Solar sail formation flying for deep-space remote sensing

In this paper we consider how 'near' term solar sails can be used in formation above the ecliptic plane to provide platforms for accurate and continuous remote sensing of the polar regions of the Earth. The dynamics of the solar sail elliptical restricted three-body problem (ERTBP) are exploited for formation flying by identifying a family of periodic orbits above the ecliptic plane. Moreover, we find a family of 1 year periodic orbits where each orbit corresponds to a unique solar sail orientation using a numerical continuation method. It is found through a number of example numerical simulations that this family of orbits can be used for solar sail formation flying. Furthermore, it is illustrated numerically that Solar Sails can provide stable formation keeping platforms that are robust to injection errors. In addition practical trajectories that pass close to the Earth and wind onto these periodic orbits above the ecliptic are identified

Social Isolation and Serious Mental Illness: The Role of Context-Aware Mobile Interventions

Social isolation is a common problem faced by individuals with serious mental illness (SMI), and current intervention approaches have limited effectiveness. This paper presents a blended intervention approach, called mobile Social Interaction Therapy by Exposure (mSITE), to address social isolation in individuals with serious mental illness. The approach combines brief in-person cognitive-behavioral therapy (CBT) with context-triggered mobile CBT interventions that are personalized using mobile sensing data. Our approach targets social behavior and is the first context-aware intervention for improving social outcomes in serious mental illness

Time-lapse ultrashort pulse microscopy of infection in three-dimensional versus two-dimensional culture environments reveals enhanced extra-chromosomal virus replication compartment formation

The mechanisms that enable viruses to harness cellular machinery for their own survival are primarily studied in cell lines cultured in two-dimensional (2-D) environments. However, there are increasing reports of biological differences between cells cultured in 2-D versus three-dimensional (3-D) environments. Here we report differences in host-virus interactions based on differences in culture environment. Using ultrashort pulse microscopy (UPM), a form of two-photon microscopy that utilizes sub-10-fs pulses to efficiently excite fluorophores, we have shown that de novo development of extra-chromosomal virus replication compartments (VRCs) upon murine cytomegalovirus (mCMV) infection is markedly enhanced when host cells are cultured in 3-D collagen gels versus 2-D monolayers. In addition, time-lapse imaging revealed that mCMV-induced VRCs have the capacity to grow by coalescence. This work supports the future potential of 3-D culture as a useful bridge between traditional monolayer cultures and animal models to study host-virus interactions in a more physiologically relevant environment for the development of effective anti-viral therapeutics. These advances will require broader adoption of modalities, such as UPM, to image deep within scattering tissues

RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes

Quantitative data on red cell measures of iron status and their relation to the magnitude of the systemic inflammatory response and survival in patients with colorectal cancer

Background: Inflammation is recognised to be associated with perturbation of serum measures of iron status. However, the impact of colorectal cancer associated host inflammation on red cell measures of iron status has not been previously quantified. Methods: Patients undergoing elective surgery with curative intent, for colorectal cancer, at a single centre between 2008 and 2017 were included (n = 824). Blood samples taken for C-reactive protein (CRP), albumin, and full blood count (FBC) allowed patients to be grouped by modified Glasgow Prognostic Score (mGPS), and anaemia subtype (haemoglobin (Hb) M < 130 mg/L and F < 120 mg/L, with microcytic anaemia being mean corpuscular volume (MCV) < 80 f/L, and normocytic anaemia with MCV 80–100 f/L). Relationships between these groupings and red cell measures iron status including Hb, MCV, mean corpuscular haemoglobin (MCH) and red cell distribution width (RDW) were examined. Results: The combination of increasing T stage and increasing mGPS was associated with lower Hb, lower MCV, lower MCH, higher RDW, and higher prevalence of both microcytic and normocytic anaemia (all p < 0.001). The combination of CRP >10 mg/L and albumin <35  g/L was associated with lower Hb, lower MCV, lower MCH, higher RDW, and higher prevalence of both microcytic and normocytic anaemia (all p < 0.010). At multivariate Cox regression only Hb remained significantly associated with cancer specific (HR 0.98, 95% CI 0.97–0.99, p < 0.001), and overall survival (HR 0.98, 95% CI 0.97–0.99, p = 0.001). Conclusions: The presence of a host systemic inflammatory response to colorectal cancer was associated with significant perturbation of red cell measure of iron status

Perioperative blood transfusion is associated with the postoperative systemic inflammatory response and poorer outcomes following surgery for colorectal cancer

Background: The present study investigated relationships between perioperative blood transfusion, postoperative systemic inflammatory response, and outcomes following surgery for colorectal cancer. Methods: Data were recorded for patients (n = 544) undergoing potentially curative, elective surgery for colorectal cancer at a single center between 2012 and 2017. Transfusion history was obtained retrospectively from electronic records. Associations between blood transfusion, postoperative C-reactive protein (CRP), albumin, hemoglobin, complications, cancer-specific survival and overall survival (OS) were assessed using propensity score matching (n =116). Results: Of 544 patients, the majority were male (n =294, 54%), over 65 years of age (n =350, 64%), and with colonic (n =347, 64%) node-negative disease (n =353, 65%). Eighty-six patients (16%) required perioperative blood transfusion. In the unmatched cohort, blood transfusion was associated with higher median postoperative day (POD) 3 CRP {143 [interquartile range (IQR) 96–221 mg/L] vs. 120 (IQR 72–188 mg/L); p = 0.004}, lower median POD 3 albumin [24 (IQR 20–26 g/L) vs. 27 (IQR 24–30 g/L); p < 0.001], more postoperative complications [odds ratio (OR) 3.28, 95% confidence interval (CI) 2.03–5.29] and poorer OS [hazard ratio (HR) 3.18, 95% CI 2.08–4.84]. In the propensity score matched cohort, blood transfusion was similarly associated with higher median POD 3 CRP [130 (IQR 93–196 mg/L) vs. 113 (IQR 66–173 mg/L); p = 0.046], lower median POD 3 albumin [24 (IQR 20–26 g/L) vs. 26 (IQR 24–30 g/L); p < 0.001], more postoperative complications (OR 2.91, 95% CI 1.36–6.20) and poorer OS (HR 2.38, 95% CI 0.99–5.73). Conclusions: Perioperative blood transfusion was associated with postoperative inflammation, complications, and poorer survival in patients undergoing colorectal cancer surgery, with and without propensity score techniques

A model of tuberculosis clustering in low incidence countries reveals more transmission in the United Kingdom than the Netherlands between 2010 and 2015

Tuberculosis (TB) remains a public health threat in low TB incidence countries, through a combination of reactivated disease and onward transmission. Using surveillance data from the United Kingdom (UK) and the Netherlands (NL), we demonstrate a simple and predictable relationship between the probability of observing a cluster and its size (the number of cases with a single genotype). We demonstrate that the full range of observed cluster sizes can be described using a modified branching process model with the individual reproduction number following a Poisson lognormal distribution. We estimate that, on average, between 2010 and 2015, a TB case generated 0.41 (95% CrI 0.30,0.60) secondary cases in the UK, and 0.24 (0.14,0.48) secondary cases in the NL. A majority of cases did not generate any secondary cases. Recent transmission accounted for 39% (26%,60%) of UK cases and 23%(13%,37%) of NL cases. We predict that reducing UK transmission rates to those observed in the NL would result in 538(266,818) fewer cases annually in the UK. In conclusion, while TB in low incidence countries is strongly associated with reactivated infections, we demonstrate that recent transmission remains sufficient to warrant policies aimed at limiting local TB spread