25 research outputs found
Free-stream coherent structures in parallel compressible boundary-layer flows at subsonic Mach numbers
As a first step towards the asymptotic description of coherent structures in
compressible shear flows, we present a description of nonlinear equilibrium
solutions of the Navier--Stokes equations in the compressible asymptotic
suction boundary layer (ASBL). The free-stream Mach number is assumed to be so that the flow is in the subsonic regime and we assume a perfect gas. We
extend the large-Reynolds number free-stream coherent structure theory of
\cite{deguchi_hall_2014a} for incompressible ASBL flow to describe a nonlinear
interaction in a thin layer situated just below the free-stream which produces
streaky disturbances to both the velocity and temperature fields, which can
grow exponentially towards the wall. We complete the description of the growth
of the velocity and thermal streaks throughout the flow by solving the
compressible boundary-region equations numerically. We show that the velocity
and thermal streaks obtain their maximum amplitude in the unperturbed boundary
layer. Increasing the free-stream Mach number enhances the thermal streaks,
whereas varying the Prandtl number changes the location of the maximum
amplitude of the thermal streak relative to the velocity streak. Such nonlinear
equilibrium states have been implicated in shear transition in incompressible
flows; therefore, our results indicate that a similar mechanism may also be
present in compressible flows.Comment: 20 pages, 3 figure
Sexual Risk Behaviors for HIV/AIDS in Chuuk State, Micronesia: The Case for HIV Prevention in Vulnerable Remote Populations
BACKGROUND: After the first two cases of locally-acquired HIV infection were recognized in Chuuk State, Federated States of Micronesia (FSM), a public health response was initiated. The purpose of the response was to assess the need for HIV education and prevention services, to develop recommendations for controlling further spread of HIV in Chuuk, and to initiate some of the prevention measures. METHODOLOGY/PRINCIPAL FINDINGS: A public health team conducted a survey and rapid HIV testing among a sample of residents on the outer islands in Chuuk. Local public health officials conducted contact tracing and testing of sex partners of the two locally-acquired cases of HIV infection. A total of 333 persons completed the survey. The majority knew that HIV is transmitted through unprotected sexual contact (81%), injection drug use (61%), or blood transfusion (64%). Sexual activity in the past 12 months was reported among 159 participants, including 90 females and 69 males. Compared to women, men were more likely to have had multiple sex partners, to have been drunk during sex, but less likely to have used a condom in the past 12 months. The two men with locally acquired HIV infection had unprotected anal sex with a third Chuukese man who likely contracted HIV while outside of Chuuk. All 370 persons who received voluntary, confidential HIV counseling and testing had HIV negative test results. CONCLUSIONS/SIGNIFICANCE: Despite the low HIV seroprevalence, risky sexual behaviors in this small isolated population raise concerns about the potential for rapid spread of HIV. The lack of knowledge about risks, along with stigmatizing attitudes towards persons infected with HIV and high risk sexual behaviors indicate the need for resources to be directed toward HIV prevention in Chuuk and on other Pacific Islands
The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy.
Peer reviewe
Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.
BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
Background
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
Methods
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Findings
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
Interpretation
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
Background
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
Methods
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and
ClinicalTrials.gov
,
NCT00541047
.
Findings
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
Interpretation
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
Funding
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society
Free-stream coherent structures in the unsteady Rayleigh boundary layer
Abstract
Results are presented for nonlinear equilibrium solutions of the Navier–Stokes equations in the boundary layer set up by a flat plate started impulsively from rest. The solutions take the form of a wave–roll–streak interaction, which takes place in a layer located at the edge of the boundary layer. This extends previous results for similar nonlinear equilibrium solutions in steady 2D boundary layers. The results are derived asymptotically and then compared to numerical results obtained by marching the reduced boundary-region disturbance equations forward in time. It is concluded that the previously found canonical free-stream coherent structures in steady boundary layers can be embedded in unbounded, unsteady shear flows.</jats:p
Free-stream coherent structures in parallel compressible boundary-layer flows at subsonic and moderate supersonic Mach numbers
As a first step towards the description of coherent structures in compressible shear flows, we present an asymptotic description of nonlinear travelling-wave solutions of the Navier–Stokes equations in the compressible asymptotic suction boundary layer (ASBL). We consider free-stream Mach numbers
in the subsonic and moderate supersonic regime so that
. We extend the large-Reynolds-number asymptotic theory of Deguchi & Hall (J. Fluid Mech., vol. 752, 2014, pp. 602–625) describing ‘free-stream’ coherent structures in incompressible ASBL flow to describe a nonlinear interaction in a thin layer situated just below the free stream. Crucially, the nonlinear interaction equations for the velocity field in this layer are identical to those obtained in the incompressible problem, and thus the asymptotic analysis supporting free-stream coherent structures in compressible ASBL is easily deduced from its incompressible counterpart. The nonlinear interaction produces streaky disturbances to both the velocity and temperature fields, which can grow exponentially towards the wall. We complete the description of the growth of the velocity and thermal streaks throughout the flow by solving the compressible boundary-region equations numerically. We show that the velocity and thermal streaks obtain their maximum amplitude in the unperturbed boundary layer. Increasing the free-stream Mach number enhances the thermal streaks and suppresses the velocity streaks, whereas varying the Prandtl number suppresses the velocity streaks, and can either enhance or suppress the thermal streaks depending on whether the flow is in the subsonic or moderate supersonic regime. Such nonlinear equilibrium states have been implicated in shear transition in incompressible flows; therefore, our results indicate that a similar mechanism may also be present in compressible flows.</jats:p
The effect of isolated ridges and grooves on static menisci in rectangular channels
We present theoretical and numerical results that demonstrate the sensitivity of the shape of a static meniscus in a rectangular channel to localised geometric perturbations in the form of narrow ridges and grooves imposed on the channel walls. The Young–Laplace equation is solved for a gas/liquid interface with fixed contact angle using computations, analytical arguments and semi-analytical solutions of a linearised model for small-amplitude perturbations. We find that the local deformation of the meniscus's contact line near a ridge or groove is strongly dependent on the shape of the perturbation. In particular, small-amplitude perturbations that change the channel volume induce a change in the pressure difference across the meniscus, resulting in long-range curvature of its contact line. We derive an explicit expression for this induced pressure difference directly in terms of the boundary data. We show how contact lines can be engineered to assume prescribed patterns using suitable combinations of ridges and grooves.</jats:p