5,061 research outputs found
Topological Interactions in Warped Extra Dimensions
Topological interactions will be generated in theories with compact extra
dimensions where fermionic chiral zero modes have different localizations. This
is the case in many warped extra dimension models where the right-handed top
quark is typically localized away from the left-handed one. Using
deconstruction techniques, we study the topological interactions in these
models. These interactions appear as trilinear and quadrilinear gauge boson
couplings in low energy effective theories with three or more sites, as well as
in the continuum limit. We derive the form of these interactions for various
cases, including examples of Abelian, non-Abelian and product gauge groups of
phenomenological interest. The topological interactions provide a window into
the more fundamental aspects of these theories and could result in unique
signatures at the Large Hadron Collider, some of which we explore.Comment: 40 pages, 10 figures, 2 tables; modifications in the KK parity
discussion, final version at JHE
An Exit Strategy for Resuming Nonemergency Neurosurgery after Severe Acute Respiratory Syndrome Coronavirus 2: A United Kingdom Perspective
INTRODUCTION: Substantial healthcare resources have been diverted to manage the effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and nonemergency neurosurgery has been effectively closed. As we begin to emerge from the crisis, we will need to manage the backlog of nonemergency neurosurgical patients whose treatment has been delayed and remain responsive to further possible surges of SARS-CoV-2 infections. METHODS: In the present study, we aimed to identify the core themes and challenges that will limit resumption of a normal neurosurgical service after the SARS-CoV-2 pandemic and to provide pragmatic advice and solutions that could be of utility to clinicians seeking to resume nonemergency neurosurgical care. We reviewed the relevant international policies, a wide range of journalistic and media sources, and expert opinion documents to address the stated aims. RESULTS: We have presented and discussed a range of factors that could become potential barriers to resuming full elective neurosurgical provision and important steps that must be completed to achieve pre-SARS-CoV-2 surgical capacity. We also explored how these challenges can be overcome and outlined the key requirements for a successful neurosurgical exit strategy from the pandemic. CONCLUSION: The performance of nonemergency neurosurgery can start once minimum criteria have been fulfilled: 1) a structured prioritization of surgical cases; 2) virus infection incidence decreased sufficiently to release previously diverted healthcare resources; 3) adequate safety criteria met for patients and staff, including sufficient personal protective equipment and robust testing availability; and 4) maintenance of systems for rapid communication at organizational and individual levels
Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: Different boosting intervals and implications for efficacy trials
Objectives. To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen
85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and
second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. Design. There
are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG.
These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naı¨ve adults. Subjects were vaccinated with BCG
alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety
and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime–MVA85A
boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination
was administered many years after vaccination with BCG. Results. MVA85A was safe and highly immunogenic when
administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were
compared with the previous long interval trial data, there were no significant differences in the magnitude of immune
responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. Conclusions. The
clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses.
This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These
findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial
immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data
presented here. Trial Registration. ClinicalTrials.Oxford University was the sponsor for all the clinical trials reported here
Stretchable liquid-crystal blue-phase gels
Liquid crystalline polymers are materials of considerable scientific interest
and technological value to society [1-3]. An important subset of such materials
exhibit rubber-like elasticity; these can combine the remarkable optical
properties of liquid crystals with the favourable mechanical properties of
rubber and, further, exhibit behaviour not seen in either type of material
independently [2]. Many of their properties depend crucially on the particular
mesophase employed. Stretchable liquid crystalline polymers have previously
been demonstrated in the nematic, chiral nematic, and smectic mesophases [2,4].
Here were report the fabrication of a stretchable gel of blue phase I, which
forms a self-assembled, three-dimensional photonic crystal that may have its
optical properties manipulated by an applied strain and, further, remains
electro-optically switchable under a moderate applied voltage. We find that,
unlike its undistorted counterpart, a mechanically deformed blue phase exhibits
a Pockels electro-optic effect, which sets out new theoretical challenges and
new possibilities for low-voltage electro-optic devices.Comment: 15 pages, 6 figures, additional data and discussion included.
Supplementary videos available from F. Castles on reques
Challenges in Developing Evidence-Based Recommendations Using the GRADE Approach: The Case of Mental, Neurological, and Substance Use Disorders
Corrado Barbui and colleagues describe their use and adaptation of the GRADE approach in developing the guidelines for the WHO mental health Gap Action Programme (mhGAP)
Chaos game representation for comparison of whole genomes
BACKGROUND: Chaos game representation of genome sequences has been used for visual representation of genome sequence patterns as well as alignment-free comparisons of sequences based on oligonucleotide frequencies. However the potential of this representation for making alignment-based comparisons of whole genome sequences has not been exploited. RESULTS: We present here a fast algorithm for identifying all local alignments between two long DNA sequences using the sequence information contained in CGR points. The local alignments can be depicted graphically in a dot-matrix plot or in text form, and the significant similarities and differences between the two sequences can be identified. We demonstrate the method through comparison of whole genomes of several microbial species. Given two closely related genomes we generate information on mismatches, insertions, deletions and shuffles that differentiate the two genomes. CONCLUSION: Addition of the possibility of large scale sequence alignment to the repertoire of alignment-free sequence analysis applications of chaos game representation, positions CGR as a powerful sequence analysis tool
Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition
BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations
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