In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy.

A new empirical reduced-form model for credit rating transitions is introduced. It is a parametric intensity-based duration model with multiple states and driven by exogenous covariates and latent dynamic factors. The model has a generalized semi-Markov structure designed to accommodate many of the stylized facts of credit rating migrations. Parameter estimation is based on Monte Carlo maximum likelihood methods for which the details are discussed in this paper. A simulation experiment is carried out to show the effectiveness of the estimation procedure. An empirical application is presented for transitions in a 7 grade rating system. The model includes a common dynamic component that can be interpreted as the credit cycle. Asymmetric effects of this cycle across rating grades and additional semi-Markov dynamics are found to be statistically significant. Finally, we investigate whether the common factor model suffices to capture systematic risk in rating transition data by introducing multiple factors in the model. r

BackgroundAlthough neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP) in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP.FindingsIn this study, we examined the regional μ-opioid receptor (μOR) availability in vivo (non-displaceable binding potential BPND) of TNP patients with positron emission tomography (PET) using the μOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced μOR BPND in the left nucleus accumbens (NAc), an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the μOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients.ConclusionsOur findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous μ-opioid system, rather than only to the peripheral pathology. The decreased availability of μORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.

No abstract

No abstract

A new empirical reduced-form model for credit rating transitions is introduced. It is a parametric intensity-based duration model with multiple states and driven by exogenous covariates and latent dynamic factors. The model has a generalized semi-Markov structure designed to accommodate many of the stylized facts of credit rating migrations. Parameter estimation is based on Monte Carlo maximum likelihood methods for which the details are discussed in this paper. A simulation experiment is carried out to show the effectiveness of the estimation procedure. An empirical application is presented for transitions between investment grade, subinvestment grade, and default ratings for U.S. corporates. The model strongly suggests the presence of a common dynamic component that can be interpreted as the credit cycle. We also show that the impact of this credit cycle is asymmetric with respect to downgrade and upgrade probabilities.

The ability to perceive the emotions of others is crucial for everyday social interactions. Important aspects of visual socioemotional processing, such as the recognition of facial expressions, are known to depend on largely automatic mechanisms. However, whether and how properties of automaticity extend to the auditory domain remains poorly understood. Here we ask if nonverbal auditory emotion recognition is a controlled deliberate or an automatic efficient process, using vocalizations such as laughter, crying, and screams. In a between-subjects design (N = 112), and covering eight emotions (four positive), we determined whether emotion recognition accuracy (a) is improved when participants actively deliberate about their responses (compared with when they respond as fast as possible) and (b) is impaired when they respond under low and high levels of cognitive load (concurrent task involving memorizing sequences of six or eight digits, respectively). Response latencies were also measured. Mixed-effects models revealed that recognition accuracy was high across emotions, and only minimally affected by deliberation and cognitive load; the benefits of deliberation and costs of cognitive load were significant mostly for positive emotions, notably amusement/laughter, and smaller or absent for negative ones; response latencies did not suffer under low or high cognitive load; and high recognition accuracy (approximately 90%) could be reached within 500 ms after the stimulus onset, with performance exceeding chance-level already between 300 and 360 ms. These findings indicate that key features of automaticity, namely fast and efficient/effortless processing, might be a modality-independent component of emotion recognition. (PsycINFO Database Record

Introduction: Several questions about pregnancy in women with multiple sclerosis (MS) have been discussed, but clarification is still needed in some very practical issues. Portuguese data on this subject remain scattered and need to be analyzed in order to standardize clinical practice. Objective: This study aimed to describe and analyze the impact of MS on pregnancy and perinatal health of children born to Portuguese mothers with the disease. Material and methods: This is a multicenter, retrospective study of a cohort of Portuguese women with MS who were pregnant and who gave birth between 01/01/2011 and 31/12/2015. Demographic and clinical data related to maternal disease, pregnancy progression and events, childbirth and newborn health were collected. Results: Ninety-seven women were recruited and 90 live births were evaluated. The mean maternal age at conception was 32.5 years, and 63.9% had no relapses in the previous year (98.0% had a relapsing-remitting MS and the EDSS score was ≤ 3 in 92.8% of the cases). Only 50.5% of the women had a preconception specific evaluation and 60 children were exposed to immunomodulatory therapies during pregnancy. Nineteen women had relapses during pregnancy. Childbirth was induced in 22.7% of the cases, and the caesarean section rate was 34%. Children exposed to immunomodulatory drugs during pregnancy had a lower birth length (p = 0.014), and there was also a trend toward lower birth weight (p = 0.054) in these newborns. Pre-conception EDSS score negatively correlated with the duration of pregnancy (r = -0.22; p = 0.029), weight (r = -0.23; p = 0.031) and cephalic perimeter at birth (r = -0.24; p = 0.033). There was no relationship between the occurrence of relapses or progression in EDSS score during pregnancy with any variables related to the newborn. Conclusions: In our cohort, it has been confirmed that MS has no negative effect on pregnancy or on children's perinatal health. However, the use of immunomodulatory drugs may have some impact on newborns' somatometric features.