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The BICEP/Keck series of experiments target the cosmic microwave background at degree-scale resolution from the South Pole. Over the next few years, the “Stage-3” BICEP Array (BA) telescope will improve the program’s frequency coverage and sensitivity to primordial B-mode polarization by an order of magnitude. The first receiver in the array, BA1, began observing at 30/40 GHz in early 2020. The next two receivers, BA2 and BA3, are currently being assembled and will map the southern sky at frequencies ranging from 95 to 150 GHz. Common to all BA receivers is a refractive, on-axis, cryogenic optical design that focuses microwave radiation onto a focal plane populated with antenna-coupled bolometers. High-performance antireflective coatings up to 760 mm in aperture are needed for each element in the optical chain, and must withstand repeated thermal cycles down to 4 K. Here, we present the design and fabrication of the 30/40 GHz anti-reflection coatings for the recently deployed BA1 receiver, with indices matched to its various polyethylene, nylon and alumina optical components. We describe an epoxy coating technique designed for alumina optics, which achieves better than 80% transmission at room temperature. For polyethylene optical elements, we present a new heat-compression approach that allows low-density polytetrafluoroethylene AR layers to reach sub-percent reflected power. We describe the planned use of these methods for the next BA cryostats, which may inform technological choices for future small-aperture telescopes of the CMB-S4 experiment.

Background: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation. Methods: Patients with stage IV/recurrent NSCLC were randomized 1: 1: 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan. Results: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified. Conclusions: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these

INTRODUCTION: Adjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA. METHODS: Patients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB-IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage. RESULTS: Overall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10-0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13-0.40), regardless of disease stage. CONCLUSIONS: These findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy.

PURPOSE: In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful disease-free survival benefit in completely resected stage IB-IIIA EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA. PATIENTS AND METHODS: Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation. HRQoL (secondary endpoint) was measured using the Short Form-36 (SF-36) health survey at baseline, 12, and 24 weeks, then every 24 weeks until recurrence or treatment completion/discontinuation. Exploratory analyses of SF-36 score changes from baseline until week 96 and time to deterioration (TTD) were performed in the overall population (stage IB-IIIA; N = 682). Clinically meaningful changes were defined using the SF-36 manual. RESULTS: Baseline physical/mental component summary (PCS/MCS) scores were comparable between osimertinib and placebo (range, 46-47) and maintained to Week 96, with no clinically meaningful differences between arms; difference in adjusted least squares (LS) mean [95% confidence intervals (CI), -1.18 (-2.02 to -0.34) and -1.34 (-2.40 to -0.28), for PCS and MCS, respectively. There were no differences between arms for TTD of PCS and MCS; HR, 1.17 (95% CI, 0.82-1.67) and HR, 0.98 (95% CI, 0.70-1.39), respectively. CONCLUSIONS: HRQoL was maintained with adjuvant osimertinib in patients with stage IB-IIIA EGFRm NSCLC, who were disease-free after complete resection, with no clinically meaningful differences versus placebo, further supporting adjuvant osimertinib as a new treatment in this setting. See related commentary by Patil and Bunn, p. 2204.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD(S): This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH<7.3 and a Base Excess<-4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULT(S): We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSION(S): Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction fo

Background: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. Method(s): This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. Result(s): We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. Conclusion(s): Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correctio

Here, we summarize the initial results from the ADAURA clinical study looking at treatment with osimertinib in patients with a specific type of non-small cell lung cancer (also called NSCLC). Osimertinib (TAGRISSO®) is a medication used to treat a type of NSCLC with a change (mutation) in the EGFR gene, known as EGFR-mutated NSCLC. EGFR stands for 'epidermal growth factor receptor'. It is a protein present on the surface of both healthy and cancer cells that can regulate how cells grow and divide. Sometimes, certain mutations in EGFR can result in the EGFR protein malfunctioning, which can lead to the formation of cancer, like EGFR-mutated NSCLC. Based on previous clinical studies, osimertinib is already approved for use in patients with EGFR-mutated NSCLC that has spread beyond the lung (metastatic disease). This medication works to stop, prevent, or slow the growth of EGFR-mutated NSCLC tumors, by specifically blocking the activity of EGFR. In the ADAURA clinical study, participants had resectable EGFR-mutated NSCLC, which means they had tumors that can be removed by surgery. Participants took either osimertinib or a placebo (a dummy drug with no active ingredient) after having their tumors removed by surgery. Post-surgery chemotherapy was allowed, but not compulsory (this was decided by the participant and their doctor). To date, the study has shown that osimertinib could be beneficial for patients with resectable EGFR-mutated NSCLC. Participants who took osimertinib have stayed cancer-free for longer than those who took the placebo, regardless of whether or not they received chemotherapy after surgery. Osimertinib treatment also reduced the risk of tumors spreading to the brain and spinal cord, otherwise known as the central nervous system (also called CNS). The side effects experienced by the participants taking osimertinib have been consistent with what we already know. Based on the results from ADAURA, osimertinib has been approved for the treatment of resect

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for w

This article focused on the research of anaerobic digestion conditions using low-temperature pyrolysis oil, including the fresh inoculum acclimatization, the operation conditions of pyrolysis oil (PO) digestion and the influence of biomass pyrolysis parameters. The coupling process was studied by controlling different pyrolysis parameters and anaerobic digestion parameters. It can be concluded that the fresh sludge inoculum acclimatization can significantly improve the tolerance to the inhibitors contained in the PO, thus, the methane production from the PO digestion to a great degree. The mesophilic condition was favorable to the biooil biomethanation for the low POs under 4% as used in the experiment, whereas the thermophilic condition was favorable for the high PO concentration of 10%. Besides, more methane production can be given by 0.85mm biomass particle size, 300℃ pyrolysis temperature in the downstream step of PO digestion.