T1 bladder cancer: comparison of the prognostic impact of two substaging systems on disease recurrence and progression and suggestion of a novel nomogram

Background: The T1 substaging of bladder cancer (BCa) potentially impacts disease progression. The objective of the study was to compare the prognostic accuracy of two substaging systems on the recurrence and progression of primary pathologic T1 (pT1) BCa and to test a nomogram based on pT1 substaging for predicting recurrence-free survival (RFS) and progression-free survival (PFS). Methods: The medical records of 204 patients affected by pT1 BCa were retrospectively reviewed. Substaging was defined according to the depth of lamina propria invasion in T1a-c and the extension of the lamina propria invasion to T1-microinvasive (T1m) or T1-extensive (T1e). Uni- and multivariable Cox regression models evaluated the independent variables correlated with recurrence and progression. The predictive accuracies of the two substaging systems were compared by Harrell's C index. Multivariate Cox regression models for the RFS and PFS were also depicted by a nomogram. Results: The 5-year RFS was 47.5% with a significant difference between T1c and T1a (p = 0.02) and between T1e and T1m (p < 0.001). The 5-year PFS was 75.9% with a significant difference between T1c and T1a (p = 0.011) and between T1e and T1m (p < 0.001). Model T1m-e showed a higher predictive power than T1a-c for predicting RFS and PFS. In the univariate and multivariate model subcategory T1e, the diameter, location, and number of tumors were confirmed as factors influencing recurrence and progression after adjusting for the other variables. The nomogram incorporating the T1m-e model showed a satisfactory agreement between model predictions at 5 years and actual observations. Conclusions: Substaging is significantly associated with RFS and PFS for patients affected by T1 BCa and should be included in innovative prognostic nomograms

Role of the Chemokine Receptors CCR1, CCR2 and CCR4 in the Pathogenesis of Experimental Dengue Infection in Mice

Dengue virus (DENV), a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1-/- mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2-/- mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4-/- mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection

Gender identity rather than sexual orientation impacts on facial preferences.

Introduction. Differences in facial preferences between heterosexual men and women are well documented. It is still a matter of debate, however, how variations in sexual identity/sexual orientation may modify the facial preferences. Aim. This study aims to investigate the facial preferences of male-to-female (MtF) individuals with gender dysphoria (GD) and the influence of short-term/long-term relationships on facial preference, in comparison with healthy subjects. Methods. Eighteen untreated MtF subjects, 30 heterosexual males, 64 heterosexual females, and 42 homosexual males from university students/staff, at gay events, and in Gender Clinics were shown a composite male or female face. The sexual dimorphism of these pictures was stressed or reduced in a continuous fashion through an opensource morphing program with a sequence of 21 pictures of the same face warped from a feminized to a masculinized shape. Main Outcome Measures. An open-source morphing program (gtkmorph) based on the X-Morph algorithm. Results. MtF GD subjects and heterosexual females showed the same pattern of preferences: a clear preference for less dimorphic (more feminized) faces for both short- and long-term relationships. Conversely, both heterosexual and homosexual men selected significantly much more dimorphic faces, showing a preference for hyperfeminized and hypermasculinized faces, respectively. Conclusions. These data show that the facial preferences of MtF GD individuals mirror those of the sex congruent with their gender identity. Conversely, heterosexual males trace the facial preferences of homosexual men, indicating that changes in sexual orientation do not substantially affect preference for the most attractive faces

Development of a Quantitative Evaluation Tool of Cognitive Workload in Field Studies Through Eye Tracking.

Eye tracking is mainly employed as mean of tracking visual attention of an observer/operator. Still, eye tracking is also capable of recording a wider variety of data such as traces of mental workload. Pupil diameter have been validated as such measure. Most of the studies that have validated this are in laboratory conditions, where the perceived luminance (measured in candela per square meter) can be controlled. Luminance affects the pupil diameter as well; this means if the pupil diameter varies for an operator/observer in field conditions it cannot be accurately determined if the change in the pupil diameter is due to mental workload alone. Although there are some studies, which have attempted to simultaneously account for the contribution of the change in pupil diameter due to luminance and mental workload, not many have attempted to account for this in field conditions for safety-critical systems such as a helicopter or a maritime ship bridge. In this study as a first step, we define a method to measure luminance while tracking the gaze point. We will record eye-tracking data simultaneously recording the video feed of the field of view of the operator/observer. We will use the video feed to estimate the luminous flux from the point of view of the subject. We will be collecting this data from a helicopter pilot and his co-pilot during an actual operation (e.g. transportation of personnel and carrying a payload for an electrical power provider company in Norway or Sweden). We will also be collecting data from a navigator and his first officer in a high-speed marine craft of the Norwegian navy. We will also be collecting subjective data using paper-based tools such as NASA-TLX in addition to a conventional video recording of the scene of activity and handwritten notes of observation for validation purposes. We will also capture mental workload data from a few other objective sources such as heart rate variability (ECG). We expect to clearly define an approach to separately account for the effect of mental workload independent of the impact of changing light conditions in field situations for safety-critical systems. This includes a mathematical model that we innovate based on other mathematical models that are already available in the literature