Under utilisation of the 2-week wait initiative for lung cancer by primary care and its effect on the urgent referral pathway

The ‘2-week wait' scheme for referral of patients with cancer to secondary care coincided with the introduction of Department of Health (DoH) Guidelines on referral of patients with suspected lung cancer. The aim of this study was to examine the impact of this process on the urgent referral pathway for lung cancer. Medical records of all patients referred with suspected lung cancer were reviewed for the year prior to introduction of the 2-week wait and DoH guidelines and for the subsequent 24 months. A total of 1044 patients were referred, of which 650 (62%) were found to have malignancy. In the first and second years of the 2-week wait scheme, only 57 and 58% were referred via the scheme. Department of Health guidelines were followed in all but a small number. Median wait time increased from 7 to 9 days. The proportion of all urgent referrals seen within 2 weeks fell from 84 to 71%. The proportion of non-2-week wait urgent referrals being seen within 2 weeks was only 75.5% in the first year of the scheme and fell further to 60.9% in the second year. The absolute number of referrals rose and the proportion having cancer fell from 78% before the scheme to 46% in the second year. During this time, there was no change in stage at presentation. Symptoms were not helpful in discriminating benign from malignant disease and haemoptysis was actually more common in the benign group. However, over 50% of patients in the benign group were appropriate to be seen in secondary care. The 2-week wait scheme has so far failed to reduced waiting times for lung cancer. The findings of this study suggest that this is partly due to continued usage of urgent referral routes outside the 2-week wait scheme and secondly due to a large increase in referrals, probably generated by the introduction of the DoH guidelines. Some adjustment to the guidelines may be appropriate to reflect more emphasis on the early performance of a chest X-ray and the use of direct access to other imaging modalities such as CT. Patients referred outside the 2-week wait are disadvantaged and thus practitioners would be wise to refer all their patients through the 2-week wait system

Exciton Spin Dynamics in Semiconductor Quantum Wells

In this paper we will review Exciton Spin Dynamics in Semiconductor Quantum Wells. The spin properties of excitons in nanostructures are determined by their fine structure. We will mainly focus in this review on GaAs and InGaAs quantum wells which are model systems.Comment: 55 pages, 27 figure

Ultra High Energy Cosmology with POLARBEAR

Observations of the temperature anisotropy of the Cosmic Microwave Background (CMB) lend support to an inflationary origin of the universe, yet no direct evidence verifying inflation exists. Many current experiments are focussing on the CMB's polarization anisotropy, specifically its curl component (called "B-mode" polarization), which remains undetected. The inflationary paradigm predicts the existence of a primordial gravitational wave background that imprints a unique B-mode signature on the CMB's polarization at large angular scales. The CMB B-mode signal also encodes gravitational lensing information at smaller angular scales, bearing the imprint of cosmological large scale structures (LSS) which in turn may elucidate the properties of cosmological neutrinos. The quest for detection of these signals; each of which is orders of magnitude smaller than the CMB temperature anisotropy signal, has motivated the development of background-limited detectors with precise control of systematic effects. The POLARBEAR experiment is designed to perform a deep search for the signature of gravitational waves from inflation and to characterize lensing of the CMB by LSS. POLARBEAR is a 3.5 meter ground-based telescope with 3.8 arcminute angular resolution at 150 GHz. At the heart of the POLARBEAR receiver is an array featuring 1274 antenna-coupled superconducting transition edge sensor (TES) bolometers cooled to 0.25 Kelvin. POLARBEAR is designed to reach a tensor-to-scalar ratio of 0.025 after two years of observation -- more than an order of magnitude improvement over the current best results, which would test physics at energies near the GUT scale. POLARBEAR had an engineering run in the Inyo Mountains of Eastern California in 2010 and will begin observations in the Atacama Desert in Chile in 2011.Comment: 8 pages, 6 figures, DPF 2011 conference proceeding

Development and characterization of the readout system for POLARBEAR-2

POLARBEAR-2 is a next-generation receiver for precision measurements of the polarization of the cosmic microwave background (Cosmic Microwave Background (CMB)). Scheduled to deploy in early 2015, it will observe alongside the existing POLARBEAR-1 receiver, on a new telescope in the Simons Array on Cerro Toco in the Atacama desert of Chile. For increased sensitivity, it will feature a larger area focal plane, with a total of 7,588 polarization sensitive antenna-coupled Transition Edge Sensor (TES) bolometers, with a design sensitivity of 4.1 uKrt(s). The focal plane will be cooled to 250 milliKelvin, and the bolometers will be read-out with 40x frequency domain multiplexing, with 36 optical bolometers on a single SQUID amplifier, along with 2 dark bolometers and 2 calibration resistors. To increase the multiplexing factor from 8x for POLARBEAR-1 to 40x for POLARBEAR-2 requires additional bandwidth for SQUID readout and well-defined frequency channel spacing. Extending to these higher frequencies requires new components and design for the LC filters which define channel spacing. The LC filters are cold resonant circuits with an inductor and capacitor in series with each bolometer, and stray inductance in the wiring and equivalent series resistance from the capacitors can affect bolometer operation. We present results from characterizing these new readout components. Integration of the readout system is being done first on a small scale, to ensure that the readout system does not affect bolometer sensitivity or stability, and to validate the overall system before expansion into the full receiver. We present the status of readout integration, and the initial results and status of components for the full array.Comment: Presented at SPIE Astronomical Telescopes and Instrumentation 2014: Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VII. Published in Proceedings of SPIE Volume 915

Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a pet study

Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) in Parkinson's disease is thought to produce adverse events such as emotional disorders, and in a recent study, we found fear recognition to be impaired as a result. These changes have been attributed to disturbance of the STN's limbic territory and would appear to confirm that the negative emotion recognition network passes through the STN. In addition, it is now widely acknowledged that damage to the orbitofrontal cortex (OFC), especially the right side, can result in impaired recognition of facial emotions (RFE). In this context, we hypothesized that this reduced recognition of fear is correlated with modifications in the cerebral glucose metabolism of the right OFC. The objective of the present study was first, to reinforce our previous results by demonstrating reduced fear recognition in our Parkinson's disease patient group following STN DBS and, second, to correlate these emotional performances with glucose metabolism using 18FDG-PET. The 18FDG-PET and RFE tasks were both performed by a cohort of 13 Parkinson's disease patients 3 months before and 3 months after surgery for STN DBS. As predicted, we observed a significant reduction in fear recognition following surgery and obtained a positive correlation between these neuropsychological results and changes in glucose metabolism, especially in the right OFC. These results confirm the role of the STN as a key basal ganglia structure in limbic circuits

Safety of Postoperative Administration of Human Urinary Trypsin Inhibitor in Lung Cancer Patients with Idiopathic Pulmonary Fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) undergoing pulmonary resection for lung cancer carry risks of acute exacerbations of IPF (AE) postoperatively. Currently, agents which may attenuate AE are actively sought. Urinary trypsin inhibitor, ulinastatin, is a synthetic glycoprotein which may potentially inhibit various inflammatory factors associated with the development and progression of IPF. The present study was done to evaluate the effects of administration of high dose ulinastatin in lung cancer patients with IPF immediately following lung resection.Patients with IPFs radiologically diagnosed on high resolution CT, and histologically diagnosed resectable lung cancers, were eligible for the study. The effects of escalating doses of ulinastatin 3×10(5), 6×10(5), and 9×10(5) units/body/day, administered postoperatively for 3 days were evaluated. The endpoints were safety and feasibility.Nine patients were evaluated, in cohorts of 3 patients per dosage. Postoperative follow up ranged from 3 to 12 months (median 9 months). The postoperative courses were uneventful in all patients. No subjective adverse events such as abdominal symptoms or skin rashes, or objective adverse events as per serum laboratory tests, such as liver or kidney dysfunctions potentially attributable to ulinastatin administration were observed. AE was seen in one patient at 3 months after surgery, but since this occurred shortly after administration of chemotherapy, it was considered to be attributable to the chemotherapy rather than surgery.Ulinastatin administration after lung resection in lung cancer patients with IPF was considered to be safe and feasible. Further study is planned at the highest dose of this study to evaluate efficacy.UMIN.ac.jp/ctr/UMIN000002410

Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial

Background: Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding. Methods: In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532. Findings: Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=0·04). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in the restrictive policy vs 83% (25) in the liberal policy (difference 14%; 95% CI 7–21; p=0·005). Mean last recorded haemoglobin concentration was 116 (SD 24) g/L for patients on the restrictive policy and 118 (20) g/L for those on the liberal policy (difference −2·0 [95% CI −12·0 to 7·0]; p=0·50). Fewer patients received RBCs on the restrictive policy than on the liberal policy (restrictive policy 133 [33%] vs liberal policy 247 [46%]; difference −12% [95% CI −35 to 11]; p=0·23), with fewer RBC units transfused (mean 1·2 [SD 2·1] vs 1·9 [2·8]; difference −0·7 [–1·6 to 0·3]; p=0·12), although these differences were not significant. We noted no significant difference in clinical outcomes. Interpretation: A cluster randomised design led to rapid recruitment, high protocol adherence, separation in degree of anaemia between groups, and non-significant reduction in RBC transfusion in the restrictive policy. A large cluster randomised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding. Funding: NHS Blood and Transplant Research and Development

Origin of enhanced dynamic nuclear polarization and all-optical nuclear magnetic resonance in GaAs quantum wells

Time-resolved optical measurements of electron-spin dynamics in a (110) GaAs quantum well are used to study the consequences of a strongly anisotropic electron g-tensor, and the origin of previously discovered all-optical nuclear magnetic resonance. All components of the g-tensor are measured, and a strong anisotropy even along the in-plane directions is found. The amplitudes of the spin signal allow the study of the spatial directions of the injected spin and its precession axis. Surprisingly efficient dynamic nuclear polarization in a geometry where the electron spins are injected almost transverse to the applied magnetic field is attributed to an enhanced non-precessing electron spin component. The small absolute value of the electron g-factor combined with efficient nuclear spin polarization leads to large nuclear fields that dominate electron spin precession at low temperatures. These effects allow for sensitive detection of all-optical nuclear magnetic resonance induced by periodically excited quantum-well electrons. The mechanism of previously observed Delta m = 2 transitions is investigated and found to be attributable to electric quadrupole coupling, whereas Delta m = 1 transitions show signatures of both quadrupole and electron-spin induced magnetic dipole coupling.Comment: 40 pages, 8 figure

Planck intermediate results. VIII. Filaments between interacting clusters

About half of the baryons of the Universe are expected to be in the form of filaments of hot and low density intergalactic medium. Most of these baryons remain undetected even by the most advanced X-ray observatories which are limited in sensitivity to the diffuse low density medium. The Planck satellite has provided hundreds of detections of the hot gas in clusters of galaxies via the thermal Sunyaev-Zel'dovich (tSZ) effect and is an ideal instrument for studying extended low density media through the tSZ effect. In this paper we use the Planck data to search for signatures of a fraction of these missing baryons between pairs of galaxy clusters. Cluster pairs are good candidates for searching for the hotter and denser phase of the intergalactic medium (which is more easily observed through the SZ effect). Using an X-ray catalogue of clusters and the Planck data, we select physical pairs of clusters as candidates. Using the Planck data we construct a local map of the tSZ effect centered on each pair of galaxy clusters. ROSAT data is used to construct X-ray maps of these pairs. After having modelled and subtracted the tSZ effect and X-ray emission for each cluster in the pair we study the residuals on both the SZ and X-ray maps. For the merging cluster pair A399-A401 we observe a significant tSZ effect signal in the intercluster region beyond the virial radii of the clusters. A joint X-ray SZ analysis allows us to constrain the temperature and density of this intercluster medium. We obtain a temperature of kT = 7.1 +- 0.9, keV (consistent with previous estimates) and a baryon density of (3.7 +- 0.2)x10^-4, cm^-3. The Planck satellite mission has provided the first SZ detection of the hot and diffuse intercluster gas.Comment: Accepted by A&