Leaves are arguably the most complex and important physicobiological systems in the ecosphere. Yet, water transport outside the leaf xylem remains poorly understood, despite its impacts on stomatal ...function and photosynthesis. We applied anatomical measurements from 14 diverse species to a novel model of water flow in an areole (the smallest region bounded by minor veins) to predict the impact of anatomical variation across species on outside-xylem hydraulic conductance (Kox). Several predictions verified previous correlational studies: (1) vein length per unit area is the strongest anatomical determinant of Kox, due to effects on hydraulic pathlength and bundle sheath (BS) surface area; (2) palisade mesophyll remains well hydrated in hypostomatous species, which may benefit photosynthesis, (3) BS extensions enhance Kox; and (4) the upper and lower epidermis are hydraulically sequestered from one another despite their proximity. Our findings also provided novel insights: (5) the BS contributes a minority of outside-xylem resistance; (6) vapor transport contributes up to two-thirds of Kox; (7) Koxis strongly enhanced by the proximity of veins to lower epidermis; and (8) Koxis strongly influenced by spongy mesophyll anatomy, decreasing with protoplast size and increasing with airspace fraction and cell wall thickness. Correlations between anatomy and Koxacross species sometimes diverged from predicted causal effects, demonstrating the need for integrative models to resolve causation. For example, (9) Koxwas enhanced far more in heterobaric species than predicted by their having BS extensions. Our approach provides detailed insights into the role of anatomical variation in leaf function.
Although getting married is no longer a requirement for social acceptance, most people do marry in their lifetimes, and couples across the socioeconomic spectrum wish their marriages to be satisfying ...and long lasting. This review evaluates the past decade of research on the determinants of satisfaction and stability in marriage, concluding that the scholarship of the past 10 years has undermined three assumptions that were formerly accepted as conventional wisdom. First, research exploiting methods such as latent class growth analyses reveal that, for most couples, marital satisfaction does not decline over time but in fact remains relatively stable for long periods. Second, contrary to predictions of behavioral models of marriage, negative communication between spouses can be difficult to change, does not necessarily lead to more satisfying relationships when it is changed, and does not always predict distress in the first place. Third, dyadic processes that are reliably adaptive for middle‐class and more affluent couples may operate differently in lower income couples, suggesting that influential models of marriage may not generalize to couples living in diverse environments. Thus, the accumulated research of the past 10 years indicates that the tasks of understanding and promoting marital satisfaction and stability are more complex than we appreciated at the start of the decade, raising important questions that beg to be answered in the years ahead.
Abstract
Background
Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 ...vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States.
Methods
We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States.
Results
Vaccination reduced the overall attack rate to 4.6% (95% credible interval CrI: 4.3%–5.0%) from 9.0% (95% CrI: 8.4%–9.4%) without vaccination, over 300 days. The highest relative reduction (54%–62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%–66.7%), 65.6% (95% CrI: 62.2%–68.6%), and 69.3% (95% CrI: 65.5%–73.1%), respectively, across the same period.
Conclusions
Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact.
Vaccination with a 95% efficacy against disease could substantially mitigate future attack rates, hospitalizations, and deaths, even if only adults are vaccinated. Nonpharmaceutical interventions remain an important part of outbreak response as vaccines are distributed over time.
Obesity is one of the best-documented outcomes of screen media exposure. Many observational studies find relationships between screen media exposure and increased risks of obesity. Randomized ...controlled trials of reducing screen time in community settings have reduced weight gain in children, demonstrating a cause and effect relationship. Current evidence suggests that screen media exposure leads to obesity in children and adolescents through increased eating while viewing; exposure to high-calorie, low-nutrient food and beverage marketing that influences children's preferences, purchase requests, consumption habits; and reduced sleep duration. Some evidence also suggests promise for using interactive media to improve eating and physical activity behaviors to prevent or reduce obesity. Future interdisciplinary research is needed to examine the effects of newer mobile and other digital media exposures on obesity; to examine the effectiveness of additional interventions to mitigate the adverse effects of media exposures on obesity and possible moderators and mediators of intervention effects; to effectively use digital media interventions to prevent and reduce obesity; and to uncover the mechanisms underlying the causal relationships and interactions between obesity-related outcomes and media content, characteristics, and context.
The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income ...countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.
First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval CI: 238,400-398,800) in 2010 to 404,200 (CI: 242,500-657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA CI: 77,900-106,100; 2050: 140,800 CI: 95,500-200,600) and the Democratic Republic of the Congo (2010: 39,700 CI: 32,600-48,800; 2050: 44,700 CI: 27,100-70,500) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 CI: 33,700-59,100; 2050: 33,900 CI: 15,900-64,700). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 CI: 3,174,800-6,699,100 newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800-14,232,700) newborns with SCA globally, 85% (CI: 81%-88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions.
Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India.
Equations for stomatal density and maximum theoretical stomatal conductance as functions of stomatal initiation rate, epidermal cell size, and stomatal size enable scaling from development to flux.
Io is the most volcanically-active object in the solar system. The moon ejects a tonne per second of sulphur-rich gases that fill the vast magnetosphere of Jupiter and drives million-amp electrical ...currents that excite strong auroral emissions. We present the case for including a detailed study of Io within Voyage 2050 either as a standalone mission or as a contribution to a NASA New Frontiers mission, possibly within a Solar System theme centred around current evolutionary or dynamical processes. A comprehensive investigation will provide answers to many outstanding questions and will simultaneously provide information on processes that have formed the landscapes of several other objects in the past. A mission investigating Io will also study processes that have shaped the Earth, Moon, terrestrial planets, outer planet moons, and potentially extrasolar planets. The aim would be simple – tracing the mass and energy flows in the Io-Jupiter system.
Sickle Cell Anemia and Its Phenotypes Williams, Thomas N; Thein, Swee Lay
Annual review of genomics and human genetics,
08/2018, Letnik:
19, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In the 100 years since sickle cell anemia (SCA) was first described in the medical literature, studies of its molecular and pathophysiological basis have been at the vanguard of scientific discovery. ...By contrast, the translation of such knowledge into treatments that improve the lives of those affected has been much too slow. Recent years, however, have seen major advances on several fronts. A more detailed understanding of the switch from fetal to adult hemoglobin and the identification of regulators such as
BCL11A
provide hope that these findings will be translated into genomic-based approaches to the therapeutic reactivation of hemoglobin F production in patients with SCA. Meanwhile, an unprecedented number of new drugs aimed at both the treatment and prevention of end-organ damage are now in the pipeline, outcomes from potentially curative treatments such as allogeneic hematopoietic stem cell transplantation are improving, and great strides are being made in gene therapy, where methods employing both antisickling β-globin lentiviral vectors and gene editing are now entering clinical trials. Encouragingly, after a century of neglect, the profile of the vast majority of those with SCA in Africa and India is also finally improving.
Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution ...capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval CrI: 7.8-29.7) infections, 0.69 (95% CrI: 0.52-0.97) hospitalizations, and 0.34 (95% CrI: 0.25-0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37-0.89) hospitalizations and 0.32 (95% CrI: 0.23-0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.
We report the synthesis and photochemical and biological characterization of the first selective and potent metal-based inhibitors of cytochrome P450 3A4 (CYP3A4), the major human drug metabolizing ...enzyme. Five Ru(II)-based derivatives were prepared from two analogs of the CYP3A4 inhibitor ritonavir, 4 and 6: Ru(tpy)(L)(6)Cl2 (tpy = 2,2′:6′,2″-terpyridine) with L = 6,6′-dimethyl-2,2′-bipyridine (Me2bpy; 8), dimethylbenzoidipyrido3,2-a:2′,3′-cphenazine (Me2dppn; 10) and 3,6-dimethyl-10,15-diphenylbenzoidipyrido3,2-a:2′,3′-cphenazine (Me2Ph2dppn; 11), Ru(tpy)(Me2bpy)(4)Cl2 (7) and Ru(tpy)(Me2dppn)(4)Cl2 (9). Photochemical release of 4 or 6 from 7–11 was demonstrated, and the spectrophotometric evaluation of 7 showed that it behaves similarly to free 4 (type II heme ligation) after irradiation with visible light but not in the dark. Unexpectedly, the intact Ru(II) complexes 7 and 8 were found to inhibit CYP3A4 potently and specifically through direct binding to the active site without heme ligation. Caged inhibitors 9–11 showed dual action properties by combining photoactivated dissociation of 4 or 6 with efficient 1O2 production. In prostate adenocarcinoma DU-145 cells, compound 9 had the best synergistic effect with vinblastine, the anticancer drug primarily metabolized by CYP3A4 in vivo. Thus, our study establishes a new paradigm in CYP inhibition using metalated complexes and suggests possible utilization of photoactive CYP3A4 inhibitory compounds in clinical applications, such as enhancement of therapeutic efficacy of anticancer drugs.
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