The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Black Queen rule

The nature and dynamics of mutations associated with the emergence, spread and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant (Marseille-4) for 10 months since its onset in July 2020. Here, we analysed and classified into subvariants and lineages 7,453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1+/-1.4 months, during which 4.1+/-2.6 mutations accumulated. Growth rate was 0.079+/-0.045, varying from 0.010 to 0.173. All the lineages exhibited a gamma distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marseille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in several mink lineages and in the alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.

Cost-effectiveness of meningococcal vaccination of infants in the Russian Federation

Generalized forms of invasive meningococcal desease (IMD) are very dangerous because they have a high mortality rate.The aim of the work was to assess the cost-effectiveness of meningococcal vaccination of infants with the 4-valent MenACWY-D conjugate vaccine in the Russian Federation.Material and methods. Cost-effectiveness analysis based on epidemiological data for the Russian Federation was carried out by a modeling method with a horizon of 80 years from the position of the healthcare system and taking into account the social perspective. Vaccination costs were calculated on the basis of the registered price of the vaccine, including VAT, the costs of GFMI therapy and patient rehabilitation – based on the compulsory medical insurance tariffs in St. Petersburg for 2021. Indirect costs due to temporary disability of patients’ parents, disability of patients and premature death were estimated by the lost GDP. In the base case, costs were discounted by 3,5% per year, life expectancy – by 1,5% per year.Results. Given the assumptions made, the average lifetime burden of a child’s illness is 17,556 million rubles. (no discounting). In the base case, the incremental cost per LYG from the payer perspective – 7,821 million rubles, and from the social perspective – 3,328 million rubles. Incremental cost per QALY – 5,350 million rubles and 2,277 million rubles, respectively. The most important factors that have a significant impact on the cost-effectiveness of vaccination are the incidence of IMD, the price of the vaccine, and the value of the discounting of costs and life expectancy.Conclusions. Given the assumptions made, meningococcal vaccination of infants with 4-valent meningococcal vaccine can be considered as a viable option.

Determining the main criteria for selecting appropriate methods for repair and maintenance of commercial real estate in Iran

Purpose The average lifetime of a building in Iran is only one-quarter of the reported global average lifespan. A major reason why buildings in Iran have shorter service life is attributed to the inappropriate selection of the facility repair and maintenance (R&M) methods. Hence, selecting the appropriate R&M methods is critical in upholding or even extending the lifespan of the building. The purpose of this paper is to determine the main criteria for selecting the suitable R&M methods of commercial real estate (CRE) in Iran as a major challenge encountered by the Iranian construction industry. Design/methodology/approach The total number of identified criteria (related to the selection of the suitable R&M methods) is 16, which is divided into five clusters (referred as main criteria in this study): human resources; flexibility and technical capability; safety and risk; cost of maintenance; and facilities and technology. To analyze the identified criteria, the expert opinions were collected through both face-to-face interviews and distribution of Delphi survey questionnaires. A total of 12 industrial experts in the construction industry were invited to participate in a Delphi survey to solicit their perceptions and opinions on the identified criteria in this research. Findings The findings indicated that, among the five main criteria, the cost of maintenance is the most important criteria for selecting appropriate R&M methods of CRE in Iran. In addition, the criterion of facilities and technology was recognized as the least important among the main criteria. Originality/value The research, significantly, justified the configuration of non-compliance with the practice and its deliverables and developed a diagnostic study on the grounds of failure in the Iranian construction industry regarding the issues which are threatening the expected and desirable outcomes. The research achievements and suggested effective recommendations can serve as a useful policy and consultative instrument for the relevant stakeholders in the construction industry engaged in building R&M work.

Development and Validation of A Long-Term Incident Heart Failure Risk Model

Background: Average lifetime risk for heart failure (HF) is high, but differs significantly across and within sex-race groups. No models for estimating long-term risk for HF exist, which would allow for earlier identification and interventions in high-risk subsets. The authors aim to derive 30-year HF risk equations. Methods: Adults between the ages of 20 to 59 years and free of cardiovascular disease at baseline from 5 population-based cohorts were included. Among 24,838 participants (55% women, 25% Black based on self-report), follow-up consisted of 599,551 person-years. Sex- and race-specific 30-year HF risk equations were derived and validated accounting for competing risk of non-HF death. HF was based on a clinical diagnosis. Model discrimation and calibration were assessed using 10-fold cross-validation. Finally, the model was applied to varying risk factor patterns for systematic examination. Results: The rate of incident HF was 4.0 per 1000 person-years. Harrell's c statistics were 0.82 (0.80-0.83) and 0.84 (0.82-0.85) in White and Black men, and 0.84 (0.82-0.85) and 0.85 (0.83-0.87) in White and Black women, respectively. Hosmer-Lemeshow calibration was acceptable, with x 2 <30 in all subgroups. Risk estimation varied across sex-race groups: for example, in an average 40-year-old non-smoker with an untreated systolic blood pressure of 140 mm Hg and body mass index of 30 kg/m 2 , risk was estimated to be 22.8% in a Black man, 13.7% in a White man, 13.0% in a Black woman, and 12.1% in a White woman. Conclusions: Sex- and race-specific equations for prediction of long-term risk of HF demonstrated high discrimination and adequate calibration.

Value and Cost Savings From Access to Multi-disciplinary Rehabilitation Services After Severe Acquired Brain Injury

Acquired brain injury (ABI) is a major global public health problem and source of disability. A major contributor to disability after severe ABI is limited access to multidisciplinary rehabilitation, despite evidence of sustained functional gains, improved quality of life, increased return-to-work, and reduced need for long-term care. A societal model of value in rehabilitation matches patient and family expectations of outcomes and system expectations of value for money. A policy analysis of seven studies (2009–2019) exploring outcomes and cost-savings from access to multi-disciplinary rehabilitation identified average lifetime savings of $1.50M per person, with costs recouped within 18 months.Recommendations: Increase access to multi-disciplinary rehabilitation following severe ABI; strengthen prevention focus; increase access to case management; support return-to-work; and systematically collect outcome and cost data.

Characterization and Lifetime Dietary Risk Assessment of Eighteen Pyrrolizidine Alkaloids and Pyrrolizidine Alkaloid N-Oxides in New Zealand Honey

Pyrrolizidine alkaloids (PAs) are a large group of botanical toxins of concern, as they are considered genotoxic carcinogens, with long-term dietary exposure presenting an elevated risk of liver cancer. PAs can contaminate honey through honeybees visiting the flowers of PA-containing plant species. A program of monitoring New Zealand honey has been undertaken over several years to build a comprehensive dataset on the concentration, regional and seasonal distribution, and botanical origin of 18 PAs and PA N-oxides. A bespoke probabilistic exposure model has then been used to assess the averaged lifetime dietary risk to honey consumers, with exposures at each percentile of the model characterized for risk using a margin of exposure from the Joint World Health Organization and United Nations Food and Agriculture Organization Expert Committee on Food Additives (JECFA) Benchmark Dose. Survey findings identify the typical PA types for New Zealand honey as lycopsamine, echimidine, retrorsine and senecionine. Regional and seasonal variation is evident in the types and levels of total PAs, linked to the ranges and flowering times of certain plants. Over a lifetime basis, the average exposure an individual will receive through honey consumption is considered within tolerable levels, although there are uncertainties over high and brand-loyal consumers, and other dietary contributors. An average lifetime risk to the general population from PAs in honey is not expected. However, given the uncertainties in the assessment, risk management approaches to limit or reduce exposures through honey are still of value.

Average Lifetime Hemoglobin Concentration Improves Prediction of Cognitive Outcomes in Pediatric Patients with Sickle Cell Anemia

Background: Sickle cell anemia (SCA) is associated with cognitive challenges that often worsen as children age. Previous work has established relationships between hematological markers of disease severity (i.e., hemoglobin concentration) and various neurological outcomes, including cognitive impairment. However, most studies have related static, often isolated hemoglobin concentration (Hb) values obtained from a single time-point closest to data collection. Studies of pediatric patients with phenylketonuria and Type I diabetes have demonstrated that longitudinal change and variability in phenylalanine and glucose, respectively, are better indicators of neurological and cognitive outcomes than a single value alone. Our study aimed to be the first study of pediatric patients with SCA to examine the extent to which indices of Hb control (e.g., lifetime average and variability), collected routinely in this patient group, may provide additional prognostic information. Methods: Data were collected from pediatric patients (aged 4-18 years at enrolment) with and without SCA enrolled on the Sleep Asthma Cohort-III (SAC-III) follow-up study. SAC is a mixed retrospective-prospective study assessing the impact of nocturnal oxygen desaturation on SCA complications. The present investigation assessed participants (see Figure 1 for complete participant demographics) who underwent cognitive evaluation using Wechsler scales measuring domains of IQ, processing speed (i.e., processing speed index [PSI] and Cancellation subtest), and executive function (working memory index [WMI]). Participant demographics and appropriate medical data and history (i.e., hydroxyurea therapy, silent infarction) were obtained via questionnaires and analysis of medical records. Hb (d/L) measures assessed included average lifetime values (i.e., mean and median), variability over the lifetime (i.e., standard deviation), and the single value obtained closest to data collection. Results: Correlation analyses indicated a strong positive relationship between the mean and median Hb values along with large positive associations between the average and contemporaneous values. Small non-significant correlations were demonstrated between variability and average Hb values (see Figure 1). Initial hierarchical linear regression analyses demonstrated that neither hydroxyurea use nor silent infarct (SCI) status were predictors of any cognitive outcomes or Hb values, so they were not included in any further analyses. Separate regression analyses for each cognitive outcome found that mean lifetime Hb values was the only significant predictor of IQ (p = .04, η 2 = .13) and the Cancellation subtest (p = .005, η 2 = .22). Mean lifetime Hb values approached significance for PSI (p = .09, η 2 = .08), but was not a predictor for WMI (p = .33, η 2 = .03). Conclusion: Our study demonstrated that despite strong correlations between Hb obtained closest to testing and average lifetime values (i.e., rs = .64 and .69), only lifetime Hb predicted cognitive outcomes, particularly processing speed scores from the Cancellation subtest. Variability was not strongly related to other indices of Hb control and did not predict any cognitive outcomes. These results mirror those obtained from other pediatric populations indicating that static, one time values may not best represent clinical manifestations of chronic illness, and the choice of Hb value can differentially influence research study results and clinical prognosis. Future longitudinal work in larger samples is needed, but Hb obtained over the lifetime appears to provide a more precise picture of patients' cognitive developmental trajectory than a single contemporaneous Hb value alone. Figure 1 Figure 1. Disclosures Kirkham: Bluebird Bio: Honoraria; Novartis: Honoraria; Global Blood Therapeutics: Consultancy. Howard: Imara: Consultancy, Honoraria; Global Blood Therapeutics: Consultancy; Novartis: Consultancy, Honoraria; Resonance Health: Honoraria; Novo Nordisk: Consultancy; Agios Pharmaceuticals: Consultancy; Forma Therapeutics: Consultancy; Bluebird Bio: Research Funding.

Solar coronal rotation according to soft X-ray solar radiation during the 22nd, 23rd, and 24th solar cycles

Using the developed method of combining numerous scattered time series of the same type of measurements into a single weighted average series, according to the data of the GOES series satellites, a single series of daily data was synthesized during the 22nd, 23rd and 24th solar cycles (1986 – 2019 years). The flare and background components were distinguished from this data series, which were investigated by means the method of constructing a composite spectral periodogram for the presence of quasiperiodic oscillations at various solar cycles. Some of these found quasiperiods may be explained by both synodic and sidereal rotation of the Sun, while others coincide with the average lifetime of the solar atmosphere active formations such as the sunspot groups and the facular plages. Special attention was paid to the study of the change over time the revealed quasiperiodic values over the course of solar cycles by calculating the sample normalized spectral density of the analyzed data in a sliding time window with a value of up to two years. Based on the revealed quasiperiodic value changes presented on the dynamic diagrams, it can be concluded that the differential rotation of the solar corona is unstable and manifests itself only at certain stages of the development and existence of solar activity cycles.

Cost Implications of Menstrual Hygiene Management in Nigeria and Its Associated Impacts

There has been a steady rise in the recognition of menstrual hygiene management (MHM) as a pressing public health issue due to several advocacy campaigns against its high cost. However, not much of such recognition has been given to it outside the non-profit sector in Nigeria. This is paradoxical considering that most menstruators in Nigeria cannot afford MHM whose cost is considered high even in developed countries. We estimated that the average lifetime cost of MHM in Nigeria is US$1,122.3 per menstruator and US$113.58 billion for the entire menstruating population. Although this cost is relatively lower than in other countries, Nigeria&rsquo;s low-income level explains why there is a high prevalence of period poverty among menstruators in Nigeria. This commentary highlights the intersected impacts of the cost of MHM and period poverty on the average Nigerian menstruator, his/her family, the economy, the environment and the United Nations Sustainable Development Goals. To alleviate the discussed negative effects, we suggested, as a key recommendation, the national shift from the use of disposable MHM products to that of reusable ones.

Increasing Wells Lifetime by Using PAR VALVE to Overcome Sand Settling Problems at Pertamina EP Asset 1 Field Jambi

In the Jambi oil field, sand production can create unattainable production targets and short-lived well lifetime. One function of the Jambi Engineering and Planning Field is to look for solutions to these problems, such as the installation of progressive cavity pumps (PCP) into wells. Although successful, a problem that often arises in PCP wells is sand settling when the PCP is off, for example during electric trips, engine maintenance and repair of flowlines. This settling can lead to a stuck PCP. A recent solution has been to install a Pressure Actuated Relief (PAR) valve, where the tool directs sand deposits out of the tubing to the annulus so that it does not enter the pump. Installation of this tool has increased the average lifetime of sandy wells from 2 months to 6 months, and has increased oil production in these wells by up to 47%.This paper will discuss the successful installation of a PAR Valve into well KTT-08 in the Jambi Field.