Palliative stenting for oesophagogastric cancer: tumour and host factors and prognosis

Objectives: Palliative self-expandable metallic stent (SEMS) insertion is common in patients not suitable for resection of oesophagogastric (OG) cancer. Factors which may determine survival, however, are not clear. The present study examined the relationship between tumour and host factors, including the systemic inflammatory response and survival of patients undergoing palliative SEMS insertion. Methods: Patients with a diagnosis of OG cancer who were considered suitable for palliative SEMS only without systemic therapy were identified. Patient characteristics including Eastern Cooperative Oncology Group performance status, radiological stage and modified Glasgow Prognostic Score (mGPS: 0—C-reactive protein (CRP) ≤10 mg/L; 1—CRP >10 mg/L; 2—CRP >10 mg/L; albumin <35 g/L) were recorded prospectively. The relationship between such characteristics and 3-month survival was examined. Results: 203 patients were included in the final analysis. All patients died during follow-up, with median survival from diagnosis 75 days (IQR 47–157). 78% of patients were systemically inflamed (mGPS >1). On multivariate analysis, only poor performance status (HR 1.23, p=0.025), metastatic disease (HR 2.27, p<0.001) and mGPS (HR 1.25, p=0.021) were associated with shorter survival. The combination of performance status and mGPS stratified 3-month survival of patients without metastatic disease from 88% to 20% (p<0.001) and patients with metastases from 43% to 6% (p=0.059). Similar results were observed when analysis was restricted to patients with oesophageal and junctional cancer (M0: 83%–20%, p=0.008; M1: 33%–8%, p=0.082). Conclusion: Performance status, metastatic disease and mGPS are independent predictors of survival in patients with OG cancer undergoing palliative SEMS insertion. These routinely available markers provide a rational system on which to base decisions regarding prognosis and treatment

Designing signaling environments to steer transcriptional diversity in neural progenitor cell populations

Stem cell populations within developing embryos are diverse, composed of many different subpopulations of cells with varying developmental potential. The structure of stem cell populations in cell culture remains poorly understood and presents a barrier to differentiating stem cells for therapeutic applications. In this paper we develop a framework for controlling the architecture of stem cell populations in cell culture using high-throughput single cell mRNA-seq and computational analysis. We find that the transcriptional diversity of neural stem cell populations collapses in cell culture. Cell populations are depleted of committed neuron progenitor cells and become dominated by a single pre-astrocytic cell population. By analyzing the response of neural stem cell populations to forty distinct signaling conditions, we demonstrate that signaling environments can restructure cell populations by modulating the relative abundance of pre-astrocyte and pre-neuron subpopulations according to a simple linear code. One specific combination of BMP4, EGF, and FGF2 ligands switches the default population balance such that 70% of cells correspond to the committed neurons. Our work demonstrates that single-cell RNA-seq can be applied to modulate the diversity of in vitro stem cell populations providing a new strategy for population-level stem cell control

Long-term follow-up of patients undergoing resection of tnm stage i colorectal cancer: an analysis of tumour and host determinants of outcome

Background Screening for colorectal cancer improves cancer-specific survival (CSS) through the detection of early-stage disease; however, its impact on overall survival (OS) is unclear. The present study examined tumour and host determinants of outcome in TNM Stage I disease. Methods All patients with pathologically confirmed TNM Stage I disease across 4 hospitals in the North of Glasgow between 2000 and 2008 were included. The preoperative modified Glasgow Prognostic Score (mGPS) was used as a marker of the host systemic inflammatory response (SIR). Results There were 191 patients identified, 105 (55 %) were males, 91 (48 %) were over the age of 75 years and 7 (4 %) patients underwent an emergency operation. In those with a preoperative CRP result (n = 150), 35 (24 %) patients had evidence of an elevated mGPS. Median follow-up of survivors was 116 months (minimum 72 months) during which 88 (46 %) patients died; 7 (8 %) had postoperative deaths, 15 (17 %) had cancer-related deaths and 66 (75 %) had non-cancer-related deaths. 5-year CSS was 95 % and OS was 76 %. On univariate analysis, advancing age (p < 0.001), emergency presentation (p = 0.008), and an elevated mGPS (p = 0.012) were associated with reduced OS. On multivariate analysis, only age (HR = 3.611, 95 % CI 2.049–6.365, p < 0.001) and the presence of an elevated mGPS (HR = 2.173, 95 % CI 1.204–3.921, p = 0.010) retained significance. Conclusions In patients undergoing resection for TNM Stage I colorectal cancer, an elevated mGPS was an objective independent marker of poorer OS. These patients may benefit from a targeted intervention

In reply to "Hynes S.O. et al. Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study"

No abstract available

Strain-induced gauge and Rashba fields in ferroelectric Rashba lead chalcogenide PbX monolayers (X = S, Se, Te)

One of the exciting features of two-dimensional (2D) materials is their electronic and optical tunability through strain engineering. Previously, we found a class of 2D ferroelectric Rashba semiconductors PbX (X = S, Se, Te) with tunable spin-orbital properties. In this work, based on our previous tight-binding (TB) results, we derive an effective low-energy Hamiltonian around the symmetry points that captures the effects of strain on the electronic properties of PbX. We find that strains induce gauge fields which shift the Rashba point and modify the Rashba parameter. This effect is equivalent to the application of in-plane magnetic fields. The out-of-plane strain, which is proportional to the electric polarization, is also shown to modify the Rashba parameter. Overall, our theory connects strain and spin splitting in ferroelectric Rashba materials, which will be important to understand the strain-induced variations in local Rashba parameters that will occur in practical applications

Evaluation of a tumor microenvironment-based prognostic score in primary operable colorectal cancer

Purpose: The tumor microenvironment is recognized as an important determinant of progression and outcome in colorectal cancer. The aim of the present study was to evaluate a novel tumor microenvironment–based prognostic score, based on histopathologic assessment of the tumor inflammatory cell infiltrate and tumor stroma, in patients with primary operable colorectal cancer. Experimental Design: Using routine pathologic sections, the tumor inflammatory cell infiltrate and stroma were assessed using Klintrup–Mäkinen (KM) grade and tumor stroma percentage (TSP), respectively, in 307 patients who had undergone elective resection for stage I–III colorectal cancer. The clinical utility of a cumulative score based on these characteristics was examined. Results: On univariate analysis, both weak KM grade and high TSP were associated with reduced survival (HR, 2.42; P = 0.001 and HR, 2.05; P = 0.001, respectively). A cumulative score based on these characteristics, the Glasgow Microenvironment Score (GMS), was associated with survival (HR, 1.93; 95% confidence interval, 1.36–2.73; P < 0.001), independent of TNM stage and venous invasion (both P < 0.05). GMS stratified patients in to three prognostic groups: strong KM (GMS = 0), weak KM/low TSP (GMS = 1), and weak KM/high TSP (GMS = 2), with 5-year survival of 89%, 75%, and 51%, respectively (P < 0.001). Furthermore, GMS in combination with node involvement, venous invasion, and mismatch repair status further stratified 5-year survival (92% to 37%, 93% to 27%, and 100% to 37%, respectively). Conclusions: The present study further confirms the clinical utility of assessment of the tumor microenvironment in colorectal cancer and introduces a simple, routinely available prognostic score for the risk stratification of patients with primary operable colorectal cancer

AN APPROACH TO DEVELOPING A NON-COMMUNICABLE DISEASE MODEL OF CARE IN SIERRA LEONE

ABSTRACT: Due to the rising and endemic burdens of noncommunicable diseases (NCDs) in sub-Saharan Africa including Sierra Leone, innovative approaches to developing NCD care models are urgently needed and should leverage on lessons learned from other countries. We discuss an approach that can be used to develop NCD chronic care clinics in Sierra Leone with a focus on task shifting, integrating care, developing an NCD package, developing and standardising guidelines, and piloting and decentralising NCD care to rural areas

Tuning and Switching a Plasmonic Quantum Dot Sandwich in a Nematic Line Defect

We study the quantum-mechanical effects arising in a single semiconductor core/shell quantum dot controllably sandwiched between two plasmonic nanorods. Control over the position and the sandwich confinement structure is achieved by the use of a linear-trap, liquid-crystal line defect and laser tweezers that push the sandwich together. This arrangement allows for the study of exciton plasmon interactions in a single structure, unaltered by ensemble effects or the complexity of dielectric interfaces. We demonstrate the effect of plasmonic confinement on the photon-antibunching behavior of the quantum dot and its luminescence lifetime. The quantum dot behaves as a single emitter when nanorods are far away from the quantum dot but shows possible multiexciton emission and a significantly decreased lifetime when tightly confined in a plasmonic sandwich. These findings demonstrate that liquid crystal defects, combined with laser tweezers, enable a versatile platform to study plasmonic coupling phenomena in a nanoscale laboratory, where all elements can be arranged almost at will.Comment: Supporting information at the en

Spin-Orbit Dirac Fermions in 2D Systems

We propose a novel model for including spin-orbit interactions in buckled two dimensional systems. Our results show that in such systems, intrinsic spin-orbit coupling leads to a formation of Dirac cones, similar to Rashba model. We explore the microscopic origins of this behaviour and confirm our results using DFT calculations

Two-dimensional square buckled Rashba lead chalcogenides

We propose the lead sulphide (PbS) monolayer as a two-dimensional semiconductor with a large Rashba-like spin-orbit effect controlled by the out-of-plane buckling. The buckled PbS conduction band is found to possess Rashba-like dispersion and spin texture at the M and Γ points, with large effective Rashba parameters of λ∼5 eV Å and λ∼1 eV Å, respectively. Using a tight-binding formalism, we show that the Rashba effect originates from the very large spin-orbit interaction and the hopping term that mixes the in-plane and out-of-plane p orbitals of Pb and S atoms. The latter, which depends on the buckling angle, can be controlled by applying strain to vary the spin texture as well as the Rashba parameter at Γ and M. Our density functional theory results together with tight-binding formalism provide a unifying framework for designing Rashba monolayers and for manipulating their spin properties.P.Z.H., H.S.P., and D.K.C. acknowledge the support of the Physics and Mechanical Engineering Department at Boston University. P.Z.H. is grateful for the hospitality of the NUS Centre for Advanced 2D Materials and Graphene Research Centre where this work was initiated. D.K.C. acknowledges the hospitality of the Aspen Center for Physics, which is supported by the US National Science Foundation Grant No. PHY-1607611. A.S.R., A.C.,and A.H.C.N. acknowledge support by the National Research Foundation, Prime Minister Office, Singapore, under its Medium Sized Centre Programme and CRP award "Novel 2D materials with tailored properties: Beyond graphene" (Grant No. R-144-000295-281). (Physics and Mechanical Engineering Department at Boston University; PHY-1607611 - US National Science Foundation; R-144-000295-281 - National Research Foundation, Prime Minister Office, Singapore, under its Medium Sized Centre Programme and CRP award "Novel 2D materials with tailored properties: Beyond graphene")Published versio