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DK resumeVi har i artiklen fokus på anvendelsen af brugerperspektiver i forskning om og med voksne i udsatte marginaliserede positioner. Herunder hvilke metodiske udfordringer og etiske dilemmaer, der kan opstå, når vi ønsker at give stemme til målgrupper, som ikke nødvendigvis ellers deltager i demokratiske sammenhænge. Baseret på vores egen forskning med voksne domfældte med udviklingshæmning og udsatte brugere på væresteder viser vi i artiklen, hvordan vi selv er gået metodisk til værks. Med særligt fokus på at få adgang til grupperne diskuterer vi fordele og ulemper ved at kontakte disse grupper via gatekeepere. Ud fra et interaktionistisk perspektiv analyserer vi betydningen af udsathed samt af den institutionelle kontekst for de interviewteknikker, vi vælger, og for den tillid, der kan udvikles. Undervejs og afslutningsvist diskuterer vi de etiske dilemmaer vi møder, når vi inddrager personer, der er i udsatte positioner som informanter. Vi tager udgangspunkt i de forskningsetiske retningslinjer og bidrager med en nuancering heraf, hvor en hensyntagen til de interviewedes udsatte position og sensitive livssituation kalder på en nærhedsmoral i interviewet. Artiklen bidrager således med refleksions-redskaber for forskere og studerende til at inddrage udsatte stemmer i forskningen, hvorved vi kan sikre en demokratisk kvalificering af det sociale og socialpædagogiske arbejde fremover. Abstract – UK Voices of the vulnerable in institutional research – methodological and ethically reflections This article sheds light on the methodological challenges and ethical dilemmas we as researchers faced in our research achievement to give voice to vulnerable target groups who live in marginalized positions and consequently rarely participate in democratic processes. Based on our research practice with offenders with intellectual disabilities and vulnerable users in drop-in centres, we demonstrate how we methodologically have reached these “hard to reach” groups. We illustrate

DK resumeVi har i artiklen fokus på anvendelsen af brugerperspektiver i forskning om og med voksne i udsatte marginaliserede positioner. Herunder hvilke metodiske udfordringer og etiske dilemmaer, der kan opstå, når vi ønsker at give stemme til målgrupper, som ikke nødvendigvis ellers deltager i demokratiske sammenhænge. Baseret på vores egen forskning med voksne domfældte med udviklingshæmning og udsatte brugere på væresteder viser vi i artiklen, hvordan vi selv er gået metodisk til værks. Med særligt fokus på at få adgang til grupperne diskuterer vi fordele og ulemper ved at kontakte disse grupper via gatekeepere. Ud fra et interaktionistisk perspektiv analyserer vi betydningen af udsathed samt af den institutionelle kontekst for de interviewteknikker, vi vælger, og for den tillid, der kan udvikles. Undervejs og afslutningsvist diskuterer vi de etiske dilemmaer vi møder, når vi inddrager personer, der er i udsatte positioner som informanter. Vi tager udgangspunkt i de forskningsetiske retningslinjer og bidrager med en nuancering heraf, hvor en hensyntagen til de interviewedes udsatte position og sensitive livssituation kalder på en nærhedsmoral i interviewet. Artiklen bidrager således med refleksions-redskaber for forskere og studerende til at inddrage udsatte stemmer i forskningen, hvorved vi kan sikre en demokratisk kvalificering af det sociale og socialpædagogiske arbejde fremover. Abstract – UK Voices of the vulnerable in institutional research – methodological and ethically reflections This article sheds light on the methodological challenges and ethical dilemmas we as researchers faced in our research achievement to give voice to vulnerable target groups who live in marginalized positions and consequently rarely participate in democratic processes. Based on our research practice with offenders with intellectual disabilities and vulnerable users in drop-in centres, we demonstrate how we methodologically have reached these “hard to reach” groups. We illustrate

DK resumeVi har i artiklen fokus på anvendelsen af brugerperspektiver i forskning om og med voksne i udsatte marginaliserede positioner. Herunder hvilke metodiske udfordringer og etiske dilemmaer, der kan opstå, når vi ønsker at give stemme til målgrupper, som ikke nødvendigvis ellers deltager i demokratiske sammenhænge. Baseret på vores egen forskning med voksne domfældte med udviklingshæmning og udsatte brugere på væresteder viser vi i artiklen, hvordan vi selv er gået metodisk til værks. Med særligt fokus på at få adgang til grupperne diskuterer vi fordele og ulemper ved at kontakte disse grupper via gatekeepere. Ud fra et interaktionistisk perspektiv analyserer vi betydningen af udsathed samt af den institutionelle kontekst for de interviewteknikker, vi vælger, og for den tillid, der kan udvikles. Undervejs og afslutningsvist diskuterer vi de etiske dilemmaer vi møder, når vi inddrager personer, der er i udsatte positioner som informanter. Vi tager udgangspunkt i de forskningsetiske retningslinjer og bidrager med en nuancering heraf, hvor en hensyntagen til de interviewedes udsatte position og sensitive livssituation kalder på en nærhedsmoral i interviewet. Artiklen bidrager således med refleksions-redskaber for forskere og studerende til at inddrage udsatte stemmer i forskningen, hvorved vi kan sikre en demokratisk kvalificering af det sociale og socialpædagogiske arbejde fremover. Abstract – UK Voices of the vulnerable in institutional research – methodological and ethically reflections This article sheds light on the methodological challenges and ethical dilemmas we as researchers faced in our research achievement to give voice to vulnerable target groups who live in marginalized positions and consequently rarely participate in democratic processes. Based on our research practice with offenders with intellectual disabilities and vulnerable users in drop-in centres, we demonstrate how we methodologically have reached these “hard to reach” groups. We illustrate

DK resumeVi har i artiklen fokus på anvendelsen af brugerperspektiver i forskning om og med voksne i udsatte marginaliserede positioner. Herunder hvilke metodiske udfordringer og etiske dilemmaer, der kan opstå, når vi ønsker at give stemme til målgrupper, som ikke nødvendigvis ellers deltager i demokratiske sammenhænge. Baseret på vores egen forskning med voksne domfældte med udviklingshæmning og udsatte brugere på væresteder viser vi i artiklen, hvordan vi selv er gået metodisk til værks. Med særligt fokus på at få adgang til grupperne diskuterer vi fordele og ulemper ved at kontakte disse grupper via gatekeepere. Ud fra et interaktionistisk perspektiv analyserer vi betydningen af udsathed samt af den institutionelle kontekst for de interviewteknikker, vi vælger, og for den tillid, der kan udvikles. Undervejs og afslutningsvist diskuterer vi de etiske dilemmaer vi møder, når vi inddrager personer, der er i udsatte positioner som informanter. Vi tager udgangspunkt i de forskningsetiske retningslinjer og bidrager med en nuancering heraf, hvor en hensyntagen til de interviewedes udsatte position og sensitive livssituation kalder på en nærhedsmoral i interviewet. Artiklen bidrager således med refleksions-redskaber for forskere og studerende til at inddrage udsatte stemmer i forskningen, hvorved vi kan sikre en demokratisk kvalificering af det sociale og socialpædagogiske arbejde fremover. Abstract – UK Voices of the vulnerable in institutional research – methodological and ethically reflections This article sheds light on the methodological challenges and ethical dilemmas we as researchers faced in our research achievement to give voice to vulnerable target groups who live in marginalized positions and consequently rarely participate in democratic processes. Based on our research practice with offenders with intellectual disabilities and vulnerable users in drop-in centres, we demonstrate how we methodologically have reached these “hard to reach” groups. We illustrate

Attention-deficit hyperactivity disorder (ADHD) is a common behavioural disorder that affects not only children and adolescents but also adults; however, diagnosis of adult ADHD is difficult because patients seem to have reduced externalized behaviour. ADHD is a multifactorial disorder in which many genes, all with small effects, are thought to cause the disorder in the presence of unfavourable environmental conditions. Therefore, in this pilot study, we explored the expression profile of a list of previously established candidate genes in peripheral blood samples from adult ADHD subjects (n=108) and compared these results with those of healthy controls (n=35). We demonstrate that combining the gene expression levels of dopamine transporter (SLC6A3), dopamine D5 receptor, tryptophan hydroxylase-1, and SNAP25 as predictors in a regression model resulted in sensitivity and specificity of over 80% (ROC: max R 2=0.587, AUC=0.917, P<0.001, 95% CI: 0.900-0.985). In conclusion, the combination of these four genes could represent a potential method for estimating risk and could be of diagnostic value for ADHD. Nevertheless, further investigation in a larger independent population including different subtypes of ADHD (inattentive, hyperactive, or combined type) patients is required to obtain more specific sets of biomarkers for each subtype as well as to differentiate between child, adolescent, and adulthood forms

Aims Coronary late stent thrombosis, a rare but devastating complication, remains an important concern in particular with the increasing use of drug-eluting stents. Notably, pathological studies have indicated that the proportion of uncovered coronary stent struts represents the best morphometric predictor of late stent thrombosis. Intracoronary optical frequency domain imaging (OFDI), a novel second-generation optical coherence tomography (OCT)-derived imaging method, may allow rapid imaging for the detection of coronary stent strut coverage with a markedly higher precision when compared with intravascular ultrasound, due to a microscopic resolution (axial ∼10-20 µm), and at a substantially increased speed of image acquisition when compared with first-generation time-domain OCT. However, a histological validation of coronary OFDI for the evaluation of stent strut coverage in vivo is urgently needed. Hence, the present study was designed to evaluate the capacity of coronary OFDI by electron (SEM) and light microscopy (LM) analysis to detect and evaluate stent strut coverage in a porcine model. Methods and results Twenty stents were implanted into 10 pigs and coronary OFDI was performed after 1, 3, 10, 14, and 28 days. Neointimal thickness as detected by OFDI correlated closely with neointimal thickness as measured by LM (r = 0.90, P < 0.01). The comparison of stent strut coverage as detected by OFDI and SEM analysis revealed an excellent agreement (r = 0.96, P < 0.01). In particular, stents completely covered by OFDI analysis were also completely covered by SEM analysis. All incompletely covered stents by OFDI were also incompletely covered by SEM. Analyses of fibrin-covered stent struts suggested that these may rarely be detected as uncovered stent struts by OFDI. Importantly, optical density measurements revealed a significant difference between fibrin- and neointima-covered coronary stent struts [0.395 (0.35-0.43) vs. 0.53 (0.47-0.57); P < 0.001], suggesting that

OBJECTIVE Proangiogenic effects of mobilized bone marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. We investigated the differential regulation of angio-miRs, that is, miRNAs regulating neovascularization, in mobilized CD34$^+$ progenitor cells obtained from patients with an acute ST-segment-elevation myocardial infarction (STEMI) as compared with those with stable coronary artery disease or healthy subjects. APPROACH AND RESULTS CD34$^+$ progenitor cells were isolated from patients with STEMI (on day 0 and day 5), stable coronary artery disease, and healthy subjects (n=27). CD34$^+$ progenitor cells of patients with STEMI exhibited increased proangiogenic activity as compared withCD34$^+$ cells from the other groups. Using a polymerase chain reaction-based miRNA-array and real-time polymerase chain reaction validation, we identified a profound upregulation of 2 known angio-miRs, that are, miR-378 and let-7b, in CD34$^+$ cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the proangiogenic capacity of CD34$^+$ progenitor cells and its stimulatory effects on endothelial cells in vitro and in vivo, whereas let-7b upregulation in CD34$^+$ cells failed to proof its effect on endothelial cells in vivo. CONCLUSIONS The present study demonstrates a significant upregulation of the angio-miRs miR-378 and let-7b in mobilized CD34$^+$ progenitor cells of patients with STEMI. The increased proangiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34$^+$ progenitor cells in vivo suggest that this unique miRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.

Reduktionen af sociale ydelser til de i forvejen dårligst stillede i Danmark i perioden 2002 til 2011 bevirkede, at mange mennesker uventet blev kastet ud i dyb fattigdom. Individer og familier måtte planlægge og udvikle strategier for, hvordan den pludselig opståede mangelsituation skulle håndteres. I forskningsprojektet ”Konsekvenser af at have de laveste sociale ydelser som forsørgelsesgrundlag” har vi ud over at undersøge modtagernes økonomiske situation og afsavn sat fokus på, hvorledes de ramte familier og enkeltindivider reagerede på den nedsatte ydelse, og hvorledes de håndterede den nye situation, som på én gang var præget af økonomisk knaphed, afsavn og arbejdsløshed og altså skabte krise i familien. Vores studie kan betragtes som et casestudie, der omhandler coping med den særlige situation, som indførelsen af de laveste ydelser medførte. Vi skitserer indledningsvist et begrebsapparat, der kan tydeliggøre, at de fattige blev udsat for et ensartet strukturelt pres, men at de både reflekterede over deres unikke situation og handlede forskelligt. Dernæst behandler vi copingstrategier i forhold til at opnå arbejde, håndtere den trange økonomi og beskytte børnene mod virkningerne af fattigdom. Vi viser, hvorledes fattige individer og familier gennem problemfokuseret og følelsesfokuseret coping samt refleksioner over deres vanskeligheder håndterede arbejdsløshed og afsavn.

Reduktionen af sociale ydelser til de i forvejen dårligst stillede i Danmark i perioden 2002 til 2011 bevirkede, at mange mennesker uventet blev kastet ud i dyb fattigdom. Individer og familier måtte planlægge og udvikle strategier for, hvordan den pludselig opståede mangelsituation skulle håndteres. I forskningsprojektet ”Konsekvenser af at have de laveste sociale ydelser som forsørgelsesgrundlag” har vi ud over at undersøge modtagernes økonomiske situation og afsavn sat fokus på, hvorledes de ramte familier og enkeltindivider reagerede på den nedsatte ydelse, og hvorledes de håndterede den nye situation, som på én gang var præget af økonomisk knaphed, afsavn og arbejdsløshed og altså skabte krise i familien. Vores studie kan betragtes som et casestudie, der omhandler coping med den særlige situation, som indførelsen af de laveste ydelser medførte. Vi skitserer indledningsvist et begrebsapparat, der kan tydeliggøre, at de fattige blev udsat for et ensartet strukturelt pres, men at de både reflekterede over deres unikke situation og handlede forskelligt. Dernæst behandler vi copingstrategier i forhold til at opnå arbejde, håndtere den trange økonomi og beskytte børnene mod virkningerne af fattigdom. Vi viser, hvorledes fattige individer og familier gennem problemfokuseret og følelsesfokuseret coping samt refleksioner over deres vanskeligheder håndterede arbejdsløshed og afsavn.

BACKGROUND: Endothelial injury is considered critical for progression of atherosclerosis and its complications in coronary artery disease (CAD). The endothelial-supportive effects of bradykinin have mainly been attributed to activation of the resident endothelium. Here we newly investigate the role of bradykinin and its B2 receptor for the recruitment and functional activation of circulating mononuclear cell subsets with endothelial-repair promoting capacity, such as CD34(+)CXCR4(+)cells, at sites of arterial injury. METHODS AND RESULTS: Bradykinin-B2-receptor (B2R) blockade by icatibant substantially impaired recruitment of circulating CD34(+)CXCR4(+) mononuclear cells (expressing high levels of B2R) to endothelial cells in vitro and to injured arterial wall in vivo, whereas recruitment of CD14(hi) monocytes (expressing low levels of B2R) was unchanged. Moreover, the capacity of genetically B2R-deficient bone marrow cells to promote endothelial repair in vivo was markedly impaired as compared with wild-type bone marrow cells. B2R expression was reduced on CD34(+)CXCR4(+)mononuclear cells and endothelial repair-promoting early outgrowth cells, but not on CD14(hi)monocytes, from CAD patients as compared with healthy subjects. B2R stimulation induced CD18 activation in early outgrowth cells of healthy subjects, but not in early outgrowth cells of CAD patients. Adenoviral B2R overexpression enhanced in vivo vascular recruitment and rescued impaired endothelial repair capacity of early outgrowth cells from CAD patients. CONCLUSIONS: We newly report that bradykinin/B2R signaling may promote endothelial repair after arterial injury by selective recruitment and functional activation of B2R-expressing circulating mononuclear cell subsets. In CAD patients, B2R downregulation on endothelial repair-promoting circulating mononuclear cells substantially impairs the bradykinin-dependent endothelial repair, representing a novel mechanism promoting endothelial injury in CAD patient

Reduktionen af sociale ydelser til de i forvejen dårligst stillede i Danmark i perioden 2002 til 2011 bevirkede, at mange mennesker uventet blev kastet ud i dyb fattigdom. Individer og familier måtte planlægge og udvikle strategier for, hvordan den pludselig opståede mangelsituation skulle håndteres. I forskningsprojektet ”Konsekvenser af at have de laveste sociale ydelser som forsørgelsesgrundlag” har vi ud over at undersøge modtagernes økonomiske situation og afsavn sat fokus på, hvorledes de ramte familier og enkeltindivider reagerede på den nedsatte ydelse, og hvorledes de håndterede den nye situation, som på én gang var præget af økonomisk knaphed, afsavn og arbejdsløshed og altså skabte krise i familien. Vores studie kan betragtes som et casestudie, der omhandler coping med den særlige situation, som indførelsen af de laveste ydelser medførte. Vi skitserer indledningsvist et begrebsapparat, der kan tydeliggøre, at de fattige blev udsat for et ensartet strukturelt pres, men at de både reflekterede over deres unikke situation og handlede forskelligt. Dernæst behandler vi copingstrategier i forhold til at opnå arbejde, håndtere den trange økonomi og beskytte børnene mod virkningerne af fattigdom. Vi viser, hvorledes fattige individer og familier gennem problemfokuseret og følelsesfokuseret coping samt refleksioner over deres vanskeligheder håndterede arbejdsløshed og afsavn.

Reduktionen af sociale ydelser til de i forvejen dårligst stillede i Danmark i perioden 2002 til 2011 bevirkede, at mange mennesker uventet blev kastet ud i dyb fattigdom. Individer og familier måtte planlægge og udvikle strategier for, hvordan den pludselig opståede mangelsituation skulle håndteres. I forskningsprojektet ”Konsekvenser af at have de laveste sociale ydelser som forsørgelsesgrundlag” har vi ud over at undersøge modtagernes økonomiske situation og afsavn sat fokus på, hvorledes de ramte familier og enkeltindivider reagerede på den nedsatte ydelse, og hvorledes de håndterede den nye situation, som på én gang var præget af økonomisk knaphed, afsavn og arbejdsløshed og altså skabte krise i familien. Vores studie kan betragtes som et casestudie, der omhandler coping med den særlige situation, som indførelsen af de laveste ydelser medførte. Vi skitserer indledningsvist et begrebsapparat, der kan tydeliggøre, at de fattige blev udsat for et ensartet strukturelt pres, men at de både reflekterede over deres unikke situation og handlede forskelligt. Dernæst behandler vi copingstrategier i forhold til at opnå arbejde, håndtere den trange økonomi og beskytte børnene mod virkningerne af fattigdom. Vi viser, hvorledes fattige individer og familier gennem problemfokuseret og følelsesfokuseret coping samt refleksioner over deres vanskeligheder håndterede arbejdsløshed og afsavn.

Aims Coronary late stent thrombosis, a rare but devastating complication, remains an important concern in particular with the increasing use of drug-eluting stents. Notably, pathological studies have indicated that the proportion of uncovered coronary stent struts represents the best morphometric predictor of late stent thrombosis. Intracoronary optical frequency domain imaging (OFDI), a novel second-generation optical coherence tomography (OCT)-derived imaging method, may allow rapid imaging for the detection of coronary stent strut coverage with a markedly higher precision when compared with intravascular ultrasound, due to a microscopic resolution (axial ∼10–20 µm), and at a substantially increased speed of image acquisition when compared with first-generation time-domain OCT. However, a histological validation of coronary OFDI for the evaluation of stent strut coverage in vivo is urgently needed. Hence, the present study was designed to evaluate the capacity of coronary OFDI by electron (SEM) and light microscopy (LM) analysis to detect and evaluate stent strut coverage in a porcine model.Methods and results Twenty stents were implanted into 10 pigs and coronary OFDI was performed after 1, 3, 10, 14, and 28 days. Neointimal thickness as detected by OFDI correlated closely with neointimal thickness as measured by LM (r = 0.90, P < 0.01). The comparison of stent strut coverage as detected by OFDI and SEM analysis revealed an excellent agreement (r = 0.96, P < 0.01). In particular, stents completely covered by OFDI analysis were also completely covered by SEM analysis. All incompletely covered stents by OFDI were also incompletely covered by SEM. Analyses of fibrin-covered stent struts suggested that these may rarely be detected as uncovered stent struts by OFDI. Importantly, optical density measurements revealed a significant difference between fibrin- and neointima-covered coronary stent struts [0.395 (0.35–0.43) vs. 0.53 (0.47–0.57); P < 0.001], suggesting that

BACKGROUND: Flow-mediated dilation (FMD) of human conduit arteries is, in part, related to shear stress-induced release of endothelium-derived nitric oxide (NO). However, NO synthase inhibitors do not completely abolish this FMD-response. Recently, a cytochrome P450 (CYP) epoxygenase of the 2C family was linked to NO- and prostacyclin-independent relaxation of conduit arteries. We therefore evaluated the contribution of CYP 2C9 to FMD in humans. METHODS AND RESULTS: FMD of the radial artery was determined in 12 healthy volunteers by high-resolution ultrasound and analyzed before and after intra-arterial infusion of sulfaphenazole, a specific CYP 2C9 inhibitor, L-NMMA (NO synthase inhibitor) and co-infusion of both. Endothelium-independent vasodilation was characterized after intra-arterial infusion of SNP. FMD was reduced after sulfaphenazole (11.5+/-0.87% vs. 7.4+/-0.95%, p<0.01), after L-NMMA (6.0+/-0.71%; p<0.01), and after co-infusion 3.9+/-0.73% (p<0.05 vs. L-NMMA; p<0.01 vs. sulfaphenazole). Sulfaphenazole had no effect on endothelium-independent vasodilation. In patients with chronic heart failure, the portion of FMD blocked by sulfaphenazole was not affected. CYP 2C was detected by immunohistochemistry in radial artery samples obtained from patients undergoing coronary bypass surgery. CONCLUSIONS: FMD in human conductance arteries is reduced after inhibition of CYP 2C9, supporting the concept that CYP 2C metabolites contribute to endothelium-mediated vasodilation of peripheral conduit arteries in vivo. In patients with heart failure, the CYP-dependent FMD appears to be preserved.

Aims Coronary late stent thrombosis, a rare but devastating complication, remains an important concern in particular with the increasing use of drug-eluting stents. Notably, pathological studies have indicated that the proportion of uncovered coronary stent struts represents the best morphometric predictor of late stent thrombosis. Intracoronary optical frequency domain imaging (OFDI), a novel second-generation optical coherence tomography (OCT)-derived imaging method, may allow rapid imaging for the detection of coronary stent strut coverage with a markedly higher precision when compared with intravascular ultrasound, due to a microscopic resolution (axial ∼10–20 µm), and at a substantially increased speed of image acquisition when compared with first-generation time-domain OCT. However, a histological validation of coronary OFDI for the evaluation of stent strut coverage in vivo is urgently needed. Hence, the present study was designed to evaluate the capacity of coronary OFDI by electron (SEM) and light microscopy (LM) analysis to detect and evaluate stent strut coverage in a porcine model.Methods and results Twenty stents were implanted into 10 pigs and coronary OFDI was performed after 1, 3, 10, 14, and 28 days. Neointimal thickness as detected by OFDI correlated closely with neointimal thickness as measured by LM (r = 0.90, P < 0.01). The comparison of stent strut coverage as detected by OFDI and SEM analysis revealed an excellent agreement (r = 0.96, P < 0.01). In particular, stents completely covered by OFDI analysis were also completely covered by SEM analysis. All incompletely covered stents by OFDI were also incompletely covered by SEM. Analyses of fibrin-covered stent struts suggested that these may rarely be detected as uncovered stent struts by OFDI. Importantly, optical density measurements revealed a significant difference between fibrin- and neointima-covered coronary stent struts [0.395 (0.35–0.43) vs. 0.53 (0.47–0.57); P < 0.001], suggesting that