PEDIA: prioritization of exome data by image analysis.

PURPOSE: Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. METHODS: Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. RESULTS: The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20-89% and the top 10 accuracy rate by more than 5-99% for the disease-causing gene. CONCLUSION: Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

"I am here! But, I actually shouldn\u27t be!!" An auto-ethnography on the remittance experience of an African international student in Canada

Papers about international students are typically quantitative, reducing individual international students to projections, statistics and numbers. Coincidentally, the other major keyword of this study, remittance, is also mainly studied using numbers and statistics. In this research however, the researcher, an international student who engages in remittance activities, uses her own experience to contest this ‘numeralization’. By exploring in great depth her own cultural background and the specific motivations for remittance, this paper demonstrates that remittance has a human face. Furthermore, the complexity of remittance is contextualized through the lens of culture

Characterising a UK cohort with retinal ischaemic events

Objective: Retinal ischaemic events (RIE), consisting of central retinal artery occlusions (CRAO), branch retinal artery occlusion (BRAO), and amaurosis fugax (Amfug), are commonly observed in older adults, often manifesting as sudden painless monocular visual loss. CRAO and BRAO are regarded as minor strokes, while Amfug is likened to a cerebral TIA. We present an RIE patient cohort, their clinical characteristics, and outcomes as a first step in evaluating our patient outcomes, service provision, and potentially highlighting areas for improvement.Design and method: This study is a retrospective consecutive case series from a major stroke centre in the UK: Royal Sussex County Hospital, Brighton. The electronic patient records of the stroke department were reviewed to identify all patients between August 2018 and December 2021 who had been managed following a diagnosis of RIE. Descriptive and inferential statistics were conducted on detailed clinical and demographic data of study participants, exploring their frequency distributions and testing associations between the three groups of RIE.Results: One hundred and eleven (111) study participants with RIE were identified from the stroke register, with 56.8% (n=63) diagnosed with amaurosis fugax, 25.2% (n=28) with BRAO, and 18.0% (n=20) with CRAO. Mean age was 70.6 ± 1.2 years (SEM) and 35.1% (n=39) were female. Characteristics such as blood pressure, total cholesterol, glucose and inflammatory markers (ESR and CRP) were noted to be higher in CRAO and BRAO compared to Amfug, though not statistically significant (p>0.05). Similarly, 97%(n=195) carotid doppler scans showed greater or equal stenosis ipsilateral to the RIE, with calculated Fazeka scores showing 1.2 ± 0.1 (SEM) (n=49). Outcomes post RIE demonstrated 6.8% mortality within one year of RIE diagnosis and 14.3% of this attributable to ischaemic stroke.Conclusions: Our cohort demonstrates that RIE is largely a large vessel disease as depicted in the risk factors identified and scores from carotid doppler and Fazeka. With RIE showing similar risk factors as that for strokes, it is essential that patients presenting with RIE should have their risk factors strictly addressed to reduce complications, morbidity and mortality associated with RIE as in all large vessel diseases.</p