Oral rehydration solution (ORS) is a simple intervention that can prevent childhood deaths from severe diarrhea and dehydration. In a previous study, we mapped the use of ORS treatment subnationally ...and found that ORS coverage increased over time, while the use of home-made alternatives or recommended home fluids (RHF) decreased, in many countries. These patterns were particularly striking within Senegal, Mali, and Sierra Leone. It was unclear, however, whether ORS replaced RHF in these locations or if children were left untreated, and if these patterns were associated with health policy changes.
We used a Bayesian geostatistical model and data from household surveys to map the percentage of children with diarrhea that received (1) any ORS, (2) only RHF, or (3) no oral rehydration treatment between 2000 and 2018. This approach allowed examination of whether RHF was replaced with ORS before and after interventions, policies, and external events that may have impacted healthcare access.
We found that RHF was replaced with ORS in most Sierra Leone districts, except those most impacted by the Ebola outbreak. In addition, RHF was replaced in northern but not in southern Mali, and RHF was not replaced anywhere in Senegal. In Senegal, there was no statistical evidence that a national policy promoting ORS use was associated with increases in coverage. In Sierra Leone, ORS coverage increased following a national policy change that abolished health costs for children.
Children in parts of Mali and Senegal have been left behind during ORS scale-up. Improved messaging on effective diarrhea treatment and/or increased ORS access such as through reducing treatment costs may be needed to prevent child deaths in these areas.
Doping is a fundamental requirement for tuning and improving the properties of conventional semiconductors. Recent doping studies including niobium (Nb) doping of molybdenum disulfide (MoS2) and ...tungsten (W) doping of molybdenum diselenide (MoSe2) have suggested that substitutional doping may provide an efficient route to tune the doping type and suppress deep trap levels of 2D materials. To date, the impact of the doping on the structural, electronic, and photonic properties of in situ‐doped monolayers remains unanswered due to challenges including strong film substrate charge transfer, and difficulty achieving doping concentrations greater than 0.3 at%. Here, in situ rhenium (Re) doping of synthetic monolayer MoS2 with ≈1 at% Re is demonstrated. To limit substrate film charge transfer, r‐plane sapphire is used. Electronic measurements demonstrate that 1 at% Re doping achieves nearly degenerate n‐type doping, which agrees with density functional theory calculations. Moreover, low‐temperature photoluminescence indicates a significant quench of the defect‐bound emission when Re is introduced, which is attributed to the MoO bond and sulfur vacancies passivation and reduction in gap states due to the presence of Re. The work presented here demonstrates that Re doping of MoS2 is a promising route toward electronic and photonic engineering of 2D materials.
This work demonstrates in situ rhenium (Re) doping of synthetic monolayer MoS2 with ≈1 at% Re on r‐plane sapphire. Electronic measurements elucidate that 1 at% Re doping achieves nearly degenerate n‐type doping, which agrees with density functional theory calculations. Low‐temperature photoluminescence measurements reveal suppression of defect emission induced by Re doping, resulting from the passivation of defects due to the presence of Re.
Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)
. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ...ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS
. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes-in particular the ECM protease ADAMTS4-and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections.
Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among ...numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.
In article number 1706950, Joshua A. Robinson and co‐workers demonstrate in‐situ Re doping of synthetic monolayer MoS2 with ≈1 at% Re on r‐plane sapphire. Electronic measurements and density ...functional theory calculations show that 1 at% Re doping achieves nearly degenerate n‐type doping. Low‐temperature photoluminescence reveals a suppression of defect emission, resulting from the passivation of defects due to the presence of Re. Picture Credit: Donna Deng.
Leukotrienes (LTs) are a class of lipid mediators implicated in numerous inflammatory disorders. Caffeic acid phenethyl ester (CAPE) possesses potent anti‐LTs activity through the inhibition of ...5‐lipoxygenase (5‐LO), the key enzyme in the biosynthesis of LTs. In this study, we describe the design and synthesis of CAPE analogs as radical scavengers and 5‐LO inhibitors. Caffeic esters bearing propargyl and allyl linkers between the caffeoyl and aryl moieties (4a–i and 5a–i, respectively) were synthesized by Sonogashira and Heck cross‐coupling reactions to probe the effects of flexibility and aryl substitution on 5‐LO inhibition. Caffeoyl alcohol and ethers (6, 7a–b) as well as caffeoyl aldehyde and ketones (8a–e) were synthesized to elucidate the importance of the ester linkage for inhibitory activity. All tested compounds proved to be good radical scavengers (IC50 of 10–30 μm). After preliminary anti‐LTs activity screening in HEK293 cell models, 5‐LO inhibition potential of selected compounds was determined in human polymorphonuclear leukocytes (PMNL). Most screened compounds outperformed CAPE 3 in concentration‐dependent assays on PMNL, with ester dimers 4i and 5i along with caffeoyl ethers 7a–b being roughly eight‐, seven‐, and 16‐fold more potent than Zileuton, with IC50 values of 0.36, 0.43, and 0.18 μm, respectively.
A series of caffeic acid phenethyl ester (CAPE) analogs was synthesized and screened in vitro for their ability to inhibit 5‐lipoxygenase (5‐LO) along with 2,2‐diphenyl‐1‐picrylhydrazyl free radical scavenging assay. Many screened compounds outperformed CAPE in concentration‐dependent assays on HEK293 cell models and human polymorphonuclear leukocytes, caffeoyl ethers 7a–b being roughly sevenfold and 16‐fold more potent than Zileuton, the only 5‐LO inhibitor currently approved for human therapy.
This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control.
In this ...prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing.
A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants <1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants <1 year was –2.5 for girls and −3.2 for boys and decreased up to the age 5 years (−5.3 for girls; −4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged <1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward.
This study represents one of the largest datasets of prospectively collected medical and longitudinal growth data in children with achondroplasia. It serves as a robust historical control to measure therapeutic interventions against and to further delineate the natural history of this condition.
Abstract
Doping is a fundamental requirement for tuning and improving the properties of conventional semiconductors. Recent doping studies including niobium (Nb) doping of molybdenum disulfide (MoS
2
...) and tungsten (W) doping of molybdenum diselenide (MoSe
2
) have suggested that substitutional doping may provide an efficient route to tune the doping type and suppress deep trap levels of 2D materials. To date, the impact of the doping on the structural, electronic, and photonic properties of in situ‐doped monolayers remains unanswered due to challenges including strong film substrate charge transfer, and difficulty achieving doping concentrations greater than 0.3 at%. Here, in situ rhenium (Re) doping of synthetic monolayer MoS
2
with ≈1 at% Re is demonstrated. To limit substrate film charge transfer,
r
‐plane sapphire is used. Electronic measurements demonstrate that 1 at% Re doping achieves nearly degenerate n‐type doping, which agrees with density functional theory calculations. Moreover, low‐temperature photoluminescence indicates a significant quench of the defect‐bound emission when Re is introduced, which is attributed to the MoO bond and sulfur vacancies passivation and reduction in gap states due to the presence of Re. The work presented here demonstrates that Re doping of MoS
2
is a promising route toward electronic and photonic engineering of 2D materials.
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