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| 4. |
- Kløcker Larsen, Rasmus, et al.
(författare)
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Omtvistade landskap : Navigering mellan konkurrerande markanvändning och kumulativa effekter
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten presenterar ny kunskap om hur staten, exploatörer och samebyar kan förbättra hanteringen av exploateringars kumulativa effekter på renskötseln och samisk markanvändning.Rapporten bygger på ett forskningsprojekt som genomförts i partnerskap mellan samiska organisationer knutna till renskötseln, och forskningsinstitutionerna. Sex delstudier ingår i rapporten.•Hänsynen till kumulativa effekter i gruvbolags miljökonsekvensbeskrivningar, •samiskt inflytande i samband med miljöbedömningar, •vindkraftens påverkan under driftsfas på renskötseln i kalvningsområde, •metodik för att beräkna störningszoner, •konsekvenserna för renskötseln av vattenkraftutbyggnaden i Porjus och Vojmån samt möjliga skadelindrande åtgärder, samt •hur myndigheter kan efterleva sina skyldigheter mot samebyar i samband med tillståndsprocesser för konkurrerande markanvändning.Forskningen har finansierats av Naturvårdsverkets miljöforskningsanslag till stöd för Naturvårdsverket och Havs- och vattenmyndighetens verksamhet.
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| 5. |
- Larsen, Henrik Gutzon, et al.
(författare)
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Retten til byen
- 2012
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Ingår i: Byen i bevægelse : Mobilitet - politik - performativitet - Mobilitet - politik - performativitet. - 9788778673862 ; , s. 131-147
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Bokkapitel (refereegranskat)
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| 6. |
- Lindqvist, Maria, et al.
(författare)
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Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.
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| 9. |
- Bergkvist, Karin, et al.
(författare)
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General health, symptom occurrence, and self-efficacy in adult survivors after allogeneic hematopoietic stem cell transplantation : a cross-sectional comparison between hospital care and home care
- 2015
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Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 23:5, s. 1273-83
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Earlier studies have shown that home care during the neutropenic phase after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically safe, with positive outcomes. However, there have been few results on long-term outcomes after home care. The aims of this study were to compare general health, symptom occurrence, and self-efficacy in adult survivors who received either home care or hospital care during the early neutropenic phase after allo-HSCT and to investigate whether demographic or medical variables were associated with general health or symptom occurrence in this patient population.METHODS: In a cross-sectional survey, 117 patients (hospital care: n = 78; home care: n = 39) rated their general health (SF-36), symptom occurrence (SFID-SCT, HADS), and self-efficacy (GSE) at a median of 5 (1-11) years post-HSCT.RESULTS: No differences were found regarding general health, symptom occurrence, or self-efficacy between groups. The majority of patients in both hospital care (77 %) and home care (78 %) rated their general health as "good" with a median of 14 (0-36) current symptoms. Symptoms of fatigue and sexual problems were among the most common. Poor general health was associated with acute graft-versus-host disease (GVHD), low self-efficacy, and cord blood stem cells. A high symptom occurrence was associated with female gender, acute GVHD, and low self-efficacy.CONCLUSIONS: No long-term differences in general health and symptom occurrence were observed between home care and hospital care. Thus, home care is an alternative treatment method for patients who for various reasons prefer this treatment option. We therefore encourage other centers to offer home care to patients.
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| 10. |
- Bergkvist, Karin, et al.
(författare)
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Hospital care or home care after allogeneic hematopoietic stem cell transplantation : patients' experiences of care and support
- 2013
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Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889 .- 1532-2122. ; 48, s. S468-S468
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:Treatment at home during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation (HSCT) has been an option for patients at our center since 1998. Earlier studies have shown that home care is safe and has medical advantages. In this study, we present patients' experiences of care and support while being treated in hospital or at home during the acute post-transplantation phase.METHOD:Patients (n = 41, 22 in hospital care and 19 in home care) answered the SAUC questionnaire at discharge (when home, or from hospital). Both statistical analysis and deductive content analysis were used.RESULTS:The patients were highly satisfied with the care and support during the acute post-transplantation phase. Patients in home care were found to be more satisfied with care in general than patients in hospital care. The importance of safety, empathy, and encouragement from healthcare staff were expressed regardless of where care was given. Patients also felt that receipt of continuous, updated information during treatment was important and they had a strong belief in HSCT but were uncertain of the future regarding recovery.CONCLUSIONS:The main findings of this study were that in comparison to hospital care, home care does not appear to have a significant negative effect on patients' experiences of care and support during the acute post-transplantation phase. In addition patients in home care felt safe, seen as a person and encouragement seem to empower the patients at home. Thus, this study may encourage other transplantation centers to provide home care if the patients want it.
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| 11. |
- Bergkvist, Karin
(författare)
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Life situation in patients and their family members after allogeneic hematopoietic stem cell transplantation : aspects of health and support in different care settings
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Allogeneic hematopoietic stem cell transplantation (HSCT) is mainly an intensive treatment option for hematology malignancies. During the past decades, improved care and treatment have been systematically developed. One example is the possibility for patients to choose to be at home rather than in the hospital during the early neutropenic phase after HSCT. Recent studies have shown positive medical advantages with home care. The overall aim of this thesis was to describe patients and family members’ life situation after HSCT, as well their experiences from two different care setting: the patient’s home or the hospital. Data from patient-reported experiences were used in studies I and II and patient reported- outcomes in study III. In study IV data from family members experiences were used. Data from 173 (study I n=41; study II n= 15; study III n= 117) patients and 14 family members (study IV) were included in the thesis.In study I patients in both the hospital care group and the home care group expressed high satisfaction with the care and support during the acute post- transplantation phase.In study II four categories were identified from the interviews with patients To be in a safe place, To have a supportive network, My way of taking control, and My uncertain way back to normal.In study III, a cross-sectional survey was conducted and the majority of patients in both hospital care (77%) and home care (78%) rated their general health as ‘good’. A median of 14 symptoms were reported by patients in both hospital (0- 36) and home care (1-29). There were no significant differences regarding general health, symptom occurrence or self-efficacy between patients in hospital and those in home care.In study IV interviews with family members generated a main category, Being me and being us in an uncertain time was identified and five generic categories To receive the information I need, To meet a caring organization, To be in different care settings, To be a family member, and To have a caring relationship.In summary, numerous factors (the care routines, information, the competence and support from the health care team) related to the care were shown to influence the feeling of being safe regardless of care setting. Both patients and family members express the uncertainty associated with the HSCT. Different strategies (to have faith, being positive, hope and live in the present) were used to balancing the uncertainty. The majority of patients in both hospital care and home care rated their general health as ‘good’. A high symptom occurrence was reported in both groups in median five years post HSCT.
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| 14. |
- Bredin, Karin, 1977-
(författare)
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Human Resource Management in Project-Based Organisations : Challenges, Changes, and Capabilities
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This doctoral thesis addresses human resource management in project-based organisations. The aim is to explore the challenges for HRM in project-based organisations and the changes in people management systems to meet these challenges. The thesis consists of a compilation of six papers and an extended summary. The research reported in the thesis is based on a combination of multiple, comparative, and single case studies of project-based organisations. The core case studies have been conducted at Saab Aerosystems, AstraZeneca, Volvo Car Corporation, and Tetra Pak. The results indicate central challenges regarding competence development and career structures, performance review processes and reputation of project workers, and the increased responsibility and pressured work environment for project workers. They further indicate that many of these challenges are handled through a more HR-oriented line manager role, while HR departments are downsized and centralised. The thesis hence emphasises the need to understand HRM as a dimension of management in which various players share the responsibility for its design and performance. To conclude, the thesis applies a capabilities perspective on project-based organisations and develops a conceptual framework that embraces people capability: the organisational capability to manage the relation between people and their organisational context. In this framework, people management systems improve people capability when they integrate it with strategic, functional, and project capabilities. It is suggested that the people capability framework provides new possibilities to analyse HRM in project-based organisations and to explain the changes in people management systems that are needed to align them to the project-based context.
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| 15. |
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| 16. |
- Collins, Pamela Y, et al.
(författare)
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RISING SUN : Prioritized Outcomes for Suicide Prevention in the Arctic
- 2019
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Ingår i: Psychiatric Services. - : American Psychiatric Association. - 1075-2730 .- 1557-9700. ; 70:2, s. 152-155
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Tidskriftsartikel (refereegranskat)abstract
- The Arctic Council, a collaborative forum among governments and Arctic communities, has highlighted the problem of suicide and potential solutions. The mental health initiative during the United States chairmanship, Reducing the Incidence of Suicide in Indigenous Groups: Strengths United Through Networks (RISING SUN), used a Delphi methodology complemented by face-to-face stakeholder discussions to identify outcomes to evaluate suicide prevention interventions. RISING SUN underscored that multilevel suicide prevention initiatives require mobilizing resources and enacting policies that promote the capacity for wellness, for example, by reducing adverse childhood experiences, increasing social equity, and mitigating the effects of colonization and poverty.
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| 18. |
- Ek, Richard, et al.
(författare)
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A Dynamic Framework of Tourist Experiences: Spatial Temporalities and Performances in the Experience Economy
- 2008
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Ingår i: Scandinavian Journal of Hospitality and Tourism. - : Informa UK Limited. - 1502-2250 .- 1502-2269. ; 8:2, s. 122-140
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Tidskriftsartikel (refereegranskat)abstract
- This article outlines a conceptual model that allows a discussion regarding tourist experiences. Through the notion and deconstruction of the concept experience design it is argued that in order to be able to analyze tourism and develop new innovative strategic approaches to tourism management, dynamic notions of space, time and performance have to be especially attended to. This is done through a discussion of experience and design as both nouns and verbs. This makes it possible to work with four definitions of experience design, all situated on a continuum from a static starting point to a dynamic endpoint. It is argued that most research findings are placed in the more static half of this continuum, even if there are tendencies toward more dynamic approaches. These efforts are however usually based on a spatial ontology that is situated in the static half of the continuum. This paper aims to enhance these tendencies by focusing on the more dynamic half of the continuum. Notions of space-time as relational processes that should be understood as a hermeneutic circle and a view on the tourist as an active performer and producer of space are stressed. This conceptual model is crystallized and exemplified through the case of tourist photography, showing that the ontology chosen has a direct result on the concrete conduct of method and area of research interest.
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| 19. |
- Ekspong, Joakim, et al.
(författare)
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Solar-driven water splitting at 13.8 % solar-to-hydrogen efficiency by an earth-abundant PV-electrolyzer
- 2021
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Ingår i: ACS Sustainable Chemistry and Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 9:42, s. 14070-14078
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Tidskriftsartikel (refereegranskat)abstract
- We present the synthesis and characterization of an efficient and low cost solar-driven electrolyzer consisting of Earth-abundant materials. The trimetallic NiFeMo electrocatalyst takes the shape of nanometer-sized flakes anchored to a fully carbon-based current collector comprising a nitrogen-doped carbon nanotube network, which in turn is grown on a carbon fiber paper support. This catalyst electrode contains solely Earth-abundant materials, and the carbon fiber support renders it effective despite a low metal content. Notably, a bifunctional catalyst–electrode pair exhibits a low total overpotential of 450 mV to drive a full water-splitting reaction at a current density of 10 mA cm–2 and a measured hydrogen Faradaic efficiency of ∼100%. We combine the catalyst–electrode pair with solution-processed perovskite solar cells to form a lightweight solar-driven water-splitting device with a high peak solar-to-fuel conversion efficiency of 13.8%.
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| 20. |
- Erlinge, David, et al.
(författare)
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Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II) : a prospective natural history study
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10278, s. 985-995
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Tidskriftsartikel (refereegranskat)abstract
- Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2%, 95% CI 11.0-15.6) of 898 patients, with 66 (8.0%, 95% CI 6.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9% [SD 15.9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95% CI 1.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.0% (95% CI 4.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.2% (95% CI 9.4-17.6).Interpretation: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.
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| 21. |
- Ghouse, Jonas, et al.
(författare)
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Association of Variants Near the Bradykinin Receptor B2 Gene With Angioedema in Patients Taking ACE Inhibitors
- 2021
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 78:7, s. 696-709
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Angioedema is a rare but potentially life-threatening adverse reaction associated with angiotensinconverting enzyme (ACE) inhibitors. Identification of potential genetic factors related to this adverse event may help identify at-risk patients. OBJECTIVES The aim of this study was to identify genetic factors associated with ACE inhibitor-associated angioedema. METHODS A genomewide association study involving patients of European descent, all taking ACE inhibitors, was conducted in a discovery cohort (Copenhagen Hospital Biobank), and associations were confirmed in a replication cohort (Swedegene). Cases were defined as subjects with angioedema events and filled prescriptions for ACE inhibitors #180 days before the events. Control subjects were defined as those with continuous treatment with ACE inhibitors without any history of angioedema. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for angioedema risk using logistic mixed model regression analysis. Summary statistics from the discovery and replication cohorts were analyzed using a fixed-effects meta-analysis model. RESULTS The discovery cohort consisted of 462 cases and 53,391 ACE inhibitor-treated control subjects. The replication cohort consisted of 142 cases and 1,345 ACE inhibitor-treated control subjects. In the discovery cohort, 1 locus, residing at chromosome 14q32.2, was identified that associated with angioedema at the genomewide significance level of P <5 x 10-8. The lead variant at this locus, rs34485356, is an intergenic variant located 60 kb upstream of BDKRB2 (OR: 1.62; 95% CI: 1.38 to 1.90; P = 4.3 x 10-9). This variant was validated in our replication cohort with a similar direction and effect size (OR: 1.60; 95% CI: 1.13 to 2.25; P = 7.2 x 10-3). We found that carriers of the risk allele had significantly lower systolic (-0.46 mm Hg per T allele; 95% CI:-0.83 to-0.10; P = 0.013) and diastolic (-0.26 mm Hg per T allele; 95% CI:-0.46 to-0.05; P = 0.013) blood pressure. CONCLUSIONS In this genomewide association study involving individuals treated with ACE inhibitors, we found that common variants located in close proximity to the bradykinin receptor B2 gene were associated with increased risk for ACE inhibitor-related angioedema.
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| 22. |
- Golman, Klaes, et al.
(författare)
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13C-angiography.
- 2002
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Ingår i: Academic Radiology. - 1878-4046. ; 9:Suppl 2, s. 507-510
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Tidskriftsartikel (refereegranskat)
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| 23. |
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| 24. |
- Graae, Anne-Sofie, et al.
(författare)
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ADAMTS9 Regulates Skeletal Muscle Insulin Sensitivity Through Extracellular Matrix Alterations
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:3, s. 502-514
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Tidskriftsartikel (refereegranskat)abstract
- The ADAMTS9 rs4607103 C allele is one of the few gene variants proposed to increase the risk of type 2 diabetes through an impairment of insulin sensitivity. We show that the variant is associated with increased expression of the secreted ADAMTS9 and decreased insulin sensitivity and signaling in human skeletal muscle. In line with this, mice lacking Adamts9 selectively in skeletal muscle have improved insulin sensitivity. The molecular link between ADAMTS9 and insulin signaling was characterized further in a model where ADAMTS9 was overexpressed in skeletal muscle. This selective over expression resulted in decreased insulin signaling presumably mediated through alterations of the integrin 131 signaling pathway and disruption of the intracellular cytoskeletal organization. Furthermore, this led to impaired mitochondria! function in mouse muscle-an observation found to be of translational character because humans carrying the ADAMTS9 risk allele have decreased expression of mitochondrial markers. Finally, we found that the link between ADAMTS9 overexpression and impaired insulin signaling could be due to accumulation of harmful lipid intermediates. Our findings contribute to the understanding of the molecular mechanisms underlying insulin resistance and type 2 diabetes and point to inhibition of ADAMTS9 as a potential novel mode of treating insulin resistance.
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| 25. |
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| 26. |
- Gyldenkerne, Christine, et al.
(författare)
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Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients : PROSPECT II
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:6, s. 469-481
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content.METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics.RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]).CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging.
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| 27. |
- Heggdal, Peder O.Laugen, et al.
(författare)
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Reduced grey- and white matter volumes due to unilateral hearing loss following treatment for vestibular schwannoma
- 2020
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Previous studies of the consequences of unilateral hearing loss (UHL) on the functional-structural organization of the brain has included subjects with various degrees of UHL. We suggest that the consequences of a total loss of hearing in one ear might differ from those seen in subjects with residual hearing in the affected ear. Thus, the main aim of the present study was to compare the structural properties of auditory and non-auditory brain regions in persons with complete UHL to those of normal hearing controls. We hypothesize that the consequences of complete UHL following treatment for vestibular schwannoma will differ between ipsi- and contralateral structures, as well as between right- and left side deafness. Design: A 3T Siemens Prisma MR-scanner was used. Anatomical images were acquired using a high-resolution T1-weighted sequence. Grey- and white matter volumes were assessed using voxel-based morphometry. Study sample: Twenty-two patients with left- or right-side unilateral hearing loss. Fifty normal hearing controls. Results: Reductions in grey- and white matter volumes were seen in cortical and sub-cortical regions, mainly in the right hemisphere including the auditory cortex, lingual gyrus, cuneus, middle temporal gyrus, occipital fusiform gyrus, middle cingulate gyrus and the superior temporal gyrus. Patients displayed reduced grey- and white matter volumes in cerebellar exterior structures ipsilateral to the tumor side. Conclusion: When compared to controls, right side hearing loss yields more widespread reduction of grey matter volume than left side hearing loss. The findings of reduced grey- and white matter volumes in auditory and non-auditory brain regions could be related to problems with speech perception in adverse listening conditions, increased listening effort and reduced quality of life reported by persons with unilateral hearing loss despite normal hearing in the unaffected ear.
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| 28. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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Ingår i: The American Journal of Psychiatry. - 1535-7228. ; 181:8, s. 728-740
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 29. |
- Hvidtfeldt, Morten, et al.
(författare)
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Bronchoscopic mucosal cryobiopsies as a method for studying airway disease
- 2019
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 49:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- Background: Investigating disease mechanisms and treatment responses in obstructive airway diseases with invasive sampling are hampered by the small size and mechanical artefacts that conventional forceps biopsies suffer from. Endoscopic cryobiopsies are larger and more intact and are being increasingly used. However, the technique has not yet been explored for obtaining mucosa biopsies. Objective: To investigate differences in size and quality of endobronchial mucosal biopsies obtained with cryotechnique and forceps. Further, to check for eligibility of cryobiopsies to be evaluated with immunohistochemistry and in situ hybridization and to investigate tolerability and safety of the technique. Methods: Endobronchial mucosal biopsies were obtained with cryotechnique and forceps from patients with haemoptysis undergoing bronchoscopy and evaluated by quantitative morphometry, automated immunohistochemistry and in situ hybridization. Results: A total of 40 biopsies were obtained from 10 patients. Cross-sectional areas were threefold larger in cryobiopsies (median: 3.08 mm2 (IQR: 1.79) vs 1.03 mm2 (IQR: 1.10), P < 0.001). Stretches of intact epithelium were 8-fold longer (median: 4.61 mm (IQR: 4.50) vs 0.55 mm (IQR: 1.23), P = 0.001). Content of glands (median: 0.095 mm2 (IQR: 0.30) vs 0.00 mm2 (IQR: 0.01), P = 0.002) and airway smooth muscle (median: 0.25 mm2 (IQR: 0.30) vs 0.060 mm2 (IQR: 0.11), P = 0.02) was higher in the cryobiopsies compared with forceps biopsies. Further, the cryobiopsies had well-preserved protein antigens and mRNA. Mild to moderate bleeding was the only complication observed. Conclusion and clinical relevance: By yielding significantly larger and more intact biopsies, the cryotechnique represents a valuable new research tool to explore the bronchi in airway disease. Ultimately with the potential to create better understanding of underlying disease mechanisms and improvement of treatments.
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| 30. |
- Jensen, Benjamin A H, et al.
(författare)
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Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.
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| 31. |
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| 32. |
- Jönsson, Li, et al.
(författare)
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Grief and Hope in Transition : An orienteering guide
- 2023
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Bok (populärvet., debatt m.m.)abstract
- In the project Grief and Hope in Transition, our approach to transition has been one of reorientation, a departure from the belief in new technologies as the solution to all kinds of problems, an attempt at deviation from modernity’s familiar territories and road maps. Together with people living in different rural areas in Sweden’s southern most landscape Scania, we formed a study group in future orienteering.This book is an outcome of the collaborative work done to explore how to transition into becoming fossil-free and how to let go of optimism that places agency elsewhere (such as in others' roadmaps and tech-fixes). It describes how we through designerly ways have addressed the challenge of how to restore a sense of attachments and commitment to the unfolding of the future.
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| 33. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 34. |
- Larsen, Henrik Svarrer, 1962-
(författare)
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Tangible participation : engaging designs and design engagements in pedagogical praxes
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation contributes to three fields within design research:- Explorations of a design space related to aesthetics of Tangible Interaction, which have led to a set of design imaginations as well as perspectives on salient design qualities.- Views on and a designerly example of knowledge construction related to Research through Design as well as to programmatic approaches to design research.- Rich and reflected examples of how to co-develop design and pedagogy in the field of profound disabilities.Through the programme Tangible Participation the research seeks and expresses alternatives by critical questioning and imaginations of change. Such alternatives are articu¬lated in a set of designs making the possible present.These designs have been part of collaborative question¬ing and imaginations in a long-term engagement with pedagogical praxes. Through this engagement, design and pedagogy have co-developed; and from this, the programme has matured and collaborative ways of criticality has been developed.The matured programme presented in this dissertation entails seven designs built and used in the pedagogical praxes as well as evolved framings able to generatively address a design space: a tangible interaction designer’s palette, a sensuous perspective, a compositional principle and potentials of tangibles for participation.
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| 35. |
- Lindahl, Jonas, 1978-
(författare)
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In search of future excellence : bibliometric indicators, gender differences, and predicting research performance in the early career
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The governance of higher education institutions and science have endured significant changes during the last decades, emphasizing competitiveness, performance, and excellence. Embedded in this development is an increased use of bibliometric indicators as decision support tools in contexts of e.g., employment, appointment, and funding. These changes have gradually extended to the early career phase and the doctoral education.The aim of this thesis is to make a contribution to an ongoing discussion about the predictability of research performance and the reasonability of using bibliometric indicators in the early career, with a focus on gender differences. The thesis revolves around three overarching research questions focusing the early career and the doctoral education: (1) the degree to which research performance, as operationalized with bibliometric indicators, is predictable; (2) the degree to which gender differences in early career performance can be explained by research performance during the doctoral education; and (3) to what degree factors such as collaboration and supervisor behaviour, might affect gender differences in research performance.The main results suggests that research performance in the early career, as operationalized by bibliometric indicators, is predictable. Individuals who publish larger volumes, publish more in high prestige journals, and more excellent research early in their career, are more likely to attain excellence later on. The results also indicates that gender differences in performance can be observed as early asduring doctor education and that these differences partly explain the observed performance differences between males and females in the early career.Finally, the results suggests that gender differences in performance during doctoral education can largely be explained by the doctoral student’s collaborative networks and supervisor behaviour. It is concluded that while research performance, as operationalized by bibliometric indicators, duringthe early career is predictable, there are gender differences in performance that have to be taken into consideration. If they are not, the use of these types of performance indicators in science policy and management might increase the gender gap in science.
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| 36. |
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| 37. |
- Lukasczyk, Jonas, et al.
(författare)
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Cinema Darkroom : A Deferred Rendering Framework for Large-Scale Datasets
- 2020
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Ingår i: 2020 IEEE 10TH SYMPOSIUM ON LARGE DATA ANALYSIS AND VISUALIZATION (LDAV). - : IEEE. - 9781728184685 ; , s. 37-41
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a framework that fully leverages the advantages of a deferred rendering approach for the interactive visualization of large-scale datasets. Geometry buffers (G-Buffers) are generated and stored in situ, and shading is performed post hoc in an interactive image-based rendering front end. This decoupled framework has two major advantages. First, the G-Buffers only need to be computed and stored once-which corresponds to the most expensive part of the rendering pipeline. Second, the stored G-Buffers can later be consumed in an image-based rendering front end that enables users to interactively adjust various visualization parameters-such as the applied color map or the strength of ambient occlusion-where suitable choices are often not known a priori. This paper demonstrates the use of Cinema Darkroom on several real-world datasets, highlighting CDs ability to effectively decouple the complexity and size of the dataset from its visualization.
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| 38. |
- Löwgren, Jonas, et al.
(författare)
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Towards programmatic design research
- 2013
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Ingår i: Designs for Learning. - : Department of Didactic Sciences, Stockholm university. - 2001-7480. ; 6:1-2, s. 80-100
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Tidskriftsartikel (refereegranskat)abstract
- The notion of design research entails research where design practice forms part of the knowledge production. Based on our characterization of the nature of design, we propose to conceptualize this kind of research as programmatic design research. Two ongoing PhD projects in interaction design are presented as examples of programmatic research processes, highlighting issues to do with the virtues and qualities of the processes, the interplay of optics and engagements in a hermeneutical dynamic, and the production of takeaways for the academic community.
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| 39. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 40. |
- Matsumura, Mitsuaki, et al.
(författare)
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Serial NIRS-IVUS Assessment of Changes in Coronary Lumen Area During 2-Year Follow-Up : Insights From the PROSPECT ABSORB Trial
- 2021
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 78:19 Suppl., s. B35-B36
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: In PROSPECT II, 182 patients with plaque burden (PB) ≥ 65% were randomized to bioresorbable vascular scaffold (BVS) + guideline-directed medical therapy (GDMT) versus GDMT alone. Protocol-directed 3-vessel near-infrared spectroscopy (NIRS)-IVUS was repeated at 25 months.Methods: Excluding lesions treated by BVS, paired (baseline and follow-up) NIRS-IVUS was available in 626 nonculprit lesions in 165 patients. Follow-up minimum lumen area (MLA) and the corresponding baseline sites were measured: rapid lesion progression (RLP) was a ≥ 0.5 mm2 decrease of MLA, and rapid lesion regression (RLR) was a ≥ 0.5 mm2 increase of MLA.Results: RLP occurred in 34.5%, RLR occurred in 15.5%, and 49.8% had “no change.” The % change in vessel area correlated with the % change of plaque area (r = 0.81, P < 0.001), demonstrating vessel remodeling (Figure 1). At baseline, the RLP lesions had larger plaque areas, longer lesions, and higher prevalence of lipid-rich plaque (maxLCBI4mm ≥ 324.7). During follow-up, 80.2% of RLP lesions had negative remodeling irrespective of the change in plaque area, whereas 76.3% of RLR lesions had a decrease in plaque area irrespective of negative or positive remodeling. In lesions without change in lumen area, there were compensatory changes in plaque and vessel areas.Conclusion: In stabilized patients post-MI treated with GDMT, half of untreated non–flow- limiting lesions had significant lumen changes at 25 months, with RLP twice as frequent as RLR. The predominant mechanism of RLP was negative vessel remodeling whereas the predominant mechanism of RLR was reduction in plaque area.
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| 41. |
- Nilsson, Simon R O, et al.
(författare)
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A mouse model of the 15q13.3 microdeletion syndrome shows prefrontal neurophysiological dysfunctions and attentional impairment
- 2016
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Ingår i: Psychopharmacologia. - : Springer Science and Business Media LLC. - 0033-3158. ; 233:11, s. 2151-2163
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: A microdeletion at locus 15q13.3 is associated with high incidence rates of psychopathology, including schizophrenia. A mouse model of the 15q13.3 microdeletion syndrome has been generated (Df[h15q13]/+) with translational utility for modelling schizophrenia-like pathology. Among other deficits, schizophrenia is characterised by dysfunctions in prefrontal cortical (PFC) inhibitory circuitry and attention. Objectives: The objective of this study is to assess PFC-dependent functioning in the Df(h15q13)/+ mouse using electrophysiological, pharmacological, and behavioural assays. Method: Experiments 1–2 investigated baseline firing and auditory-evoked responses of PFC interneurons and pyramidal neurons. Experiment 3 measured pyramidal firing in response to intra-PFC GABAAreceptor antagonism. Experiments 4–6 assessed PFC-dependent attentional functioning through the touchscreen 5-choice serial reaction time task (5-CSRTT). Experiments 7–12 assessed reversal learning, paired-associate learning, extinction learning, progressive ratio, trial-unique non-match to sample, and object recognition. Results: In experiments 1–3, the Df(h15q13)/+ mouse showed reduced baseline firing rate of fast-spiking interneurons and in the ability of the GABAAreceptor antagonist gabazine to increase the firing rate of pyramidal neurons. In assays of auditory-evoked responses, PFC interneurons in the Df(h15q13)/+ mouse had reduced detection amplitudes and increased detection latencies, while pyramidal neurons showed increased detection latencies. In experiments 4–6, the Df(h15q13)/+ mouse showed a stimulus duration-dependent decrease in percent accuracy in the 5-CSRTT. The impairment was insensitive to treatment with the partial α7nAChR agonist EVP-6124. The Df(h15q13)/+ mouse showed no cognitive impairments in experiments 7–12. Conclusion: The Df(h15q13)/+ mouse has multiple dysfunctions converging on disrupted PFC processing as measured by several independent assays of inhibitory transmission and attentional function.
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| 42. |
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| 43. |
- Qu, Shuai, et al.
(författare)
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Experimental IPTV and IPv6 Extended Provisioning in a Virtual Testbed
- 2011
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Konferensbidrag (refereegranskat)abstract
- The increasing interest in Internet Protocol Television (IPTV) and Internet Protocol version 6 (IPv6) has driven the need to find a solution to run IPTV and IPv6 outside of a normal public access network. To find new solutions a virtual testbed based on Virtual Private Network (VPN) was built. VPN is a technology that can provide global networking and extended geographic connectivity, also with native security features and good control of the VPN clients. An experimental solution “Virtual Testbed” based on VPN technology to extend provision of IPTV and IPv6 is presented in this paper. This solution allows remote end users over a wider geographical area to participate in IPTV and IPv6 trial since the public network can be used. This also allows researchers an easier access to the test pilots home network and customer premises equipment (CPE), thus makes user behavior research and traffic measurements possible. Evaluation and performance tests on this solution are also illustrated and discussed.
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| 44. |
- Ràfols-Ribé, Joan, et al.
(författare)
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Controlling the Emission Zone by Additives for Improved Light-Emitting Electrochemical Cells
- 2022
-
Ingår i: Advanced Materials. - : John Wiley and Sons Inc. - 0935-9648 .- 1521-4095. ; 34:8
-
Tidskriftsartikel (refereegranskat)abstract
- The position of the emission zone (EZ) in the active material of a light-emitting electrochemical cell (LEC) has a profound influence on its performance because of microcavity effects and doping- and electrode-induced quenching. Previous attempts of EZ control have focused on the two principal constituents in the active material—the organic semiconductor (OSC) and the mobile ions—but this study demonstrates that it is possible to effectively control the EZ position through the inclusion of an appropriate additive into the active material. More specifically, it is shown that a mere modification of the end group on an added neutral compound, which also functions as an ion transporter, results in a shifted EZ from close to the anode to the center of the active material, which translates into a 60% improvement of the power efficiency. This particular finding is rationalized by a lowering of the effective electron mobility of the OSC through specific additive: OSC interactions, but the more important generic conclusion is that it is possible to control the EZ position, and thereby the LEC performance, by the straightforward inclusion of an easily tuned additive in the active material. © 2022 The Authors.
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| 45. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
-
Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 46. |
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| 47. |
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| 48. |
- Reisner, Walter, et al.
(författare)
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Directed self-organization of single DNA molecules in a nanoslit via embedded nanopit arrays
- 2009
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 106:1, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- We show that arrays of nanopit structures etched in a nanoslit can control the positioning and conformation of single DNA molecules in nanofluidic devices. By adjusting the spacing, organization and placement of the nanopits it is possible to immobilize DNA at predetermined regions of a device without additional chemical modification and achieve a high degree of control over local DNA conformation. DNA can be extended between two nanopits and in closely spaced arrays will self-assemble into "connect-the-dots" conformations consisting of locally pinned segments joined by fluctuating linkers. These results have broad implications for nanotechnology fields that require methods for the nanoscale positioning and manipulation of DNA.
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| 49. |
- Reisner, Walter, et al.
(författare)
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Nanoconfinement-enhanced conformational response of single DNA molecules to changes in ionic environment
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- We show that the ionic environment plays a critical role in determining the configurational properties of DNA confined in silica nanochannels. The extension of DNA in the nanochannels increases as the ionic strength is reduced, almost tripling over two decades in ionic strength for channels around 100x100 nm in dimension. Surprisingly, we find that the variation of the persistence length alone with ionic strength is not enough to explain our results. The effect is due mainly to increasing self-avoidance created by the reduced screening of electrostatic interactions at low ionic strength. To quantify the increase in self-avoidance, we introduce a new parameter into the de Gennes theory: an effective DNA width that gives the increase in the excluded volume due to electrostatic repulsion.
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| 50. |
- Reisner, Walter, et al.
(författare)
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Single-molecule denaturation mapping of DNA in nanofluidic channels
- 2010
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 107:30, s. 13294-13299
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Tidskriftsartikel (refereegranskat)abstract
- Here we explore the potential power of denaturation mapping as a single-molecule technique. By partially denaturing YOYO (R)-1-labeled DNA in nanofluidic channels with a combination of formamide and local heating, we obtain a sequence-dependent "barcode" corresponding to a series of local dips and peaks in the intensity trace along the extended molecule. We demonstrate that this structure arises from the physics of local denaturation: statistical mechanical calculations of sequence-dependent melting probability can predict the barcode to be observed experimentally for a given sequence. Consequently, the technique is sensitive to sequence variation without requiring enzymatic labeling or a restriction step. This technique may serve as the basis for a new mapping technology ideally suited for investigating the long-range structure of entire genomes extracted from single cells.
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