324139 research outputs found
Sort by
Patient expectations for outcome with psychological intervention for psychosis
No full textBackground: Initial patient perceptions of a treatment’s credibility, and expectations for improvement, have been shown to predict to a small degree outcomes for common mental health disorders. This study aimed to discover: how patients with psychosis initially perceive psychological therapy’s credibility and likely success; whether there are predictors of these first views; and, primarily, if such ideas predict improvement in persecutory delusions. Methods: We analysed first therapy session data on credibility and expectancy from 195 patients with non-affective psychosis taking part in clinical trials treating persecutory delusions. Baseline assessments before randomisation to therapy were used to identify potential predictors of credibility and expectancy. First session credibility and expectancy scores were tested as predictors of persecutory delusion severity six months later. Results: Most patients were optimistic about therapy’s potential. Baseline delusion severity did not predict credibility, β=-.02, p=.742, or expectancy, β=-.03, p=.632. Higher psychological well-being predicted higher levels of expectancy, β=.23, p=.001. Higher levels of credibility, β=-.17, p=.021, and expectancy, β=-.17, p=.020, predicted lower severity of persecutory delusions six months later. Credibility, β=.00, p=.970, and expectancy, β=-.21, p=.074, did not significantly predict uptake of therapy sessions. Conclusions: Treatment credibility and expectancy may account for a small proportion of improvement when psychological interventions are used to treat severe paranoia. The results are comparable to those for common mental health disorders. There was little prediction of patient variability in credibility and expectancy. It will be helpful to understand a patient’s initial views on intervention so that any concerns can be addressed
Lytic IFNγ is stored in cytotoxic granules and coreleased with granzyme B to mediate cytotoxic T lymphocyte killing
Get PDFCytotoxic T lymphocytes (CTLs) eliminate target cells by forming immunological synapses and releasing effector molecules, including interferon gamma (IFNγ). However, how IFNγ contributes to cytotoxicity remains unclear. Here, we identify a subset of IFNγ stored within granzyme B⁺ cytotoxic granules (CGs) in activated mouse and human CTLs, which we term lytic IFNγ. This CG-associated IFNγ represents the primary pool released in a polarized manner at the immunological synapse together with canonical lytic molecules. Lytic IFNγ is present in tumor-infiltrating CTLs and is cosecreted with granzyme B (GzmB) in both soluble form and as part of supramolecular attack particles (SMAPs). Functional assays indicate that IFNγ contributes to CTL-mediated tumor cell death by acting in concert with granzyme B and perforin to increase cytotoxicity and promote apoptosis via the IFNγ-STAT1-caspase-3 pathway. CTLs lacking the vesicle priming factor Munc13-4 exhibit impaired release of both CGs and early-phase IFNγ. However, prolonged synapse engagement restores IFNγ secretion at distal membrane sites, revealing a second, nonpolarized IFNγ pool. Consistently, endogenous IFNγ is detected in both CG-enriched and multivesicular body (MVB)-enriched fractions. We propose that while lytic IFNγ is released from CGs at the synapse to directly promote target cell killing, nonpolarized IFNγ secretion originates from MVBs or small vesicles during sustained activation. Together, these findings reveal a previously unrecognized mechanism of IFNγ storage and release, establishing lytic IFNγ as a critical effector component of CTL cytotoxicity and antitumor immunity
Integrated action for skin NTDs: Deconstructing transmission, addressing knowledge gaps, and championing one health strategies
Get PDFSkin Neglected Tropical Diseases (skin NTDs) are a critical, underestimated source of chronic pathology, severely impacting vulnerable, rural populations with poor healthcare access. These diseases heighten the risk of systemic infection, amputation, and premature mortality. Their visibility and co-endemic nature present a pivotal opportunity for integrated diagnostics and management at the primary care level. Aligned with the WHO roadmap, this review advocates for a robust One Health framework, examining the complex interplay of human, animal, and environmental transmission factors. We contrast diseases with understood transmission against those requiring research. Leveraging the skin as a common pathway, we argue for strategic, integrated public health action to substantially improve patient outcomes globally
State-of-the-art and tomorrow’s challenges and opportunities in constitutive modeling of soft biological tissues with a focus on arterial, cardiac and brain biomechanics
Get PDFThe aim of this paper is to provide an up-to-date overview of the constitutive modeling of soft biological tissues, both from a simulation and experimental perspective by taking into account different length scales. After providing some essential ingredients on continuum mechanics, especially nonlinear elasticity, the focus is on mechanical and structural modeling of fiber-reinforced materials, including the features of soft tissues such as collagen fiber dispersion, and residual stresses. Materials testing and data acquisition for constitutive modeling of soft tissue are also discussed, with emphasis on measuring strain fields using imaging techniques and digital image correlation. The topics are illustrated for three tissues. First, applications to arteries are illustrated and the effects of vascular adaptation in diseases such as aneurysms and aortic dissections are discussed. The second application includes cardiac biomechanical modeling, touching on the nonlinear anisotropic and viscoelastic nature of the myocardium, the synthesis and integration of these concepts into whole-organ models, and the assimilation of image-based data for patient-specific modeling. The third focus is on brain mechanics, including the unusual response of brain tissues and axons under loads, the formation of the brain and skull during development, and the study of brain trauma and diseases. The important area of machine learning for discovering constitutive models and parameter identification is also covered. To show how constitutive models can be selected, a model discovery approach is reviewed. Because the mechanical properties of soft tissues may vary with age, sex, health and disease an account of uncertainty quantification in the model assumptions and measurement errors is provided. Future directions and challenges for research in multiscale biomechanics and mechanobiology are identified involving mechanical, biological, electrical and fluid-structure interactions
denim: An R package for deterministic compartmental models with flexible dwell‐time distributions
Get PDFCompartmental models are widely used for dynamical systems where states are discrete, such as in infectious disease epidemiology with the so‐called Susceptible‐Infectious‐Recovered (SIR) framework. For mathematical simplicity, rates of transition between compartments are generally assumed to be independent of the dwell time (or secondary timescale in survival analysis): they are either constant or dependent on the epidemiological time (or primary timescale in survival analysis) only, either directly (e.g. environmental or behavioural forcings in epidemiological models) or indirectly through dependence on other variables of the system (e.g. the force of infection in epidemiological models). In some domains of application, this memoryless assumption leads to distributions of dwelling times that are incompatible with those observed in data (e.g. infectious periods for childhood diseases), which can lead to serious problems since the model predictions are highly sensitive to the exact shape of these distributions. Here, we propose a deterministic, continuous‐variable, numerical modelling approach that allows full flexibility on the dwell‐time distributions. The accompanying denim package provides a user‐friendly interface to implement our proposed method through a dedicated language for model definition. The package is open source and available on CRAN. As more detailed data on the clinical process of infections become available, the denim package will be extremely useful for building more realistic epidemiological models that provide more accurate projections
Yb 2 ‐Tb Upconversion in a Hetero‐Trimetallic Molecular Lanthanide Complex
Get PDFPhoton Upconversion in molecular hetero‐metallic lanthanide systems is challenged by the lack of chemical diversity displayed by the lanthanide ions. Here, we report the multi‐photon photophysical properties of a series of molecular hetero‐trimetallic lanthanide complexes Yb2Ln (Ln = Eu3+, Gd3+, Tb3+) assembled from kinetically inert building blocks providing site‐specific chemical control regarding introduction of differing lanthanide ions. The hetero‐trimetallic complex Yb2Tb shows efficient Yb2 → Tb photon upconversion via cooperative sensitization in both D2O and H2O. By contrast, Yb2Eu does not show Yb2 → Eu upconversion, while Yb2Gd has been used as a spectroscopic blank. We find that the Yb2 → Tb energy transfer appears to be independent of OH quenching from the solvent. Additionally, we report the intermetallic distances in the complex using density functional theory and molecular dynamics simulations. We find that the Yb2 → Tb cooperative sensitization upconversion energy transfer remains effective despite relatively long intermetallic distances between donor pairs (13.5–25 Å) and between the Yb donors and the Tb acceptor (11.5–13.5 Å)
Galectin-3 in the Lateral Ventricle Regulates Immune Functions
No full textGalectin-3 (Gal-3) is a protein expressed by glia that belongs to an ancient family. Gal-3 recognises molecular patterns on pathogens due to the high degree of its binding specificity with carbohydrate recognition domains. Thus, in sponges as well as other invertebrates, galectins are an important component of the primitive innate immune system. Whereas Gal-3′s function in driving mammalian inflammation is well known, its function in warding off bacterial and viral infections is not well appreciated. One route of brain infection is via the cerebrospinal fluid brain interface (CSFBI) which is primarily composed of ependymal cells (EC). ECs express high levels of Gal-3, and their motile cilia are compromised in Gal-3 KOs. In this mini-review, we discuss fundamentally important potential roles of Gal-3 in pathogen recognition at the CSFBI and suggest avenues of further study
High Power Laser Science and Engineering Editorial – a celebration of ultra-high-power lasers
Get PDFIn 2019 we published the extensive review paper ‘Petawatt and exawatt class lasers worldwide’ in High Power Laser Science and Engineering. We are delighted that the review has achieved over 1000 citations on Google Scholar and over 750 on Web of Science. We take this opportunity to reflect on the current state of the field
Estimating the economic burden of diabetes in young adults: A global analysis based on the GBD 2021 and a value of statistical life year framework
Get PDFAims: The rising prevalence of diabetes in young adults threatens global health and sustainable development. However, its full macroeconomic impact, especially the welfare losses beyond conventional productivity costs, has not been systematically quantified at a global level. We aimed to estimate the current and future global economic burden of diabetes in individuals aged 15–39 years using a welfare‐based approach. Methods: Using disability‐adjusted life‐years (DALYs) from the Global Burden of Disease Study 2021, we monetized health losses into a value of lost welfare (VLW) via a value of a statistical life year approach. We estimated the VLW globally, regionally and nationally, analysed its distribution by Socio‐Demographic Index (SDI) and made projections to 2050. Results: In 2021, the global economic burden was Int240.30 billion) and Oceania the highest relative impact (3.03% of GDP). Projections show the burden will more than double by 2050 to 1.32% of global GDP, driven almost entirely by type 2 diabetes. Conclusions: Diabetes in young adults represents a significant and growing macroeconomic burden. Our findings underscore the urgent need for public health strategies and economic policies focused on preventing type 2 diabetes. Such interventions are especially critical for countries with fragile health systems to mitigate substantial future economic and health losses