Spatial heterogeneity affects predictions from early-curve fitting of pandemic outbreaks: a case study using population data from Denmark.

The modelling of pandemics has become a critical aspect in modern society. Even though artificial intelligence can help the forecast, the implementation of ordinary differential equations which estimate the time development in the number of susceptible, (exposed), infected and recovered (SIR/SEIR) individuals is still important in order to understand the stage of the pandemic. These models are based on simplified assumptions which constitute approximations, but to what extent this are erroneous is not understood since many factors can affect the development. In this paper, we introduce an agent-based model including spatial clustering and heterogeneities in connectivity and infection strength. Based on Danish population data, we estimate how this impacts the early prediction of a pandemic and compare this to the long-term development. Our results show that early phase SEIR model predictions overestimate the peak number of infected and the equilibrium level by at least a factor of two. These results are robust to variations of parameters influencing connection distances and independent of the distribution of infection rates.

The Influence of Perioperative Fluid Therapy on N-terminal-pro-brain Natriuretic Peptide and the Association With Heart and Lung Complications in Patients Undergoing Colorectal Surgery: Secondary Results of a Clinical Randomized Assessor-blinded Multicenter Trial.

OBJECTIVE: To investigate the influence of intravenous (iv) fluid volumes on the secretion of N-terminal-pro-brain natriuretic peptide (NT-Pro-BNP) in colorectal surgical patients and its association with cardiopulmonary complications (CPC). In addition, to examine if preoperative NT-Pro-BNP can predict the risk for postoperative CPC. METHODS: Blood samples from patients enrolled in a previously published clinical randomized assessor-blinded multicenter trial were analyzed. Included were adult patients undergoing elective colorectal surgery with the American-Society-of-Anesthesiologists-scores of 1-3. Samples from 135 patients were available for analysis. Patients were allocated to either a restrictive (R-group) or a standard (S-group) iv-fluid regimen, commencing preoperatively and continuing until discharge. Blood was sampled every morning until the fourth postoperative day. The primary outcome for this study was NT-Pro-BNP changes and its association with fluid therapy and CPC. RESULTS: The S-group received more iv-fluid than the R-group on the day-of-surgery [milliliter, median (range) 6485 (4401-10750) vs 3730 (2250-8510); P < 0.001] and on the first postoperative day. NT-Pro-BNP was elevated in the S-group compared with the R-group on all postoperative days [area under the curve: median (interquartile range) pg/mL: 3285 (1697-6179) vs 1290 (758-3719); P < 0.001 and in patients developing CPC vs no-CPC (area under the curve), median (interquartile range): 5196 (1823-9061) vs 1934 (831-5301); P = 0.005]. NT-pro-BNP increased with increasing fluid volumes all days (P < 0.003). Preoperative NT-Pro-BNP predicted CPC [odds ratio (confidence interval): 1.573 (0.973-2.541), P = 0.032; positive predictive value = 0.257, negative predictive value = 0.929]. CONCLUSIONS: NT-pro-BNP increases with iv-fluid volumes given to colorectal surgical patients, and the level of NT-Pro-BNP is associated with CPC. Preoperative NT-Pro-BNP is predictive for CPC, but the diagnostic value is low.Clinicaltrials.gov NCT03537989.

Direct observation of multiple conformational states in Cytochrome P450 oxidoreductase and their modulation by membrane environment and ionic strength.

Cytochrome P450 oxidoreductase (POR) is the primary electron donor in eukaryotic cytochrome P450 (CYP) containing systems. A wealth of ensemble biophysical studies of Cytochrome P450 oxidoreductase (POR) has reported a binary model of the conformational equilibrium directing its catalytic efficiency and biomolecular recognition. In this study, full length POR from the crop plant Sorghum bicolor was site-specifically labeled with Cy3 (donor) and Cy5 (acceptor) fluorophores and reconstituted in nanodiscs. Our single molecule fluorescence resonance energy transfer (smFRET) burst analyses of POR allowed the direct observation and quantification of at least three dominant conformational sub-populations, their distribution and occupancies. Moreover, the state occupancies were remodeled significantly by ionic strength and the nature of reconstitution environment, i.e. phospholipid bilayers (nanodiscs) composed of different lipid head group charges vs. detergent micelles. The existence of conformational heterogeneity in POR may mediate selective activation of multiple downstream electron acceptors and association in complexes in the ER membrane.

Constraints on new physics from baryogenesis and Large Hadron Collider data.

We demonstrate the power of constraining theories of new physics by insisting that they lead to electroweak baryogenesis, while agreeing with current data from the Large Hadron Collider. The general approach is illustrated with a singlet scalar extension of the standard model. Stringent bounds can already be obtained, which reduce the viable parameter space to a small island.