| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 5. |
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| 6. |
- Aartsen, M. G., et al.
(författare)
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Very high-energy gamma-ray follow-up program using neutrino triggers from IceCube
- 2016
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- We describe and report the status of a neutrino-triggered program in IceCube that generates real-time alerts for gamma-ray follow-up observations by atmospheric-Cherenkov telescopes (MAGIC and VERITAS). While IceCube is capable of monitoring the whole sky continuously, high-energy gamma-ray telescopes have restricted fields of view and in general are unlikely to be observing a potential neutrino-flaring source at the time such neutrinos are recorded. The use of neutrino-triggered alerts thus aims at increasing the availability of simultaneous multi-messenger data during potential neutrino flaring activity, which can increase the discovery potential and constrain the phenomenological interpretation of the high-energy emission of selected source classes (e. g. blazars). The requirements of a fast and stable online analysis of potential neutrino signals and its operation are presented, along with first results of the program operating between 14 March 2012 and 31 December 2015.
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| 7. |
- Aartsen, M. G., et al.
(författare)
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The IceCube realtime alert system
- 2017
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 92, s. 30-41
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Tidskriftsartikel (refereegranskat)abstract
- Although high-energy astrophysical neutrinos were discovered in 2013, their origin is still unknown. Aiming for the identification of an electromagnetic counterpart of a rapidly fading source, we have implemented a realtime analysis framework for the IceCube neutrino observatory. Several analyses selecting neutrinos of astrophysical origin are now operating in realtime at the detector site in Antarctica and are producing alerts for the community to enable rapid follow-up observations. The goal of these observations is to locate the astrophysical objects responsible for these neutrino signals. This paper highlights the infrastructure in place both at the South Pole site and at IceCube facilities in the north that have enabled this fast follow-up program to be implemented. Additionally, this paper presents the first realtime analyses to be activated within this framework, highlights their sensitivities to astrophysical neutrinos and background event rates, and presents an outlook for future discoveries.
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| 8. |
- Aartsen, M. G., et al.
(författare)
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Neutrino emission from the direction of the blazar TXS 0506+056 prior to the IceCube-170922A alert
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 361:6398, s. 147-151
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Tidskriftsartikel (refereegranskat)abstract
- A high-energy neutrino event detected by IceCube on 22 September 2017 was coincident in direction and time with a gamma-ray flare from the blazar TXS 0506+056. Prompted by this association, we investigated 9.5 years of IceCube neutrino observations to search for excess emission at the position of the blazar. We found an excess of high-energy neutrino events, with respect to atmospheric backgrounds, at that position between September 2014 and March 2015. Allowing for time-variable flux, this constitutes 3.5 sigma evidence for neutrino emission from the direction of TXS 0506+056, independent of and prior to the 2017 flaring episode. This suggests that blazars are identifiable sources of the high-energy astrophysical neutrino flux.
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| 9. |
- Aartsen, M. G., et al.
(författare)
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Constraints on Galactic Neutrino Emission with Seven Years of IceCube Data
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 849:1
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Tidskriftsartikel (refereegranskat)abstract
- The origins of high-energy astrophysical neutrinos remain a mystery despite extensive searches for their sources. We present constraints from seven years of IceCube Neutrino Observatory muon data on the neutrino flux coming from the Galactic plane. This flux is expected from cosmic-ray interactions with the interstellar medium or near localized sources. Two methods were developed to test for a spatially extended flux from the entire plane, both of which are maximum likelihood fits but with different signal and background modeling techniques. We consider three templates for Galactic neutrino emission based primarily on gamma-ray observations and models that cover a wide range of possibilities. Based on these templates and in the benchmark case of an unbroken E-2.5 power-law energy spectrum, we set 90% confidence level upper limits, constraining the possible Galactic contribution to the diffuse neutrino flux to be relatively small, less than 14% of the flux reported in Aartsen et al. above 1 TeV. A stacking method is also used to test catalogs of known high-energy Galactic gamma-ray sources.
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| 10. |
- Aartsen, M. G., et al.
(författare)
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Search for Astrophysical Sources of Neutrinos Using Cascade Events in IceCube
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 846:2
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube neutrino observatory has established the existence of a flux of high-energy astrophysical neutrinos, which is inconsistent with the expectation from atmospheric backgrounds at a significance greater than 5 sigma. This flux has been observed in analyses of both track events from muon neutrino interactions and cascade events from interactions of all neutrino flavors. Searches for astrophysical neutrino sources have focused on track events due to the significantly better angular resolution of track reconstructions. To date, no such sources have been confirmed. Here we present the first search for astrophysical neutrino sources using cascades interacting in IceCube with deposited energies as small as 1 TeV. No significant clustering was observed in a selection of 263 cascades collected from 2010 May to 2012 May. We show that compared to the classic approach using tracks, this statistically independent search offers improved sensitivity to sources in the southern sky, especially if the emission is spatially extended or follows a soft energy spectrum. This enhancement is due to the low background from atmospheric neutrinos forming cascade events and the additional veto of atmospheric neutrinos at declinations less than or similar to-30 degrees.
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| 11. |
- Aartsen, M. G., et al.
(författare)
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Search for neutrinos from dark matter self-annihilations in the center of the Milky Way with 3 years of IceCube/DeepCore
- 2017
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Ingår i: European Physical Journal C. - : SPRINGER. - 1434-6044 .- 1434-6052. ; 77:9
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Tidskriftsartikel (refereegranskat)abstract
- We present a search for a neutrino signal from dark matter self-annihilations in the Milky Way using the Ice-Cube Neutrino Observatory (IceCube). In 1005 days of data we found no significant excess of neutrinos over the background of neutrinos produced in atmospheric air showers from cosmic ray interactions. We derive upper limits on the velocity averaged product of the darkmatter self-annihilation cross section and the relative velocity of the dark matter particles . Upper limits are set for darkmatter particle candidate masses ranging from 10GeV up to 1TeV while considering annihilation through multiple channels. This work sets the most stringent limit on a neutrino signal from dark matter with mass between 10 and 100GeV, with a limit of 1.18 . 10-23 cm(3)s(-1) for 100GeV dark matter particles self-annihilating via iota(+)iota(-) t-to neutrinos (assuming the Navarro-Frenk-White dark matter halo profile).
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| 12. |
- Aartsen, M. G., et al.
(författare)
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Detection of the Temporal Variation of the Sun's Cosmic Ray Shadow with the IceCube Detector
- 2019
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Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 872:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the observation of a deficit in the cosmic ray flux from the directions of the Moon and Sun with five years of data taken by the IceCube Neutrino Observatory. Between 2010 May and 2011 May the IceCube detector operated with 79 strings deployed in the glacial ice at the South Pole, and with 86 strings between 2011 May and 2015 May. A binned analysis is used to measure the relative deficit and significance of the cosmic ray shadows. Both the cosmic ray Moon and Sun shadows are detected with high statistical significance (>10σ) for each year. The results for the Moon shadow are consistent with previous analyses and verify the stability of the IceCube detector over time. This work represents the first observation of the Sun shadow with the IceCube detector. We show that the cosmic ray shadow of the Sun varies with time. These results make it possible to study cosmic ray transport near the Sun with future data from IceCube.
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| 13. |
- Aartsen, M. G., et al.
(författare)
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Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 98:6
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Tidskriftsartikel (refereegranskat)abstract
- We report a quasidifferential upper limit on the extremely-high-energy (EHE) neutrino flux above 5 x 10(6) GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above 10(6) GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between 5 x 10(6) and 2 x 10(10) GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of E-nu(2)phi(nu e+nu mu+nu tau) similar or equal to 2 x 10(-8) GeV/cm(2) sec sr at 10(9) GeV. A significant part of the parameter space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is disfavored independently of uncertain models of the extragalactic background light which previous IceCube constraints partially relied on.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Galluzzi, L, et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Forskningsöversikt (refereegranskat)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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| 18. |
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| 19. |
- Godoy, Patricio, et al.
(författare)
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
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Forskningsöversikt (refereegranskat)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
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| 20. |
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| 21. |
- Loureiro, J. A., et al.
(författare)
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Fluorinated beta-sheet breaker peptides
- 2014
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Ingår i: Journal of Materials Chemistry B. - : Royal Society of Chemistry (RSC). - 2050-7518 .- 2050-750X. ; 2:16, s. 2259-2264
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of amyloid-beta peptide (Ab) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease. We synthesized peptides containing fluorinated amino acids and studied their effect on the Ab aggregation. The peptides were based on the sequence LVFFD, in which valine was substituted by either 4,4,4-trifluorovaline or 4-fluoroproline, or the phenylalanine at position 3 was replaced by 3,4,5-trifluorophenylalanine. Our results demonstrate that fluorination of the hydrophobic residue valine or phenylalanine is effective in preventing the Ab aggregation. This study opens up the possibility of using new sequences based on fluorinated amino acids to inhibit the amyloid- fibril formation.
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| 22. |
- Derksen, Jeroen W. G., et al.
(författare)
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European practice patterns and barriers to smoking cessation after a cancer diagnosis in the setting of curative versus palliative cancer treatment
- 2020
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 138, s. 99-108
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking cessation after a cancer diagnosis is associated with improved overall survival. Few studies have reported oncologists' cessation practice patterns, but differences between the curative and palliative settings have not been described. We aimed to study the oncologist's perceptions on patients' tobacco use, current practices and barriers to providing smoking cessation support, while distinguishing between treatment with curative (C) and palliative (P) intent.Methods: In 2019, an online 34-item survey was sent to approximately 6235 oncologists from 16 European countries. Responses were descriptively reported and compared by treatment setting.Results: Responses from 544 oncologists were included. Oncologists appeared to favour addressing tobacco in the curative setting more than in the palliative setting. Oncologists believe that continued smoking impacts treatment outcomes (C: 94%, P: 74%) and that cessation support should be standard cancer care (C: 95%, P: 63%). Most routinely assess tobacco use (C: 93%, P: 78%) and advise patients to stop using tobacco (C: 88%, P: 54%), but only 24% (P)–39% (C) routinely discuss medication options, and only 18% (P)–31% (C) provide cessation support. Hesitation to remove a pleasurable habit (C: 13%, P: 43%) and disbelieve on smoking affecting outcomes (C: 3%, P: 14%) were disparate barriers between the curative and palliative settings (p < 0.001), but dominant barriers of time, resources, education and patient resistance were similar between settings.Conclusion: Oncologists appear to favour addressing tobacco use more in the curative setting; however, they discuss medication options and/or provide cessation support in a minority of cases. All patients who report current smoking should have access to evidence-based smoking cessation support, also patients treated with palliative intent given their increasing survival.
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| 23. |
- Asker, Mohammed, et al.
(författare)
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Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects
- 2023
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 25:3, s. 856-877
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesOxytocin (OT) has a well-established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT-R) are found in peripheral tissues relevant to energy balance regulation. Here, we aim to determine whether peripheral OT-R activation is sufficient to alter energy intake and expenditure.Methods and ResultsWe first show that systemic OT potently reduced food intake and food-motivated behaviour for a high-fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood-brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled-OT (fAF546-OT, Roxy), for the presence of IP-injected Roxy in CNS tissue relevant to feeding control and compared such with BBB-impermeable fluorescent OT-B-12 (fCy5-OT-B-12; BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT-R, we generated a novel BBB-impermeable OT (OT-B-12), with equipotent binding at OT-R in vitro. In vivo, IP-injected OT and OT-B-12 were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT-R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT-B-12 did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose-dependent reduction of emesis in male shrews. While both OT and OT-B-12 proved to have similar effects on body temperature, only OT resulted in home-cage locomotor depression.ConclusionsTogether our data indicate that limiting systemic OT CNS penetrance preserves the anorexic effects of the peptide and reduces the clinically undesired side effects of OT: emesis, taste avoidance and locomotor depression. Thus, therapeutic targeting of peripheral OT-R may be a viable strategy to achieve appetite suppression with better patient outcomes.
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| 24. |
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| 25. |
- Dunn, Jennifer A, et al.
(författare)
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Toward Consensus in Assessing Upper Limb Muscle Strength and Pinch and Grip Strength in People With Tetraplegia Having Upper Limb Reconstructions.
- 2021
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Ingår i: Topics in spinal cord injury rehabilitation. - : American Spinal Injury Association. - 1945-5763 .- 1082-0744. ; 27:3, s. 70-82
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Tidskriftsartikel (refereegranskat)abstract
- To reach agreement on standardized protocols for assessing upper limb strength and grip and pinch force for upper limb reconstructive surgery for tetraplegia.Selected members of an expert panel composed of international therapists formed at the 2018 International Congress for Upper Limb Surgery for Tetraplegia conducted a literature review of current practice that identified gaps and inconsistencies in measurement protocols and presented to workshop attendees. To resolve discrepancies, a set of questions was presented to workshop attendees who voted electronically. Consensus was set at 75% agreement.For manual muscle testing, consensus was reached for using the Medical Research Council scale, without plus or minus, and the use of resistance through range when testing grade 4 and grade 5 strength. Pectoralis major and serratus anterior should be routinely tested, however there was no consensus on other shoulder muscles. Grip and pinch strength should be tested according to the American Society of Hand Therapists positioning. For grip strength, either the Jamar or Biometrics dynamometer expressed in kilograms should be used. For grip and pinch strength, three measurements should be performed at each testing. No consensus was reached on a device for pinch strength.This work is an important step to enable comparable data in the future. Further consensus methods will work toward developing more comprehensive guidelines in this population. Building international consensus for pre- and postoperative measures of function supports objective evaluation of novel therapies and interpretation of multicenter studies.
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