65 research outputs found
Tackling teenage obesity: literature review and project proposal
The aim of this report is to assess the available scientific literature which examines predictors of obesity in 11-18 years, with specific reference to the East London
region, and in particular in relation to the boroughs of Barking and Dagenham (B&D).
Through such examination this report thereafter aims to formulate a proposal for an intervention with this age-group in order to reduce the prevalence and incidence of
obesity in teenagers
Noiseless nonreciprocity in a parametric active device
Nonreciprocal devices such as circulators and isolators belong to an
important class of microwave components employed in applications like the
measurement of mesoscopic circuits at cryogenic temperatures. The measurement
protocols usually involve an amplification chain which relies on circulators to
separate input and output channels and to suppress backaction from different
stages on the sample under test. In these devices the usual reciprocal symmetry
of circuits is broken by the phenomenon of Faraday rotation based on magnetic
materials and fields. However, magnets are averse to on-chip integration, and
magnetic fields are deleterious to delicate superconducting devices. Here we
present a new proposal combining two stages of parametric modulation emulating
the action of a circulator. It is devoid of magnetic components and suitable
for on-chip integration. As the design is free of any dissipative elements and
based on reversible operation, the device operates noiselessly, giving it an
important advantage over other nonreciprocal active devices for quantum
information processing applications.Comment: 17 pages, 4 figures + 12 pages Supplementary Informatio
Static non-reciprocity in mechanical metamaterials
Reciprocity is a fundamental principle governing various physical systems,
which ensures that the transfer function between any two points in space is
identical, regardless of geometrical or material asymmetries. Breaking this
transmission symmetry offers enhanced control over signal transport, isolation
and source protection. So far, devices that break reciprocity have been mostly
considered in dynamic systems, for electromagnetic, acoustic and mechanical
wave propagation associated with spatio-temporal variations. Here we show that
it is possible to strongly break reciprocity in static systems, realizing
mechanical metamaterials that, by combining large nonlinearities with suitable
geometrical asymmetries, and possibly topological features, exhibit vastly
different output displacements under excitation from different sides, as well
as one-way displacement amplification. In addition to extending non-reciprocity
and isolation to statics, our work sheds new light on the understanding of
energy propagation in non-linear materials with asymmetric crystalline
structures and topological properties, opening avenues for energy absorption,
conversion and harvesting, soft robotics, prosthetics and optomechanics.Comment: 19 pages, 3 figures, Supplementary information (11 pages and 5
figures
Rac1 Deletion Causes Thymic Atrophy
The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation
Adherent Human Alveolar Macrophages Exhibit a Transient Pro-Inflammatory Profile That Confounds Responses to Innate Immune Stimulation
Alveolar macrophages (AM) are thought to have a key role in the immunopathogenesis of respiratory diseases. We sought to test the hypothesis that human AM exhibit an anti-inflammatory bias by making genome-wide comparisons with monocyte derived macrophages (MDM). Adherent AM obtained by bronchoalveolar lavage of patients under investigation for haemoptysis, but found to have no respiratory pathology, were compared to MDM from healthy volunteers by whole genome transcriptional profiling before and after innate immune stimulation. We found that freshly isolated AM exhibited a marked pro-inflammatory transcriptional signature. High levels of basal pro-inflammatory gene expression gave the impression of attenuated responses to lipopolysaccharide (LPS) and the RNA analogue, poly IC, but in rested cells pro-inflammatory gene expression declined and transcriptional responsiveness to these stimuli was restored. In comparison to MDM, both freshly isolated and rested AM showed upregulation of MHC class II molecules. In most experimental paradigms ex vivo adherent AM are used immediately after isolation. Therefore, the confounding effects of their pro-inflammatory profile at baseline need careful consideration. Moreover, despite the prevailing view that AM have an anti-inflammatory bias, our data clearly show that they can adopt a striking pro-inflammatory phenotype, and may have greater capacity for presentation of exogenous antigens than MDM
Emotional Responses to Disfigured Faces: The Influences of Perceived Anonymity, Empathy, and Disgust Sensitivity
Methods for the evaluation of biomarkers in patients with kidney and liver diseases: multicentre research programme including ELUCIDATE RCT
Background:
Protein biomarkers with associations with the activity and outcomes of diseases are being identified by modern proteomic technologies. They may be simple, accessible, cheap and safe tests that can inform diagnosis, prognosis, treatment selection, monitoring of disease activity and therapy and may substitute for complex, invasive and expensive tests. However, their potential is not yet being realised.
Design and methods:
The study consisted of three workstreams to create a framework for research: workstream 1, methodology – to define current practice and explore methodology innovations for biomarkers for monitoring disease; workstream 2, clinical translation – to create a framework of research practice, high-quality samples and related clinical data to evaluate the validity and clinical utility of protein biomarkers; and workstream 3, the ELF to Uncover Cirrhosis as an Indication for Diagnosis and Action for Treatable Event (ELUCIDATE) randomised controlled trial (RCT) – an exemplar RCT of an established test, the ADVIA Centaur® Enhanced Liver Fibrosis (ELF) test (Siemens Healthcare Diagnostics Ltd, Camberley, UK) [consisting of a panel of three markers – (1) serum hyaluronic acid, (2) amino-terminal propeptide of type III procollagen and (3) tissue inhibitor of metalloproteinase 1], for liver cirrhosis to determine its impact on diagnostic timing and the management of cirrhosis and the process of care and improving outcomes.
Results:
The methodology workstream evaluated the quality of recommendations for using prostate-specific antigen to monitor patients, systematically reviewed RCTs of monitoring strategies and reviewed the monitoring biomarker literature and how monitoring can have an impact on outcomes. Simulation studies were conducted to evaluate monitoring and improve the merits of health care. The monitoring biomarker literature is modest and robust conclusions are infrequent. We recommend improvements in research practice. Patients strongly endorsed the need for robust and conclusive research in this area. The clinical translation workstream focused on analytical and clinical validity. Cohorts were established for renal cell carcinoma (RCC) and renal transplantation (RT), with samples and patient data from multiple centres, as a rapid-access resource to evaluate the validity of biomarkers. Candidate biomarkers for RCC and RT were identified from the literature and their quality was evaluated and selected biomarkers were prioritised. The duration of follow-up was a limitation but biomarkers were identified that may be taken forward for clinical utility. In the third workstream, the ELUCIDATE trial registered 1303 patients and randomised 878 patients out of a target of 1000. The trial started late and recruited slowly initially but ultimately recruited with good statistical power to answer the key questions. ELF monitoring altered the patient process of care and may show benefits from the early introduction of interventions with further follow-up. The ELUCIDATE trial was an ‘exemplar’ trial that has demonstrated the challenges of evaluating biomarker strategies in ‘end-to-end’ RCTs and will inform future study designs.
Conclusions:
The limitations in the programme were principally that, during the collection and curation of the cohorts of patients with RCC and RT, the pace of discovery of new biomarkers in commercial and non-commercial research was slower than anticipated and so conclusive evaluations using the cohorts are few; however, access to the cohorts will be sustained for future new biomarkers. The ELUCIDATE trial was slow to start and recruit to, with a late surge of recruitment, and so final conclusions about the impact of the ELF test on long-term outcomes await further follow-up. The findings from the three workstreams were used to synthesise a strategy and framework for future biomarker evaluations incorporating innovations in study design, health economics and health informatics
- …