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1.	Sourander, Birger, et al. (författare) No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study 2022 Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:10, s. 703-712 Tidskriftsartikel (refereegranskat)abstract Background The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. Results We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.
2.	Abdollahi Sani, Negar, et al. (författare) All-printed diode operating at 1.6 GHz 2014 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:33, s. 11943-11948 Tidskriftsartikel (refereegranskat)abstract Printed electronics are considered for wireless electronic tags and sensors within the future Internet-of-things (IoT) concept. As a consequence of the low charge carrier mobility of present printable organic and inorganic semiconductors, the operational frequency of printed rectifiers is not high enough to enable direct communication and powering between mobile phones and printed e-tags. Here, we report an all-printed diode operating up to 1.6 GHz. The device, based on two stacked layers of Si and NbSi2 particles, is manufactured on a flexible substrate at low temperature and in ambient atmosphere. The high charge carrier mobility of the Si microparticles allows device operation to occur in the charge injection-limited regime. The asymmetry of the oxide layers in the resulting device stack leads to rectification of tunneling current. Printed diodes were combined with antennas and electrochromic displays to form an all-printed e-tag. The harvested signal from a Global System for Mobile Communications mobile phone was used to update the display. Our findings demonstrate a new communication pathway for printed electronics within IoT applications.
3.	Andersson, Christer, et al. (författare) Manifest för lämplig styrning av hälso- och sjukvården 2018 Ingår i: Läkartidningen. - 0023-7205. ; 115:3 Tidskriftsartikel (refereegranskat)
4.	Ekstrom, Magnus, et al. (författare) Body mass index, weight gain and activity-related breathlessness : the Swedish CArdioPulmonary bioImage Study 2019 Ingår i: European Respiratory Journal. - : European Respiratory Society Journals. - 0903-1936 .- 1399-3003. ; 54 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
5.	Ekström, Magnus Pär, et al. (författare) The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study 2019 Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964 Tidskriftsartikel (refereegranskat)abstract Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
6.	Johansson, Karl-Axel, et al. (författare) The quality assurance process for the ARTSCAN head and neck study - a practical interactive approach for QA in 3DCRT and IMRT. 2008 Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 87:2, s. 290-9 Tidskriftsartikel (refereegranskat)abstract AIM: This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT. MATERIALS AND METHODS: The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results. RESULTS AND DISCUSSION: This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations. CONCLUSIONS: This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.
7.	Kanberg, Nelly, et al. (författare) Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. 2020 Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 95:12 Tidskriftsartikel (refereegranskat)abstract To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
8.	Karlsson, Lars, et al. (författare) A clinical decision support tool for improving adherence to guidelines on anticoagulant therapy in patients with atrial fibrillation at risk of stroke : A cluster-randomized trial in a Swedish primary care setting (the CDS-AF study) 2018 Ingår i: PLoS Medicine. - San Francisco, United States : Public Library of Science. - 1549-1277 .- 1549-1676. ; 15:3 Tidskriftsartikel (refereegranskat)abstract BackgroundAtrial fibrillation (AF) is associated with substantial morbidity, in particular stroke. Despite good evidence for the reduction of stroke risk with anticoagulant therapy, there remains significant undertreatment. The main aim of the current study was to investigate whether a clinical decision support tool (CDS) for stroke prevention integrated in the electronic health record could improve adherence to guidelines for stroke prevention in patients with AF.Methods and findingsWe conducted a cluster-randomized trial where all 43 primary care clinics in the county of Östergötland, Sweden (population 444,347), were randomized to be part of the CDS intervention or to serve as controls. The CDS produced an alert for physicians responsible for patients with AF and at increased risk for thromboembolism (according to the CHA2DS2-VASc algorithm) without anticoagulant therapy. The primary endpoint was adherence to guidelines after 1 year. After randomization, there were 22 and 21 primary care clinics in the CDS and control groups, respectively. There were no significant differences in baseline adherence to guidelines regarding anticoagulant therapy between the 2 groups (CDS group 70.3% [5,186/7,370; 95% CI 62.9%–77.7%], control group 70.0% [4,187/6,009; 95% CI 60.4%–79.6%], p = 0.83). After 12 months, analysis with linear regression with adjustment for primary care clinic size and adherence to guidelines at baseline revealed a significant increase in guideline adherence in the CDS (73.0%, 95% CI 64.6%–81.4%) versus the control group (71.2%, 95% CI 60.8%–81.6%, p = 0.013, with a treatment effect estimate of 0.016 [95% CI 0.003–0.028]; number of patients with AF included in the final analysis 8,292 and 6,508 in the CDS and control group, respectively). Over the study period, there was no difference in the incidence of stroke, transient ischemic attack, or systemic thromboembolism in the CDS group versus the control group (49 [95% CI 43–55] per 1,000 patients with AF in the CDS group compared to 47 [95% CI 39–55] per 1,000 patients with AF in the control group, p = 0.64). Regarding safety, the CDS group had a lower incidence of significant bleeding, with events in 12 (95% CI 9–15) per 1,000 patients with AF compared to 16 (95% CI 12–20) per 1,000 patients with AF in the control group (p = 0.04). Limitations of the study design include that the analysis was carried out in a catchment area with a high baseline adherence rate, and issues regarding reproducibility to other regions.ConclusionsThe present study demonstrates that a CDS can increase guideline adherence for anticoagulant therapy in patients with AF. Even though the observed difference was small, this is the first randomized study to our knowledge indicating beneficial effects with a CDS in patients with AF.
9.	Karlsson, Lars O., et al. (författare) Clinical decision support for stroke prevention in atrial fibrillation (CDS-AF): Rationale and design of a cluster randomized trial in the primary care setting 2017 Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 187, s. 45-52 Tidskriftsartikel (refereegranskat)abstract Background Atrial fibrillation (AF) is associated with substantial morbidity, in particular stroke. Despite good evidence for the reduction of stroke risk with anticoagulant therapy, there remains a significant undertreatment. The main aim of the current study is to investigate whethera clinical decision support tool for stroke prevention (CDS) integrated in the electronic health record can improve adherence to guidelines for stroke prevention in patients with AF. Methods We will conduct a cluster randomized trial where 43 primary care clinics in the county of Ostergotland, Sweden (population 444,347), will be randomized to be part of the CDS intervention or serve as controls. The CDS will alert responsible physicians of patients with AF and increased risk for thromboembolism according to the CHA(2)DS(2)VASc (Congestive heart failure, Hypertension, Age 74 years, Diabetes mellitus, previous Stroke/TIA/thromboembolism, Vascular disease, Age 65-74 years, Sex category (i.e. female sex)) algorithm without anticoagulant therapy. The primary end point will be adherence to guidelines after 1 year. Conclusion The present study will investigate whether a clinical decision support system integrated in an electronic health record can increase adherence to guidelines regarding anticoagulant therapy in patients with AF.
10.	Marklund, Emelie, et al. (författare) Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders. 2020 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10 Tidskriftsartikel (refereegranskat)abstract To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
11.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
12.	Nilsson, E.J.C., et al. (författare) Using microdispensing to manufacture a customized cell dish for microbeam irradiation of single, living cells 2009 Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 267:7, s. 1199-1205 Tidskriftsartikel (refereegranskat)abstract In this paper is described the preparation of patterned cell dishes to be used in studies of low dose irradiation effects on living cells. Using a droplet microdispenser, an 8 mu m thick polypropylene cell substrate, to which cells do not naturally adhere, was coated in a matrix pattern with the cell adhesive mussel protein Cell-Tak. Cells were shown to adhere and grow on the protein-coated spots, but not on the uncoated parts, providing for guided cell growth. Cultivation of isolated cell colonies provides an opportunity to study how low doses of ionizing radiation affect neighbouring un-irradiated cell colonies. (C) 2009 Elsevier B.V. All rights reserved.
13.	Yilmaz, Aylin, 1974, et al. (författare) Upper respiratory tract levels of SARS-CoV-2 RNA and duration of viral RNA shedding do not differ between patients with mild and severe/critical COVID-19. 2021 Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:1, s. 15-18 Tidskriftsartikel (refereegranskat)abstract This study reports longitudinal viral RNA loads from nasopharynx/throat in patients with mild and severe/critical COVID-19. We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract, nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
14.	Yilmaz, Aylin, et al. (författare) Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019 2021 Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:1, s. 15-18 Tidskriftsartikel (refereegranskat)abstract This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
15.	Ahlgren, Erika, et al. (författare) Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection 2016 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7 Tidskriftsartikel (refereegranskat)abstract Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
16.	Andersson, Anders, et al. (författare) Global analysis of mRNA stability in the archaeon Sulfolobus 2006 Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 7:10, s. R99- Tidskriftsartikel (refereegranskat)abstract Background: Transcript half-lives differ between organisms, and between groups of genes within the same organism. The mechanisms underlying these differences are not clear, nor are the biochemical properties that determine the stability of a transcript. To address these issues, genome-wide mRNA decay studies have been conducted in eukaryotes and bacteria. In contrast, relatively little is known about RNA stability in the third domain of life, Archaea. Here, we present a microarray-based analysis of mRNA half-lives in the hyperthermophilic crenarchaea Sulfolobus solfataricus and Sulfolobus acidocaldarius, constituting the first genome-wide study of RNA decay in archaea. Results: The two transcriptomes displayed similar half-life distributions, with medians of about five minutes. Growth-related genes, such as those involved in transcription, translation and energy production, were over-represented among unstable transcripts, whereas uncharacterized genes were over-represented among the most stable. Half-life was negatively correlated with transcript abundance and, unlike the situation in other organisms, also negatively correlated with transcript length. Conclusion: The mRNA half-life distribution of Sulfolobus species is similar to those of much faster growing bacteria, contrasting with the earlier observation that median mRNA half-life is proportional to the minimal length of the cell cycle. Instead, short half-lives may be a general feature of prokaryotic transcriptomes, possibly related to the absence of a nucleus and/or more limited post-transcriptional regulatory mechanisms. The pattern of growth-related transcripts being among the least stable in Sulfolobus may also indicate that the short half-lives reflect a necessity to rapidly reprogram gene expression upon sudden changes in environmental conditions.
17.	Andersson Ersman, Peter, et al. (författare) Screen printed digital circuits based on vertical organicelectrochemical transistors 2017 Ingår i: Flexible and Printed Electronics. - : IOP Publishing. - 2058-8585. ; 2 Tidskriftsartikel (refereegranskat)abstract Vertical organic electrochemical transistors (OECTs) have been manufactured solely using screenprinting. The OECTs are based on PEDOT:PSS (poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonic acid)), which defines the active material for both the transistor channel and the gateelectrode. The resulting vertical OECT devices and circuits exhibit low-voltage operation, relativelyfast switching, small footprint and high manufacturing yield; the last three parameters are explainedby the reliance of the transistor configuration on a robust structure in which the electrolyte verticallybridges the bottom channel and the top gate electrode. Two different architectures of the verticalOECT have been manufactured, characterized and evaluated in parallel throughout this report. Inaddition to the experimental work, SPICE models enabling simulations of standalone OECTs andOECT-based circuits have been developed. Our findings may pave the way for fully integrated, lowvoltageoperating and printed signal processing systems integrated with e.g. printed batteries, solarcells, sensors and communication interfaces. Such technology can then serve a low-cost basetechnology for the internet of things, smart packaging and home diagnostics applications.
18.	Andersson, Lars-Magnus, 1968, et al. (författare) Lopinavir/ritonavir, atazanavir/ritonavir, and efavirenz in antiretroviral-naïve HIV-1-infected individuals over 144 weeks: An open-label randomized controlled trial. 2013 Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:7, s. 543-551 Tidskriftsartikel (refereegranskat)abstract Background: The objective of this study was to compare the efficacy of ritonavir boosted atazanavir versus ritonavir boosted lopinavir or efavirenz, all in combination with 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs), over 144 weeks in antiretroviral-naïve HIV-1-infected individuals. Methods: A prospective open-label randomized controlled trial was conducted at 29 sites in Sweden and Norway between April 2004 and December 2009. Patients were randomized to receive either efavirenz 600 mg once daily (EFV), or atazanavir 300 mg and ritonavir 100 mg once daily (AZV/r), or lopinavir 400 mg and ritonavir 100 mg twice daily (LPV/r). The primary endpoints were the proportion of patients with HIV-1 RNA 100,000 copies/ml at baseline had similar response rates in all arms. Conclusion: EFV was superior to LPV/r at week 48, but there were no significant differences between the 3 arms in the long-term (144 weeks) follow-up.
19.	Björkelund, Anders, et al. (författare) On the Integration of Skilled Robot Motions for Productivity in Manufacturing 2011 Ingår i: IEEE International Symposium on Assembly and Manufacturing (ISAM), 2011. - 9781612843438 - 9781612843421 ; , s. 1-9 Konferensbidrag (refereegranskat)abstract Robots used in manufacturing today are tailored to their tasks by system integration based on expert knowledge concerning both production and machine control. For upcoming new generations of even more flexible robot solutions, in applications such as dexterous assembly, the robot setup and programming gets even more challenging. Reuse of solutions in terms of parameters, controls, process tuning, and of software modules in general then gets increasingly important. There has been valuable progress within reuse of automation solutions when machines comply with standards and behave according to nominal models. However, more flexible robots with sensor-based manipulation skills and congnitive functions for human inteaction are far too complex to manage, and solutions are rarely reusable since knowledge is either implicit in imperative software or not captured in machine readable form. We propose techniques that build on existing knowledge by converting structured data into an RDF-based knowledge base. By enhancements of industrial control systems and available engineering tools, such knowledge can be gradually extended as part of the interaction during the definition of the robot task.
20.	Bonander, Carl, et al. (författare) A Capture-Recapture-based Ascertainment Probability Weighting Method for Effect Estimation With Under-ascertained Outcomes. 2024 Ingår i: Epidemiology (Cambridge, Mass.). - : Lippincott Williams & Wilkins. - 1531-5487 .- 1044-3983. ; 35:3, s. 340-348 Tidskriftsartikel (refereegranskat)abstract Outcome under-ascertainment, characterized by the incomplete identification or reporting of cases, poses a substantial challenge in epidemiologic research. While capture-recapture methods can estimate unknown case numbers, their role in estimating exposure effects in observational studies is not well established. This paper presents an ascertainment probability weighting framework that integrates capture-recapture and propensity score weighting. We propose a nonparametric estimator of effects on binary outcomes that combines exposure propensity scores with data from two conditionally independent outcome measurements to simultaneously adjust for confounding and under-ascertainment. Demonstrating its practical application, we apply the method to estimate the relationship between health care work and coronavirus disease 2019 testing in a Swedish region. We find that ascertainment probability weighting greatly influences the estimated association compared to conventional inverse probability weighting, underscoring the importance of accounting for under-ascertainment in studies with limited outcome data coverage. We conclude with practical guidelines for the method's implementation, discussing its strengths, limitations, and suitable scenarios for application.
21.	Buttazzoni, Christian, et al. (författare) A Pediatric Bone Mass Scan Has Poor Ability to Predict Adult Bone Mass: A 28-Year Prospective Study in 214 Children. 2014 Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 94:2, s. 232-239 Tidskriftsartikel (refereegranskat)abstract As the correlation of bone mass from childhood to adulthood is unclear, we conducted a long-term prospective observational study to determine if a pediatric bone mass scan could predict adult bone mass. We measured cortical bone mineral content (BMC [g]), bone mineral density (BMD [g/cm(2)]), and bone width (cm) in the distal forearm by single photon absorptiometry in 120 boys and 94 girls with a mean age of 10 years (range 3-17) and mean 28 years (range 25-29) later. We calculated individual and age-specific bone mass Z scores, using the control cohort included at baseline as reference, and evaluated correlations between the two measurements with Pearson's correlation coefficient. Individual Z scores were also stratified in quartiles to register movements between quartiles from growth to adulthood. BMD Z scores in childhood and adulthood correlated in both boys (r = 0.35, p < 0.0001) and girls (r = 0.50, p < 0.0001) and in both children ≥10 years at baseline (boys r = 0.43 and girls r = 0.58, both p < 0.0001) and children <10 years at baseline (boys r = 0.26 and girls r = 0.40, both p < 0.05). Of the children in the lowest quartile of BMD, 58 % had left the lowest quartile in adulthood. A pediatric bone scan with a value in the lowest quartile had a sensitivity of 48 % (95 % confidence interval [CI] 27-69 %) and a specificity of 76 % (95 % CI 66-84 %) to identify individuals who would remain in the lowest quartile also in adulthood. Childhood forearm BMD explained 12 % of the variance in adult BMD in men and 25 % in women. A pediatric distal forearm BMD scan has poor ability to predict adult bone mass.
22.	Buttazzoni, Christian, et al. (författare) A Pediatric Bone Mass Scan has Poor Ability to Predict Peak Bone Mass: An 11-Year Prospective Study in 121 Children. 2015 Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 96:5, s. 379-388 Tidskriftsartikel (refereegranskat)abstract This 11-year prospective longitudinal study examined how a pre-pubertal pediatric bone mass scan predicts peak bone mass. We measured bone mineral content (BMC; g), bone mineral density (BMD; g/cm(2)), and bone area (cm(2)) in femoral neck, total body and lumbar spine by dual-energy X-ray absorptiometry in a population-based cohort including 65 boys and 56 girls. At baseline all participants were pre-pubertal with a mean age of 8 years (range 6-9), they were re-measured at a mean 11 years (range 10-12) later. The participants were then mean 19 years (range 18-19), an age range that corresponds to peak bone mass in femoral neck in our population. We calculated individual BMC, BMD, and bone size Z scores, using all participants at each measurement as reference and evaluated correlations between the two measurements. Individual Z scores were also stratified in quartiles to register movements between quartiles from pre-pubertal age to peak bone mass. The correlation coefficients (r) between pre-pubertal and young adulthood measurements for femoral neck BMC, BMD, and bone area varied between 0.37 and 0.65. The reached BMC value at age 8 years explained 42 % of the variance in the BMC peak value; the corresponding values for BMD were 31 % and bone area 14 %. Among the participants with femoral neck BMD in the lowest childhood quartile, 52 % had left this quartile at peak bone mass. A pediatric bone scan with a femoral neck BMD value in the lowest quartile had a sensitivity of 47 % [95 % confidence interval (CI) 28, 66] and a specificity of 82 % (95 % CI 72, 89) to identify individuals who would remain in the lowest quartile at peak bone mass. The pre-pubertal femoral neck BMD explained only 31 % of the variance in femoral neck peak bone mass. A pre-pubertal BMD scan in a population-based sample has poor ability to predict individuals who are at risk of low peak bone mass.
23.	Buttazzoni, Christian, et al. (författare) Preterm Children Born Small for Gestational Age are at Risk for Low Adult Bone Mass. 2016 Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 98:2, s. 105-113 Tidskriftsartikel (refereegranskat)abstract Cross-sectional studies suggest that premature birth and low birth weight may both be associated with low peak bone mass. We followed bone traits in preterm individuals and controls for 27 years and examined the effects of birth weight relative to gestational age [stratified as small for gestational age (SGA) or appropriate for gestational (AGA)] on adult bone mineral density (BMD). We measured distal forearm BMC (g/cm) and BMD (g/cm(2)) with single-photon absorptiometry (SPA) in 46 preterm children (31 AGA and 15 SGA) at mean age 10.1 years (range 4-16) and in 84 healthy age-matched children. The measurements were repeated 27 years later with the same SPA apparatus but then also with dual energy absorptiometry and peripheral computed tomography (pQCT). Preterm individuals were shorter (p = 0.03) in adulthood than controls. Preterm AGA individuals had similar BMC and BMD height-adjusted Z-scores in adulthood compared to controls. Preterm SGA individuals had lower distal forearm BMC and BMD height-adjusted Z-scores in adulthood than both controls and preterm AGA individuals. Preterm SGA individuals had lower gain from childhood to adulthood in distal forearm BMC height-adjusted Z-scores than controls (p = 0.03). The deficits in preterm SGA individuals in adulthood were also captured by DEXA in height-adjusted femoral neck (FN) BMC Z-score and height-adjusted FN BMD Z-score and by pQCT in tibial cross-sectional area (CSA) Z-score and stress strain index (SSI) Z-score, where all measurements were lower than controls (all p values <0.05). Preterm SGA individuals are at increased risk of reaching low adult bone mass, at least partly due to a deficit in the accrual of bone mineral during growth. In our cohort, we were unable to find a similar risk in preterm AGA individuals.
24.	Cöster, Marcus E., et al. (författare) How does a physical activity programme in elementary school affect fracture risk? : A prospective controlled intervention study in Malmo, Sweden 2017 Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:2 Tidskriftsartikel (refereegranskat)abstract Objectives: Recent evidence from the 7-year followup of the Pediatric Osteoporosis Prevention (POP) study indicates an inverse correlation between years of participation in a physical activity (PA) intervention and fracture risk in children. However, we could not see a statistically significant reduction in fracture risk, which urged for an extension of the intervention. Setting: The study was conducted in 4 neighbouring elementary schools, where 1 school functioned as intervention school. Participants: We included all children who began first grade in these 4 schools between 1998 and 2012. This resulted in 1339 children in the intervention group and 2195 children in the control group, all aged 6-8 years at the state of the study. Intervention: We launched an 8-year intervention programme with 40 min of moderate PA per school day, while the controls continued with the Swedish national standard of 60 min of PA per week. Primary outcome measure: We used the regional radiographic archive to register objectively verified fractures and we estimated annual fracture incidences and incidence rate ratios (IRRs). Results: During the first year after initiation of the intervention, the fracture IRR was 1.65 (1.05 to 2.08) (mean 95% CI). For each year of the study, the fracture incidence rate in the control group compared with the intervention group increased by 15.7% (5.6% to 26.8%) (mean 95% CI). After 8 years, the IRR of fractures was 52% lower in the intervention group than in the control group (IRR 0.48 (0.25 to 0.91) (mean 95% CI))]. Conclusions: Introduction of the school-based intervention programme is associated with a higher fracture risk in the intervention group during the first year followed by a gradual reduction, so that during the eighth year, the fracture risk was lower in the intervention group.
25.	Danielsson, Angelika, 1981-, et al. (författare) An ex vivo loop system models the toxicity and efficacy of PEGylated and unmodified adenovirus serotype 5 in whole human blood 2010 Ingår i: Gene Therapy. - : Nature Publishing Group. - 0969-7128 .- 1476-5462. ; 17:6, s. 752-762 Tidskriftsartikel (refereegranskat)abstract Polyethylene glycol coating (PEGylation) of adenovirus serotype 5 (Ad5) has been shown to effectively reduce immunogenicity and increase circulation time of intravenously administered virus in mouse models. Herein, we monitored clot formation, complement activation, cytokine release and blood cell association upon addition of uncoated or PEGylated Ad5 to human whole blood. We used a novel blood loop model where human blood from healthy donors was mixed with virus and incubated in heparin-coated PVC tubing while rotating at 37°C for up to 8 hours. Production of the complement components C3a and C5a and the cytokines IL-8, RANTES and MCP-1 was significantly lower with 20K-PEGylated Ad5 than with uncoated Ad5. PEGylation prevented clotting and reduced Ad5 binding to blood cells in blood with low ability to neutralize Ad5. The effect was particularly pronounced in monocytes, granulocytes, B-cells and T-cells, but could also be observed in erythrocytes and platelets. In conclusion, PEGylation of Ad5 can reduce the immune response mounted in human blood, although the protective effects are rather modest in contrast to published mouse data. Our findings underline the importance of developing reliable models and we propose the use of human whole blood models in pre-clinical screening of gene therapy vectors.
26.	Deland, Lily, et al. (författare) Discovery of a rare GKAP1-NTRK2 fusion in a pediatric low-grade glioma, leading to targeted treatment with TRK-inhibitor larotrectinib 2021 Ingår i: Cancer Biology & Therapy. - : Taylor & Francis. - 1538-4047 .- 1555-8576. ; 22:3, s. 184-195 Tidskriftsartikel (refereegranskat)abstract Here we report a case of an 11-year-old girl with an inoperable tumor in the optic chiasm/hypothalamus, who experienced several tumor progressions despite three lines of chemotherapy treatment. Routine clinical examination classified the tumor as a BRAF-negative pilocytic astrocytoma. Copy-number variation profiling of fresh frozen tumor material identified two duplications in 9q21.32–33 leading to breakpoints within the GKAP1 and NTRK2 genes. RT-PCR Sanger sequencing revealed a GKAP1-NTRK2 exon 10–16 in-frame fusion, generating a putative fusion protein of 658 amino acids with a retained tyrosine kinase (TK) domain. Functional analysis by transient transfection of HEK293 cells showed the GKAP1-NTRK2 fusion protein to be activated through phosphorylation of the TK domain (Tyr705). Subsequently, downstream mediators of the MAPK- and PI3K-signaling pathways were upregulated in GKAP1-NTRK2 cells compared to NTRK2 wild-type; phosphorylated (p)ERK (3.6-fold), pAKT (1.8- fold), and pS6 ribosomal protein (1.4-fold). Following these findings, the patient was enrolled in a clinical trial and treated with the specific TRK-inhibitor larotrectinib, resulting in the arrest of tumor growth. The patient’s condition is currently stable and the quality of life has improved significantly. Our findings highlight the value of comprehensive clinical molecular screening of BRAF-negative pediatric low-grade gliomas, to reveal rare fusions serving as targets for precision therapy.
27.	Deland, Lily, et al. (författare) Novel TPR::ROS1 Fusion Gene Activates MAPK, PI3K and JAK/STAT Signaling in an Infant-type Pediatric Glioma. 2022 Ingår i: Cancer genomics & proteomics. - : Anticancer Research USA Inc.. - 1109-6535 .- 1790-6245. ; 19:6, s. 711-726 Tidskriftsartikel (refereegranskat)abstract Although fusion genes involving the proto-oncogene receptor tyrosine kinase ROS1 are rare in pediatric glioma, targeted therapies with small inhibitors are increasingly being approved for histology-agnostic fusion-positive solid tumors.Here, we present a 16-month-old boy, with a brain tumor in the third ventricle. The patient underwent complete resection but relapsed two years after diagnosis and underwent a second operation. The tumor was initially classified as a low-grade glioma (WHO grade 2); however, methylation profiling suggested the newly WHO-recognized type: infant-type hemispheric glioma. To further refine the molecular background, and search for druggable targets, whole genome (WGS) and whole transcriptome (RNA-Seq) sequencing was performed.Concomitant WGS and RNA-Seq analysis revealed several segmental gains and losses resulting in complex structural rearrangements and fusion genes. Among the top-candidates was a novel TPR::ROS1 fusion, for which only the 3' end of ROS1 was expressed in tumor tissue, indicating that wild type ROS1 is not normally expressed in the tissue of origin. Functional analysis by Western blot on protein lysates from transiently transfected HEK293 cells showed the TPR::ROS1 fusion gene to activate the MAPK-, PI3K- and JAK/STAT- pathways through increased phosphorylation of ERK, AKT, STAT and S6. The downstream pathway activation was also confirmed by immunohistochemistry on tumor tissue slides from the patient.We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse.
28.	Dereke, Jonatan, et al. (författare) Soluble CD163 and TWEAK in early pregnancy gestational diabetes and later glucose intolerance 2019 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:5 Tidskriftsartikel (refereegranskat)abstract Gestational diabetes mellitus (GDM) is today universally diagnosed during late pregnancy. Treating hyperglycaemia during pregnancy reduces the risk of complications, the effect of interventions is however limited due to the late diagnosis. It is thus important to identify biomarkers reaching a high precision for GDM development in early pregnancy. Here we aim to investigate soluble CD163 (sCD163) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) in early pregnancy GDM and their association to the development of later glucose intolerance. In this case-control study, women diagnosed with GDM in early pregnancy (n = 70) at Lund University Hospital, Lund, Sweden in 2011–2015 were age- and BMI matched to pregnant volunteers without diabetes (n = 70) recruited in early pregnancy from maternal health care centres in 2014–2015. Plasma levels of sCD163 and sTWEAK were analysed using commercial ELISA. Plasma levels of sCD163 did not differ between patients with and without GDM in early pregnancy (p = 0.86), plasma levels of sTWEAK however was decreased in women with GDM (0.71 [0.4–1.75] ng/ml) compared to controls (1.38 [0.63–4.86] ng/ml; p = 0.003). Women with sTWEAK levels in the lowest tertile had an increased risk of GDM in early pregnancy (p = 0.014). Neither sCD163 nor sTWEAK were associated with later glucose intolerance in women with GDM. This study reports decreased levels of sTWEAK in women with early pregnancy GDM, independent of age and BMI. Neither sCD163 nor sTWEAK were found to be associated to later glucose intolerance.
29.	Detter, Fredrik, et al. (författare) A 3-year school-based exercise intervention improves muscle strength - a prospective controlled population-based study in 223 children 2014 Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: Intense physical activity (PA) improves muscle strength in children, but it remains uncertain whether moderately intense PA in a population-based cohort of children confers these benefits. Methods: We included children aged 6-9 years in four schools where the intervention school increased the school curriculum of PA from 60 minutes/week to 40 minutes/school day while the control schools continued with 60 minutes/week for three years. We measured muscle strength, as isokinetic Peak Torque (PT) (Nm) of the knee flexors in the right leg at speeds of 60 degrees/second and 180 degrees/second, at baseline and at follow-up, in 47 girls and 76 boys in the intervention group and 46 girls and 54 boys in the control group and then calculated annual changes in muscle strength. Data are provided as means with 95% confidence intervals. Results: Girls in the intervention group had 1.0 Nm (0.13, 1.9) and boys 1.9 Nm (0.9, 2.9) greater annual gain in knee flexor PT at 60 degrees/second, than girls and boys in the control group. Boys in the intervention group also had 1.5 Nm (0.5, 2.5) greater annual gain in knee flexors PT at 180 degrees/second than boys in the control group. Conclusion: A 3-year moderately intense PA intervention program within the school curriculum enhances muscle strength in both girls and boys.
30.	Detter, Fredrik, et al. (författare) A 5-Year Exercise Program in Pre- and Peripubertal Children Improves Bone Mass and Bone Size Without Affecting Fracture Risk. 2013 Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 92:4, s. 385-393 Tidskriftsartikel (refereegranskat)abstract We studied the effect in children of an exercise intervention program on fracture rates and skeletal traits. Fractures were registered for 5 years in a population-based prospective controlled exercise intervention study that included children aged 6-9 years at study start, 446 boys and 362 girls in the intervention group and 807 boys and 780 girls in the control group. Intervention subjects received 40 min/school day of physical education and controls, 60 min/week. In 73 boys and 48 girls in the intervention group and 52 boys and 48 girls in the control group, bone mineral density (BMD, g/cm(2)) and bone area (mm(2)) were followed annually by dual-energy X-ray absorptiometry, after which annual changes were calculated. At follow-up we also assessed trabecular and cortical volumetric BMD (g/cm(3)) and bone structure by peripheral computed tomography in the tibia and radius. There were 20.0 fractures/1,000 person-years in the intervention group and 18.5 fractures/1,000 person-years in the control group, resulting in a rate ratio of 1.08 (0.79-1.47) (mean and 95 % CI). The gain in spine BMD was higher in both girls (difference 0.01 g/cm(2), 0.005-0.019) and boys (difference 0.01 g/cm(2), 0.001-0.008) in the intervention group. Intervention girls also had higher gain in femoral neck area (difference 0.04 mm(2), 0.005-0.083) and at follow-up larger tibial bone mineral content (difference 0.18 g, 0.015-0.35), larger tibial cortical area (difference 17 mm(2), 2.4-31.3), and larger radial cross-sectional area (difference 11.0 mm(2), 0.63-21.40). As increased exercise improves bone mass and in girls bone size without affecting fracture risk, society ought to encourage exercise during growth.
31.	Detter, Fredrik, et al. (författare) A Six-Year Exercise Program Improves Skeletal Traits without Affecting Fracture Risk - a Prospective Controlled Study in 2621 Children 2014 Ingår i: Journal of bone and mineral research. - : Wiley. - 0884-0431 .- 1523-4681. ; 29:6, s. 1325-1336 Tidskriftsartikel (refereegranskat)abstract Most pediatric exercise intervention studies, that evaluates the effect on skeletal traits include volunteers and follow bone mass for less than three years. We present a population-based six-year controlled exercise intervention study in children with also bone structure and incident fractures as endpoints. Fractures were registered in 417 girls and 500 boys in the intervention group (3969 person-years) and 835 girls and 869 boys in the control group (8245 person-years), all aged 6-9 years at study start, during the six-year study period. Children in the intervention group had 40 minutes daily school physical education (PE) and the control group 60 minutes per week. In a sub-cohort with 78 girls and 111 boys in the intervention group and 52 girls and 54 boys in the control group, bone mineral density (g/cm2 ) and bone area (mm2 ) were measured repeatedly by dual energy X-ray absorptiometry (DXA). Peripheral quantitative computed tomography (pQCT) measured bone mass and bone structure at follow-up. There were 21.7 low and moderate energy related fractures per 1000 person-years in the intervention group and 19.8 fractures in the control group, leading to a Rate Ratio (RR) of 1.12 (0.85, 1.46). Girls in the intervention group, in comparison with girls in the control group, had 0.009 g/cm2 (0.003, 0.015) larger gain annually in spine BMD, 0.07 g (0.014, 0.123) larger gain in femoral neck BMC and 4.0 mm2 (0.5, 7.8) larger gain in femoral neck area, and at follow-up 24.1 g (7.6, 40.6) higher tibial cortical BMC (g) and 23.9 mm2 (5.27, 42.6) larger tibial cross-sectional area. Boys with daily PE had 0.006 g/cm2 (0.002, 0.010) larger gain annually in spine BMD than control boys but at follow-up no higher pQCT values than boys in the control group. Daily PE for six years in at study start 6-9 year old improves bone mass and bone size in girls and bone mass in boys, without affecting the fracture risk. (c) 2014 American Society for Bone and Mineral Research.
32.	Edén, Arvid, 1975, et al. (författare) Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients. 2010 Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 26:5, s. 533-40 Tidskriftsartikel (refereegranskat)abstract Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.
33.	Edén, Arvid, 1975, et al. (författare) Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms. 2022 Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:5 Tidskriftsartikel (refereegranskat)abstract Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF).To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity.This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included.SARS-CoV-2 infection.Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, β2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]).Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r=0.38; P=.03) and interferon γ (r=0.42; P=.01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, β2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P=.03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P=.04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P=.002). No differences were seen in any CSF biomarkers in moderate compared with severe disease.In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
34.	Ekman, Jonas, et al. (författare) Projekt: Rymdforskarskolan 2015 Annan publikation (populärvet., debatt m.m.)abstract The Graduate School of Space Technology
35.	Ekström, Ulf, et al. (författare) An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F) 1999 Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 55:5, s. 332-339 Tidskriftsartikel (refereegranskat)abstract Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.
36.	Engström, Gunnar, et al. (författare) Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications 2024 Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49 Tidskriftsartikel (refereegranskat)abstract Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
37.	Fritz, Jesper, et al. (författare) A 5-year exercise program in children improves muscle strength without affecting fracture risk. 2016 Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 116:4, s. 707-715 Tidskriftsartikel (refereegranskat)abstract High level of physical activity (PA) is associated with great muscle strength and high fracture risk. This prospective controlled population-based study evaluated how a pediatric PA intervention program influenced muscle strength and fracture risk.
38.	Fritz, Jesper, et al. (författare) The associations of physical activity with fracture risk-a 7-year prospective controlled intervention study in 3534 children. 2016 Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 27:3, s. 915-922 Tidskriftsartikel (refereegranskat)abstract This is the first study indicating an association between gradually diminished risk of fractures and years of increased physical activity. Our results could imply great benefits not only for the individual but also for the healthcare burden and cost of society.
39.	Habibovic, Azra, et al. (författare) Evaluating interactions with non-existing automated vehicles: three Wizard of Oz approaches 2016 Ingår i: 2016 IEEE Intelligent Vehicles Symposium (IV). - Piscataway, NJ : IEEE. - 9781509018215 - 9781509018222 ; , s. 32-37 Konferensbidrag (refereegranskat)abstract Highly automated test vehicles are rare today, and (independent) researchers have often limited access to them. Also, developing fully functioning system prototypes is time and effort consuming. In this paper, we present three adaptions of the Wizard of Oz technique as a means of gathering data about interactions with highly automated vehicles in early development phases. Two of them address interactions between drivers and highly automated vehicles, while the third one is adapted to address interactions between pedestrians and highly automated vehicles. The focus is on the experimental methodology adaptations and our lessons learned.
40.	Hansen, Karin B., et al. (författare) Flocked nasal swab versus nasopharyngeal aspirate in adult emergency room patients: similar multiplex PCR respiratory pathogen results and patient discomfort 2016 Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:3, s. 246-250 Tidskriftsartikel (refereegranskat)abstract Fifty adult emergency room patients with symptoms of respiratory tract infections or acute onset of extreme fatigue were sampled by both nasopharyngeal aspirate (NPA) and flocked nasal swab (fNS). Respiratory agents were detected by a qualitative influenza PCR and an 18-valent multiplex PCR in 20 of 29 patients with a clinical diagnosis of respiratory tract infection, and in 3 of 21 without such a diagnosis. PCR detected influenza A and B in NPA samples from 11 patients and in fNS samples from 10 patients. Little or no discomfort was perceived by 60% of the patients when sampled by NPA and by 66% when sampled by fNS. We conclude that NPA and fNS were equally sensitive for detection of respiratory agents by multiplex PCR, and the two sampling methods did not differ significantly regarding discomfort perceived by patients (p=0.171, Wilcoxon signed rank test). Hence less invasive sampling by fNS might be preferable in certain settings and situations.
41.	Hedberg, Jakob, et al. (författare) Randomized controlled trial of nasogastric tube use after esophagectomy : study protocol for the kinetic trial 2024 Ingår i: Diseases of the esophagus. - : John Wiley & Sons. - 1120-8694 .- 1442-2050. ; 37:6 Tidskriftsartikel (refereegranskat)abstract Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.
42.	Huang, Ranyang, et al. (författare) Expression of a Mast Cell Tryptase in the Human Monocytic Cell Lines U-937 and Mono Mac 6 1993 Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 38:4, s. 359-367 Tidskriftsartikel (refereegranskat)abstract Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood(PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon-gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non-induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'.
43.	Kanberg, Nelly, et al. (författare) Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up. 2021 Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 70 Tidskriftsartikel (refereegranskat)abstract Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19.Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15).One hundred patients with mild (n=24), moderate (n=28), and severe (n=48) COVID-19 were followed for a median (IQR) of 225 (187-262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r=0·53, p < 0·001) and GFAp (r=0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n=40), "brain-fog" (n=29), and changes in cognition (n=25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase.The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury.The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project.
44.	Karlsson, Martin, et al. (författare) Measurement of the differential cross section for the two-body photodisintegration of He-3 at theta(LAB)=90 degrees using tagged photons in the energy range 14-31 MeV 2009 Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:4 Tidskriftsartikel (refereegranskat)abstract The two-body photodisintegration of He-3 has been investigated using tagged photons with energies from 14-31 MeV at MAX-lab in Lund, Sweden. The two-body breakup channel was unambiguously identified by the (nonsimultaneous) detection of both protons and deuterons. This approach was made feasible by the overdetermined kinematic situation afforded by the tagged-photon technique. Proton-and deuteron-energy spectra were measured using four silicon surface-barrier detector telescopes located at a laboratory angle of 90 degrees with respect to the incident photon-beam direction. Average statistical and systematic uncertainties of 5.7% and 6.6% in the differential cross section were obtained for 11 photon-energy bins with an average width of 1.2 MeV. The results are compared to previous experimental data measured at comparable photon energies as well as to the results of two recent Faddeev calculations which employ realistic potential models and take into account three-nucleon forces and final-state interactions. Both the accuracy and precision of the present data are improved over those obtained in the previous measurements. The data are in good agreement with most of the previous results, and favor the inclusion of three-nucleon forces in the calculations.
45.	Karlsson, S. C. Hannah, et al. (författare) Combining CAR T cells and the Bcl-2 family apoptosis inhibitor ABT-737 for treating B-cell malignancy 2013 Ingår i: Cancer Gene Therapy. - : Springer Science and Business Media LLC. - 0929-1903 .- 1476-5500. ; 20:7, s. 386-393 Tidskriftsartikel (refereegranskat)abstract B-cell malignancies upregulate the B-cell lymphoma 2 (Bcl-2) family inhibitors of the intrinsic apoptosis pathway, making them therapy resistant. However, small-molecule inhibitors of Bcl-2 family members such as ABT-737 restore a functional apoptosis pathway in cancer cells, and its oral analog ABT-263 (Navitoclax) has entered clinical trials. Gene engineered chimeric antigen receptor (CAR) T cells also show promise in B-cell malignancy, and as they induce apoptosis via the extrinsic pathway, we hypothesized that small-molecule inhibitors of the Bcl-2 family may potentiate the efficacy of CAR T cells by engaging both apoptosis pathways. CAR T cells targeting CD19 were generated from healthy donors as well as from pre-B-ALL (precursor-B acute lymphoblastic leukemia) patients and tested together with ABT-737 to evaluate apoptosis induction in five B-cell tumor cell lines. The CAR T cells were effective even if the cell lines exhibited different apoptosis resistance profiles, as shown by analyzing the expression of apoptosis inhibitors by PCR and western blot. When combining T-cell and ABT-737 therapy simultaneously, or with ABT-737 as a presensitizer, tumor cell apoptosis was significantly increased. In conclusion, the apoptosis inducer ABT-737 enhanced the efficacy of CAR T cells and could be an interesting drug candidate to potentiate T-cell therapy.
46.	Kawahara, Jun, et al. (författare) Flexible active matrix addressed displays manufactured by printing and coating techniques 2013 Ingår i: Journal of Polymer Science Part B. - : Wiley-Blackwell. - 0887-6266 .- 1099-0488. ; 51:4, s. 265-271 Tidskriftsartikel (refereegranskat)abstract A flexible electrochromic active matrix addressed display, including 8 × 8 pixels, is demonstrated by using solution processing based on standard printing and coating manufacturing techniques. Each organic electrochromic display (OECD) pixel and its corresponding organic electrochemical transistor (OECT) are located on different sides of the flexible PET substrate. Electronic vias generated through the plastic substrate connects each OECD pixel with one addressing OECT. When comparing this display with actively addressed OECDs with all its components located on the same side, the present approach based on this electronic via substrate provides an enhanced pixel resolution and a relatively more simplified manufacturing process.
47.	Kudahettige-Nilsson, Rasika L., et al. (författare) Biobutanol Production by Clostridium acetobutylicum Using Xylose Recovered from Birch Kraft Black Liquor 2015 Ingår i: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 176, s. 71-79 Tidskriftsartikel (refereegranskat)abstract Acetone-Butanol-Ethanol (ABE) fermentation was studied using acid-hydrolyzed xylan recovered from hardwood Kraft black liquor by CO2 acidification as the only carbon source. Detoxification of hydrolyzate using activated carbon was conducted to evaluate the impact of inhibitor removal and fermentation. Xylose hydrolysis yields as high as 18.4% were demonstrated at the highest severity hydrolysis condition. Detoxification using active carbon was effective for removal of both phenolics (76-81%) and HMF (38-52%). Batch fermentation of the hydrolyzate and semi-defined P2 media resulted in a total solvent yield of 0.12-0.13 g/g and 0.34 g/g, corresponding to a butanol concentration of 1.8-2.1 g/L and 7.3 g/L respectively. This work is the first study of a process for the production of a biologically-derived biofuel from hemicelluloses solubilized during Kraft pulping and demonstrates the feasibility of utilizing xylan recovered directly from industrial Kraft pulping liquors as a feedstock for biological production of biofuels such as butanol.
48.	Kvarnung, Malin, et al. (författare) Genomic screening in rare disorders : new mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability 2018 Ingår i: Clinical Genetics. - : John Wiley & Sons. - 0009-9163 .- 1399-0004. ; 94:6, s. 528-537 Tidskriftsartikel (refereegranskat)abstract We have investigated 20 consanguineous families with multiple children affected by rare disorders. Detailed clinical examinations, exome sequencing of affected as well as unaffected family members and further validation of likely pathogenic variants were performed. In 16/20 families, we identified pathogenic variants in autosomal recessive disease genes (ALMS1, PIGT, FLVCR2, TFG, CYP7B1, ALG14, EXOSC3, MEGF10, ASAH1, WDR62, ASPM, PNPO, ERCC5, KIAA1109, RIPK4, MAN1B1). A number of these genes have only rarely been reported previously and our findings thus confirm them as disease genes, further delineate the associated phenotypes and expand the mutation spectrum with reports of novel variants. We highlight the findings in two affected siblings with splice altering variants in ALG14 and propose a new clinical entity, which includes severe intellectual disability, epilepsy, behavioral problems and mild dysmorphic features, caused by biallelic variants in ALG14.
49.	Lahti, Amanda, et al. (författare) Daily School Physical Activity Is Associated with Higher Level of Physical Activity Independently of Other Socioecological Factors 2020 Ingår i: Sports. - : MDPI AG. - 2075-4663. ; 8:8 Tidskriftsartikel (refereegranskat)abstract Only one fifth of children aged 11–17 years are physically active for 60 min (min)/day. As physical activity (PA) levels track from childhood to adulthood, it is important to establish healthy PA behavior early in life. This study aims to evaluate whether daily school PA is associated with objectively measured PA independently of other socioecological factors. This study includes 209 children (120 boys) aged 9.8 ± 0.6 (mean ± SD) years from four government-funded schools in Sweden. One school including 113 children (70 boys) had 40 min of daily school PA (intervention) and three schools including 96 children (50 boys) had 60 min of school PA/week (control). PA was measured during four serial days with accelerometers. General PA (GPA) was defined as mean counts per minute (cpm). Socioecological factors were collected by questionnaires, and anthropometric traits by measurements. Analysis of covariance (ANCOVA) was used to test whether sex, age, relative age, body height, fat mass, lean mass, screen time activity, parental educational level, parental attitude towards PA, parental PA, sibling(s)’ PA, living in a house or apartment, and whether the child was allocated to 40 min daily school PA or 60 min school PA/week, was independently associated with GPA. Daily GPA was found to be 686.9 ± 211.9 cpm. Independently of the other included factors, daily school PA was associated with +81.8 (15.7, 147.8) cpm compared with 60 min PA/week. This study infers that daily school PA is an appropriate strategy to promote PA in 10-year-old children, independently of different socioecological factors.
50.	Lahti, Amanda, et al. (författare) Socioecological and biological associations of lower levels of physical activity in 8-year-old children : A 2-year prospective study 2019 Ingår i: BMJ Open Sport & Exercise Medicine. - 2055-7647. ; 5:1 Tidskriftsartikel (refereegranskat)abstract Objectives: Evaluate if socioecological and biological factors, at the age of 8 years, are associated with lower level of physical activity (PA) 2 years later. Method: In a study cohort of 199 children aged 7.8±0.6 years, we used questionnaires and physical measurements to evaluate biological (eg, sex), social (eg, parental PA) and environmental (eg, school settings) factors. Objective PA was measured 2 years later with accelerometers. General PA (GPA) was defined as mean counts per minute (cpm) and moderate to vigorous PA (MVPA) as min/day >3500 cpm. We used analysis of covariance to evaluate if socioecological factors at age 8 are associated with level of PA 2 years later. Results: Daily GPA was 690.5±216.6 cpm and the children spent 40.9±18.3 min on MVPA. Female sex is associated with-131.1 (-183.4,-78.7) cpm GPA, each 10 cm shorter body height with-48.7 (-94.8,-26.5), each unit higher body mass index (BMI) with-26.0 (-37.5,-14.5) and allocation to 60 min school PA/week with-73.8 (-131.5,-16.2) compared with allocation to 200 min school PA/week. Female sex is associated with-10.3 (-14.8,-5.7) min of MVPA and each unit higher BMI with-1.9 (-2.9,-0.9) min. Conclusion: Female sex, shorter body height and higher BMI are at age 8 years associated with lower level of PA 2 years later. It appears possible to increase PA by daily school PA.

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