Technical Bulletins: Public Meeting, Open Record Laws

This Technical Bulletin discusses the Tennessee Public Meeting Law - better known as the Sunshine Law. The law (Tennessee Code Annotated 8-44-101--106) provides that all meetings of any governing body are declared to be public meetings open to the public at all times, except as provided in the Tennessee Constitution

Technical Bulletins: IRS regulations on personal use of city-owned vehicles: Complying with the final 1989 rules

On July 6, 1989, the Internal Revenue Service (IRS) published final regulations on the Taxation of Fringe Benefits, including taxation on personal use of a city-owned vehicle. This Technical Bulletin summarize the rules and advises cities on how to follow them

Integrating synchronous and asynchronous internet distributed education for maximum effectiveness

Distributed education delivered via the Internet is a growing practice, with most institutions offering at least course websites and many expanding to full course offerings and even degree offerings. There are two schools of thought with regard to delivery mode; the larger group has focused on asynchronous delivery, accessible at any time via web pages and interactive tutorials and quizzes, while a smaller group advocates synchronous delivery where students are online and interact during class time. This paper summarizes the advantages and disadvantages of the two delivery modes and describes our successful and growing experience of more than a decade using an open source synchronous delivery tool blended with a variety of asynchronous capabilities and classroom instruction. We conclude that a synergistic combination of the two modes with in-person instruction, designed to provide maximum flexibility to the student within the constraints of the subject, offers the best support for student learning.Education for the 21 st century - impact of ICT and Digital Resources ConferenceRed de Universidades con Carreras en Informática (RedUNCI

Synchronous Internet Distance Education: Wave of the Future or Wishful Thinking?

Heralded as an important future delivery means for higher education, synchronous Internet distance education with live presenters is, to date, far less often used than its counterpart asynchronous distance education which offers materials stored on a website. The author has practiced synchronous Internet teaching since 1994 at George Mason University (GMU). This practice now is increasing, with a doubling of GMU Computer Science courses taught this way each year for the past three. This paper describes the lessons learned in finding a successful way to teach synchronous over the Internet. Technologies and class organization needed for success are described and compared. The results appear to indicate that synchronous Internet distance education may in fact become an important future delivery means for higher education

Integrating synchronous and asynchronous internet distributed education for maximum effectiveness

Distributed education delivered via the Internet is a growing practice, with most institutions offering at least course websites and many expanding to full course offerings and even degree offerings. There are two schools of thought with regard to delivery mode; the larger group has focused on asynchronous delivery, accessible at any time via web pages and interactive tutorials and quizzes, while a smaller group advocates synchronous delivery where students are online and interact during class time. This paper summarizes the advantages and disadvantages of the two delivery modes and describes our successful and growing experience of more than a decade using an open source synchronous delivery tool blended with a variety of asynchronous capabilities and classroom instruction. We conclude that a synergistic combination of the two modes with in-person instruction, designed to provide maximum flexibility to the student within the constraints of the subject, offers the best support for student learning.Education for the 21 st century - impact of ICT and Digital Resources ConferenceRed de Universidades con Carreras en Informática (RedUNCI

Extensible Modeling and Simulation Framework (XMSF) Opportunities for Web-Based Modeling and Simulation

Technical Opportunities Workshop Whitepaper, 14 June 2002Purpose: As the Department of Defense (DoD) is engaged in both warfighting and institutional transformation for the new millennium, DoD Modeling & Simulation (M&S) also needs to identify and adopt transformational technologies which provide direct tactical relevance to warfighters. Because the only software systems that composably scale to worldwide scope utilize the World Wide Web, it is evident that an extensible Web-based framework shows great promise to scale up the capabilities of M&S systems to meet the needs of training, analysis, acquisition, and the operational warfighter. By embracing commercial web technologies as a shared-communications platform and a ubiquitous-delivery framework, DoD M&S can fully leverage mainstream practices for enterprise-wide software development

The effect of acute angiotensin-converting enzyme and neutral endopeptidase 24.11 inhibition on plasma extravasation in the rat

ABSTRACT The effect of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) inhibition on microvascular plasma leakage (extravasation) was evaluated in a rat model. Progressive inhibition of ACE using captopril caused increased extravasation when lung ACE was inhibited by Ͼ55%. In contrast, the selective inhibition of renal NEP by Ͼ90% using ecadotril did not increase extravasation. In NEP-inhibited rats, extravasation produced by the ACE inhibitors captopril and lisinopril was markedly enhanced. The dual ACE and NEP inhibitor omapatrilat, at oral doses of 0.03, 0.1, and 0.3 mg/kg, selectively inhibited lung ACE by 19, 61, and 76%, respectively, and did not cause significant extravasation. Doses of 1 and 10 mg/kg omapatrilat, which produced Ͼ90% inhibition of ACE and also inhibited renal NEP by 54 and 78%, respectively, significantly increased extravasation. In this model, bradykinin and substance P produced extravasation that could be abolished by the bradykinin 2 (B2) receptor antagonist Hoe 140 (icatibant) or the neurokinin1 (NK1) antagonist CP99994 [(ϩ)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine], respectively. Bradykinin induced extravasation was also partially (ϳ40%) inhibited by CP99994, indicating that a portion of the response involves B2 receptor-mediated release of substance P. In conclusion, this study is the first to relate the degree of ACE and/or NEP inhibition to extravasation liability in the rat model. Our data clearly demonstrate that ACE inhibitor-induced plasma extravasation is enhanced by concomitant inhibition of NEP. In addition, this study provides further evidence for the role for B2 and NK1 receptors in mediating plasma extravasation in the rat. Since their introduction nearly three decades ago, the angiotensin I-converting enzyme inhibitors (ACEIs) have become one of the more effective and highly used treatments for hypertension and heart failure. The therapeutic efficacy of these agents is derived in large part from their ability to inhibit the conversion of angiotensin I to angiotensin II, a vasoactive peptide whose direct vasoconstrictor and aldosterone-releasing actions promote increased blood pressure. There are some data to suggest that part of the therapeutic effect of these agents may be due to decreased breakdown of bradykinin (BK), which is also a substrate for ACE 1141 esterase inhibitor deficiency in humans leads to angioedema Materials and Methods Experimental Preparation(s). Male Sprague-Dawley strain rats weighing between 250 and 350 g were used in these studies. The procedures involving the use of rats in these experiments were reviewed and approved by the Institutional Animal Care and Use Committee in accordance with National Institutes of Health guidelines (NIH publication 85-23). The animals were housed two per cage with free access to food and water and a 12-h light/dark cycle. To determine the role of ACE and/or NEP inhibition on plasma extravasation, groups of rats received drug treatment orally using an 18-gauge dosing needle and 5-ml syringe. Approximately 50 to 55 min after dosing, the rats were anesthetized via intraperitoneal injection of 70 mg/kg sodium pentobarbital. When anesthesia was achieved (typically less than 10 min), Evans blue dye (30 mg/kg) in heparinized saline (30 U/ml) was administered intravenously at a dose volume of 0.2 ml/100 g b.wt. via the tail vein using a 26-gauge, 1.5-inch-long needle. Five minutes post-Evans blue injection, the thoracic and peritoneal cavities were opened via a single midline incision. A 0.8 to 1.0 cc blood sample was obtained by cardiac puncture using a heparinized 1-ml syringe and 23-gauge needle and placed on ice. The tip of the right atrium was then cut and a steel cannula, attached by latex tubing to a peristaltic pump (Harvard Apparatus Inc., Holliston, MA), was inserted into the heart at the bottom of the left ventricle and was slid up through ventricle until the tip of the cannula was visible in the aortic arch. The cannula was manually held in place using forceps clamped across the heart. The pump was then started and the vascular system was perfused with 120 ml of saline delivered at a rate of 40 ml/min, which results in a perfusion pressure pulse of 80 to 100 mm Hg. This procedure is similar to that described by others For determination of extravasation liability of proinflammatory peptides, rats were anesthetized by intraperitoneal injection of 70 mg/kg pentobarbital sodium. The rats then received an intravenous dose of 30 mg/kg Evans blue dye in saline containing 30 U/ml heparin administered at a dose volume of 200 l/100 g b.wt. via tail vein injection. The Evans blue injection was followed immediately by intravenous injection of bradykinin, des-Arg9-bradykinin, or substance P. In some studies, the effect of selective B2 receptor blockade with Hoe 140 (10 g/kg i.v.) or selective NK1 receptor blockade with CP99994 (3 mg/kg i.v.) on bradykinin and substance P-mediated extravasation was also determined. In those studies, the selective antagonists were administered 3 to 5 min before Evans Blue injection. Five minutes after bradykinin, des-Arg9-bradykinin, or substance P injection, the thoracic and peritoneal cavities were opened via a single midline incision, and the rat was perfused as described above. For evaluation of plasma ex vivo ACE activity, the blood collected by cardiac puncture was spun for 2 min at maximum speed in a Microfuge. Plasma was collected from the top. Thirty-five microliters of plasma was added to a conical-bottomed 96-well plate with 5 l of 1 M KCl, 0.5 M sodium borate, pH 8.3, and 3 M zinc sulfate. Ten microliters of 12.5 mM hippuryl-his-leu substrate For determination of lung ACE activity and kidney NEP activity, approximately 250 mg of tissue was homogenized in 6 volumes of 0.1 M KH 2 PO 4 , pH 8.3, 0.3 M NaCl, and 1 M ZnSO 4 using a Teflonglass motor-driven pestle. For lung ACE activity, 40 l of homogenate was added to conical-bottomed 96-well plates and warmed to 37°C for 5 min. Ten microliters of 7.5 mM hippuryl-his-leu (1.5 mM final) was added to each sample and incubated for 10 min at 37°C. One hundred microliters of 10% TCA was added to each well, and the plates were centrifuged to pellet precipitated proteins. Fifty microliters of supernatant was added to 100 l of 2 mg/ml o-phthaldialdehyde in 10% ethanol and 50 l of 1 N NaOH in a black fluorometric plate. After 60 min, the plate was read in a fluorometer at 390-nm excitation and 460-nm emission. Standard curves were generated using his-leu. Kidney NEP activity was measured by adding 35 l of homogenate to wells containing 5 l of buffer or 10 M phosphoramidon. Plates were warmed to 37°C for 5 min. Ten microliters of 2.5 mM N-dansyl-D-ala-gly-p-nitrophe-gly substrate Drugs. The selective ACE inhibitors captopril and lisinopril were dissolved in water and administered orally at doses of 0.3, 1, 3, 10, and 30 mg/kg (captopril) or 1 and 3 mg/kg (lisinopril) at a dose volume of 1.0 ml/100 g b.wt. The dual ACE/NEP inhibitor omapatrilat was dissolved in a 30% polyethylene glycol200/70% of 25% cyclodextran vehicle and was administered orally as described above at doses of 0.03, 0.1, 0.3, 1, or 10 mg/kg. The selective NEP inhibitor ecadotril was dissolved in the polyethylene glycol200/cyclodextrin vehicle and was administered orally at doses of 3, 10, neutral endopeptidase or 30 mg/kg. Sulpizio et al. In some studies, inhibition of both ACE and NEP was produced by the oral administration of various doses of the selective ACE inhibitor captopril or lisinopril in rats pretreated orally with the selective NEP inhibitor ecadotril. Statistics. All data are expressed as the mean Ϯ S.E.M. The analysis of the differences in the extravasation measurement values between levels of treatments regimes used two-sample Wilcoxon tests. Based on the assumption of increasing extravasation with larger drug doses, one-sided tests were appropriate for the identification of the lowest dosage level with a significant increase in the extravasation values. The identification of these lowest dosages applied a fixed sequence test strategy All other comparisons between dosage levels also had predetermined directions of changes in the extravasation values and used single-sided values from two-sample Wilcoxon tests. The reported p values for these comparisons were all less than 0.05 (Bonferroni adjusted p values were reported for the four comparisons of the captopril and ecadotril combinations and the two comparisons of the bradykinin and CP99994 combinations). The trend comparison for the bradykinin and Hoe combinations used the single-sided Jonckheere-Terpstra trend test. All statistical tests used SAS System Release 8.01 as the analysis software (proc npar1way for the exact Wilcoxon tests and proc freq for the Jonckheere-Terpstra test). An unpaired Student's t test was used to test the effect of drug treatment on enzyme activity. Absolute enzyme rates of drug-treated rats were compared with enzyme rates of the vehicle-treated (control) rats. Acceptance of a significant difference between the groups was at the 0.05 p value level. Results Basal extravasation of Evans blue into the trachea of 29 vehicle-treated rats accumulated over the course of these studies was 8.3 Ϯ 0.43 ng/mg tissue. Baseline plasma ACE, lung ACE, and renal NEP enzyme activity in vehicle-treated rats was 32.7 Ϯ 1.7 nmol/ml/min and 6.5 Ϯ 1.8 and 2.6 Ϯ 0.2 nmol/mg protein/min, respectively. Treatment with increasing oral doses of captopril produced dose-related inhibition of plasma and lung ACE activity and was without effect on renal NEP. The reductions in ACE activity were associated with increased extravasation as measured by tracheal Evans blue concentration Oral doses of 0.03, 0.1, and 0.3 mg/kg of the dual ACE/NEP inhibitor omapatrilat produced dramatic, dose-related inhibition of both plasma and lung ACE with no inhibition of renal NEP Effect of Increasing Lung ACE Inhibition in NEPInhibited Rats. The data with ompatrilat did not clearly define the role that NEP inhibition played in the extravasation of Evans blue into the trachea because the degree of both ACE and NEP inhibition varied with dose. To define the role of NEP in extravasation further, rats were treated with 3.0 mg/kg ecadotril, which resulted in a relatively consistent ACE/NEP Inhibition and Plasma Extravasation in Rat 1143 background inhibition of ϳ74% in renal NEP The selective ACE inhibitor lisinopril was also tested alone and in combination with ecadotril. Doses of 1 and 3 mg/kg lisinopril alone inhibited lung ACE by 63 and 83%, respectively, and did not increase tracheal Evans blue extravasatio

Bacterial flora-typing with targeted, chip-based Pyrosequencing

<p>Abstract</p> <p>Background</p> <p>The metagenomic analysis of microbial communities holds the potential to improve our understanding of the role of microbes in clinical conditions. Recent, dramatic improvements in DNA sequencing throughput and cost will enable such analyses on individuals. However, such advances in throughput generally come at the cost of shorter read-lengths, limiting the discriminatory power of each read. In particular, classifying the microbial content of samples by sequencing the < 1,600 bp 16S rRNA gene will be affected by such limitations.</p> <p>Results</p> <p>We describe a method for identifying the phylogenetic content of bacterial samples using high-throughput Pyrosequencing targeted at the 16S rRNA gene. Our analysis is adapted to the shorter read-lengths of such technology and uses a database of 16S rDNA to determine the most specific phylogenetic classification for reads, resulting in a weighted phylogenetic tree characterizing the content of the sample. We present results for six samples obtained from the human vagina during pregnancy that corroborates previous studies using conventional techniques.</p> <p>Next, we analyze the power of our method to classify reads at each level of the phylogeny using simulation experiments. We assess the impacts of read-length and database completeness on our method, and predict how we do as technology improves and more bacteria are sequenced. Finally, we study the utility of targeting specific 16S variable regions and show that such an approach considerably improves results for certain types of microbial samples. Using simulation, our method can be used to determine the most informative variable region.</p> <p>Conclusion</p> <p>This study provides positive validation of the effectiveness of targeting 16S metagenomes using short-read sequencing technology. Our methodology allows us to infer the most specific assignment of the sequence reads within the phylogeny, and to identify the most discriminative variable region to target. The analysis of high-throughput Pyrosequencing on human flora samples will accelerate the study of the relationship between the microbial world and ourselves.</p

Improving outcomes in adults with epilepsy and intellectual disability (EpAID) using a nurse-led intervention: study protocol for a cluster randomised controlled trial.

BACKGROUND: In adults with intellectual disability (ID) and epilepsy there are suggestions that improvements in management may follow introduction of epilepsy nurse-led care. However, this has not been tested in a definitive clinical trial and results cannot be generalised from general population studies as epilepsy tends to be more severe and to involve additional clinical comorbidities in adults with ID. This trial investigates whether nurses with expertise in epilepsy and ID, working proactively to a clinically defined role, can improve clinical and quality of life outcomes in the management of epilepsy within this population, compared to treatment as usual. The trial also aims to establish whether any perceived benefits represent good value for money. METHODS/DESIGN: The EpAID clinical trial is a two-arm cluster randomised controlled trial of nurse-led epilepsy management versus treatment as usual. This trial aims to obtain follow-up data from 320 participants with ID and drug-resistant epilepsy. Participants are randomly assigned either to a 'treatment as usual' control or a 'defined epilepsy nurse role' active arm, according to the cluster site at which they are treated. The active intervention utilises the recently developed Learning Disability Epilepsy Specialist Nurse Competency Framework for adults with ID. Participants undergo 4 weeks of baseline data collection, followed by a minimum of 20 weeks intervention (novel treatment or treatment as usual), followed by 4 weeks of follow-up data collection. The primary outcome is seizure severity, including associated injuries and the level of distress manifest by the patient in the preceding 4 weeks. Secondary outcomes include cost-utility analysis, carer strain, seizure frequency and side effects. Descriptive measures include demographic and clinical descriptors of participants and clinical services in which they receive their epilepsy management. Qualitative study of clinical interactions and semi-structured interviews with clinicians and participants' carers are also undertaken. DISCUSSION: The EpAID clinical trial is the first cluster randomised controlled trial to test possible benefits of a nurse-led intervention in adults with epilepsy and ID. This research will have important implications for ID and epilepsy services. The challenges of undertaking such a trial in this population, and the approaches to meeting these are discussed. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN96895428 version 1.1. Registered on 26 March 2013.Cambridgeshire and Peterborough NHS Foundation TrustThis is the final version of the article. It first appeared from BioMed Central via https://doi.org/10.1186/s13063-016-1429-