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| 2. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 5. |
- Okhuijsen-Pfeifer, C, et al.
(författare)
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Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 145-
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Tidskriftsartikel (refereegranskat)abstract
- Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.
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| 6. |
- Kalaria, Raj, et al.
(författare)
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The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.
- 2024
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
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| 8. |
- Van Der Wateren, E., et al.
(författare)
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The LOFAR Tied-Array All-Sky Survey: Timing of 35 radio pulsars and an overview of the properties of the LOFAR pulsar discoveries
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 669
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Tidskriftsartikel (refereegranskat)abstract
- The LOFAR Tied-Array All-Sky Survey (LOTAAS) is the most sensitive untargeted radio pulsar survey performed at low radio frequencies (119-151 MHz) to date and has discovered 76 new radio pulsars, including the 23.5-s pulsar J0250+5854, which up until recently was the slowest spinning radio pulsar known. In this paper, we report on the timing solutions of 35 pulsars discovered by LOTAAS, which include a nulling pulsar and a mildly recycled pulsar, and thereby complete the full timing analysis of the LOTAAS pulsar discoveries. We give an overview of the findings from the full LOTAAS sample of 76 pulsars, discussing their pulse profiles, radio spectra, and timing parameters. We found that the pulse profiles of some of the pulsars show profile variations in time or frequency, and while some pulsars show signs of scattering, a large majority display no pulse broadening. The LOTAAS discoveries have on average steeper radio spectra and longer spin periods (1.4×), as well as lower spin-down rates (3.1×) compared to the known pulsar population. We discuss the cause of these differences and attribute them to a combination of selection effects of the LOTAAS survey as well as previous pulsar surveys, though we cannot rule out that older pulsars tend to have steeper radio spectra.
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| 10. |
- Munch, Marie W., et al.
(författare)
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Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
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Tidskriftsartikel (refereegranskat)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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| 11. |
- Ren, Fanghui, et al.
(författare)
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ER stress induces caspase-2-tBID-GSDMEdependent cell death in neurons lytically infected with herpes simplex virus type 2
- 2023
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Ingår i: EMBO JOURNAL. - 0261-4189 .- 1460-2075. ; 42:19
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Tidskriftsartikel (refereegranskat)abstract
- Neurotropic viruses, including herpes simplex virus (HSV) types 1 and 2, have the capacity to infect neurons and can cause severe diseases. This is associated with neuronal cell death, which may contribute to morbidity or even mortality if the infection is not controlled. However, the mechanistic details of HSV-induced neuronal cell death remain enigmatic. Here, we report that lytic HSV-2 infection of human neuron-like SH-SY5Y cells and primary human and murine brain cells leads to cell death mediated by gasdermin E (GSDME). HSV-2-induced GSDME-mediated cell death occurs downstream of replication-induced endoplasmic reticulum stress driven by inositol-requiring kinase 1 alpha (IRE1 alpha), leading to activation of caspase-2, cleavage of the pro-apoptotic protein BH3interacting domain death agonist (BID), and mitochondriadependent activation of caspase-3. Finally, necrotic neurons released alarmins, which activated inflammatory responses in human iPSC-derived microglia. In conclusion, lytic HSV infection in neurons activates an ER stress-driven pathway to execute GSDMEmediated cell death and promote inflammation.
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| 12. |
- Balogh, Dora B., et al.
(författare)
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FEMaLe: The use of machine learning for early diagnosis of endometriosis based on patient self-reported data—Study protocol of a multicenter trial
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:5 May
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Endometriosis is a chronic disease that affects up to 190 million women and those assigned female at birth and remains unresolved mainly in terms of etiology and optimal therapy. It is defined by the presence of endometrium-like tissue outside the uterine cavity and is commonly associated with chronic pelvic pain, infertility, and decreased quality of life. Despite the availability of various screening methods (e.g., biomarkers, genomic analysis, imaging techniques) intended to replace the need for invasive surgery, the time to diagnosis remains in the range of 4 to 11 years. Aims This study aims to create a large prospective data bank using the Lucy mobile health application (Lucy app) and analyze patient profiles and structured clinical data. In addition, we will investigate the association of removed or restricted dietary components with quality of life, pain, and central pain sensitization. Methods A baseline and a longitudinal questionnaire in the Lucy app collects real-world, self-reported information on symptoms of endometriosis, socio-demographics, mental and physical health, economic factors, nutritional, and other lifestyle factors. 5,000 women with confirmed endometriosis and 5,000 women without diagnosed endometriosis in a control group will be enrolled and followed up for one year. With this information, any connections between recorded symptoms and endometriosis will be analyzed using machine learning. Conclusions We aim to develop a phenotypic description of women with endometriosis by linking the collected data with existing registry-based information on endometriosis diagnosis, healthcare utilization, and big data approach. This may help to achieve earlier detection of endometriosis with pelvic pain and significantly reduce the current diagnostic delay. Additionally, we may identify dietary components that worsen the quality of life and pain in women with endometriosis, upon which we can create real-world data-based nutritional recommendations.
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| 13. |
- Hedlund, Martin, et al.
(författare)
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BlocklyVR : Exploring Block-based Programming in Virtual Reality
- 2023
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Ingår i: MUM'23: Proceedings of the 22nd International Conference on Mobile and Ubiquitous Multimedia. - : Association for Computing Machinery. - 9798400709210 ; , s. 251-263
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Konferensbidrag (refereegranskat)abstract
- As programming is typically a static activity in front of a screen, we perform an initial exploration around the capabilities of block-based programming in the immersive space using Virtual Reality (VR) to make an early charting on how programming could involve moving the programmer's body. We created a block-based programming interface in a VR space called BlocklyVR based on the existing Blockly programming environment. To investigate programmer performance and experience in BlocklyVR, we conducted a controlled lab experiment (N = 20) with eight programming tasks that covered mathematical operations, if-statements, and function creation. Our initial exploration contributes by classifying movement types made by BlocklyVR programmers and reflecting on how these movements are related to the programming tasks. Additionally, our data suggests that participant performance in BlocklyVR was not affected compared to the 2D Blockly, even if participants were physically moving in VR space. We also found that the virtual reality sickness was marginal. Lastly, we identified four types of interaction that can potentially be employed by VR designers and developers aiming to convert a static task, like programming at a desk, into a "mobile"immersive experience. © 2023 Owner/Author.
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| 14. |
- Kokorelias, Kristina M., et al.
(författare)
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The impact on employment and education of caregiving for a family member with young onset dementia: A scoping review
- 2024
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Ingår i: Dementia. - : SAGE PUBLICATIONS LTD. - 1471-3012 .- 1741-2684.
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Tidskriftsartikel (refereegranskat)abstract
- Young-onset dementia (YOD) affects individuals under 65 years of age, often leading to loss of employment and independence. Families provide increasing levels of care to family members with YOD, resulting in changes to their daily lives, including their occupational pursuits. This review examines evidence of the occupational implications for family members who provide care to a family with YOD to identify: (i) the influence and impact caregiving tasks and responsibilities have on employment, volunteering, and education, and (ii) caregiver, and caregiving situation factors associated with changes in employment, volunteering, and education. A scoping review was performed using eight electronic databases. Included articles were narratively synthesized using a thematic analysis. Sixteen studies met the inclusion criteria and were included for review. The over-arching (main) theme of 'decision-making' was identified, with family members required to make choices about their own occupational goals and roles to be able to provide care to family living with YOD. The outcomes of these decisions are dynamic and changeable across the caregiving trajectory. Three caregiving factors influence decision-making: (1) Implications of Combining Caregiving and Occupations, (2) Altered Identity (3) Strategies to Support Caregivers of Individuals Living with YOD. A fourth theme was also identified 'Guidance for Researchers To Support Caregivers'. There is a scarce body of literature examining the influence caregiving has on occupational outcomes for the YOD caregiver population. Much of this work is descriptive and lacks focus on the implications, particularly long-term impacts. This review provides a foundational guide for future research and practices to support YOD family caregivers to obtain and sustain occupations.
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| 16. |
- Söderström Malmborg, Julia, 1988-
(författare)
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Pain and health in adolescents and young adults – pieces of a puzzle
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Musculoskeletal pain is a burden for the individual and for society, and it has a negative impact on overall health. The biological, psychological, and social factors that govern pain and health form a complex puzzle to put together. Musculoskeletal pain conditions may be alleviated by physical activity, but a too high level of physical activity may also increase the risk of pain. Youth athletes may be especially vulnerable to developing pain due to factors related to training load and physical maturity. Being physically active and maintaining a healthy diet is associated with better health, but if carried out to excess these health behaviours may become unhealthy. Our understanding of musculoskeletal pain and health in adolescents and young adults needs to be developed, both in individuals involved in sports and exercise and in the general population.Aim: The overall aim was to study musculoskeletal pain and its relationship to various health-related factors in adolescents and young adults enrolled in sport or general education programmes.Methods: Study I was a cross-sectional study on university students (aged 19–29) from an exercise science programme (n = 118) and a business programme (n = 89), assessing health status, physical activity, and orthorexia nervosa (an exaggerated fixation on healthy food). Study II was a cross-sectional study (n = 178), and Study III a 2-year longitudinal (n = 131) study on sport school students (aged 14 at baseline), assessing musculoskeletal pain, health status, physical maturity, and sports performance. Study IV was a 3-year longitudinal study on students from a general upper secondary school (n = 256, aged 16 at baseline), assessing chronic musculoskeletal pain, health status, physical activity, sleep, stress, anxiety, and depression.Results: In Study I, compared to business students, exercise science students reported more pain, but better general health. A high level of physical activity in combination with orthorexia nervosa was most prevalent in men from the exercise science programme. In Studies II and III, pain was common in sport school students. At baseline, boys with constant pain were not as physically mature as boys with infrequent pain. Students with constant pain reported a worse health status than students with infrequent pain. At follow-up, frequent pain, frequent pain in two or more body regions, and a worse health status at baseline were identified as risk factors for having frequent pain at follow-up in girls. For boys, late physical maturation at baseline was a risk factor. Involvement in non-contact sports was also an identified risk factor over time in both sexes. Pain was associated with a worse sports performance in boys at both baseline and follow-up. In Study IV, chronic musculoskeletal pain was common in students from a general upper secondary school. A worse health status, severe sleeping problems, anxiety, and chronic musculoskeletal pain at baseline were associated with reporting chronic musculoskeletal pain at follow-up.Conclusions: Pain was prevalent, and also persistent, in adolescents and young adults, irrespective of attending sport or general education programmes. Pain is a biopsychosocial phenomenon and must be treated as such. Pain should be frequently monitored, and treatment should be introduced early on to prevent pain from becoming persistent.
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