Beyond the blank cheque: Arming iran during the ford administration

© 2016 Taylor & Francis. When President Gerald Ford decided tomaintain and deepen arms relations with Iran, he cemented a momentum that became near impossible for a successor to break by continuing the policy of his predecessor Richard Nixon. Nixon had given the Shah of Iran a "blank cheque" to purchase whatever American arms he desired- short of nuclear weapons. Although Ford’s authority would be challenged by members of his own Administration and a Congress seeking to claw back some of its authority, the need to support allies in the Middle East against the threat of the Soviet Union, even during a time of détente, remained paramount

Data-quality assessment for digital twins targeting multi-component degradation in industrial internet of things (IIoT)-enabled smart infrastructure systems

In the development of analytics for PHM applications, a lot of emphasis has been placed on data transformation for optimal model development without enough consideration for the repeatability of the measurement systems producing the data. This paper explores the relationship between data quality, defined as the measurement system analysis (MSA) process, and the performance of fault detection and isolation (FDI) algorithms within smart infrastructure systems. This research employs a comprehensive methodology, starting with an MSA process for data-quality evaluation and leading to the development and evaluation of fault detection and isolation (FDI) algorithms. During the MSA phase, the repeatability of a water distribution system’s measurement system is examined to characterise variations within the system. A data-quality process is defined to gauge data quality. Synthetic data are introduced with varying data-quality levels to investigate their impact on FDI algorithm development. Key findings reveal the complex relationship between data quality and FDI algorithm performance. Synthetic data, even with lower quality, can improve the performance of statistical process control (SPC) models, whereas data-driven approaches benefit from high-quality datasets. The study underscores the importance of customising FDI algorithms based on data quality. A framework for instantiating the MSA process for IIoT applications is also suggested. By bridging data-quality assessment with data-driven FDI, this research contributes to the design of digital twins for IIoT-enabled smart infrastructure systems. Further research on the practical implementation of the MSA process for edge analytics for PHM applications will be considered as part of our future research

Near infrared spectroscopy for the assessment of peripheral tissue oxygenation in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterised by increased pulmonary vascular resistance and results in increased morbidity and mortality due to right heart failure and a progressive decline in cardiac output [1, 2]. The latter disturbs oxygen delivery to the periphery and may lead to pathological changes in tissue oxygenation. The balance between global oxygen supply and demand is reflected in mixed venous oxygen saturation (SvO2), an index that is generally reduced in patients with PAH [3]. SvO2 at baseline is one of the strongest predictors of survival in PAH [4–6]; this is also true for changes in SvO2 during follow-up [5]. Cut-off values of 60% [7] and 65% [5] have been used to distinguish between prognostic groups suggesting that these may be suitable treatment goals. SvO2 is measured invasively in the pulmonary artery, where venous blood mixes after circulating through the superior and inferior vena cava, coronary sinuses and the right-heart chambers

Water color from Sentinel-2 MSI data for monitoring large rivers: Yangtze and Danube

Rivers provide key ecosystem services that are inherently engineered and optimized to meet the strategic and economic needs of countries around the world. However, limited water quality records of a full river continuum hindered the understanding of how river systems response to the multiple stressors acting on them. This study highlights the use of Sentinel-2 Multi-Spectral Imager (MSI) data to monitor changes in water color in two optically complex river systems: the Yangtze and Danube using the Forel-Ule Index (FUI). FUI divides water color into 21 classes from dark blue to yellowish brown stemming from the historical Forel-Ule water color scale and has been promoted as a useful indicator showing water turbidity variations in water bodies. The results revealed contrasting water color patterns in the two rivers on both spatial and seasonal scales. Spatially, the FUI of the Yangtze River gradually increased from the upper reaches to the lower reaches, while the FUI of the Danube River declined in the lower reaches, which is possibly due to the sediment sink effect of the Iron Gate Dams. The regional FUI peaks and valleys observed in the two river systems have also been shown to be related to the dams and hydropower stations along them. Seasonally, the variations of FUI in both systems can be attributed to climate seasonality, especially precipitation in the basin and the water level. Moreover, land cover within the river basin was possibly a significant determinant of water color, as higher levels of vegetation in the Danube basin were associated with lower FUI values, whereas higher FUI values and lower levels of vegetation were observed in the Yangtze system. This study furthers our knowledge of using Sentinel-2 MSI to monitor and understand the spatial-temporal variations of river systems and highlights the capabilities of the FUI in an optically complex environment

Potent Immune Modulation by MEDI6383, an Engineered Human OX40 Ligand IgG4P Fc Fusion Protein.

Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution-phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells. The resulting costimulation of OX40 on T cells induced NFκB promoter activity in OX40-expressing T cells and induced Th1-type cytokine production, proliferation, and resistance to regulatory T cell (Treg)-mediated suppression. MEDI6383 enhanced the cytolytic activity of tumor-reactive T cells and reduced tumor growth in the context of an alloreactive human T cell:tumor cell admix model in immunocompromised mice. Consistent with the role of OX40 costimulation in the expansion of memory T cells, MEDI6383 administered to healthy nonhuman primates elicited peripheral blood CD4 and CD8 central and effector memory T-cell proliferation as well as B-cell proliferation. Together, these results suggest that OX40 agonism has the potential to enhance antitumor immunity in human malignancies

Defining the phylogenetics and resistome of the major clostridioides difficile ribotypes circulating in Australia

Clostridioides difficile infection (CDI) remains a significant public health threat globally. New interventions to treat CDI rely on an understanding of the evolution and epidemiology of circulating strains. Here we provide longitudinal genomic data on strain diversity, transmission dynamics and antimicrobial resistance (AMR) of C. difficile ribotypes (RTs) 014/020 (n=169), 002 (n=77) and 056 (n=36), the three most prominent C. difficile strains causing CDI in Australia. Genome scrutiny showed that AMR was uncommon in these lineages, with resistance-conferring alleles present in only 15/169 RT014/020 strains (8.9 %), 1/36 RT056 strains (2.78 %) and none of 77 RT002 strains. Notably, ~90 % of strains were resistant to MLSB agents in vitro, but only ~5.9 % harboured known resistance alleles, highlighting an incongruence between AMR genotype and phenotype. Core genome analyses revealed all three RTs contained genetically heterogeneous strain populations with limited evidence of clonal transmission between CDI cases. The average number of pairwise core genome SNP (cgSNP) differences within each RT group ranged from 23.3 (RT056, ST34, n=36) to 115.6 (RT002, ST8, n=77) and 315.9 (RT014/020, STs 2, 13, 14, 49, n=169). Just 19 clonal groups (encompassing 40 isolates), defined as isolates differing by ≤2 cgSNPs, were identified across all three RTs (RT014/020, n=14; RT002, n=3; RT056, n=2). Of these clonal groups, 63 % (12/19) comprised isolates from the same Australian State and 37 % (7/19) comprised isolates from different States. The low number of plausible transmission events found for these major RTs (and previously documented populations in animal and environmental sources/reservoirs) points to widespread and persistent community sources of diverse C. difficile strains as opposed to ongoing nationwide healthcare outbreaks dominated by a single clone. Together, these data provide new insights into the evolution of major lineages causing CDI in Australia and highlight the urgent need for enhanced surveillance, and for public health interventions to move beyond the healthcare setting and into a One Health paradigm to effectively combat this complex pathogen

AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein–specific T H 1 response with a diverse TCR repertoire

AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus–vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 in clinical trials and real-world studies. We characterized CD4+ and CD8+ T cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells from 296 unique vaccine recipients aged 18 to 85 years who enrolled in the phase 2/3 COV002 trial. Total spike protein–specific CD4+ T cell helper type 1 (TH1) and CD8+ T cell responses were increased in AZD1222-vaccinated adults of all ages after two doses of AZD1222. CD4+ TH2 responses after AZD1222 vaccination were not detected. Furthermore, AZD1222-specific TH1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T cell receptor β (TCRβ) sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for both AZD1222-induced CD4+ and CD8+ T cell responses. Overall, AZD1222 vaccination induced a polyfunctional TH1-dominated T cell response, with broad CD4+ and CD8+ T cell coverage across the SARS-CoV-2 spike protein