Solubility of Indium-Tin Oxide in simulated lung and gastric fluids: Pathways for human intake

ArticleThis is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.From being a metal with very limited natural distribution, indium (In) has recently become disseminated throughout the human society. Little is know of how In compounds behave in the natural environment, but recent medical studies link exposure to In compounds to elevated risk of respiratory disorders. Animal tests suggest that exposure may lead to more widespread damage in the body, notably the liver, kidneys and spleen. In this paper, we investigate the solubility of the most widely used In compound, indium-tin oxide (ITO) in simulated lung and gastric fluids in order to better understand the potential pathways for metals to be introduced into the bloodstream. Our results show significant potential for release of In and tin (Sn) in the deep parts of the lungs (artificial lysosomal fluid) and digestive tract, while the solubility in the upper parts of the lungs (the respiratory tract or tracheobronchial tree) is very low. Our study confirms that ITO is likely to remain as solid particles in the upper parts of the lungs, but that particles are likely to slowly dissolve in the deep lungs. Considering the prolonged residence time of inhaled particles in the deep lung, this environment is likely to provide the major route for uptake of In and Sn from inhaled ITO nano- and microparticles. Although dissolution through digestion may also lead to some uptake, the much shorter residence time is likely to lead to much lower risk of uptake.This paper was in part supported by the Natural Environment Research Council (NERC, NE/L001896/1). The authors benefited from advice from and discussions with Dr Adam Feldman, sample preparation and X-ray diffraction by Dr Gavyn Rollinson, and ICP- MS analysis by Sharon Uren

Synthetic RNA modules for fine-tuning gene expression levels in yeast by modulating RNase III activity

The design of synthetic gene networks requires an extensive genetic toolbox to control the activities and levels of protein components to achieve desired cellular functions. Recently, a novel class of RNA-based control modules, which act through post-transcriptional processing of transcripts by directed RNase III (Rnt1p) cleavage, were shown to provide predictable control over gene expression and unique properties for manipulating biological networks. Here, we increase the regulatory range of the Rnt1p control elements, by modifying a critical region for enzyme binding to its hairpin substrates, the binding stability box (BSB). We used a high throughput, cell-based selection strategy to screen a BSB library for sequences that exhibit low fluorescence and thus high Rnt1p processing efficiencies. Sixteen unique BSBs were identified that cover a range of protein expression levels, due to the ability of the sequences to affect the hairpin cleavage rate and to form active cleavable complexes with Rnt1p. We further demonstrated that the activity of synthetic Rnt1p hairpins can be rationally programmed by combining the synthetic BSBs with a set of sequences located within a different region of the hairpin that directly modulate cleavage rates, providing a modular assembly strategy for this class of RNA-based control elements

Public Health Preparedness & Response: An Exercise in Administrative Law

Responses to epidemics, pandemics, and other biological disasters require multiple coordinated initiatives that combine sophisticated planning, sound emergency management, effective stockpiles, solid geographic information systems, well-developed laboratory surveillance and response, and effective management capabilities. Critical to the noted elements of planning and response is the existence of a legal structure, which underpins the operations of necessary programs. While the law may not be the first public health tool considered in a disaster, it is fundamental to the effective functioning of multiple actors and must be harmonized across jurisdictional lines. This article explores the role of law in pandemics and other biological catastrophes, highlighting broad developments in public health law that have been sparked by recent events. The piece will consider general responses and trends in health disaster management in the context of administrative law with a particular focus on agency responses. Background discussion will also offer a broad overview of the evolution of federal and state laws, highlighting core areas where parallel legal frameworks have developed. The second half of this essay will paint a more detailed portrait of administrative law responses to public health disasters focusing on the Food and Drug Administration (“FDA”), exploring medical countermeasures pursued by this agency to enhance preparedness and response. Key FDA legislation and recent guidance, as well as emergency use authorization (“EUA”) policies, will be analyzed, as a case study of how a pivotal agency has been shaped through law to deal with public health crises

Teaching Chinese to international students in China: political rhetoric and ground realities

This paper presents an on-going study of the enactment of The International Promotion of Chinese Policy (国际汉语推广政策). It explores how Chinese teaching and learning take place in a Chinese university under the Study in China Programme which allows international students, after a period of intensive Chinese language learning, to transfer to academic courses taught in Chinese for Chinese students at the tertiary level. This programme has expanded in recent years in response to the government's goal to enhance China's soft power globally. By studying policy documents, engaging in conversations with students and teachers, and observing classrooms, our study reveals that there are conflicting interests of social actors at national, institutional and individual levels, causing considerable conflicts and tensions in three aspects:1) the divergent goals of internationalisation between the government and the higher education institution; 2) the imperative need of academic Chinese for subject learning and the actual offer of Chinese for everyday communication; and 3) the competing role of English versus Chinese as a lingua franca for communication in the university setting. These conflicts make it difficult for international students to benefit from the subject courses, and for universities to implement successful language programmes for international students, and this renders the political objective of this programme difficult to achieve

Public Health Preparedness & Response: An Exercise in Administrative Law

Responses to epidemics, pandemics, and other biological disasters require multiple coordinated initiatives that combine sophisticated planning, sound emergency management, effective stockpiles, solid geographic information systems, well-developed laboratory surveillance and response, and effective management capabilities. Critical to the noted elements of planning and response is the existence of a legal structure, which underpins the operations of necessary programs. While the law may not be the first public health tool considered in a disaster, it is fundamental to the effective functioning of multiple actors and must be harmonized across jurisdictional lines. This article explores the role of law in pandemics and other biological catastrophes, highlighting broad developments in public health law that have been sparked by recent events. The piece will consider general responses and trends in health disaster management in the context of administrative law with a particular focus on agency responses. Background discussion will also offer a broad overview of the evolution of federal and state laws, highlighting core areas where parallel legal frameworks have developed. The second half of this essay will paint a more detailed portrait of administrative law responses to public health disasters focusing on the Food and Drug Administration (“FDA”), exploring medical countermeasures pursued by this agency to enhance preparedness and response. Key FDA legislation and recent guidance, as well as emergency use authorization (“EUA”) policies, will be analyzed, as a case study of how a pivotal agency has been shaped through law to deal with public health crises

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

A Feline-Specific Anti-Nerve Growth Factor Antibody Improves Mobility in Cats with Degenerative Joint Disease-Associated Pain: A Pilot Proof of Concept Study

BACKGROUND: Neutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occurring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans. OBJECTIVES: To evaluate the efficacy of a fully felinized anti-NGF antibody (NV-02) for the treatment of DJD pain and mobility impairment in cats. ANIMALS: Thirty-four client-owned cats with DJD-associated pain and mobility impairment. METHODS: In a placebo-controlled, pilot, masked clinical study, cats were randomized to a single treatment with NV-02 (0.4 mg/kg SC [n = 11] or 0.8 mg/kg SC [n = 12]) or placebo (saline, SC [n = 11]). Activity was measured objectively. Additionally, owners completed clinical metrology instruments (client-specific outcome measures [CSOM] and feline musculoskeletal pain index [FMPI]) on days 0 (screening), 14 (baseline), 35, 56, and 77. A repeated-measures model was used to evaluate the objective activity data. RESULTS: NV-02 significantly increased objectively measured activity overall (P = .017) and at 2 (P = .035), 3 (P = .007), 4 (P = .006), 5 (P = .007), and 6 (P = .017) weeks after treatment. CSOM scores (P = .035) and pain (P = .024) showed a significant effect of treatment 3 weeks after administration. In the treatment group, 83% of the owners correctly identified the treatment administered compared with 45% of owners in the placebo group (P = .013). No treatment-related adverse effects were identified. CONCLUSIONS: These pilot data demonstrate a 6-week duration positive analgesic effect of this fully felinized anti-NGF antibody in cats suffering from DJD-associated pain

Racial/Ethnic Disparities in Access to Care among Children: How Does Medicaid Do in Closing the Gaps?

While Medicaid and the Children\u27s Health Insurance Program (CHIP) have become increasingly important sources of health coverage for low-income children in all racial and ethnic groups, the program plays an especially large role for children of color, who are more likely than white children to be low-income. In 2007, Medicaid and CHIP covered nearly one in five white children, but roughly two in five African American and Hispanic children. As policymakers engaged in health reform consider the merits of public and private approaches to expanding coverage, this report provides an assessment of Medicaid\u27s relative impact on racial and ethnic disparities in access. The analysis compared health care access for white, African American and Hispanic children who were privately insured, uninsured, or enrolled in Medicaid or CHIP. Key findings include: Racial and ethnic disparities in access to care were no more likely among children enrolled in Medicaid than among privately insured children. Insurance coverage – both private and Medicaid – often improved access for children in each racial and ethnic group, but generally did not significantly narrow racial and ethnic disparities in their access to health care. This report analyzes data for more than 15,000 children from the 2003 and 2004 Medical Expenditure Panel Survey, a nationally representative household survey conducted by the Agency for Healthcare Research and Quality

Environmental determinants of macroinvertebrate diversity in small water bodies: insights from tank-bromeliads

The interlocking leaves of tank-forming bromeliads (Bromeliaceae) collect rainwater and detritus, thus creating a freshwater habitat for specialized organisms. Their abundance and the possibility of quantifying communities with accuracy give us unparalleled insight into how changes in local to regional environments influence community diversity in small water bodies. We sampled 365 bromeliads (365 invertebrate communities) along a southeastern to northwestern range in French Guiana. Geographic locality determined the species pool for bromeliad invertebrates, and local environments determined the abundance patterns through the selection of traits that are best adapted to the bromeliad habitats. Patterns in community structure mostly emerged from patterns of predator species occurrence and abundance across local-regional environments, while the set of detritivores remained constant. Water volume had a strong positive correlation with invertebrate diversity, making it a biologically relevant measure of the pools' carrying capacity. The significant effects of incoming detritus and incident light show that changes in local environments (e.g., the conversion of forest to cropping systems) strongly influence freshwater communities. Because changes in local environments do not affect detritivores and predators equally, one may expect functional shifts as sets of invertebrates with particular traits are replaced or complemented by other sets with different traits