The Alpha 7 Nicotinic Acetylcholine Receptor Does Not Affect Neonatal Brain Injury

Inflammation plays a central role in the development of neonatal brain injury. The alpha 7 nicotinic acetylcholine receptor (α7nAChR) can modulate inflammation and has shown promising results as a treatment target in rodent models of adult brain injury. However, little is known about the role of the α7nAChR in neonatal brain injury. Hypoxic-ischemic (HI) brain injury was induced in male and female C57BL/6 mice, α7nAChR knock-out (KO) mice and their littermate controls on postnatal day (PND) 9–10. C57BL/6 pups received i.p. injections of α7nAChR agonist PHA 568487 (8 mg/kg) or saline once daily, with the first dose given directly after HI. Caspase-3 activity and cytokine mRNA expression in the brain was analyzed 24 h after HI. Motor function was assessed 24 and 48 h after HI, and immunohistochemistry was used to assess tissue loss at 24 h and 7 days after HI and microglial activation 7 days after HI. Activation of α7nAChR with the agonist PHA 568487 significantly decreased CCL2/MCP-1, CCL5/RANTES and IL-6 gene expression in the injured brain hemisphere 24 h after HI compared with saline controls in male, but not female, pups. However, α7nAChR activation did not alter caspase-3 activity and TNFα, IL-1β and CD68 mRNA expression. Furthermore, agonist treatment did not affect motor function (24 or 48 h), neuronal tissue loss (24 h or 7 days) or microglia activation (7 days) after HI in either sex. Knock-out of α7nAChR did not influence neuronal tissue loss 7 days after HI. In conclusion, targeting the α7nAChR in neonatal brain injury shows some effect on dampening acute inflammatory responses in male pups. However, this does not lead to an effect on overall injury outcome

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Picture books that scare adults : A picture book analysis of a selection of Gro Dahles and Svein Nyhus children's books

I denna uppsats analyseras Gro Dahles och Svein Nyhus bilderböcker Snäll (2008), Den Arge (2009) och Akvarium (2015) ur ett etnometodologiskt görande-perspektiv och ett symboliskt interaktionistiskt synsätt kring känslor. Analysen är en kvalitativ bilderboksanalys och syftet är att bidra med en fördjupad förståelse kring litteratur som pedagogiskt verktyg i arbetet kring svårpratade ämnen i förskolan. Det framkom att bilderböcker kan utgöra ett adekvat, pedagogiskt verktyg i arbetet kring svårpratade ämnen i förskolan. Genom att arbeta med litteratur som behandlar svårpratade ämnen i förskolan skapas förutsättning för barn att känna igen sig i situationer som litteraturen innehåller. Barnen kan då koppla sina egna erfarenheter och sammanhang till litteraturens handling och bearbeta sin egen verklighet genom bilderböckernas föreställningsvärldar. This essay consists of an analysis of Gro Dahles and Svein Nyhus picture books Snäll (2008), Den Arge (2009) and Akvarium (2015) from an ethnomethodological perspective of agency and a symbolic interactionist perspective of emotions. The analysis is a qualitative picture book analysis with the aim to contribute to a deeper understanding of literature as a pedagogical tool when working with difficult topics in preschool education. It appeared that picture books can contribute as an adequate, pedagogical tool in working with difficult topics in preschool education. Working with literature that refers to difficult topics can create conditions where children can recognize themselves through the content of the book. Therefore, they can relate their own experiences to the content and process their own reality through imaginary worlds of the picture books

The Development of Debt Policies : A Case Study of Investor’s and Industrivärden’s Portfolio Companies

Debt financing can be seen as both an opportunity to increase profits as well as a financial risk and is thus an important issue for company owners to consider. This study examines the portfolio companies of the investment firms Investor and Indsutrivärden, and how their debt policies have developed from 2004 to 2022. In addition, factors that have been taken into consideration in their debt decisions are studied as well. The thesis uses a mixed methods approach by creating time series of debt levels and by conducting a content analysis of the companies’ reports and presentations. The findings show that Investor’s and Industrivärden’s portfolio companies take similar approaches to their debt policies. However, changes in the debt policies of Industrivärden’s portfolio companies indicate an impact of leadership changes within Industrivärden. Generally, the companies try to minimise the risks of their debt, considering factors such as liquidity and refinancing, financial flexibility, and credit ratings. Macroeconomic risks are also considered, which is exemplified in the management of debt maturities. Over time, an increased focus on green financing and the use of the debt-to-EBITDA ratio is identified. Consequently, the thesis contributes to the literature on corporate debt and ownership

"It’s time to shape up, lets sing!" : A qualitative study about how preschool teachers express the meaning of singing in preschool.

Studiens syfte är att undersöka hur några förskollärare uttrycker vad sång har för mening i förskolan. Frågeställningarna som har besvarats lyder: I vilka sammanhang används sång i förskolan? Hur beskriver förskollärare deras upplevelser av vad sång har för syfte i förskolan? Studien har genomförts genom en kvalitativ metod, med utgångspunkt i sex semistrukturerade intervjuer med förskollärare. Den teoretiska utgångspunkten är fenomenologi och resultatet har bearbetats utifrån begreppen: mening, erfarenheter och upplevelser. Resultatet visar att sångens mening kommer till uttryck på en variation av sätt eftersom varje människas upplevelser är unika. Ett av dessa sätt att förstå sångens mening beskrivs som en pedagogisk mening som är riktad mot ett lärande. Resultatet visar alltså dels på hur sången används som ett hjälpmedel för lärande och utveckling. En annan beskrivning som lyfts är sången som ett relationellt meningsskapande som bidrar till glädje. Resultatet visar även att förskollärarnas tidigare erfarenheter och upplevelser av sång påverkar sångens mening i förskolan. Slutsatsen landar i att sången har en betydelsefull mening som bör prioriteras.

"It’s time to shape up, lets sing!" : A qualitative study about how preschool teachers express the meaning of singing in preschool.

Studiens syfte är att undersöka hur några förskollärare uttrycker vad sång har för mening i förskolan. Frågeställningarna som har besvarats lyder: I vilka sammanhang används sång i förskolan? Hur beskriver förskollärare deras upplevelser av vad sång har för syfte i förskolan? Studien har genomförts genom en kvalitativ metod, med utgångspunkt i sex semistrukturerade intervjuer med förskollärare. Den teoretiska utgångspunkten är fenomenologi och resultatet har bearbetats utifrån begreppen: mening, erfarenheter och upplevelser. Resultatet visar att sångens mening kommer till uttryck på en variation av sätt eftersom varje människas upplevelser är unika. Ett av dessa sätt att förstå sångens mening beskrivs som en pedagogisk mening som är riktad mot ett lärande. Resultatet visar alltså dels på hur sången används som ett hjälpmedel för lärande och utveckling. En annan beskrivning som lyfts är sången som ett relationellt meningsskapande som bidrar till glädje. Resultatet visar även att förskollärarnas tidigare erfarenheter och upplevelser av sång påverkar sångens mening i förskolan. Slutsatsen landar i att sången har en betydelsefull mening som bör prioriteras.

SKAMlig ohälsa : En studie i hur psykisk ohälsa representeras i webbserien SKAM

This essay examines how the Norwegian web series SKAM presents mental illness; how discourse structures concerning mental illnesses are consolidated and challenged. Our analysis examines seasons one, two and three. The essay is based on Stuart Hall's representation theory, Michel Foucault's theories about madness, and Norman Fairclough's discourse theory. The starting point of the methodology used in this study is a critical discourse analysis based on Norman Fairclough's three-dimensional model. The analysis primarily examines three levels: textual level, dialogues of the characters, and visual expression apparent in the scenography of the series. We analyze how the format is used, how the story is distributed through web and social media, and how this relates to a larger social context in addition to how the narrative of mental illness is inevitably part of cultural, institutional, and social order. Our findings reveal that SKAM reinforces cultural beliefs about mental ill health by representing mental illnesses as taboo and stigmatized as well as as being a problem that is (primarily) at the individual level. Mental illness in the series is presented as a threat to community norms where mental ill health is presented at an individual level and not as a product of society's constructed desires or structural problems. The series presents very limited help for the mentally ill. The absence of acceptance of and cure for the mentally ill causes them to wind up outside society and they have greater difficulty contributing in manners similar to those of healthy, working people.Denna uppsats undersöker hur webbserien SKAM representerar psykisk ohälsa; på vilket sätt diskursiva konstruktioner kring psykiska sjukdomar befästs och utmanas. För att analysera detta undersöks säsong ett, två och tre. Uppsatsen bygger på Stuart Halls representationsteori, Michel Foucaults teorier kring vansinnet och Norman Faircloughs diskursteori. Den metodologi som används för studien är en kritisk diskursanalys där Norman Faircloughs tredimensionella modell är utgångspunkt. Analysen sker främst på tre olika nivåer: textuell nivå; karaktärernas dialoger och seriens visuella uttryck. Hur formatet används; hur berättelsen distribueras genom webb och sociala medier. Samt hur detta sker i en större social kontext; hur berättelsen om psykisk ohälsa ofrånkomligen också är en del av en kulturell, institutionell och samhällelig ordning. Vårt resultat visar att SKAM befäster kulturella föreställningar kring psykisk ohälsa genom att representera psykiska sjukdomar som tabubelagda och stigmatiserade samt som ett problem som (främst) ligger på individnivå. De psykiskt sjuka i serien framställs som hot mot samhällets normer där den psykiska ohälsan läggs på individnivå och inte som en produkt av samhällets konstruerade begär eller strukturella problem. Mycket begränsad hjälp till psykiskt sjuka presenteras i serien. Utlämnandet av acceptans och botemedel för de psykiskt sjuka medför att de hamnar utanför samhället och får svårare att bidra på samma sätt som en frisk, arbetande person kan

Arbetsterapeutiska interventioner och dess betydelse för personer med depression i vuxen ålder

Syftet med studien var att beskriva arbetsterapeutiska åtgärder för personer med depression i vuxen ålder. För att besvara studiens syfte valdes en litteraturöversikt för att få en överblick av tidigare forskning och sammanställa till en ny helhet.Data insamlades genom sökning i databaser som resulterade i 12 artiklar som kvalitetsgranskades och analyserades med Fishers (2009) interventionsmodeller som raster. Analysen visade att arbetsterapeutiska åtgärder kunde placeras under tre av interventionsmodellerna och kunde summeras i form av fritidsaktivitet, fritidssysselsättning, fysisk träning, skrivterapier, gruppterapier, coopingstrategier, The Tree Theme Metod, byte av erfarenheter i grupp och livsberättelser. Resultatet visade vidare på att de arbetsterapeutiska åtgärderna är varierande och att det fanns sparsamt vetenskapliga artiklar som tar upp arbetsterapeutiska åtgärder för personer med depression i vuxen ålder. Arbetsterapeutiska åtgärder ger positiva resultat när det gäller åtgärder för personer med depression i vuxen ålder. The Tree Theme Metod (TTM) är en klientcentrerad metod som var mer framträdande i de granskade studierna och författarna kunde summera metoden som betydelsefull åtgärd för arbetsterapeuter att använda i arbete med personer med depression, detta speciellt då depression är ett växande problem i samhället