Focused ultrasound for treatment of bone tumours.

PURPOSE: Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions. METHODS: A comprehensive literature search and review of abstracts presented at the recently completed fourth International Focused Ultrasound Symposium was performed. Case reports and older publications revisited in more recent studies were excluded. For clinical studies that extend beyond bone tumours, only the data regarding bone tumours are presented. RESULTS: Fifteen studies assessing the use of focused ultrasound in treatment of primary benign bone tumours, primary malignant tumours, and metastatic tumours meeting the search criteria were identified. For these clinical studies the responders group varied within 91-100%, 85-87% and 64-94%, respectively. Major complications were reported in the ranges 0%, 0-28% and 0-4% for primary benign, malignant and metastatic tumours, respectively. CONCLUSIONS: Image-guided FUS is both safe and effective in the treatment of primary and secondary tumours. Additional phase III trials are warranted to more fully define the role of FUS in treatment of both benign and malignant bone tumours

Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A)

PURPOSE To determine the value of tumor cell programmed death-ligand 1 (PD-L1) expression as a predictive biomarker of nivolumab monotherapy efficacy in treatment-naive patients with clear cell renal cell carcinoma (ccRCC) and the efficacy of salvage nivolumab/ipilimumab in patients with tumors unresponsive to nivolumab monotherapy. METHODS Eligible patients with treatment-naive ccRCC received nivolumab until progressive disease (PD), toxicity, or completing 96 treatment weeks (part A). Patients with PD before or stable disease at 48 weeks could receive salvage nivolumab/ipilimumab (part B). The primary end point was improvement in 1-year progression-free survival in patients with tumor PD-L1 expression > 20% versus 0%. RESULTS One hundred twenty-three patients were enrolled. The objective response rate (ORR) was 34.1% (95% CI, 25.8 to 43.2). ORR by International Metastatic RCC Database Consortium category was favorable-risk 57.1%, intermediate-risk/poor-risk 25.0%, and by sarcomatoid features 36.4%. The ORR was 26.9%, 50.0%, and 75.0% for patients with the tumor PD-L1 expression of 0, 1-20, or > 20%, respectively (trend test P value = .002). The median duration of response was 27.6 (19.3 to not reached) months, with 26 of 42 responders including 17 of 20 with favorable-risk disease remaining progression-free. The 1-year progression-free survival was 34.6% and 75.0% in the PD-L1 = 0% and > 20% categories, respectively (P = .050). Ninety-seven patients with PD or prolonged stable disease were potentially eligible for part B, and 35 were enrolled. The ORR for part B was 11.4%. Grade >= 3 treatment-related adverse events occurred in 35% of patients on nivolumab and 43% of those on salvage nivolumab/ipilimumab. CONCLUSION Nivolumab monotherapy is active in treatment-naive ccRCC. Although efficacy appears to be less than that of nivolumab/ipilimumab in patients with intermediate-risk/poor-risk disease, favorable-risk patients had notable benefit. Efficacy correlated with tumor PD-L1 status. Salvage nivolumab/ipilimumab was frequently not feasible and of limited benefit

Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B)

Background To determine the efficacy and toxicity of nivolumab monotherapy in treatment-naive patients with non-clear cell renal cell carcinoma (nccRCC) and the efficacy of nivolumab/ipilimumab salvage therapy in patients with tumors unresponsive to initial nivolumab monotherapy.Methods Eligible patients with treatment-naive nccRCC received nivolumab until progressive disease (PD), toxicity, or completion of 96 weeks of treatment (Part A). Patients with PD prior to, or stable disease (SD) at 48 weeks (prolonged SD) were potentially eligible to receive salvage nivolumab/ipilimumab (Part B). Patients were required to submit tissue from a metastatic lesion obtained within 12 months prior to study entry and prior to Part B for correlative studies.Results 35 patients with nccRCC were enrolled: 19 (54%) had papillary, 6 (17%) had chromophobe and 10 (29%) had unclassified histology. At median follow-up of 22.9 months, RECIST-defined objective response rate (ORR) was 5 of 35 (14.3% 95% CI 4.8% to 30.3%) (complete response (CR) 2 (5.7%) and partial response (PR) 3 (8.6%)). ORR by histology was: papillary-1/19 (5%); chromophobe-1/6 (17%); and unclassified-3/10 (30%). Nine patients (26%) had tumors with sarcomatoid features with 3 (33%) (2 unclassified and 1 papillary) responding. ORR was 0/18, 3/11 (27%) and 2/6 (33%) for patients with tumor progammed death ligand 1 (PD-L1) expression of = 5% or not measured, respectively. Median progression-free survival was 4.0 (2.7-4.3) months. Two of five responders have progressed. Thirty-two patients had PD or prolonged SD and therefore, were potentially eligible for salvage nivolumab/ipilimumab (Part B), but 15 patients did not enroll due to grade 2-3 toxicity (6) on nivolumab, symptomatic disease progression (5), or other reasons including no biopsy tissue (4). In the 17 Part B patients, there was one PR (6%) (unclassified/non-sarcomatoid). Grade >3 treatment-related adverse events were seen in 7/35 (20%) on nivolumab and 7/17 (41%) on salvage nivolumab/ipilimumab with one patient experiencing sudden death.Conclusions Nivolumab monotherapy has limited activity in treatment-naive nccRCC with most responses (4 of 5) seen in patients with sarcomatoid and/or unclassified tumors. Toxicity is consistent with prior nivolumab studies. Salvage treatment with nivolumab/ipilimumab was provided in half of these patients with minimal activity

Celebrating 20 Years of the ExCEEd Teaching Workshop

In response to the clear need for faculty training, the American Society of Civil Engineers (ASCE) developed and funded Project ExCEEd (Excellence in Civil Engineering Education) which is celebrating its twentieth year of existence. For the past two decades, 38 ExCEEd Teaching Workshops (ETW) have been held at six different universities. The program has 910 graduates from over 267 different U.S. and international colleges and universities. The ExCEEd effort has transformed from one that relied on the grass roots support of its participants to one that is supported and embraced by department heads and deans. This paper summarizes the history of Project ExCEEd, describes the content of the ETW, assesses its effectiveness, highlights changes in the program as a result of the assessment, and outlines the future direction of the program

Celebrating 20 Years of the ExCEEd Teaching Workshop

In response to the clear need for faculty training, the American Society of Civil Engineers (ASCE) developed and funded Project ExCEEd (Excellence in Civil Engineering Education) which is celebrating its twentieth year of existence. For the past two decades, 38 ExCEEd Teaching Workshops (ETW) have been held at six different universities. The program has 910 graduates from over 267 different U.S. and international colleges and universities. The ExCEEd effort has transformed from one that relied on the grass roots support of its participants to one that is supported and embraced by department heads and deans. This paper summarizes the history of Project ExCEEd, describes the content of the ETW, assesses its effectiveness, highlights changes in the program as a result of the assessment, and outlines the future direction of the program

The effects of hip muscle strengthening on knee load, pain, and function in people with knee osteoarthritis: a protocol for a randomised, single-blind controlled trial

BACKGROUND: Lower limb strengthening exercises are an important component of the treatment for knee osteoarthritis (OA). Strengthening the hip abductor and adductor muscles may influence joint loading and/or OA-related symptoms, but no study has evaluated these hypotheses directly. The aim of this randomised, single-blind controlled trial is to determine whether hip abductor and adductor muscle strengthening can reduce knee load and improve pain and physical function in people with medial compartment knee OA. METHODS/DESIGN: 88 participants with painful, radiographically confirmed medial compartment knee OA and varus alignment will be recruited from the community and randomly allocated to a hip strengthening or control group using concealed allocation stratified by disease severity. The hip strengthening group will perform 6 exercises to strengthen the hip abductor and adductor muscles at home 5 times per week for 12 weeks. They will consult with a physiotherapist on 7 occasions to be taught the exercises and progress exercise resistance. The control group will be requested to continue with their usual care. Blinded follow up assessment will be conducted at 12 weeks after randomisation. The primary outcome measure is the change in the peak external knee adduction moment measured during walking. Questionnaires will assess changes in pain and physical function as well as overall perceived rating of change. An intention-to-treat analysis will be performed using linear regression modelling and adjusting for baseline outcome values and other demographic characteristics. DISCUSSION: Results from this trial will contribute to the evidence regarding the effect of hip strengthening on knee loads and symptoms in people with medial compartment knee OA. If shown to reduce the knee adduction moment, hip strengthening has the potential to slow disease progression. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTR12607000001493

Quantifying the Performance of Low-Noise Rumble Strips

SPR 800Shoulder or centerline rumble strips (RS) generate noise and vibration to alert drivers when they are departing the lane of travel. Although inexpensive to install, easy to maintain, and very long-lasting, RS are not installed on many roadway segments primarily due to noise concerns of nearby property owners. This study evaluated the feasibility of using sinusoidal RS as a substitute for rounded milled RS on roadway segments in Oregon with lane-departure crash problems. Exterior and interior sound levels and interior vibrations generated by rounded and sinusoidal RS strikes were compared to baseline and no-strike sound levels for 3 vehicle classes (passenger car, van, and heavy vehicle) to establish sound generation and alerts of the 2 designs. A total of 114 vehicle strikes of RS were recorded. Rumble strip strikes by the passenger car and van generated less exterior noise with the sinusoidal than with the rounded design. Interior noise generated by striking the sinusoidal design generated a clearly noticeable alert, suggesting that the sinusoidal rumble strip is still an effective countermeasure. Based on thresholds of human perception for vibration, both rumble strip types generated sufficient vibration to alert the driver. Results for the heavy vehicle were complicated due to bridging of the harrower rounded rumble strip by the tires. The wider cut of the sinusoidal RS generated a clearly detectable increase in exterior roadside noise for the Heavy Vehicle. Likewise, the sinusoidal design created a noticeable interior alert for the HV but the rounded design did not

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations