Publikationer från Linköpings universitet
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    Expression Divergence in Response to Sex-biased Selection

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    It remains debated whether greater degrees of sexual dimorphism would evolve if not for intersexual genetic constraints. Here, we used experimental evolution to partially break the intersexual genetic constraint in Drosophila melanogaster to investigate the effects of a shared gene pool on the evolution of sexual dimorphism in gene expression. In six replicate populations of 1,000 flies, a dominant marker (DsRed) was used to force a "Red" pool of genetically variable Chromosome 2 copies through exclusive father-to-son inheritance, while a complimentary pool of "NonRed" chromosomes was inherited primarily from mothers to daughters. After 100 generations, we demonstrated the effect of Red male-limited chromosomes in increasing male mating success. Differentially expressed genes between flies with and without Red chromosomes had on average higher intersexual genetic correlations (rMF), as expected if such correlations represent a constraint to sex-specific adaptation under normal inheritance. If conflict hinders the evolution of further dimorphism, the transcriptomes of male-selected Red chromosomes were predicted to evolve to be "masculinized" relative to female-selected NonRed chromosomes. Consistent with this, splicing patterns in Red males (but not Red females) were masculinized relative to NonRed males. Contrastingly, gene expression levels were largely feminized in Red flies of both sexes compared with NonRed. We discuss alternative forms of intralocus sexual conflict that may explain these patterns.Funding Agencies|Natural Sciences and Engineering Research Council of Canada; Swedish Research Council [2018-06775]; University of Toronto's Faculty of Arts and Science; Swedish Research Council [2018-06775] Funding Source: Swedish Research Council</p

    Exploring Different Levels of Contact Frequency in Multiple Sclerosis Care

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    IntroductionPrevious studies have identified differences in healthcare contacts, needs, and cost of care among persons living with multiple sclerosis (MS). The need for a deeper understanding of factors influencing healthcare contacts has been highlighted. The aim of this study was to explore different levels of healthcare contact frequency among persons living with MS.MethodBoth quantitative and qualitative data were collected, analyzed, and integrated in a parallel mixed-methods approach with data integration through joint display. Data were retrieved from the hospital administrative system, the Swedish national MS registry, and a previously conducted interview study. The population was divided into four segments based on healthcare contact frequency, ranging from Segment 1, with the fewest visits, to Segment 4, representing those with the most frequent contacts. Analyses were conducted using descriptive statistics, statistical tests on differences between segments, multinomial logistic regression, deductive content analysis, and integration.ResultsThe mean and median distribution of individual study variables increased or decreased (depending on scale direction) between segments for most variables toward more symptoms, reduced function, and declining experiences of health from the lowest to the highest contact frequency. The probability of belonging to a certain segment was influenced by the explanatory variables age, gender, overall health, and expanded disability status with the different variables playing different roles for each segment. Qualitative findings also suggested increased physical limitations with increased level of healthcare contacts. This was not necessarily due to MS and influence of comorbidities was sometimes expressed. Both requests of less and more healthcare contacts existed and content of healthcare contacts could have more personalized design overall, health care was perceived positively across all segments. Data integration with merged interpretation included eight themes, characteristics of the population, neurological assessment and gait function, symptoms and consequences, fatigue and cognition, perspectives on health, examinations, interactions with health care, and disease duration and future. The merged interpretation confirmed patterns of symptoms, reduced function, and declining experiences of health from the lowest to the highest contact frequency and expanded on individual variation within segments and influenced by comorbidities. Discord in data regarded relations with others, aspects of medication, and knowledge building and type of MS.ConclusionThe findings on distribution of variables and experiences across segments, were increase in symptoms, loss of function, and deterioration of health experience correlating with increased levels of contact frequency from Segments 1 to 4. The explanatory variables found were age, gender, overall health, and expanded disability. The merged interpretation, expand on individual differences on how symptoms were experienced and influenced by comorbidities. Discord found, regarding for example personal context and aspects of self-care where areas that may be overlooked in healthcare contacts. The explanatory variables identified in this study are suggested to be further explored together with the knowledge of persons living with MS and professionals.Funding Agencies|Futurum-the Academy for Health and Care, Region Jonkoping, Sweden; The Research Council of Southeast Sweden (FORSS)</p

    Undergraduate Nursing Students' Perceptions of Learning During Clinical Practice When Using a Conceptual Learning Model Grounded in a Caritative Caring Perspective: A Phenomenographic Study

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    AimTo describe the variations in undergraduate nursing students' perceptions of learning during clinical practice when using the conceptual learning model, Model for Improvements in Learning Outcomes (MILO), grounded in a caritative caring perspective.BackgroundA conceptual learning model grounded in hermeneutics and a caritative caring perspective addressing ethical values of caring and learning, intertwining didactics, nursing, pathophysiology and medicine to facilitate nursing students' learning during clinical practice and ease challenges in relation to healthcare and supervision was implemented.MethodsA qualitative descriptive design with a phenomenographic approach was used. Twenty strategically sought undergraduate nursing students in semester six from one university participated (19 women and 1 man aged between 23 and 40 years). Data were collected through semi-structured individual interviews after the model had been applied in a 7-week clinical practice course in different departments (surgical, medical and psychiatric/medical rehabilitation care) at 3 hospitals and in 13 municipalities (home care in southern Sweden) and then analysed to identify variations (similarities and differences) in ways of understanding the phenomenon of students' learning using MILO.ResultsFive mutually exclusive descriptive categories of what MILO's concepts and applications had meant for the students' learning emerged; the outcome space was illustrated by the following metaphors: a way to bridge the learning threshold; a way to learn to incorporate the spirit of meaning in caring; a way to learn to put one's soul into something; a way to notice the atmosphere's impact on learning; and a twosome's contradiction in the learning.ConclusionsAchieving a synthesis of ethical, aesthetical, theoretical and practical knowledge in becoming professional caring nurses was found to be facilitated using MILO. However, the use of peer learning was perceived as contradictory.Funding Agencies|Futurum-the Academy for Health and Care, Region Jonkoeping County, Sweden [Futurum-987497, 981975]</p

    An identity work theory of temporary organizations: On tensions and temporalities

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    Current literature on temporary organizations has paid scant attention to identity and identity work. That oversight amounts to a missed opportunity hindering cross-fertilization between research on temporary organizing and the wider field of organization studies. This paper addresses this missed opportunity by proposing a set of defining elements of an identity work theory of temporary organizations. Underlying our suggested theorization is a belief that temporary organizations are strongly associated with specific temporal tensions, which have implications for the nature and process of identity work. The paper develops this argument and discusses temporal tensions along three dimensions: (1) emergent futures, (2) indeterminate pasts, and (3) liminal presents of temporary organizations. We argue that temporal tensions trigger active and ongoing processes of identity work, which are necessary to build and maintain the temporary organization's identity

    Proteins associated with preserved ratio impaired spirometry

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    Background Preserved ratio impaired spirometry (PRISm) is a spirometry pattern of interest regarding incident airflow obstruction and higher mortality risk. We applied a proteomic approach to gain more insight into the biological mechanisms associated with PRISm. Methods From the population-based Swedish Cardiopulmonary Bioimage Study (SCAPIS), participants in the Main (n=4835) and Pilot (n=1054) studies, were included as discovery and replication cohorts. The lower limit of normal (LLN) of post-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC was defined as the fifth percentile in healthy, never-smoking SCAPIS participants. Participants were subdivided into five groups: reference: FEV1/FVC &amp;gt;= LLN and FEV1 LLN and FVC &amp;gt;= LLN (n=4084)); mild chronic airflow limitation (CAL): FEV1/FVC1 LLN (n=278); moderate-severe CAL: FEV1/FVC1170); restrictive spirometric pattern (RSP): FEV1/FVC ,LLN and FVC238); and PRISm: FEV1/FVC &amp;gt;= LLN and FEV1238). Proximity extension assays were used to measure 168 proteins. The associations of each standardised protein were assessed with each study group by multiple linear regression models, adjusting for age, sex, body mass index (BMI), smoking, physical activity and study centres, and corrected for multiple testing to control for a false discovery rate of 5%. Results Eight proteins were associated with PRISm and replicated: tumour necrosis factor receptor superfamily member 10A, interleukin-6, paraoxonase 3 (negative association), renin, urokinase plasminogen activator surface receptor (U-PAR), E-selectin, matrix metalloproteinase 7 and chitinase-3-like protein 1. Interleukin-6 and U-PAR were also associated with moderate-severe CAL and E-selectin with RSP. In addition, five other proteins were associated with moderate-severe CAL and three with RSP. Conclusion Protein profile in PRISm differs from other spirometric patterns suggesting specific disease mechanisms.Funding Agencies|Swedish Heart and Lung Foundation; Swedish Research Council; VINNOVA (Sweden's Innovation agency); University of Gothenburg and Sahlgrenska University Hospital, Karolinska Institutet and Region Stockholm; Knut and Alice Wallenberg Foundation; Linkoeping University and University Hospital; Lund University and Skane University Hospital; Umea University and University Hospital; Uppsala University; University Hospital.</p

    Simultaneous MRI and laser Doppler Flowmetry: Assessing cerebral Macro-and microcirculation in neurointensive care

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    Objective: Subarachnoid hemorrhage (SAH) patients are monitored in the neurointensive care unit (NICU) to avoid additional brain injuries, yet methods for monitoring cerebral blood flow (CBF) are limited. The aim was to investigate the feasibility of simultaneous MRI, using arterial spin labeling (ASL) and 2D-flow MRI, and probe-based laser Doppler flowmetry (LDF) in NICU patients. Method: Four SAH patients, three of whom received optical probes during routine surgery, were included. Compatibility of simultaneous LDF and MRI was evaluated before performing MRI 3-4 times over several days per patient. The methods were compared using mean CBF in grey matter obtained from the absolute ASL CBFmaps, the total inflow calculated from 2D-flow MRI, and local average LDF perfusion. Additionally, regional mean CBF from ASL and each arterial flowrate was compared for each hemisphere. Result: Twelve MRI measurements were successfully performed, eight of which included simultaneous LDF. With careful routines and the MR scanner uniquely located in the NICU, neither patient safety nor data quality was compromised, demonstrating the feasibility of concurrent measurements. All methods showed longitudinal dynamic changes, following the same increasing or decreasing trends. In three patients, ASL and 2D-flow data were closely related, with dynamic changes within 10 %. Conclusion: This novel approach offers longitudinal, simultaneous estimates of macro-and microcirculatory components locally, regionally, and globally in the human brain. This concept has potential to provide insights into the interplay of different aspects of CBF in NICU patients and thereby aid in prevention of secondary brain injuries

    Stochastic Dynamics of Gross Soil Nitrogen Transformations in Amazon Forests-High Local Variation but Lack of Basin-Wide Patterns

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    Tropical forests play a critical role in global climate regulation by taking up and storing significant amounts of carbon. Soil nitrogen (N) dynamics is the key to understanding forest productivity. However, we have only a very rudimentary understanding of in situ soil N transformations in the Amazon Basin, the largest intact tropical forest. This study investigated gross soil N dynamics across 12 locations in the Brazilian Amazon Basin using 15N labeling to quantify gross N transformations in situ. Our results revealed significant variation in both gross N mineralization and nitrification at the local and basin-scales. Unexpectedly, no spatial patterns were observed across locations, nor were gross N rates correlated with any measured soil properties. Our results suggest a stochastic and unpredictable nature of gross N transformation rates in the rainforests of the Amazon basin. These findings highlight the need for a more nuanced understanding of N cycling in tropical forests, which could improve ecological models and inform strategies for managing these ecosystems in the face of climate change and deforestation.Funding Agencies|Instituto Nacional de Cincia e Tecnologia da Criosfera</p

    Outcomes of inflammatory bowel disease in patients with obesity following bariatric surgery: propensity score-matched cohort study

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    Background Obesity is increasing among patients with inflammatory bowel disease, but bariatric surgery has been rare in this group owing to concerns about worsening the inflammatory bowel disease. The aim of the study was to evaluate inflammatory bowel disease-related outcomes following bariatric surgery.Methods Nationwide cohort of all adult patients in Sweden between 2007 and 2020 with obesity and inflammatory bowel disease. Patients were matched 1 : 1 with a two-stage matching process between those undergoing bariatric surgery with those who did not (classified by inflammatory bowel disease subtype followed by a propensity score match including sex, age, number of previous targeted therapies, presence of immunotherapy, cumulative oral corticosteroid dose, and previous intestinal surgery). The primary composite outcome comprised inflammatory bowel disease-related hospitalization, initiation of corticosteroid therapy, immunomodulation, commencement of a new targeted therapy or major inflammatory bowel disease-related surgery.Results The study included 798 patients with inflammatory bowel disease and obesity: 399 who underwent bariatric surgery (145 Crohn's disease, 238 ulcerative colitis, 16 unclassified inflammatory bowel disease) versus 399 who did not. Over a median observation period of 3.3 years in the surgery group and 3.0 years in the non-surgery group, the composite primary endpoint occurred in 201 patients who had surgery (incidence rate 11.9 (95% confidence interval (c.i.) 10.2 to 13.5) per 100 person-years) and 226 without surgery (incidence rate 15.1 (13.1 to 17.0) per 100 person-years), corresponding to an adjusted hazard ratio of 0.66 (95% c.i. 0.51 to 0.85) in those undergoing bariatric surgery compared with those who did not.Conclusion Bariatric surgery was associated with improved inflammatory bowel disease-related outcomes among patients with inflammatory bowel disease and obesity, suggesting a potential benefit from bariatric surgery among patients with concomitant obesity and inflammatory bowel disease. Bariatric surgery in patients with obesity and inflammatory bowel disease (IBD) remains controversial. In this matched cohort study of 399 patients who underwent bariatric surgery and 399 matched controls, bariatric surgery was associated with improved IBD-related outcomes suggesting a potential benefit from bariatric surgery among patients with concomitant obesity and IBD.Funding Agencies|Ake Wiberg stiftelse [MS24-0083]; Region Orebro County [OLL-1010727]; Swedish Research Council [2020-02002, 2019-00738]; Regional Agreement on Medical Training and Clinical Research between Stockholms Lans Landsting and Karolinska Institutet [ALF RS2021-0855]</p

    Noninvasive Bedside Approaches for Assessing Microvascular Dysfunction

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    Background: Microvascular dysfunction is implicated in a range of acute and chronic conditions, ranging from cardiovascular disease to sepsis, often preceding organ damage and clinical symptoms. Within conditions such as diabetes or septic shock, microvascular compromise frequently correlates with disease severity and outcomes, emphasizing the importance of timely, targeted assessment. Noninvasive bedside methods for evaluating microvascular function have rapidly evolved, driven by advances in computational power, artificial intelligence, and novel imaging hardware. Summary: This review provides an overview of clinically feasible noninvasive techniques - including optical coherence tomography angiography, handheld videomicroscopy, laser speckle contrast imaging, reflectance spectroscopy, and related techniques. These methods allow observation under resting conditions and can be combined with functional tests such as post-occlusive reactive hyperemia, heating provocation, or iontophoresis to evaluate microvascular function. Key Messages: Collectively, these methods provide valuable insights into the structural and functional aspects of the microcirculation, but their clinical application is constrained by need for standardized protocols, validation, and evidence linking microvascular metrics to meaningful patient outcomes. Collaborations among academia, industry, and healthcare remain pivotal to transitioning these methods into regulated, accessible devices. As standardization progresses and evidence grows, this integrative approach of evaluating microvascular function may emerge as a mainstay in clinical practice and translational research

    The Art of Arteriovenous Fistula Cannulation : In a Complication Preventive Direction

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    Blood dialysis requires a functioning access to the bloodstream. The arteriovenous fistula (AVF) is the vascular access with the longest patency and lowest complication rate. Patients usually undergo blood dialysis treatment three times per week, necessitating over 300 cannulations over the course of a year. The use of a good cannulation technique can reduce the risk of needle-related complications and improve the patient experience. The five main cannulation techniques are ropeladder, area puncture, buttonhole with blunt needle, buttonhole with sharp needle, and multiple single cannulation technique; however, scarce data are available regarding the impacts of these different techniques. The overall aim of this thesis was to explore how the selected cannulation technique affects AVF development and the risk of complications. In Study I, the Swedish Renal Registry (SRR) was used to examine the occurrence of complications with each cannulation technique. In Sweden, the most commonly used technique was buttonhole using sharp needles (55%), followed by buttonhole using blunt needles (29%), ropeladder (13%) and area puncture (3%). Buttonhole using blunt needles was associated with the lowest risk of complications—including stenosis, infiltrations, and cannulation difficulties. The incidence of infections did not differ between the different cannulation techniques. For Studies II and III, data were collected using a questionnaire distributed to nurses in all dialysis units in Sweden. These units were also invited to participate by sending their local guidelines describing cannulation technique and AVF care. Data were analysed using mixed methods. Study II revealed that the cannulation technique was primarily chosen by the nurses, based on their own and their colleagues’ experience, as well as local guidelines and patient preferences. Study III described the cannulation technique as a five-step process, in which all parts influence the outcome. Study IV was an observational study, in which ten patients with new AVFs were assessed during five sessions over one year. The AVFs were examined by ultrasound, the cannulating nurses were asked to describe cannulation-related parameters, and the patients were asked to describe cannulation-associated pain. The observations over time showed the development of buttonhole-related tunnel tracks, and an increasing thickness of the vessel wall behind the puncture sites. The patient-reported pain varied among individuals. However, patients cannulated using buttonhole with blunt needles described decreasing pain after the initial months, while this trend was not seen among patients cannulated using buttonhole with sharp needles. Study V was a randomised crossover trial comparing the effects of two disinfectants: chlorhexidine 5 mg/ml and ethanol 70%. Twenty patients with AVFs were disinfected using both agents, on a total of four occasions, and the outcomes were compared in terms of the bacteria remaining in the normal skin flora (CFU/ml). Bacterial colonisation immediately after disinfection was more common in samples from skin treated with ethanol (10.8%), compared to with chlorhexidine (1.4%). Additionally, the bacterial counts of normal skin flora regrew faster after disinfection with ethanol when disinfection was preceded by arm washing with soap and water. The conclusion of the thesis is that cannulation technique should be described from a broader perspective than simply the technique used to insert the needle into the vessel. For example, descriptions of the cannulation process should include the utilised hygiene routines, since the disinfectant type and method may affect the outcome regarding infections. Buttonhole using blunt needles was the technique that was associated with the least number of complications, and the longest survival rate. However, the tunnel tracks and vessel wall at the needling site were affected over time. Patients’ perceptions of pain also varied over time, and widely differed among individuals. In Sweden, nurses selected the cannulation technique, with the aim of applying a good cannulation technique that is adjusted to the individual patient. At the same time, the main aim is that the majority should use the buttonhole technique.För att bloddialys ska vara möjlig behövs en fungerande tillgång till blodbanan. Den kärlaccess som har längst överlevnad och ger minst komplikationer är den arteriovenösa fisteln (AV-fistel). Vid bloddialys behandlas vanligtvis patienten tre gånger per vecka, detta innebär mer än 300 stick i AV-fisteln per år. För att minska risken för stickrelaterade komplikationer och förbättra patientens upplevelse behövs en god stickteknik. Det finns idag fem kända tekniker för att kanylera i AV-fistel: ropeladder, area puncture, buttonhole med trubbig nål, buttonhole med vass nål och multipel stickhålsteknik. Hur dessa tekniker påverkar AV-fisteln och risken för komplikationer är sparsamt beforskat och genomförandet baseras vanligen på beprövad erfarenhet. Avhandlingens övergripande syfte var att undersöka hur valet av stickteknik i AV-fistlar påverkar dess utveckling och risken för komplikationer. Studie I var en registerstudie. Svenskt NjurRegisters (SNR) accessdel användes och förekomsten av komplikationer vid respektive stickteknik undersöktes. Buttonhole med vass nål var den teknik som var vanligast i Sverige (55%) följt av buttonhole med trubbig nål (29%), ropeladder (13%) och area puncture (3%). Buttonhole med trubbig nål hade lägst risk för komplikationer. Tydligast var detta vid stenoser, perforationer och sticksvårigheter. Det sågs ingen skillnad i förekomst av infektioner vid de olika stickteknikerna. Studie II och III baserades på datainsamling via en enkät som erbjöds sjuksköterskor på samtliga dialysenheter i Sverige. Enheterna erbjöds även att skicka in sina lokala styrande dokument som beskrev omhändertagande av AV-fistel och stickteknik. Materialet analyserades med mixed methods. Studie II undersökte vad valet av stickteknik baseras på. Det visade sig att det framförallt är sjuksköterskan som väljer stickteknik och detta val baseras på egna och kollegors erfarenhet, lokala riktlinjer och patientens preferenser. Studie III beskrev stickteknik som en process med fem olika delar där alla delar har betydelse för utfallet. Studie IV var en observationsstudie där tio patienter med nya AV-fistlar följdes vid fem tillfällen under ett år. AV-fistlarna undersöktes med ultraljud samtidigt som kanylernade sjuksköterska fick beskriva stickrelaterade parametrar i ett protokoll. Patienterna fick även beskriva sin smärta i samband med stick. Studien visade hur stickkanaler (som används vid tekniken buttonhole) utvecklas över tid. Det framkom även att kärlväggen bakom stickställena ofta förtjockas. Patienterna beskrev sin smärta med stora individuella skillnader men hos de som blev stuckna med trubbiga nålar fanns en avtagande trend. De beskrev att det gjorde mindre ont efter de första inledande månaderna. Hos de patienter som stacks med buttonhole teknik med vassa nålar syntes inte denna trend. Studie V var en randomiserad överkorsningsstudie där effekten av desinfektionsmedlen klorhexidinsprit 5 mg/ml och etanol 70 % jämfördes. Tjugo patienter med AV-fistel fick prova båda desinfektionsmedlen vid totalt fyra tillfällen. Utfallet mättes sedan i antalet kvarvarande bakterier i hudens normalflora (CFU/ml). Direkt efter desinfektion sågs bakterietillväxt på fler prov vid etanol (10,8%) än vid klorhexidinsprit (1,4%). Bakterieantalet i normalfloran växte även tillbaka fortare efter desinfektion med etanol då den kombinerats med armtvätt med tvål och vatten direkt före desinfektion. Avhandlingens slutsats är att stickteknik bör beskrivas från ett bredare perspektiv än den stickteknik som används för att föra in nålen i kärlet. Beskrivning av de hygienrutiner som används bör t ex inkluderas då typ av desinfektionsmedel kan påverka utfallet för infektioner. Sticktekniken buttonhole med trubbig nål är den teknik som leder till minst antal komplikationer och har längst överlevnad. Stickkanalerna och kärlvägg vid stickområdet påverkas över tid. Så även upplevelsen av smärta. I Sverige är det sjuksköterskor som väljer stickteknik. Det görs med utgångspunkt att uppnå en god stickteknik som anpassas efter den enskilda patienten samtidigt som målet är att majoriteten ska använda buttonhole

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