Generation of circumferential velocity contours associated with pulsed point suction on a rotating disk

Numerous experimental studies were conducted on the steady, three-dimensional boundary layer over a disk rotating at constant angular speed in an otherwise undisturbed fluid. The subject flow geometry is of interest because it provides a relatively simple way to study the cross-flow instability phenomenon which occurs in three-dimensional boundary layers, as on swept wings. This flow instability results in the formation of a stationary spiral vortex flow field over the disk, as shown by Wilkinson and Malik. Using a hot-wire probe, the spatial wave pattern of stationary vortices, which filled the entire circumference of the disk was mapped. The subject flow instability caused transition-to-turbulent flow as the periphery of the disk was approached. The effect on receptivity and transition of discrete disturbance modes, such as three-dimensional toughness elements and acoustic excitation was investigated. The present study (an extension of the work of Wilkinson and Malik) is focused on the effect of pulsed point suction on flow instability and transition, and consequently, on the classical stationary vortical flow pattern

Boundary-layer measurements on a high Reynolds number three-element airfoil

An experimental investigation is being conducted to evaluate the boundary layer associated with a two-dimensional three-element single-flap airfoil at high Reynolds numbers. The present measurements are being made in the Langley Low-Turbulence (centerline turbulence intensity level is 0.034 percent at a Mach number of 0.2 and a total pressure of 60 psia) Pressure Tunnel (LTPT). The LTPT is a closed-circuit wind tunnel with a test section which is 3 ft wide, 7.5 ft high, and 7.5 ft long. Operating total pressure for the LTPT varies from 10 atmospheres to near-vacuum conditions. Tests are being conducted at a Mach number of 0.2 and Reynolds numbers (based on chord length) of 5, 9, and 16 million. Measurements include boundary-layer velocity surveys at several chordwise locations and surface skin-friction measurements using Preston tubes

An Experimental Investigation of Wall-Cooling Effects on Hypersonic Boundary-Layer Stability in a Quiet Wind Tunnel

One of the primary reasons for developing quiet tunnels is for the investigation of high-speed boundary-layer stability and transition phenomena without the transition-promoting effects of acoustic radiation from tunnel walls. In this experiment, a flared-cone model under adiabatic- and cooled-wall conditions was placed in a calibrated, 'quiet' Mach 6 flow and the stability of the boundary layer was investigated using a prototype constant-voltage anemometer. The results were compared with linear-stability theory predictions and good agreement was found in the prediction of second-mode frequencies and growth. In addition, the same 'N=10' criterion used to predict boundary-layer transition in subsonic, transonic, and supersonic flows was found to be applicable for the hypersonic flow regime as well. Under cooled-wall conditions, a unique set of continuous spectra data was acquired that documents the linear, nonlinear, and breakdown regions associated with the transition of hypersonic flow under low-noise conditions

Non-linear boundary-layer receptivity due to distributed surface roughness

The process by which a laminar boundary layer internalizes the external disturbances in the form of instability waves is known as boundary-layer receptivity. The objective of the present research was to determine the effect of acoustic excitation on boundary-layer receptivity for a flat plate with distributed variable-amplitude surface roughness through measurements with a hot-wire probe. Tollmien-Schlichting (T-S) mode shapes due to surface-roughness receptivity have also been determined, analyzed, and shown to be in agreement with theory and other experimental work. It has been shown that there is a linear relationship between the surface roughness and receptivity for certain roughness configurations with constant roughness wavelength. In addition, strong nonlinear receptivity effects exist for certain surface roughness configurations over a band where the surface roughness and T-S wavelength are matched. The results from the present experiment follow the trends predicted by theory and other experimental work for linear receptivity. In addition, the results show the existence of nonlinear receptivity effects for certain combinations of surface roughness elements

A quiet tunnel investigation of hypersonic boundary-layer stability over a cooled, flared cone

A flared-cone model under adiabatic and cooled-wall conditions was placed in a calibrated, low-disturbance Mach 6 flow and the stability of the boundary layer was investigated using a prototype constant-voltage anemometer. The results were compared with linear-stability theory predictions and good agreement was found in the prediction of second-mode frequencies and growth. In addition, the same 'N = 10' criterion used to predict boundary-layer transition in subsonic, transonic, and supersonic flows under low freestream noise conditions was found to be applicable for the hypersonic flow regime as well. Under cooled-wall conditions, a unique set of spectral data was acquired that documents the linear, nonlinear, and breakdown regions associated with the transition of hypersonic flow under low-noise conditions

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

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

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial

Abstract Background The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). Methods The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. Discussion The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. Trial registration ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.https://deepblue.lib.umich.edu/bitstream/2027.42/142379/1/13063_2018_Article_2473.pd