STS-40 descent BET products: Development and results

Descent Best Estimate Trajectory (BET) Data were generated for the final Orbiter Experiments Flight, STS-40. This report discusses the actual development of these post-flight products: the inertial BET, the Extended BET, and the Aerodynamic BET. Summary results are also included. The inertial BET was determined based on processing Tracking and Data Relay Satellite (TDRSS) coherent Doppler data in conjunction with observations from eleven C-band stations, to include data from the Kwajalein Atoll and the usual California coastal radars, as well as data from five cinetheodolite cameras in the vicinity of the runways at EAFB. The anchor epoch utilized for the trajectory reconstruction was 53,904 Greenwich Mean Time (GMT) seconds which corresponds to an altitude at epoch of approximately 708 kft. Atmospheric data to enable development of an Extended BET for this mission were upsurped from the JSC operational post-flight BET. These data were evaluated based on Space Shuttle-derived considerations as well as model comparisons. The Aerodynamic BET includes configuration information, final mass properties, and both flight-determined and predicted aerodynamic performance estimates. The predicted data were based on the final pre-operational databook, updated to include flight determined incrementals based on an earlier ensemble of flights. Aerodynamic performance comparisons are presented and correlated versus statistical results based on twenty-two previous missions

Final STS-35 Columbia descent BET products and results for LaRC OEX investigations

Final STS-35 'Columbia' descent Best Estimate Trajectory (BET) products have been developed for Langley Research Center (LaRC) Orbiter Experiments (OEX) investigations. Included are the reconstructed inertial trajectory profile; the Extended BET, which combines the inertial data and, in this instance, the National Weather Service atmospheric information obtained via Johnson Space Center; and the Aerodynamic BET. The inertial BET utilized Inertial Measurement Unit 1 (IMU1) dynamic measurements for deterministic propagation during the ENTREE estimation process. The final estimate was based on the considerable ground based C-band tracking coverage available as well as Tracking Data and Relay Satellite System (TDRSS) Doppler data, a unique use of the latter for endo-atmospheric flight determinations. The actual estimate required simultaneous solutions for the spacecraft position and velocity, spacecraft attitude, and six IMU parameters - three gyro biases and three accelerometer scale factor correction terms. The anchor epoch for this analysis was 19,200 Greenwich Mean Time (GMT) seconds which corresponds to an initial Shuttle altitude of approximately 513 kft. The atmospheric data incorporated were evaluated based on Shuttle derived considerations as well as comparisons with other models. The AEROBET was developed based on the Extended BET, the measured spacecraft configuration information, final mass properties, and the final Orbiter preoperation databook. The latter was updated based on aerodynamic consensus incrementals derived by the latest published FAD. The rectified predictions were compared versus the flight computed values and the resultant differences were correlated versus ensemble results for twenty-two previous STS entry flights

The core planar cell polarity gene, Vangl2, directs adult corneal epithelial cell alignment and migration

This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) DTG PhD studentship to A.F., an Anatomical Society PhD Studentship (‘The Roles of planar cell polarity genes in a classical anatomical system: the cornea’) to D.A.P./J.M.C. and BBSRC Project Grants BB/J015172/1 and BB/J015237/1 to J.D.W. and J.M.C., respectively.Peer reviewedPublisher PD

Urban-Focused Comprehensive Economic Development Strategy (CEDS)

This Comprehensive Economic Development Strategy (CEDS) is the outgrowth of a long running effort by the John S. Watson Institute for Public Policy at Thomas Edison State College (Watson Institute) to support economic and community development in New Jersey with a particular focus on urban areas in need of revitalization. The Watson Institute was previously awarded a United States Economic Development Administration (USEDA) grant to complete an economic analysis of the North Central New Jersey Region. The USEDA approved that analysis and awarded additional funds to continue our work, culminating in this CEDS plan. Several years ago, the Watson Institute recognized that there was an opportunity and need to engage in regional economic development planning and cooperation amongst members of the New Jersey Urban Mayors Association. Rapidly advancing technology and economies necessitate partnerships amongst local governments, non-profits, private firms, and universities to address broad economic development problems and reach long-term goals. Although many of the municipalities participating in the CEDS effort are not contiguous, they nonetheless share histories that have led to their current problems. Allowing geographic boundaries to limit the extent of opportunity is no longer a viable option for regions that want to see broad based and sustainable economic growth. The purpose of a CEDS is to bring together the public, non- profit, and private sectors to establish a comprehensive framework for economic growth and revitalization in a region. In this case, the “Region” is defined as 19 specific municipalities within a seven-county area of the state, including: Asbury Park, Bayonne, Bloomfield, East Orange, Elizabeth, Hoboken, Irvington, Jersey City, Lakewood, Neptune, New Brunswick, Newark, Orange, Passaic, Paterson, Perth Amboy, Plainfield, Roselle and Woodbridge. The geographic composition of this CEDS is unique in that the Region is not strictly speaking contiguous. What binds our Region together are the threads of common issues, opportunities, constraints, and the hope that, collectively, the communities can create solutions that would otherwise not be obtained individually. One of the most significant binding events of this region’s recent history is Superstorm Sandy. Minimizing disruption from natural disaster events is critical to any economic development goals and objectives of a community. There are a wide variety of reports and recommendations available to municipalities in helping them develop resiliency plans that are customized to meet the needs of their community. Discussions regarding resilient infrastructure have been an ongoing theme during this urban focused CEDS, and is reflected in several projects and initiatives focused on resiliency as well as it being a theme in projects that are not necessarily resiliency focused, but incorporate resiliency elements to reduce the stress put on other systems. Two of the more forward thinking projects included as part of resiliency strategies in this CEDS are the City of Hoboken’s flood wall and the Township of Woodbridge’s plan for a township wide microgrid. Although discussion about resiliency in general tends to focus on natural disaster, this CEDS discussion on resiliency also encompassed a wide variety of activities and topics. When at all possible, resilience focused projects should incorporate other resiliency related elements The steering committee met many times over the course of several years, for both the economic base analysis and for this CEDS plan. Steering committee members included representatives and officials from each community; non-profit organizations such as universities, community colleges, libraries and community-based organizations; and representatives of the private sector ranging from Fortune 100 corporations to small businesses. The steering committee’s work culminated in the Action Plan. The Action Plan serves as the roadmap that the Watson Institute, together with the New Jersey Urban Mayors Association and the CEDS steering committee itself, will use to implement sustainable economic development in the Region’s constituent municipalities. The challenges faced by the steering committee in formulating the CEDS plan were commensurate with those faced by each of the communities. The goals and objectives include: Enhancing, preserving and making resilient critical infrastructure assets; Promoting small business development; Addressing persistent and complex workforce issues; Marketing effectively to attract new businesses, residents and tourists; Promulgating best practices in economic development across all 19 communities; Providing adequate implementation assistance to execute the CEDS plan. The steering committee engaged in many planning exercises, including stakeholder and issues mapping, brainstorming, resource assessments, inventorying existing networks and programs, etc. The consulting team brought data, national economic development experience and certain stakeholder engagement techniques to elicit creative, non-linear thinking. The Watson Institute provided a Senior Fellow to meet and communicate with each community individually on multiple occasions to understand specific needs and encourage participation in the process. Following all these efforts, the steering committee agreed that, to be included in the CEDS plan, each action has to meet the following criteria: It must address one of the critical goals/objectives identified above, It must be realistic, clear and actionable, It must either require few local resources to implement or have a funding source identified, It must have a real and sustainable impact, and, It should be relatively short term to show progress and generate enthusiasm, It should be something that, if successful, can be quickly replicated across all 19 communities, It should have performance metrics that can be tracked and reported on. These criteria weighed considerably on the process and the steering committee’s deliberations. Unlike a “traditional” CEDS vested at the County or State level, with existing power structures and funding sources, this CEDS relies on the power of persuasion; the more effective utilization of existing resources; and the ability to realign stakeholders in a truly novel way

Carbon dioxide and ocean acidification observations in UK waters. Synthesis report with a focus on 2010–2015

Key messages: 1.1 The process of ocean acidification is now relatively well-documented at the global scale as a long-term trend in the open ocean. However, short-term and spatial variability can be high. 1.2 New datasets made available since Charting Progress 2 make it possible to greatly improve the characterisation of CO2 and ocean acidification in UK waters. 3.1 Recent UK cruise data contribute to large gaps in national and global datasets. 3.2 The new UK measurements confirm that pH is highly variable, therefore it is important to measure consistently to determine any long term trends. 3.3 Over the past 30 years, North Sea pH has decreased at 0.0035±0.0014 pH units per year. 3.4 Upper ocean pH values are highest in spring, lowest in autumn. These changes reflect the seasonal cycles in photosynthesis, respiration (decomposition) and water mixing. 3.5 Carbonate saturation states are minimal in the winter, and lower in 7 more northerly, colder waters. This temperature-dependence could have implications for future warming of the seas. 3.6 Over the annual cycle, North-west European seas are net sinks of CO2. However, during late summer to autumn months, some coastal waters may be significant sources. 3.7 In seasonally-stratified waters, sea-floor organisms naturally experience lower pH and saturation states; they may therefore be more vulnerable to threshold changes. 3.8 Large pH changes (0.5 - 1.0 units) can occur in the top 1 cm of sediment; however, such effects are not well-documented. 3.9 A coupled forecast model estimates the decrease in pH trend within the North Sea to be -0.0036±0.00034 pH units per year, under a high greenhouse gas emissions scenario (RCP 8.5). 3.10 Seasonal estimates from the forecast model demonstrate areas of the North Sea that are particularly vulnerable to aragonite undersaturation

Temporal validation of metabolic nodal response of esophageal cancer to neoadjuvant chemotherapy as an independent predictor of unresectable disease, survival, and recurrence

Objectives We recently described metabolic nodal stage (mN) and response (mNR) of cancer of the esophagus and gastro-esophageal junction (GEJ) to neoadjuvant chemotherapy (NAC) using 18F-FDG PET-CT as new markers of disease progression, recurrence, and death. We aimed to validate our findings. Methods Our validation cohort comprised all patients consecutive to our discovery cohort, staged before and after NAC using PET-CT from 2014 to 2017. Multivariate binary logistic and Cox regression were performed. Results Fifty-one of the 200 patients had FDG-avid nodes after NAC (25.5%; i.e., lack of complete mNR), and were more likely to progress during NAC to incurable disease on PET-CT or at surgery: odds ratio 3.84 (1.46–10.1; p = 0.006). In 176 patients undergoing successful resection, patients without complete mNR had a worse prognosis: disease-free survival hazard ratio 2.46 (1.34–4.50); p = 0.004. These associations were independent of primary tumor metabolic, pathological response, and stage. In a hybrid pathological/metabolic nodal stage, avid nodal metastases conferred a worse prognosis than non-avid metastases. Lack of complete mNR predicted recurrence or death at 1 and 2 years: positive predictive values 44.4% (31.7–57.8) and 74.1% (56.6–86.3) respectively. Conclusions This study provides temporal validation for mNR as a new and independent predictive and prognostic marker of esophageal and GEJ cancer treated with NAC and surgery, although external validation is required to assess generalizability. mNR may provide surrogate information regarding the phenotype of metastatic cancer clones beyond the mere presence of nodal metastases, and might be used to better inform patients, risk stratify, and personalize management, including adjuvant therapy

First circumglobal assessment of Southern Hemisphere humpback whale mitochondrial genetic variation and implications for management

The description of genetic population structure over a species\u27 geographic range can provide insights into its evolutionary history and also support effective management efforts. Assessments for globally distributed species are rare, however, requiring significant international coordination and collaboration. The global distribution of demographically discrete populations for the humpback whale Megaptera novaeangliae is not fully known, hampering the definition of appropriate management units. Here, we present the first circumglobal assessment of mito - chondrial genetic population structure across the species\u27 range in the Southern Hemisphere and Arabian Sea. We combine new and existing data from the mitochondrial (mt)DNA control region that resulted in a 311 bp consensus sequence of the mtDNA control region for 3009 individuals sampled across 14 breeding stocks and subpopulations currently recognized by the International Whaling Commission. We assess genetic diversity and test for genetic differentiation and also estimate the magnitude and directionality of historic matrilineal gene flow between putative populations. Our results indicate that maternally directed site fidelity drives significant genetic population structure between breeding stocks within ocean basins. However, patterns of connectivity differ across the circumpolar range, possibly as a result of differences in the extent of longitudinal movements on feeding areas. The number of population comparisons observed to be significantly differentiated were found to diminish at the subpopulation scale when nucleotide differences were examined, indicating that more complex processes underlie genetic structure at this scale. It is crucial that these complexities and uncertainties are afforded greater consideration in management and regulatory efforts

Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial

Background: Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European Medicines Agency recommended a post-licensing study assessing the cardiovascular safety of febuxostat compared with allopurinol.Methods: We did a prospective, randomised, open-label, blinded-endpoint, non-inferiority trial of febuxostat versus allopurinol in patients with gout in the UK, Denmark, and Sweden. Eligible patients were 60 years or older, already receiving allopurinol, and had at least one additional cardiovascular risk factor. Those who had myocardial infarction or stroke in the previous 6 months or who had severe congestive heart failure or severe renal impairment were excluded. After a lead-in phase in which allopurinol dose was optimised towards achieving a serum urate concentration of less than 0·357 mmol/L ( < 6 mg/dL), patients were randomly assigned (1:1, with stratification according to previous cardiovascular events) to continue allopurinol (at the optimised dose) or start febuxostat at 80 mg/day, increasing to 120 mg/day if necessary to achieve the target serum urate concentration. The primary outcome was a composite of hospitalisation for non-fatal myocardial infarction or biomarker-positive acute coronary syndrome; non-fatal stroke; or cardiovascular death. The hazard ratio (HR) for febuxostat versus allopurinol in a Cox proportional hazards model (adjusted for the stratification variable and country) was assessed for non-inferiority (HR limit 1·3) in an on-treatment analysis. This study is registered with the EU Clinical Trials Register (EudraCT 2011-001883-23) and ISRCTN (ISRCTN72443728) and is now closed.Findings: From Dec 20, 2011, to Jan 26, 2018, 6128 patients (mean age 71·0 years [SD 6·4], 5225 [85·3%] men, 903 [14·7%] women, 2046 [33·4%] with previous cardiovascular disease) were enrolled and randomly allocated to receive allopurinol (n=3065) or febuxostat (n=3063). By the study end date (Dec 31, 2019), 189 (6·2%) patients in the febuxostat group and 169 (5·5%) in the allopurinol group withdrew from all follow-up. Median follow-up time was 1467 days (IQR 1029–2052) and median on-treatment follow-up was 1324 days (IQR 870–1919). For incidence of the primary endpoint, on-treatment, febuxostat (172 patients [1·72 events per 100 patient-years]) was non-inferior to allopurinol (241 patients [2·05 events per 100 patient-years]; adjusted HR 0·85 [95% CI 0·70–1·03], p less than 0·0001). In the febuxostat group, 222 (7·2%) of 3063 patients died and 1720 (57·3%) of 3001 in the safety analysis set had at least one serious adverse event (with 23 events in 19 [0·6%] patients related to treatment). In the allopurinol group, 263 (8·6%) of 3065 patients died and 1812 (59·4%) of 3050 had one or more serious adverse events (with five events in five [0·2%] patients related to treatment). Randomised therapy was discontinued in 973 (32·4%) patients in the febuxostat group and 503 (16·5%) patients in the allopurinol group.Interpretation:Febuxostat is non-inferior to allopurinol therapy with respect to the primary cardiovascular endpoint, and its long-term use is not associated with an increased risk of death or serious adverse events compared with allopurinol