Simple and objective prediction of survival in patients with lung cancer: staging the host systemic inflammatory response

Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer

Orion Entry Display Feeder and Interactions with the Entry Monitor System

The Orion spacecraft is designed to return astronauts to a landing within 10 km of the intended landing target from low Earth orbit, lunar direct-entry, and lunar skip-entry trajectories. Al pile the landing is nominally controlled autonomously, the crew can fly precision entries manually in the event of an anomaly. The onboard entry displays will be used by the crew to monitor and manually fly the entry, descent, and landing, while the Entry Monitor System (EMS) will be used to monitor the health and status of the onboard guidance and the trajectory. The entry displays are driven by the entry display feeder, part of the Entry Monitor System (EMS). The entry re-targeting module, also part of the EMS, provides all the data required to generate the capability footprint of the vehicle at any point in the trajectory, which is shown on the Primary Flight Display (PFD). It also provides caution and warning data and recommends the safest possible re-designated landing site when the nominal landing site is no longer within the capability of the vehicle. The PFD and the EMS allow the crew to manually fly an entry trajectory profile from entry interface until parachute deploy having the flexibility to manually steer the vehicle to a selected landing site that best satisfies the priorities of the crew. The entry display feeder provides data from the ENIS and other components of the GNC flight software to the displays at the proper rate and in the proper units. It also performs calculations that are specific to the entry displays and which are not made in any other component of the flight software. In some instances, it performs calculations identical to those performed by the onboard primary guidance algorithm to protect against a guidance system failure. These functions and the interactions between the entry display feeder and the other components of the EMS are described

Pond Action: Promoting the conservation of ponds in Britain

Pond Action is an independent freshwater conservation project whichwas started in 1987 by Anne Powell, Roger Sweeting and Jeremy Biggs.It is based in the School of Biological and Molecular Sciences in OxfordPolytechnic and has five full-time staff with two senior advisors.The main aim of Pond Action's work has been to promote theconservation of ponds by creating a sound, scientific basis for pondconservation. An essential aspect of this work is the need to make theresults of scientific work available and understandable to everybodyconcerned with pond conservation

TRA-928: FISH BARRIER MITIGATION OF AN OVERSTEEPENED CULVERT WITHIN SAUGEEN FIRST NATION RESERVE

A deteriorated concrete box culvert conveying a tributary of the Saugeen River under Highway 21 in Ontario had reached the end of its lifespan and was in need of replacement. The tributary supports a diverse range of coldwater fish species such as Rainbow Trout; however, fish passage, particularly upstream migration, has been cut off since the culvert and highway were constructed over seventy-five years ago. Specifically, fish passage has been hindered by shallow sheet flow along the sixty metre flat bottom, excessive velocities associated with the smooth, seven percent gradient, and a perched barrier at the downstream outlet. A key component of the culvert replacement was an effort to improve the overall condition of the tributary’s natural environment, including the promotion of fish passage and migration opportunities. The culvert replacement project undertaken by the Ontario Ministry of Transportation (MTO) and MMM Group, coupled resources with the Saugeen Ojibway Nation (SON) Environment office, Parsons biologists, and Aquafor geomorphologists. The most ecologically sensitive replacement methodology of an open bottom structure was not viable for this project as it would have required a full closure of the Highway for approximately four months. A circular steel pipe culvert installed through tunneling was designed to by-pass and replace the existing concrete box culvert. In an effort to mitigate the current barriers to fish with the new pipe culvert, a prefabricated corrugated steel slip liner with engineered baffle arrangement was integrated into the design. The baffle configuration and geometry was designed by Jason Duguay (Université de Sherbrooke) and Ken Hannaford (Gov. NFLD), and the slip liner construction by the Corrugated Steel Pipe Institute. Construction of the new culvert and slip liner was completed in December, 2015, and a two year monitoring program will be undertaken to assess the effectiveness of barrier mitigation and geomorphic stability of the tributary

Decline of a rare moth at its last known English site : causes and lessons for conservation

The conditions required by rare species are often only approximately known. Monitoring such species over time can help refine management of their protected areas. We report population trends of a rare moth, the Dark Bordered Beauty Epione vespertaria (Linnaeus, 1767) (Lepidoptera: Geometridae) at its last known English site on a protected lowland heath, and those of its host-plant, Salix repens (L.) (Malpighiales: Salicaceae). Between 2007 and 2014, adult moth density reduced by an average of 30-35% annually over the monitored area, and its range over the monitored area contracted in concert. By comparing data from before this decline (2005) with data taken in 2013, we show that the density of host-plants over the monitored area reduced three-fold overall, and ten-fold in the areas of highest host-plant density. In addition, plants were significantly smaller in 2013. In 2005, moth larvae tended to be found on plants that were significantly larger than average at the time. By 2013, far fewer plants were of an equivalent size. This suggests that the rapid decline of the moth population coincides with, and is likely driven by, changes in the hostplant population. Why the host-plant population has changed remains less certain, but fire, frost damage and grazing damage have probably contributed. It is likely that a reduction in grazing pressure in parts of the site would aid host-plant recovery, although grazing remains an important site management activity. Our work confirms the value of constant monitoring of rare or priority insect species, of the risks posed to species with few populations even when their populations are large, of the potential conflict between bespoke management for species and generic management of habitats, and hence the value of refining our knowledge of rare species' requirements so that their needs can be incorporated into the management of protected areas

Hats off to you, Jim!

Jim’s intellectual curiosity was an inspiration. In addition to those whose comments follow, he clearly touched the careers and lives of many others

A new reference genome for Sorghum bicolor reveals high levels of sequence similarity between sweet and grain genotypes: implications for the genetics of sugar metabolism.

BackgroundThe process of crop domestication often consists of two stages: initial domestication, where the wild species is first cultivated by humans, followed by diversification, when the domesticated species are subsequently adapted to more environments and specialized uses. Selective pressure to increase sugar accumulation in certain varieties of the cereal crop Sorghum bicolor is an excellent example of the latter; this has resulted in pronounced phenotypic divergence between sweet and grain-type sorghums, but the genetic mechanisms underlying these differences remain poorly understood.ResultsHere we present a new reference genome based on an archetypal sweet sorghum line and compare it to the current grain sorghum reference, revealing a high rate of nonsynonymous and potential loss of function mutations, but few changes in gene content or overall genome structure. We also use comparative transcriptomics to highlight changes in gene expression correlated with high stalk sugar content and show that changes in the activity and possibly localization of transporters, along with the timing of sugar metabolism play a critical role in the sweet phenotype.ConclusionsThe high level of genomic similarity between sweet and grain sorghum reflects their historical relatedness, rather than their current phenotypic differences, but we find key changes in signaling molecules and transcriptional regulators that represent new candidates for understanding and improving sugar metabolism in this important crop

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN