Risk factors for unfavourable postoperative outcome in patients with Crohn's disease undergoing right hemicolectomy or ileocaecal resection An international audit by ESCP and S-ECCO

Background Patient and disease-related factors, as well as operation technique all have the potential to impact on postoperative outcome in Crohn's disease. The available evidence is based on small series and often displays conflicting results. Aim To investigate the effect of pre- and intra-operative risk factors on 30-day postoperative outcome in patients undergoing surgery for Crohn's disease. Method International prospective snapshot audit including consecutive patients undergoing right hemicolectomy or ileocaecal resection. This study analysed a subset of patients who underwent surgery for Crohn's disease. The primary outcome measure was the overall Clavien-Dindo postoperative complication rate. The key secondary outcomes were anastomotic leak, re-operation, surgical site infection and length of stay at hospital. Multivariable binary logistic regression analyses were used to produce odds ratios (OR) and 95% confidence intervals (CI). Results Three hundred and seventy five resections in 375 patients were included. The median age was 37 and 57.1% were female. In multivariate analyses, postoperative complications were associated with preoperative parenteral nutrition (OR 2.36 95% CI 1.10-4.97)], urgent/expedited surgical intervention (OR 2.00, 95% CI 1.13-3.55) and unplanned intraoperative adverse events (OR 2.30, 95% CI 1.20-4.45). The postoperative length of stay in hospital was prolonged in patients who received preoperative parenteral nutrition (OR 31, CI [1.08-1.61]) and those who had urgent/expedited operations (OR 1.21, CI [1.07-1.37]). Conclusion Preoperative parenteral nutritional support, urgent/expedited operation and unplanned intraoperative adverse events were associated with unfavourable postoperative outcome. Enhanced preoperative optimization and improved planning of operation pathways and timings may improve outcomes for patients

Dynamical systems associated to separated graphs, graph algebras, and paradoxical decompositions

We attach to each finite bipartite separated graph (E,C) a partial dynamical system (\Omega(E,C), F, \theta), where \Omega(E,C) is a zero-dimensional metrizable compact space, F is a finitely generated free group, and {\theta} is a continuous partial action of F on \Omega(E,C). The full crossed product C*-algebra O(E,C) = C(\Omega(E,C)) \rtimes_{\theta} F is shown to be a canonical quotient of the graph C*-algebra C^*(E,C) of the separated graph (E,C). Similarly, we prove that, for any *-field K, the algebraic crossed product L^{ab}_K(E,C) = C_K(\Omega(E,C)) \rtimes_\theta^{alg} F is a canonical quotient of the Leavitt path algebra L_K(E,C) of (E,C). The monoid V(L^{ab}_K(E,C)) of isomorphism classes of finitely generated projective modules over L^{ab}_K(E,C) is explicitly computed in terms of monoids associated to a canonical sequence of separated graphs. Using this, we are able to construct an action of a finitely generated free group F on a zero-dimensional metrizable compact space Z such that the type semigroup S(Z, F, K) is not almost unperforated, where K denotes the algebra of clopen subsets of Z. Finally we obtain a characterization of the separated graphs (E,C) such that the canonical partial action of F on \Omega(E,C) is topologically free.Comment: Final version to appear in Advances in Mathematic

Multidisciplinary Management of Patients with Metastatic Colorectal Cancer

Colorectal cancer Colorectal cancer is the third most common malignant tumor worldwide. Globally, more than 600.000 people die from colorectal cancer every year, mainly from metastatic disease. Before the era of chemotherapy, patients with mCRC had a median overall survival of 9 months. With the introduction chemotherapeutic agents and targeted agents against VEGF and the EGF receptor, overall survival has improved to over 30 months. Originally, when patients presented with metastases, the disease was viewed as always being widespread and patients have typically been treated with systemic therapy. However, local treatment of metastases is technically feasible in an increasing number of patients with mCRC by either resection, radiofrequency ablation or stereotactic radiotherapy. Preliminary and retrospective evidence suggests that patients with extensive multi-organ mCRC may benefit from local treatment of metastases. This results in a growing debate in multidisciplinary teams on whether local treatment of metastases should be performed in these patients. Part One: Debulking in metastatic colorectal cancer In Chapter 2, the rationale of debulking therapy for patients with multi-organ mCRC is reviewed. The ORCHESTRA trial is the first multicenter randomized clinical trial in which is evaluated if multidisciplinary local treatment in addition to first line palliative systemic treatment (NCT01792934) results in survival benefit for patients with extensive mCRC. A preplanned safety and feasibility evaluation was performed aftercompletion of study treatment of the first 100 patients enrolled in the trial and reported in Chapter 3. A translational study program was embedded in the ORCHESTRA trial protocol and blood and tissue samples were collected from all patients enrolled. Part Two: Predicting response to systemic therapy MicroRNA MicroRNAs (miRNAs) are small non-coding RNAs that have an impact on many important biological processes by regulation of protein expression levels. Previous studies have shown significant correlations between circulating miRNAs and tumor stage and between paired tissue and serum miRNA expression levels. These circulating miRNAs could function as a minimally invasive predictive biomarker and as biomarker for disease monitoring. We aimed to prospectively validate the predictive value of a previously identified miRNA signature in the patients enrolled in the ORCHESTRA trial, which is reported in Chapter 4. Circulating Endothelial Cells (CECs) Circulating endothelial cells (CECs) are cells detached from both damaged normal vasculature as well as tumor vasculature. Previously, it has been shown that in patients with metastatic cancer, CEC numbers at baseline and changes in CEC numbers during systemic therapy are associated with prognosis. Consequently, enumeration of CEC is considered a promising biomarker in oncology. In Chapter 5 the results of (CD276+)CECs measurements from patients enrolled in the ORCHESTRA trial are reported. The primary objective of the study was to establish the prevalence of CD276+CECs in patients with mCRC and evaluating the dynamics of CD276+CECs during systemic therapy. Zr89-labeled PET Imaging In Chapter 6 Zr89-labeled PET Imaging is used to acquire more insight in the body distribution of cetuximab, a monoclonal antibody targeting the EGF receptor. We hypothesized that response to treatment is dependent on uptake of cetuximab in tumor lesions. We performed 89Zr-cetuximab PET imaging in patients with wt K-RAS mCRC with an indication for anti- EGFR mAb monotherapy to investigate biodistribution and tumor uptake as well as to establish the optimal scanning time point to visualize tumor targeting. Most importantly, we evaluated whether uptake on 89Zr-cetuximab PET imaging can discriminate between patients responding to treatment with cetuximab versus non-responding patients. In Chapter 7 the main findings presented in this thesis are summarized and discussed

C*-algebras of separated graphs

The construction of the C*-algebra associated to a directed graph $E$ is extended to incorporate a family $C$ consisting of partitions of the sets of edges emanating from the vertices of $E$. These C*-algebras $C^*(E,C)$ are analyzed in terms of their ideal theory and K-theory, mainly in the case of partitions by finite sets. The groups $K_0(C^*(E,C))$ and $K_1(C^*(E,C))$ are completely described via a map built from an adjacency matrix associated to $(E,C)$. One application determines the K-theory of the C*-algebras $U^{\text{nc}}_{m,n}$, confirming a conjecture of McClanahan. A reduced C*-algebra \Cstred(E,C) is also introduced and studied. A key tool in its construction is the existence of canonical faithful conditional expectations from the C*-algebra of any row-finite graph to the C*-subalgebra generated by its vertices. Differences between \Cstred(E,C) and $C^*(E,C)$, such as simplicity versus non-simplicity, are exhibited in various examples, related to some algebras studied by McClanahan.Comment: 29 pages. Revised version, to appear in J. Functional Analysi

Pr\"ufer modules over Leavitt path algebras

Let $L_K(E)$ denote the Leavitt path algebra associated to the finite graph $E$ and field $K$. For any closed path $c$ in $E$, we define and investigate the uniserial, artinian, non-noetherian left $L_K(E)$-module $U_{E,c-1}$. The unique simple factor of each proper submodule of $U_{E,c-1}$ is isomorphic to the Chen simple module $V_{[c^\infty]}$. In our main result, we classify those closed paths $c$ for which $U_{E,c-1}$ is injective. In this situation, $U_{E,c-1}$ is the injective hull of $V_{[c^\infty]}$.Comment: 24 pages. Submitted for publication July 2017. Comments are welcome

Pr\ufcfer modules over Leavitt path algebras

Let LK(E) denote the Leavitt path algebra associated to the finite graph E and field K. For any closed path c in E, we define and investigate the uniserial, artinian, non-Noetherian left LK(E)-module U_{E,c 121}. The unique simple factor of each proper submodule of U_{E,c 121}is isomorphic to the Chen simple module V_[c 1e]. In our main result, we classify those closed paths c for which U_{E,c 121} is injective. In this situation, U_{E,c 121} is the injective hull of V_[c 1e]

Search for eccentric binary black hole mergers with Advanced LIGO and Advanced Virgo during their first and second observing runs

When formed through dynamical interactions, stellar-mass binary black holes (BBHs) may retain eccentric orbits (e > 0.1 at 10 Hz) detectable by ground-based gravitational-wave detectors. Eccentricity can therefore be used to differentiate dynamically formed binaries from isolated BBH mergers. Current template-based gravitational-wave searches do not use waveform models associated with eccentric orbits, rendering the search less efficient for eccentric binary systems. Here we present the results of a search for BBH mergers that inspiral in eccentric orbits using data from the first and second observing runs (O1 and O2) of Advanced LIGO and Advanced Virgo. We carried out the search with the coherent WaveBurst algorithm, which uses minimal assumptions on the signal morphology and does not rely on binary waveform templates. We show that it is sensitive to binary mergers with a detection range that is weakly dependent on eccentricity for all bound systems. Our search did not identify any new binary merger candidates. We interpret these results in light of eccentric binary formation models. We rule out formation channels with rates greater than about 100 Gpc−3 yr−1 for e > 0.1, assuming a black hole mass spectrum with a power-law index less than about 2

Convex subshifts, separated Bratteli diagrams, and ideal structure of tame separated graph algebras

We introduce a new class of partial actions of free groups on totally disconnected compact Hausdorff spaces, which we call convex subshifts. These serve as an abstract framework for the partial actions associated with finite separated graphs in much the same way as classical subshifts generalize the edge shift of a finite graph. We define the notion of a finite type convex subshift and show that any such subshift is Kakutani equivalent to the partial action associated with a finite bipartite separated graph. We then study the ideal structure of both the full and the reduced tame graph C*-algebras, $\mathcal{O}(E,C)$ and $\mathcal{O}^r(E,C)$, of a separated graph $(E,C)$, and of the abelianized Leavitt path algebra $L_K^{\text{ab}}(E,C)$ as well. These algebras are the (reduced) crossed products with respect to the above-mentioned partial actions, and we prove that there is a lattice isomorphism between the lattice of induced ideals and the lattice of hereditary $D^{\infty}$-saturated subsets of a certain infinite separated graph $(F_{\infty},D^{\infty})$ built from $(E,C)$, called the separated Bratteli diagram of $(E,C)$. We finally use these tools to study simplicity and primeness of the tame separated graph algebras.Comment: 60 page