Southeast Asia consists of several microcontinents that detached from the northeastern margin of Gondwanaland. The Song Ma belt in northern Vietnam consists of ophiolite, metabasite, metasedimentary ...rocks and eclogite, and it is thought to be a suture zone between the Indochina and South China blocks. However, the nature and boundaries of the Song Ma belt and the collision age of the two blocks have long been debated. In this article, petrological and geochemical studies on the Song Ma ophiolite and eclogite and first sensitive high‐resolution ion microprobe (SHRIMP) age dating of eclogite provide new light to resolve such debate. Eclogite consisting of garnet, omphacite, phengite, quartz, barroisite and rutile is closely associated with garnet–phengite–quartz schist in the ‘Nam Co antiform’, a northern subunit of the Song Ma belt. The eclogite experienced a three‐stage metamorphic evolution: (I) pre‐eclogite stage (amphibolite facies) defined by inclusions of taramite, barroisite, quartz, zoisite/epidote, mica, rutile & rare chlorite in garnet, (II) eclogite stage and (III) retrograde stage of amphibolite to greenschist facies. The P–T conditions of the three stages are of 14–16 kbar and 520–550 °C (I), 24–27 kbar and 650–750 °C (II), and 3–7 kbar and 430–510 °C (III), and show a clockwise P–T path based on their mineral assemblages and stability fields in the P–T pseudosection. Thermobarometric results yield similar peak pressure and temperature (26–28 kbar and 650–710 °C). These data suggest that the Song Ma eclogite underwent high‐pressure metamorphism in subduction zone with a low thermal gradient ∼8 °C km−1. The Song Ma ophiolite is composed of serpentinized peridotite, gabbro, basalt, mafic dyke and chert, and experienced ocean‐floor metamorphism. Metabasalt and gabbro of ophiolite suite and eclogite all have MORB‐type geochemical affinities. Zircon separates from eclogite have very low Th/U ratios of 0.01–0.05, indicating a metamorphic origin. SHRIMP U–Pb isotopic analyses of this zircon yield a 206Pb/238U weighted mean age of 230.5 ± 8.2 Ma. This age is interpreted as the closure age of the Paleotethys Ocean that separated the South China and Indochina blocks, and the subsequent collision of the two blocks that took place at the Middle Triassic corresponding to the major episode of the Indosinian Orogeny.
We present microlensing events in the 2015 Korea Microlensing Telescope Network (KMTNet) data and our procedure for identifying these events. In particular, candidates were detected with a novel ..."completed-event" microlensing event-finder algorithm. The algorithm works by making linear fits to a grid of point-lens microlensing models. This approach is rendered computationally efficient by restricting u0 to just two values (0 and 1), which we show is quite adequate. The implementation presented here is specifically tailored to the commission-year character of the 2015 data, but the algorithm is quite general and has already been applied to a completely different (non-KMTNet) data set. We outline expected improvements for 2016 and future KMTNet data. The light curves of the 660 "clear microlensing" and 182 "possible microlensing" events that were found in 2015 are presented along with our policy for their public release.
The chemical composition of the Gaoping River in Taiwan reflects the weathering of both silicate and carbonate rocks found in its metasedimentary catchment. Major dissolved ion chemistry and ...radiocarbon signatures of dissolved inorganic carbon (DIC) reveal the importance of pyrite-derived sulphuric acid weathering on silicates and carbonates. Two-thirds of the dissolved load of the Gaoping River derives from sulphuric acid-mediated weathering of rocks within its catchment. This is reflected in the lowest reported signatures DI
C for a small mountainous river (43 to 71 percent modern carbon), with rock-derived carbonate constituting a
C-free DIC source. Using an inverse modelling approach integrating riverine major dissolved ion chemistry and DI
C, we provide quantitative constraints of mineral weathering pathways and calculate atmospheric CO
fluxes resulting from the erosion of the Taiwan orogeny over geological timescales. The results reveal that weathering on Taiwan releases 0.31 ± 0.12 MtC/yr, which is offset by burial of terrestrial biospheric organic carbon in offshore sediments. The latter tips the balance with respect to the total CO
budget of Taiwan such that the overall system acts as a net sink, with 0.24 ± 0.13 MtC/yr of atmospheric CO
consumed over geological timescales.
Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of ...global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs.
Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis.
One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001).
Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs.
•Before undertaking this study, we searched academic databases for all English systematic reviews on global orphan drug policies published before July 2019. We identified 1 review on orphan drug policies published in 2015 and 2 reviews on laws and national strategies for rare diseases from selected countries that were published in 2017 and 2018, respectively. These 3 reviews uncovered a plethora of governmental efforts that facilitate the availability of and access to orphan drugs, with critical differences in scope and approaches among countries.•Vast areas worldwide were omitted from previous reviews, such as Africa, India, Latin America, and Russia. No studies attempted an overview of orphan drug policies in all countries with both governmental and academic evidence. The current global landscape of orphan drug policy (ODP) remains unclear. By systematically reviewing pharmaceutical policies and academic literature from 200 countries/areas, our study presents the most comprehensive review on global ODP to date.•Of the 200 countries or areas examined, 92 had ODPs alongside a notable increase in ODP establishment in non-high-income countries/areas over the last decade. Our findings highlight disparities in ODP establishment and scope in countries/areas with different income levels. This allows respective stakeholders to reference orphan drug regulatory standards of countries/areas with similar political realities while informing policy formulation and advocacy direction for treatment access of patients with rare diseases.
SUMMARY
Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We ...investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)‐γ, inflammatory cytokines interleukin (IL)‐1, IL‐6 and IL‐12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)‐α, anti‐inflammatory cytokine IL‐10, Th1 cytokine IL‐2 and Th2 cytokine IL‐4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL‐8, monocyte chemoattractant protein‐1 (MCP‐1), and Th1 chemokine IFN‐γ‐inducible protein‐10 (IP‐10). Corticosteroid reduced significantly IL‐8, MCP‐1 and IP‐10 concentrations from 5 to 8 days after treatment (all P < 0·001). Together, the elevation of Th1 cytokine IFN‐γ, inflammatory cytokines IL‐1, IL‐6 and IL‐12 and chemokines IL‐8, MCP‐1 and IP‐10 confirmed the activation of Th1 cell‐mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.
The Red River shear zone (RRSZ) is a major left‐lateral strike‐slip shear zone, containing a ductilely deformed metamorphic core bounded by brittle strike‐slip and normal faults, which stretches for ...>1000 km from Tibet through Yunnan and North Vietnam to the South China Sea. The RRSZ exposes four high‐grade metamorphic core complexes along its length. Various lithologies from the southernmost core complex, the Day Nui Con Voi (DNCV), North Vietnam, provide new constraints on the tectonic and metamorphic evolution of this region prior to and following the initial India–Asia collision. Analysis of a weakly deformed anatectic paragneiss using P–T pseudosections constructed in the MnO–Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–O (MnNCKFMASHTO) system provides prograde, peak and retrograde metamorphic conditions, and in situ U–Th–Pb geochronology of metamorphic monazite yields texturally controlled age constraints. Tertiary metamorphism and deformation, overprinting earlier Triassic metamorphism associated with the Indosinian orogeny and possible Cretaceous metamorphism, are characterized by peak metamorphic conditions of ~805 °C and ~8.5 kbar between c. 38 and 34 Ma. Exhumation occurred along a steep retrograde P–T path with final melt crystallizing at the solidus at ≥~5.5 kbar at ~790 °C. Further exhumation at ~640–700 °C and ~4–5 kbar at c. 31 Ma occurred at subsolidus conditions. U–Pb geochronological analysis of monazite from a strongly deformed pre‐kinematic granite dyke from the flank of the DNCV provides further evidence for exhumation at this time. Magmatic grains suggest initial emplacement at 66.0 ± 1.0 Ma prior to the India–Asia collision, whereas grains with metamorphic characteristics indicate later growth at 30.6 ± 0.4 Ma. Monazite grains from a cross‐cutting post‐kinematic dyke within the core of the DNCV antiform provide a minimum age constraint of 25.2 ± 1.4 Ma for the termination of fabric development. A separate and significant episode of monazite growth at c. 83–69 Ma is suggested to be the result of fluid‐assisted recrystallization following the emplacement of magmatic units.
In recent years, food supply chains have faced increased quality risk, caused by the extended global supply chain and increased consumer demands on quality and safety. Given the concern regarding ...quality sustainability in the food supply chain, much attention is being paid to continuous planning and monitoring of quality assurance practices in the supply chain network. In this research, we propose a supply chain quality sustainability decision support system (QSDSS), adopting association rule mining and Dempster's rule of combination techniques. The aim of QSDSS is to support managers in food manufacturing firms to define good logistics plans in order to maintain the quality and safety of food products. We conduct a case study of a Hong Kong red wine company in order to illustrate the applicability and effectiveness of QSDSS. Implications of the proposed approach are discussed, and suggestions for future work are outlined.
•We propose a decision support system of supply chain quality sustainability (QSDSS) by adopting association rule mining and Dempster's rule of combination techniques.•The aim of QSDSS is to support manager in food manufacturing firms to define good logistics plan in order to maintain quality and safety of food product.•A case study of Hong Kong red wine company is conducted in order to illustrate the applicability and effectiveness of QSDSS.
The Danba Structural Culmination is a tectonic window into the late Triassic to early Jurassic Songpan‐Garzê Fold Belt of eastern Tibet, which exposes an oblique section through a complete ...Barrovian‐type metamorphic sequence. Systematic analysis of a suite of metapelites from this locality has enabled a general study of Barrovian metamorphism, and provided new insights into the early thermotectonic history of the Tibetan plateau. The suite was used to create a detailed petrographic framework, from which four samples ranging from staurolite to sillimanite grade were selected for thermobarometry and geochronology. Pseudosection analysis was applied to calculate P–T path segments and determine peak conditions between staurolite grade at ∼5.2 kbar and 580 °C and sillimanite grade at ∼6.0 kbar and 670 °C. In situ U–Pb monazite geochronology reveals that staurolite‐grade conditions were reached at 191.5 ± 2.4 Ma, kyanite‐grade conditions were attained at 184.2 ± 1.5 Ma, and sillimanite‐grade conditions continued until 179.4 ± 1.6 Ma. Integration of the results has provided constraints on the evolution of metamorphism in the region, including a partial reconstruction of the regional metamorphic field gradient. Several key features of Barrovian metamorphism are documented, including nested P–T paths and a polychronic field gradient. In addition, several atypical features are noted, such as P–T path segments having similar slopes to the metamorphic field gradient, and Tmax and Pmax being reached simultaneously in some samples. These features are attributed to the effects of slow tectonic burial, which allows for thermal relaxation during compression. While nested, clockwise P–T–t loops provide a useful framework for Barrovian metamorphism, this study shows that the effects of slow burial can telescope this model in P–T space. Finally, the study demonstrates that eastern Tibet experienced a significant phase of crustal thickening during the Mesozoic, reinforcing the notion that the plateau may have a long history of uplift and growth.
Abstract
Aims
Adipocyte fatty acid-binding protein (A-FABP) is an adipokine implicating in various metabolic diseases. Elevated circulating levels of A-FABP correlate positively with poor prognosis ...in ischaemic stroke (IS) patients. No information is available concerning the role of A-FABP in the pathogenesis of IS. Experiments were designed to determine whether or not A-FABP mediates blood–brain barrier (BBB) disruption, and if so, to explore the molecular mechanisms underlying this deleterious effects.
Methods and results
Circulating A-FABP and its cerebral expression were increased in mice after middle cerebral artery occlusion. Genetic deletion and pharmacological inhibition of A-FABP alleviated cerebral ischaemia injury with reduced infarction volume, cerebral oedema, neurological deficits, and neuronal apoptosis; BBB disruption was attenuated and accompanied by reduced degradation of tight junction proteins and induction of matrix metalloproteinases-9 (MMP-9). In patients with acute IS, elevated circulating A-FABP levels positively correlated with those of MMP-9 and cerebral infarct volume. Mechanistically, ischaemia-induced elevation of A-FABP selectively in peripheral blood monocyte-derived macrophages and cerebral resident microglia promoted MMP-9 transactivation by potentiating JNK/c-Jun signalling, enhancing degradation of tight junction proteins and BBB leakage. The detrimental effects of A-FABP were prevented by pharmacological inhibition of MMP-9.
Conclusion
A-FABP is a key mediator of cerebral ischaemia injury promoting MMP-9-mediated BBB disruption. Inhibition of A-FABP is a potential strategy to improve IS outcome.
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