Modelling the impact of reopening schools in the UK in early 2021 in the presence of the alpha variant and with roll-out of vaccination against SARS-CoV-2.

Following the resurgence of the COVID-19 epidemic in the UK in late 2020 and the emergence of the alpha (also known as B117) variant of the SARS-CoV-2 virus, a third national lockdown was imposed from January 4, 2021. Following the decline of COVID-19 cases over the remainder of January 2021, the question of when and how to reopen schools became an increasingly pressing one in early 2021. This study models the impact of a partial national lockdown with social distancing measures enacted in communities and workplaces under different strategies of reopening schools from March 8, 2021 and compares it to the impact of continual full national lockdown remaining until April 19, 2021. We used our previously published agent-based model, Covasim, to model the emergence of the alpha variant over September 1, 2020 to January 31, 2021 in presence of Test, Trace and Isolate (TTI) strategies. We extended the model to incorporate the impacts of the roll-out of a two-dose vaccine against COVID-19, with 200,000 daily vaccine doses prioritised by age starting with people 75 years or older, assuming vaccination offers a 95% reduction in disease acquisition risk and a 30% reduction in transmission risk. We used the model, calibrated until January 25, 2021, to simulate the impact of a full national lockdown (FNL) with schools closed until April 19, 2021 versus four different partial national lockdown (PNL) scenarios with different elements of schooling open: 1) staggered PNL with primary schools and exam-entry years (years 11 and 13) returning on March 8, 2021 and the rest of the schools years on March 15, 2020; 2) full-return PNL with both primary and secondary schools returning on March 8, 2021; 3) primary-only PNL with primary schools and exam critical years (years 11 and 13) going back only on March 8, 2021 with the rest of the secondary schools back on April 19, 2021 and 4) part-rota PNL with both primary and secondary schools returning on March 8, 2021 with primary schools remaining open continuously but secondary schools on a two-weekly rota-system with years alternating between a fortnight of face-to-face and remote learning until April 19, 2021. Across all scenarios, we projected the number of new daily cases, cumulative deaths and effective reproduction number R until April 30, 2021. Our calibration across different scenarios is consistent with alpha variant being around 60% more transmissible than the wild type. We find that strict social distancing measures, i.e. national lockdowns, were essential in containing the spread of the virus and controlling hospitalisations and deaths during January and February 2021. We estimated that a national lockdown over January and February 2021 would reduce the number of cases by early March to levels similar to those seen in October 2020, with R also falling and remaining below 1 over this period. We estimated that infections would start to increase when schools reopened, but found that if other parts of society remain closed, this resurgence would not be sufficient to bring R above 1. Reopening primary schools and exam critical years only or having primary schools open continuously with secondary schools on rotas was estimated to lead to lower increases in cases and R than if all schools opened. Without an increase in vaccination above the levels seen in January and February, we estimate that R could have increased above 1 following the reopening of society, simulated here from April 19, 2021. Our findings suggest that stringent measures were integral in mitigating the increase in cases and bringing R below 1 over January and February 2021. We found that it was plausible that a PNL with schools partially open from March 8, 2021 and the rest of the society remaining closed until April 19, 2021 would keep R below 1, with some increase evident in infections compared to continual FNL until April 19, 2021. Reopening society in mid-April, without an increase in vaccination levels, could push R above 1 and induce a surge in infections, but the effect of vaccination may be able to control this in future depending on the transmission blocking properties of the vaccines.

Modelling the potential impact of mask use in schools and society on COVID-19 control in the UK.

As the UK reopened after the first wave of the COVID-19 epidemic, crucial questions emerged around the role for ongoing interventions, including test-trace-isolate (TTI) strategies and mandatory masks. Here we assess the importance of masks in secondary schools by evaluating their impact over September 1-October 23, 2020. We show that, assuming TTI levels from August 2020 and no fundamental changes in the virus's transmissibility, adoption of masks in secondary schools would have reduced the predicted size of a second wave, but preventing it would have required 68% or 46% of those with symptoms to seek testing (assuming masks' effective coverage 15% or 30% respectively). With masks in community settings but not secondary schools, the required testing rates increase to 76% and 57%.

Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial.

PURPOSE: The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA ≥ 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6-0.89. METHODS: Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA ≥ 0.6-0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline. RESULTS: At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (- 0.5, 19.5) vs. 4 mmHg (- 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P = 0.005]. The median EAA change in the population was - 12.9% (range: increase 49.2%-reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P = 0.08. CONCLUSIONS: These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA ≥ 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

Clar theory for radical benzenoids.

Eric Clar's ideas concerning "aromatic sextets" are extended from closed-shell benzenoids to the case of radical benzenoids, particularly those where the unpaired electrons are largely localized on sites of one "type" (starred or unstarred). A quantitative format in terms of a new Clar polynomial is introduced to make quantitative correlations with a selection of numerical data, including delocalization energies, spin densities, and energy gaps between states of different spin multiplicities. The correlations are generally quite good, thereby further validating Clar's ideas and our extension and quantification of them.

Clar theory for molecular benzenoids.

Eric Clar's ideas concerning "aromatic sextets" are extended to a quantitative format in terms of a polynomial called the "Clar 2-nomial", along with related derivative quantities. The quantification is successfully tested to make correlations with a selection of numerical data, including resonance energies, bond lengths, and NICS ring-aromaticity values.

Optimized geometry of the cluster Gd2O3 and proposed antiferromagnetic alignment of f-electron magnetic moment.

There is currently experimental interest in assemblies of Gd2O3 clusters. This has motivated the present study in which a single such cluster in free space is examined quantitatively by spin-density functional theory, with appropriate relativistic corrections incorporated for Gd. First, the nuclear geometry of the cluster is optimized, and it is found to be such that the two Gd atoms lie in a symmetry axis perpendicular to the isosceles triangle formed by the O atoms. Then, a careful study is made of the magnetic arrangement of the localized f-electron moments on the two Gd atoms. The prediction of the present treatment is that the localized spins are aligned antiferromagnetically. An alternative picture using superexchange ideas leads to the same conclusion.

Tobacco use in the Dominican Republic: understanding the culture first.

OBJECTIVE: To conduct formative research on the landscape of tobacco use to guide survey and subsequent intervention development in the Dominican Republic (DR). DESIGN: Rapid Assessment Procedures, systematic qualitative methods (participant-observations, in-depth interviewing, focus groups) using bilingual mixed age and gendered teams from the United States and DR. SUBJECTS: Over 160 adults (men and women), ages 18 to 90 years, current, former and never smokers, community members and leaders from six underserved, economically disadvantaged DR communities. MAIN OUTCOME MEASURES: Key domains: tobacco use patterns and attitudes; factors affecting smoking initiation, continuation, quitting; perceived risks/benefits/effects of smoking; and awareness/effects of advertising/regulations. RESULTS: Perceptions of prevalence varied widely. While "everybody" smokes, smokers or ex-smokers were sometimes difficult to find. Knowledge of health risks was limited to the newly mandated statement "Fumar es prejudicial para la salud" [Smoking is harmful to your health]. Smokers started due to parents, peers, learned lifestyle, fashion or as something to do. Smoking served as an escape, relaxation or diversion. Quit attempts relied on personal will, primarily for religious or medical reasons. Social smoking (custom or habit) (< 10 cigarettes per day) was viewed as a lifestyle choice rather than a vice or addiction. Out of respect, smokers selected where they smoked and around whom. Health care providers typically were reactive relative to tobacco cessation, focusing on individuals with smoking related conditions. Tobacco advertising was virtually ubiquitous. Anti-tobacco messages were effectively absent. Cultures of smoking and not smoking coexisted absent a culture of quitting. CONCLUSIONS: Systematic qualitative methods provided pertinent information about tobacco attitudes and use to guide subsequent project steps. Integrating qualitative then quantitative research can be replicated in similar countries that lack empirical data on the cultural dimensions of tobacco use.

The roles of ribosomal proteins in the structure assembly, and evolution of the large ribosomal subunit.

The structures of ribosomal proteins and their interactions with RNA have been examined in the refined crystal structure of the Haloarcula marismortui large ribosomal subunit. The protein structures fall into six groups based on their topology. The 50S subunit proteins function primarily to stabilize inter-domain interactions that are necessary to maintain the subunit's structural integrity. An extraordinary variety of protein-RNA interactions is observed. Electrostatic interactions between numerous arginine and lysine residues, particularly those in tail extensions, and the phosphate groups of the RNA backbone mediate many protein-RNA contacts. Base recognition occurs via both the minor groove and widened major groove of RNA helices, as well as through hydrophobic binding pockets that capture bulged nucleotides and through insertion of amino acid residues into hydrophobic crevices in the RNA. Primary binding sites on contiguous RNA are identified for 20 of the 50S ribosomal proteins, which along with few large protein-protein interfaces, suggest the order of assembly for some proteins and that the protein extensions fold cooperatively with RNA. The structure supports the hypothesis of co-transcriptional assembly, centered around L24 in domain I. Finally, comparing the structures and locations of the 50S ribosomal proteins from H.marismortui and D.radiodurans revealed striking examples of molecular mimicry. These comparisons illustrate that identical RNA structures can be stabilized by unrelated proteins.

Parameter-free structure-property correlation via progressive reaction posets for substituted benzenes.

Progressive reaction networks as frequently arise in chemistry are naturally identifiable as "partially ordered sets" (or posets). Here the direction of the reaction identifies the partial ordering of the set of molecular species. The possibility that different properties are similarly ordered is a further natural consideration and is here investigated for a suite of over 30 properties for (methyl and chloro) substituted benzenes. Such a posetic correlation is favorably demonstrated for these substituted benzenes, and it is illustrated how suitable properties may be simply predicted in an interpolative parameter-free (albeit not model-free) fashion through the use of the reaction poset. Some numerical model-quality indicators are identified, and the simple approach is deemed quite reasonable.

Characterization of cyclo-polyphenacenes.

Cyclo-polyphenacenes belt-type compounds are considered here in terms of some simple chemico-graph-theoretic invariants. First the compounds of this group are neatly encoded in an unambiguous way. Then all the isomers in this system are categorized with respect to their "combinatorial curvature", and for the case of the 52 cyclo-hexaphenacenes it is found to correlate with steric stresses. A systematic effort is made to correlate the reactivity (via additive oxidation) of the various isomers with their Kekule-structure counts.

Quantitative structure-property relationships generated with optimizable even/odd Wiener polynomial descriptors.

Chemical structures of organic compounds are characterized numerically by a variety of structural descriptors, one of the earliest and most widely used being the Wiener index W, derived from the interatomic distances in a molecular graph. Extensive use of distance-based structural descriptors or topological indices has been made in QSPR and QSAR models, drug design, toxicology, virtual screening of combinatorial libraries, similarity and diversity assessment. Novel topological indices are introduced representing a partitioning of the Wiener polynomial based on counts of even and odd molecular graph distances. During the QSAR/QSPR modeling process the variables of the even and odd power functions are optimized in order to offer an improved mapping of the investigated property. These novel topological indices are tested in QSPR models for the boiling temperature, molar heat capacity, standard Gibbs energy of formation, vaporization enthalpy, refractive index, and density of alkanes. In many cases, the even/odd Wiener polynomial indices proposed here give notably improved correlations or suggest simpler QSPR models.

The kink-turn: a new RNA secondary structure motif.

Analysis of the Haloarcula marismortui large ribosomal subunit has revealed a common RNA structure that we call the kink-turn, or K-turn. The six K-turns in H.marismortui 23S rRNA superimpose with an r.m.s.d. of 1.7 A. There are two K-turns in the structure of Thermus thermophilus 16S rRNA, and the structures of U4 snRNA and L30e mRNA fragments form K-turns. The structure has a kink in the phosphodiester backbone that causes a sharp turn in the RNA helix. Its asymmetric internal loop is flanked by C-G base pairs on one side and sheared G-A base pairs on the other, with an A-minor interaction between these two helical stems. A derived consensus secondary structure for the K-turn includes 10 consensus nucleotides out of 15, and predicts its presence in the 5'-UTR of L10 mRNA, helix 78 in Escherichia coli 23S rRNA and human RNase MRP. Five K-turns in 23S rRNA interact with nine proteins. While the observed K-turns interact with proteins of unrelated structures in different ways, they interact with L7Ae and two homologous proteins in the same way.

Predictors of late-onset smoking and cessation over 10 years.

PURPOSE: To identify predictors of smoking onset and cessation between early (age 13 years) and late adolescence (age 18 years) and between late adolescence (age 18 years) and young adulthood (age 23 years). METHODS: We employed logistic regression to predict smoking initiation and cessation for an ethnically diverse sample of 3056 adolescents recruited from 30 West Coast schools in 1985 and observed from age 13 to age 23 years. Fifty-six percent of the sample was female. Predictors tapping sociodemographic characteristics, environmental influences, attitudes and beliefs about smoking, bonds with school, and problem behavior were measured at age 13 years (older teenager models) and at age 18 years (young adult models). RESULTS: Robust predictors of both initiation and cessation across the two developmental periods included doing poorly in middle/high school and prior smoking behavior. Predictors common to three of the four models included being young for one's grade cohort and intending to smoke in the next 6 months. Early deviant behavior and drinking fostered initiation among older teenagers, but problem behavior as an older teenager did not predict young adult initiation. Smokers who had few or no high school friends who smoked and felt able to resist prosmoking pressures at age 18 years were more likely to quit by age 23 years. Being female predicted initiation by age 18 years; being African-American, Hispanic, or Asian inhibited it. CONCLUSIONS: The strong association of prior smoking behavior and intentions with later smoking status among both adolescents and young adults underscores the importance of starting smoking prevention early and continuing it through high school. Such programs might also consider the greater vulnerability of females, youth who are young for their grade cohort, and those who are doing poorly in school.

Wiener index extension by counting even/odd graph distances.

Chemical structures of organic compounds are characterized numerically by a variety of structural descriptors, one of the earliest and most widely used being the Wiener index W, derived from the interatomic distances in a molecular graph. Extensive use of such structural descriptors or topological indices has been made in drug design, screening of chemical databases, and similarity and diversity assessment. A new set of topological indices is introduced representing a partitioning of the Wiener index based on counts of even and odd molecular graph distances. These new indices are further generalized by weighting exponents which can be optimized during the quantitative structure-activity/-property relationship (QSAR/QSPR) modeling process. These novel topological indices are tested in QSPR models for the boiling temperature, molar heat capacity, standard Gibbs energy of formation, vaporization enthalpy, refractive index, and density of alkanes. In many cases, the even/odd distance indices proposed here give notably improved correlations.

Curvature matching and strain relief in bucky-tori: usage of sp3-hybridization and nonhexagonal rings.

The relief of different types of curvature strain in bucky-tori of elemental carbon is considered in a general formal framework. This theory then is used to aid in the design of several structures, which are treated via molecular mechanics. Novel illustrations of the remnant strain are made, and some modest conclusions as to the nature of the structure of the experimentally observed bucky-tori are suggested.

Sex differences in predictors of adolescent smoking cessation.

Sex differences in predictors of smoking cessation were investigated among 337 male and 490 female participants in the RAND adolescent panel study. Participants reported smoking at least 11-20 times during the past year at Grade 10, with cessation defined as not smoking during the past year at Grade 12. Controlling for demographics, sex-specific analyses indicated that girls who quit smoking within 2 years had friends who smoked less frequently, perceived less parental approval of their smoking, had weaker intentions to continue smoking, used marijuana less frequently, attended fewer different schools, were more likely to have an intact nuclear family, experienced greater peer support, and rated themselves as healthier. Similar analyses for boys yielded results that were generally weaker and nonsignificant, with smoking quantity accounting for several associations in the sex-specific models. Despite these differences, interaction tests revealed significant sex differences for only three predictors. Implications of these results for understanding adolescent smoking cessation are discussed.

Directed self-avoiding walks in random media.

Two types of directed self-avoiding walks (SAW's), namely, three-choice directed SAW and outwardly directed SAW, have been studied on infinite percolation clusters on the square lattice in two dimensions. The walks on the percolation clusters are generated via a Monte Carlo technique. The longitudinal extension R(N) and the transverse fluctuation W(N) have been measured as a function of the number of steps N. Slight swelling is observed in the longitudinal direction on the random lattices. A crossover from shrinking to swelling of the transverse fluctuations is found at a certain length N(c) of the walks. The exponents related to the transverse fluctuations are seen to be unchanged in the random media even as the percolation threshold is reached. The scaling function form of the extensions are verified.

Quantitative structure-retention relationships for gas chromatographic retention indices of alkylbenzenes with molecular graph descriptors.

Quantitative structure-retention relationships (QSRR) represent statistical models that quantify the connection between the molecular structure and the chromatographic retention indices of organic compounds, allowing the prediction of retention indices of novel, not yet synthesized compounds, solely from their structural descriptors. Using multiple linear regression, QSRR models for the gas chromatographic Kováts retention indices of 129 alkylbenzenes are generated using molecular graph descriptors. The correlational ability of structural descriptors computed from 10 molecular matrices is investigated, showing that the novel reciprocal matrices give numerical indices with improved correlational ability. A QSRR equation with 5 graph descriptors gives the best calibration and prediction results, demonstrating the usefulness of the molecular graph descriptors in modeling chromatographic retention parameters. The sequential orthogonalization of descriptors suggests simpler QSRR models by eliminating redundant structural information.

Structural characterization of quinoxaline homopolymers and quinoxaline/ether sulfone copolymers by matrix-assisted laser desorption ionization mass spectrometry.

Polyphenylquinoxalines (PPQs) are prepared from self-polymerizable quinoxaline monomers that carry fluorine, hydroxyaryl (ArOH), and phenyl substituents. In basic media, these monomers self-polymerize via a series of nucleophilic aromatic substitution reactions (SNAr), in which aromatic enolates (ArO- nucleophiles) attack the electrophilic carbons bearing F leaving groups to effect fluoride displacement. Polyphenylquinoxaline/polyether-sulfone (PPQ/PES) copolymers are synthesized similarly by combining self-polymerizable quinoxaline monomers with a 1:1 molar mixture of 4,4'-dichlorodiphenyl sulfone and bisphenol A. The MALDI mass spectra of the polymers reveal that the major products up to approximately 15,000 Da molecular mass are homo- or copolymeric macrocycles. Linear byproducts are also observed, arising from nucleophilic ring opening of already formed macrocycles. Oligomers containing at least one PPQ unit readily protonate upon MALDI, whereas PES homopolymers require alkali metal ion addition to become detectable. Molecular orbital calculations point out that the nucleophilic and electrophilic reactivities of the PPQ monomer and the PPQ growing chains generated during propagation are comparable, allowing for continued condensations via SN-Ar, until cyclization terminates this process. The calculations also predict a significantly lower electrophilic reactivity for carbons substituted by chlorine instead of fluorine, justifying the discrimination against incorporation of PES units observed for the copolymers. The computationally optimized structures of PPQ and PPQ/PES macrocycles show a diverse array of cavity sizes and geometries which depend on the size of the macrocycle, the sequence of the repeat units, and the position of the substituents in the quinoxaline ring; quinoxaline pendants (phenyl groups) are found to favor helical arrangements in the prepared macrocycles.

High-risk behaviors associated with early smoking: results from a 5-year follow-up.

PURPOSE: To compare grade 7 nonsmokers, experimenters, and smokers on the basis of prevalence of other problem behaviors at both grade 7 and grade 12. METHODS: Based on longitudinal self-report data from 4327 California and Oregon students, we used logistic regression to develop weighted estimates of the prevalence of academic difficulties, substance use, and delinquent behavior within the three smoking status groups at grades 7 and 12. Huber variance estimates, which adjust for weighting and clustering of observations, were used to assess the statistical significance of differences across groups. RESULTS: Compared with nonsmokers, early smokers were at least 3 times more likely by grade 12 to regularly use tobacco and marijuana, use hard drugs, sell drugs, have multiple drug problems, drop out of school, and experience early pregnancy and parenthood. These adolescents were also at higher risk for low academic achievement and behavioral problems at school, stealing and other delinquent behaviors, and use of predatory and relational violence. Early experimenters were at significantly greater risk for these problems as well, although to a lesser extent than smokers. Importantly, the higher risk among experimenters and smokers of experiencing many of these problems was evident as early as grade 7. CONCLUSIONS: Early experimenters and smokers are more likely than nonsmokers to experience various problem behaviors by grade 12, with many of these problems evident as early as grade 7. Results suggest that substance use programs that target multiple problems in addition to smoking may be most effective for these high-risk adolescents.