Publikationer från Uppsala Universitet
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A global survey on the associations between the lockdown group, free memory recall and emotional responses during the COVID-19 lockdown
No full textThe unprecedented outbreak of the COVID-19 pandemic has altered the course of many lives, resulting in multiple health and social challenges. Due to the speed at which this pandemic spread, various public health 'lockdown' measures were introduced to mitigate its spread. The outcome of adherence to these measures has revealed the possible influence on individuals' varying cognitive abilities. Accordingly, this study aimed to explore the predictive relationships between lockdown responses and COVID-19 restrictions, memory recall performance, and associated emotional responses while examining the sociodemographic influences of age and sex. Participants were drawn from a secondary dataset of an international online survey study of 1634 individuals aged 18-75 years across 49 countries. Participants' demographic questionnaires, free memory recall, and hospital anxiety and depression scale scores were used to collect the data for analysis. Four-way MANOVA and hierarchical multiple regression were utilised to explore the mean differences and predict relationships between the study variables. Significant differences were found in memory recall performance and anxiety and depression scores across lockdown groups (the comply, sufferer, and defiant). Regression analysis indicated that age and gender were predictive markers of lockdown responses and anxiety (R2 = 0.14, F4,1625 = 66.15, p < .001, f2 = 0.17), while age was the only predictor of lockdown responses and depression association (b = -0.78, t(1625) = -4.35, p < .001). Lockdown compliance was associated with better free recall (M = 8.51, SD = 6.38, p < .001; η2 = 0.01), lockdown suffering was associated with greater anxiety (M = 9.97, SD = 4.36, p < .001; η2 = 0.06), and lockdown deviance was associated with greater depression (M = 7.90, SD = 3.12, p < .001; η2 = 0.05). The current study provides valuable information on the mechanisms of cognitive interpretations and emotional arousal in individuals' social isolation responses to recent life stress and potential severe pandemics. This may support the need for robust interventions aimed at improving people's psychological appraisals associated with anxiety in preparation for any new potential waves or future pandemics
Mush system heterogeneities control magma composition and eruptive style on the Ocean Island of El Hierro, Canary Islands
No full textThe study of recent eruptions in Ocean Islands (OIs) provides a unique window into the magma dynamics governing their plumbing systems and the mechanisms leading to eruptions. Here we present an integrated approach to unravel the dynamics of magmatic plumbing systems through detailed spatial, petrological, and geochemical characterisation of volcanic products ranging from crystal-rich ankaramitic lavas to trachytic tephras. We focus on the textural and geochemical spatial variations of 42 Holocene subaerial eruptions at the OI of El Hierro (Canary Islands), as well as on their petrogenetic significance for magmatic evolution and plumbing system architecture. Integrating geochemical data within fractional crystallisation modelling and mass balance calculations reveals that ankaramitic and porphyritic lavas with phenocryst modal abundances > 10 vol% result from melt extraction and crystal accumulation. Aphyric to sub-aphyric eruption products and porphyritic lavas with phenocryst modal abundances < 10 vol% usually follow fractional crystallisation trajectories that start at similar to 10 wt% MgO. Periodic extraction of evolved melt from crystal mushes likely led to the occurrence of minor trachytic eruptions, which are difficult to reconcile with simple closed system fractional crystallisation trends. A complex, heterogeneous crustal mush system beneath El Hierro is, in fact, the most reliable scenario to explain the wide range of textures, whole-rock and mineral compositions, and the overall surface distribution of vents and eruptive styles displayed by the Holocene volcanism on the island. Our integrated findings highlight the importance of a combined field, petrological, and geochemical study to decipher plumbing system dynamics of OI magmatism. The results allow us to put forward an updated conceptual model of the current plumbing architecture of El Hierro's volcanic system during the Holocene
A Flexible Interpenetrated Diamondoid Metal-Organic Framework with Aromatic-Enriched Channels as a Preconcentrator for the Detection of Fluorinated Anesthetics
No full textFlexible metal-organic frameworks (MOFs) are dynamic materials that combine long-range structural order with reversible stimulus-responsive phase transitions. In this study, we report the synthesis and characterization of two isoreticular flexible MOFs, TPPM-CPW(Me) and TPPM-CPW(Ph), constructed by combining the ligand tetra-4-(4-pyridyl)phenylmethane (TPPM) with specific Cu(II) paddle-wheel (CPW) secondary building units (SBUs). These MOFs exhibit reversible transitions between open- and closed-pore forms triggered by external stimuli, such as temperature- and pressure-induced guest removal and uptake. The stability of these frameworks is influenced by the residual equatorial groups on the Cu(II) SBUs, with phenyl-functionalized TPPM-CPW(Ph) displaying dynamic behavior characteristic of third-generation soft porous crystals. Notably, TPPM-CPW(Ph) exhibited high adsorption affinity toward fluorinated guests, including SF6 and volatile anesthetics (VAs) such as desflurane and sevoflurane. This material, when used in solid-phase microextraction (SPME) as fiber coating for the preconcentration of these VAs in air, outperformed commercial CAR/PDMS fibers, underscoring the potential of these versatile flexible MOFs in addressing environmental challenges associated with the use of volatile fluorinated compounds
Early Ezetimibe Initiation After Myocardial Infarction Protects Against Later Cardiovascular Outcomes in the SWEDEHEART Registry
No full textBackground Combination lipid-lowering therapy (LLT) after myocardial infarction (MI) achieves lower low-density lipoprotein cholesterol (LDL-C) levels and better cardiovascular outcomes vs statin monotherapy. As a result, global guidelines recommend lower LDL-C but, paradoxically, advise treatment through a stepwise approach. Yet the need for combination therapy is inevitable as <20% of patients achieve goals with statins alone. Whether combining ezetimibe with a statin early vs late after MI results in better outcomes is unknown. Objectives In this study, the authors sought to assess the impact of delayed treatment escalation on outcomes by comparing early vs late oral combination LLT (statins plus ezetimibe) in patients with MI. Methods LLT-naïve patients (SWEDEHEART registry) hospitalized for MI (2015-2022) and discharged on statins were included. Using clone-censor-weight and Cox proportional hazards models, we compared differences in risks of MACE (death, MI, stroke), components of MACE, and cardiovascular death between patients with ezetimibe added to statins ≤12 weeks after discharge as reference (early combination therapy), from 13 weeks to 16 months (late combination therapy), or not at all. Results Of 35,826 patients (median age 65.1 years, 26.0% women), 6,040 (16.9%) received ezetimibe early, 6,495 (18.1%) ezetimibe late, and 23,291 (65.0%) received no ezetimibe. High-intensity statin use was ≥98% in all groups. Over a median 3.96 years (Q1-Q3: 2.15-5.81 years), 2,570 patients had MACE (440 cardiovascular deaths). One-year MACE incidences were 1.79 (early), 2.58 (late), and 4.03 (none) per 100 patient-years. Compared with early combination therapy, weighted risk differences in MACE for late combination therapy at 1, 2, and 3 years were 0.6% (95% CI: 0.1%-1.1%; P < 0.01), 1.1% (95% CI: 0.3%-2.0%; P < 0.01), and 0.7% (95% CI:-0.2% to 1.3%; P = 0.18), and 3-year HR was 1.14 (95% CI: 0.95-1.41). For those receiving no ezetimibe, risk differences were 0.7% (95% CI: 0.2%-1.3%), 1.6% (95% CI: 0.8%-2.5%), and 1.9% (95% CI: 0.8%-3.1%; P for all <0.01; 3-year HR: 1.29 [95% CI: 1.12-1.55]). Similar differences in risk of cardiovascular death at 3 years were observed (HRs vs early: late: 1.64 [95% CI: 1.15-2.63]; none: 1.83 [95% CI: 1.35-2.69]). Conclusions MI care pathways should implement early combination therapy with statins and ezetimibe as standard care, because delaying use of combination LLT or using high-intensity statin monotherapy is associated with avoidable harm
Engineering of extracellular vesicles for efficient intracellular delivery of multimodal therapeutics including genome editors
No full textIntracellular delivery of protein and RNA therapeutics represents a major challenge. Here, we develop highly potent engineered extracellular vesicles (EVs) by incorporating bio-inspired attributes required for effective delivery. These comprise an engineered mini-intein protein with self-cleavage activity for active cargo loading and release, and fusogenic VSV-G protein for endosomal escape. Combining these components allows high efficiency recombination and genome editing in vitro following EV-mediated delivery of Cre recombinase and Cas9/sgRNA RNP cargoes, respectively. In vivo, infusion of a single dose Cre loaded EVs into the lateral ventricle in brain of Cre-LoxP R26-LSL-tdTomato reporter mice results in greater than 40% and 30% recombined cells in hippocampus and cortex respectively. In addition, we demonstrate therapeutic potential of this platform by showing inhibition of LPS-induced systemic inflammation via delivery of a super-repressor of NF-ĸB activity. Our data establish these engineered EVs as a platform for effective delivery of multimodal therapeutic cargoes, including for efficient genome editing
Robust Systemic and Mucosal Immune Responses to Coxsackievirus B3 Elicited by Spider Silk Protein Based Nanovaccines via Subcutaneous Immunization
No full textCoxsackievirus B3 (CVB3) is a member of the enterovirus genus and linked to several diseases, including myocarditis, which can progress to dilated cardiomyopathy. Despite ongoing preclinical efforts, no clinically approved vaccines against CVB3 are currently available, highlighting the urgent need for effective prophylactic solutions. In this study, a nanovaccine platform based on spider minor ampullate silk protein (MiSp) is introduced. This platform utilizes protein nanoparticles engineered from chimeric proteins that incorporate CVB3 antigenic peptides into customized MiSp, subsequently loaded with all-trans retinoic acid (RA). These functional nanovaccines are capable of eliciting both mucosal and systemic immune responses following subcutaneous administration and demonstrate significant protective effects against CVB3 infection in mice. This study signifies an approach in peptide-based parenteral vaccine strategies, utilizing engineered MiSp nanoparticles combined with RA. This methodology represents a promising pathway for preventing enterovirus infections by leveraging the unique immunomodulatory properties of spidroins and RA to combat these pathogens effectively.
From Heavy Rainfall to Rising Seas: Multiple Flood Risk for Critical Infrastructure inGothenburg’s Urban Environment
No full textKlimatförändringarna har lett till en ökning av extrema väderhändelser, vilket i sin tur ökar risken föröversvämningar. Denna studie undersöker hur tre typer av översvämningar (kust-, vattendrag- ochskyfallsöversvämning) sammanfaller med kritisk infrastruktur i Göteborg. Studien syftar till attidentifiera områden med enskilda samt överlappande översvämningsrisker och analysera deras påverkanpå kritisk infrastruktur. Med kritisk infrastruktur menas strukturer (exempelvis byggnader eller vägar)nödvändiga för samhället vid krissituationer.Göteborg, som är en viktig industri- och hamnstad på Sveriges västkust, är särskilt utsatt föröversvämning från flera källor. Staden har identifierats som ett högriskområde för översvämning frånhavet, vattendrag samt skyfall. Med hjälp av geografiska informationssystem (GIS) haröversvämningsdata från MSB och Göteborgs stad analyserats. Genom att kombinera kartor för olikaöversvämningstyper med data för kritisk infrastruktur har särskilt utsatta områden identifierats.Resultaten visade att skyfallsöversvämningar har störst geografisk utbredning (7% avstudieområdet), följt av kustöversvämning (6%) och vattendragsöversvämning (1%). Överlappandeöversvämningsrisker är mindre vanliga, där kust- och vattendragsöversvämning som den störstaöverlappande risken (1%). Skyfallsöversvämning sammanfaller med flest byggnader (33%), medanöverlappande risker sammanfaller med cirka 2% av byggnaderna. Kustöversvämning utgör det störstahotet mot hamnområdet (täcker 31%), medan överlappande risker sammanfaller med upp till 3%.Vägnätet är den mest utsatta kritiska infrastrukturen, där kustöversvämning täcker 19% ochöverlappande kartor täcker upp till 10%. Järnvägar påverkas i mindre utsträckning, men även här harkustöversvämning det största sammanfallet (12%), medan överlappande översvämningskartor täckerupp till 3%. Den mest utsatta områdena återfinns i centrala Göteborg, särskilt längs Göta älv. Vägar ärden mest utsatta kategorin, följt av byggnader, hamn och järnväg. Bland byggnadstyperna ärlivsmedelsindustrier, distributionsbyggnader och skolor mest utsatta.Studien fokuserar på överlappande översvämningskartor, även om dom täcker mindre ytor, eftersomdom kan innebära större konsekvenser än enskilda översvämningar. Därför är det viktigt att inkluderadessa i framtida planering och riskbedömning. Resultaten understryker behovet av att vidareutvecklaöversvämningskartering för samtidiga översvämningsrisker. Climate change has led to an increase in extreme weather events, which in turn raises the risk of flooding.This study examines how three types of flooding (coastal, fluvial and pluvial) coincide with criticalinfrastructure in Gothenburg. The aim of the study is to identify areas with individual and multiple floodrisks and to analyze their overlap on critical infrastructure. Critical infrastructure refers to structures(such as buildings or roads) essential to society during crisis situations.Gothenburg, a major industrial and port city on Sweden’s west coast, is particularly vulnerable toflooding from multiple sources. The city has been identified as a high-risk area for flooding from thesea, rivers, and heavy rainfall. Using Geographic Information Systems (GIS), flood data from theSwedish Civil Contingencies Agency (MSB) and the City of Gothenburg were analyzed. By combiningflood maps with data on critical infrastructure, the study identifies areas of heightened vulnerability.The results show that heavy rainfall flooding has the largest spatial extent (7% of the study area),followed by coastal flooding (6%) and river flooding (1%). Overlapping flood risks are less common,with coastal and river flooding being the most significant overlapping combination (1%). Heavy rainfallflooding coincides with the highest number of buildings (33%), while overlapping risks coincide withabout 2% of buildings. Coastal flooding poses the greatest threat to the port area (covering 31%), whileoverlapping risks coincide with up to 3%.The road network is the most exposed category of critical infrastructure, with coastal floodingcovering 19% and overlapping risks up to 10%. Railways are less affected, though coastal flooding stilloverlaps with 12% of the network, and overlapping risks with up to 3%. The most vulnerable areas arelocated in central Gothenburg, particularly along the Göta River. Roads are the most affectedinfrastructure type, followed by buildings, the port, and railways. Among building types, food industries,distribution centers, and schools are the most exposed.The study emphasizes the importance of analyzing overlapping flood risks, which, despite coveringsmaller areas, may lead to more severe consequences than individual flood events. These risks shouldbe considered in future planning and risk assessments. The findings highlight the need to further developflood mapping methods that account for simultaneous flood scenarios
Basic Needs and Aid Allocation : A Quantitative Analysis on Aid Allocation to Developing Countries From the US, China and Ireland 2019
No full textObservation of Cosmic-Ray Anisotropy in the Southern Hemisphere with 12 yr of Data Collected by the IceCube Neutrino Observatory
No full textWe analyzed the 7.92 x 10(11) cosmic-ray-induced muon events collected by the IceCube Neutrino Observatory from 2011 May 13, when the fully constructed experiment started to take data, to 2023 May 12. This data set provides an up-to-date cosmic-ray arrival direction distribution in the Southern Hemisphere with unprecedented statistical accuracy covering more than a full period length of a solar cycle. Improvements in Monte Carlo event simulation and better handling of year-to-year differences in data processing significantly reduce systematic uncertainties below the level of statistical fluctuations compared to the previously published results. We confirm the observation of a change in the angular structure of the cosmic-ray anisotropy between 10 TeV and 1 PeV, more specifically in the 100-300 TeV energy range. For the first time, we analyzed the angular power spectrum at different energies. The observed variations of the power spectra with energy suggest relatively reduced large-scale features at high energy compared to those of medium and small scales. The large volume of data enhances the statistical significance at higher energies, up to the PeV scale, and smaller angular scales, down to approximately 6 degrees compared to previous findings.For complete list of authors see http://dx.doi.org/10.3847/1538-4357/adb1de</p
Deep representation clustering for histology annotation using few-shot learning and semi-supervised learning
No full textProstate cancer is one of the most common malignancies affecting male health all around the world, and the precise measurement of prostate-specific antigen (PSA) is important for prostate cancer diagnosis and prognosis. PSA levels can be measured directly from the urine. It is also possible to visualize the distribution of PSA expression in tissue samples. The staining pattern is believed to be relevant for the prognosis of the development of cancer. However, visual analysis of the staining pattern of PSA in the pathology image is difficult and tedious. In this research, we propose a few-shot learning and semi-supervised model for prostate cancer pathology images to improve the accuracy of PSA measurement with a few labeled data. Each sample has four equally large regions labeled with PSA scores, and is split into patches to fine-tune a pretrained deep learning model. Then we generate an embedding for those patches. We thereafter reduce the dimensionality of the embedding using UMAP. The UMAP-generated 3-dimension feature map shows the distribution of patch characteristics, where each point's color corresponds to a patch's feature distribution. We project the points' colors from the feature map back to the original pathology images, and the PSA distribution across the prostate sample is shown. Next, we perform clustering in the UMAP space, which is calculated on the 3D feature map to judge between positive and negative regions to calculate the percentage of positive area in each quarter. This research provides novel methods for calculating PSA scores on pathology images, improving the accuracy of PSA-based diagnosis and aiding in the identification of clinically significant prostate cancer regions.