CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

Abstract: CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL

Gas content effects on cavitation number in water in a cavitating venturi

http://deepblue.lib.umich.edu/bitstream/2027.42/5312/5/bac3441.0001.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/5312/4/bac3441.0001.001.tx

Damage of the Endothelial Glycocalyx in Dialysis Patients

Damage to the endothelial glycocalyx, which helps maintain vascular homeostasis, heightens the sensitivity of the vasculature to atherogenic stimuli. Patients with renal failure have endothelial dysfunction and increased risk for cardiovascular morbidity and mortality, but the state of the endothelial glycocalyx in these patients is unknown. Here, we used Sidestream Darkfield imaging to detect changes in glycocalyx dimension in dialysis patients and healthy controls from in vivo recordings of the sublingual microcirculation. Dialysis patients had increased perfused boundary region and perfused diameters, consistent with deeper penetration of erythrocytes into glycocalyx, indicating a loss of glycocalyx barrier properties. These patients also had higher serum levels of the glycocalyx constituents hyaluronan and syndecan-1 and increased hyaluronidase activity, suggesting the shedding of these components. Loss of residual renal function had no influence on the imaging parameters but did associate with greater shedding of hyaluronan in blood. Furthermore, patients with higher levels of inflammation had more significant damage to the glycocalyx barrier. In conclusion, these data suggest that dialysis patients have an impaired glycocalyx barrier and shed its constituents into blood, likely contributing to the sustained endothelial cell activation observed in ESR

Blood pressure response to uncomplicated hemodialysis: the importance of changes in stroke volume

BACKGROUND: The cause of blood pressure (BP) changes during uncomplicated hemodialysis (HD) has not been fully investigated. Controversy exists whether changes in BP result from changes in stroke volume (SV) or total peripheral resistance (TPR). METHODS: We investigated 19 patients using continuous BP monitoring (Portapres) and subsequent Modelflow analysis, yielding continuous SV, cardiac output (CO) and TPR values. Blood volume (BV) monitoring was also performed. For each patient, the sensitivity index (SI) was calculated. The SI is the slope of the curve depicting the relationship between the systolic BP (SBP) response and the BV response. The patients were divided into two groups: group A had an SI >1 which means a decrease in SBP in response to BV change, and group B had an SI <1. In these patients, SBP remained stable despite a BV change. RESULTS: Baseline characteristics and baseline values of all parameters were similar between the groups. In group A, SBP decreased by 25 +/- 19 mm Hg and in group B the SBP increased by 5.0 +/- 29 mm Hg (p < 0.05), while BV change was similar (10.6 +/- 4.9 and 11.2 +/- 4.2%, respectively). The difference in SBP response was caused by a different SV response (group A -44 +/- 16% and group B -26 +/- 18%, p = 0.04), while the TPR response was similar (71 +/- 27% in group A vs. 59 +/- 58% in group B). CONCLUSION: Patients responding with a BP decrease to BV reduction during uncomplicated HD differ in their SV response from patients with a stable B

Influence of four different PTH methods on the classification of chronic kidney disease patients according to the new KDIGO guideline

Secondary hyperparathyroidism develops frequently with chronic kidney disease (CKD) and is associated with poor outcome. The new CKD-MBD guideline, Kidney Disease: Improving Global Outcomes (KDIGO), recommends a target range for PTH which is based on the locally used, upper reference range limit (URL). We examined the impact of the KDIGO guideline on the classification of dialysis patients in two different hospitals using 4 different intact-PTH assays. Blood samples from 76 consecutive hemodialysis CKD patients were measured for PTH concentration. Classification of the patients was performed according to the previous KDOQI and the KDIGO guideline using the manufacturers' and laboratory determined URLs. Classification of patients based on 3 different PTH methods (Siemens ADVIA Centaur, Siemens Immulite 2000, and Beckman Coulter Unicel DxI) was compared with the classification found in another hospital using the Roche Modular E170 PTH assay. Depending on the PTH assay used, between 9 (12%) to 14 (18%) of the patients were classified differently in the two hospitals if the KDOQI guideline was followed. Application of the KDIGO-PTH target range resulted in a similar or decreased number of differently classified patients if the PTH concentration was measured using the Advia Centaur and Immulite assays. With the Beckman Coulter PTH assay, however, the number of differently KDIGO-classified patients increased if the manufacturers' URL (9.3 pmol/L) was used to calculate the PTH-target range. Application of the laboratory determined URL (7.0 pmol/L) improved concordance in classification, although the number of differently classified patients was still higher than with the other PTH assays. The best concordance in classification for the Beckman Coulter assay was found at a PTH value of 6.0 pmol/L. Regarding the Roche and Siemens assays, no significant difference was found in the classification using the URL either determined by the laboratory or the manufacturers. Compared with the KDOQI guideline, the new KDIGO guideline may increase the number of discrepancies in the classification of CKD patients if the Access Beckman Coulter PTH assay is used in conjunction with the calculated target range based on the manufacturers' URL. The best concordance in the classification for the Beckman Coulter assay was found at a PTH value below the manufacturers' and laboratory determined UR

Incremental prognostic value of an abnormal baseline spatial QRS-T angle in chronic dialysis patients

In order to improve the abysmal outcome of dialysis patients, it is critical to identify patients with a high mortality risk. The spatial QRS-T angle, which can be easily calculated from the 12 lead electrocardiogram (ECG), might be useful in the prognostication in dialysis patients. The objective of this study was to establish the prognostic value of the spatial QRS-T angle. All patients who initiated dialysis therapy between 2002 and 2009 in the hospitals of Leiden (LUMC) and Amsterdam (AMC) at least 3 months on dialysis were included. The spatial QRS-T angle was calculated, from a routinely acquired ECG, and its relationship with mortality was assessed. An abnormal spatial QRS-T angle was defined as ≥ 130° in men and ≥ 116° in women. In total, 277 consecutive patients (172 male, mean age 56.3 ± 17.0) were included. An abnormal spatial QRS-T angle was associated with a higher risk of death from all causes [hazard ratio (HR) 2.33; 95% confidence interval (CI) 1.46-3.70] and especially a higher risk of sudden cardiac death (HR 2.99; 95% CI 1.04-8.60). Furthermore, an abnormal spatial QRS-T angle was of incremental prognostic value, when added to a risk model consisting of known risk factors. In chronic dialysis patients the spatial QRS-T angle is a significant and independent predictor of all-cause and especially sudden cardiac death. It implies that this parameter can be used to identify high risk patient

The association between changes in muscle mass and quality of life in patients with metastatic colorectal cancer

Background: Skeletal muscle mass (SMM) loss is common in metastatic colorectal cancer (mCRC) patients and associated with poor clinical outcomes, including increased treatment-related toxicities and reduced survival. Muscle loss may contribute to reduced health-related quality of life (HRQoL), including fatigue. Our aim was to study associations between changes in SMM and concomitant changes in patient-reported HRQoL. Methods: This was a secondary analysis of mCRC patients in the CAIRO3 randomized clinical trial who were—after initial treatment—randomized between maintenance treatment with capecitabine plus bevacizumab (CAP-B) and observation until first disease progression (PD1). Included patients had computed tomography images for SMM quantification, together with HRQoL assessments available at randomization and PD1. Changes in SMM (categorized as >2% loss, stable, and >2% gain) and HRQoL were computed between randomization and PD1. Changes in HRQoL score >10 points were considered clinically relevant. Associations between SMM and HRQoL changes were studied by multiple linear regression models. We also investigated whether associations differed by treatment arm for global health and the 13 other HRQoL subscales. Results: Of 221 patients included (mean age 63.5 ± 8.4 years), 24% lost, 27% remained stable, and 49% gained SMM. At randomization, mean global health status was 73.5 ± 15.9 in the CAP-B arm and 75.1 ± 17.5 in the observation arm (P = 0.48). A stable or gain in SMM was significantly associated with a clinically relevant improvement in global health status (9.9 and 14.7 points, respectively), compared with patients who lost SMM. From the subscales that did not show significant differences between the two treatment arms, we found significant and clinically relevant associations for stable or gain in SMM with improved role functioning (12.0 and 17.9, respectively) and with less fatigue (−10.0 and −15.0, respectively) and pain (−16.3 for SMM gain). From the subscales that did show significantly different associations with SMM between the two treatment arms, we only found significant results in the observation arm. Here, associations were found for stable or gain in SMM with clinically relevant improved physical (12.4 for SMM gain), cognitive (10.7 and 9.7, respectively), and social functioning (15.5 and 15.6, respectively) as well as reduced appetite loss (−28.5 and −30.7, respectively). Conclusions: In mCRC, SMM preservation during CAP-B and observation treatment is associated with significant and clinically relevant improvements in global health status and multiple functional and symptom scales. Studies are warranted to investigate whether interventions targeting SMM lead to improved HRQoL, fewer symptoms, and better functioning

The association between changes in muscle mass and quality of life in patients with metastatic colorectal cancer

Background: Skeletal muscle mass (SMM) loss is common in metastatic colorectal cancer (mCRC) patients and associated with poor clinical outcomes, including increased treatment-related toxicities and reduced survival. Muscle loss may contribute to reduced health-related quality of life (HRQoL), including fatigue. Our aim was to study associations between changes in SMM and concomitant changes in patient-reported HRQoL. Methods: This was a secondary analysis of mCRC patients in the CAIRO3 randomized clinical trial who were—after initial treatment—randomized between maintenance treatment with capecitabine plus bevacizumab (CAP-B) and observation until first disease progression (PD1). Included patients had computed tomography images for SMM quantification, together with HRQoL assessments available at randomization and PD1. Changes in SMM (categorized as >2% loss, stable, and >2% gain) and HRQoL were computed between randomization and PD1. Changes in HRQoL score >10 points were considered clinically relevant. Associations between SMM and HRQoL changes were studied by multiple linear regression models. We also investigated whether associations differed by treatment arm for global health and the 13 other HRQoL subscales. Results: Of 221 patients included (mean age 63.5 ± 8.4 years), 24% lost, 27% remained stable, and 49% gained SMM. At randomization, mean global health status was 73.5 ± 15.9 in the CAP-B arm and 75.1 ± 17.5 in the observation arm (P = 0.48). A stable or gain in SMM was significantly associated with a clinically relevant improvement in global health status (9.9 and 14.7 points, respectively), compared with patients who lost SMM. From the subscales that did not show significant differences between the two treatment arms, we found significant and clinically relevant associations for stable or gain in SMM with improved role functioning (12.0 and 17.9, respectively) and with less fatigue (−10.0 and −15.0, respectively) and pain (−16.3 for SMM gain). From the subscales that did show significantly different associations with SMM between the two treatment arms, we only found significant results in the observation arm. Here, associations were found for stable or gain in SMM with clinically relevant improved physical (12.4 for SMM gain), cognitive (10.7 and 9.7, respectively), and social functioning (15.5 and 15.6, respectively) as well as reduced appetite loss (−28.5 and −30.7, respectively). Conclusions: In mCRC, SMM preservation during CAP-B and observation treatment is associated with significant and clinically relevant improvements in global health status and multiple functional and symptom scales. Studies are warranted to investigate whether interventions targeting SMM lead to improved HRQoL, fewer symptoms, and better functioning