790-2 Baseline Electrocardiogram Predicts 30-day Mortality Among 32,812 Patients with Acute Myocardial Infarction Treated with Thrombolysis

To determine the initial electrocardiographic variables predictive of survival among patients with acute myocardial infarction, we analyzed the baseline 12-lead ECGs in 32,812 patients enrolled into the GUSTO trial. All patients had≥0.1mV of ST segment elevation in at least one lead and received thrombolytic therapy. Those with LBBB or ventricular rhythm were excluded from analysis. Clinical follow-up was > 99.5% complete. 2218 (6.8%) patients died within 30 days of the initial ECG. Death within 30 days was more common in patients with RBBB (17%), LAFB (14%), and LPFB (17%), than in those with a normal conduction pattern (6%). Patients with ECG evidence of previous MI in a location distinct from the acute MI had a higher risk of death (9.8% vs. 5.9%) than those without prior infarction (p<0.0001). The variable having the greatest univariate predictive power for 30-day survival was the sum of the absolute ST-segment deviation in each lead (x2=341), as shown in the following mortality curve.Other ST segment variables that predicted 30-day survival were the sum of ST-segment elevation in each lead (x2=287). the maximum ST elevation in anyone lead (X2=257), and the number of leads with ST elevation (x2=250). When multivariate modeling was performed the sum of the absolute ST deviations, number of leads with ST elevation, prior ECG MI, RBBB, and LAFB each added independent prognostic information.We conclude that an ECG at the time of presentation contains substantial prognostic information which can be used to help stratify risk among thrombelytic-treated patients with acute myocardial infarction

The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease

BACKGROUND: The R47H variant of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) confers greatly increased risk for Alzheimer's disease (AD), reflective of a central role for myeloid cells in neurodegeneration. Understanding how this variant confers AD risk promises to provide important insights into how myeloid cells contribute to AD pathogenesis and progression. METHODS: In order to investigate this mechanism, CRISPR/Cas9 was used to generate a mouse model of AD harboring one copy of the single nucleotide polymorphism (SNP) encoding the R47H variant in murine Trem2. TREM2 expression, myeloid cell responses to amyloid deposition, plaque burden, and neuritic dystrophy were assessed at 4 months of age. RESULTS: AD mice heterozygous for the Trem2 R47H allele exhibited reduced total Trem2 mRNA expression, reduced TREM2 expression around plaques, and reduced association of myeloid cells with plaques. These results were comparable to AD mice lacking one copy of Trem2. AD mice heterozygous for the Trem2 R47H allele also showed reduced myeloid cell responses to amyloid deposition, including a reduction in proliferation and a reduction in CD45 expression around plaques. Expression of the Trem2 R47H variant also reduced dense core plaque number but increased plaque-associated neuritic dystrophy. CONCLUSIONS: These data suggest that the AD-associated TREM2 R47H variant increases risk for AD by conferring a loss of TREM2 function and enhancing neuritic dystrophy around plaques

Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections

Application of single-molecule switching nanoscopy (SMSN) beyond the coverslip surface poses substantial challenges due to sample-induced aberrations that distort and blur single-molecule emission patterns. We combined active shaping of point spread functions and efficient adaptive optics to enable robust 3D-SMSN imaging within tissues. This development allowed us to image through 30-μm-thick brain sections to visualize and reconstruct the morphology and the nanoscale details of amyloid-β filaments in a mouse model of Alzheimer's disease

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

A Joint Fermi-GBM and Swift-BAT Analysis of Gravitational-wave Candidates from the Third Gravitational-wave Observing Run

We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift- BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers