a case study

This paper is based on an explorative case study of all.department e-mails that were sent on the Intranet of a Danish university department. Following a social constructionist approach, our analysis assumes that language use shapes relations, identities, and representations. We thus investigate which social relations are expressed and constructed in the e-mail discourse and how the organizational world of the department is represented in the all.department e-mails. Our analyses of the e-mails show that the managerial voices are dominant as well as the perception of e-mail communication as a tool of information transmission. However, a few e-mails sent by employees without specific organizational functions differ significantly from the "managerial" mails. In these mails employee voices articulate a latent and unfulfilled need for a community and a forum for dialogue. The usage of the all.department e-mail communication is also related to the ongoing change of managing university departments in Denmark

Effects of the TLR2 Agonists MALP-2 and Pam3Cys in Isolated Mouse Lungs

Background: Gram-positive and Gram-negative bacteria are main causes of pneumonia or acute lung injury. They are recognized by the innate immune system via toll-like receptor-2 (TLR2) or TLR4, respectively. Among all organs, the lungs have the highest expression of TLR2 receptors, but little is known about the pulmonary consequences of their activation. Here we studied the effects of the TLR2/6 agonist MALP-2, the TLR2/1 agonist Pam 3Cys and the TLR4 agonist lipopolysaccharide (LPS) on pro-inflammatory responses in isolated lungs. Methodology/Principal Findings: Isolated perfused mouse lungs were perfused for 60 min or 180 min with MALP-2 (25 ng/ mL), Pam3Cys (160 ng/mL) or LPS (1 mg/mL). We studied mediator release by enzyme linked immunosorbent assay (ELISA), the activation of mitogen activated protein kinase (MAPK) and AKT/protein kinase B by immunoblotting, and gene induction by quantitative polymerase chain reaction. All agonists activated the MAPK ERK1/2 and p38, but neither JNK or AKT kinase. The TLR ligands upregulated the inflammation related genes Tnf, Il1b, Il6, Il10, Il12, Ifng, Cxcl2 (MIP-2a) and Ptgs2. MALP-2 was more potent than Pam 3Cys in inducing Slpi, Cxcl10 (IP10) and Parg. Remarkable was the strong induction of Tnc by MALP2, which was not seen with Pam 3Cys or LPS. The growth factor related genes Areg and Hbegf were not affected. In addition, all three TLR agonists stimulated the release of IL-6, TNF, CXCL2 and CXCL10 protein from the lungs

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Regulation of acute lung injury by the sympathetic nervous system and neuropeptide Y

The acute respiratory distress syndrome (ARDS) is a life-threatening medical condition caused by insults to the lung. Since ventilation strategies are critical for the outcome of ARDS patients, experimental models of ventilator-induced lung injury (VILI) are frequently used. Unfortunately, many models of VILI are poorly defined. There is a strong need for models, which focus on oxygenation, the most important clinical aspect of ARDS and also provide substantial information about relevant physiological parameters. Consequently, one aim was to develop an experimental VILI model that is characterised by ARDS-like hypoxemia and controlled by inflammation. This study shows that lung failure occurs rapidly once peak airway pressure exceeds 24 cmH2O and leads to diminished pulmonary compliance, hypoxemia and edema formation. Alongside several inflammatory mediators, neuropeptide Y (NPY) expression was strongly increased. Anti-inflammatory treatment with steroids attenuated inflammation, but did not prevent lung injury, strongly indicating a mechanical failure of the lung. Moreover, the present study demonstrates that maximising the duration of experimental ventilation protocols is crucial.The sympathetic nervous system (SNS) acts via the neurotransmitters norepinephrine, adenosine triphosphate and NPY, which are co-released. The SNS innervates the lung and is involved in different inflammatory processes. Most immune-modulatory effects of NPY are mediated by the Y1 receptor. One goal of the present study was to address the role of NPY and its receptor in ARDS. This thesis reports that ventilation together with a second insult (acid inspiration) is leading to a mild lung injury with increased levels of NPY. Administration of an Y1 receptor agonist is leading to increased pro-inflammatory mediators and deteriorated lung functions. Similar effects were obtained with an Y1 receptor antagonist. This could be due to increased signalling via the Y2/Y5 receptors and needs further research.A further common cause of ARDS is pneumonia induced by influenza virus infection. Therefore, the present study aimed to investigate the participation of NPY in the pathogenesis of ARDS caused by influenza virus. In summary, it was shown that besides well-known pro-inflammatory mediators pulmonary NPY levels were increased as well. Knockout of NPY significantly improved survival of mice infected with influenza viruses. Virus replication decreased while anti-viral and anti-inflammatory genes showed increased expression.Overall, this study demonstrates that NPY is activated in inflammatory processes in the lung and holds a crucial role in regulating respiratory infections

Towards Digital Constitutionalism? Mapping Attempts to Craft an Internet Bill of Rights

The idea of an “Internet Bill of Rights” is by no means a new one: in fact, serious efforts to draft such a document can be traced at least as far back as the mid-1990s. Though the form, function and scope of such initiatives has evolved, the concept has had remarkable staying power, and now — two full decades later — principles which were once radically aspirational have begun to crystallize into law. In this paper, we propose a unified term to describe these efforts using the umbrella of “digital constitutionalism” and conduct an analysis of thirty initiatives spanning from 1999 to 2015. These initiatives have great differences, and range from advocacy statements to official positions of intergovernmental organizations to proposed legislation. However, in their own way, they are each engaged in the same conversation, seeking to advance a relatively comprehensive set of rights, principles, and governance norms for the Internet, and are usefully understood as part of a broader proto-constitutional discourse. While this paper does not attempt to capture every facet of this complex political behavior, we hope to offer a preliminary map of the landscape, provide a comparative examination of these diverse efforts toward digital constitutionalism, and — most importantly — provoke new questions for further research and study. The paper proceeds in four parts, beginning with a preliminary definition for the concept of digital constitutionalism and a summary of our research methodology. Second, we present our core observations related to the full range of substantive rights, principles and themes proposed by these initiatives. Third, we build on that analysis to explore their perceived targets, the key actors and deliberative processes which have informed their character, and the changes in their substantive content over time. Finally, we look forward, identifying future directions for research in this rapidly changing policy arena and for the broader Internet governance community

Nebenwirkungsmeldungen in Deutschland: Aktuelles und Hintergründe

Das Wissen um die Sicherheit von Arzneimitteln zum Zeitpunkt ihrer Markteinführung ist begrenzt. Spezifische Risiken eines neuen Wirkstoffes oder einer neuen Kombination etablierter Wirkstoffe oder auch nur einer neuen Darreichungsform in der breiten ärztlichen Anwendung, beispielsweise für bestimmte Patientengruppen, zeigen sich manchmal erst Jahre nach der Zulassung des Arzneimittels. Aufgabe der Pharmakovigilanz ist es, die Sicherheit von Arzneimitteln kontinuierlich zu überwachen, d.h., alle Daten und Informationen auszuwerten, die zu einem Arzneimittel bekannt werden. Neben wissenschaftlicher Literatur und Studienberichten sind insbesondere die Fallberichte zu Nebenwirkungen Gegenstand dieser Untersuchungen. Es bedarf daher der intensiven Mitwirkung von Ärzten, Apothekern und Patienten, da ohne deren Meldungen über Nebenwirkungen keine solche Beurteilung möglich ist. Obwohl seit vielen Jahren, insbesondere bei Patientenmeldungen, ein deutlicher Anstieg der Meldezahlen festzustellen ist, legt die Entwicklung der aktuellen Meldezahlen an das BfArM die Vermutung nahe, dass das aktuelle Pandemiegeschehen dazu führt, dass ein signifikanter Anteil von Nebenwirkungen ohne Vakzinbezug nicht gemeldet wird, also ein Underreporting von Nebenwirkungsfällen, die nicht mit Covid-19-Impfungen assoziiert sind, vorliegt

Cluster analysis of the gene expression data.

<p>After 60 min of perfusion under baseline conditions, isolated mouse lungs were perfused for another 180 min with Pam₃Cys (160 ng/mL, n = 5), MALP-2 (25 ng/mL, n = 5), LPS (1 µg/mL, n = 3) or under control conditions (n = 5). The different colors (red, brown, green, blue) identify genes that clustered together.</p