Effects of reverberation conditions and physical versus virtual source placement on localization in virtual sound environments

Sound field synthesis systems vary in number and arrangement of loudspeakers and methods used to generate virtual sound environments to study human hearing perception. While previous work has evaluated the accuracy with which these systems physically reproduce room acoustic conditions, less is known on assessing subjective perception of those conditions, such as how well such systems preserve source localization. This work quantifies the accuracy and precision of perceived localization from a multi-channel sound field synthesis system at Boys Town National Research Hospital, which used 24 physical loudspeakers and vector-based amplitude panning to generate sound fields. Short bursts of broadband speech-shaped noise were presented from source locations (either coinciding with a physical loudspeaker location, or panned between loudspeakers) under free-field and modeled reverberant-room conditions. Listeners used a HTC Vive remote laser tracking system to point to the perceived source location.Results show that the system synthesizes source locations accurately for both physical and panned sources, in both azimuth and elevation. Panned sources, though, are localized less precisely than physical sources. Reverberant condition is also found to affect both the accuracy and precision of localization in the azimuthal plane, with dry conditions producing greater accuracy and better precision. Only accuracy (not precision) of localization in elevation was impacted by reverberant condition, with reverberant cases producing results closer to the target than dry cases. An interaction effect of reverberant condition with elevation on localization in elevation, though, indicates that dry conditions result in better localization in elevation than reverberant ones at an elevation close to head height, but the situations at higher elevations are where subjects localized dry sources lower than the target height, while reverberant ones were more accurately placed. Other laboratories with sound field synthesis systems are encouraged to gather similar data on the accuracy and precision of localization in azimuth and elevation, so that results from studies using these systems can be better interpreted in light of the capabilities of the system to generate accurate and precise reproductions of source locations. [Work supported by NIH GM109023.] Advisor: Lily M. Wan

Treatment of Emerging Contaminants in Wastewater by Advanced Oxidation Processes

This study evaluated the effectiveness of ozonation and activated carbon for the degradation and removal of three main emerging contaminants (ECs) in wastewater; fluoranthene (FLT), di (2- ethyl hexyl) phthalate (DEHP) and cypermethrin (CYM). The effects of key semi-batch ozonation parameters related to gas-liquid mass transfer and reaction kinetics were identified for all contaminants. The degradation rates were evaluated in solutions of DI water, using concentration change of ozone and EC versus time. With an ozone gas concentration of 20 g/m3 NTP, the change in concentration from an initial concentration of 0.05 mg/L over time was measured using HPLC. To decrease by 75 %, it took less than a minute for FLT, two minutes for DEHP and six minutes for CYM. The adsorption of the emerging contaminants with granulated activated carbon (GAC) were evaluated in solutions of DI water at an initial concentration of 1 mg/L. For the decrease in concentration of 60 %, the time for each contaminant varied. For FLT this was achieved in 5 minutes, DEHP was decreased within 20 minutes, and it took CYM 20 minutes to reach this decrease. The effects of ozonation and adsorption onto GAC were also investigated in samples of final wastewater effluent

Evaluating the impact of patient and public involvement (PPI) in the life after prostate cancer diagnosis study (LAPCD)

Background. While the PPI evidence base has expanded significantly over the last decade, the reporting of PPI impact has often been inconsistent and partial. Inconsistent reporting creates a fragmented evidence base making it difficult to draw together our collective understanding of what works, for whom, why and in what context. We set out to evaluate and report a novel method of PPI in a large national study in the UK exploring life after a prostate cancer diagnosis, where PPI was integrated into the study as an independent work-stream. Aim. To evaluate the impact of patient and public involvement in the life after prostate cancer diagnosis study. Methods. A link to an online survey was emailed to all members of the research team (n=38), including researchers, service users, in 2018 at the end of this 3 year study. Semi-structured interviews were conducted with 16 members of the research team. Survey results were reported using descriptive statistics and interviews were analysed with thematic analysis using the framework approach. Results were reported using the GRIPP2 guidelines. Results. Embedding PPI into the study as an independent work-stream was identified as a particular strength, and benefitted from effective organisation and leadership. Research team members recognised that a supportive environment that valued PPI was fostered which helped sustain engagement. Case studies of PPI methods used that showed impact on the study are reported. Conclusion. Providing PPI as an independent funded work-stream helped provide the contextual and process factors important to enable service users to have a real impact on the LAPCD study

Evaluating the impact of patient and public involvement (PPI) in the Life After Prostate Cancer Diagnosis (LAPCD) study

Background. Insights from patient and public involvement (PPI) can help researchers understand what it is like to live with cancer, and thus make cancer research more relevant to the needs of service users (patients and carers). Evaluation and reporting of PPI in health studies is important to build a strong evidence base concerning what works for whom and in what circumstances. We evaluated the impact of PPI in a large national study in the UK exploring Life After Prostate Cancer Diagnosis (LAPCD). Methods. An online survey was mailed to all researchers and service users (N=38) in 2018 at the end of this three year study, followed by semi-structured interviews (n=30). Analysis of survey and interview data was informed by realist evaluation principles. Results were reported using the GRIPP2 guidelines. Results. Strong contextual factors and robust processes for PPI facilitated positive impacts on the LAPCD study. Contextual factors included strong leadership of the service user group, commitment and expertise of the service users, clear roles, a positive attitude to involvement from researchers, and sufficient funding for PPI. Processes included a strong collaboration between the service users and the other research team members developed by embedding the PPI into a work-stream that ran alongside all the other 5 work-streams in the study. PPI impacts are reported on the design of the study, sense checking of patient information, at team meetings, analysis of qualitative data, paper writing, developing lay summaries, and dissemination of results. The study size and geographical distance sometimes created challenges for both service users and researchers. More formal feedback channels were suggested for future PPI. Conclusion. Well-resourced, carefully planned PPI ensured effective involvement and positive impacts on the LAPCD study

Ki67 Is an Independent Predictor of Recurrence in the Largest Randomized Trial of 3 Radiation Fractionation Schedules in Localized Prostate Cancer

Purpose: To assess whether the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiation therapy fractionation in patients with localized prostate tumors participating in a randomized trial of 3 radiation therapy fractionation schedules (74 Gy/37 fractions vs 60 Gy/20 fractions vs 57 Gy/19 fractions). Methods and Materials: A matched case–control study design was used; patients with biochemical/clinical failure >2 years after radiation therapy (BCR) were matched 1:1 to patients without recurrence using established prognostic factors (Gleason score, prostate-specific antigen, tumor stage) and fractionation schedule. Immunohistochemistry was used to stain diagnostic biopsy specimens for Ki67, which were scored using the unweighted global method. Conditional logistic regression models estimated the prognostic value of mean and maximum Ki67 scores on BCR risk. Biomarker–fractionation interaction terms determined whether Ki67 was predictive of BCR by fractionation. Results: Using 173 matched pairs, the median for mean and maximum Ki67 scores were 6.6% (interquartile range, 3.9%-9.8%) and 11.0% (interquartile range, 7.0%-15.0%) respectively. Both scores were significant predictors of BCR in models adjusted for established prognostic factors. Conditioning on matching variables and age, the odds of BCR were estimated to increase by 9% per 1% increase in mean Ki67 score (odds ratio 1.09; 95% confidence interval 1.04-1.15, P =.001). Interaction terms between Ki67 and fractionation schedules were not statistically significant. Conclusions: Diagnostic Ki67 did not predict BCR according to fractionation schedule in CHHiP; however, it was a strong independent prognostic factor for BCR

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

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

Effects of reverberation conditions and physical versus virtual source placement on localization in virtual sound environments

Sound field synthesis systems vary in number and arrangement of loudspeakers and methods used to generate virtual sound environments to study human hearing perception. While previous work has evaluated the accuracy with which these systems physically reproduce room acoustic conditions, less is known on assessing subjective perception of those conditions, such as how well such systems preserve source localization. This work quantifies the accuracy and precision of perceived localization from a multi-channel sound field synthesis system at Boys Town National Research Hospital, which used 24 physical loudspeakers and vector-based amplitude panning to generate sound fields. Short bursts of broadband speech-shaped noise were presented from source locations (either coinciding with a physical loudspeaker location, or panned between loudspeakers) under free-field and modeled reverberant-room conditions. Listeners used a HTC Vive remote laser tracking system to point to the perceived source location.Results show that the system synthesizes source locations accurately for both physical and panned sources, in both azimuth and elevation. Panned sources, though, are localized less precisely than physical sources. Reverberant condition is also found to affect both the accuracy and precision of localization in the azimuthal plane, with dry conditions producing greater accuracy and better precision. Only accuracy (not precision) of localization in elevation was impacted by reverberant condition, with reverberant cases producing results closer to the target than dry cases. An interaction effect of reverberant condition with elevation on localization in elevation, though, indicates that dry conditions result in better localization in elevation than reverberant ones at an elevation close to head height, but the situations at higher elevations are where subjects localized dry sources lower than the target height, while reverberant ones were more accurately placed. Other laboratories with sound field synthesis systems are encouraged to gather similar data on the accuracy and precision of localization in azimuth and elevation, so that results from studies using these systems can be better interpreted in light of the capabilities of the system to generate accurate and precise reproductions of source locations. [Work supported by NIH GM109023.] Advisor: Lily M. Wan