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Synchrotron x-ray spectra characterisation for radiation therapy applications at the ESRF - ID17 biomedical beamline
Get PDFData-driven biomarkers better associate with stroke motor outcomes than theory-based biomarkers.
Get PDFChronic motor impairments are a leading cause of disability after stroke. Previous studies have associated motor outcomes with the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to model chronic motor outcomes after stroke and compares the accuracy of these associations to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients from the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Stroke Recovery Working Group. Using the explained variance metric to measure the strength of the association between chronic motor outcomes and imaging biomarkers, we compared theory-based biomarkers, like lesion load to known motor tracts, to three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had stronger associations with chronic motor outcomes accuracy than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R 2 = 0.210, P < 0.001), performing significantly better than the theory-based biomarkers of lesion load of the corticospinal tract (R 2 = 0.132, P < 0.001) and of multiple descending motor tracts (R 2 = 0.180, P < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R 2 = 0.200, P < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R 2 = 0.167, P < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved the strength of associations for theory-based and data-driven biomarkers. Combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R 2 = 0.241, P < 0.001. Overall, these results demonstrate that out-of-sample associations between chronic motor outcomes and data-driven imaging features, particularly when lesion data is represented in terms of structural disconnection, are stronger than associations between chronic motor outcomes and theory-based biomarkers. However, combining both theory-based and data-driven models provides the most robust associations
Can vacuum-formed retainers maintain arch dimensions and alignment compared to Hawley and fixed bonded retainers after treatment with fixed appliances? A systematic review and meta-analysis.
No full textBACKGROUND
Different types of retention appliances have been proposed over the years, but their effectiveness in maintaining arch dimensions and alignment after orthodontic treatment is still unclear.
AIM
To assess the efficacy of vacuum-formed retainers (VFRs) in preserving arch widths, arch length, and anterior alignment in maxillary and mandibular arches, compared to removable Hawley retainers (HRs) or fixed bonded retainers (FBRs). Search methods: unrestricted literature search of five major databases up to March 2024.
SELECTION CRITERIA
randomized/non-randomized clinical studies comparing VFRs to removable HRs or FBRs.
DATA COLLECTION AND ANALYSIS
after duplicate study selection, data extraction, and risk of bias assessment, random effects meta-analyses of standardized mean differences and their 95% confidence intervals were performed, followed by meta-regressions, sensitivity analyses, and assessment of the quality of evidence with GRADE.
RESULTS
Twenty-two prospective studies (4 non-randomized and 18 randomized controlled trials) involving 1797 patients (mean age 17.01 years, 38.3% males) were included. No significant differences were found in the intercanine width, intermolar width, and arch length between VFRs and HRs, in both arches (P > 0.05). However, VFRs were statistically more effective than HRs in terms of Little's irregularity scores (LII) in the maxilla (eight studies; SMD = -0.42; 95% CI: -1.03 to -0.09; P = 0.02; I2 = 73.4%) but not in the mandible (P = 0.12). No significant differences were reported for all considered outcomes between VFRs and FBRs in in both arches (P > 0.05), except for lower LII, where VFRs were significantly less efficient (eight studies; SMD = 1.49; 95% CI = 0.26-2.7; P = 0.02; I2 = 93%). Follow-up times, risk of bias, and wire type (of FBRs) did not show statistically significant effects on outcome variables. Sensitivity analyses showed robustness of the findings for including non-randomized and postretention studies. The certainty in these estimates was from moderate to low due to the risk of bias and inconsistency.
CONCLUSIONS
Low to moderate quality evidence indicates that VFRs are as effective as HRs in maintaining arch widths, length, and alignment. Low-quality evidence found similar efficacy between VFRs and FBRs, with FBRs being statistically more effective at maintaining lower arch alignment, but the difference was not clinically significant.
REGISTRATION
PROSPERO registration (CRD42024518433)
Functional Characterization of the Lysosomal Peptide/Histidine Transporter PHT1 (SLC15A4) by Solid Supported Membrane Electrophysiology (SSME).
Get PDFThe peptide/histidine transporter PHT1 (SLC15A4) is expressed in the lysosomal membranes of immune cells where it plays an important role in metabolic and inflammatory signaling. PHT1 is an H+-coupled/histidine symporter that can transport a wide range of oligopeptides, including a variety of bacterial-derived peptides. Moreover, it enables the scaffolding of various metabolic signaling molecules and interacts with key regulatory elements of the immune response. Not surprisingly, PHT1 has been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Unfortunately, the pharmacological development of PHT1 modulators has been hampered by the lack of suitable transport assays. To address this shortcoming, a novel transport assay based on solid-supported membrane-based electrophysiology (SSME) is presented. Key findings of the present SSME studies include the first recordings of electrophysiological properties, a pH dependence analysis, an assessment of PHT1 substrate selectivity, as well as the transport kinetics of the identified substrates. In contrast to previous work, PHT1 is studied in its native lysosomal environment. Moreover, observed substrate selectivity is validated by molecular docking. Overall, this new SSME-based assay is expected to contribute to unlocking the pharmacological potential of PHT1 and to deepen the understanding of its functional properties
A patient empowerment program for primary immunodeficiency improves quality of life in children and adolescents.
Get PDFAim: To assess a patient empowerment program (PEP) for children/adolescents with primary immunodeficiency (PID) on IgG replacement therapy regarding quality of life (QoL) in patients and proxy. Patients & methods: Health-related QoL was assessed using KIDSCREEN-27 and DISABKIDS-37 before and 6 months after PID-PEP kids in 19 children/adolescents and their parents. Results: The following three dimensions of the KIDSCREEN-27 significantly increased in children/adolescents after PID-PEP kids as compared with baseline: Psychological Well-Being, Parents & Autonomy and School Environment. Total DISABKIDS-37 index, as well as 5 of the 6 DISABKIDS-37 dimensions, significantly increased, in other words, Independence, Emotion, Social Inclusion, Social Exclusion and Physical. Evaluation of proxy instruments showed comparable results. Conclusion: PID-PEP kids significantly improved QoL in patients with PID
Three taphonomic stories of three new fossil species of Darwin wasps (Hymenoptera, Ichneumonidae).
Get PDFAmber captures a snapshot of life and death from millions of years in the past. Here, the fate of three fossil Darwin wasps in Baltic amber is virtually dissected with the help of micro-CT scanning, to better understand the taphonomic processes that affected their preservation. The states of the fossils range from nearly perfect preservation, including remains of internal organs, to empty casts that were strongly affected by decomposition. We describe the three specimens as new taxa, Osparvis aurorae gen. et sp. nov., Grana harveydenti gen. et sp. nov. and Xorides? romeo sp. nov. Based on the taphonomic and morphological interpretations, we conclude that two specimens were trapped alive, and the third ended up in resin post-mortem. The morphology and classification of the specimens provide clues regarding their ecology, and we discuss their likely hosts and parasitation modes. Taken together, our three wasp fossils showcase how an integrative analysis of amber taphonomy, taxonomic association and morphology can shed light onto past biodiversity and offer valuable insights for interpreting their evolutionary history
RT2T: A Global Collaborative Project to Study Chromosomal Evolution in the Suborder Ruminantia
Get PDFBridging Concepts: "Presence/Presenza/Anwesenheit"; "Co-Becoming/Mit-Sein/Mutuality of Being";"Coevalness";"Positioning" and "Critical Ethnocentrism"
No full textIn diesem Workshop steht die Lektüre der Arbeiten von Ernesto de Martino und Julius Lips mit Blick auf „Ko-Präsenz“ im Vordergrund. Beide Autoren waren für die Anthropologie in ähnlicher Weise von Bedeutung, so dass beide Autoren parallel gelesen werden. Die Teilnehmenden reflektieren Möglichkeiten und Hindernisse für „Ko-Präsenz“ im Sinne von Gleichörtlichkeit und Gleichzeitigkeit in zunehmend fragmentierten Gesellschaften sowie die Rolle von ethnographisch Fremdem in einer globalisierten Welt
Determinants of Interpatient Variability in Treosulfan Pharmacokinetics in AML Patients Undergoing Autologous Stem Cell Transplantation.
Get PDFLimited data on treosulfan pharmacokinetics in adults, particularly regarding autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML), is available to date. Furthermore, correlations between treosulfan exposure, toxicity, and clinical outcome remain understudied. In this single-center retrospective study, we analyzed data from 55 AML patients who underwent HDCT with treosulfan (14 g/m2) and melphalan (140 mg/m2 or 200 mg/m2) (TreoMel) between August 2019 and November 2023 at the University Hospital of Bern. We assessed treosulfan pharmacokinetics and correlations with several physiological parameters with potential impact on its interpatient variability. We further analyzed how treosulfan exposure correlates with toxicity and clinical outcomes. Women above 55 years showed higher area under the curve (AUC) levels (median: 946 mg*h/L, range: 776-1370 mg*h/L), as compared to women under 55 (median: 758 mg*h/L, range: 459-1214 mg*h/L, p = 0.0487). Additionally, women above 55 showed higher peak levels (median: 387 mg/L, range: 308-468 mg/L), as compared to men of the same age range (median: 326 mg/L, range: 264-395 mg/L, p = 0.0159). Treosulfan levels varied significantly with body temperature, liver enzymes, hemoglobin/hematocrit., and treosulfan exposure correlated with diarrhea severity in women over 55 (p = 0.0076). Our study revealed age- and gender-related variability in treosulfan pharmacokinetics, with higher plasma levels observed in female patients above 55. Moreover, our data suggest that treosulfan plasma levels may vary with several physiological parameters and that higher treosulfan exposure may impact toxicity. Our study underlines the need for further research on treosulfan pharmacokinetics, especially in older patients undergoing HDCT in the ASCT setting
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