Effect of scatter correction when comparing attenuation maps: Application to brain PET/MR

Email Print Request Permissions In PET imaging, attenuation and scatter corrections are an essential requirement to accurately quantify the radionuclide uptake. In the context of PET/MR scanners, obtaining the attenuation information can be challenging. Various authors have quantified the effect of an imprecise attenuation map on the reconstructed PET image but its influence on scatter correction has usually been ignored. In this paper, we investigate the effects of imperfect attenuation maps (μmaps) on the scatter correction in a simulation setting. We focused our study on three μmaps: the reference μmap derived from a CT image, and two MR-based methods. Two scatter estimation strategies were implemented: a μmap-specific scatter estimation and an ideal scatter estimation relying only on the reference CT μmap. The scatter estimation used the Single Scatter Simulation algorithm with tail-fitting. The results show that, for FDG brain PET, regardless of the μmap used in the reconstruction, the difference on PET images between μmap-specific and ideal scatter estimations is small (less than 1%). More importantly, the relative error between attenuation correction methods does not change depending on the scatter estimation method included in the simulation and reconstruction process. This means that the effect of errors in the μmap on the PET image is dominated by the attenuation correction, while the scatter estimate is relatively unaffected. Therefore, while scatter correction improves reconstruction accuracy, it is unnecessary to include scatter in the simulation when comparing different attenuation correction methods for brain PET/MR

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

Placental transfusion: a review

Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut-umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution

Genome-wide analyses identify common variants associated with macular telangiectasia type 2

Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 × 10−8) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 × 10−17; rs715 at 2q34, P = 9.97 × 10−14; rs477992 at 1p12, P = 2.60 × 10−12) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 × 10−6) and serine (P = 2.48 × 10−4) between MacTel cases and controls

Sustainability disclosure and reputation: a comparative study

“This is a post-peer-review, pre-copyedit version of an article published in Corporate Reputation Review. The definitive publisher-authenticated version Corporate Reputation Review 14(2), pp.79-96 is available online at: http://www.palgrave-journals.com/crr/index.html”Drawing on legitimacy theory, we discuss that a company’s reputation is a determinant of sustainability disclosure. Specifically, we consider the concept of reputation into three dimensions for analysis: stakeholders’ commitment, financial performance and media exposure. This paper differs from previous social and environmental reporting studies in that it investigates both internal and external contextual factors that influence disclosure practice. We claim that companies with a good financial performance, that are adopting an active strategic position towards stakeholders and that are exposed to significant public pressure are more likely to use sustainability disclosure in order to communicate their legitimacy to operate to stakeholders. Moreover the paper analyses a wide range of corporate reports for their social and environmental content using an international sample that allows for a comparison of disclosure practices among Continental European, UK and USA companies. Our results show that stakeholder commitment and media exposure are positively associated with sustainability disclosure. Moreover, we find evidence that the drivers of disclosure vary by information type

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-

Global collaborative networks on meta-analyses of randomized trials published in high impact factor medical journals: a social network analysis

BackgroundResearch collaboration contributes to the advancement of knowledge by exploiting the results of scientific efforts more efficiently, but the global patterns of collaboration on meta-analysis are unknown. The purpose of this research was to describe and characterize the global collaborative patterns in meta-analyses of randomized trials published in high impact factor medical journals over the past three decades.MethodsThis was a cross-sectional, social network analysis. We searched PubMed for relevant meta-analyses of randomized trials published up to December 2012. We selected meta-analyses (including at least randomized trials as primary evidence source) published in the top seven high impact factor general medical journals (according to Journal Citation Reports 2011): The New England Journal of Medicine, The Lancet, the BMJ, JAMA, Annals of Internal Medicine, Archives of Internal Medicine (now renamed JAMA Internal Medicine), and PLoS Medicine. Opinion articles, conceptual papers, narrative reviews, reviews without meta-analysis, reviews of reviews, and other study designs were excluded.ResultsOverall, we included 736 meta-analyses, in which 3,178 authors, 891 institutions, and 51 countries participated. The BMJ was the journal that published the greatest number of articles (39%), followed by The Lancet (18%), JAMA (15%) and the Archives of Internal Medicine (15%). The USA, the UK, and Canada headed the absolute global productivity ranking in number of papers. The 64 authors and the 39 institutions with the highest publication rates were identified. We also found 82 clusters of authors (one group with 55 members and one group with 54 members) and 19 clusters of institutions (one major group with 76 members). The most prolific authors were mainly affiliated with the University of Oxford (UK), McMaster University (Canada), and the University of Bern (Switzerland).ConclusionsOur analysis identified networks of authors, institutions and countries publishing meta-analyses of randomized trials in high impact medical journals. This valuable information may be used to strengthen scientific capacity for collaboration and to help to promote a global agenda for future research of excellence

The <i>N</i>-myristoylome of <i>Trypanosoma cruzi</i>

Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas’ disease. Here we have employed whole cell labelling with azidomyristic acid and click chemistry to identify N-myristoylated proteins in different life cycle stages of the parasite. Only minor differences in fluorescent-labelling were observed between the dividing forms (the insect epimastigote and mammalian amastigote stages) and the non-dividing trypomastigote stage. Using a combination of label-free and stable isotope labelling of cells in culture (SILAC) based proteomic strategies in the presence and absence of the NMT inhibitor DDD85646, we identified 56 proteins enriched in at least two out of the three experimental approaches. Of these, 6 were likely to be false positives, with the remaining 50 commencing with amino acids MG at the N-terminus in one or more of the T. cruzi genomes. Most of these are proteins of unknown function (32), with the remainder (18) implicated in a diverse range of critical cellular and metabolic functions such as intracellular transport, cell signalling and protein turnover. In summary, we have established that 0.43–0.46% of the proteome is N-myristoylated in T. cruzi approaching that of other eukaryotic organisms (0.5–1.7%)

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease