Unusual Experiences, Beliefs and Paranoia: Exploring the Relationships with Shame Memories and Compassion

Background: Individuals with psychotic-type experiences (unusual experiences, beliefs and paranoia) have been found to have high levels of shame. Early shame memories, which can act as traumatic memories and become central to one’s identity, have been associated with shame in adulthood. Whilst shame has been examined in relation to paranoia, the relationship between shame and unusual experiences and beliefs warrants further attention. Furthermore, shame memories have not yet been investigated in individuals with unusual beliefs and experiences. Self-compassion has been found to reduce shame, psychotic-type experiences and their associated distress, but is yet to be investigated within this population. Aims: To explore the relationships between shame memories containing traumatic and centrality features, current experiences of shame, psychotic-type experiences and their associated distress, and self-compassion. Method: A cross-sectional design was employed and a mixed clinical/non clinical sample of adults from the UK was recruited (N = 35) through convenience and purposive sampling. Participants completed a series of established self-report measures via an online survey platform. Results: Multiple regression analyses showed that shame memories containing traumatic features were a significant predictor of external shame and the distress associated with all three psychotic-type experiences. Internal shame was found to moderate this relationship. Conclusion: Several tentative clinical implications can be drawn from the findings including the importance of attending to the properties of shame memories in the experience of distressing psychotic-type experiences. This may be particularly relevant for individuals who also experience external shame. Internal shame should also be considered as a focus for therapeutic interventions when working with distressing psychotic-type experiences

Analysis of Parametric Oscillatory Instability in Power Recycled LIGO Interferometer

We present the analysis of a nonlinear effect of parametric oscillatory instability in power recycled LIGO interferometer with the Fabry-Perot (FP) cavities in the arms. The basis for this effect is the excitation of the additional (Stokes) optical mode and the mirror elastic mode, when the optical energy stored in the main FP cavity main mode exceeds the certain threshold and the frequencies are related so that sum of frequencies of Stokes and elastic modes are approximately equal to frequencyof main mode. The presence of anti-Stokes modes (with frequency approximately equal to sum of frequencies of main and elastic modes) can depress parametric instability. However, it is very likely that the anti-Stokes modes will not compensate the parametric instability completely.Comment: 9 pages, 2 figures. submitted to Physics Letters

Part Variation Modeling to Avoid Scrap Parts in Multi-stage Production Systems

Manufacturing systems for today's products are complex systems requiring a variety of different processes in order to be able to manufacture all necessary part features. This also applies to the production of rotating components, which have experienced increasing demand at the latest due to the growth in mobility. As in almost every manufacturing process, quality-reducing defects can occur due to deviations for example tool wear, which cannot always be avoided. Those, that have accumulated from previous process steps can cause the occurrence of superimposed defects. This leads to complex relationships between quality defects in the end product and the numerous parameters of the manufacturing processes. To remain competitive, production must be optimized in order to identify defects as early as possible, as well as their dependencies and variation patterns. The paper presents an approach to identify and model part variations within multi-stage production systems. Subsequently, based on a detected deviation, a downstream compensation strategy can be proposed at an early stage of the manufacturing process, which uses the capability of the overall system to fundamentally eliminate rejects

Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model

B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility "conventional" (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora

Lower-limb amputees can reduce the energy cost of walking when assisted by an Active Pelvis Orthosis

Exoskeletons could compete with active prostheses as effective aids to reduce the increased metabolic demands faced by lower-limb amputees during locomotion. However, little evidence of their efficacy with amputees has been provided so far. In this paper, a portable hip exoskeleton has been tested with seven healthy subjects and two transfemoral amputees, with the final goal to verify whether a hip flexion-extension assistance could be effective in reducing the metabolic cost of walking. The metabolic power of the participants was estimated through indirect calorimetry during alternated repetitions of three treadmill-based walking conditions: without the exoskeleton (NoExo), with the exoskeleton in zero-torque mode (ExoTM) and with the exoskeleton providing hip flexion-extension assistance (ExoAM). The results showed that the exoskeleton reduced the net metabolic power of the two amputees in ExoAM with respect to NoExo, by 5.0% and 3.4%. With healthy subjects, a 5.5±3.1% average reduction in the metabolic power was observed during ExoAM compared to ExoTM (differences were not statistically significant), whereas ExoAM required 3.9±3.0% higher metabolic power than NoExo (differences were not statistically significant). These results provide initial evidence of the potential of exoskeletal technologies for assisting lower-limb amputees, thereby paving the way for further experimentations

Spatiotemporal in vivo tracking of polyclonal human regulatory T cells reveals a role for innate immune cells in Treg transplant recruitment

Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs was shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive which hampers clinical translation. Here, we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behaviour, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nanoSPECT/CT for up to 40 days and results validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1⁺ innate immune cells. We demonstrated the utility of radionuclide reporter gene afforded quantitative Treg in vivo tracking thereby addressing a fundamental need in Treg therapy development and offering clinically compatible methodology for future Treg therapy imaging in humans

B lymphocytes contribute to indirect pathway T cell sensitisation via acquisition of extracellular vesicles

B cells have been implicated in transplant rejection via antibody‐mediated mechanisms and more recently by presenting donor‐antigens to T cells. We have shown in patients with chronic antibody‐mediated rejection that B cells control the indirect T cell alloresponses. To understand more about the role of B cells as antigen presenting cells for CD4⁺ T cell with indirect allospecificity, B cells were depleted in C57BL/6 mice, using an anti‐CD20 antibody, prior to receiving MHC‐class I‐mismatched (Kᵈ) skin. The absence of B cells at the time of transplantation prolonged skin graft survival. To study the mechanisms behind this observation, T cells with indirect allospecificity were transferred in mice receiving a Kᵈ skin transplant. T cell proliferation was markedly inhibited in the absence of recipient B cells, suggesting that B cells contribute to indirect pathway sensitisation. Furthermore, we have shown that a possible way in which B cells present alloantigens is via acquisition of MHC‐peptide complexes. Finally, we demonstrate that the addition of B cell depletion to the transfer of Tregs with indirect alloresponse further prolonged skin graft survival. This study supports an important role for B cells in indirect T cell priming and further emphasises the advantage of combination therapies in prolonging transplant survival

Nox2-deficient Tregs improve heart transplant outcomes via their increased graft recruitment and enhanced potency

Nox2 is a ROS-generating enzyme, deficiency of which increases suppression by Tregs in vitro and in an in vivo model of cardiac remodelling. Since Tregs have emerged as a candidate therapy in autoimmunity and transplantation, we hypothesised that Nox2 deficiency in Tregs in recipient mice may improve outcomes in a heart transplant model. A novel B6129 mouse model with Treg-targeted Nox2 deletion (Nox2ᶠˡ/ᶠˡFoxP3Cre⁺) was generated and transplanted with hearts from CB6F1 donors. As compared to littermate controls, Nox2ᶠˡ/ᶠˡFoxP3Cre⁺ mice had lower plasma levels of alloantibodies and troponin-I, reduced levels of IFN-γ in heart allograft homogenates and diminished cardiomyocyte necrosis and allograft fibrosis. Single cell analyses of allografts revealed higher absolute numbers of Tregs and lower CD8⁺ T cell infiltration in Nox2-deficient recipients compared to Nox2-replete mice. Mechanistically, in addition to a greater suppression of CD8⁺CD25⁻ T effector cell proliferation and IFN-γ production, Nox2-deficient Tregs expressed higher levels of CCR4 and CCR8, driving cell migration to allografts; this was associated with increased expression of miR214-3p. These data indicate that Nox2 deletion in Tregs enhances their suppressive ability and migration to heart allografts. Therefore, Nox2 inhibition in Tregs may be a useful approach to improve their therapeutic efficacy

Spatiotemporal in vivo tracking of polyclonal human regulatory T cells (Tregs) reveals a role for innate immune cells in Treg transplant recruitment

Supplemental information is available online at: https://www.sciencedirect.com/science/article/pii/S2329050120302515#appsec2 .Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1+ innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans.This work was supported by the British Heart Foundation (RG/13/12/30395), the MRC Centre for Transplantation at King's College London (MR/J006742/1), Cancer Research UK (C48390/A21153), and the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z). This research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility