Publikationer från Uppsala Universitet
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Preventing suicide with Safe Alternatives for Teens and Youths (SAFETY) : a randomised feasibility trial
No full textBackground Suicide attempts are common in youth and have potentially lethal outcomes. Effective treatments targeting suicide attempts are scarce. Objective To assess the feasibility and preliminary efficacy of a family-based cognitive behavioural treatment relative to an active control for youth with suicidal behaviour. Methods 30 youths (93% female; mean (SD) age=14.6 (1.5) years) residing in Sweden with recent suicidal behaviour (last 3 months) and at least one available parent were randomised to 12 weeks of the family-based cognitive behavioural treatment Safe Alternatives for Teens and Youths (SAFETY) or supportive therapy, an active control treatment. Primary endpoint was 3-month post-treatment. Feasibility outcomes included treatment and assessment compliance, adverse events, treatment credibility and treatment satisfaction. Secondary outcomes included suicide attempt, non-suicidal self-injury, anxiety, depression, quality of life and emotion dysregulation. Findings Both treatments showed high compliance, satisfaction, credibility and session completion, with few adverse events and dropouts as well as low attrition (7% at primary endpoint). At the primary endpoint, two (14%) participants in SAFETY and four (27%) in supportive therapy had attempted suicide. Non-suicidal self-injury was reduced by 95% (incidence rate ratio=0.05 (95% CI 0.01 to 0.20)) in SAFETY and 69% (incidence rate ratio=0.31 (0.11 to 0.83)) in supportive therapy. Participation in SAFETY, but not in supportive therapy, was associated with moderate-to-large within-group improvements in anxiety and depression (Cohen's d=0.85 [0.33 to 1.40]), quality of life (d=1.01 [0.48 to 1.56]) and emotion dysregulation (d=1.22 [0.45 to 2.03]). Conclusions The results suggest that SAFETY is feasible and promising for youth with suicidal behaviour. Clinical implications A large randomised controlled trial is warranted to further examine the efficacy of SAFETY. Trial registration number NCT05537623
Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis
No full textCell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether plasticity is actively suppressed by lineage-specific repressors. Here we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing that prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity by direct repression of alternative fate master regulators. In mice, Prox1 was required for efficient hepatocyte regeneration after injury and was sufficient to prevent liver tumorigenesis. In line with patient data, Prox1 depletion caused hepatocyte fate loss in vivo and enabled the transition of hepatocellular carcinoma to cholangiocarcinoma. Conversely, overexpression promoted cholangiocarcinoma to hepatocellular carcinoma transdifferentiation. Our findings provide evidence for PROX1 as a hepatocyte-specific safeguard and support a model where cell-type-specific repressors actively suppress plasticity throughout life to safeguard lineage identity and thus prevent disease
Rendering the European neutron research landscape
No full textNeutrons, owing to their unique properties, serve as indispensable probes for investigating the structure and dynamics of materials across various length scales. The scientific community utilizing neutron research infrastructures encompasses a diverse range of disciplines, making it challenging to quantify its scientific and societal impact. To address this challenge, we apply Natural Language Processing (NLP) and machine learning techniques to analyze the scientific output of the European neutron science community. Leveraging open-source software toolkits, our method allows for the quantitative assessment of community evolution and research focus. Our analysis reveals consistent growth in the neutron community despite a reduction in sources, underscoring the enduring significance of neutron methods in scientific research. Furthermore, an increase in unique authors and an even distribution of publications across diverse scientific topics highlight the community's interdisciplinary nature and collaborative spirit. While this study emphasizes neutron scattering, our methodology holds promise for a broad range of scientific communities reliant on Large Research Infrastructures (LRIs), offering opportunities for collaboration, optimization of experimental approaches, and informed decision-making by governmental and funding bodies
Addressing grand ecological challenges in aquatic ecosystems : how can mesocosms be used to advance solutions?
No full textRapid and drastic anthropogenic impacts are affecting global biogeochemical processes and driving biodiversity loss across Earth's ecosystems. In aquatic ecosystems, species distributions are shifting, abundances of many species have declined dramatically, and many are threatened with extinction. In addition to loss of diversity, the ecosystem functions, processes and services on which humans depend are also being heavily impacted. Addressing these challenges not only requires direct action to mitigate environmental impacts but also innovative approaches to identify, quantify and treat their effects in the environment. Mesocosms are valuable tools for achieving these goals as they provide controlled environments for evaluating effects of stressors and testing novel mitigation measures at multiple levels of biological organisation. Here, we summarise discussions from a survey of marine and freshwater researchers who use mesocosm systems to synthesise their opportunities and limitations for advancing solutions to grand ecological challenges in aquatic ecosystems. While most research utilising mesocosm systems in aquatic ecology has focused on quantifying the effects of environmental threats, there is a largely unexplored potential for using them to test solutions. To overcome spatio-temporal constraints, there are opportunities to scale up the size and time-scales of mesocosm studies, or alternatively, test the outcomes of habitat-scale restoration at a smaller scale. Enhancing connectivity in future studies can help to overcome the limitation of isolation and test an important aspect of ecological recovery. Conducting 'metacosm' studies: coordinated, distributed mesocosm experiments spanning wide climatic and environmental gradients and utilising more regression-based experimental designs can help to tackle the challenge of context dependent results. Finally, collaboration of theoretical, experimental and applied ecologists and biogeochemists with environmental engineers and technological developers will be necessary to develop and test the tools required to advance solutions to the impacts of human activities on Earth's vulnerable aquatic ecosystems
Pushing the boundaries of asteroseismic individual frequency modelling : Unveiling two evolved very low-metallicity red giants
No full textContext. Metal-poor stars play a crucial role in understanding the nature and evolution of the first stellar generation in the Galaxy. Previously, asteroseismic characterisation of red-giant stars has relied on constraints from the global asteroseismic parameters and not the full spectrum of individual oscillation modes. Using the latter, we present for the first time the characterisation of two evolved very metal-poor stars including the detail-rich mixed-mode patterns. Aims. We will demonstrate that incorporating individual frequencies into grid-based modelling of red-giant stars enhances its precision, enabling detailed studies of these ancient stars and allowing us to infer the stellar properties of two very metal-poor [Fe/H] similar to -2.5 dex Kepler stars: KIC 4671239 and KIC 7693833. Methods. Recent developments in both observational and theoretical asteroseismology have allowed for detailed studies of the complex oscillation pattern of evolved giants. In this work, we employ Kepler timeseries and surface properties from high-resolution spectroscopic data within a grid-based modelling approach to asteroseismically characterise KIC 4671239 and KIC 7693833 using the BAyesian STellar Algorithm, BASTA. Results. Both stars show agreement between constraints from seismic and classical observables, an overlap unrecoverable when purely considering the global asteroseismic parameters. KIC 4671239 and KIC 7693833 were determined to have masses of 0.78(-0.03)(+0.04)and 0.83(-0.01)(+0.03)Mwith ages of12.1(-1.5)(+1.6)and 10.3(-1.4)(+0.6)Gyr, respectively. Particularly, for KIC 4671239 the rich spectrum of model frequencies closely matches the observed. Conclusions. A discrepancy between the observed and modelled nu max of similar to 10% was found, indicating a metallicity dependence of the nu max scaling relation. For metal-poor populations, this results in overestimations of the stellar masses and wrongful age inferences. Utilising the full spectra of individual oscillation modes lets us circumvent the dependence on the asteroseismic scaling relations through direct constraints on the stars themselves. This allows us to push the boundaries of state-of-the-art detailed modelling of evolved stars at metallicities far different from solar
Fiber Activation in Bipolar Deep Brain Stimulation : A Patient Case Study
No full textDeep brain stimulation (DBS) is a therapy widely used for treating the symptoms of neurological disorders. Electrical pulses are chronically delivered in DBS to a disease-specific brain target via a surgically implanted electrode. The stimulating contact configuration, stimulation polarity, as well as amplitude, frequency, and pulse width of the DBS pulse sequence are utilized to optimize the therapeutic effect. In this paper, the utility of therapy individualization by means of patient-specific mathematical modeling is investigated with respect to a specific case of a patient diagnosed with Essential tremor (ET). Two computational models are compared in their ability to elucidate the impact of DBS stimulation on the Dentato-Rubro-Thalamic tract (DRTT): (i) a conventional model of volume of tissue activated (VTA) and (ii) a well-established, open-source simulation (OSS) neural fiber activation modeling framework known as OSS-DBS. The simulation results are compared with tremor measured in the patient under different DBS settings using a smartphone application. The findings of the study highlight that temporally static VTA models do not adequately describe the differences in the outcomes of bipolar stimulation settings with switched polarity, whereas neural fiber activation models hold potential in this regard. However, it is noted that neither of the investigated models fully accounts for the measured symptom pattern, particularly regarding a bilateral effect produced by unilateral stimulation
PRIAM1 participates in the inhibition of inflammation and acetylcholinesterase activity in goose fatty liver formation
No full textGoose fatty liver, a product of short-term overfeeding, is notable for its high nutritional value and unique tolerance to severe steatosis without inflammation, in contrast to human nonalcoholic fatty liver disease (NAFLD). It is known that choline can alleviate nonalcoholic steatohepatitis and liver cirrhosis, inhibit cell apoptosis, promote lecithin synthesis and fat transportation out of the liver, and relieve cardiovascular diseaserelated symptoms (e.g., hyperlipidemia and hypercholesterolemia). This study investigates the role of Proline Rich Membrane Anchor 1 (PRIMAL) in inhibiting inflammation through choline metabolism during goose fatty liver formation. Overfeeding of geese resulted in increased body and liver weights, elevated fat content, and significantly higher expression of PRIMAL, accompanied by decreased LITAF and CRP (important proinflammatory cytokines) expression and reduced acetylcholinesterase (AchE) activity, which was assessed by the amount of produced choline. The overexpression of PRIMAL in goose primary hepatocytes (GPHs) enhanced AchE activity. Consistently, glucose-induced upregulation of PRIMAL expression in GPHs was accompanied by increased AchE activity. Further combined treatment with glucose and PRIMAL knockdown in GPHs showed that downregulation of PRIMAL attenuated the suppression of LITAF and CRP expression caused by glucose addition, but had no effect on the rise in AchE activity. These findings indicate that PRIMAL may play a role in promoting choline metabolism and protecting against liver inflammation, offering insights into potential therapeutic targets for NAFLD
The rise of the Milky Way Disk through EMP stars
No full textWe present a chemo-dynamical study conducted with 2dF+AAOmega of'- 6 000 Gaia DR3 non-variable candidate metal-poor stars that lie in the direction of the Galactic plane. Our spectral analysis reveals 15 new extremely metal-poor (EMP) stars, with the lowest metallicity at [Fe/H] = -4.0 f 0.2 dex. Two of the EMP stars are also carbon enhanced, with the largest enhancement of [C/Fe] = 1.3 f 0.1 occurring in a dwarf. Using our [C/Fe] results, we demonstrate that the number of carbon-depleted stars decreases with lower metallicities, and the fraction of carbon-enhanced stars increases, in agreement with previous studies. Our dynamical analysis reveals that the fraction of prograde and retrograde disk stars, defined as z(max)< 3 kpc, with J(phi)/J(tot) > 0.75 and J(phi)/J(tot) < -0.75, respectively, changes as metallicities decrease. Disk stars on retrograde orbits make up 10% of all the stars in our sample with metallicities below-2.1 dex. Interestingly, the portion of retrograde disk stars compared with the number of kinematically classified halo stars is approximately constant at 4.6% for all metallicities below-1.5 dex. We also see that Jincreases from 380 f 50 to 1320 f 90 km s(-1) kpc across metallicity range-1.5 to-1.1, consistent with the spin-up of the Galactic disk. Over the metallicity range-3.0 < [Fe/H] < -2.0, the slopes of the metallicity distribution functions for the prograde and retrograde disk stars are similar and comparable to that for the halo population. However, detailed chemical analyses based on high-resolution spectra are needed to distinguish the accreted versus in situ contributions. Finally, we show that our spectroscopic parameters reveal serious systematics in the metallicities published in recent studies that apply various machine learning techniques to Gaia XP spectra
Continental Orientation and the Climate of Land-dominated, Arid Planets
No full textThe climate and habitability of exoplanets are particularly difficult to constrain due to a lack of planetary information (e.g., obliquity and rotation rate) alongside current observational limitations. Surface water content is one of the most highly sought variables given its connections to the origins of life on Earth. Unfortunately, surface water is impossible to constrain due to uncertainties in (i) water content observations and (ii) surface-mantle water differentiation. Global ocean scenarios are prevalent in the literature, but it is vital to investigate the alternative arid scenarios with varied continental orientations and surface water abundances. Here, we use an ensemble of ROCKE-3D global climate model simulations to investigate the potential habitability of single-continent, land-dominated planets. This ensemble simulates climate over a range of water surface areas (WSAs; global ocean coverage) and continental orientations (pole- and equator-centered continents). We find that pole-centered orientations are 2 degrees C-5 degrees C warmer than equator-centered orientations across most WSAs due to the lack of highlands in the northern pole preventing snow and ice accumulation. These differences between continental orientations are completely diminished under the most arid scenarios. This is due to water limitation that results in a breakdown of the ice-albedo feedback, causing warming. Our results show that both WSA and continental orientation play roles in the global mean surface temperature of exoplanets. Future direct imaging missions, such as the Habitable Worlds Observatory, will play a crucial role in constraining the climate of exoplanets due to their ability to assess surface water and land dichotomies
Pelvic Organ Prolapse Repair Using Robotic-Assisted Sacral Hysterocolpopexy vs Vaginal Surgery with the Upholdâ\u84¢ System : 1-Year Clinical Outcomes
No full textIntroduction and Hypothesis: The aim of the study was to compare clinical outcomes when using robotic-assisted sacral hysterocolpopexy (RASC) and vaginal surgery using the Uphold (TM) Vaginal Support System mesh for pelvic organ prolapse repair. Methods: This was a nonrandomized, prospective, multicenter study in which 72 women underwent RASC, and 73 Uphold (TM) surgery, for apical prolapse (POP-Q C >= stage II). Anatomical outcomes were assessed using the Pelvic Organ Prolapse Quantification (POP-Q) system. Subjective outcomes were evaluated using the Pelvic Floor Distress Inventory 20 (PFDI-20), the Pelvic Floor Impact Questionnaire - short form (PFIQ-7), and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), as well as pain estimation using the visual analog scale (0-10). Results: One year after surgery, an optimal apical segment outcome (POP-Q C stage 0-1) was achieved in 96.4% and 93.3% for the RASC and Uphold (TM) respectively, p = 0.49. However, reoperation for prolapse recurrence was significantly more common after RASC (11 out of 72 [15.3%] vs Uphold (TM) (2 out of 71 [2.8%], p = 0.005), and an optimal outcome of the anterior vaginal wall was higher after Uphold (TM) (p < 0.001). Postoperative PFDI-20, PFIQ-7, and pain significantly improved for both RASC and Uphold (TM) (p = 0.004 to < 0.001), but a more pronounced improvement in the total PFDI-20 and POPDI-6 sub-scores was observed after Uphold (TM) than after RASC (-73 +/- 55.6 vs -49.2 +/- 43.7, p = 0.005 and -39.6 +/- 23.6 vs -27 +/- 23.9, p < 0.001 respectively). Conclusions: Reoperation for prolapse recurrence within 1 year was more common after RASC than after Uphold (TM). However, the rate of complications was low overall and there were few and largely insignificant differences in outcomes when comparing RASC and Uphold (TM)