parish in southwestern Uganda. Bed nets were categorized as either purchased or free. Purchased and free bed net ownership ratios were calculated based on the WHO Universal Coverage Criteria. Using network name generators and complete census of parish residents, the complete social network of households in the parish was generated. Linear regression models that account for network autocorrelation were fitted to estimate the association between households’ bed net ownership ratios and bed net ownership ratios of network peer households, adjusting for sociodemographics and network centrality. Results One thousand seven hundred forty-seven respondents were interviewed, accounting for 716 households. The median number of peer households to which a household was directly connected was 7. Eighty-six percent of households owned at least one bed net, and 41% of households met the WHO Universal Coverage Criterion. The median bed net ownership ratios were 0.67 for all bed nets, 0.33 for free bed nets, and 0.20 for purchased bed nets. In adjusted multivariable models, purchased bed net ownership ratio was associated with average household wealth among peer households (b = 0.06, 95% CI 0.03, 0.10), but not associated with average purchased bed net ownership ratio of peer households. Free bed net ownership ratio was associated with the number of children under 5 (b = 0.08, 95% CI 0.05, 0.10) and average free bed net ownership ratios of peer households (b = 0.66, 95% CI 0.46, 0.85). Conclusions Household bed net ownership was associated with bed net ownership of peer households for free bed nets, but not for purchased bed nets. The findings suggest that public health interventions may consider leveraging social networks as tools for dissemination, particularly for bed nets that are provided free of charge

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.

BACKGROUND: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α. OBJECTIVE: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy. DESIGN: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study. SETTING: Eight secondary care centres, the United Kingdom between April 2015 and June 2017. PATIENTS: Thirty-three patients undergoing elective transthoracic oesophagectomy. INTERVENTIONS: Patients randomly received a single nebulised dose (26 mg) of GSK2862277 (n = 17) or placebo (n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study. MAIN OUTCOME MEASUREMENTS: Physiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models. RESULTS: The mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (-0.23, 0.39) in the placebo and 0.00 (-0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO2/FiO2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms. CONCLUSION: Pre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation. TRIAL REGISTRATION: clinicaltrials.gov: NCT02221037