Airborne Forward-Looking Interferometer for the Detection of Terminal-Area Hazards

The Forward Looking Interferometer (FLI) program was a multi-year cooperative research effort to investigate the use of imaging radiometers with high spectral resolution, using both modeling/simulation and field experiments, along with sophisticated data analysis techniques that were originally developed for analysis of data from space-based radiometers and hyperspectral imagers. This investigation has advanced the state of knowledge in this technical area, and the FLI program developed a greatly improved understanding of the radiometric signal strength of aviation hazards in a wide range of scenarios, in addition to a much better understanding of the real-world functionality requirements for hazard detection instruments. The project conducted field experiments on three hazards (turbulence, runway conditions, and wake vortices) and analytical studies on several others including volcanic ash, reduced visibility conditions, in flight icing conditions, and volcanic ash

Experimental Validation of a Forward Looking Interferometer for Detection of Clear Air Turbulence due to Mountain Waves

The Forward-Looking Interferometer (FLI) is an airborne sensor concept for detection and estimation of potential atmospheric hazards to aircraft. The FLI concept is based on high-resolution Infrared Fourier Transform Spectrometry technologies that have been developed for satellite remote sensing. The FLI is being evaluated for its potential to address multiple hazards, during all phases of flight, including clear air turbulence, volcanic ash, wake vortices, low slant range visibility, dry wind shear, and icing. In addition, the FLI is being evaluated for its potential to detect hazardous runway conditions during landing, such as wet or icy asphalt or concrete. The validation of model-based instrument and hazard simulation results is accomplished by comparing predicted performance against empirical data. In the mountain lee wave data collected in the previous FLI project, the data showed a damped, periodic mountain wave structure. The wave data itself will be of use in forecast and nowcast turbulence products such as the Graphical Turbulence Guidance and Graphical Turbulence Guidance Nowcast products. Determining how turbulence hazard estimates can be derived from FLI measurements will require further investigation

Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer

Background: Phenoxodiol is a novel isoflavone currently being studied in clinical trials for the treatment of cancer. This study reports the pharmacokinetics of phenoxodiol in patients with cancer.Methods: The pharmacokinetics of phenoxodiol was studied following a single intravenous (iv) bolus dose and during a continuous intravenous infusion. Three men with prostate cancer and 3 women with breast cancer received IV bolus phenoxodiol (5 mg/kg) and plasma was sampled for free and total phenoxodiol levels. On a separate occasion 5 of the same patients received a continuous intravenous infusion of phenoxodiol (2 mg/kg/h) and plasma was again sampled for free and total phenoxodiol levels. Phenoxodiol was measured using gradient HPLC with ultraviolet detection.Results: Following bolus injection, free and total phenoxodiol appeared to follow first order pharmacokinetics. The elimination half-lives for free and total phenoxodiol were 0.67 ± 0.53 h and 3.19 ± 1.93 h, respectively, while the total plasma clearance rates were 2.48 ± 2.33 L/h and 0.15 ± 0.08 L/h, respectively. The respective apparent volumes of distribution were 1.55 ± 0.69 L/kg and 0.64 ± 0.51 L/kg. During continuous intravenous infusion, free phenoxodiol accumulated rapidly to reach a mean concentration at steady state of 0.79 ± 0.14 μg/ml after 0.87 ± 0.18 h. The apparent accumulation half-life of free phenoxodiol was 0.17 ± 0.04 h while the plasma clearance during continuous infusion was 1.29 ± 0.23 L/h.Conclusions: Phenoxodiol has a short plasma half-life, particularly in the free form, leading to a rapid attainment of steady state levels during continuous intravenous infusion.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000334000

Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria.

Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.)

‘Remembering as Forgetting’: Organizational commemoration as a politics of recognition

This paper considers the politics of how organizations remember their past through commemorative settings and artefacts. Although these may be seen as ‘merely’ a backdrop to organizational activity, they form part of the lived experience of organizational spaces that its members enact on a daily basis as part of their routes and routines. The main concern of the paper is with how commemoration is bound up in the reflection and reproduction of hierarchies of organizational recognition. Illustrated with reference to two commemorative settings, the paper explores how organizations perpetuate a narrow set of symbolic ideals attributing value to particular forms of organizational membership while appearing to devalue others. In doing so, they communicate values that undermine attempts to achieve equality and inclusion. Developing a recognition-based critique of this process, the discussion emphasizes how commemorative settings and practices work to reproduce established patterns of exclusion and marginalization. To this end, traditional forms of commemorative portraiture that tend to close off difference are contrasted with a memorial garden, in order to explore the potential for an alternative, recognition-based ethics of organizational commemoration that is more open to the Other

Hazard Detection Analysis for a Forward-Looking Interferometer

The Forward-Looking Interferometer (FLI) is a new instrument concept for obtaining the measurements required to alert flight crews to potential weather hazards to safe flight. To meet the needs of the commercial fleet, such a sensor should address multiple hazards to warrant the costs of development, certification, installation, training, and maintenance. The FLI concept is based on high-resolution Infrared Fourier Transform Spectrometry (FTS) technologies that have been developed for satellite remote sensing. These technologies have also been applied to the detection of aerosols and gases for other purposes. The FLI concept is being evaluated for its potential to address multiple hazards including clear air turbulence (CAT), volcanic ash, wake vortices, low slant range visibility, dry wind shear, and icing during all phases of flight (takeoff, cruise, and landing). The research accomplished in this second phase of the FLI project was in three major areas: further sensitivity studies to better understand the potential capabilities and requirements for an airborne FLI instrument, field measurements that were conducted in an effort to provide empirical demonstrations of radiometric hazard detection, and theoretical work to support the development of algorithms to determine the severity of detected hazard

Internet of Things for Sustainability: Perspectives in Privacy, Cybersecurity, and Future Trends

In the sustainability IoT, the cybersecurity risks to things, sensors, and monitoring systems are distinct from the conventional networking systems in many aspects. The interaction of sustainability IoT with the physical world phenomena (e.g., weather, climate, water, and oceans) is mostly not found in the modern information technology systems. Accordingly, actuation, the ability of these devices to make changes in real world based on sensing and monitoring, requires special consideration in terms of privacy and security. Moreover, the energy efficiency, safety, power, performance requirements of these device distinguish them from conventional computers systems. In this chapter, the cybersecurity approaches towards sustainability IoT are discussed in detail. The sustainability IoT risk categorization, risk mitigation goals, and implementation aspects are analyzed. The openness paradox and data dichotomy between privacy and sharing is analyzed. Accordingly, the IoT technology and security standard developments activities are highlighted. The perspectives on opportunities and challenges in IoT for sustainability are given. Finally, the chapter concludes with a discussion of sustainability IoT cybersecurity case studies

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood : An individual participant data meta-analysis

Background Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and findings We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestylerelated characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p <0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. Conclusions In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.Peer reviewe

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment