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Nazmije Kelmendi,1,2 Marie Nilsson,2,3 Marina Taloyan,2,3 Kay Sundberg,1 Ann Langius-Eklöf,1 Åsa G Craftman1 1Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden; 2Academic Primary Health Care Center, Region Stockholm, Stockholm, Sweden; 3Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, SwedenCorrespondence: Nazmije Kelmendi, Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Alfred Nobels Allé 23, Stockholm, 141 52, Sweden, Tel +46 702 677 869, Email nazmije.kelmendi@ki.sePurpose: There is an increase in the number of men undergoing screening for prostate cancer, and advancements in treatments, which implies current knowledge about symptoms and self-management. This study aims to explore experiences of symptom distress, and self-management strategies during the first year after curatively intended treatment for prostate cancer, as identified by patients and health care professionals.Methods: A qualitative design was used, including data triangulation from individual interviews with patients (n =17) and one focus group interview with healthcare professionals (n =5). Thematic analysis was used.Results: The two main themes were identified: living with the consequences of treatment and navigating a new situation. Living with the consequences of treatment illustrated how losing control of bodily functions such as bladder, bowel, and sexual functions interfered with daily life. A stigma around the disease was described, and a life living in an unfamiliar body challenged ideas of masculinity. The first months after treatment ended was a distressing period related to the abruption in frequent contact with healthcare providers, and concerns about the future. The second theme, navigating a new situation, illustrates that self-management strategies varied, due to individual factors as did the need for tailored information and support provided from healthcare professionals and family, which was highly valued. Information and support were described as complex topics and healthcare professionals emphasized the need for appropriate education for staff to provide proper support to men after ended treatment.Conclusion: Lingering symptoms and concerns were evident during the first year after treatment. Self-management strategies varied, and timely and tailored information and support during the first year were considered highly valued, important, and preferred by patients. Our results indicate that support should be offered immediately after curatively intended treatment.Keywords: prostate cancer, self-management, symptoms, support, survivorship, information

Spin transfer torque magnetic random access memory (STT-MRAM) is a promising candidate for next generation memory as it is non-volatile, fast, and has unlimited endurance. Another important aspect of STT-MRAM is that its core component, the nanoscale magnetic tunneling junction (MTJ), is thought to be radiation hard, making it attractive for space and nuclear technology applications. However, studies on the effects of ionizing radiation on the STT-MRAM writing process are lacking for MTJs with perpendicular magnetic anisotropy (pMTJs) required for scalable applications. Particularly, the question of the impact of extreme total ionizing dose on perpendicular magnetic anisotropy, which plays a crucial role on thermal stability and critical writing current, remains open. Here we report measurements of the impact of high doses of gamma and neutron radiation on nanoscale pMTJs used in STT-MRAM. We characterize the tunneling magnetoresistance, the magnetic field switching, and the current-induced switching before and after irradiation. Our results demonstrate that all these key properties of nanoscale MTJs relevant to STT-MRAM applications are robust against ionizing radiation. Additionally, we perform experiments on thermally driven stochastic switching in the gamma ray environment. These results indicate that nanoscale MTJs are promising building blocks for radiation-hard non-von Neumann computing.

Athanasia Skriapa-Manta,1,2 Mattias Nilsson,1 Jan Svoboda,3 Monica Olsson,1,2 Maria Nilsson,4 Kristina Teär Fahnehjelm1,2 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 2Department of Paediatric Ophthalmology, Strabismus and Electrophysiology, St. Erik Eye Hospital, Stockholm, Sweden; 3Department of Paediatric Radiology, Karolinska University Hospital, Stockholm, Sweden; 4Unit of Optometry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenCorrespondence: Athanasia Skriapa-Manta, St Erik Eye Hospital, Eugeniavägen 12, Stockholm, 17164, Sweden, Tel +46 739 491 186, Email athanasia.skriapa-manta@ki.sePurpose: Optic nerve hypoplasia (ONH) is a common cause of visual impairment in children. Clinical complexity can cause diagnostic delay and difficulties predicting visual outcome. We evaluated whether optical coherence tomography (OCT) can improve the diagnosis and prediction of vision.Methods: Thirty-seven eyes with ONH from 12 girls and 8 boys, median age 10.5 years (range 2.8– 18.9 years), were included in this cross-sectional cohort study. The majority, 17/20, had bilateral ONH. Ophthalmological assessments included best corrected visual acuity (BCVA), fundus photography, measurement of the peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell complex (GCC), Bruch’s membrane opening (BMO) and visual fields. We compared OCT parameters with comparison data collected on 140 healthy individuals 5 to 25 years old. Pearson’s correlation coefficient was used to determine the correlation of OCT parameters and BCVA.Results: OCT demonstrated thinner mean pRNFL (p < 0.001) and mean GCC compared to the reference material (p < 0.001). BCVA displayed a strong or moderate correlation to pRNFL and to all sectors of the GCC except the inferotemporal. BCVA correlated strongly to Bruch’s membrane opening (BMO) (0.71, p < 0.001), and moderately to the Zeki ratio (− 0.52, p < 0.001). Multivariate analyses showed that BMO explained 48% of the variance in BCVA. Visual fields correlated strongly to pRNFL and GCC thickness. GCC thinning corresponded to visual field defects presence and location.Conclusion: OCT can facilitate the diagnosis of ONH. Parameters such as pRNFL, GCC and BMO can be predictors of visual acuity whereas GCC and pRNFL thinning can indicate location and severity of visual field defects.Keywords: optic nerve hypoplasia, OCT, ganglion cell complex, RNFL, visual fields, paediatric ophthalmology

Magnus Nilsson,1 Magdalena Rhedin,2 Ramon Hendrickx,3 Susanne Berglund,1 Antonio Piras,2 Parmis Blomgran,2 Anders Cavallin,2 Mia Collins,2 Göran Dahl,4 Bilel Dekkak,5 Therese Ericsson,3 Niklas Hagberg,6 Ann Aurell Holmberg,3 Agnes Leffler,2 Anders J Lundqvist,3 Thomais Markou,5,7 James Pinkerton,5,7 Lars Rönnblom,6 Stacey Siu,8 Vanessa Taylor,8 Tiiu Wennberg,2 Dimitrios Zervas,5,7 Arian D J Laurence,9 Suman Mitra,2 Maria G Belvisi,5,7 Mark Birrell,5,7 Annika Borde2 1Medicinal Chemistry, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 2Bioscience, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 3DMPK, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 4Discovery Science, R&D, AstraZeneca, Gothenburg, Sweden; 5Respiratory Pharmacology Group, Division of Airway Disease, National Heart and Lung Institute, Imperial College London, London, UK; 6Rheumatology and Science for Life Laboratories, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 7Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 8Rigel Pharmaceuticals, South San Francisco, CA, USA; 9Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UKCorrespondence: Magnus Nilsson, Medicinal Chemistry, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, SE-431 83, Sweden, Tel +46722237222, Email Magnus.Nilsson@astrazeneca.comPurpose: Janus kinase 1 (JAK1) is implicated in multiple inflammatory pathways that are critical for the pathogenesis of asthma, including the interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin cytokine signaling pathways, which have previously been targeted to treat allergic asthma. Here, we describe the development of AZD0449 and AZD4604, two novel and highly selective JAK1 inhibitors with promising properties for inhalation.Methods: The effects of AZD0449 and AZD4604 in JAK1 signaling pathways were assessed by measuring phosphorylation of signal transducer and activator of transcription (STAT) proteins and chemokine release using immunoassays of whole blood from healthy human volunteers and rats. Pharmacokinetic studies performed on rats evaluated AZD0449 at a lung deposited dose of 52 μg/kg and AZD4604 at 30 μg/kg. The efficacy of AZD0449 and AZD4604 was assessed by evaluating lung inflammation (cell count and cytokine levels) and the late asthmatic response (average enhanced pause [Penh]).Results: Both compounds inhibited JAK1-dependent cytokine signaling pathways in a dose-dependent manner in human and rat leukocytes. After intratracheal administration in rats, both compounds exhibited low systemic exposures and medium-to-long terminal lung half-lives (AZD0449, 34 hours; AZD4604, 5 hours). Both compounds inhibited STAT3 and STAT5 phosphorylation in lung tissue from ovalbumin (OVA)-challenged rats. AZD0449 and AZD4604 also inhibited eosinophilia in the lung and reduced the late asthmatic response, measured as Penh in the OVA rat model.Conclusion: AZD0449 and AZD4604 show potential as inhibitors of signaling pathways involved in asthmatic immune responses, with target engagement demonstrated locally in the lung. These findings support the clinical development of AZD0449 and AZD4604 for the treatment of patients with asthma.Keywords: AZD0449, AZD4604, JAK, STAT

This paper discusses the playworlds of the Playworld of Creative Research (PWCR) research group. Play¬worlds are created from a relatively new form of play that can be described as a combination of adult forms of creative imagination (art, science, etc.), which require extensive real life experience, and children’s forms of creative imagination (play), which require the embodiment of ideas and emotions in the material world. In playworlds, adults and children (or teenagers or seniors) enter into a common fantasy that is designed to support the development of both adults and children (or teenagers or seniors). The PWCR understands play¬worlds and the study of playworlds as ways of being. In this paper we present unique, individual playworlds that we truly love from the perspective of researchers, artists, teachers, children, administrators, and imagi¬nary characters, who participate in playworlds. We use a master fiction writer’s words on the love of literature to frame our discussion of playworlds, focusing on truth, time, human magic, infinite possibilities, fun, and the enriching and intensifying (and so, creating) of the real in playworlds in Japan, Finland, Sweden and the US.

Kerstin Herrström, 1,* Stina Larsson, 1,* Eva-Lena Einberg, 2 Marie Nilsson, 2 Kerstin Blomqvist, 2 Pernilla Garmy 2, 3 1Library and Higher Education Development, Kristianstad University, Kristianstad, Sweden; 2Faculty of Health Science, Kristianstad University, Kristianstad, Sweden; 3Department of Health Sciences, WHO-CC Clinical Health Promotion Centre, Lund University, Lund, Sweden*These authors contributed equally to this workCorrespondence: Pernilla GarmyFaculty of Health Science, Kristianstad University, Kristianstad 291 88, SwedenTel +46 739791316Email pernilla.garmy@hkr.seBackground: The majority of candidate theses in baccalaureate nursing programs in Sweden are written as literature studies. Being able to carry out a systematic and structured literature search is an essential part of thesis-related work.Aim: The aim of the current study was to investigate changes in nursing students’ search strategies in candidate theses.Methods: A retrospective, quantitative study design was obtained. Librarians (n = 2) and teachers (n = 4) randomly examined selected candidate theses (every third thesis, n = 89) from the years 2012, 2014, and 2016.Results: The result showed a significant improvement over the years (from 2012 and 2014 to 2016) regarding the use of a sufficient number of synonyms, matching search terms to the respective database, use of the Boolean operator OR, and the use of subject headings and free text searches. Use of the title/abstract search largely disappeared. There was a significant change in the types of searches being done. The searches have become more structured in later years as the use of block searches increased significantly; in other words, more systematic and relevant searches have been done in recent years.Conclusion: The result of this study shows that the quality of the students’ search strategies improved significantly during the studied years. It is recommended that search documents are used in both formative and summative assessments to evaluate students’ search strategies. Educational development in the form of enhanced collaboration between librarians and teachers in nursing programs is recommended because it might help to develop student search strategies in literature-based candidate theses.Keywords: information literacy, information retrieval, search strategies, literature-review-based candidate thesis, nurse education, nursing program, library instruction

Peatlands are major terrestrial soil carbon stores, and open mires in boreal landscapes hold a considerable fraction of the global peat carbon. Despite decades of study, large‐scale spatiotemporal analyses of mire arrangement have been scarce, which has limited our ability to scale‐up mire properties, such as carbon accumulation to the landscape level. Here, we use a land‐uplift mire chronosequence in northern Sweden spanning 9,000 years to quantify controls on mire distribution patterns. Our objectives include assessing changes in the spatial arrangement of mires with land surface age, and understanding modifications by upland hydrotopography. Characterizing over 3,000 mires along a 30 km transect, we found that the time since land emergence from the sea was the dominant control over mire coverage, especially for the establishment of large mire complexes. Mires at the youngest end of the chronosequence were small with heterogenous morphometry (shape, slope, and catchment‐to‐mire areal ratios), while mires on the oldest surfaces were variable in size, but included larger mires with more complex shapes and smaller catchment‐to‐mire ratios. In general, complex topography fragmented mires by constraining the lateral expansion, resulting in a greater number of mires, but reduced total mire area regardless of landscape age. Mires in this study area occurred on slopes up to 4%, indicating a hydrological boundary to peatland expansion under local climatic conditions. The consistency in mire responses to spatiotemporal controls illustrates how temporal limitation in peat initiation and accumulation, and topographic constraints to mire expansion together have shaped present day mire distribution patterns. Plain Language Summary: Peatlands store nearly one third of the global soil carbon, despite covering only around three percent of the land surface. Open mires, which are characteristic peatland types at high latitudes, represent an important peat carbon store. Few studies have explored how mire patterns in the landscape change over time and space. This knowledge gap has limited our ability to estimate and scale‐up mire properties, such as the peat carbon store, from the individual mire to the entire mire landscape. Here, we study the mire patch distribution in a landscape that covers nine thousand years of landscape development. Using this aging landscape, we can separate temporal controls on mire patterns from spatial controls related to local topography. We found that mire cover was mainly controlled by age, while the abundance of mires and their fragmentation was defined by local topography, for example, through the catchment‐to‐mire ratio and the slope of the surrounding upland areas, which define the limits for mire expansion upland. Our results provide an important step in understanding the spatial and temporal controls that give rise to present mire distribution patterns. Such information can further support landscape‐level estimations of mire properties and functions, such as the long‐term peat carbon store. Key Points: Mire cover and shape are linked to the formation of large mire complexes, while abundance and fragmentation are driven by topographyAreas of recent isostatic uplift hold small mires, while diverse initiation and expansion lead to heterogeneous mire patches in older areasScaling up mire properties to the landscape level requires an understanding of spatiotemporal controls behind mire distribution patterns [ABSTRACT FROM AUTHOR]

Alex J Scott,1 Gustaf Drevin,2 Lordan Pavlović,2 Magnus Nilsson,3 Jake EJ Krige,4 Eduard Jonas4 1Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; 2Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 3Division of Surgery, Karolinska Institutet, Stockholm, Sweden; 4Department of Surgery, University of Cape Town, Cape Town, South AfricaCorrespondence: Alex J ScottFaculty of Health Sciences, University of Cape Town, Observatory, Barnard Fuller Building, Cape Town 7935, South AfricaTel +27 21 406 6346Email sctale001@uct.ac.zaPurpose: To evaluate and compare medical student and faculty perceptions of undergraduate surgical training and compare results between South Africa and Sweden.Patients and methods: An electronic, online questionnaire was anonymously distributed to medical students and surgical faculty at the University of Cape Town (UCT), South Africa, and the Karolinska Institutet (KI), Sweden. The questionnaire explored the perceptions of medical students and surgical faculty regarding the current undergraduate surgical curriculum, as well as existing clinical and theoretical instructional methods.Results: A total of 120 students (response rate of 24.4%) and 41 faculty (response rate of 74.5%) responded. Students believed they ought to receive significantly more teaching when compared to surgical faculty (p=0.018). Students and faculty generally agreed that students should expect to study approximately six to 20 hrs per week outside of clinical duty. There was general agreement that “small-group tutorials” was the area students learn the most from, whereas students reported “lectures” least helpful. Registrars were reported as the first person students should consult regarding patient care. Fifty-one (42.5%) medical students believed that faculty viewed students as an inconvenience, and 42 (35.0%) students believed that faculty would rather not have students on the clinical team. The majority of faculty (68.3%) reported significantly more negative views on the current undergraduate surgical curriculum when compared to students (p=0.002). UCT faculty reported giving significantly less feedback to students during their surgical rotation when compared to KI faculty (p=0.043).Conclusion: Significant differences exist between surgical faculty and medical student perceptions regarding undergraduate surgical training in developing and developed countries. In order to increase surgical interest among undergraduate medical students, it is imperative for surgical educators to be aware of these differences and find specific strategies to bridge this gap.Keywords: surgical education, curriculum, perception, survey

Orjan Skogar,1,2 Mats Nilsson1,3 1FUTURUM, Academy for Health and Care, Region Jönköping County, Jönköping, Sweden; 2Institution of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden; 3Department of Medical and Health Sciences, Linköping University, Linköping, Sweden Background: Non-motor symptoms (NMS) are frequent in patients with idiopathic Parkinson’s disease (IPD). Clinical expressions, postulated pathophysiological mechanisms, and responsiveness to antiparkinson medication represent differences between IPD and secondary Parkinsonism (SP).Objective: To evaluate NMS expressions in IPD, SP, and a matched control group.Methods: The accepted criteria for IPD and SP were controlled for the participants who were consecutively recruited at two outdoor patient clinics. The Well-Being Map™ was used as the evaluation instrument. These were completed by the participants before their visit. The controls consisted of non-Parkinsonian individuals who were matched by age and gender.Results: A total of 185 participants participated in the study, IPD/SP/controls; n=73/53 and 59, respectively. The mean age was 74 years, and the median duration of disease was 6/3 years. Differences were shown between the combined IPD/SP groups and the controls. Limited differences between the IPD and SP groups could be demonstrated. Symptoms such as pain, decreased taste, as well as sleep and bladder disturbances were more frequent in the IPD group. When more than minor problems with moving were reported, disturbances in sleep and digestion were also noted to a large extent.Conclusion: Despite differences in the pathophysiological mechanisms between IPD and SP, the study showed only minor differences in the expression of NMS. IPD and SP reported statistically more significant problems in all items compared to the controls. Sleeping problems were strongly associated with symptoms from the gastrointestinal tract, but sleep was only affected by longer disease duration to a minor extent. Motor symptoms, such as morning stiffness, were common in all three groups. Neurodegenerative diseases might have more complex expressions in common than what we have known before and it is certainly not a part of normal aging. Keywords: idiopathic Parkinson’s disease, motor symptoms, non-motor symptoms, secondary Parkinsonism, well-being map, Health related Quality of Life

Jakob Lykke Poulsen,1 Christina Brock,1,2 Anne Estrup Olesen,1,2 Matias Nilsson,1 Asbjørn Mohr Drewes1,3 1Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkAbstract: Opioid-induced bowel dysfunction (OIBD) is a burdensome condition which limits the therapeutic benefit of analgesia. It affects the entire gastrointestinal tract, predominantly by activating opioid receptors in the enteric nervous system, resulting in a wide range of symptoms, such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation. The majority of studies evaluating OIBD focus on constipation experienced in approximately 60% of patients. Nevertheless, other presentations of OIBD seem to be equally frequent. Furthermore, laxative treatment is often insufficient, which in many patients results in decreased quality of life and discontinuation of opioid treatment. Novel mechanism-based pharmacological approaches targeting the gastrointestinal opioid receptors have been marketed recently and even more are in the pipeline. One strategy is prolonged release formulation of the opioid antagonist naloxone (which has limited systemic absorption) and oxycodone in a combined tablet. Another approach is peripherally acting, µ-opioid receptor antagonists (PAMORAs) that selectively target µ-opioid receptors in the gastrointestinal tract. However, in Europe the only PAMORA approved for OIBD is the subcutaneously administered methylnaltrexone. Alvimopan is an oral PAMORA, but only approved in the US for postoperative ileus in hospitalized patients. Finally, naloxegol is a novel, oral PAMORA expected to be approved soon. In this review, the prevalence and pathophysiology of OIBD is presented. As PAMORAs seem to be a promising approach, their potential effect is reviewed with special focus on naloxegol's pharmacological properties, data on safety, efficacy, and patient-focused perspectives. In conclusion, as naloxegol is administered orally once daily, has proven efficacious compared to placebo, has an acceptable safety profile, and can be used as add-on to existing pain treatment, it is a welcoming addition to the targeted treatment possibilities for OIBD.Keywords: opioids, gut, dysfunction, constipation, naloxegol, opioid antagonists

Örjan Skogar,1,2 Mats Nilsson,1 Carl-Johan Törnhage,3 Johan Lökk2 1Futurum Health Care Academy, Jönköping, 2Institution of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, 3Department of Pediatrics, Skaraborg Hospital, Skövde, Sweden Background: The purpose of this study was to draw conclusions from patient-reported experiences in two national surveys from Scandinavia with the intention of comparing treatment strategies and increasing our knowledge of factors that affect the experiences of patients with Parkinson's disease (PD). Methods: A total of 2000 individuals in Sweden and 1300 in Norway were invited to complete postal surveys covering PD-related issues. Patient experiences of diagnostic procedures, symptom control, and follow-up in PD and the effects on symptom-related quality of life were collected. Pharmaceutical prescription data on anti-PD drugs and administrative data were collected from national registries. Results: The surveys were completed by 1553 (78%) of the Swedish cohort and 1244 (96%) of the Norwegian cohort. Only small differences were seen in disease duration and age distribution. Statistically as well as clinically significant differences in symptom control, diagnostic, and follow-up procedures, as well as in pharmacological treatment and impact on quality of life, were found between the national cohorts independent of disease duration. Conclusion: Information from separate national surveys has the potential to increase our knowledge of patient experiences in PD and can be used to compare, evaluate, educate, and guide health care staff and administrators in optimizing health care for patients with the disease. Keywords: parkinson's disease, diagnosis, follow-up, pharmaceutical prescription, quality of life, survey