Early Asymmetric Cardio-Cerebral Causality and Outcome after Severe Traumatic Brain Injury.

The brain and heart are two vital systems in health and disease, increasingly recognized as a complex, interdependent network with constant information flow in both directions. After severe traumatic brain injury (TBI), the causal, directed interactions between the brain, heart, and autonomic nervous system have not been well established. Novel methods are needed to probe unmeasured, potentially prognostic information in complex biological networks that are not revealed by traditional means. In this study, we examined potential bidirectional causality between intracranial pressure (ICP), mean arterial pressure (MAP), and heart rate (HR) and its relationship to mortality in a 24-h period early post-TBI. We applied Granger causality (GC) analysis to cardio-cerebral monitoring data from 171 severe TBI patients admitted to a single neurocritical care center over a 10-year period. There was significant bidirectional causality between ICP and MAP, MAP and HR, and ICP and HR in the majority of patients (p < 0.01). MAP influenced both ICP and HR to a greater extent (higher GC, p < 0. 00001), but there was no dominant unidirectional causality between ICP and HR (p = 0.85). Those who died had significantly lower GC for ICP causing MAP and HR causing ICP (p = 0.006 and p = 0.004, respectively) and were predictors of mortality independent of age, sex, and traditional intracranial variables (ICP, cerebral perfusion pressure, GCS, and pressure reactivity index). Examining the brain and heart with GC-based features for the first time in severe TBI patients has confirmed strong interdependence and reveals a significant relationship between select causality pairs and mortality. These results support the notion that impaired causal information flow between the cerebrovascular, autonomic, and cardiovascular systems are of central importance in severe TBI.A.E. acknowledges the financial support of the Academy of Medical Sciences in this work

Systematic study of the effect of short range correlations on the form factors and densities of s-p and s-d shell nuclei

Analytical expressions of the one- and two-body terms in the cluster expansion of the charge form factors and densities of the s-p and s-d shell nuclei with N=Z are derived. They depend on the harmonic oscillator parameter b and the parameter $\beta$ which originates from the Jastrow correlation function. These expressions are used for the systematic study of the effect of short range correlations on the form factors and densities and of the mass dependence of the parameters b and $\beta$. These parameters have been determined by fit to the experimental charge form factors. The inclusion of the correlations reproduces the experimental charge form factors at the high momentum transfers ($q\geq 2 1/fm$). It is found that while the parameter $\beta$ is almost constant for the closed shell nuclei, $^4$He, $^{16}$O and $^{40}$Ca, its values are larger (less correlated systems) for the open shell nuclei, indicating a shell effect in the closed shell nuclei.Comment: Latex, 21 pages, 6 figures, 1 tabl

Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy