Sonnerose8162

Over the last twenty years advances in systems biology have changed our views on microbial communities and promise to revolutionize treatment of human diseases. In almost all scientific breakthroughs since time of Newton, mathematical modeling has played a prominent role. Regulatory networks emerged as preferred descriptors of how abundances of molecular species depend on each other. However, the central question on how cellular phenotypes emerge from dynamics of these network remains elusive. The principal reason is that differential equation models in the field of biology (while so successful in areas of physics and physical chemistry), do not arise from first principles, and these models suffer from lack of proper parameterization. In response to these challenges, discrete time models based on Boolean networks have been developed. In this review, we discuss an emerging modeling paradigm that combines ideas from differential equations and Boolean models, and has been developed independently within dynamical systems and computer science communities. The result is an approach that can associate a range of potential dynamical behaviors to a network, arrange the descriptors of the dynamics in a searchable database, and allows for multi-parameter exploration of the dynamics akin to bifurcation theory. Since this approach is computationally accessible for moderately sized networks, it allows, perhaps for the first time, to rationally compare different network topologies based on their dynamics. For decades already, the human fear conditioning paradigm has been used to study and develop treatments for anxiety disorders. This research is guided by theoretical assumptions that, in some cases indirectly, stem from the tradition of association formation models (e.g., the Rescorla-Wagner model). We argue that one of these assumptions - fear responding as a monotonic function of the associative activation of aversive memory representations - restricts the types of treatment that the research community currently considers. We discuss the importance of this assumption in the context of research on extinction-enhancing and reconsolidation interference techniques. While acknowledging the merit of this research, we argue that unstrapping the straitjacket of this assumption can lead to exploring new directions for utilizing fear conditioning procedures in treatment research. We discuss two determinants of fear responding other than associative memory activation. First, fear responding might also depend on relational information. Second, a recent goal-directed emotion theory suggests that goals might be the primary determinant of the response pattern characterized as fear. Cannabis use is associated with increased risk of psychotic symptoms and in a small number of cases it can lead to psychoses. This review examines the neurobiological mechanisms that mediate the link between cannabis use and psychosis risk. We use an established preclinical model of psychosis, the methylazoxymethanol acetate (MAM) rodent model, as a framework to examine if psychosis risk in some cannabis users is mediated by the effects of cannabis on the hippocampus, and this region's role in the regulation of mesolimbic dopamine. We also examine how cannabis affects excitatory neurotransmission known to regulate hippocampal neural activity and output. Whilst there is clear evidence that cannabis/cannabinoids can affect hippocampal and medial temporal lobe function and structure, the evidence that cannabis/cannabinoids increase striatal dopamine function is less robust. There is limited evidence that cannabis use affects cortical and striatal glutamate levels, but there are currently too few studies to draw firm conclusions. Future work is needed to test the MAM model in relation to cannabis using multimodal neuroimaging approaches. Crown All rights reserved.BACKGROUND We aimed to clarify clinical profiles of patients with adenocarcinoma presenting as multifocal ground-glass opacities (MGGOs) to assess their prognosis and the optimal management method for residual satellite lesions. METHODS We identified 190 patients with cN0 MGGOs (MGGO cohort) and 1,426 patients with solitary lung adenocarcinoma (Control cohort) who underwent complete resection between 2004 and 2016. Propensity score matching was performed to adjust for differences in baseline characteristics of both cohorts for survival analyses. MGGOs consist of a main tumor and satellite lesions. MGGOs were subdivided into three groups; the PG-group (multifocal pure GGOs), the GD-group (the main tumor presenting GGO-dominant), and the SD-group (the main tumor presenting solid-dominant). PI3K inhibitor RESULTS No significant differences in recurrence-free survival (RFS) were observed between the two cohorts before and after the propensity score matching. Patients with MGGOs included 22 in PG, 47 in GD, and 121 in SD. Type of MGGOs was a significant factor for RFS both in the entire population (SD vs. PG-GD, p = 0.008) and p-stage I cohorts (p = 0.004) on multivariable analysis. Among 116 patients (61.1%) with residual satellite lesions, there were 38 patients with progressed lesions and 69 patients with stable lesions. Although the emergence of new lesions during the follow-up period was an independent predictor for satellite lesion progression, neither progressed lesions nor the emergence of new lesions influenced survival. CONCLUSIONS Patients with MGGOs and solitary adenocarcinoma had a similar prognosis. The biological behavior of main tumors dominates clinical outcomes in patients with MGGOs. Two high-risk patients have been successfully treated with concomitant implantation of a transapical off-pump beating heart semi-rigid D-shape annuloplasty device combined in one case with transfemoral edge-to-edge device and in another with transapical chordal implantation. The significant anteroposterior diameter reduction offered by the annuloplasty implantation maximized the leaflet coaptation obtained by the prolapse correction performed with the leaflet devices. BACKGROUND Stapling across lung-parenchyma may lead to tissue-granulation which could be confused radiographically with recurrence. We sought to define the time-course and radiographic characteristics of such thickening and to determine association with recurrence. METHODS Patients who underwent limited-resection for NSCLC were included. Surveillance CT-scans were reviewed to characterize the morphology/size of staple-line granulation-tissue. Radiological/clinical findings were analyzed and univariate-predictors of recurrence were examined. RESULTS Seventy-eight patients were characterized for tissue-granulation a total of 314 times in serial scans. On initial postoperative scans, 3.8%(N=3) of staple-lines showed no thickening and 17.9%(N=14) showed thickening less then 2mm, while (78.2%-N=61) showed thickening ≥2mm. Of the 75 staple-lines with thickening, soft-tissue was characterized as linear in 32.0%(N=24), as focal along the pleura/hilum/parenchyma in 24.0%(N=18), and as nodular in 44.0%(N=33). Subsequent scans revealed that 25.