Short-term activity cycles impede information transmission in ant colonies.

Rhythmical activity patterns are ubiquitous in nature. We study an oscillatory biological system: collective activity cycles in ant colonies. Ant colonies have become model systems for research on biological networks because the interactions between the component parts are visible to the naked eye, and because the time-ordered contact network formed by these interactions serves as the substrate for the distribution of information and other resources throughout the colony. To understand how the collective activity cycles influence the contact network transport properties, we used an automated tracking system to record the movement of all the individuals within nine different ant colonies. From these trajectories we extracted over two million ant-to-ant interactions. Time-series analysis of the temporal fluctuations of the overall colony interaction and movement rates revealed that both the period and amplitude of the activity cycles exhibit a diurnal cycle, in which daytime cycles are faster and of greater amplitude than night cycles. Using epidemiology-derived models of transmission over networks, we compared the transmission properties of the observed periodic contact networks with those of synthetic aperiodic networks. These simulations revealed that contrary to some predictions, regularly-oscillating contact networks should impede information transmission. Further, we provide a mechanistic explanation for this effect, and present evidence in support of it

Physiological and clinical consequences of relief of right ventricular outflow tract obstruction late after repair of congenital heart defects.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is a common problem after repair of congenital heart disease. Percutaneous pulmonary valve implantation (PPVI) can treat this condition without consequent pulmonary regurgitation or cardiopulmonary bypass. Our aim was to investigate the clinical and physiological response to relieving RVOTO. METHODS AND RESULTS: We studied 18 patients who underwent PPVI for RVOTO (72% male, median age 20 years) from a total of 93 who had this procedure for various indications. All had a right ventricular outflow tract (RVOT) gradient >50 mm Hg on echocardiography without important pulmonary regurgitation (less than mild or regurgitant fraction <10% on magnetic resonance imaging [MRI]). Cardiopulmonary exercise testing, tissue Doppler echocardiography, and MRI were performed before and within 50 days of PPVI. PPVI reduced RVOT gradient (51.4 to 21.7 mm Hg, P<0.001) and right ventricular systolic pressure (72.8 to 47.3 mm Hg, P<0.001) at catheterization. Symptoms and aerobic (25.7 to 28.9 mL.kg(-1).min(-1), P=0.002) and anaerobic (14.4 to 16.2 mL.kg(-1).min(-1), P=0.002) exercise capacity improved. Myocardial systolic velocity improved acutely (tricuspid 4.8 to 5.3 cm/s, P=0.05; mitral 4.7 to 5.5 cm/s, P=0.01), whereas isovolumic acceleration was unchanged. The tricuspid annular velocity was not maintained on intermediate follow-up. Right ventricular end-diastolic volume (99.9 to 89.7 mL/m2, P<0.001) fell, whereas effective stroke volume (43.7 to 48.3 mL/m2, P=0.06) and ejection fraction (48.0% to 56.8%, P=0.01) increased. Left ventricular end-diastolic volume (72.5 to 77.4 mL/m2, P=0.145), stroke volume (45.3 to 50.6 mL/m2, P=0.02), and ejection fraction (62.6% to 65.8%, P=0.03) increased. CONCLUSIONS: PPVI relieves RVOTO, which leads to an early improvement in biventricular performance. Furthermore, it reduces symptoms and improves exercise tolerance. These findings have important implications for the management of this increasingly common condition

Safety of co-administration versus separate administration of the same vaccines in children: a systematic literature review

The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant but complex. We aimed to synthesize the available scientific evidence on the safety of vaccine co-administrations in children by performing a systematic literature review of studies assessing the safety of vaccine co-administrations in children between 1999 and 2019, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty studies compared co-administered vaccines versus the same vaccines administered separately. The most frequently studied vaccines included quadrivalent meningococcal conjugate (MenACWY) vaccine, diphtheria and tetanus toxoids and acellular pertussis (DTaP) or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines, diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b conjugate (DTaP-HepB-IPV/Hib) vaccine, measles, mumps, and rubella (MMR) vaccine, and pneumococcal conjugate 7-valent (PCV7) or 13-valent (PCV13) vaccines. Of this, 16% (n = 8) of the studies reported significantly more adverse events following immunization (AEFI) while in 10% (n = 5) significantly fewer adverse events were found in the co-administration groups. Statistically significant differences between co-administration and separate administration were found for 16 adverse events, for 11 different vaccine co-administrations. In general, studies briefly described safety and one-third of studies lacked any statistical assessment of AEFI. Overall, the evidence on the safety of vaccine co-administrations compared to separate vaccine administrations is inconclusive and there is a paucity of large post-licensure studies addressing this issue

Percutaneous pulmonary valve implantation in humans - Results in 59 consecutive patients

Background - Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life.Methods and Results - Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n = 36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n = 8). The right ventricular (RV) pressure (64.4 +/- 17.2 to 50.4 +/- 14 mm Hg, P < 0.001), RVOT gradient (33 +/- 24.6 to 19.5 +/- 15.3, P < 0.001), and pulmonary regurgitation ( PR) (grade 2 of greater before, none greater than grade 2 after, P < 0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21 +/- 13% versus 3 +/- 4%, P < 0.001) and in RV end-diastolic volume (EDV) (94 +/- 28 versus 82 +/- 24 mL (.) beat(-1) (.) m(-2), P < 0.001) and a significant increase in left ventricular EDV ( 64 +/- 12 versus 71 +/- 13 mL (.) beat(-1.) m(-2), P = 0.005) and effective RV stroke volume ( 37 +/- 7 versus 42 +/- 9 mL (.) beat(-1) (.) m(-2), P = 0.006) in 28 patients (age 19 +/- 8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in V(O2)max (26 +/- 7 versus 29 +/- 6 mL (.) kg(-1) (.) min(-1), P < 0.001). There was no mortality.Conclusions - PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity

Guidance for the collection of case report form variables to assess safety in clinical trials of vaccines in pregnancy.

Vaccination in pregnancy is an effective strategy to prevent serious infections in mothers and their infants. Safety of this strategy is of principal importance to all stakeholders. As the number of studies assessing safety of vaccines in pregnancy increases, the need to ensure consistent collection and reporting of critical data to allow comparisons and data pooling becomes more important. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project aims to improve data collection and create a shared understanding of maternal, fetal and neonatal outcomes in order to progress the global agenda for vaccination in pregnancy. The guidance in this document has been developed to harmonize the data collected in case report forms used for safety monitoring in clinical trials of vaccination in pregnant women. Data to be collected is prioritized to allow applicability in diverse research settings, including low and middle-income countries. Standardized data will enable the research community to have a common base upon which to conduct meta-analyses, strengthening the applicability of outcomes to different settings

Evolutionary Interactions between N-Linked Glycosylation Sites in the HIV-1 Envelope

The addition of asparagine (N)-linked polysaccharide chains (i.e., glycans) to the gp120 and gp41 glycoproteins of human immunodeficiency virus type 1 (HIV-1) envelope is not only required for correct protein folding, but also may provide protection against neutralizing antibodies as a “glycan shield.” As a result, strong host-specific selection is frequently associated with codon positions where nonsynonymous substitutions can create or disrupt potential N-linked glycosylation sites (PNGSs). Moreover, empirical data suggest that the individual contribution of PNGSs to the neutralization sensitivity or infectivity of HIV-1 may be critically dependent on the presence or absence of other PNGSs in the envelope sequence. Here we evaluate how glycan–glycan interactions have shaped the evolution of HIV-1 envelope sequences by analyzing the distribution of PNGSs in a large-sequence alignment. Using a “covarion”-type phylogenetic model, we find that the rates at which individual PNGSs are gained or lost vary significantly over time, suggesting that the selective advantage of having a PNGS may depend on the presence or absence of other PNGSs in the sequence. Consequently, we identify specific interactions between PNGSs in the alignment using a new paired-character phylogenetic model of evolution, and a Bayesian graphical model. Despite the fundamental differences between these two methods, several interactions are jointly identified by both. Mapping these interactions onto a structural model of HIV-1 gp120 reveals that negative (exclusive) interactions occur significantly more often between colocalized glycans, while positive (inclusive) interactions are restricted to more distant glycans. Our results imply that the adaptive repertoire of alternative configurations in the HIV-1 glycan shield is limited by functional interactions between the N-linked glycans. This represents a potential vulnerability of rapidly evolving HIV-1 populations that may provide useful glycan-based targets for neutralizing antibodies

Error Thresholds on Dynamic Fittness-Landscapes

In this paper we investigate error-thresholds on dynamics fitness-landscapes. We show that there exists both lower and an upper threshold, representing limits to the copying fidelity of simple replicators. The lower bound can be expressed as a correction term to the error-threshold present on a static landscape. The upper error-threshold is a new limit that only exists on dynamic fitness-landscapes. We also show that for long genomes on highly dynamic fitness-landscapes there exists a lower bound on the selection pressure needed to enable effective selection of genomes with superior fitness independent of mutation rates, i.e., there are distinct limits to the evolutionary parameters in dynamic environments.Comment: 5 page

COVID-19 infectivity profile correction

The infectivity profile of an individual with COVID-19 is attributed to the paper Temporal dynamics in viral shedding and transmissibility of COVID-19 by He et al., published in Nature Medicine in April 2020. However, the analysis within this paper contains a mistake such that the published infectivity profile is incorrect and the conclusion that infectiousness begins 2.3 days before symptom onset is no longer supported. In this document we discuss the error and compute the correct infectivity profile. We also establish confidence intervals on this profile, quantify the difference between the published and the corrected profiles, and discuss an issue of normalisation when fitting serial interval data. This infectivity profile plays a central role in policy and decision making, thus it is crucial that this issue is corrected with the utmost urgency to prevent the propagation of this error into further studies and policies. We hope that this preprint will reach all researchers and policy makers who are using the incorrect infectivity profile to inform their work.Comment: 5 pages, 2 figure

Theory of nuclear spin conversion in ethylene

First theoretical analysis of the nuclear spin conversion in ethylene molecules (13^CCH4) has been performed. The conversion rate was found equal approx. 3x10^{-4} 1/s*Torr, which is in qualitative agreement with the recently obtained experimental value. It was shown that the ortho-para mixing in 13^CCH4 is dominated by the spin-rotation coupling. Mixing of only two pairs of ortho-para levels were found to contribute significantly to the spin conversion.Comment: 20 pages, 5 eps figure

Antibiotic-Resistant Neisseria gonorrhoeae Spread Faster with More Treatment, Not More Sexual Partners.

The sexually transmitted bacterium Neisseria gonorrhoeae has developed resistance to all antibiotic classes that have been used for treatment and strains resistant to multiple antibiotic classes have evolved. In many countries, there is only one antibiotic remaining for empirical N. gonorrhoeae treatment, and antibiotic management to counteract resistance spread is urgently needed. Understanding dynamics and drivers of resistance spread can provide an improved rationale for antibiotic management. In our study, we first used antibiotic resistance surveillance data to estimate the rates at which antibiotic-resistant N. gonorrhoeae spread in two host populations, heterosexual men (HetM) and men who have sex with men (MSM). We found higher rates of spread for MSM (0.86 to 2.38 y-1, mean doubling time: 6 months) compared to HetM (0.24 to 0.86 y-1, mean doubling time: 16 months). We then developed a dynamic transmission model to reproduce the observed dynamics of N. gonorrhoeae transmission in populations of heterosexual men and women (HMW) and MSM. We parameterized the model using sexual behavior data and calibrated it to N. gonorrhoeae prevalence and incidence data. In the model, antibiotic-resistant N. gonorrhoeae spread with a median rate of 0.88 y-1 in HMW and 3.12 y-1 in MSM. These rates correspond to median doubling times of 9 (HMW) and 3 (MSM) months. Assuming no fitness costs, the model shows the difference in the host population's treatment rate rather than the difference in the number of sexual partners explains the differential spread of resistance. As higher treatment rates result in faster spread of antibiotic resistance, treatment recommendations for N. gonorrhoeae should carefully balance prevention of infection and avoidance of resistance spread