| 1. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 2. |
- Midtvedt, Benjamin, et al.
(författare)
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Single-shot self-supervised object detection in microscopy
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Object detection is a fundamental task in digital microscopy, where machine learning has made great strides in overcoming the limitations of classical approaches. The training of state-of-the-art machine-learning methods almost universally relies on vast amounts of labeled experimental data or the ability to numerically simulate realistic datasets. However, experimental data are often challenging to label and cannot be easily reproduced numerically. Here, we propose a deep-learning method, named LodeSTAR (Localization and detection from Symmetries, Translations And Rotations), that learns to detect microscopic objects with sub-pixel accuracy from a single unlabeled experimental image by exploiting the inherent roto-translational symmetries of this task. We demonstrate that LodeSTAR outperforms traditional methods in terms of accuracy, also when analyzing challenging experimental data containing densely packed cells or noisy backgrounds. Furthermore, by exploiting additional symmetries we show that LodeSTAR can measure other properties, e.g., vertical position and polarizability in holographic microscopy.
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| 3. |
- Singleton, Rosie K., et al.
(författare)
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Risk prediction for renal cell Carcinoma : Results from the European Prospective Investigation into Cancer and nutrition (EPIC) prospective cohort study
- 2021
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - : AACR. - 1055-9965 .- 1538-7755. ; 30:3, s. 507-512
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives. Methods: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure. Results: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679–0.721]). Our model had slightly improved discrimination (0.714 [0.694–0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025. Conclusions: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population. Impact: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.
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| 4. |
- Slöetjes, Sam D., et al.
(författare)
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Effects of array shape and disk ellipticity in dipolar-coupled magnetic metamaterials
- 2021
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Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 104:13
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Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional lattices of dipolar-coupled thin film ferromagnetic nanodisks give rise to emergent superferromagnetic (SFM) order when the spacing between dots becomes sufficiently small. In this paper, we define micron-sized arrays of permalloy nanodisks arranged on a hexagonal lattice. The arrays were shaped as hexagons, squares, and rectangles to investigate finite-size effects in the SFM domain structure for such arrays. The resulting domain patterns were examined using x-ray magnetic circular dichroism photoemission electron microscopy. At room temperature, we find these SFM metamaterials to be below their blocking temperature. Distinct differences were found in the magnetic switching characteristics of horizontally and vertically oriented rectangular arrays. The results are corroborated by micromagnetic simulations.
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| 5. |
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| 6. |
- Jaffe, J Douglas, et al.
(författare)
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Bone Cement Implantation Syndrome: Incidence and Associated Factors in a United States Setting.
- 2022
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Ingår i: Cureus. - 2168-8184. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of bone cement implantation syndrome (BCIS) following cemented hemiarthroplasty for the treatment of hip fracture in the United States (US) population is not previously described. We sought to describe the incidence and factors associated with BCIS as well as its impact on mortality.In this retrospective observational study, electronic health records were examined for all relevant cases and BCIS was identified and graded according to accepted criteria. Demographic data was collected and an adjusted Cox proportional model was performed to determine the impact of severe BCIS on mortality.Following exclusions for documentation error and misclassification, 69 patients were included in the final analysis. BCIS, regardless of grade, was present in 24 (35%) patients, while severe BCIS (grades 2 and 3) was found in 7 (10%) of patients. Cox proportional hazard estimation adjusted for American Society of Anesthesiologists (ASA) grade, male sex, and age did not show severe BCIS to be independently associated with mortality, hazard ratio (CI) 1.96 (0.22-17.22).The incidence of BCIS in a selected hip fracture population is comparable in the US to those found in European studies. This study did not establish the occurrence of BCIS with mortality. As cemented hemiarthroplasty is recommended for displaced hip fractures and its use escalates in the US, one can expect an increase in the absolute number of patients experiencing BCIS as well.
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| 7. |
- Khanna, Ashish K, et al.
(författare)
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Role of continuous pulse oximetry and capnography monitoring in the prevention of postoperative respiratory failure, postoperative opioid-induced respiratory depression and adverse outcomes on hospital wards: A systematic review and meta-analysis.
- 2024
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Ingår i: Journal of clinical anesthesia. - 1873-4529. ; 94
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Forskningsöversikt (refereegranskat)abstract
- The current standards of postoperative respiratory monitoring on medical-surgical floors involve spot-pulse oximetry checks every 4-8h, which can miss the opportunity to detect prolonged hypoxia and acute hypercapnia. Continuous respiratory monitoring can recognize acute respiratory depression episodes; however, the existing evidence is limited. We sought to review the current evidence on the effectiveness of continuous pulse oximetry (CPOX) with and without capnography versus routine monitoring and their effectiveness for detecting postoperative respiratory failure, opioid-induced respiratory depression, and preventing downstream adverse events.We performed a systematic literature search on Ovid Medline, Embase, and Cochrane Library databases for articles published between 1990 and April 2023. The study protocol was registered in Prospero (ID: 439467), and PRISMA guidelines were followed. The NIH quality assessment tool was used to assess the quality of the studies. Pooled analysis was conducted using the software R version 4.1.1 and the package meta. The stability of the results was assessed using sensitivity analysis.Systematic Review and Meta-Analysis.Postoperative recovery area.56,538 patients, ASA class II to IV, non-invasive respiratory monitoring, and post-operative respiratory depression.Continuous pulse oximetry with or without capnography versus routine monitoring.Respiratory rate, oxygen saturation, adverse events, and rescue events.23 studies (17 examined CPOX without capnography and 5 examined CPOX with capnography) were included in this systematic review. CPOX was better at recognizing desaturation (SpO2<90%) OR: 11.94 (95% CI: 6.85, 20.82; p<0.01) compared to standard monitoring. No significant differences were reported for ICU transfer, reintubation, and non-invasive ventilation between the two groups.Oxygen desaturation was the only outcome better detected with CPOX in postoperative patients in hospital wards. These comparisons were limited by the small number of studies that could be pooled for each outcome and the heterogeneity between the studies.
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| 8. |
- Niklasson, Lars, et al.
(författare)
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Effects of Cortisol on the Intestinal Mucosal Immune Response during Cohabitant Challenge with IPNV in Atlantic Salmon (Salmo salar)
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Infectious pancreatic necrosis virus (IPNV) causes high incidence of disease in salmonids during the first period after SW transfer. During this period as well as during periods of stress, cortisol levels increase and indications of a relationship between IPNV susceptibility and cortisol have been suggested. The intestine is an entry route and a target tissue for IPNV displaying severe enteritis and sloughing of the mucosa in infected fish. The mechanisms behind effects of the virus on the intestinal tissue and the impact of cortisol on the effect remain unclear. In the present study, Atlantic salmon post smolts treated with or without slow release cortisol implants were subjected to a cohabitant IPNV challenge. Analysis of genes and proteins related to the innate and acquired immune responses against virus was performed 6 days post-challenge using qPCR and immunohistochemistry. An increased mRNA expression of anti-viral cytokine interferon type I was observed in the proximal intestine and head kidney as a response to the viral challenge and this effect was suppressed by cortisol. No effect was seen in the distal intestine. T-cell marker CD3 as well as MHC-I in both intestinal regions and in the head kidney was down regulated at the mRNA level. Number of CD8 alpha lymphocytes decreased in the proximal intestine in response to cortisol. On the other hand, mRNA expression of Mx and IL-1 beta increased in the proximal intestine and head kidney in IPNV challenged fish in the presence of cortisol suggesting that the immune activation shifts in timing and response pathway during simulated stress. The present study clearly demonstrates that IPNV infection results in a differentiated epithelial immune response in the different intestinal regions of the Atlantic salmon. It also reveals that the epithelial immune response differs from the systemic, but that both are modulated by the stress hormone cortisol.
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| 9. |
- Olsen, Fredrik, 1973, et al.
(författare)
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Respiratory monitoring of nonintubated patients in nonoperating room settings: old and new technologies
- 2022
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Ingår i: Current Opinion in Anaesthesiology. - 0952-7907 .- 1473-6500. ; 35, s. 521-527
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of reviewPostoperative mortality in the 30 days after surgery remains disturbingly high. Inadequate, intermittent and incomplete monitoring of vital signs in the nonoperating room environment is common practice. The rise of nonoperating room anaesthesia and sedation outside the operating room has highlighted the need to develop new and robust methods of portable continuous respiratory monitoring. This review provides a summary of old and new technologies in this environment.Recent findingsTechnical advances have made possible the utilization of established monitoring to extrapolate respiratory rate, the increased availability and user friendliness of side stream capnography and the advent of other innovative systems. The use of aggregate signals wherein different modalities compensate for individual shortcomings seem to provide a reliable and artefact-free system.SummaryRespiratory monitoring is required in several situations and patient categories outside the operating room. The chosen modality must be able to detect respiratory compromise in a timely and accurate manner. Combing several modalities in a nonobtrusive, nontethered system and having an integrated output seems to give a reliable and responsive signal.
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| 10. |
- Olsen, Fredrik, 1973, et al.
(författare)
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Respiratory monitoring of nonintubated patients in nonoperating room settings: old and new technologies.
- 2022
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Ingår i: Current opinion in anaesthesiology. - 1473-6500. ; 35:4, s. 521-527
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Forskningsöversikt (refereegranskat)abstract
- Postoperative mortality in the 30 days after surgery remains disturbingly high. Inadequate, intermittent and incomplete monitoring of vital signs in the nonoperating room environment is common practice. The rise of nonoperating room anaesthesia and sedation outside the operating room has highlighted the need to develop new and robust methods of portable continuous respiratory monitoring. This review provides a summary of old and new technologies in this environment.Technical advances have made possible the utilization of established monitoring to extrapolate respiratory rate, the increased availability and user friendliness of side stream capnography and the advent of other innovative systems. The use of aggregate signals wherein different modalities compensate for individual shortcomings seem to provide a reliable and artefact-free system.Respiratory monitoring is required in several situations and patient categories outside the operating room. The chosen modality must be able to detect respiratory compromise in a timely and accurate manner. Combing several modalities in a nonobtrusive, nontethered system and having an integrated output seems to give a reliable and responsive signal.
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