High-altitude erythrocytosis: mechanisms of adaptive and mal-adaptive responses

Erythrocytosis, or increased production of red blood cells, is one of the most well-documented physiological traits that varies within and among in high-altitude populations. Although a modest increase in blood O2-carrying capacity may be beneficial for life in highland environments, erythrocytosis can also become excessive and lead to maladaptive syndromes such as Chronic Mountain Sickness (CMS).

The Effects of Tax Penalty on Retained Earnings: Evidence from Quasi-Natural Experiment in South Korea

This paper evaluated how the tax penalty, corporate income feedback tax (CIFT), on retained earnings affected firms’ managerial decisions in South Korea. We focused on how the firms allocated the retained earnings to minimize the additional tax liability. We employed a quasi-natural experiment design resulting from the enactment of the CIFT in 2015 to identify how the tax penalty on earning retention affected investment, dividend, and employment. We took advantage of the eligibility condition of the CIFT to construct a quasi-natural experimental design. Our estimation results show that most firms subject to the CIFT paid out dividends to equity holders to avoid additional tax liabilities despite of modest increase of investment. They did not change wages much. Rather, they decreased wage payment. In sum, the CIFT was not as successful as Korean government wished.

Employment changes during the COVID-19-pandemic and mental health: Evidence from a longitudinal study

We report on how changes in employment during the COVID-19 pandemic affected mental health using a large Norwegian longitudinal study. In addition to showing a modest increase in symptoms of depression in the full sample, we find a substantially stronger increase in depressive symptoms among those experiencing job loss. We also present evidence on the heterogeneity of the effect across socioeconomic status, and find that while the highest educated men had the lowest risk of job loss, highly educated women experienced the strongest deterioration of mental health following job loss. Last, we investigate the mechanism and find suggestive evidence that economic worries play an important role.

Structural and Biochemical Rationale for Enhanced Spike Protein Fitness in Delta and Kappa SARS-CoV-2 Variants

The Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this study, we assess structural and biochemical aspects of viral fitness for these two variants using cryo-electron microscopy (cryo-EM), ACE2-binding and antibody neutralization analyses. Both variants demonstrate escape of antibodies targeting the N-terminal domain, an important immune hotspot for neutralizing epitopes. Compared to wild-type and Kappa lineages, Delta variant spike proteins show modest increase in ACE2 affinity, likely due to enhanced electrostatic complementarity at the RBD-ACE2 interface, which we characterize by cryo-EM. Unexpectedly, Kappa variant spike trimers form a novel head-to-head dimer-of-trimers assembly, which we demonstrate is a result of the E484Q mutation. The combination of increased antibody escape and enhanced ACE2 binding provides an explanation, in part, for the rapid global dominance of the Delta variant.

In Defense of Limited Manufacturing Cost Control: Disciplining Acquisition of Private information by Suppliers

When a firm's input supplier can acquire and misreport private information to gain an edge in negotiations, we show that the firm can blunt the supplier's informational advantage by permitting inefficiencies in its own internal production. Specifically, we establish that a modest increase in the cost of the input(s) a firm makes internally credibly commits it to be more aggressive in negotiations with a supplier for the input(s) the firm buys. Recognizing that its potential information rents will be limited, the supplier, in turn, becomes less aggressive in information acquisition. The paper fully characterizes the equilibrium - the firm's investments, the supplier's information acquisition and reporting decisions, and the terms of trade - to demonstrate that often-maligned internal bloat can be an endogenous facilitator of efficient outsourcing.

1397. Long term impact of the 13-valent pneumococcal conjugate vaccine use in infant immunization program on all-cause pneumonia hospitalizations in British Columbia, Canada: a time series analysis

Background Pneumonia is a leading cause of hospitalization and in-patient mortality globally. We determined the impact of 13-valent pneumococcal conjugate vaccine (PCV13) use on all-cause pneumonia hospitalization rates eight years after the vaccine was introduced in British Columbia, Canada. Methods Routine administrative databases, such as, hospital discharge abstract databases, registry and demographics were used to build the cohort. Overall and age-specific all-cause pneumonia hospital admissions per month (Jan 2000 to Dec 2018) for those aged < 2 years, 2-5 years, 6-17 years, 18-64 years and ≥ 65 years were obtained using International Classification of Diseases 9 and 10 codes (480-486, J12-J18). Changes in the all-cause pneumonia hospitalization incidence rates before and after the PCV13 vaccine program introduction were evaluated using a negative binomial regression and time-series modelling while adjusting for seasonality, influenza-likeness illnesses, 7-valent pneumococcal conjugate vaccine (PCV7) program and pre-PCV13 vaccine secular trends. Results Long term use of the PCV13 vaccine in the infant immunization program was associated with significant declines in all-cause pneumonia hospitalization rates among all children, < 2 years (IRR: 0.63; 95% Confidence Interval (CI): 0.59-0.67), 2-5 years (IRR: 0.82; 95%CI: 0.77-0.87) and 6-17 years (IRR: 0.73; 95%CI: 0.69-0.78). All-cause pneumonia rates did not change significantly in those aged 18-64 years (IRR: 0.98; 95%CI: 0.96-1), whereas a modest increase was observed in those 65 years and over (IRR: 1.05; 95%CI: 1.02-1.07). Consequently, we did not observe significant change in the overall rate (IRR: 1.02; 95%CI: 1-1.02). Conclusion Significant reduction in all-cause pneumonia hospitalization rates in children demonstrates long term beneficial effect of PCV13 use. A modest increase in all-cause pneumonia hospitalization rates in adults aged 65 years and over indicates a need for further microbial investigation. Disclosures Nirma Khatri Vadlamudi, BA, BS, MPH, Pfizer Inc (Research Grant or Support) Fawziah Marra, BSc (Pharm), PharmD, Pfizer Inc (Research Grant or Support)

Faster Montgomery and double-add ladders for short Weierstrass curves

The Montgomery ladder and Joye ladder are well-known algorithms for elliptic curve scalar multiplication with a regular structure. The Montgomery ladder is best known for its implementation on Montgomery curves, which requires 5M+4S+1m+8A per scalar bit, and 6 field registers. Here (M, S,m,A) represent respectively field Multiplications, Squarings, multiplications by a curve constant, and Additions or subtractions. This ladder is also complete, meaning that it works on all input points and all scalars. Many protocols do not use Montgomery curves, but instead use prime-order curves in short Weierstrass form. These have historically been much slower, with ladders costing at least 14 multiplications or squarings per bit: 8M + 6S + 27A for the Montgomery ladder and 8M+ 6S + 30A for the Joye ladder. In 2017, Kim et al. improved the Montgomery ladder to 8M+ 4S + 12A + 1H per bit using 9 registers, where the H represents a halving. Hamburg simplified Kim et al.’s formulas to 8M+ 4S + 8A + 1H per bit using 6 registers. Here we present improved formulas which compute the Montgomery ladder on short Weierstrass curves using 8M+ 3S + 7A per bit, and requiring 6 registers. We also give formulas for the Joye ladder that use 9M+3S+7A per bit, requiring 5 registers. One of our new formulas supports very efficient 4-way vectorization. We also discuss curve invariants, exceptional points, side-channel protection and how to set up and finish these ladder operations. Finally, we show a novel technique to make these ladders complete when the curve order is not divisible by 2 or 3, at a modest increase in cost. A sample implementation of these techniques is given in the supplementary material, also posted at https://github.com/bitwiseshiftleft/ladder_formulas

Education May Increase Emissions but Mitigate Human Cost of Climate Change

Increasing education in the developing world could lead to a modest increase in carbon emissions due to economic growth, but education could also reduce the negative impact of climate change on vulnerable populations.