Hepatic Spheroid Formation on Carbohydrate-Functionalized Supramolecular Hydrogels.

Two synthetic supramolecular hydrogels, formed from bis-urea amphiphiles containing lactobionic acid (LBA) and maltobionic acid (MBA) bioactive ligands, are applied as cell culture matrices in vitro. Their fibrillary and dynamic nature mimics essential features of the extracellular matrix (ECM). The carbohydrate amphiphiles self-assemble into long supramolecular fibers in water, and hydrogels are formed by physical entanglement of fibers through bundling. Gels of both amphiphiles exhibit good self-healing behavior, but remarkably different stiffnesses. They display excellent bioactive properties in hepatic cell cultures. Both carbohydrate ligands used are proposed to bind to asialoglycoprotein receptors (ASGPRs) in hepatic cells, thus inducing spheroid formation when seeding hepatic HepG2 cells on both supramolecular hydrogels. Ligand nature, ligand density, and hydrogel stiffness influence cell migration and spheroid size and number. The results illustrate the potential of self-assembled, carbohydrate-functionalized hydrogels as matrices for liver tissue engineering.

Photo-Crosslinked Coumarin-Containing Bis-Urea Amphiphile Hydrogels.

The design of photo-responsive supramolecular hydrogels based on coumarin dimerization and de-dimerization is described. The photo-responsive coumarin unit is chemically incorporated into an oligo(ethylene glycol) (OEG) bis-urea amphiphile that is capable of co-assembling with non-functionalized OEG amphiphile, to form supramolecular fibers. UV light with two different wavelengths (365 nm and 254 nm) is employed to induce a photo-reversible dimerization and de-dimerization process of coumarin units, respectively. The co-assembled solutions could be photo-crosslinked to induce a sol-to-gel transition through dimerization of coumarin with 365 nm UV light, and de-dimerization occurs with 254 nm UV light, to provide a weaker gel. In this system, the mechanical strength of supramolecular hydrogels can be tuned using the irradiation time, providing precise control of gelation in a supramolecular hydrogelator.

Statistical analysis and first-passage-time applications of a lognormal diffusion process with multi-sigmoidal logistic mean.

We consider a lognormal diffusion process having a multisigmoidal logistic mean, useful to model the evolution of a population which reaches the maximum level of the growth after many stages. Referring to the problem of statistical inference, two procedures to find the maximum likelihood estimates of the unknown parameters are described. One is based on the resolution of the system of the critical points of the likelihood function, and the other is on the maximization of the likelihood function with the simulated annealing algorithm. A simulation study to validate the described strategies for finding the estimates is also presented, with a real application to epidemiological data. Special attention is also devoted to the first-passage-time problem of the considered diffusion process through a fixed boundary.

Factors Associated with Delayed or Missed Second-Dose mRNA COVID-19 Vaccination among Persons >12 Years of Age, United States.

To identify demographic factors associated with delaying or not receiving a second dose of the 2-dose primary mRNA COVID-19 vaccine series, we matched 323 million single Pfizer-BioNTech (https://www.pfizer.com) and Moderna (https://www.modernatx.com) COVID-19 vaccine administration records from 2021 and determined whether second doses were delayed or missed. We used 2 sets of logistic regression models to examine associated factors. Overall, 87.3% of recipients received a timely second dose (≤42 days between first and second dose), 3.4% received a delayed second dose (>42 days between first and second dose), and 9.4% missed the second dose. Persons more likely to have delayed or missed the second dose belonged to several racial/ethnic minority groups, were 18-39 years of age, lived in more socially vulnerable areas, and lived in regions other than the northeastern United States. Logistic regression models identified specific subgroups for providing outreach and encouragement to receive subsequent doses on time.

Access to verb bias and plausibility information during syntactic processing in adult Spanish-English bilinguals.

In two experiments, we examine how proficient second language speakers integrate verb bias and plausibility information during online sentence comprehension. Spanish-English speakers and native English speakers read sentences in English in which a post-verbal noun phrase (NP) could be interpreted as a direct object or a sentential subject. To examine the role of verb bias, the post-verbal NP was preceded by a verb that is preferentially followed by a direct object (DO-bias verbs) or a sentential complement (SC-bias verbs). To assess the role of plausibility, the semantic fit between the verb and the post-verbal NP was either congruent or incongruent with the direct object interpretation. The results show that both second language speakers and native speakers used verb bias information to assign a grammatical role to the post-verbal ambiguous NP with small differences. Syntactic revision of an initially incorrect DO interpretation was facilitated by the presence of an implausible NP.

Disparities in COVID-19 Vaccination Coverage Between Urban and Rural Counties - United States, December 14, 2020-January 31, 2022.

Higher COVID-19 incidence and mortality rates in rural than in urban areas are well documented (1). These disparities persisted during the B.1.617.2 (Delta) and B.1.1.529 (Omicron) variant surges during late 2021 and early 2022 (1,2). Rural populations tend to be older (aged ≥65 years) and uninsured and are more likely to have underlying medical conditions and live farther from facilities that provide tertiary medical care, placing them at higher risk for adverse COVID-19 outcomes (2). To better understand COVID-19 vaccination disparities between urban and rural populations, CDC analyzed county-level vaccine administration data among persons aged ≥5 years who received their first dose of either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccine or a single dose of the Ad.26.COV2.S (Janssen [Johnson & Johnson]) COVID-19 vaccine during December 14, 2020-January 31, 2022, in 50 states and the District of Columbia (DC). COVID-19 vaccination coverage with ≥1 doses in rural areas (58.5%) was lower than that in urban counties (75.4%) overall, with similar patterns across age groups and sex. Coverage with ≥1 doses varied among states: 46 states had higher coverage in urban than in rural counties, one had higher coverage in rural than in urban counties. Three states and DC had no rural counties; thus, urban-rural differences could not be assessed. COVID-19 vaccine primary series completion was higher in urban than in rural counties. However, receipt of booster or additional doses among primary series recipients was similarly low between urban and rural counties. Compared with estimates from a previous study of vaccine coverage among adults aged ≥18 years during December 14, 2020-April 10, 2021, these urban-rural disparities among those now eligible for vaccination (aged ≥5 years) have increased more than twofold through January 2022, despite increased availability and access to COVID-19 vaccines. Addressing barriers to vaccination in rural areas is critical to achieving vaccine equity, reducing disparities, and decreasing COVID-19-related illness and death in the United States (2).

Changes in Native Sentence Processing Related to Bilingualism: A Systematic Review and Meta-Analysis.

The native language changes as a result of contact with a second language, and the pattern and degree of such change depend on a variety of factors like the bilingual experience or the linguistic level. Here, we present a systematic review and meta-analysis of works that explore variations in native sentence comprehension and production by comparing monolinguals and bilinguals. Fourteen studies in the meta-analysis provided information regarding the bilingual experience and differences at the morphosyntactic level using behavioral methods. Overall, we observed that first language processing is subject to small transformations in bilinguals that occur in sentence comprehension and production. The magnitude of the changes depended on bilingual experiences, but only length of residence in an L2 setting predicted the degree of change, where shorter length of residence was associated with larger changes. Results are discussed and related to the cognitive processes that potentially cause the transformations in the first language. The present work reveals some limitations in the field that should be addressed in future studies to better understand the mechanisms behind language attrition.

Pregnancy Risk Assessment Monitoring System for Dads: A piloted randomized trial of public health surveillance of recent fathers' behaviors before and after infant birth.

BACKGROUND: Becoming a father impacts men's health and wellbeing, while also contributing to the health and wellbeing of mothers and children. There is no large-scale, public health surveillance system aimed at understanding the health and behaviors of men transitioning into fatherhood. The purpose of this study was to describe piloted randomized approaches of a state-based surveillance system examining paternal behaviors before and after their infant's birth to better understand the health needs of men and their families during the transition to parenthood. METHODS: During October 2018-July 2019, 857 fathers in Georgia were sampled 2-6 months after their infant's birth from birth certificates files and surveyed via mail, online or telephone, in English or Spanish, using two randomized approaches: Indirect-to-Dads and Direct-to-Dads. Survey topics included mental and physical health, healthcare, substance use, and contraceptive use. FINDINGS: Weighted response rates (Indirect-to-Dads, 33%; Direct-to-Dads, 31%) and population demographics did not differ by approach. Respondents completed the survey by mail (58%), online (28%) or telephone (14%). Among 266 fathers completing the survey, 55% had a primary care physician, and 49% attended a healthcare visit for themselves during their infant's mother's pregnancy or since their infant's birth. Most fathers were overweight or had obesity (70%) while fewer reported smoking cigarettes (19%), binge drinking (13%) or depressive symptoms (10%) since their infant's birth. CONCLUSIONS: This study tests a novel approach for obtaining population-based estimates of fathers' perinatal health behaviors, with comparable response rates from two pragmatic approaches. The pilot study results quantify a number of public health needs related to fathers' health and healthcare access.

Influenza Vaccinations During the COVID-19 Pandemic - 11 U.S. Jurisdictions, September-December 2020.

Influenza causes considerable morbidity and mortality in the United States. Between 2010 and 2020, an estimated 9-41 million cases resulted in 140,000-710,000 hospitalizations and 12,000-52,000 deaths annually (1). As the United States enters the 2021-22 influenza season, the potential impact of influenza illnesses is of concern given that influenza season will again coincide with the ongoing COVID-19 pandemic, which could further strain overburdened health care systems. The Advisory Committee on Immunization Practices (ACIP) recommends routine annual influenza vaccination for the 2021-22 influenza season for all persons aged ≥6 months who have no contraindications (2). To assess the potential impact of the COVID-19 pandemic on influenza vaccination coverage, the percentage change between administration of at least 1 dose of influenza vaccine during September-December 2020 was compared with the average administered in the corresponding periods in 2018 and 2019. The data analyzed were reported from 11 U.S. jurisdictions with high-performing state immunization information systems.* Overall, influenza vaccine administration was 9.0% higher in 2020 compared with the average in 2018 and 2019, combined. However, in 2020, the number of influenza vaccine doses administered to children aged 6-23 months and children aged 2-4 years, was 13.9% and 11.9% lower, respectively than the average for each age group in 2018 and 2019. Strategic efforts are needed to ensure high influenza vaccination coverage among all age groups, especially children aged 6 months-4 years who are not yet eligible to receive a COVID-19 vaccine. Administration of influenza vaccine and a COVID-19 vaccine among eligible populations is especially important to reduce the potential strain that influenza and COVID-19 cases could place on health care systems already overburdened by COVID-19.

Nanoporous Films with Photoswitchable Absorption Kinetics Based on Polymerizable Columnar Discotic Liquid Crystals.

A photoresponsive nanoporous polymer film has been produced from the templated self-assembly of a columnar liquid crystal containing azo units. A liquid crystalline complex of polymerizable azobenzoic acid and a tris-benzimidazolyl benzene template molecule was cross-linked via thiol-ene radical copolymerization with dodecanedithiol. Subsequent removal of the template yielded nanoporous polymer films with pores of approximately 1 nm in diameter. Both trans-cis and cis-trans photoisomerizations of azobenzoic acid took place in the porous films. At room temperature, the cis isomer was sufficiently long-lived to establish a difference in dye absorption kinetics of the two isomers. The cationic dye rhodamine 6G was bound to both isomers, but the rate of binding to films enriched in the cis isomer was 8 times faster.

Are All Code-Switches Processed Alike? Examining Semantic v. Language Unexpectancy.

Prior studies using the event-related potential (ERP) technique show that integrating sentential code-switches during online processing leads to a broadly distributed late positivity component (LPC), while processing semantically unexpected continuations instead leads to the emergence of an N400 effect. While the N400 is generally assumed to index lexico-semantic processing, the LPC has two different interpretations. One account suggests that it reflects the processing of an improbable or unexpected event, while an alternative account proposes sentence-level reanalysis. To investigate the relative costs of semantic to language-based unexpectancies (i.e., code-switches), the current study tests 24 Spanish-English bilinguals in an ERP reading study. Semantically constrained Spanish frames either varied in their semantic expectancy (high vs. low expectancy) and/or their language continuation (same-language vs. code-switch) while participants' electrophysiological responses were recorded. The Spanish-to-English switch direction provides a more naturalistic test for integration costs to code-switching as it better approximates the code-switching practices of the target population. Analyses across three time windows show a main effect for semantic expectancy in the N400 time window and a main effect for code-switching in the LPC time window. Additional analyses based on the self-reported code-switching experience of the participants suggest an early positivity linked to less experience with code-switching. The results highlight that not all code-switches lead to similar integration costs and that prior experience with code-switching is an important additional factor that modulates online processing.

Comparación de concentración y excreción de flúor, con y sin fortificación de flúor en sal, costa rica 2005 / Comparison of fluoride concentration and excretion in fortified and non-fortified salt use. Costa Rica 2005

Resumen Objetivo: Determinar la concentración y excreción de flúor en orina de 24 horas en 4 grupos de edad y la exposición de flúor en uñas, sin y con fluoruración de la sal, después de un periodo de interrupción de siete meses. Cartago 2004-2005. Metodología: Muestra no probabilística y secuencial de 127 individuos distribuidos en cuatro grupos poblacionales (4-6, 10-12, 15-17 y 35-60 años de edad). El análisis de flúor en orina, agua y sal se realizó con el electrodo específico. El análisis de flúor en uñas se realizó mediante el análisis de difusión facilitada con hexametildisiloxano (HMDS). Se calculó la concentración de flúor en orina, uñas, agua y sal, así como la excreción de flúor en orina. Resultados: En el periodo sin sal fluorurada (fase 1), 90,5% de muestras de sal tenían menos de 15,8 mgF/kg (promedio 22,7 mgF/kg) y el agua un promedio de 0,25 mgF/l; en el periodo con sal fluorurada (fase 2) el promedio de flúor en sal fue de 143,5 mgF/kg, siempre con la concentración de agua de 0,25 mgF/l. La excreción urinaria de 24 horas y la concentración de flúor con 7 meses sin sal fluorurada en ambos casos fue menor en la fase I en los cuatro grupos de edad. Con sal fluorurada (fase II) la excreción aumentó en 80% en promedio, en todos los grupos de edad. Por el contrario, la concentración de flúor en uñas, fue más elevada durante la fase 1, sin diferencias significativas entre grupos ni entre fases. Conclusión: La interrupción de la fluoruración de la sal en Costa Rica permitió medir la presencia de éste elemento en la población centinela (control), confirmando que el organismo mantiene el flúor aún por 7 meses después de dejar de ingerir flúor independiente de la edad. La medición de la concentración de flúor en uñas podría constituirse en un método de medición de éste elemento para complementar el estudio de flúor en el organismo humano.

Abstract Objective: To determine the concentration and excretion of fluoride in urine of 24 hours in 4 age groups and fluoride exposure in nails, without and with fluoridation of the salt, after a period of interruption of seven months. Cartago 2004-2005. Methodology: Non-probabilistic and sequential sample of 127 individuals distributed in four population groups (4-6, 10-12, 15-17 and 35-60 years of age). The analysis of fluorine in urine, water and salt was performed with the specific electrode. Nail fluoride analysis was performed by diffusion analysis provided with hexamethyldisiloxane (HMDS). The concentration of fluoride in urine, nails, water and salt, as well as the excretion of fluoride in urine was calculated. Results: In the period without fluoridated salt (phase 1), 90.5% of salt samples had less than 15.8 mgF / kg (average 22.7 mgF / kg) and water averaged 0.25 mgF / L; In the period with fluorided salt (phase 2) the average fluoride in salt was 143.5 mgF / kg, always with the water concentration of 0.25 mgF / l. The 24-hour urinary excretion and fluoride concentration at 7 months without fluoridated salt in both cases was lower in phase I in all four age groups. With fluoridated salt (phase II) excretion increased by 80% on average in all age groups. In contrast, the fluoride concentration in nails was higher during phase 1, without significant differences between groups or between phases. Conclusion: The interruption of fluoridation of salt in Costa Rica allowed the measurement of the presence of this element in the sentinel population (control), confirming that the organism maintains the fluoride still for 7 months after stopping ingesting fluorine independent of age. The measurement of the concentration of fluoride in nails could constitute a method of measuring this element to complement the study of fluorine in the human organism.

A hyperbolastic type-I diffusion process: Parameter estimation by means of the firefly algorithm.

A stochastic diffusion process, whose mean function is a hyperbolastic curve of type I, is presented. The main characteristics of the process are studied and the problem of maximum likelihood estimation for the parameters of the process is considered. To this end, the firefly metaheuristic optimization algorithm is applied after bounding the parametric space by a stagewise procedure. Some examples based on simulated sample paths and real data illustrate this development.

Modeling tumor growth in the presence of a therapy with an effect on rate growth and variability by means of a modified Gompertz diffusion process.

In experimental studies on tumor growth, whenever the time evolution of the relative volume of a tumor in an untreated (control) group can be fitted by a Gompertz diffusion process there is a possibility that an antiproliferative therapy, which modifies the growth rate of the process that fits the treated group, may also affect its variability. The present paper proposes several procedures for the estimation of the time function included in the infinitesimal variance of the new process, as well as the time function affecting the growth rate (which is included in the infinitesimal mean). Also, a hypothesis testing is designed to confirm or refute the need for including such a time-dependent function in the infinitesimal variance. In order to validate and compare the proposed procedures a simulation study has been carried out. In addition, a proposal is made for a strategy aimed at finding the optimal combination of procedures for each case. A real data application concerning the effects of cisplatin on a patient-derived xenograft (PDX) tumor model showcases the advantages of this model over others that have been used in the past.

Estimating and determining the effect of a therapy on tumor dynamics by means of a modified Gompertz diffusion process.

A modified Gompertz diffusion process is considered to model tumor dynamics. The infinitesimal mean of this process includes non-homogeneous terms describing the effect of therapy treatments able to modify the natural growth rate of the process. Specifically, therapies with an effect on cell growth and/or cell death are assumed to modify the birth and death parameters of the process. This paper proposes a methodology to estimate the time-dependent functions representing the effect of a therapy when one of the functions is known or can be previously estimated. This is the case of therapies that are jointly applied, when experimental data are available from either an untreated control group or from groups treated with single and combined therapies. Moreover, this procedure allows us to establish the nature (or, at least, the prevalent effect) of a single therapy in vivo. To accomplish this, we suggest a criterion based on the Kullback-Leibler divergence (or relative entropy). Some simulation studies are performed and an application to real data is presented.

A stochastic model of cancer growth subject to an intermittent treatment with combined effects: reduction in tumor size and rise in growth rate.

A model of cancer growth based on the Gompertz stochastic process with jumps is proposed to analyze the effect of a therapeutic program that provides intermittent suppression of cancer cells. In this context, a jump represents an application of the therapy that shifts the cancer mass to a return state and it produces an increase in the growth rate of the cancer cells. For the resulting process, consisting in a combination of different Gompertz processes characterized by different growth parameters, the first passage time problem is considered. A strategy to select the inter-jump intervals is given so that the first passage time of the process through a constant boundary is as large as possible and the cancer size remains under this control threshold during the treatment. A computational analysis is performed for different choices of involved parameters. Finally, an estimation of parameters based on the maximum likelihood method is provided and some simulations are performed to illustrate the validity of the proposed procedure.

Processing ser and estar to locate objects and events: An ERP study with L2 speakers of Spanish.

In Spanish locative constructions, a different form of the copula is selected in relation to the semantic properties of the grammatical subject: sentences that locate objects require estar while those that locate events require ser (both translated in English as 'to be'). In an ERP study, we examined whether second language (L2) speakers of Spanish are sensitive to the selectional restrictions that the different types of subjects impose on the choice of the two copulas. Twenty-four native speakers of Spanish and two groups of L2 Spanish speakers (24 beginners and 18 advanced speakers) were recruited to investigate the processing of 'object/event + estar/ser' permutations. Participants provided grammaticality judgments on correct (object + estar; event + ser) and incorrect (object + ser; event + estar) sentences while their brain activity was recorded. In line with previous studies (Leone-Fernández, Molinaro, Carreiras, & Barber, 2012; Sera, Gathje, & Pintado, 1999), the results of the grammaticality judgment for the native speakers showed that participants correctly accepted object + estar and event + ser constructions. In addition, while 'object + ser' constructions were considered grossly ungrammatical, 'event + estar' combinations were perceived as unacceptable to a lesser degree. For these same participants, ERP recording time-locked to the onset of the critical word 'en' showed a larger P600 for the ser predicates when the subject was an object than when it was an event (*La silla es en la cocina vs. La fiesta es en la cocina). This P600 effect is consistent with syntactic repair of the defining predicate when it does not fit with the adequate semantic properties of the subject. For estar predicates (La silla está en la cocina vs. *La fiesta está en la cocina), the findings showed a central-frontal negativity between 500-700 ms. Grammaticality judgment data for the L2 speakers of Spanish showed that beginners were significantly less accurate than native speakers in all conditions, while the advanced speakers only differed from the natives in the event+ser and event+estar conditions. For the ERPs, the beginning learners did not show any effects in the time-windows under analysis. The advanced speakers showed a pattern similar to that of native speakers: (1) a P600 response to 'object + ser' violation more central and frontally distributed, and (2) a central-frontal negativity between 500-700 ms for 'event + estar' violation. Findings for the advanced speakers suggest that behavioral methods commonly used to assess grammatical knowledge in the L2 may be underestimating what L2 speakers have actually learned.

Bilinguals use language-control brain areas more than monolinguals to perform non-linguistic switching tasks.

We tested the hypothesis that early bilinguals use language-control brain areas more than monolinguals when performing non-linguistic executive control tasks. We do so by exploring the brain activity of early bilinguals and monolinguals in a task-switching paradigm using an embedded critical trial design. Crucially, the task was designed such that the behavioural performance of the two groups was comparable, allowing then to have a safer comparison between the corresponding brain activity in the two groups. Despite the lack of behavioural differences between both groups, early bilinguals used language-control areas--such as left caudate, and left inferior and middle frontal gyri--more than monolinguals, when performing the switching task. Results offer direct support for the notion that, early bilingualism exerts an effect in the neural circuitry responsible for executive control. This effect partially involves the recruitment of brain areas involved in language control when performing domain-general executive control tasks, highlighting the cross-talk between these two domains.

On the effect of a therapy able to modify both the growth rates in a Gompertz stochastic model.

A Gompertz-type diffusion process characterized by the presence of exogenous factors in the drift term is considered. Such a process is able to describe the dynamics of populations in which both the intrinsic rates are modified by means of time-dependent terms. In order to quantify the effect of such terms the evaluation of the relative entropy is made. The first passage time problem through suitable boundaries is studied. Moreover, some simulation results are shown in order to capture the dependence of the involved functions on the parameters. Finally, an application to tumor growth is presented and simulation results are shown.

Fitting dynamic growth models of biological phenomena from sample observations through Gaussian diffusion processes.

This paper addresses the building of stochastic models that adequately describe dynamic phenomena and, in particular, those that occur in the Biosciences. In this context, the empirical fitting of a Gaussian diffusion process from sample data of a dynamic growth phenomenon is considered. In order to do this, a methodology based on approximations to its mean and variance functions is presented. Finally, several applications based on simulated and real data have been carried out.