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LRP2 is a potential molecular target for nonsyndromic pathological myopia
Get PDFHigh myopia (HM) and posterior staphyloma (PS) are major causes of vision loss worldwide. Genetic and environmental factors, especially light exposure, influence myopia. This study shows that low-density lipoprotein-related receptor type 2 (LRP2) levels are decreased in the vitreous of patients with HM and PS, and that in human donor eyes affected by PS, LRP2 expression was reduced in the neural retina and retinal pigment epithelium (RPE), with morphologic changes similar to those observed in the Foxg1-Cre-Lrp2fl/fl mouse that also develops PS. In human induced pluripotent stem cell-derived RPE cells, LRP2 silencing regulated genes involved in eye and neuronal development, visual perception, tissue remodeling, hormone metabolism, and RPE structure. Its expression increased under light exposure, particularly red light, but was downregulated by cortisol. These findings establish a link between LRP2, myopization, and environmental factors, highlighting its crucial role in nonsyndromic HM and PS. LRP2 appears to be a promising therapeutic target for HM treatment.</p
Association of Non-Cardiac Depolarization-Blocking Drugs with First-Registered Heart Rhythm and Survival in Out-of-Hospital Cardiac Arrest
Get PDFObjective: Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of mortality worldwide. Survival following OHCA largely depends on whether the initial heart rhythm is shockable or non-shockable. Previous research has suggested that drugs with an off-target effect of blocking cardiac depolarization (non-cardiac depolarization-blocking (DB) drugs) may be associated with a higher likelihood of having a non-shockable rhythm. In this study, we examined whether the use of non-cardiac DB-drugs affects the initial rhythm and survival in OHCA. Methods: We identified all patients with OHCA of medical causes from the nationwide Danish Cardiac Arrest Registry (2001–2020). Non-cardiac DB-drug use was defined by prescriptions within 90 days prior to OHCA. Multiple logistic regression models with adjustments for relevant confounders were employed to estimate the odds ratio (OR) for the association between non-cardiac DB-drugs and initial heart rhythm and 30-day survival following OHCA. Additionally, stratified analyses were performed based on sex, age, cardiovascular and psychiatric comorbidities, and the year of OHCA occurrence. Results: We included 54,370 OHCA patients (63.1 % male, median age 74 years). Non-cardiac DB-drugs was used by 6284 (11.6 %) OHCA patients and was associated with increased odds of non-shockable rhythm compared with non-users after adjustment for relevant confounders (OR 1.62, 95 % CI: 1.48–1.79). This increased odds of non-shockable rhythm was consistent in men and women (OR men: 1.72, 95 % CI: 1.53–1.95, OR women 1.46, 95 % CI: 1.26–1.70), in all age categories (OR <60 years 1.91, 95 % CI: 1.54–2.39, OR >60 years 1.57, 95 % CI: 1.41–1.74), in the absence of pre-existing psychiatric or non-cardiovascular disease, or when stratified by the year of OHCA occurrence. Finally, we found that users of non-cardiac DB-drugs had lower 30-day survival chances following OHCA when compared to non-users (OR 0.81, 95 % CI: 0.69–0.95). Conclusion: Use of non-cardiac DB-drugs was associated with increased odds of non-shockable rhythm in OHCA and with lower 30-day survival following OHCA.</p
Co-Investigating for Sustainable Futures—Interventions for Extending the Lifetime of Connected Products
No full textGiven the urgent need for transitions towards sustainability in the design and manufacturing sectors that adhere to environmental limits, this study focuses on how to create targeted interventions within existing socio technical regimes that catalyse these transitions in the area of connected (smart) products. This category, which depends on both the hardware and software industries, introduces unique sustainability challenges and opportunities. Designing and manufacturing durable products requires a collaborative approach, given that the production of hardware and software is intricately linked to a global supply chain deeply embedded within the current production ecosystem and mass production values. To improve understanding and disseminate knowledge about product lifecycle extension, this work presents a co-investigation tool. This tool is based on insights from previous interviews and literature reviews, and it aims to promote collaboration among industry experts, such as designers and engineers, in how to implement product life extension strategies. A key aspect of our methodology is incorporating the perspectives of these industry players and acknowledging their pivotal role in realising sustainable solutions. Employing this conversation tool, we facilitated five focus groups with industry professionals to identify and formulate strategies for extending the lifespan of products. This paper details the design of the tool and the insights derived from the focus groups. The results of this study provide insightful pathways for firms engaged in sustainable product design and manufacturing, steering them towards a more sustainable future
Severe mental illness, chest pain, and emergency response
No full textAIMS: How the prehospital chest pain triage contributes to inequities in cardiovascular outcomes remains poorly understood in patients with severe mental illness (SMI). We aimed to examine the association between SMI, emergency response, and cardiovascular health disparities in chest pain-related calls.METHODS: This registry-based cohort study included first-time chest pain-related calls to the Copenhagen Emergency Medical Services (emergency number and out-of-hours service) during the study period 2014-2018. We compared patients with SMI to patients without SMI (controls). We examined emergency response following telephone triage and diagnoses assigned during hospitalization by multivariable logistic regression.RESULTS: Of 64,937 chest pain-related calls, 4,303 (7%) were from patients with SMI and 60,634 (93%) from controls. Patients with SMI more often received an acute ambulance dispatch than controls (66% vs 63%, OR: 1.24, 95%CI: 1.16-1.32). However, patients with SMI were less likely than controls to be admitted within 24 hours after the call (81% vs 85%, OR: 0.82, 95%CI: 0.76-0.89), assigned a cardiovascular diagnosis during hospitalization following the call (16% vs 26%, OR: 0.61, 95%CI: 0.56-0.67), or undergo revascularization within 30-days after the call (4% vs 7%, OR: 0.65, 95%CI: 0.55-0.78). The 30-days mortality was similar in patients with SMI and controls (1% vs 2%, OR: 1.18, 95%CI: 0.90-1.55).CONCLUSION: Prehospital triage of chest pain did not contribute substantially to inequity in cardiovascular care of patients with SMI, whereas care disparities were observed in hospitalization, diagnostics, and treatment. Further examination of the symptom presentation is needed to improve identification of the acutely ill cardiovascular patients.</p
Debat:Partnerskaber risikerer at blive en sovepude for arkitektonisk kvalitet
No full textFrygten var, at strategiske partnerskaber ville prioritere pris over kvalitet. Variation er ikke udeblevet, men kun et projekt har udmærket sig, skriver forskere og fagdommere i et debatindlæg. Debatindlægget baserer sig på arkitekturevalueringen: Arkitektonisk kvalitet i strategiske partnerskaber af Sidse Grangaard og Stefan Christoffer Gottlieb
Forfatterskabets reaktorkerne: Katrine Marie Guldager: Hvis vi havde tvunget dig til at være social. Digte.
No full textMens de fleste forfatterskaber er enten lyriske eller episke, finder man også en mindre gruppe forfatterskaber, der består af en stor mængde romaner og noveller og en lille håndfuld digtsamlinger, hvor betydningen og kvaliteten af de sidste langtfra står tilbage for de første. Det gælder for giganter som Johannes V. Jensen og Klaus Rifbjerg, af hvilke sidstnævnte talte om sine i antal færre lyriske værker som forfatterskabets reaktorkerne, hvor livsværkets mest essentielle problematikker og poetologiske overvejelser optrådte i en koncentreret form. Og så er det tilfældet for et af samtidens vigtigste forfatterskaber, nemlig Katrine Marie Guldagers. Hvad er det så, der gør, at en afgørende del af Guldagers forfatterskab er den lyriske? Årsagen er, at de lyriske tekster modsat de episke ofte bevæger sig dybt ned under dagliglivets overflade og borer i de smertepunkter, som vores sociale liv skøjter hen over. Mens Guldagers snes romaner og noveller med en kuldslået og elegant hemingwaysk isbjergteknik fremlægger handlingsforløb fra familie- og arbejdslivet, oftest med biografisk reference til henholdsvis en barndom blandt Danida-arbejdere i Afrika og et parcelhusliv i Danmark, så kommer vi ganske anderledes ned i følelser af forladthed, ensomhed og angst i de lyriske tekster, hvor især de to samlinger ”Ankomst. Husumgade” (2001) og ”Et sted i verden” (2014) har været markante. Det virker faktisk som om digtsamlingen ”Hvis vi havde tvunget dig til at være social” er et opgør med den episke fortællemodus i forfatterskabet og et forsøg på at komme dybere ned i den psykiske hovedstol, som ligger og styrer vores liv – og hos kunstnere, den kreative impuls og produktivitet. I hvert fald er digtsamlingen raffineret komponeret efter den ovennævnte ide, for værket består af to typer af tekster, nemlig dels de episk fremadskridende, hvor forfatteren har interviewet sin mor om sin barndom, som blev tilbragt på et ulandsprojekt i Zambia, dels en lyrisk del med fragmenter fra barndommen, som den voksne digter erindrer. Og der er i den grad forskel på disse, skulle jeg hilse at sige. Moren pludrer i afsnit efter afsnit konfliktskyet, jovialt og floskelpræget derudaf. Tænderskærende er morens overfladiske fortælling, hvis grundmelodi er, hvor lidt hun forstår af sin lille pige, og hvor langt hun er fra at kunne komme og ville i kontakt med sin datter. For der er jo så meget andet vigtigt, der kræver morens opmærksomhed som tjenestefolkene, selskaber, kontorarbejde samt at være irriteret på den hyperaktive far. Vi hører: ”Enten hvilede du meget i dig selv, eller også havde du bare ikke brug for nogen”. Eller man får salver af selvretfærdige klicheer som i den følgende undskyldning for det svigt, familien udsætter den utilpassede pige for: ”Vi var nødt til at lade dig blive derhjemme. Du fik en hund, og så var du alene hjemme, til vi andre kom hjem ved et-tiden. Vi ville havde gjort vold på dig, hvis vi havde tvunget dig til at være social.” Ganske anderledes ser verden naturligvis ud datteren, der senere bliver digter. For den psykiske vold, som moren selvretfærdigt mener at have afværget, er jo netop foregået. Fra det voksne jeg hører vi i tekst efter tekst om, hvordan barndommens traume af på én gang at føle sig afmægtig, angst, ulykkelig og skyldig over ikke at kunne indgå i de sociale relationer og samtidig at leve kompensatorisk i sin egen fantasiverden er blevet den livstråd, som har strakt sig gennem hele jegets liv. Eller som det hedder programmatisk: ”Barndommens rum holder ikke op / med at vokse.” Og i et mere udfoldet, blændende og uhyggeligt billede af, hvordan barndommens oplevelsesmatricer holder os i et jerngreb gennem hele livet: ”Måske var det aldrig nogen flydende bevægelse / mere små ryk / fra barndom til ungdom / og tilbage igen / måske var billedet altid rystet: / et barns sjæl fanget under blå is.” Sådan er Guldagers lyriske tekster enormt intense i deres emotionelle udtryk. Der skiftes mellem fortid og nutid, her og der, og drømme og virkelighed – men følelsen af eksistentiel forladthed ser man sjældent skarpere spiddet end i disse skitser. Her er som afslutning en fabelagtig tekst, hvor jeget som hvid overklassefrue sidder på en afrikansk restaurant: ”Restauranten er næsten tom. / Jeg spørger, om jeg må sidde udenfor, helt ude ved vejen / bestiller lam og hvidvin, ét glas. / På Kenyatta Avenue gemmer de hjemløse børn sig / i buskene på den anden side af vejen.” ”Hvis vi havde tvunget dig til at være social” er en dyb, kompleks, inciterende, smertefuld og smuk rejse ind i det sarte sind, som vi alle har fra barndommen – og bevarer hele livet.<br/
Recent Advances in Hydraulic Model Testing Techniques
No full textOver the last 40 years, many hydraulic laboratories able to generate irregular waves have been established. Most of these utilize wave generation and analysis procedures developed for linear or mildly nonlinear irregular waves. Such procedures are usually not sufficient to accurately replicate the waves that occur during design conditions for coastal structures. The present paper provides an overview of the recent developments in hydraulic model testing techniques that allow accurate generation and analysis of highly nonlinear irregular waves. The three main topics dealt with are generation of highly nonlinear waves by piston wavemakers using cyber-physical modelling, active absorption of reflected waves and analysis of highly nonlinear long-crested and short-crested waves. The methods have already been applied in several commercial and research projects at Aalborg University. Application of the methods are demonstrated by examples in the paper
The digital transformation of the public sector in Denmark and its influence on urban planning
No full textMachine learning-based prediction of atrial fibrillation in patients with atrial high-rate episodes
No full textBackground: Given the modest performance of available predictive models in estimating the risk of atrial fibrillation (AF) in patients with atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs), this study explores the potential use of machine learning (ML) algorithms in this context. Purpose: To assess the ability of ML techniques in identifying patients with AHRE at high risk of AF. Methods: In this prospective study, we enrolled patients without a prior history of AF who experienced at least one AHRE episode detected by CIEDs. ML techniques were applied to predict the 1-year risk of developing new-onset AF based on the following variables: age, BMI, sex, smoking, hypertension, diabetes, coronary artery disease, chronic kidney disease, dyslipidaema, history of stroke or transient ischaemic attack, vascular heart disease, left atrial enlargement (LAE) and congestive heart failure. Results: Study population consists of 100 patients (48% male, mean age 66.0 ± 18.0 years), of whom 24 developed AF (24%) after 1-year follow-up. The CatBoost ML model achieved the highest AUC (.857, 95% CI.671–.999) when compared to other ML models and all clinical risk scores. The top four most influential predictors of AF in the CatBoost model were LAE, hypertension, diabetes and age. Conclusions: ML techniques are robust in predicting AF in patients with AHREs. Further validation in larger, independent cohorts is warranted.</p
