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Modeling outdoor environmental sound levels is a challenging problem. This paper reports on a validation study of two continental-scale machine learning models using geospatial layers as inputs and the summer daytime A-weighted L50 as a validation metric. The first model was developed by the National Park Service while the second was developed by the present authors. Validation errors greater than 20 dBA are observed. Large errors are attributed to limited acoustic training data. Validation environments are geospatially dissimilar to training sites, requiring models to extrapolate beyond their training sets. Results motivate further work in optimal data collection and uncertainty quantification.

This study investigates source-related noise characteristics of the Falcon 9, a modern launch vehicle with a high operational tempo. Empirical prediction of the noise characteristics of launched rockets has long been a topic of study; however, there are relatively few comparisons with high-fidelity, far-field data, and historical inconsistencies persist. Various quantities are considered: overall directivity, overall sound power, maximum overall sound pressure level (OASPL), and peak frequency. The noise directivity of the Falcon 9 vehicle is shown to be between two disparate ranges given in the historical literature, but the observed peak directivity angle is well represented using convective Mach number concepts. A comparison between mechanical and acoustic power yields a radiation efficiency is consistent with the literature. Two independent methods of predicting maximum OASPL produce results accurate within 2 dB, even at distances of several kilometers. Various scaling parameters are calculated for observed spectral peak frequency and connect these measurements with prior observations. Finally, the impact of terrain shielding on levels and spectra is assessed. These determined source characteristics of the Falcon 9 vehicle provide a connection to prior launch vehicle acoustics studies, which helps identify useful models and methods for understanding rocket noise.

Objectives Rapid delivery of antibiotics is a cornerstone of sepsis therapy, although time targets for specific components of antibiotic delivery are unknown. We quantified time intervals comprising the task of antibiotic delivery and evaluated the association between interval delays and hospital mortality among patients treated in the emergency department for suspected sepsis. Design Retrospective cohort. Setting Twelve hospitals in Southeastern United States from 2014 to 2017. Patients Twenty-four thousand ninety-three encounters among 20,026 adults with suspected sepsis in 12 emergency departments. Measurements and main results We divided antibiotic administration into two intervals: time from emergency department triage to antibiotic order (recognition delay) and time from antibiotic order to infusion (administration delay). We used generalized linear mixed models to evaluate associations between these intervals and hospital mortality. Median time from emergency department triage to antibiotic administration was 3.4 hours (interquartile range, 2.0-6.0 hr), separated into a median recognition delay (time from emergency department triage to antibiotic order) of 2.7 hours(interquartile range, 1.5-4.7 hr) and median administration delay (time from antibiotic order to infusion) of 0.6 hours (0.3-1.2 hr). Adjusting for other risk factors, both recognition delay and administration delay were associated with mortality, but pairwise comparison with a no-delay reference group was not significant for up to 6 hours of recognition delay or up to 1.5 hours of administration delay. Conclusions Both recognition delays and administration delays were associated with increased hospital mortality, but only for longer delays. These results suggest that both metrics may be important to measure and improve for patients with suspected sepsis but do not support targets less than 1 hour.

Objective Increased infant birth weight and adiposity are associated with altered risk of adult chronic diseases. The objective was to investigate the association between maternal dietary fat intake during pregnancy and newborn adiposity. Study Design The study included 79 singleton pregnancies. Associations between maternal dietary fat intake during each trimester and infant adiposity at birth were assessed. Result Average total grams of maternal total dietary fat and unsaturated fat intake during pregnancy correlated with infant percent body fat after adjusting for potential confounding variables (r=0.23, p=0.045; r =0.24, p=0.037). Maternal average daily intake of total fat, saturated fat, and unsaturated fat during the second trimester of pregnancy were each associated with infant percent body fat (r =0.25, p=0.029; r =0.23, p=0.046; r =0.25, p=0.031; respectively). Conclusion The second trimester of pregnancy is a key time period for fetal adipose tissue metabolic programming and therefore a target for nutritional intervention.

BackgroundThe number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival.ResultsThis prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81–86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7,p p p p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86–1.15),p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87–1.17),p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7–60.7) vs. 57.1% (95% CI 53.7–60.1),p = 0.85].ConclusionsAfter adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.

An orally administered, fixed‐dose coformulation of sodium phenylbutyrate‐taurursodiol (PB‐TURSO) significantly slowed functional decline in a randomized, placebo‐controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long‐term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB‐TURSO or placebo. Participants completing the 6‐month (24‐week) randomized phase were eligible to receive PB‐TURSO in the open‐label extension. An all‐cause mortality analysis (35‐month maximum follow‐up post‐randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow‐up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB‐TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34‐0.92; P = .023). Initiation of PB‐TURSO treatment at baseline resulted in a 6.5‐month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB‐TURSO has both functional and survival benefits in ALS.

Background The purpose of this study was to determine the intraoperative and 30-day postoperative complication rates in a large consecutive cohort of pediatric patients who had orthopaedic surgery at a freestanding ambulatory surgery center (ASC). The authors also wanted to identify the rates of same-day, urgent hospital transfers, and 30-day hospital admissions. The authors hypothesized that pediatric orthopaedic procedures at a freestanding ASC can be done safely with a low rate of complications. Methods A retrospective review identified patients aged 17 years or younger who had surgery at a freestanding ASC over a 9-year period. Adverse outcomes were divided into intraoperative complications, postoperative complications, need for the secondary procedure, unexpected hospital admission on the same day of the procedure, and unexpected hospital admission within 30 days of the index procedure. Complications were graded as grade 1, the complication could be treated without additional surgery or hospitalization; grade 2, the complication resulted in an unplanned return to the operating room (OR) or hospital admission; or grade 3, the complication resulted in an unplanned return to the OR or hospitalization with a change in the overall treatment plan. Results Adequate follow-up was available for 3780 (86.1%) surgical procedures. Overall, there were 9 (0.24%) intraoperative complications, 2 (0.08%) urgent hospital transfers, 114 (3%) complications, and 16 (0.42%) readmissions. Seven of the 9 intraoperative complications resolved before leaving the OR, and 2 required return to the OR.Neither complications nor hospitalizations correlated with age, race, gender, or length or type of surgery. There was no correlation between the presence of medical comorbidities, body mass index, or American Society of Anesthesiologists score and complication or hospitalization. Conclusions Pediatric orthopaedic surgical procedures can be performed safely in an ASC because of multiple factors that include dedicated surgical teams, single-purpose ORs, and strict preoperative screening criteria. The rates of an emergency hospital transfer, surgical complications, and 30-day readmission, even by stringent criteria, are lower than those reported for outpatient procedures performed in the hospital setting. Level of evidence Level IV-case series.

Objective: Women with overweight/obesity have significantly lower rates of exclusive breastfeeding (EBF) at 6 weeks postpartum compared with women of normal weight. We sought to determine whether differences in Baby-Friendly Hospital Initiative (BFHI) adherence, obstetric practices, or social support explain these weight-related EBF disparities. Methods: One hundred forty-two healthy women who intended EBF (61 normal weight, 50 overweight, and 31 obese by preconception body mass index [BMI]) were enrolled in a cross-sectional study. Obstetric data were collected and participants completed modified Infant Feeding Practices Study II surveys at 6 weeks postpartum. Results: Women with obesity were significantly less likely to undergo spontaneous labor and more likely to receive synthetic oxytocin and epidural anesthesia compared with women with overweight or normal weight. Women who were overweight were less likely to report extended family support for breastfeeding compared with women with obesity or normal weight; however, BFHI components and composite BFHI score did not differ by maternal BMI. Furthermore, regardless of BMI, women with greater adherence to BFHI practices were more likely to be EBF at 6 weeks postpartum (p-value

The traditional method for intensity-based sound power estimates often used in engineering applications is limited in bandwidth by microphone phase mismatch at low frequencies and by microphone spacing at high frequencies. To overcome these limitations, the Phase and Amplitude Gradient Estimator (PAGE) method [Gee, Neilsen, Sommerfeldt, Akamine, and Okamoto, J. Acoust. Soc. Am. 141(4), EL357-EL362 (2017)] is applied to sound power for a reference sound source, a blender, and a vacuum cleaner. Sound power measurements taken according to ISO 3741:2010 (2010) are compared against traditional- and PAGE-processed intensity-based sound power estimates measured according to ANSI S12.12-1992 (R2017). While the traditional method underestimates the sound power at the spatial Nyquist frequency by 7-10 dB, the PAGE-based sound power is accurate up to the spatial Nyquist frequency, and above when phase unwrapping is successful.

Birthweight is a well-known predictor of adult-onset chronic disease. The placenta plays a necessary role in regulating fetal growth and determining birth size. Maternal stressors that affect placental function and prenatal growth include maternal overnutrition and undernutrition, toxic social stress, and exposure to toxic chemicals. These stressors lead to increased vulnerability to disease within any population. This vulnerability arises from placental and fetal exposure to stressors during fetal life. The biological drivers linking various social determinants of health to compromised placental function and fetal development have been little studied.

Low weight in early infancy is a known risk factor for cardio-metabolic syndrome in adult life. However, little is known either about developmental programming in subjects of normal birthweight or about events between the ages which separate early programming and the occurrence of disease at late adulthood. We tested the hypothesis that circulating concentrations of leptin, adiponectin and insulin in young, healthy adults, born with a birth size within the normal range, are influenced by early life growth patterns. In an observational study of 188 healthy volunteers aged 18–25 years (97 males, 91 females) we investigated the association of metabolic function with their birth size, their growth during childhood and their body composition. High plasma leptin in early adulthood, a risk factor for cardio-metabolic syndrome, was associated with low weight at age 2 years (correlation coefficient controlled for adult weight = −0.21, P P

A 16-year-old patient presented with abdominal pain and sustained hypertension. Thorough evaluation including renography with and without captopril and renal vein renin sampling were normal. Duplex ultrasound, however, raised suspicion of a renal artery stenosis. This was confirmed by computed tomography angiography which showed a severe branch artery stenosis with post-stenotic dilatation consistent with focal fibromuscular dysplasia (FMD). As the hypertension was resistant to 3 classes of antihypertensive treatment, percutaneous transluminal renal angioplasty (PTRA) was offered. The procedure had immediate effect on the blood pressure. Without medication the patient remains normotensive 4 years after and the abdominal pain has only sporadically returned. The presented case illustrates the challenging process of diagnosing FMD-related renal branch artery stenosis as well as the potential benefits of PTRA in this patient group.

SUMMARYAndrogen deprivation therapy (ADT) induces regression of recurrent and advanced prostate cancer (PrCa), but many tumors recur. To understand the response to ADT, changes in tumor volume were imaged after castration of murine PrCa models. While mouse (non-tumor) prostate begins to regress within two days of castration, murine PrCa regresses after a delay of 3-14 days in two distinct mouse models. Intra-tumoral androgens are undetectable after castration, but tumor cells proliferate during this period. Intratumoral glucocorticoids and glucocorticoid receptor (GR) protein increase, as does GR mRNA and a set of GR-regulated genes specifically in tumor epithelial cells identified using scRNAseq. A selective GR antagonist (CORT125281, relacorilant), in clinical trials for late-state PrCa, eliminates the delayed regression phenotype in both models. Thus, activated GR signaling and murine tumor proliferation following castration resembles the GR-dependent escape mechanism of castrate resistant PrCa. These results suggest simultaneous inhibition of GR and androgen receptor signaling could improve PrCa therapy.In briefAndrogen deprivation therapy for high risk and recurrent prostate cancers is initially effective, but ultimately fails; better understanding the mechanisms should improve therapy. In two murine prostate cancer models, GR signaling is activated immediately following castration, substituting for the acute reduction in AR signaling, and allowing for continued tumor growth. This continued growth is blocked by relacorilant, selective GR antagonist in clinical trials for late-state PrCa.HighlightsAndrogen deprivation therapy induces regression of prostate cancer, but tumors recurMurine PrCa continues to proliferate for 3-14 days in two distinct mouse prostate cancer modelsTumor cells proliferate during this period, and intratumoral glucocorticoids and glucocorticoid receptor (GR) protein increase, as does GR mRNA and a set of GR-regulated genesRelacorilant, a selective GR antagonist in clinical trials for late-state PrCa, eliminates the delayed regression

Yttrium aluminum garnet (YAG) is a common host material for both bulk and single-crystal fiber lasers. With increasing interest in developing optical technologies in the short-wave infrared and mid-infrared wavelength range, YAG may be a potential supercontinuum medium for these applications. Here, we characterize femtosecond laser pumped supercontinuum generation with 1200–2000 nm pump wavelengths ( λ p ) for undoped, single-crystal YAG fibers, which are representative of the normal, zero, and anomalous-dispersion regimes. Supercontinuum was observed over the spectral region of about 0.2 to 1.6 λ p . Z-scan measurements were also performed of bulk YAG, which revealed little dispersion of the nonlinear index of refraction ( n 2 ) in the region of interest. The measured values of n 2 ( ∼ 1 × 10 − 6 c m 2 / G W ) indicate a regime in which the nonlinear length, L N L , is less than the dispersion length, L D , ( L N L ≪ L D ). We report intensity clamping of the generated filament in the normal group velocity dispersion (GVD) regime and an isolated anti-Stokes peak in the anomalous GVD regime, suggesting further consideration is needed to optimize supercontinuum generation in this fiber medium.

OBJECTIVES To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN Prospective cohort study. SETTING A total of 306 ICUs from 24 European countries. PARTICIPANTS Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81‐87 y]; 51.8% male). MEASUREMENTS Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30‐day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS The 30‐day‐mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30‐day mortality in 91.1% of all patients who die. CONCLUSION A predictive model of cumulative events predicts 30‐day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision‐making capacity. © 2019 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

The incidence of renal cell carcinoma (RCC) is increasing worldwide with an approximate 20% mortality rate. The challenge in RCC is the therapy-resistance. Cancer resistance to treatment employs multiple mechanisms due to cancer heterogeneity with multiple genetic and epigenetic alterations. These changes include aberrant overexpression of (1) anticancer cell death proteins (e.g., survivin/BIRC5), (2) DNA repair regulators (e.g., ERCC6) and (3) efflux pump proteins (e.g., ABCG2/BCRP); mutations and/or deregulation of key (4) oncogenes (e.g., MDM2, KRAS) and/or (5) tumor suppressor genes (e.g., TP5/p53); and (6) deregulation of redox-sensitive regulators (e.g., HIF, NRF2). Foci of tumor cells that have these genetic alterations and/or deregulation possess survival advantages and are selected for survival during treatment. We will review the significance of survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, TP5/p53, KRAS and AKT in treatment resistance as the potential therapeutic biomarkers and/or targets in RCC in parallel with our analized RCC-relevant TCGA genetic results from each of these gene/protein molecules. We then present our data to show the anticancer drug FL118 modulation of these protein targets and RCC cell/tumor growth. Finally, we include additional data to show a promising FL118 analogue (FL496) for treating the specialized type 2 papillary RCC. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-02026-1.

Background: Blood pressure (BP) control is important in chronic kidney disease (CKD), but a reduction in brachial BP may not mirror changes in central aortic BP (cBP) during antihypertensive medication. We hypothesize that a fall in cBP is better reflected during enhanced vasodilation treatment (EVT) compared with reduced vasodilation treatment (RVT) because of different hemodynamic actions of these interventions.Methods: Eighty-one hypertensive CKD stage 3-4 patients (mean measured glomerular filtration rate 36 ml/min per 1.73 m2) were randomized to either EVT based on renin--angiotensin blockade and/or amlodipine or RVT based on nonvasodilating β-blockade (metoprolol). Before randomization and following 18 months of treatment, we performed 24-h ambulatory BP measurements (ABPM) and radial artery pulse wave analysis for estimation of cBP and augmentation index (AIx). Forearm resistance (Rrest) was determined by venous occlusion plethysmography and arterial stiffness by carotid--femoral pulse wave velocity (PWV). Matched healthy controls were studied once for comparison.Results: Compared with controls, CKD patients had elevated ABPM, cBP and PWV. Although ABPM remained unchanged from baseline to follow-up in both treatment groups, cBP decreased 4.7/2.9 mmHg (systolic/diastolic) during EVT and increased 5.1/1.5 mmHg during RVT (Δ=9.8/4.4 mmHg, P=0.02 for SBP, P = 0.05 for DBP). At follow-up, the difference between systolic cBP and 24-h ABPM (ΔBPsyst) was negatively associated with heart rate and positively associated with AIx and Rrest (all P < 0.01) but not PWV (P = 0.32).Conclusion: In CKD patients, EVT and RVT have opposite effects on cBP and the difference between cBP and ambulatory BP is larger for EVT than RVT.

PURPOSE: Twenty-four hours of ambulatory blood pressure monitoring (ABPM) is recommended in several guidelines as the best method for diagnosing hypertension. In general, the prognostic value of ABPM is superior to single office blood pressure (BP) measurements. Unfortunately, some patients experience considerable discomfort during frequently repeated forceful cuff inflations.MATERIALS AND METHODS: In this study we investigated the difference in mean daytime systolic BP (SBP) between low-frequency ABPM (LF-ABPM), measuring once every hour, and high-frequency ABPM (HF-ABPM), measuring three times an hour during daytime, and two times an hour during night-time.RESULTS: Seventy-one patients were included in the analysis. All included patients had an HF-ABPM performed first and within a few weeks they underwent an LF-ABPM. The average day time difference in SBP between the two frequencies was 3.8 mmHg (p-value = 0.07) for mild, 8.2 mmHg (p-value < 0.01) for moderate and 15 mmHg (p-value < 0.001) for severe hypertension. A similar pattern was seen for night-time SBP. This study suggests that mean BP is similar between the two measuring frequencies for normotensive and mild hypertensive patients, while HF-ABPM results in a higher 24-h mean BP for moderate- and severe hypertensive patients.CONCLUSION: LF-ABPM may more correctly reflect the resting blood pressure in patients with moderate and severe hypertension.

Background The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. Methods We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. Results The median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p p Conclusion Knowledge about a patient’s frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

In our previous work, PC-9-Br, a PC-9 brain seeking line established via a preclinical animal model of lung cancer brain metastasis (LCBM), exhibited not only resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib in vitro, but also chemotherapy regimens of cisplatin plus etoposide in vivo. Using this cell line, we investigated novel potential targeted therapeutics for treating LCBM in vitro and in vivo to combat drug resistance. Significant increases in mRNA and protein expression levels of Bcl-2 were found in PC-9-Br compared with parental PC-9 (PC-9-P), but no significant changes of Bcl-XL were observed. A remarkable synergistic effect between EGFR-TKI gefitinib and Bcl-2 inhibitors ABT-263 (0.17 ± 0.010 µM at 48 h and 0.02 ± 0.004 µM at 72 h), or ABT-199 (0.22 ± 0.008 µM at 48 h and 0.02 ± 0.001 µM at 72 h) to overcome acquired resistance to gefitinib (> 0.5 µM at 48 h and 0.10 ± 0.007 µM at 72 h) in PC-9-Br was observed in MTT assays. AZD9291 was also shown to overcome acquired resistance to gefitinib in PC-9-Br in MTT assays (0.23 ± 0.031 µM at 48 h and 0.03 ± 0.008 µM at 72 h). Western blot showed significantly decreased phospho-Erk1/2 and increased cleaved-caspase-3 expressions were potential synergistic mechanisms for gefitinib + ABT263/ABT199 in PC-9-Br. Significantly decreased protein expressions of phospho-EGFR, phospho-Akt, p21, and survivin were specific synergistic mechanism for gefitinib + ABT199 in PC-9-Br. In vivo studies demonstrated afatinib (30 mg/kg) and AZD9291 (25 mg/kg) could significantly reduce the LCBM in vivo and increase survival percentages of treated mice compared with mice treated with vehicle and gefitinib (6.25 mg/kg). In conclusion, our study demonstrated gefitinib + ABT263/ABT199, afatinib, and AZD9291 have clinical potential to treat LCBM.

The standard method for growth rate determination in semiconductor thin films, by Molecular Beam Epitaxy (MBE), is through RHEED intensity oscillations prior to device layer epitaxy. High quality III-Nitride epitaxy occurs with metal-rich surfaces and under step-flow growth conditions, which do not produce RHEED oscillations. This article demonstrates the capability to monitor the growth rate of gallium nitride (GaN), at any point during film growth with high fidelity, under step-flow growth conditions. RHEED intensity vs. time measurements determine the growth rate by Metal Modulated Epitaxy (MME). Utilizing differential analysis, a factor of 2x improvement in accuracy is demonstrated, with a Standard Error less than 4%. Complementary analysis with X-Ray Diffraction and RHEED identify the Ga bilayer thickness as 2.34 ML ± 0.08 ML, representing the first time RHEED analysis has been used to characterize the thickness of the Ga bilayer on GaN.

Aim:Progression of chronic kidney disease (CKD) may be accelerated by tissue hypoxia due to impaired blood supply. This could be induced by small artery narrowing resulting in abnormally high intrarenal vascular resistance (RVR). We investigated whether a reduction in RVR achieved by adding vasodilating medical therapy (AVT) is superior to adding nonvasodilating medical therapy (AnonVT) regarding tissue oxygenation and preservation of kidney function.Methods:Eighty-three grade 3 and 4 CKD patients [estimated glomerular filtration rate (GFR) 34.6ml/min per 1.73m 2] were randomized to either AVT with amlodipine and/or renin angiotensin blockade or AnonVT with the nonvasodilating beta-blocker metoprolol. Investigations were performed at baseline and after 18 months of therapy. Systemic vasodilation was documented in the forearm vasculature using resting venous occlusion plethysmography. GFR was measured as 51Chrome-EDTA plasma clearance. Using MRI, renal artery blood flow was measured for calculation of RVR and for estimating renal oxygenation (R 2∗).Results:AVT and AnonVT achieved as planned similar blood pressure levels throughout the study. At follow-up, resistance had decreased by 7% (P2∗ values between AVT and AnonVT were observed, and the GFR decline was similar in the two groups (3.0 vs. 3.3ml/min per 1.73m 2).Conclusion:Long-term intensified vasodilation treatment reduced peripheral and RVR, but this was not associated with improvement of R 2∗ or protection against loss of kidney function in CKD patients.

This letter describes how a landmark 1960s supersonic jet noise experiment influenced subsequent noise models. A discrepancy in other researchers' application of Potter and Jones's axial decomposition of the sound power generated from a laboratory-scale jet can be traced to an erroneous plot in the original report. Whereas most jet noise research indicates the dominant sound power is generated upstream of the supersonic core tip, propagation of this error in the ubiquitous NASA SP-8072 report has caused rocket noise modelers for five decades to disproportionately allocate sound power generation to the subsonic flow.

Background Exercise-induced laryngeal obstruction (EILO) causes exertional dyspnea and is important for its effect on quality of life, diagnostic confusion with exercise-induced asthma, and health care resource utilization. There is no validated patient-reported outcome measure specific to EILO. Objective We sought to develop, validate, and define a minimal clinically important difference for a patient-reported outcome measure to be used with adolescents and young adults with EILO. Methods A multidisciplinary group created a preliminary measure, modified by a 10-member participant focus group, with 20 items scored along a 5-point Likert scale. A subsequent cohort of participants recruited from a clinic, aged 12 to 21 years, with confirmed EILO by continuous laryngoscopy during exercise testing (1) completed the measure at 3 points in time over 28 days and (2) provided anchoring data in the form of a daily exercise log and categorical self-assessments of clinical improvement. Thirty additional participants without exertional dyspnea served as controls. Results Two hundred nineteen subjects with mild to severe EILO participated in the exploratory factor analysis, which identified 7 factors within the preliminary outcome measure. After a process of item reduction, a 12-item metric with a total score ranging from 0 to 48 was developed. Mean scores of patients with EILO and healthy controls at baseline were 28.8 ± 7.4 and 4.5 ± 7.4, respectively. A minimal clinically important difference of 6 was determined by comparison of index change with changes in categorical self-assessments of improvement. Conclusions This is the first patient-reported outcome measure specifically designed for adolescents and young adults with EILO.

Benign prostatic hyperplasia (BPH) is ostensibly linked to autoimmune (AI) diseases, but whether the prostate is a target of systemic inflammation associated with AI conditions is unknown. Prostatic inflammation is linked to fibrosis, hyperplasia, and reduced responses to BPH-related medical therapies. This study was conducted to determine if AI disease correlates with BPH diagnosis and whether systemic targeting of an inflammatory mediator limits prostatic inflammation and hyperplasia. Patient medical records (n=112,152) were evaluated to determine BPH prevalence among different AI diseases. Inflammatory cells from human BPH tissues were analyzed by single-cell (sc)RNA-seq and the tumor necrosis factor (TNF)α-antagonist etanercept was tested in two murine models of prostatic enlargement. BPH prevalence was significantly higher among patients with AI disease compared to unaffected individuals. However, AI patients treated with TNFα-antagonists had a significantly reduced incidence of BPH. Data from scRNA- seq identified macrophages as a dominant source of TNFα and in vitro assays confirmed that TNFα stimulates BPH-derived fibroblast proliferation. In the AI patient cohort and murine models, systemic treatment with TNFα-antagonists decreased prostatic epithelial proliferation, macrophage infiltration, and epithelial NFκB activation compared to control tissues. These studies are the first to show that patients with AI diseases have a heightened susceptibility to BPH and that the TNFα-signaling axis is important for BPH pathogenesis. Macrophage-secreted TNFα may mechanistically drive BPH via chronic activation of the signaling axis and NFκB. TNFα blockade appears to be a promising new pharmacological approach to target inflammation and suppress BPH.One sentence summaryPatient data and mouse models suggest that repurposing tumor necrosis factor alpha blockade reduces inflammation-mediated prostatic hyperplasia.

Temperature- and wavelength-dependent values of the ordinary (no) and extra-ordinary refractive index (ne) of GaN and 4H-SiC were measured over wavelength ranges of 1.9 to 7 μm and 1.9 – 5.5 μm, respectively, and over a temperature range of 79 to 400 K. Temperature-dependent Sellmeier equations for both GaN and SiC were obtained and thermooptic coefficients determined.

CdSiP2 (CSP) is a nonlinear optical chalcopyrite semiconductor developed as a wider-band-gap analog of ZnGeP2 (ZGP) to enable mid-infrared generation. Two laser architectures were explored to pump CSP crystals at 2 microns. The first was a ring OPO with two CSP crystals that produced 27 W of average power, demonstrating the viability of CSP as a material capable of producing high average power output. The second architecture was an OPO seeded OPA train that was used to directly compare the thermal lenses generated by pumping either CSP or ZGP with high average power 2 micron light. The CSP crystals demonstrated significantly less thermal lensing than the ZGP crystals.

Repeated cuff-based blood pressure (BP) measurements may cause discomfort resulting in stress and erroneous recording values. SOMNOtouch NIBP is an alternative cuff-less BP measurement device that calculates changes in BP based on changes in pulse transit time (PTT) and a software algorithm. The device is calibrated with a single upper arm cuff-based BP measurement. We tested the device against a validated 24-h ambulatory BP monitoring (ABPM) device using both the previous (SomBP1) and the current software algorithm (SomBP2). In this study, 51 patients (mean age ± SD 61.5 ± 13.0 years) with essential hypertension underwent simultaneous 24-h ABPM with the SOMNOtouch NIBP on the left arm and a standard cuff-based oscillometric device on the right arm (OscBP). We found that mean daytime systolic BP (SBP) with OscBP was 140.8 ± 19.7 compared to 148.0 ± 25.2 (P = .008) and 146.9 ± 26.0 mmHg (P = .034) for SomBP1 and SomBP2, respectively. Nighttime SBP with OscBP was 129.5 ± 21.1 compared with 146.1 ± 25.8 (P < .0001) and 141.1 ± 27.4 mmHg (P = .001) for SomBP1 and SomBP2, respectively. Ninety-five% limits of agreement between OscBP and SomBP1 were ± 36.6 mmHg for daytime and ± 42.6 mmHg for nighttime SBP, respectively. Agreements were not improved with SomBP2. For SBP, a nocturnal dipping pattern was found in 33% of the study patients when measured with OscBP but only in 2% and 20% with SomBP1 and -2, respectively. This study demonstrates that BP values obtained with the cuff-less PTT-based SOMNOtouch device should be interpreted with caution as these may differ substantially from what would be obtained from a validated cuff-based BP device.

Cardiac pumping depends on the morphological structure of the heart, but also on its subcellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized ultrastructural disruptions that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of technologies that can image the three-dimensional (3D) heart structure, to assess malformations; and its ultrastructure, to assess organelle disruptions. We present here a multiscale, correlative imaging procedure that achieves high-resolution images of the whole heart, using 3D micro-computed tomography (micro-CT); and its ultrastructure, using 3D scanning electron microscopy (SEM). In a small animal model (chicken embryo), we achieved uniform fixation and staining of the whole heart, without losing ultrastructural preservation on the same sample, enabling correlative multiscale imaging. Our approach enables multiscale studies in models of congenital heart disease and beyond., eLife digest The heart is our hardest-working organ and beats around 100,000 times a day, pumping blood through a vast system of vessels to all areas of the body. Specialized heart cells make the heart contract rhythmically, enabling it to work efficiently. Contractile molecules inside these cells, called myofibrils, align within the heart cells, and heart cells align to each other, so that the heart tissue contracts effectively. However, when the heart has defects or is diseased this organization can be lost, and the heart may no longer pump blood efficiently, leading to sometimes life-threatening complications. For example, around one in a hundred newborn babies suffer from congenital heart defects, and despite medical advances, these conditions remain the main cause of non-infectious mortality in children. Many cases of congenital heart disease are diagnosed before a baby is born during an ultrasound scan. However, these scans, as well as subsequent diagnostic tools, lack the precision to detect problems within the heart cells. Now, Rykiel et al. used two complementary imaging techniques known as micro-computed tomography and scanning electron microscopy to acquire pictures of the whole heart as well as of the organization inside the heart cells. This made it possible to capture the structure of the heart tissue at both micrometer (the whole heart) and nanometer resolution (the inside of the cells), and to study what happens within the heart and its cells when the heart has a defect. Rykiel et al. tested the imaging technology on the hearts of chicken embryos, at stages equivalent to a five to six-month-old human fetus, and compared a healthy heart with a heart with a defect called tetralogy of Fallot. They found that the tissues in the heart with a defect had a sponge-like appearance, with increased space in between cells. Moreover, the myofibrils of the heart with a defect were aligned differently compared to those in the normal heart. More research is needed to fully understand what happens when the heart has a defect. However, the imaging technology used in this study offers the possibility of examining the heart at an unprecedented level of detail. This will deepen our understanding of how structural heart defects arise and how they affect the pumping of the heart, and will give us clues to design better treatments for patients with heart defects and other heart anomalies.

BACKGROUND: Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known. METHODS: In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate–taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization. RESULTS: A total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate–taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was −1.24 points per month with the active drug and −1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P = 0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal. CONCLUSIONS: Sodium phenylbutyrate–taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate–taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR Clinicaltrials.gov number, NCT03127514.)

The majority of intrapartum decelerations are widely believed to be mediated by the baroreflex secondary to brief umbilical cord occlusions (UCOs) but this remains unproven. We examined the responses to brief-UCOs in fetal sheep and compared these to a phenylephrine-stimulated baroreflex in a separate cohort. A further cohort was instrumented with near-infrared spectroscopy to measure cerebral oxygenation during UCO. The first 3-4 s of the brief-UCOs were consistent with a baroreflex, and associated with a minor fall in fetal heart rate (FHR). Thereafter, the remainder of the FHR decelerations were highly consistent with the peripheral chemoreflex. The baroreflex is not sufficient to produce deep, rapid decelerations characteristic of variable decelerations and it is therefore likely to be a minor contributor to intrapartum decelerations.Fetal heart rate (FHR) monitoring is widely used to assess fetal wellbeing during labour, yet the physiology underlying FHR patterns remains incompletely understood. The baroreflex is widely believed to mediate brief intrapartum decelerations, but evidence supporting this theory is lacking. We therefore investigated the physiological changes in near-term fetal sheep during brief repeated umbilical cord occlusions (brief-UCOs, n = 15). We compared this to separate cohorts that underwent a phenylephrine challenge to stimulate the baroreflex (n = 9) or were instrumented with near-infrared spectroscopy and underwent prolonged 15-min complete UCO (prolonged-UCO, n = 9). The first 3-4 s of brief-UCOs were associated with hypertension (P = 0.000), a fall in FHR by 9.7-16.9 bpm (P = 0.002). The FHR/MAP relationship during this time was consistent with that observed during a phenylephrine-induced baroreflex. At 4-5 s, the FHR/MAP relationship began to deviate from the phenylephrine baroreflex curve as FHR fell independently of MAP until its nadir in association with intense peripheral vasoconstriction (P = 0.000). During prolonged-UCO, cerebral oxygenation remained steady until 4 s after the start of prolonged-UCO, and then began to fall (P = 0.000). FHR and cerebral oxygenation then fell in parallel until the FHR nadir. In conclusion, the baroreflex has a minor role in mediating the first 3-4 s of FHR decelerations during complete UCO, but thereafter the peripheral chemoreflex is the dominant mediator. Overall, the baroreflex is neither necessary nor sufficient to produce deep, rapid decelerations characteristic of variable decelerations; it is therefore likely to be a minor contributor to intrapartum decelerations.

Many optical metrology applications require light that is both coherent and broadband. Supercontinuum (SC) spanning several wavelength octaves is an obvious candidate for such applications. Optical fibers are a natural platform for SC generation due to the long interaction length of light within the fiber which allows for broad SC which can ultimately be used as a tunable narrowband source. For tunability in the mid-IR regime, YAG fibers are an excellent candidate due to their high transparency, Kerr nonlinearity, and damage threshold. In our work, we study SC in undoped crystalline YAG fibers produced via laser-heated pedestal growth. We use femtosecond pulses to generate SC in fiber, pumping at several wavelengths ranging out to the mid-IR. Studying the power-dependence of SC generation, we use SC width and shape as indicators of mechanisms that generate SC at each pump wavelength.

Background Pregnancy complications such as preterm birth and fetal growth restriction are associated with altered prenatal and postnatal cardiac development. We studied whether there were changes related specifically to pregnancy hypertension. Methods and Results Left and right ventricular volumes, mass, and function were assessed at birth and 3 months of age by echocardiography in 134 term‐born infants. Fifty‐four had been born to mothers who had normotensive pregnancy and 80 had a diagnosis of preeclampsia or pregnancy‐induced hypertension. Differences between groups were interpreted, taking into account severity of pregnancy disorder, sex, body size, and blood pressure. Left and right ventricular mass indexed to body surface area (LVMI and RVMI) were similar in both groups at birth (LVMI 20.9±3.7 versus 20.6±4.0 g/m2, P=0.64, RVMI 17.5±3.7 versus 18.1±4.7 g/m2, P=0.57). However, right ventricular end diastolic volume index was significantly smaller in those born to hypertensive pregnancy (16.8±5.3 versus 12.7±4.7 mL/m2, P=0.001), persisting at 3 months of age (16.4±3.2 versus 14.4±4.8 mL/m2, P=0.04). By 3 months of age these infants also had significantly greater LVMI and RVMI (LVMI 24.9±4.6 versus 26.8±4.9 g/m2, P=0.04; RVMI 17.1±4.2 versus 21.1±3.9 g/m2, P

Efficient cardiac pumping depends on the morphological structure of the heart, but also on its sub-cellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized sub-cellular disruptions in architecture that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of technologies that can image the three dimensional (3D) heart structure, assessing malformations; and its ultrastructure, assessing disruptions. We present here a multiscale, correlative imaging procedure that achieves high-resolution images of the whole heart, using 3D micro-computed tomography (micro-CT); and its ultrastructure, using 3D scanning electron microscopy (SEM). This combination of technologies has not been possible before in imaging the same cardiac sample due to the heart large size, even when studying small fetal and neonatal animal models (~5×5×5mm3). Here, we achieved uniform fixation and staining of the whole heart, without losing ultrastructural preservation (at the nm resolution range). Our approach enables multiscale studies of cardiac architecture in models of congenital heart disease and beyond.

Most prostate cancers depend on androgens for growth, and therefore, the mainstay treatment for advanced, recurrent, or metastatic prostate cancer is androgen deprivation therapy (ADT). A prominent side effect in patients receiving ADT is an obese frailty syndrome that includes fat gain and sarcopenia, defined as the loss of muscle function accompanied by reduced muscle mass or quality. Mice bearing Pten-deficient prostate cancers were examined to gain mechanistic insight into ADT-induced sarcopenic obesity. Castration induced fat gain as well as skeletal muscle mass and strength loss. Catabolic TGF-β family myokine protein levels were increased immediately prior to strength loss, and pan-myokine blockade using a soluble receptor (ActRIIB-Fc) completely reversed the castration-induced sarcopenia. The onset of castration-induced strength and muscle mass loss, as well as the increase in catabolic TGF-β family myokine protein levels, were coordinately accelerated in tumor-bearing mice relative to tumor-free mice. Notably, growth differentiation factor 11 (GDF11) increased in muscle after castration only in tumor-bearing mice, but not in tumor‑free mice. An early surge of GDF11 in prostate tumor tissue and in the circulation suggests that endocrine GDF11 signaling from tumor to muscle is a major driver of the accelerated ADT-induced sarcopenic phenotype. In tumor-bearing mice, GDF11 blockade largely prevented castration-induced strength loss but did not preserve muscle mass, which confirms a primary role for GDF11 in muscle function and suggests an additional role for the other catabolic myokines.

Background: Current recommendations for osteoarthritis of the metacarpophalangeal joint (MCPJ) are confined to implant arthroplasty to preserve joint motion and provide pain relief. This study documents the median 2-year results of a novel soft tissue arthroplasty technique that interposes the dorsal capsule. Methods: A retrospective review of 10 MCPJ dorsal capsule interposition arthroplasties in 8 patients was conducted. Physical evaluation assessed MCPJ range of motion (ROM), grip strength, and pain. Outcome tests used were the Michigan Hand Outcome Score, Visual Analog Scale (VAS), and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH). Kellgren and Lawrence Classification assessed severity of MCPJ osteoarthritis on preoperative radiographs. Results: The mean follow-up was 29 months from surgery. Average VAS was 2/10 postoperatively and average postoperative ROM improved 7 degrees. Average postoperative grip strength of the surgical hand was 30 kg. The QuickDASH average score was 24. Average Michigan Hand Questionnaire final score was 70. Patients with Kellgren Grades 2 or 3 osteoarthritis had the best QuickDASH and Michigan Hand Outcome scores. All patients working before surgery returned to work. No patient required a second surgery. Conclusion: This technique of dorsal capsule interposition arthroplasty provides a viable surgical option for isolated degenerative or traumatic arthritis of the MCPJ at an average follow-up of 2 years. Pain relief was most reliably provided in patients with less severe radiograph findings. The advantages of this procedure include preservation of bony anatomy, collateral ligaments, and volar plate to not preclude later implant arthroplasty.

Background Troponin T (TnT) is a well-known risk factor for negative outcome in hemodialysis (HD) patients, but little is known about variation over time, and the impact of clinical and dialysis specific factors. This study investigated the effect of angiotensin II receptor blockade (ARB), short and long-term variation in TnT and associations with clinical parameters. Methods In this analysis based on the SAFIR-cohort (Clinical Trials ID: NCT00791830) 81 HD patients were randomized double-blind for placebo (n = 40) or angiotensin II receptor blocker (ARB) treatment (n = 41) with irbesartan (150–300 mg) and followed for 12 months with six serial measurements of TnT using a high-sensitivity assay. Results Fifty-four patients (67%) completed follow-up. Baseline TnT-medians (min-max) were (placebo/ARB): 45(14–295)/46(10–343) ng/L. ARB-treatment did not significantly affect mean TnT-levels over the 12-month study period. Median week-to-week and one-year TnT-variation (5th–95th-percentile range) using all samples regardless of intervention were: 0(− 14–10) ng/L (week-to-week) and 3(− 40–71) ng/L (12 months). Median TnT-amplitude, capturing the change from the lowest to the highest TnT-value observed during the one-year study period was 38% or 20.5 ng/L. Median ratios with 95% limits of agreement were: 1.00(0.73–1.37); P = 0.92 (1 week/baseline; n = 77) and 1.07(0.52–2.25); P = 0.19 (12 months/baseline; n = 54). Baseline TnT was positively correlated with diabetes, ultrafiltration volume, arterial stiffness, change in intradialytic total peripheral resistance and N-terminal pro b-type natriuretic peptide (NT-proBNP) and negatively correlated with hematocrit, residual renal function and change in intradialytic cardiac output. High baseline TnT was associated with a higher risk of admission and cardiovascular (CV) events during follow-up. Increase in TnT over time (ΔTnT = 12-months-baseline) was significantly associated with increase in left ventricular (LV) mass and NT-proBNP and decrease in LV ejection fraction and late intradialytic stroke volume. ΔTnT was not significantly associated with admissions, CV or intradialytic hypotensive events during follow-up. Admissions were significantly more likely with a high (TnT-amplitude> 20.5 ng/L) than a low TnT-amplitude. Peaks in TnT were less frequent in aspirin-treated patients. Conclusion ARB-treatment had no significant effect on TnT-levels. Week-to-week variation was generally low, yet over 12 months individual patients had considerable TnT fluctuations. Rise in TnT over time was significantly correlated with markers of cardiac deterioration. Trial registration ClinicalTrials.gov Identifier: NCT00791830. Date of registration: November 17, 2008. EudraCT no: 2008–001267-11.

We measure the birefringence of nonlinear optical properties of cadmium silicon phosphide via the Z-scan technique at common pumping wavelengths. We discuss the implications of the NLO properties on the parametric conversion efficiency

Using ~3.6pm, 200fs, 500Hz laser pulses, we observed supercontinuum generation in 50 and 150pm outer dameter uidoped, single-crystal YAG fibers with sol-gel cladding. We note differences in supercontinuum based on diameter and cladding thickness.

Biotechnology products present unique characteristics including large molecular size, higher-order structure, and complicated manufacturing processes utilizing living organisms that often require orthogonal analytical methods to characterize the product and evaluate its quality. In light of this complexity, there is an absolute requirement to retain the biological activity in addition to achieving all product quality attributes normally expected of a parenteral pharmaceutical product. This chapter presents a systematic approach to specification setting for biotechnology products, discussing how the three components of a specification—critical quality attributes, analytical methods, and acceptance criteria—are defined, evaluated, and established. Common challenges in establishing specification for biotechnology products are also discussed.

For an adequate understanding of the broadband acoustic phenomena generated by a rocket exhaust jet impinging on a flame deflector, this study experimentally clarifies the factors that cause the di...

Public opinion regarding smoking and health has been of interest to polling companies since the 1940s – virtually since the beginning of modern-day public opinion polling. In this manuscript we document the rate of change in the public’s awareness and beliefs about smoking and health in North America (the United States and Canada). We report on four broad categories of opinions – public awareness of reports that smoking has been linked to lung cancer, belief that smoking is harmful to health and a cause of lung cancer, belief that smoking is a cause of diseases other than lung cancer, and belief about the health hazards of second-hand smoke.

At the time of writing this abstract, a review article is being finalized for publication in JASA entitled a “Supersonic jet noise from launch vehicles: 50 years since NASA SP-8072,” it describes the current state-of-the-art in rocket and launch vehicle noise research, including how highly heated, supersonic rocket plumes differ from other jets, the origin and nature of the radiated sound from both free and impinging rocket plumes, and techniques for pad noise mitigation during rocket launches. Existing and candidate methods (both empirical and numerical) for modeling rocket launch noise are reviewed, including the ubiquitous NASA SP-8072 methodology, which has formed the cornerstone of many rocket launch noise prediction models over the past half century. This talk will briefly discuss some of the insights gained as a result of writing this review and show how they led to the inevitable conclusion that an entirely new approach to rocket plume noise modeling—one that incorporates the underlying physics of the noise generation mechanisms—must be pursued.

Rocket launch noise has historically been analyzed for directivity and sound power. To compare against previous findings, this study uses data acquired from the NROL-82 Delta IV Heavy launch from Vandenberg Space Force Base, CA, USA. Rocket trajectory data are used to calculate the 3D angle between the plume and several measurement stations in the near and far fields. Overall sound pressure level, directivity, and sound power level are calculated, and the results compared across stations.