Semiconductor surface plasmons: a route to terahertz waveguides and sensors

The terahertz regime has until recently been some what neglected due to the difficulty of generating and measuring terahertz radiation. Terahertz time domain spectroscopy has allowed for affordable and broadband probing of this frequency regime with phase sensitive measurements (chapter 3). This thesis aims to use this tool to add to the knowledge of the interactions between electromagnetic radiation and matter specifically in regard to plasmonics. This thesis covers several distinct phenomena related to plasmonics at terahertz frequencies. The generation of terahertz radiation from metal nanoparticles is first described in chapter 4. It is shown that the field strength of the plasmon appears to relate to the strength of the generated field. It is also shown that the power dependence of the generated terahertz radiation is not consistent with the optical rectification description of this phenomenon. An alternative explanation is developed which appears more consistent with the observations. A simple model for the power dependence is derived and compared to the experimental results. In chapter 5 the parameters that make good plasmonic materials are discussed. These parameters are used to assess the suitability of semiconductors for terahertz surface plasmon experiments. The Drude permittivity of InSb is measured here, leading to a discussion of terahertz particle plasmons in chapter 6. Finite element method modelling is used to show some merits of these over optical particle plasmons. This also includes a discussion of fabrication methods for arrays of these particles. Finally, chapter 7 is a discussion of so called spoof surface plasmons. This includes some experimental work at microwave frequencies and an in depth analysis of open ended square hole arrays supported by model matching method modelling. Perfect endoscope effects are discussed and compared to superlensing. The thesis ends with a brief conclusions chapter where some of the ideas presented are brought together.EPSR

Comparing diagnosed observation uncertainties with independent estimates: a case study using aircraft‐based observations and a convection‐permitting data assimilation system

Aircraft can report in situ observations of the ambient temperature by using aircraft meteorological data relay (AMDAR) or these can be derived using mode‐select enhanced tracking data (Mode‐S EHS). These observations may be assimilated into numerical weather prediction models to improve the initial conditions for forecasts. The assimilation process weights the observation according to the expected uncertainty in its measurement and representation. The goal of this paper is to compare observation uncertainties diagnosed from data assimilation statistics with independent estimates. To quantify these independent estimates, we use metrological comparisons, made with in‐situ research‐grade instruments, as well as previous studies using collocation methods between aircraft (mostly AMDAR reports) and other observing systems such as radiosondes. In this study, we diagnose a new estimate of the vertical structure of the uncertainty variances using observation‐minus‐background and observation‐minus‐analysis statistics from a Met Office limited area three‐dimensional variational data assimilation system (3 km horizontal grid‐length, 3‐hourly cycle). This approach for uncertainty estimation is simple to compute but has several limitations. Nevertheless, the resulting diagnosed variances have a vertical structure that is like that provided by the independent estimates of uncertainty. This provides confidence in the uncertainty estimation method, and in the diagnosed uncertainty estimates themselves. In the future, our methodology, along with other results, could provide ways to estimate the uncertainty for the assimilation of aircraft‐based temperature observations

Comparison of aircraft-derived observations with in situ research aircraft measurements

Mode Selective Enhanced Surveillance (Mode-S EHS) reports are aircraft-based observations that have value in numerical weather prediction (NWP). These reports contain the aircraft's state vector in terms of its speed, direction, altitude and Mach number. Using the state vector, meteorological observations of temperature and horizontal wind can be derived. However, Mode-S EHS processing reduces the precision of the state vector from 16-bit to 10-bit binary representation. We use full precision data from research grade instruments, on-board the United Kingdom's Facility for Atmospheric Airborne Measurements, to emulate Mode-S EHS reports and to compare with derived observations. We aim to understand the observation errors due to the reduced precision of Mode-S EHS reports. We derive error models to estimate these observation errors. The temperature error increases from 1.25 K to 2.5 K between an altitude of 10 km and the surface due to its dependency on Mach number and also Mode-S EHS precision. For the cases studied, the zonal wind error is around 0.50 ms− 1 and the meridional wind error is 0.25 ms− 1. The wind is also subject to systematic errors that are directionally dependent. We conclude that Mode-S EHS derived horizontal winds are suitable for data assimilation in high-resolution NWP. Temperature reports may be usable when aggregated from multiple aircraft. While these reduced precision, high frequency data provide useful, albeit noisy, observations; direct reports of the higher precision data would be preferable

Management of rheumatoid arthritis: consensus recommendations from the Hong Kong Society of Rheumatology

Given the recent availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), the Hong Kong Society of Rheumatology has developed consensus recommendations on the management of RA, which aim at providing guidance to local physicians on appropriate, literature-based management of this condition, specifically on the indications and monitoring of the biologic disease-modifying anti-rheumatic drugs (DMARDs). The recommendations were developed using the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis as a guide, along with local expert opinion. As significant joint damage occurs early in the course of RA, initiating therapy early is key to minimizing further damage and disability. Patients with serious disease or poor prognosis should receive early, aggressive therapy. Because of its good efficacy and safety profile, methotrexate is considered the standard first-line DMARD for most treatment-naïve RA patients. Patients with a suboptimal response to methotrexate monotherapy should receive step-up (combination) therapy with either the synthetic or biologic DMARDs. In recent years, combinations of methotrexate with tocilizumab, abatacept, or rituximab have emerged as effective therapies in patients who are unresponsive to traditional DMARDs or the anti-tumor necrosis factor (TNF)-α agents. As biologic agents can increase the risk of infections such as tuberculosis and reactivation of viral hepatitis, screening for the presence of latent tuberculosis and chronic viral hepatitis carrier state is recommended before initiating therapy

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicine’s clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves

Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue

BACKGROUND:The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. METHODS AND FINDINGS:Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1beta, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-beta2, the delta-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as beta-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1beta, PKD2L1, phospholipase C-beta2, and delta-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. CONCLUSIONS:These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals ("natural knockouts") suggests a cell lineage for sour that is independent of the other taste modalities

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe