Restrained shrinkage cracking of cementitious composites containing soft PCM inclusions: A paste (matrix) controlled response

The addition of phase change materials (PCMs) has been proposed as a means to mitigate thermal cracking in cementitious materials. However, the addition of PCMs, i.e., soft inclusions, degrades the compressive strength of cementitious composites. From a strength-of-materials viewpoint, such reductions in strength are suspected to increase the tendency of cementitious materials containing PCMs to crack under load (e.g., volume instability-induced stresses resulting from thermal and/or hygral deformations). Based on detailed assessments of free and restrained shrinkage, elastic modulus, and tensile strength, this study shows that the addition of PCMs does not alter the cracking sensitivity of the material. In fact, the addition of PCMs (or other soft inclusions) enhances the cracking resistance as compared to a plain cement paste or composites containing equivalent dosages of (stiff) quartz inclusions. This is because composites containing soft inclusions demonstrate benefits resulting from crack blunting and deflection, and improved stress relaxation. As a result, although the tensile stress at failure remains similar, the time to failure (i.e., macroscopic cracking) of PCM-containing composites is considerably extended. More generally, the outcomes indicate that dosages of soft(er) inclusions, and the resulting decrease in compressive strength does not amplify the cracking risk of cementitious composites

Kinesin-1-mediated axonal transport of CB1 receptors is required for cannabinoid-dependent axonal growth and guidance

Endocannabinoids (eCB) modulate growth cone dynamics and axonal pathfinding through the stimulation of cannabinoid type-1 receptors (CB1R), the function of which depends on their delivery and precise presentation at the growth cone surface. However, the mechanism involved in the axonal transport of CB1R and its transport role in eCB signaling remains elusive. As mutations in the kinesin-1 molecular motor have been identified in patients with abnormal cortical development and impaired white matter integrity, we studied the defects in axonal pathfinding and fasciculation in mice lacking the kinesin light chain 1 (Klc1^-/-^) subunit of kinesin-1. Reduced levels of CB1R were found in corticofugal projections and axonal growth cones in Klc1^-/-^ mice. By live-cell imaging of CB1R-eGFP we characterized the axonal transport of CB1R vesicles and described the defects in transport that arise after KLC1 deletion. Cofilin activation, which is necessary for actin dynamics during growth cone remodeling, is impaired in the Klc1^-/-^ cerebral cortex. In addition, Klc1^-/-^ neurons showed expanded growth cones that were unresponsive to CB1R-induced axonal elongation. Together, our data reveal the relevance of kinesin-1 in CB1R axonal transport and in eCB signaling during brain wiring.Fil: Saez, Trinidad María de Los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Fernandez Bessone, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Rodriguez, María S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Alloatti, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Otero, María G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Cromberg, Lucas Eneas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Pozo Devoto, Victorio Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Oubiña, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sosa, Lucas Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Design of Concrete Composites for Advanced Functionality and Sustainability

Concrete presents a significant challenge to the environmental sustainability of the construction sector, being responsible for nearly 9 % of annual global carbon dioxide (CO2) emissions that contribute to climate change. CO2 emissions related to concrete construction may be reduced by: (a) improving the thermal performance of building envelopes to minimize heating/air conditioning energy inputs, (b) extending the service lifetime of concrete infrastructure, or (c) replacing ordinary portland cement (OPC) by alternative binders that emit less CO2 in their production. Three pathways towards these ends are highlighted:a. Using concretes that contain functional inclusions (e.g., phase change materials – PCMs) is one method to improve the thermal performance of building envelopes. While the energy benefits of these concretes have been well-established, the potential for soft PCM inclusions to degrade the mechanical performance of concrete composites may limit their use.b. Reducing the tendency of steel reinforcement within concrete to corrode is a critical step towards extending infrastructural service lifetimes. Typical corrosion mitigation strategies do not directly reduce the abundance of deleterious chloride ions (e.g., from de-icing salts or seawater) and are therefore difficult to implement successfully. c. To directly reduce the embodied CO2 emissions of concrete, it is necessary to develop low-carbon cementitious binders, i.e., carbonate binders that gain strength by converting gaseous CO2 into stable solid minerals. Development of material formulations and processing routes for scalable production of concrete components via carbonation has remained a critical challenge.This dissertation provokes and addresses research questions pertinent to each of these pathways. First, the mechanical behavior of cementitious composites containing PCMs is studied to aid in the development of improved predictive models and PCM dosage guidelines. Second, a novel cementitious formulation featuring unprecedented chloride-scavenging potential is designed and predicted to significantly delay the onset of reinforcing steel corrosion via finite element modeling. Finally, the CO2 mineralization reactions and strength development of carbonate binders containing portlandite (Ca(OH)2) are investigated, towards the production of low-carbon concrete by CO2 capture/utilization from flue gases. These advancements stimulate pathways for the design of sustainable concrete composites that reduce CO2 emissions from the construction sector

Anion capture and exchange by functional coatings: New routes to mitigate steel corrosion in concrete infrastructure

Chloride-induced corrosion is a major cause of degradation of reinforced concrete infrastructure. While the binding of chloride ions (Cl-) by cementitious phases is known to delay corrosion, this approach has not been systematically exploited as a mechanism to increase structural service life. Recently, Falzone et al. [Cement and Concrete Research72, 54-68 (2015)] proposed calcium aluminate cement (CAC) formulations containing NO3-AFm to serve as anion exchange coatings that are capable of binding large quantities of Cl- ions, while simultaneously releasing corrosion-inhibiting NO3- species. To examine the viability of this concept, Cl- binding isotherms and ion-diffusion coefficients of a series of hydrated CAC formulations containing admixed Ca(NO3)2 (CN) are quantified. This data is input into a multi-species Nernst-Planck (NP) formulation, which is solved for a typical bridge-deck geometry using the finite element method (FEM). For exposure conditions corresponding to seawater, the results indicate that Cl- scavenging CAC coatings (i.e., top-layers) can significantly delay the time to corrosion (e.g., 5 ≤ df ≤ 10, where df is the steel corrosion initiation delay factor [unitless]) as compared to traditional OPC-based systems for the same cover thickness; as identified by thresholds of Cl-/OH- or Cl-/NO3- (molar) ratios in solution. The roles of hindered ionic diffusion, and the passivation of the reinforcing steel rendered by NO3- are also discussed

Rheology-Based Protocol to Establish Admixture Compatibility in Dense Cementitious Suspensions

Chemical admixtures are often added to concentrated cementitious suspensions in an effort to adjust their (1) rheology, i.e., yield stress and viscosity; (2) time of set, i.e., when plasticity is lost; and (3) hardening rate. Although the first adjustment is affected by dosage of dispersants, the subsequent two adjustments are made by dosing chemical additives that alter the binder\u27s reaction rate. To ensure desirable field performance, e.g., at subambient temperatures, dispersants and reaction rate enhancers may be dosed simultaneously. In such cases, it is critical to ensure that the dosed additives are compatible with each other. To assess such admixture compatibility and synergy, an original rheology-based method is developed. The method involves assessing the yield stress and plastic viscosity of cementitious suspensions with and without admixtures over a wide strain rate range (10-4 ≤ γ̇ ≤ 102). Three fluidity parameters are examined, including (1) plasticity retention; (2) placement limit, i.e., time at which pumpability/pourability is lost; and (3) the rate of hardening following loss of plasticity. To provide a basis of comparison, each of these parameters is assessed relative to neat cement suspensions, across a range of liquid-to-solid ratios (by mass). The method is demonstrated for cementitious suspensions dosed with polycarboxylate ether (PCE) dispersants and calcium nitrate (CN), a set accelerator. The results highlight a means to identify dispersant/set accelerator combinations (or more generally, chemical admixture combinations) that yield optimal synergistic benefits

The Influence of Slightly and Highly Soluble Carbonate Salts on Phase Relations in Hydrated Calcium Aluminate Cements

The addition of slightly (CaCO3) and highly soluble (Na2CO3) carbonate salts is expected to favor the formation of carboaluminate phases in hydrated calcium aluminate cements (CACs). A multi-method approach including X-ray diffraction, thermogravimetric analysis, and thermodynamic calculations is applied to highlight that the conversion phenomena in CACs cannot be mitigated by the formation of carboaluminate phases (monocarboaluminate: Mc and hemicarboaluminate: Hc) which are anticipated to form following the addition of carbonate salts. Here, carboaluminate phase formation is shown to depend on three factors: (1) water availability, (2) carbonate content of the salts, and their ability to mobilize CO32- species in solution, and (3) lime content associated with the carbonate salt. The latter two factors are linked to the composition and solubility of the carbonate agent. It is concluded that limestone (CaCO3), despite being a source of calcium and carbonate species, contributes only slightly to carboaluminate phase formation due to its low solubility and slow dissolution rate. Soluble carbonate salts (Na2CO3) fail to boost carboaluminate phase formation as the availability of Ca2+ ions and water are limiting. Detailed thermodynamic calculations are used to elucidate conditions that affect the formation of carboaluminate phases