IgE in the diagnosis and treatment of allergic disease

Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the “allergic” disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow’s milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response

Sub-lunar Tap Yielding eXplorer (STYX) & Surface Telemetry Operations and Next-generation Excavation System (STONES)

The NASA RASC-AL Moon to Mars competition challenges student teams to develop a lightweight, durable, and hands-off method for extracting water from Martian/lunar subsurface ice layers while mapping soil density profiles. Future interplanetary expeditions are dependent on the availability of clean water and this project aims to accomplish this task. The challenge description enumerates several criteria to be met for successful designs. For further information, the STYX & STONES team conducted research on Cal Poly’s competition project from last year to consider the areas for redesign. As such, the team has utilized the background research from relevant patents and journal articles to consider brainstorming potentially viable solutions. Based on these solutions for each subsystem, the team converged the ideas using a series of decision matrices into a final design direction. In addition to reviewing the STYX design, several new considerations were made for the scope of this project. Primarily, this year’s team focused on developing a prototype that has the capability of operating in an extraterrestrial environment and thoroughly fulfilling the requirements posed by NASA. To visualize the requirements, the team created a list of customer needs, a House of Quality diagram, and an engineering specifications table. Additionally, the STYX & STONES team discussed the design process it plans to follow including major project milestones. Specifically, the team plans to excel in collecting more than five quarts of water autonomously while successfully identifying the overburden layers – tasks that previous teams have struggled with. The team’s design direction includes two main components: a masonry drill bit and an auger- heater probe hybrid tool. The masonry drill bit will create a hole in the overburden using the force from a rotary hammer. The heater probe tool will then be moved to align with the hole and be driven into the loosened overburden using the force of a small gear motor. The heater probe will then melt ice using a hot waterjet and deliver water via a peristaltic pump and a two-stage filtration system. To verify the design, the team completed a multitude of analyses and tests for each subsystem and the prototype as a whole. Through drilling tests, the team found that the rotary hammer and masonry bit can easily cut through all overburden layers while keeping weight on bit (WOB) below 150N. Similarly, the load cells attached to the drill carriage were tested and proven to be accurate at recording WOB data and providing feedback to the controller to monitor WOB. Furthermore, the load cells proved successful at recording accurate WOB data that can be analyzed to determine overburden composition. The pumping system was also tested and was capable of effectively moving water through all filters and delivering fluid to the waterjet. More tests were completed to verify the heater probe tool; these tests included controlling heater temperature, melting ice, expelling water through the waterjet, and removing loose material from the hole. To verify the design requirements, the team has completed analysis pertaining to each subsystem including the drill, heater probe, frame, and control systems. The team is confident in the drilling design based on testing and vibrations analysis. In the same manner, the team verified that the 12V peristaltic pump will have enough pressure head rise based on analysis and prototype testing. Using the prototype heater probe as a reference, the team fully characterized the heat transfer parameters of the final design and is confident the auger will be effective considering surrounding debris. Finally, the team tested the water jet design using 120oF water which provided optimistic results that the water jet will significantly expand the melt radius per hole. As a next step, the team will be testing the mechanical and controls systems simultaneously using manufactured parts. The following report details the subsystems and relevant information

Asymmetries in adaptive optics point spread functions

An explanation for the origin of asymmetry along the preferential axis of the PSF of an AO system is developed. When phase errors from high altitude turbulence scintillate due to Fresnel propagation, wavefront amplitude errors may be spatially offset from residual phase errors. These correlated errors appear as asymmetry in the image plane under the Fraunhofer condition. In an analytic model with an open-loop AO system, the strength of the asymmetry is calculated for a single mode of phase aberration, which generalizes to two dimensions under a Fourier decomposition of the complex illumination. Other parameters included are the spatial offset of the AO correction, which is the wind velocity in the frozen flow regime multiplied by the effective AO time delay, and propagation distance or altitude of the turbulent layer. In this model, the asymmetry is strongest when the wind is slow and nearest to the coronagraphic mask when the turbulent layer is far away, such as when the telescope is pointing low towards the horizon. A great emphasis is made about the fact that the brighter asymmetric lobe of the PSF points in the opposite direction as the wind, which is consistent analytically with the clarification that the image plane electric field distribution is actually the inverse Fourier transform of the aperture plane. Validation of this understanding is made with observations taken from the Gemini Planet Imager, as well as being reproducible in end-to-end AO simulations

Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing Percutaneous Coronary Intervention:The ROCKET AF Trial

AbstractObjectivesThe authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).BackgroundThe frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown.MethodsThe study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial.ResultsAmong 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups.ConclusionsIn patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Left ventricular function, congestion, and effect of empagliflozin on heart failure risk after myocardial infarction

Background Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). Objective To evaluate the association between left ventricular ejection fraction (LVEF), congestion, or both on outcomes and the impact of empagliflozin in reducing HF risk post-MI. Methods In the EMPACT-MI trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF&lt;45%, congestion, or both to empagliflozin 10 mg daily or placebo and followed for a median of 17.9 months. Results Among 6522 patients, the mean baseline LVEF was 41%+9%; 2648 patients (40.6%) presented with LVEF&lt;45% alone, 1483 (22.7%) presented with congestion alone, and 2181 (33.4%) presented with both. Among patients in the placebo arm, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (hazard ratio [HR] 1.49; 95%CI, 1.31-1.69; P&lt;0.0001), first HF hospitalization (HR, 1.64; 95%CI, 1.37-1.96; P&lt;0.0001), and total HF hospitalizations (rate ratio [RR], 1.89; 95%CI, 1.51-2.36; P&lt;0.0001). Presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR 1.52, 1.94, and RR 2.03, respectively). Empagliflozin reduced the risk for first (HR 0.77, 95%CI 0.60-0.98) and total (RR 0.67, 95%CI 0.50-0.89) HF hospitalization, irrespective of LVEF or congestion or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. Conclusions In patients with AMI, severity of LV dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion

Effect of empagliflozin on heart failure outcomes after acute myocardial infarction: insights from the EMPACT-MI trial

Background: Empagliflozin reduces the risk of heart failure events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, and in those with prevalent heart failure irrespective of ejection fraction. While EMPACT-MI showed empagliflozin does not reduce the risk of the composite of hospitalization of heart failure and all-cause mortality, the impact of empagliflozin on first and recurrent heart failure events in patients after myocardial infarction is unknown. Methods: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for heart failure based on newly developed left ventricular ejection fraction of &lt;45% and/or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for heart failure outcomes. Results: Over a median of follow-up of 17.9 months, the risk for first heart failure hospitalization and total heart failure hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 (3.6%) vs. 153 (4.7%) patients with events, HR 0.77 [95% CI 0.60, 0.98], P=0.031 for first heart failure hospitalization and 148 vs. 207 events, RR 0.67 [95% CI 0.51, 0.89], P=0.006 for total heart failure hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total heart failure hospitalizations. Post-discharge need for new use of diuretics, renin-angiotensin modulators, and mineralocorticoid receptor antagonists were less in patients randomized to empagliflozin than placebo (all p&lt;0.05). Conclusions: In patients after acute myocardial infarction with left ventricular dysfunction or congestion, empagliflozin reduced the risk of heart failure

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure