The ANZUS Treaty during the Cold War: a reinterpretation of U.S. diplomacy in the Southwest Pacific

This article explains the origins of the Australia–New Zealand–United States (ANZUS) Treaty by highlighting U.S. ambitions in the Pacific region after World War II. Three clarifications to the historiography merit attention. First, an alliance with Australia and New Zealand reflected the pursuit of U.S. interests rather than the skill of antipodean diplomacy. Despite initial reservations in Washington, geostrategic anxiety and economic ambition ultimately spurred cooperation. The U.S. government's eventual recourse to coercive diplomacy against the other ANZUS members, and the exclusion of Britain from the alliance, substantiate claims of self-interest. Second, the historiography neglects the economic rationale underlying the U.S. commitment to Pacific security. Regional cooperation ensured the revival of Japan, the avoidance of discriminatory trade policies, and the stability of the Bretton Woods monetary system. Third, scholars have unduly played down and misunderstood the concept of race. U.S. foreign policy elites invoked ideas about a “White Man's Club” in Asia to obscure the pursuit of U.S. interests in the region and to ensure British exclusion from the treaty

Intervention design for artificial intelligence-enabled macular service implementation:a primary qualitative study

BackgroundNeovascular age-related macular degeneration (nAMD) is one of the largest single-disease contributors to hospital outpatient appointments. Challenges in finding the clinical capacity to meet this demand can lead to sight-threatening delays in the macular services that provide treatment. Clinical artificial intelligence (AI) technologies pose one opportunity to rebalance demand and capacity in macular services. However, there is a lack of evidence to guide early-adopters seeking to use AI as a solution to demand-capacity imbalance. This study aims to provide guidance for these early adopters on how AI-enabled macular services may best be implemented by exploring what will influence the outcome of AI implementation and why.MethodsThirty-six semi-structured interviews were conducted with participants. Data were analysed with the Nonadoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework to identify factors likely to influence implementation outcomes. These factors and the primary data then underwent a secondary analysis using the Fit between Individuals, Technology and Task (FITT) framework to propose an actionable intervention.ResultsnAMD treatment should be initiated at face-to-face appointments with clinicians who recommend year-long periods of AI-enabled scheduling of treatments. This aims to maintain or enhance the quality of patient communication, whilst reducing consultation frequency. Appropriately trained photographers should take on the additional roles of inputting retinal imaging into the AI device and overseeing its communication to clinical colleagues, while ophthalmologists assume clinical oversight and consultation roles. Interoperability to facilitate this intervention would best be served by imaging equipment that can send images to the cloud securely for analysis by AI tools. Picture Archiving and Communication Software (PACS) should have the capability to output directly into electronic medical records (EMR) familiar to clinical and administrative staff.ConclusionThere are many enablers to implementation and few of the remaining barriers relate directly to the AI technology itself. The proposed intervention requires local tailoring and prospective evaluation but can support early adopters in optimising the chances of success from initial efforts to implement AI-enabled macular services.Protocol registrationHogg HDJ, Brittain K, Teare D, Talks J, Balaskas K, Keane P, Maniatopoulos G. Safety and efficacy of an artificial intelligence-enabled decision tool for treatment decisions in neovascular age-related macular degeneration and an exploration of clinical pathway integration and implementation: protocol for a multi-methods validation study. BMJ Open. 2023 Feb 1;13(2):e069443. https://doi.org/10.1136/bmjopen-2022-069443. PMID: 36725098; PMCID: PMC9896175

Knowledge, crisis and (un)certainty in climate change education in India

This paper explores teachers’ conceptions of climate change knowledge, contributing to the growing body of work on the geographies of climate change. This paper focuses on the data generated through in-depth semi-structured interviews with a sample of forty eight teachers in India to address the research question: what discourses about climate change knowledge are being constructed by teachers in India? We argue that teachers’ lesson planning and searches for information are at the forefront of the changing ways in which individuals engage with, find out and construct meaning about climate change. These teachers’ beliefs about climate change are very strongly held, even in the face of a perceived lack of expertise or understanding: climate change is described as the ‘need of the hour’, which this work understands as not only involving material impacts and processes but also important epistemological, collaborative needs through which education might contribute to public reasoning about climate change. Through this analysis we present a ‘certainty problematic’ as a heuristic device that foregrounds tensions between the inherent uncertainty of knowledge, and (against climate denialism) certainty about anthropogenic climate change

DIAbetic macular oedema aNd diode subthreshold micropulse laser (DIAMONDS) : Ppotocol for a randomised clinical trial

Background In the UK, macular laser is the treatment of choice for people with diabetic macular oedema with central retinal subfield thickness (CST) < 400 μm, as per National Institute for Health and Care Excellence guidelines. It remains unclear whether subthreshold micropulse laser is superior and should replace standard threshold laser for the treatment of eligible patients. Methods DIAMONDS is a pragmatic, multicentre, allocation-concealed, randomised, equivalence, double-masked clinical trial that aims to determine the clinical effectiveness and cost-effectiveness of subthreshold micropulse laser compared with standard threshold laser, for the treatment of diabetic macular oedema with CST < 400 μm. The primary outcome is the mean change in best-corrected visual acuity in the study eye from baseline to month 24 post treatment. Secondary outcomes (at 24 months) include change in binocular best corrected visual acuity; CST; mean deviation of the Humphrey 10–2 visual field; change in percentage of people meeting driving standards; European Quality of Life-5 Dimensions, National Eye Institute Visual Functioning Questionnaire-25 and VisQoL scores; incremental cost per quality-adjusted life year gained; side effects; number of laser treatments and use of additional therapies. The primary statistical analysis will be per protocol rather than intention-to-treat analysis because the latter increases type I error in non-inferiority or equivalence trials. The difference between lasers for change in best-corrected visual acuity (using 95% CI) will be compared to the permitted maximum difference of five Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Linear and logistic regression models will be used to compare outcomes between treatment groups. A Markov-model-based cost-utility analysis will extend beyond the trial period to estimate longer-term cost-effectiveness. Discussion This trial will determine the clinical effectiveness and cost-effectiveness of subthreshold micropulse laser, when compared with standard threshold laser, for the treatment of diabetic macular oedema, the main cause of sight loss in people with diabetes mellitus

Stakeholder Perspectives on Clinical Decision Support Tools to Inform Clinical Artificial Intelligence Implementation: Protocol for a Framework Synthesis for Qualitative Evidence

BACKGROUND: Quantitative systematic reviews have identified clinical artificial intelligence (AI)-enabled tools with adequate performance for real-world implementation. To our knowledge, no published report or protocol synthesizes the full breadth of stakeholder perspectives. The absence of such a rigorous foundation perpetuates the "AI chasm," which continues to delay patient benefit. OBJECTIVE: The aim of this research is to synthesize stakeholder perspectives of computerized clinical decision support tools in any health care setting. Synthesized findings will inform future research and the implementation of AI into health care services. METHODS: The search strategy will use MEDLINE (Ovid), Scopus, CINAHL (EBSCO), ACM Digital Library, and Science Citation Index (Web of Science). Following deduplication, title, abstract, and full text screening will be performed by 2 independent reviewers with a third topic expert arbitrating. The quality of included studies will be appraised to support interpretation. Best-fit framework synthesis will be performed, with line-by-line coding completed by 2 independent reviewers. Where appropriate, these findings will be assigned to 1 of 22 a priori themes defined by the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability framework. New domains will be inductively generated for outlying findings. The placement of findings within themes will be reviewed iteratively by a study advisory group including patient and lay representatives. RESULTS: Study registration was obtained from PROSPERO (CRD42021256005) in May 2021. Final searches were executed in April, and screening is ongoing at the time of writing. Full text data analysis is due to be completed in October 2021. We anticipate that the study will be submitted for open-access publication in late 2021. CONCLUSIONS: This paper describes the protocol for a qualitative evidence synthesis aiming to define barriers and facilitators to the implementation of computerized clinical decision support tools from all relevant stakeholders. The results of this study are intended to expedite the delivery of patient benefit from AI-enabled clinical tools. TRIAL REGISTRATION: PROSPERO CRD42021256005; https://tinyurl.com/r4x3thvp. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33145

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this populatio

Dual site external validation of artificial intelligence-enabled treatment monitoring for neovascular age-related macular degeneration in England

BackgroundMonitoring neovascular age-related macular degeneration (nAMD) is a significant contributor to ophthalmology demands in the NHS, with clinical capacity struggling to meet the demand. This task depends upon interpreting retinal optical coherence tomography (OCT) imaging, where artificial intelligence (AI) could rebalance clinical demand and capacity. However, evidence of safety and effectiveness in nAMD monitoring is lacking.MethodsUsing a published non-inferiority design protocol, 521 pairs of ipsilateral retinal OCTs from consecutive visits for nAMD treatment were collected from two NHS ophthalmology services. Real-world binary assessments of nAMD disease activity or stability were compared to an independent ophthalmic reading centre reference standard. An AI system capable of retinal OCT segmentation analysed the OCTs, applying thresholds for intraretinal and subretinal fluid to generate binary assessments. The relative negative predictive value (rNPV) of AI versus real-world assessments was calculated.ResultsReal-world assessments of nAMD activity showed a NPV of 81.6% (57.3–81.6%) and a positive predictive value (PPV) of 41.5% (17.8–62.3%). Optimised thresholds for intraretinal fluid increase (&gt;1,000,000 µm³) and subretinal fluid increase (&gt;2,000,000 µm³) for the AI system assessments produced an NPV of 95.3% (85.5–97.9%) and PPV of 57.8% (29.4–76.0%). The rNPV of 1.17 (1.11–1.23) met predefined criteria for clinical and statistical superiority and accompanied an rPPV of 1.39 (1.10–1.76).ConclusionsThis study suggests that the same thresholds for interpreting OCT-based AI analysis could reduce undertreatment and overtreatment in nAMD monitoring at different centres. Interventional research is needed to test the potential of supportive or autonomous AI assessments of nAMD disease activity to improve the quality and efficiency of services

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Baseline Psychological Traits Contribute to Lake Louise Acute Mountain Sickness Score at High Altitude

Talks, Benjamin James, Catherine Campbell, Stephanie J. Larcombe, Lucy Marlow, Sarah L. Finnegan, Christopher T. Lewis, Samuel J.E. Lucas, Olivia K. Harrison, and Kyle T.S. Pattinson. Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude. High Alt Med Biol. 23:69-77, 2022. Background: Interoception refers to an individual's ability to sense their internal bodily sensations. Acute mountain sickness (AMS) is a common feature of ascent to high altitude that is only partially explained by measures of peripheral physiology. We hypothesized that interoceptive ability may explain the disconnect between measures of physiology and symptom experience in AMS. Methods: Two groups of 18 participants were recruited to complete a respiratory interoceptive task three times at 2-week intervals. The control group remained in Birmingham (140 m altitude) for all three tests. The altitude group completed test 1 in Birmingham, test 2 the day after arrival at 2,624 m, and test 3 at 2,728 m after an 11-day trek at high altitude (up to 4,800 m). Results: By measuring changes to metacognitive performance, we showed that acute ascent to altitude neither presented an interoceptive challenge, nor acted as interoceptive training. However, AMS symptom burden throughout the trek was found to relate to sea level measures of anxiety, agoraphobia, and neuroticism. Conclusions: This suggests that the Lake Louise AMS score is not solely a reflection of physiological changes on ascent to high altitude, despite often being used as such by researchers and commercial trekking companies alike. Keywords: acute mountain sickness; altitude; breathlessness; exercise; filter detection task; interoceptio