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- Bowman, E. M. L., et al.
(författare)
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Advancing specificity in delirium: The delirium subtyping initiative
- 2024
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 20:1, s. 183-194
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDDelirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODSThe Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTSMeeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSIONThe DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HighlightsDelirium features must be clearly defined, standardized, and operationalized.Large datasets incorporating both clinical and biomarker variables should be analyzed together.Delirium screening should incorporate communication and reasoning.
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| 2. |
- Brinkmann, I., et al.
(författare)
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Foraminiferal Mn/Ca as Bottom-Water Hypoxia Proxy: An Assessment of Nonionella stella in the Santa Barbara Basin, USA
- 2021
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Ingår i: Paleoceanography and Paleoclimatology. - 2572-4517. ; 36:11
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia is of increasing concern in marine areas, calling for a better understanding of mechanisms leading to decreasing dissolved oxygen concentrations ([O2]). Much can be learned about the processes and implications of deoxygenation for marine ecosystems using proxy records from low-oxygen sites, provided proxies, such as the manganese (Mn) to calcium (Ca) ratio in benthic foraminiferal calcite, are available and well calibrated. Here we report a modern geochemical data set from three hypoxic sites within the Santa Barbara Basin (SBB), USA, where we study the response of Mn/Caforam in the benthic foraminifer Nonionella stella to variations in sedimentary redox conditions (Mn, Fe) and bottom-water dissolved [O2]. We combine molecular species identification by small subunit rDNA sequencing with morphological characterization and assign the SBB N. stella used here to a new phylotype (T6). Synchrotron-based scanning X-ray fluorescence (XRF) imaging and Secondary Ion Mass Spectrometry (SIMS) show low Mn incorporation (partition coefficient DMn < 0.05) and limited proxy sensitivity of N. stella, at least within the range of dissolved [O2] (2.7–9.6 μmol/l) and Mnpore-water gradients (2.12–21.59 μmol/l). Notably, even though intra- and interspecimen Mn/Ca variability (33% and 58%, respectively) was only partially controlled by the environment, Mn/Caforam significantly correlated with both pore-water Mn and bottom-water [O2]. However, the prevalent suboxic bottom-water conditions and limited dissolved [O2] range complicate the interpretation of trace-elemental trends. Additional work involving other oxygenation proxies and samples from a wider oxygen gradient should be pursued to further develop foraminiferal Mn/Ca as an indicator for hypoxic conditions.
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| 4. |
- Das, Indra J., et al.
(författare)
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Report of AAPM Task Group 155 : Megavoltage photon beam dosimetry in small fields and non-equilibrium conditions
- 2021
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Ingår i: Medical physics (Lancaster). - : John Wiley & Sons. - 0094-2405 .- 2473-4209. ; 48:10, s. E886-E921
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Tidskriftsartikel (refereegranskat)abstract
- Small-field dosimetry used in advance treatment technologies poses challenges due to loss of lateral charged particle equilibrium (LCPE), occlusion of the primary photon source, and the limited choice of suitable radiation detectors. These challenges greatly influence dosimetric accuracy. Many high-profile radiation incidents have demonstrated a poor understanding of appropriate methodology for small-field dosimetry. These incidents are a cause for concern because the use of small fields in various specialized radiation treatment techniques continues to grow rapidly. Reference and relative dosimetry in small and composite fields are the subject of the International Atomic Energy Agency (IAEA) dosimetry code of practice that has been published as TRS-483 and an AAPM summary publication (IAEA TRS 483; Dosimetry of small static fields used in external beam radiotherapy: An IAEA/AAPM International Code of Practice for reference and relative dose determination, Technical Report Series No. 483; Pal-mans et al., Med Phys 45(11):e1123, 2018). The charge of AAPM task group 155 (TG-155) is to summarize current knowledge on small-field dosimetry and to provide recommendations of best practices for relative dose determination in small megavoltage photon beams. An overview of the issue of LCPE and the changes in photon beam perturbations with decreasing field size is provided. Recommendations are included on appropriate detector systems and measurement methodologies. Existing published data on dosimetric parameters in small photon fields (e.g., percentage depth dose, tissue phantom ratio/tissue maximum ratio, off-axis ratios, and field output factors) together with the necessary perturbation corrections for various detectors are reviewed. A discussion on errors and an uncertainty analysis in measurements is provided. The design of beam models in treatment planning systems to simulate small fields necessitates special attention on the influence of the primary beam source and collimating devices in the computation of energy fluence and dose. The general requirements for fluence and dose calculation engines suitable for modeling dose in small fields are reviewed. Implementations in commercial treatment planning systems vary widely, and the aims of this report are to provide insight for the medical physicist and guidance to developers of beams models for radiotherapy treatment planning systems.
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| 6. |
- Roghanian, Ali, et al.
(författare)
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Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.
- 2015
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 27:4, s. 473-488
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.
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