Association of a Simplified Finnegan Neonatal Abstinence Scoring Tool With the Need for Pharmacologic Treatment for Neonatal Abstinence Syndrome

Importance: Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment. Objectives: To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision. Design, Setting, and Participants: This multisite cohort study included 424 neonates with opioid exposure who had a gestational age of at least 36 weeks with follow-up from birth to hospital discharge in the derivation cohort and 109 neonates with opioid exposure from the Maternal Opioid Treatment: Human Experimental Research Study in the validation cohort. Neonates in the derivation cohort were included in a medical record review at the Universities of Louisville and Kentucky or in a randomized clinical trial and observational study conducted at Tufts University (2014-2018); the Maternal Opioid Treatment: Human Experimental Research was conducted from 2005 to 2008. Data analysis was conducted from May 2017 to August 2019. Exposures: Prenatal opioid exposure. Main Outcomes and Measures: All FNAST items were dichotomized as present or not present, and logistic regression was used to identify binary items independently associated with pharmacologic treatment. The final model was validated with an independent cohort of neonates with opioid exposure. Results: Among 424 neonates (gestational age, ≥36 weeks; 217 [51%] female infants), convulsions were not observed, and high-pitched cry and hyperactive Moro reflex had extremely different frequencies across cohorts. Therefore, these 3 FNAST items were removed from further analysis. The 2 tremor items were combined, and 8 of the remaining 17 items were independently associated with pharmacologic treatment, with an area under the curve of 0.86 (95% CI, 0.82-0.89) compared with 0.90 (95% CI, 0.87-0.94) for the 21-item FNAST. External validation of the 8 items resulted in an area under the curve of 0.86 (95% CI, 0.79-0.93). Thresholds of 4 and 5 on the simplified scale yielded the closest agreement with FNAST thresholds of 8 and 12 (weighted κ = 0.55; 95% CI, 0.48-0.61). Conclusions and Relevance: The findings of this study suggest that 8 signs of NAS may be sufficient to assess whether a neonate meets criteria for pharmacologic therapy. A focus on these signs could simplify the FNAST tool and may enhance its clinical utility

Roadmaps to Utopia: Tales of the Smart City

Notions of the Smart City are pervasive in urban development discourses. Various frameworks for the development of smart cities, often conceptualized as roadmaps, make a number of implicit claims about how smart city projects proceed but the legitimacy of those claims is unclear. This paper begins to address this gap in knowledge. We explore the development of a smart transport application, MotionMap, in the context of a £16M smart city programme taking place in Milton Keynes, UK. We examine how the idealized smart city narrative was locally inflected, and discuss the differences between the narrative and the processes and outcomes observed in Milton Keynes. The research shows that the vision of data-driven efficiency outlined in the roadmaps is not universally compelling, and that different approaches to the sensing and optimization of urban flows have potential for empowering or disempowering different actors. Roadmaps tend to emphasize the importance of delivering quick practical results. However, the benefits observed in Milton Keynes did not come from quick technical fixes but from a smart city narrative that reinforced existing city branding, mobilizing a growing network of actors towards the development of a smart region. Further research is needed to investigate this and other smart city developments, the significance of different smart city narratives, and how power relationships are reinforced and constructed through them

Status of the VERITAS Observatory

VERITAS, an Imaging Atmospheric Cherenkov Telescope (IACT) system for gammma-ray astronomy in the GeV-TeV range, has recently completed its first season of observations with a full array of four telescopes. A number of astrophysical gamma-ray sources have been detected, both galactic and extragalactic, including sources previously unknown at TeV energies. We describe the status of the array and some highlight results, and assess the technical performance, sensitivity and shower reconstruction capabilities.Comment: Submitted to Proceedings of "4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy 2008

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

A connection between star formation activity and cosmic rays in the starburst galaxy M 82

Although Galactic cosmic rays (protons and nuclei) are widely believed to be dominantly accelerated by the winds and supernovae of massive stars, definitive evidence of this origin remains elusive nearly a century after their discovery [1]. The active regions of starburst galaxies have exceptionally high rates of star formation, and their large size, more than 50 times the diameter of similar Galactic regions, uniquely enables reliable calorimetric measurements of their potentially high cosmic-ray density [2]. The cosmic rays produced in the formation, life, and death of their massive stars are expected to eventually produce diffuse gamma-ray emission via their interactions with interstellar gas and radiation. M 82, the prototype small starburst galaxy, is predicted to be the brightest starburst galaxy in gamma rays [3, 4]. Here we report the detection of >700 GeV gamma rays from M 82. From these data we determine a cosmic-ray density of 250 eV cm-3 in the starburst core of M 82, or about 500 times the average Galactic density. This result strongly supports that cosmic-ray acceleration is tied to star formation activity, and that supernovae and massive-star winds are the dominant accelerators.Comment: 18 pages, 4 figures; published in Nature; Version is prior to Nature's in-house style editing (differences are minimal

Discovery of Very High-Energy Gamma-Ray Radiation from the BL Lac 1ES 0806+524

The high-frequency-peaked BL-Lacertae object \objectname{1ES 0806+524}, at redshift z=0.138, was observed in the very-high-energy (VHE) gamma-ray regime by VERITAS between November 2006 and April 2008. These data encompass the two-, and three-telescope commissioning phases, as well as observations with the full four-telescope array. \objectname{1ES 0806+524} is detected with a statistical significance of 6.3 standard deviations from 245 excess events. Little or no measurable variability on monthly time scales is found. The photon spectrum for the period November 2007 to April 2008 can be characterized by a power law with photon index $3.6 \pm 1.0_{\mathrm{stat}} \pm 0.3_{\mathrm{sys}}$ between $\sim$300 GeV and $\sim$700 GeV. The integral flux above 300 GeV is $(2.2\pm0.5_{\mathrm{stat}}\pm0.4_{\mathrm{sys}})\times10^{-12}\:\mathrm{cm}^{2}\:\mathrm{s}^{-1}$ which corresponds to 1.8% of the Crab Nebula flux. Non contemporaneous multiwavelength observations are combined with the VHE data to produce a broadband spectral energy distribution that can be reasonably described using a synchrotron-self Compton model.Comment: 14 pages, 4 figures, accepted to APJ

Discovery of very high energy gamma rays from PKS 1424+240 and multiwavelength constraints on its redshift

We report the first detection of very-high-energy (VHE) gamma-ray emission above 140 GeV from PKS 1424+240, a BL Lac object with an unknown redshift. The photon spectrum above 140 GeV measured by VERITAS is well described by a power law with a photon index of 3.8 +- 0.5_stat +- 0.3_syst and a flux normalization at 200 GeV of (5.1 +- 0.9_stat +- 0.5_syst) x 10^{-11} TeV^-1 cm^-2 s^-1, where stat and syst denote the statistical and systematical uncertainty, respectively. The VHE flux is steady over the observation period between MJD 54881 and 55003 (2009 February 19 to June 21). Flux variability is also not observed in contemporaneous high energy observations with the Fermi Large Area Telescope (LAT). Contemporaneous X-ray and optical data were also obtained from the Swift XRT and MDM observatory, respectively. The broadband spectral energy distribution (SED) is well described by a one-zone synchrotron self-Compton (SSC) model favoring a redshift of less than 0.1. Using the photon index measured with Fermi in combination with recent extragalactic background light (EBL) absorption models it can be concluded from the VERITAS data that the redshift of PKS 1424+240 is less than 0.66.Comment: accepted for publication, Ap

Induction of Membrane Ceramides: A Novel Strategy to Interfere with T Lymphocyte Cytoskeletal Reorganisation in Viral Immunosuppression

Silencing of T cell activation and function is a highly efficient strategy of immunosuppression induced by pathogens. By promoting formation of membrane microdomains essential for clustering of receptors and signalling platforms in the plasma membrane, ceramides accumulating as a result of membrane sphingomyelin breakdown are not only essential for assembly of signalling complexes and pathogen entry, but also act as signalling modulators, e. g. by regulating relay of phosphatidyl-inositol-3-kinase (PI3K) signalling. Their role in T lymphocyte functions has not been addressed as yet. We now show that measles virus (MV), which interacts with the surface of T cells and thereby efficiently interferes with stimulated dynamic reorganisation of their actin cytoskeleton, causes ceramide accumulation in human T cells in a neutral (NSM) and acid (ASM) sphingomyelinase–dependent manner. Ceramides induced by MV, but also bacterial sphingomyelinase, efficiently interfered with formation of membrane protrusions and T cell spreading and front/rear polarisation in response to β1 integrin ligation or αCD3/CD28 activation, and this was rescued upon pharmacological or genetic ablation of ASM/NSM activity. Moreover, membrane ceramide accumulation downmodulated chemokine-induced T cell motility on fibronectin. Altogether, these findings highlight an as yet unrecognised concept of pathogens able to cause membrane ceramide accumulation to target essential processes in T cell activation and function by preventing stimulated actin cytoskeletal dynamics