Article image contrast, image pre-processing, and T₁ mapping affect MRI radiomic feature repeatability in patients with colorectal cancer liver metastases

Imaging biomarkers require technical, biological, and clinical validation to be translated into robust tools in research or clinical settings. This study contributes to the technical validation of radiomic features from magnetic resonance imaging (MRI) by evaluating the repeatability of features from four MR sequences: pre-contrast T_{1}- and T_{2}-weighted images, pre-contrast quantitative T_{1} maps (qT_{1}), and contrast-enhanced T_{1} weighted images. Fifty-one patients with colorectal cancer liver metastases were scanned twice, up to 7 days apart. Repeatability was quantified using the intraclass correlation coefficient (ICC) and repeatability coefficient (RC), and the impact of non-Gaussian feature distributions and image normalisation was evaluated. Most radiomic features had non-Gaussian distributions, but Box–Cox transformations enabled ICCs and RCs to be calculated appropriately for an average of 97% of features across sequences. ICCs ranged from 0.30 to 0.99, with volume and other shape features tending to be most repeatable; volume ICC > 0.98 for all sequences. 19% of features from non-normalised images exhibited significantly different ICCs in pair-wise sequence comparisons. Normalisation tended to increase ICCs for pre-contrast T_{1}- and T_{2}-weighted images, and decrease ICCs for qT_{1} maps. RCs tended to vary more between sequences than ICCs, showing that evaluations of feature performance depend on the chosen metric. This work suggests that feature-specific repeatability, from specific combinations of MR sequence and pre-processing steps, should be evaluated to select robust radiomic features as biomarkers in specific studies. In addition, as different repeatability metrics can provide different insights into a specific feature, consideration of the appropriate metric should be taken in a study-specific context

Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis

Emerging evidence shows that the efficacy of chemotherapeutic drugs are reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated DAMPs (i.e. damage-associated molecular patterns, such as CALR exposure, ATP secretion and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo. Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which lead to the activation of NF-κB-mediated CCL2 transcription and IKK2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced ER stress, which triggered PERK activation and eIF2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer

A cluster of cases of severe acute respiratory syndrome in Hong Kong

BACKGROUND: Information on the clinical features of the severe acute respiratory syndrome (SARS) will be of value to physicians caring for patients suspected of having this disorder. METHODS: We abstracted data on the clinical presentation and course of disease in 10 epidemiologically linked Chinese patients (5 men and 5 women 38 to 72 years old) in whom SARS was diagnosed between February 22, 2003, and March 22, 2003, at our hospitals in Hong Kong, China. RESULTS: Exposure between the source patient and subsequent patients ranged from minimal to that between patient and health care provider. The incubation period ranged from 2 to 11 days. All patients presented with fever (temperature, >38°C for over 24 hours), and most presented with rigor, dry cough, dyspnea, malaise, headache, and hypoxemia. Physical examination of the chest revealed crackles and percussion dullness. Lymphopenia was observed in nine patients, and most patients had mildly elevated aminotransferase levels but normal serum creatinine levels. Serial chest radiographs showed progressive air-space disease. Two patients died of progressive respiratory failure; histologic analysis of their lungs showed diffuse alveolar damage. There was no evidence of infection by Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila. All patients received corticosteroid and ribavirin therapy a mean (±SD) of 9.6±5.42 days after the onset of symptoms, and eight were treated earlier with a combination of beta-lactams and macrolide for 4±1.9 days, with no clinical or radiologic efficacy. CONCLUSIONS: SARS appears to be infectious in origin. Fever followed by rapidly progressive respiratory compromise is the key complex of signs and symptoms from which the syndrome derives its name. The microbiologic origins of SARS remain unclear.published_or_final_versio

A set of indicators for decomposing the secular increase of life expectancy

ABSTRACT: BACKGROUND: The ongoing increase in life expectancy in developed countries is associated with changes in the shape of the survival curve. These changes can be characterized by two main, distinct components: (i) the decline in premature mortality, i.e., the concentration of deaths around some high value of the mean age at death, also termed rectangularization of the survival curve; and (ii) the increase of this mean age at death, i.e., longevity, which directly reflects the reduction of mortality at advanced ages. Several recent observations suggest that both mechanisms are simultaneously taking place. METHODS: We propose a set of indicators aiming to quantify, disentangle, and compare the respective contribution of rectangularization and longevity increase to the secular increase of life expectancy. These indicators, based on a nonparametric approach, are easy to implement. RESULTS: We illustrate the method with the evolution of the Swiss mortality data between 1876 and 2006. Using our approach, we are able to say that the increase in longevity and rectangularization explain each about 50% of the secular increase of life expectancy. CONCLUSION: Our method may provide a useful tool to assess whether the contribution of rectangularization to the secular increase of life expectancy will remain around 50% or whether it will be increasing in the next few years, and thus whether concentration of mortality will eventually take place against some ultimate biological limit

Symptomatology and health attitudes of chronic hepatitis B patients in the USA

This study was conducted to understand the symptomatology, attitudes, and behaviours of chronic hepatitis B (CHB) patients in the USA. CHB patients enrolled in this study were recruited through multiple methods, including newspaper advertisements. Interviews were conducted in multiple languages, and all participants had a history of CHB infection for at least 6 months. Patients with documented human immunodeficiency virus or hepatitis C virus coinfection were excluded from data analyses, resulting in a total study population of 258 respondents who completed interviews between April and June 2004. The majority of monoinfected patients were male (57%) and non-Asian (92%, including 52% Caucasian, 32% African American and others). Length of diagnosis was 5.8 years for all participants (9.1-year Asian and 5.1-year non-Asian). Ninety-five per cent of CHB patients reported symptoms of differing severity in the 12 months prior to the survey. The most common symptoms included fatigue/loss of energy (90%) and loss of appetite (79%). Non-Asian patients described greater symptomatology, and were more likely than Asians to consider CHB an overriding concern in their daily activities. Patients were treated either currently or previously with interferon (IFN) described greater symptomatology than those treated without IFN. Survey results indicate that CHB patients may have greater symptomatology than recognized. Disease perceptions and treatment attitudes differ between Asian and non-Asian ethnic groups, with the former appearing to be more accepting and less concerned about the disease. Additional research about CHB symptomatology and health attitudes by ethnicity is needed to ensure that individuals with CHB are educated on the potential health risks and the availability of current treatment options

Autonomy support, basic need satisfaction and the optimal functioning of adult male and female sport participants: A test of basic needs theory

Grounded in Basic Needs Theory (BNT; Ryan and Deci, American Psychologist, 55, 68–78, 2000a), the present study aimed to: (a) test a theoretically-based model of coach autonomy support, motivational processes and well-/ill being among a sample of adult sport participants, (b) discern which basic psychological need(s) mediate the link between autonomy support and well-/ill-being, and (c) explore gender invariance in the hypothesized model. Five hundred and thirty nine participants (Male = 271;Female = 268; Mage = 22.75) completed a multi-section questionnaire tapping the targeted variables. Structural Equation Modeling (SEM) analysis revealed that coach autonomy support predicted participants’ basic need satisfaction for autonomy, competence and relatedness. In turn, basic need satisfaction predicted greater subjective vitality when engaged in sport. Participants with low levels of autonomy were more susceptible to feeling emotionally and physically exhausted from their sport investment. Autonomy and competence partially mediated the path from autonomy support to subjective vitality. Lastly, the results supported partial invariance of the model with respect to gender

The C2HDM revisited

The complex two-Higgs doublet model is one of the simplest ways to extend the scalar sector of the Standard Model to include a new source of CP-violation. The model has been used as a benchmark model to search for CP-violation at the LHC and as a possible explanation for the matter-antimatter asymmetry of the Universe. In this work, we re-analyse in full detail the softly broken $\mathbb{Z}_2$ symmetric complex two-Higgs doublet model (C2HDM). We provide the code C2HDM_HDECAY implementing the C2HDM in the well-known HDECAY program which calculates the decay widths including the state-of-the-art higher order QCD corrections and the relevant off-shell decays. Using C2HDM_HDECAY together with the most relevant theoretical and experimental constraints, including electric dipole moments (EDMs), we review the parameter space of the model and discuss its phenomenology. In particular, we find cases where large CP-odd couplings to fermions are still allowed and provide benchmark points for these scenarios. We examine the prospects of discovering CP-violation at the LHC and show how theoretically motivated measures of CP-violation correlate with observables.The work of D.F., J.C.R. and J.P.S. is supported in part by the Portuguese Fundacao para a Ciencia e Tecnologia (FCT) under contracts CERN/FIS-NUC/0010/2015 and UID/FIS/00777/2013. MM acknowledges financial support from the DFG project "Precision Calculations in the Higgs Sector - Paving the Way to the New Physics Landscape" (ID: MU 3138/1-1).info:eu-repo/semantics/publishedVersio

Constraining parameter space in type-II two-Higgs doublet model in light of a 126 GeV Higgs boson

We explore the implications of a 126 GeV Higgs boson indicated by the recent LHC results for two-Higgs doublet model (2HDM). Identifying the 126 GeV Higgs boson as either the lighter or heavier of CP even neutral Higgs bosons in 2HDM, we examine how the masses of Higgs fields and mixing parameters can be constrained by the theoretical conditions and experimental constraints. The theoretical conditions taken into account are the vacuum stability, perturbativity and unitarity required to be satisfied up to a cut-off scale. We also show how bounds on the masses of Higgs bosons and mixing parameters depend on the cut-off scale. In addition, we investigate whether the allowed regions of parameter space can accommodate particularly the enhanced di-photon signals, ZZ* and WW* decay modes of the Higgs boson, and examine the prediction of the signal strength of Z{\gamma} decay mode for the allowed regions of the parameter space.Comment: To be published in JHEP, 20 pages, 11 figures, Figures and results are updated for the recent LHC result

Roy-Steiner equations for pion-nucleon scattering

Starting from hyperbolic dispersion relations, we derive a closed system of Roy-Steiner equations for pion-nucleon scattering that respects analyticity, unitarity, and crossing symmetry. We work out analytically all kernel functions and unitarity relations required for the lowest partial waves. In order to suppress the dependence on the high-energy regime we also consider once- and twice-subtracted versions of the equations, where we identify the subtraction constants with subthreshold parameters. Assuming Mandelstam analyticity we determine the maximal range of validity of these equations. As a first step towards the solution of the full system we cast the equations for the $\pi\pi\to\bar NN$ partial waves into the form of a Muskhelishvili-Omn\`es problem with finite matching point, which we solve numerically in the single-channel approximation. We investigate in detail the role of individual contributions to our solutions and discuss some consequences for the spectral functions of the nucleon electromagnetic form factors.Comment: 106 pages, 18 figures; version published in JHE