A groundbreaking exploration of US-China relations as seen through the lens of international finance Rising tensions between China and the United States have kept the financial markets on edge as a ...showdown between the world's two largest economies seems inevitable. But what most people fail to recognise is the major impact that the financial markets themselves have had on the creation and acceleration of the conflict. In Financial Cold War: A View of Sino-US Relations from the Financial Markets, market structure and geopolitical finance expert James Fok explores the nuances of China-US relations from the perspective of the financial markets. The book helps readers understand how imbalances in the structure of global financial markets have singularly contributed to frictions between the two countries. In this book, readers will find: A comprehensive examination of the development of financial markets in both China and the US, as well as the current US dollar-based global financial system Insightful observations of the roles of technology, innovation, regulation, taxation, and politics in the markets, and on their resulting effect on US-Sino relations Thorough explorations of the role of Hong Kong as an intermediary for capital flows between China and the rest of the world Suggestions for how, balancing the many varying interests, policymakers might be able to devise effective strategies for de-escalating current Sino-US tensions Financial Cold War is a can't-miss resource for anyone personally or professionally interested in the intersection of economics and international relations, financial markets, and the infrastructure underlying the international financial system.
An empirical method is proposed to predict the clinical performance of resin composite dental restorations by using laboratory data derived from simple specimens subjected to chemical degradation and ...accelerated cyclic fatigue. Three resin composites were used to fill dentin disks (2-mm inner diameter, 5-mm outer diameter, and 2 mm thick) made from bovine incisor roots. The specimens (n = 30 per group) were aged with different durations of a low-pH challenge (0, 24, and 48 h under pH 4.5) before being subjected to diametral compression with either a monotonically increasing load (fast fracture) or a cyclic load with a continuously increasing amplitude (accelerated fatigue). The data from 1 material were used to establish the relationship between laboratory time (number of cycles) and clinical time to failure (years) via the respective survival probability curves. The temporal relationship was then used to predict the clinical rates of failure for restorations made of the other 2 materials, and the predictions were compared with the clinical data to assess their accuracy. Although there were significant differences in the fast fracture strength among the groups of materials or durations of chemical challenge, fatigue testing was much better at separating the groups. Linear relationships were found between the laboratory and clinical times to failure for the first material (R2 = 0.90, 0.90, and 0.62 for the 0-, 24-, and 48-h low-pH groups, respectively). The clinical life of restorations made of the other 2 materials was best predicted with data from the 48-h low-pH groups. In conclusion, an accelerated fatigue model was successfully calibrated and applied to predict the clinical failure of resin composite restorations, and the predictions based on data obtained from chemically aged specimens provided the best agreement with clinical data.
Due to the severe mechano-biochemical conditions in the oral cavity, many dental restorations will degrade and eventually fail. For teeth restored with resin composite, the major modes of failure are ...secondary caries and fracture of the tooth or restoration. While clinical studies can answer some of the more practical questions, such as the rate of failure, fundamental understanding on the failure mechanism can be obtained from laboratory studies using simplified models more effectively. Reviewed in this article are the 4 main types of models used to study the degradation of resin–composite restorations, namely, animal, human in vivo or in situ, in vitro biofilm, and in vitro chemical models. The characteristics, advantages, and disadvantages of these models are discussed and compared. The tooth–restoration interface is widely considered the weakest link in a resin composite restoration. To account for the different types of degradation that can occur (i.e., demineralization, resin hydrolysis, and collagen degradation), enzymes such as esterase and collagenase found in the oral environment are used, in addition to acids, to form biochemical models to test resin–composite restorations in conjunction with mechanical loading. Furthermore, laboratory tests are usually performed in an accelerated manner to save time. It is argued that, for an accelerated multicomponent model to be representative and predictive in terms of both the mode and the speed of degradation, the individual components must be synchronized in their rates of action and be calibrated with clinical data. The process of calibrating the in vitro models against clinical data is briefly described. To achieve representative and predictive in vitro models, more comparative studies of in vivo and in vitro models are required to calibrate the laboratory studies.
Aims
Most studies of biofilm effects on dental materials use single‐species biofilms, or consortia. Microcosm biofilms grown directly from saliva or plaque are much more diverse, but difficult to ...characterize. We used the Human Oral Microbial Identification Microarray (HOMIM) to validate a reproducible oral microcosm model.
Methods and Results
Saliva and dental plaque were collected from adults and children. Hydroxyapatite and dental composite discs were inoculated with either saliva or plaque, and microcosm biofilms were grown in a CDC biofilm reactor. In later experiments, the reactor was pulsed with sucrose. DNA from inoculums and microcosms was analysed by HOMIM for 272 species. Microcosms included about 60% of species from the original inoculum. Biofilms grown on hydroxyapatite and composites were extremely similar. Sucrose pulsing decreased diversity and pH, but increased the abundance of Streptococcus and Veillonella. Biofilms from the same donor, grown at different times, clustered together.
Conclusions
This model produced reproducible microcosm biofilms that were representative of the oral microbiota. Sucrose induced changes associated with dental caries.
Significance and Impact of the Study
This is the first use of HOMIM to validate an oral microcosm model that can be used to study the effects of complex biofilms on dental materials.
The mechanical integrity of composite restorations challenged with multi-species oral biofilms was studied. While most studies used single-species biofilms, we used a more realistic, diverse biofilm ...model produced directly from plaques collected from donors with a history of early childhood caries. Biofilm growth with sucrose pulsing caused preferential degradation of the composite–dentin interface, with significant differences in bond strength reduction and failure modes depending on the composite/adhesive system used.
Oral biofilms can degrade the components in dental resin-based composite restorations, thus compromising marginal integrity and leading to secondary caries. This study investigates the mechanical integrity of the dentin–composite interface challenged with multi-species oral biofilms. While most studies used single-species biofilms, the present study used a more realistic, diverse biofilm model produced directly from plaques collected from donors with a history of early childhood caries. Dentin–composite disks were made using bovine incisor roots filled with Z100TM or FiltekTM LS (3M ESPE). The disks were incubated for 72h in paired CDC biofilm reactors, using a previously published protocol. One reactor was pulsed with sucrose, and the other was not. A sterile saliva-only control group was run with sucrose pulsing. The disks were fractured under diametral compression to evaluate their interfacial bond strength. The surface deformation of the disks was mapped using digital image correlation to ascertain the fracture origin. Fracture surfaces were examined using scanning electron microscopy/energy-dispersive X-ray spectroscopy to assess demineralization and interfacial degradation. Dentin demineralization was greater under sucrose-pulsed biofilms, as the pH dropped <5.5 during pulsing, with LS and Z100 specimens suffering similar degrees of surface mineral loss. Biofilm growth with sucrose pulsing also caused preferential degradation of the composite–dentin interface, depending on the composite/adhesive system used. Specifically, Z100 specimens showed greater bond strength reduction and more frequent cohesive failure in the adhesive layer. This was attributed to the inferior dentin coverage by Z100 adhesive, which possibly led to a higher level of chemical and enzymatic degradation. The results suggested that factors other than dentin demineralization were also responsible for interfacial degradation. A clinically relevant in vitro biofilm model was therefore developed, which would effectively allow assessment of the degradation of the dentin–composite interface subjected to multi-species biofilm challenge.
Frontotemporal dementia and amyotrophic lateral sclerosis are closely related clinical syndromes with overlapping molecular pathogenesis. Several families have been reported with members affected by ...frontotemporal dementia, amyotrophic lateral sclerosis or both, which show genetic linkage to a region on chromosome 9p21. Recently, two studies identified the FTD/ALS gene defect on chromosome 9p as an expanded GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72). In the present study, we provide detailed analysis of the clinical features and neuropathology for 16 unrelated families with frontotemporal dementia caused by the C9ORF72 mutation. All had an autosomal dominant pattern of inheritance. Eight families had a combination of frontotemporal dementia and amyotrophic lateral sclerosis while the other eight had a pure frontotemporal dementia phenotype. Clinical information was available for 30 affected members of the 16 families. There was wide variation in age of onset (mean = 54.3, range = 34-74 years) and disease duration (mean = 5.3, range = 1-16 years). Early diagnoses included behavioural variant frontotemporal dementia (n = 15), progressive non-fluent aphasia (n = 5), amyotrophic lateral sclerosis (n = 9) and progressive non-fluent aphasia-amyotrophic lateral sclerosis (n = 1). Heterogeneity in clinical presentation was also common within families. However, there was a tendency for the phenotypes to converge with disease progression; seven subjects had final clinical diagnoses of both frontotemporal dementia and amyotrophic lateral sclerosis and all of those with an initial progressive non-fluent aphasia diagnosis subsequently developed significant behavioural abnormalities. Twenty-one affected family members came to autopsy and all were found to have transactive response DNA binding protein with M(r) 43 kD (TDP-43) pathology in a wide neuroanatomical distribution. All had involvement of the extramotor neocortex and hippocampus (frontotemporal lobar degeneration-TDP) and all but one case (clinically pure frontotemporal dementia) had involvement of lower motor neurons, characteristic of amyotrophic lateral sclerosis. In addition, a consistent and relatively specific pathological finding was the presence of neuronal inclusions in the cerebellar cortex that were ubiquitin/p62-positive but TDP-43-negative. Our findings indicate that the C9ORF72 mutation is a major cause of familial frontotemporal dementia with TDP-43 pathology, that likely accounts for the majority of families with combined frontotemporal dementia/amyotrophic lateral sclerosis presentation, and further support the concept that frontotemporal dementia and amyotrophic lateral sclerosis represent a clinicopathological spectrum of disease with overlapping molecular pathogenesis.
Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data ...provided by whole genome and transcriptome sequencing and analysis (WGTA) presents an opportunity to align a much larger proportion of patients to therapies.
Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number, and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected.
Clinically actionable targets were identified for 83% of patients, 37% of whom received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, PARP inhibitors, and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%), and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies.
Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.
NCT02155621
•A prospective study of 570 patients used whole genome and transcriptome analysis (WGTA) for real-time treatment options•Of 248 WGTA-informed treatments, 46% resulted in clinical benefit to the patient•RNA expression information was as valuable as DNA-based information for selecting treatments with clinical benefit•Integrated data informs selection of standard-of-care therapies, clinical trial enrollment and off-label use•This study supports the use of whole genome and transcriptome analysis in clinical cancer care
Aim
To simulate in a laboratory setting longitudinal cracking in root filled premolar teeth, using cyclic mechanical fatigue.
Methodology
Mesial‐occlusal‐distal (MOD) cavities were prepared in twenty ...root filled, single‐rooted, mandibular premolars restored with fibre posts and resin composites. The samples were randomly divided into two groups based on the loading approaches: static loading with a crosshead speed of 0.5 mm/min and step‐stress cyclic loading (1 Hz) with increasing amplitude. The loads and numbers of cycles to failure were recorded. Micro‐CT was also used to identify the fracture modes. Statistical analysis was performed using Student's t‐test. The level of significance was set at 0.05.
Results
The mean fracture loads for the static loading and cyclic loading groups were 769 ± 171 N and 720 ± 92 N, respectively. There was no significant difference between the two groups (P > 0.05). The proportions of longitudinal, cuspal and mixed‐mode fractures under cyclic loading were 50%, 20% and 30%, respectively. Longitudinal fractures occurred with larger numbers of cycles and higher average loads per cycle compared with the other fractures. Static loading produced only cuspal fractures.
Conclusions
Longitudinally cracked premolar teeth with root fillings were successfully produced using the step‐stress cyclic loading method. This provides a more clinically representative methodology for studying cracked teeth in a laboratory setting.
: By providing long‐term protection against infectious diseases, vaccinations have significantly reduced death and morbidity worldwide. In the 21st century, (bio)technological advances have paved the ...way for developing prophylactic vaccines that are safer and more effective as well as enabling the use of vaccines as therapeutics to treat human diseases. Here, we provide a focused review of the utility of genetic code expansion as an emerging tool for the development of vaccines. Specifically, we discuss how the incorporation of immunogenic noncanonical amino acids can aid in eliciting immune responses against adverse self‐proteins and highlight the potential of an expanded genetic code for the construction of replication‐incompetent viruses. We close the review by discussing the future prospects and remaining challenges for the application of these approaches in the development of both prophylactic and therapeutic vaccines in the near future.
Vaccine variations: This article reviews the utility of genetic code expansion as an emerging tool for the development of vaccines. It highlights how the incorporation of immunogenic noncanonical amino acids (ncAA) can aid in eliciting immune responses against adverse self‐proteins and highlights the potential of an expanded genetic code for the construction of live‐attenuated virus vaccines.
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