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"HSIAO, C.-C."
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إصلاح حقيقي للقطاع الصحي : مرشدك إلى تحسين الأداء والإنصاف
يعد هذا الكتاب \"المرجع\" للإسهام في الحوار الدائر حاليا حول مستقبل نظامنا الصحي ولعله يصبح أحد أدلة العمل المرشدة لصانعي السياسات الصحية ولقيادات القطاع الصحي العليا والوسيطة ولعله يسهم في إضاءة الطريق الملبد بالغيوم في سياق مشروع التأمين الصحي الشامل وبعد مرور أكثر من عقد كامل على البدء فى عملية إصلاح القطاع الصحى في مصر ما زالت التحديات قائمة بل يمكن أن ندعى بلا مبالغة أن بعضها قد تفاقم.
BOOK
Application of protoplast technology to CRISPR/Cas9 mutagenesis: from single‐cell mutation detection to mutant plant regeneration
Summary Plant protoplasts are useful for assessing the efficiency of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) mutagenesis. We improved the process of protoplast isolation and transfection of several plant species. We also developed a method to isolate and regenerate single mutagenized Nicotianna tabacum protoplasts into mature plants. Following transfection of protoplasts with constructs encoding Cas9 and sgRNAs, target gene DNA could be amplified for further analysis to determine mutagenesis efficiency. We investigated N. tabacum protoplasts and derived regenerated plants for targeted mutagenesis of the phytoene desaturase (NtPDS) gene. Genotyping of albino regenerants indicated that all four NtPDS alleles were mutated in amphidiploid tobacco, and no Cas9 DNA could be detected in most regenerated plants.
Journal Article
Early appraisal of China's huge and complex health-care reforms
China's 3 year, CN¥850 billion (US$125 billion) reform plan, launched in 2009, marked the first phase towards achieving comprehensive universal health coverage by 2020. The government's undertaking of systemic reform and its affirmation of its role in financing health care together with priorities for prevention, primary care, and redistribution of finance and human resources to poor regions are positive developments. Accomplishing nearly universal insurance coverage in such a short time is commendable. However, transformation of money and insurance coverage into cost-effective services is difficult when delivery of health care is hindered by waste, inefficiencies, poor quality of services, and scarcity and maldistribution of the qualified workforce. China must reform its incentive structures for providers, improve governance of public hospitals, and institute a stronger regulatory system, but these changes have been slowed by opposition from stakeholders and lack of implementation capacity. The pace of reform should be moderated to allow service providers to develop absorptive capacity. Independent, outcome-based monitoring and evaluation by a third-party are essential for mid-course correction of the plans and to make officials and providers accountable.
Journal Article
Colloidal gel elasticity arises from the packing of locally glassy clusters
Colloidal gels formed by arrested phase separation are found widely in agriculture, biotechnology, and advanced manufacturing; yet, the emergence of elasticity and the nature of the arrested state in these abundant materials remains unresolved. Here, the quantitative agreement between integrated experimental, computational, and graph theoretic approaches are used to understand the arrested state and the origins of the gel elastic response. The micro-structural source of elasticity is identified by the
l
-balanced graph partition of the gels into minimally interconnected clusters that act as rigid, load bearing units. The number density of cluster-cluster connections grows with increasing attraction, and explains the emergence of elasticity in the network through the classic Cauchy-Born theory. Clusters are amorphous and iso-static. The internal cluster concentration maps onto the known attractive glass line of sticky colloids at low attraction strengths and extends it to higher strengths and lower particle volume fractions.
Colloidal gels are typically composed of solid particles dispersed in a liquid, which show some peculiar mechanic properties but their origins remain largely unsolved. Here, Whitaker et al. show that the elasticity formed via arrested phase separation arises from the packing of glassy clusters in gels.
Journal Article
Clinical and phenotypic differences between classic and hypervirulent Klebsiella pneumonia: an emerging and under-recognized pathogenic variant
The purpose of this study was to increase awareness, gain insight into acquisition, and assess the virulence of the hypervirulent (hypermucoviscous) clinical variant (hvKP) that is entrenched in the Pacific Rim but emerging in Western countries. A case of community-acquired liver abscess with metastatic spread to the spleen is described. Comparative
in vitro
and
in vivo
virulence studies on this isolate (hvKP1) and four randomly chosen blood isolates of “classic”
K. pneumonia
strains (cKP1-4) were performed. Cases of hvKP infection are occurring in Western countries and are under-recognized. A hypermucoviscous phenotype is a surrogate laboratory marker for this variant. The propensity of hvKP strains for metastatic spread in non-compromised hosts is both a defining and unusual trait. The mode of acquisition in the described case was unclear but potential means are discussed. hvKP1 was more resistant to complement and neutrophil-mediated bactericidal activity and was more virulent in a rat subcutaneous abscess model than cKP1-4. Recognition of the hypermucoviscous phenotype, defined by a positive “string-test”, will alert the microbiologist or clinician that the infecting strain may be a hvKP, which is hypervirulent compared to cKP. This will improve our understanding of the epidemiology and clinical spectrum of infection, which may be more extensive than appreciated.
Journal Article
AquaCrop--The FAO Crop Model to Simulate Yield Response to Water: II. Main Algorithms and Software Description
The AquaCrop model was developed to replace the former FAO I&D Paper 33 procedures for the estimation of crop productivity in relation to water supply and agronomic management in a framework based on current plant physiological and soil water budgeting concepts. This paper presents the software of AquaCrop for which the concepts and underlying principles are described in the companion paper (Steduto et al., 2009). Input consists of weather data, crop characteristics, and soil and management characteristics that define the environment in which the crop will develop. Algorithms and calculation procedures modeling the infiltration of water, the drainage out of the root zone, the canopy and root zone development, the evaporation and transpiration rate, the biomass production, and the yield formation are presented. The mechanisms of crop response to cope with water shortage are described by only a few parameters, making the underlying processes more transparent to the user. AquaCrop is a menu-driven program with a well-developed user interface. With the help of graphs which are updated each time step (1 d) during the simulation run, the user can track changes in soil water content, and the corresponding changes in crop development, soil evaporation and transpiration rate, biomass production, and yield development. One can halt the simulation at each time step, to study the effect of changes in water related inputs, making the model particularly suitable for developing deficit irrigation strategies and scenario analysis.
Journal Article
Elastohydrodynamic friction of robotic and human fingers on soft micropatterned substrates
Frictional sliding between patterned surfaces is of fundamental and practical importance in the haptic engineering of soft materials. In emerging applications such as remote surgery and soft robotics, thin fluid films between solid surfaces lead to a multiphysics coupling between solid deformation and fluid dissipation. Here, we report a scaling law that governs the peak friction values of elastohydrodynamic lubrication on patterned surfaces. These peaks, absent in smooth tribopairs, arise due to a separation of length scales in the lubricant flow. The framework is generated by varying the geometry, elasticity and fluid properties of soft tribopairs and measuring the lubricated friction with a triborheometer. The model correctly predicts the elastohydrodynamic lubrication friction of a bioinspired robotic fingertip and human fingers. Its broad applicability can inform the future design of robotic hands or grippers in realistic conditions, and open up new ways of encoding friction into haptic signals.
A framework for the elastohydrodynamic lubrication between soft patterned surfaces identifies the contributions of substrate elasticity and pattern geometry for friction, which have implications for the engineering of haptic soft materials.
Journal Article
Role of isostaticity and load-bearing microstructure in the elasticity of yielded colloidal gels
We report a simple correlation between microstructure and strain-dependent elasticity in colloidal gels by visualizing the evolution of cluster structure in high strain-rate flows. We control the initial gel microstructure by inducing different levels of isotropic depletion attraction between particles suspended in refractive index matched solvents. Contrary to previous ideas from mode coupling and micromechanical treatments, our studies show that bond breakage occurs mainly due to the erosion of rigid clusters that persist far beyond the yield strain. This rigidity contributes to gel elasticity even when the sample is fully fluidized; the origin of the elasticity is the slow Brownian relaxation of rigid, hydrodynamically interacting clusters. We find a power-law scaling of the elastic modulus with the stress-bearing volume fraction that is valid over a range of volume fractions and gelation conditions. These results provide a conceptual framework to quantitatively connect the flow-induced microstructure of soft materials to their nonlinear rheology.
Journal Article
Prevalence of fibrodysplasia ossificans progressiva (FOP) in the United States: estimate from three treatment centers and a patient organization
Background
Fibrodysplasia ossificans progressiva (FOP), an ultra-rare, progressive, and permanently disabling disorder of extraskeletal ossification, is characterized by episodic and painful flare-ups and irreversible heterotopic ossification in muscles, tendons, and ligaments. Prevalence estimates have been hindered by the rarity of FOP and the heterogeneity of disease presentation. This study aimed to provide a baseline prevalence of FOP in the United States, based on contact with one of 3 leading treatment centers for FOP (University of Pennsylvania, Mayo Clinic, or University of California San Francisco), the International Fibrodysplasia Ossificans Progressiva Association (IFOPA) membership list, or the IFOPA FOP Registry through July 22, 2020.
Results
Patient records were reviewed, collected, and deduplicated using first and last name initials, sex, state, and year of birth. A Kaplan–Meier survival curve was applied to each individual patient to estimate the probability that he or she was still alive, and a probability-weighted net prevalence estimate was calculated. After deduplication, 373 unique patients were identified in the United States, 294 of whom who were not listed as deceased in any list. The average time since last contact for 284 patients was 1.5 years. Based on the application of the survival probability, it is estimated that 279 of these patients were alive on the prevalence date (22 July 2020). An adjusted prevalence of 0.88 per million US residents was calculated using either an average survival rate estimate of 98.4% or a conservative survival rate estimate of 92.3% (based on the Kaplan–Meier survival curve from a previous study) and the US Census 2020 estimate of 329,992,681 on prevalence day.
Conclusions
This study suggests that the prevalence of FOP is higher than the often-cited value of 0.5 per million. Even so, because inclusion in this study was contingent upon treatment by the authors, IFOPA membership with confirmed clinical diagnosis, and the FOP Registry, the prevalence of FOP in the US may be higher than that identified here. Thus, it is imperative that efforts be made to identify and provide expert care for patients with this ultra-rare, significantly debilitating disease.
Journal Article
Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system
Interactions between adipose tissue, liver and immune system are at the center of metabolic dysfunction-associated steatotic liver disease and type 2 diabetes. To address the need for an accurate in vitro model, we establish an interconnected microphysiological system (MPS) containing white adipocytes, hepatocytes and proinflammatory macrophages derived from isogenic human induced pluripotent stem cells. Using this MPS, we find that increasing the adipocyte-to-hepatocyte ratio moderately affects hepatocyte function, whereas macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease. We also use our MPS to identify and characterize pharmacological intervention strategies for hepatic steatosis and systemic insulin resistance and find that the glucagon-like peptide-1 receptor agonist semaglutide improves hepatocyte function by acting specifically on adipocytes. These results establish our MPS modeling the adipose tissue-liver axis as an alternative to animal models for mechanistic studies or drug discovery in metabolic diseases.
In vitro modelling of the adipose tissue-liver axis can advance understanding and therapy of metabolic disease, including by distinguishing effects of obesity and inflammation. Here, authors develop such a system based on isogenic human iPSCs and interconnected microphysiological devices.
Journal Article