UK Defence Research Agency the Two UK \u27Space Technology Research Vehicles\u27: First In-Orbit Results

The UK Defence Research Agency is about to launch two 50kg \u27Space Technology Research Vehicles\u27 which have as their major objective the demonstration and in-orbit evaluation of new technologies which have application to future space missions, both large and small. The STRVs are due for launch together on an Ariane 4 in June 1994 and will go into a geostationary transfer orbit which provides a very harsh (and therefore good) environment for the evaluation of the new technology. Areas of research for the mission include the use of advanced structural materials, use of new radiation hardened computers, sensors, solar cells and microelectronics, use of ADA software in a restricted memory space, demonstration of cryocoolers, measurement of electrostatic charge, elimination of electrostatic charge, measurement of atomic oxygen erosion, measurement of the incidence of cosmic rays and total dose radiation, improved battery charging techniques, and also the demonstration of key components from the UK ion thruster system. The two satellites not only carry a suite of 14 experiments between them, including experiments from BMDO, ESA and various universities but they also incorporate new technologies into the bus itself. This paper will give a full overview of the mission including a description of the in-orbit performance of the two spacecraft. Some of the main results from the early part of the mission with respect to spacecraft, subsystem and experiment performance will be presented together with a preview of the mission plan to follow during the remainder of the one year mission

Iatrogenic Complications of Compulsory Treatment in a Patient Presenting with an Emotionally Unstable Personality Disorder and Self-Harm.

Attempted suicide and deliberate self-harm are common and challenging presentations in the emergency department. A proportion of these patients refuse interventions and this presents the clinical, legal, and ethical dilemma as to whether treatment should be provided against their will. Multiple factors influence this decision. It is difficult to foresee the multitude and magnitude of complications that can arise once it has been decided to treat individuals who do not consent. This case illustrates a particularly complex chain of events that occurred after treating someone against their will who presented with self-harm and suicidal ideation. These consequences are contrasted with those of not intervening when similar situations arose with the same patient

Cytomegalovirus drives Vδ2neg γδ T cell inflation in many healthy virus carriers with increasing age

Cytomegalovirus (CMV) usually causes lifelong asymptomatic infection, but over time can distort immune profiles. Recent reports describe selective expansion of Vδ2(neg) γδ T cells in healthy and immunocompromised CMV carriers. Having shown previously that virus-specific CD8(+) and CD4(+) T cell responses are increased significantly in elderly CMV carriers, probably driven by chronic stimulation, we hypothesized that Vδ2(neg) γδ T cells may also be expanded with age. Our results show that Vδ2(neg) γδ T cells are increased significantly in CMV-seropositive healthy individuals compared to CMV-seronegative controls in all age groups. The differences were most significant in older age groups (P < 0·0001). Furthermore, while Vδ2(neg) γδ T- cells comprise both naive and memory cells in CMV-seronegative donors, highly differentiated effector memory cells are the dominant phenotype in CMV carriers, with naive cells reduced significantly in numbers in CMV-seropositive elderly. Although phenotypically resembling conventional CMV-specific T cells, Vδ2(neg) γδ T cells do not correlate with changes in magnitude of CMV-specific CD4(+) or CD8(+) T cell frequencies within those individuals, and do not possess ex-vivo immediate effector function as shown by CMV-specific CD4(+) and CD8(+) T cells. However, after short-term culture, Vδ2(neg) γδ T cells demonstrate effector T cell functions, suggesting additional requirements for activation. In summary, Vδ2(neg) γδ T cells are expanded in many older CMV carriers, demonstrating a further level of lymphocyte subset skewing by CMV in healthy individuals. As others have reported shared reactivity of Vδ2(neg) γδ T cells towards tumour cells, the composition of γδ T cell subsets may also have implications for risk of developing cancer in elderly people

An update: improvements in imaging perfluorocarbon-mounted plant leaves with implications for studies of plant pathology, physiology, development and cell biology.

Plant leaves are optically complex, which makes them difficult to image by light microscopy. Careful sample preparation is therefore required to enable researchers to maximize the information gained from advances in fluorescent protein labeling, cell dyes and innovations in microscope technologies and techniques. We have previously shown that mounting leaves in the non-toxic, non-fluorescent perfluorocarbon (PFC), perfluorodecalin (PFD) enhances the optical properties of the leaf with minimal impact on physiology. Here, we assess the use of the PFCs, PFD, and perfluoroperhydrophenanthrene (PP11) for in vivo plant leaf imaging using four advanced modes of microscopy: laser scanning confocal microscopy (LSCM), two-photon fluorescence microscopy, second harmonic generation microscopy, and stimulated Raman scattering (SRS) microscopy. For every mode of imaging tested, we observed an improved signal when leaves were mounted in PFD or in PP11, compared to mounting the samples in water. Using an image analysis technique based on autocorrelation to quantitatively assess LSCM image deterioration with depth, we show that PP11 outperformed PFD as a mounting medium by enabling the acquisition of clearer images deeper into the tissue. In addition, we show that SRS microscopy can be used to image PFCs directly in the mesophyll and thereby easily delimit the "negative space" within a leaf, which may have important implications for studies of leaf development. Direct comparison of on and off resonance SRS micrographs show that PFCs do not to form intracellular aggregates in live plants. We conclude that the application of PFCs as mounting media substantially increases advanced microscopy image quality of living mesophyll and leaf vascular bundle cells

Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches

Abstract Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways

Simulating a Community Mental Health Service During the COVID-19 Pandemic: Effects of Clinician-Clinician Encounters, Clinician-Patient-Family Encounters, Symptom-Triggered Protective Behaviour, and Household Clustering.

Objectives: Face-to-face healthcare, including psychiatric provision, must continue despite reduced interpersonal contact during the COVID-19 (SARS-CoV-2 coronavirus) pandemic. Community-based services might use domiciliary visits, consultations in healthcare settings, or remote consultations. Services might also alter direct contact between clinicians. We examined the effects of appointment types and clinician-clinician encounters upon infection rates. Design: Computer simulation. Methods: We modelled a COVID-19-like disease in a hypothetical community healthcare team, their patients, and patients' household contacts (family). In one condition, clinicians met patients and briefly met family (e.g., home visit or collateral history). In another, patients attended alone (e.g., clinic visit), segregated from each other. In another, face-to-face contact was eliminated (e.g., videoconferencing). We also varied clinician-clinician contact; baseline and ongoing "external" infection rates; whether overt symptoms reduced transmission risk behaviourally (e.g., via personal protective equipment, PPE); and household clustering. Results: Service organisation had minimal effects on whole-population infection under our assumptions but materially affected clinician infection. Appointment type and inter-clinician contact had greater effects at low external infection rates and without a behavioural symptom response. Clustering magnified the effect of appointment type. We discuss infection control and other factors affecting appointment choice and team organisation. Conclusions: Distancing between clinicians can have significant effects on team infection. Loss of clinicians to infection likely has an adverse impact on care, not modelled here. Appointments must account for clinical necessity as well as infection control. Interventions to reduce transmission risk can synergize, arguing for maximal distancing and behavioural measures (e.g., PPE) consistent with safe care

Retrieval of the dayside atmosphere of WASP-43b with CRIRES+

Accurately estimating the C/O ratio of hot Jupiter atmospheres is a promising pathway towards understanding planet formation and migration, as well as the formation of clouds and the overall atmospheric composition. The atmosphere of the hot Jupiter WASP-43b has been extensively analysed using low-resolution observations with HST and Spitzer, but these previous observations did not cover the K band, which hosts prominent spectral features of major carbon-bearing species such as CO and CH$_{4}$. As a result, the ability to establish precise constraints on the C/O ratio was limited. Moreover, the planet has not been studied at high spectral resolution, which can provide insights into the atmospheric dynamics. In this study, we present the first high-resolution dayside spectra of WASP-43b with the new CRIRES$^+$ spectrograph. By observing the planet in the K band, we successfully detected the presence of CO and provide evidence for the existence of H$_2$O using the cross-correlation method. This discovery represents the first direct detection of CO in the atmosphere of WASP-43b. Furthermore, we retrieved the temperature-pressure profile, abundances of CO and H$_2$O, and a super-solar C/O ratio of 0.78 by applying a Bayesian retrieval framework to the data. Our findings also shed light on the atmospheric characteristics of WASP-43b. We found no evidence for a cloud deck on the dayside, and recovered a line broadening indicative of an equatorial super-rotation corresponding to a jet with a wind speed of $\sim$ 5 km s$^{-1}$, matching the results of previous forward models and low-resolution atmospheric retrievals for this planet.Comment: 15 pages, 14 figure

Bioclimatic transect networks: powerful observatories of ecological change

First published: 19 May 2017Transects that traverse substantial climate gradients are important tools for climate change research and allow questions on the extent to which phenotypic variation associates with climate, the link between climate and species distributions, and variation in sensitivity to climate change among biomes to be addressed. However, the potential limitations of individual transect studies have recently been highlighted. Here, we argue that replicating and networking transects, along with the introduction of experimental treatments, addresses these concerns. Transect networks provide cost-effective and robust insights into ecological and evolutionary adaptation and improve forecasting of ecosystem change. We draw on the experience and research facilitated by the Australian Transect Network to demonstrate our case, with examples, to clarify how population- and community-level studies can be integrated with observations from multiple transects, manipulative experiments, genomics, and ecological modeling to gain novel insights into how species and systems respond to climate change. This integration can provide a spatiotemporal understanding of past and future climate-induced changes, which will inform effective management actions for promoting biodiversity resilience.Stefan Caddy-Retalic, Alan N. Andersen, Michael J. Aspinwall, Martin F. Breed, Margaret Byrne, Matthew J. Christmas, Ning Dong, Bradley J. Evans, Damien A. Fordham, Greg R. Guerin, Ary A. Hoffmann, Alice C. Hughes, Stephen J. van Leeuwen, Francesca A. McInerney, Suzanne M. Prober, Maurizio Rossetto, Paul D. Rymer, Dorothy A. Steane, Glenda M. Wardle, Andrew J. Low

Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases

Mesenchymal stem cells (MSCs) modulate immune responses and maintain self-tolerance. Their trophic activities and regenerative properties make them potential immunosuppressants for treating autoimmune and autoinflammatory diseases. MSCs are drawn to sites of injury and inflammation where they can both reduce inflammation and contribute to tissue regeneration. An increased understanding of the role of MSCs in the development and progression of autoimmune disorders has revealed that MSCs are passive targets in the inflammatory process, becoming impaired by it and exhibiting loss of immunomodulatory activity. MSCs have been considered as potential novel cell therapies for severe autoimmune and autoinflammatory diseases, which at present have only disease modifying rather than curative treatment options. MSCs are emerging as potential therapies for severe autoimmune and autoinflammatory diseases. Clinical application of MSCs in rare cases of severe disease in which other existing treatment modalities have failed, have demonstrated potential use in treating multiple diseases, including rheumatoid arthritis, systemic lupus erythematosus, myocardial infarction, liver cirrhosis, spinal cord injury, multiple sclerosis, and COVID-19 pneumonia. This review explores the biological mechanisms behind the role of MSCs in autoimmune and autoinflammatory diseases. It also covers their immunomodulatory capabilities, potential therapeutic applications, and the challenges and risks associated with MSC therapy.</jats:p