Information Sharing in the Regulatory Context Gil-Garcia, J. Ramon; Pardo, Theresa A.; Sutherland, Megan K.
Proceedings of the 9th International Conference on Theory and Practice of Electronic Governance,
03/2016
Conference Proceeding
Odprti dostop
Cross-Boundary Information Sharing (CBIS) has become increasingly important for public and private sector entities around the world. Studies critical to advancing what is known, have focused ...primarily on information sharing and integration among government entities at the same level of government or between governments from different levels. Within the context of government regulation, information sharing typically occurs among a more diverse network of actors and processes with overlapping regulatory responsibilities and information needs. The variety of actors and overlapping regulatory relationships can contribute to a gap between the level and nature of information sharing required for individual actors to meet their obligations. This ongoing research paper looks at the socio-technical nature of information sharing among public and private sector actors and examines what is known about public-public and private-private CBIS sector in order to inform future research..
Introduction: Factor XI (FXI) deficiency is an autosomally inherited bleeding disorder characterised by an increased risk of excessive bleeding following trauma or surgery. However, considerable ...phenotypic heterogeneity of the bleeding tendency is observed between individuals with this disorder. Treatment options for patients requiring FXI replacement are fresh frozen plasma (preferably pathogen-inactivated) or FXI concentrate. Two FXI concentrates are available: Hemoleven® ( LFB Biomedicaments, Les Ulis, France) and Factor XI Concentrate (Bio-Products Laboratory (BPL), Elstree, UK). Guidelines previously recommended a maximum replacement dose of 30 U/Kg for both concentrates but more recently a lower dose of 10-15 U/kg has been advised. The two FXI concentrates may reduce bleeding risk in FIX deficiency following surgery but indications for their use are unclear and treatment in some cases has been associated with thrombosis.
Aims: To quantify thrombin generation in major FXI deficiency (FXI:C <15 IU/dL) and to compare the in vitro effects of both FXI concentrates on thrombin generation parameters in this population with each other and with reference range values. To assess the clinical relevance of in vitro results through comparison of thrombin generation following in vitro and in vivo FXI replacement in individuals requiring surgery.
Methods: Thrombin generation (TG) was measured in controls (n=50), in individuals with FXI deficiency ( FXI < 15 IU/dL) pre and post in vitro spiking with both FXI concentrates (n=10), and in ex vivo samples following treatment with BPL FXI concentrate (n=3). Blood was drawn into S-Monovette® tubes (Sarstedt, Leicester, U.K.) containing 0.106 M trisodium citrate (1:9, V:V) and corn trypsin inhibitor (CTI) (Haematologic Technologies Inc., Essex Junction, VT, U.S.A.), at a concentration of 20 µg/mL whole blood. Thrombin generation was measured in platelet rich plasma using the Calibrated Automated Thrombography method with a tissue factor trigger of 0.5pM. Statistical analysis was performed using GraphPad prism, version 6 software package (GraphPad, san Diego, CA, USA) using student’s t-test, Mann-Whitney U test or a Wilcoxon signed rank test according to data distribution. P value <0.05 was considered significant.
Results: Major FXI deficiency (FXI:C <15 IU/dL) was associated with significantly impaired TG compared to controls, demonstrating reduced endogenous thrombin potential (ETP), peak height and velocity (all p<0.0001) and prolonged time to peak (p = 0.021). All TG parameters significantly improved from baseline with FXI replacement with both concentrates in vitro (equivalent in vivo dose 10 U/Kg). Comparison of the two FXI concentrates demonstrated that LFB Hemoleven® had greater effect on TG than BPL FXI in vitro at all doses (equivalent in vivo doses 10, 20 and 30 U/Kg): higher ETP (p < 0.0001), peak height (p < 0.01) velocity (p < 0.0002) and shorter lag time and time to peak (both p < 0.003). However, some measurements with LFB Hemoleven® exceeded the reference range. At lower doses both FXI concentrates normalised TG parameters in vitro (equivalent in vivo dose 2.5 IU/Kg LFB Hemoleven® or 5 U/Kg BPL FXI). Three patients received in vivo treatment with BPL FXI concentrate prior to surgery. TG was compared between baseline, in vitro spiked and post infusion ex vivo samples. Comparable ETP and peak height results were obtained from in vitro spiked and post infusion ex vivo samples.
Conclusions: Individuals with FXI:C levels <15 IU/dL show impaired thrombin generation. Both FXI concentrates improve thrombin generation in vitro in patients with FXI deficiency. However, when tested in vitro with the TG assay, the concentrates differ in potency and dose response and for both concentrates, doses lower than present recommendations normalised thrombin generation. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement for the BPL product.
Acknowledgments: This work is supported by a Fellowship Project Award from the Bayer Hemophilia Awards Program, an unrestricted grant from LFB Biotechnologies and a Wycherley Fellowship grant. Hemoleven® concentrate was kindly provided by LFB Biotechnologies.
Pike:Bayer: Honoraria, Research Funding; LFB Biotechnologies: Honoraria, Research Funding. Bolton-Maggs:Bio-Products Laboratory (U.K.): Consultancy; LFB Biotechnologies: Consultancy.
Abstract only Neonatal oxidative stress is a major postnatal deleterious factor predisposing preterm born infants to classical complications of prematurity (retinopathy, bronchopulmonary dysplasia) ...which are characterized by impaired vascular development. Our group has previously shown that rats transiently exposed to high O2 as newborns (mimicking human preterms oxidative stress conditions) develop high blood pressure (BP), cardiac remodeling and dysfunction later in life, in part mediated by the renin angiotensin system (RAS). Cardiac RAS activation is characterized by AT1/AT2 receptors imbalance, with increased AT1R at adult age. In order to study the role of RAS at early stages of the developmental programming of cardiac dysfunction caused by high O2 exposure, we assessed whether an early and short-term treatment with AT1R blocker Losartan, prevents cardiac alterations at young male 4 wks-old rats (prior to the elevation of BP in this model). Sprague-Dawley newborns rats were kept with their mother in 80% O2 (O2 group, n=9) or room air (Ctrl, n=9) from days 3-10 of life (P3-P10). Losartan (LOS, n=10, 20 mg/Kg) or water was administered by gavage in O2 rats from P8-P10 (last 2 days of O2 to avoid impact on nephrogenesis). At 4 wks, echocardiography reveals that O2 rats have decreased fraction of shortening compared to Ctrl (FS: 37±2 vs 42±2 %), suggesting impaired systolic function in O2. Cardiac hypertrophy evaluated by heart/body weight and cardiomyocyte surface area (CSA) is also increased in O2 vs Ctrl (141±13 vs 118±4 μm2). LOS treatment prevented the impairment of systolic function in O2 by ameliorating FS (43±2 %) and reducing CSA (121±11 μm2). LOS treatment also modulated RAS genes expression (RT-PCR): LOS restored AT1/AT2 balance in O2 hearts by decreasing AT1b subunit (0.8±0.2 O2 vs 1.3±0.3 O2+LOS vs 0.9±0.2 Ctrl) as well as increasing ACE2 (1.5±0.4 O2 vs 0.8±0.1 O2+LOS vs 1.1±0.4 Ctrl) expressions. In conclusion, a short-term treatment with LOS during neonatal O2 exposure prevents the impairment of cardiac systolic function and hypertrophy at young age. This data reinforces the key role of RAS in the developmental programming of cardiac dysfunction and reveals LOS as an effective strategy to prevent early cardiac alterations caused by neonatal high O2 exposure.
Abstract only Preterm infants are exposed to high oxygen (O2) pressure (relative to intrauterine levels) leading to systemic oxidative stress and impaired vascular development; as children and ...adults, preterm born subjects have higher blood pressure. In rats, high O2 exposure induces vascular dysfunction, in part mediated by the renin angiotensin system (RAS). However, impact of neonatal high O2 exposure on heart development and whether RAS activation prevails in the heart is unknown. We aimed to assess early heart alterations and activation of RAS after neonatal high O2 exposure. METHODS AND RESULTS: Sprague-Dawley pups were kept with their mother in 80% O2 (O2, n=8) or room air (Ctrl, n=8) from days 3-10 of life. Hearts were extracted at day 3 (pre O2-exposure, P3), day 5 (during, P5), 10 (after, P10) and 4 wks to assess myocardium hypertrophy (HE), fibrosis (Masson’s trichrome) and RAS components gene expressions by RT-PCR. Echocardiography was performed at 4 weeks to assess heart function. RAS components mRNA expression in O2 vs Ctrls shows up-regulation of AT1a and ACE2 genes at P5 (AT1a: 152±28 vs 58±16/ACE2: 140±20 vs 77±6% of P3) and P10 (AT1a: 374±35 vs 250±30 /ACE2: 326±70 vs 208±18% of P3) relative to values at P3. With age, AT1b and AT2 expressions decrease in Ctrls, whereas are maintained in O2-exposed rats to values similar to P3 (Ctrl vs O2, P5: AT1b: 18±5 vs 71±12/AT2: 48±20 vs 120±16; P10: AT1b: 33±9 vs 105±26/AT2: 27±8 vs 77±7% of P3). At P10, cardiomyocyte surface area is increased in O2 vs Ctrls (4.9±0.2 vs 2.9±0.1 μm2). At 4 wks, O2 group show increased fibrosis (49±4 vs 29±2 % pixels), left ventricular (LV) cavity diameter (3.6±0.2 vs 3.0±0.1 mm) and systolic dysfunction by decreased fraction of shortening (39±2 vs 47±2 %). AT1b gene expression (2.6±1.7 vs 0.3±0.2) is increased and AT2 receptor (7.5±0.9 vs 6.0±0.6) is decreased in O2 group vs Ctrl. CONCLUSION: Neonatal O2 exposure activates RAS in hearts. AT1 receptor is up-regulated at all ages studied in O2-exposed rat hearts while AT2 is up-regulated at P5 and P10. At 4 wks, AT1/AT2 imbalance prevails in O2 group hearts along with LV dysfunction and enhanced fibrosis and hypertrophy. RAS activation by neonatal O2-exposure might significantly impact in heart development and programming of cardiac dysfunction in rats.
A shared information resource to fight urban blight Cook, Meghan E.; Sutherland, Megan K.
Proceedings of the 16th Annual International Conference on Digital Government Research,
05/2015
Conference Proceeding
Blighted and vacant properties are a persistent and costly problem for cities throughout the world. Governments are typically charged with addressing the issues associated with urban and as many work ...to address the problem within their own jurisdiction, they are learning that sharing information and resources across the city boundaries can give them critical leverage to be more proactive in their strategies. This management paper describes the challenges and opportunities of selected New York State cities as they begin a multi-city project to develop a shared information resource to fight the blight.
Preterm neonates are exposed at birth to high oxygen concentrations relative to the intrauterine environment. We have previously shown in a rat model that a hyperoxic insult results in a reduced ...nephron number in adulthood. Therefore, the aim of this study was to determine the effects of transient neonatal hyperoxia exposure on nephrogenesis. Sprague-Dawley rat pups were raised in 80% O.sub.2 or room air from P3 to P10. Pups (n = 12/group, 6 males and 6 females) were sacrificed at P5 (during active nephrogenesis) and at P10 (after the completion of nephrogenesis). Hyperoxia exposure resulted in a significant reduction in both nephrogenic zone width and glomerular diameter at P5, and a significantly increased apoptotic cell count; however, nephron number at P10 was not affected. HIF-1alpha expression in the developing kidney was significantly reduced following hyperoxia exposure. Systemic administration of the HIF-1alpha stabilizer dimethyloxalylglycine (DMOG) resulted in enhanced expression of HIF-1alpha and improved nephrogenesis: kidneys from hyperoxia-exposed pups treated with DMOG exhibited a nephrogenic zone width and glomerular diameter similar to room-air controls. These findings demonstrate that neonatal hyperoxia exposure results in impaired nephrogenesis, which may be at least in part HIF-1alpha-mediated. Although nephron number was not significantly reduced at the completion of nephrogenesis, early indicators of maldevelopment suggest the potential for accelerated nephron loss in adulthood. Overall, this study supports the premise that prematurely born neonates exposed to high oxygen levels after birth are vulnerable to impaired renal development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Preterm birth prematurely exposes the immature heart to the haemodynamic transition at birth, which has the potential to induce abnormal cardiac remodelling. Magnetic resonance imaging studies in ...young adults born preterm have shown abnormalities in the gross structure of the ventricles (particularly the right ventricle; RV), but the cellular basis of these alterations is unknown. The aim of this study, conducted in sheep, was to determine the effect of moderate preterm birth on RV cellular structure and function in early adulthood. Male singleton lambs were delivered moderately preterm (132 ± 1 days; n = 7) or at term (147 ± 1 days; n = 7). At 14.5 months of age, intra-arterial blood pressure and heart rate were measured. Pulmonary artery diameter and peak systolic blood flow were determined using ultrasound imaging, and RV stroke volume and output calculated. Cardiomyocyte number, size, nuclearity, and levels of cardiac fibrosis were subsequently assessed in perfusion-fixed hearts using image analysis and stereological methods. Blood pressure (systolic, diastolic and mean), heart rate, levels of myocardial fibrosis and RV stroke volume and output were not different between groups. There was, however, a significant reduction in RV wall thickness in preterm sheep, and this was accompanied by a significant reduction in peak systolic blood flow in the pulmonary artery and in RV cardiomyocyte number. Cellular changes in the RV wall and reduced pulmonary artery blood flow following preterm birth have the potential to adversely impact cardiac and respiratory hemodynamics, especially when the cardiovascular system is physiologically or pathologically challenged. This article is protected by copyright. All rights reserved.
Recent disasters have highlighted the gap between existing urbancentric resilience models and the needs of rural communities, which are frequently marginalized. Large rural constituencies, ...encompassing vast and sparsely populated areas, lack broadband connectivity and rely predominantly on volunteer-based emergency workforce. The above are some of the key factors hampering rural first responders? ability to access, act upon and disseminate emergency-related information. This has an adverse effect on both residents and the agencies that serve them, as it limits residents? ability to prepare for emergencies and compromises the safety of first responders. Furthermore, the unique socio-economic structure of rural areas makes them particularly vulnerable to the effects of incipient or unfolding disasters. Hence, rural communities often develop self-reliance capabilities by creating tightknit social structures and taking charge of their own technological progress through community-driven efforts.
PDF
