Tear biomarkers for keratoconus

Keratoconus is a progressive corneal thinning, ectatic condition, which affects vision. Recent advances in corneal topography measurements has helped advance proper diagnosis of this condition and increased research and clinical interests in the disease etiopathogenesis. Considerable progress has been achieved in understanding the progression of the disease and tear fluid has played a major role in the progress. This review discusses the importance of tear fluid as a source of biomarker for keratoconus and how advances in technology have helped map the complexity of tears and thereby molecular readouts of the disease. Expanding knowledge of the tear proteome, lipidome and metabolome opened up new avenues to study keratoconus and to identify probable prognostic or diagnostic biomarkers for the disease. A multidimensional approach of analyzing tear fluid of patients layering on proteomics, lipidomics and metabolomics is necessary in effectively decoding keratoconus and thereby identifying targets for its treatment

Complex Sequential Question Answering: Towards Learning to Converse Over Linked Question Answer Pairs with a Knowledge Graph

While conversing with chatbots, humans typically tend to ask many questions, a significant portion of which can be answered by referring to large-scale knowledge graphs (KG). While Question Answering (QA) and dialog systems have been studied independently, there is a need to study them closely to evaluate such real-world scenarios faced by bots involving both these tasks. Towards this end, we introduce the task of Complex Sequential QA which combines the two tasks of (i) answering factual questions through complex inferencing over a realistic-sized KG of millions of entities, and (ii) learning to converse through a series of coherently linked QA pairs. Through a labor intensive semi-automatic process, involving in-house and crowdsourced workers, we created a dataset containing around 200K dialogs with a total of 1.6M turns. Further, unlike existing large scale QA datasets which contain simple questions that can be answered from a single tuple, the questions in our dialogs require a larger subgraph of the KG. Specifically, our dataset has questions which require logical, quantitative, and comparative reasoning as well as their combinations. This calls for models which can: (i) parse complex natural language questions, (ii) use conversation context to resolve coreferences and ellipsis in utterances, (iii) ask for clarifications for ambiguous queries, and finally (iv) retrieve relevant subgraphs of the KG to answer such questions. However, our experiments with a combination of state of the art dialog and QA models show that they clearly do not achieve the above objectives and are inadequate for dealing with such complex real world settings. We believe that this new dataset coupled with the limitations of existing models as reported in this paper should encourage further research in Complex Sequential QA.Comment: Accepted in AAAI'1

Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities

Background Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. Methods To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. Results Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. Conclusion The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO

Identifying Prognostic Groups Using Machine Learning Tools in Patients Undergoing Chemoradiation for Inoperable Locally Advanced Nonsmall Cell Lung Carcinoma

Introduction Unresectable stage III nonsmall cell lung cancer (NSCLC) continues to have dismal 5-year overall survival (OS) rate. However, a subset of the patients treated with chemoradiation show significantly better outcome. Prediction of treatment outcome can be improved by utilizing machine learning tools, such as cluster analysis (CA), and is capable of identifying complex interactions among many variables. We have utilized CA to identify a cluster with good prognosis within stage III NSCLC. Materials and Methods Retrospective analysis of treatment outcomes was done for 92 patients who underwent chemoradiation for inoperable locally advanced NSCLC from 2012 to 2018. Using various patient- and treatment-related variables, an exploratory factor analysis was performed to extract factors with eigenvalue > 1. An appropriate number of homogeneous groups were identified using agglomerative hierarchical cluster analysis. Further K-mean cluster analysis was applied to classify each patient into their homogeneous clusters. The newly formed cluster variable was used as an independent variable to estimate survival over time using Kaplan–Meier method. Results With a median follow-up of 18 months, median OS was 14 months. Using CA, three prognostic clusters were obtained. Cluster 2 with 36 patients had a median OS of 36 months, whereas Cluster 1 with 34 patients had a median OS of 20 months (p = 0.004). Conclusion A cluster could thus be identified with a relatively good prognosis within stage III NSCLC. Using CA, we have attempted to create a model which may provide more specific prognostic information in addition to that provided by tumor node metastasis-based models

Plan quality assessment of modern radiotherapy delivery techniques in left-sided breast cancer: an analysis stratified by target delineation guidelines

Objective: This study compares planning techniques stratified by consensus delineation guidelines in patients undergoing whole-breast radiotherapy based on an objective plan quality assessment scale. Methods: 10 patients with left-sided breast cancer were randomly selected, and target delineation for intact breast was performed using Tangent (RTOG 0413), ESTRO, and RTOG guidelines. Consensus Plan Quality Metric (PQM) scoring was defined and communicated to the physicist before commencing treatment planning. Field-in-field IMRT (FiF), inverse IMRT (IMRT) and volumetric modulated arc therapy (VMAT) plans were created for each delineation. Statistical analyses utilised a two-way repeated measures analysis of variance, after applying a Bonferroni correction. Results: Total PQM score of plans for Tangent and ESTRO were comparable for FiF and IMRT techniques (FiF vs IMRT for Tangent, p = 0.637; FiF vs IMRT for ESTRO, p = 0.304), and were also significantly higher compared to VMAT. Total PQM score of plans for RTOG revealed that IMRT planning achieved a significantly higher score compared to both FiF and VMAT (IMRT vs FiF, p &lt; 0.001; IMRT vs VMAT, p &lt; 0.001). Conclusions: Total PQM scores were equivalent for FiF and IMRT for both Tangent and ESTRO delineations, whereas IMRT was best suited for RTOG delineation. Advances in knowledge: FiF and IMRT planning techniques are best suited for ESTRO or Tangent delineations. IMRT also yields better results with RTOG delineation. </jats:sec

A Role for Behavior in the Relationships Between Depression and Hostility and Cardiovascular Disease Incidence, Mortality, and All-Cause Mortality: the Prime Study.

BACKGROUND: Behavioral factors are important in disease incidence and mortality and may explain associations between mortality and various psychological traits. PURPOSE: These analyses investigated the impact of behavioral factors on the associations between depression, hostility and cardiovascular disease(CVD) incidence, CVD mortality, and all-cause mortality. METHODS: Data from the PRIME Study (N = 6953 men) were analyzed using Cox proportional hazards models, following adjustment for demographic and biological CVD risk factors, and other psychological traits, including social support. RESULTS: Following initial adjustment, both depression and hostility were significantly associated with both mortality outcomes (smallest SHR = 1.24, p < 0.001). Following adjustment for behavioral factors, all relationships were attenuated both when accounting for and not accounting for other psychological variables. Associations with all-cause mortality remained significant (smallest SHR = 1.14, p = 0.04). Of the behaviors included, the most significant contribution to outcomes was found for smoking, but a role was also found for fruit and vegetable intakes and high alcohol consumption. CONCLUSIONS: These findings demonstrate well-known associations between depression, hostility, and mortality and suggest the potential importance of behaviors in explaining these relationships

Is Transcatheter Aortic Valve Replacement Better Than Surgical Aortic Valve Replacement in Patients With Chronic Obstructive Pulmonary Disease? A Nationwide Inpatient Sample Analysis

Background Chronic obstructive pulmonary disease ( COPD ) patients are at increased risk of respiratory related complications after cardiac surgery. It is unclear whether transcatheter aortic valve replacement ( TAVR ) or surgical aortic valve replacement ( SAVR ) results in favorable outcomes among COPD patients. Methods and Results Patients were identified from the Nationwide Inpatient Sample database from 2011 to 2014. Patients with age ≥60, COPD , and either went transarterial TAVR or SAVR were included in the analysis. A 1:1 propensity‐matched cohort was created to examine the outcomes. A matched pair of 1210 TAVR and 1208 SAVR patients was identified. Respiratory‐related complications such as tracheostomy (0.8% versus 5.8%; odds ratio [ OR ], 0.14; P &lt;0.001), acute respiratory failure (16.4% versus 23.7%; OR , 0.63; P =0.002), reintubation (6.5% versus 10.0%; OR , 0.49; P &lt;0.001), and pneumonia (4.5% versus 10.1%; OR , 0.41; P &lt;0.001) were significantly less frequent with TAVR versus SAVR . Use of noninvasive mechanical ventilation was similar between TAVR and SAVR (4.1% versus 4.8%; OR , 0.84; P =0.41). Non‐respiratory‐related complications, such as in‐hospital mortality (3.3% versus 4.2%; OR , 0.64; P =0.035), bleeding requiring transfusion (9.9% versus 21.7%; OR , 0.38; P &lt;0.001), acute kidney injury (17.7% versus 25.3%; OR , 0.63; P &lt;0.001), and acute myocardial infarction (2.4% versus 8.4%; OR , 0.19; P &lt;0.001), were significantly less frequent with TAVR than SAVR . Cost ($56 099 versus$63 146; P &lt;0.001) and hospital stay (mean, 7.7 versus 13.0 days; P &lt;0.001) were also more favorable with TAVR than SAVR . Conclusions TAVR portended significantly fewer respiratory‐related complications compared with SAVR in COPD patients. TAVR may be a preferable mode of aortic valve replacement in COPD patients. </jats:sec

"More than just a medical student”: a mixed methods exploration of a structured volunteering programme for undergraduate medical students

Background As a result of the COVID-19 pandemic Imperial College School of Medicine developed a structured volunteering programme involving 398 medical students, across eight teaching hospitals. This case study aims to illuminate the experiences of volunteers, mechanisms of learning and draw lessons for future emergencies and curriculum improvements. Methods Using an illuminative approach to evaluation we invited all volunteers and supervisors to complete a mixed-methods survey. This gathered nominal demographic information and qualitative data related to motivations, experiences, insights into learning, processual and contextual factors. Qualitative responses were coded, thematically organised, and categorised into an overarching framework. Mann-Whitney U tests determined whether volunteers’ overall rating of the experience varied according to demographic features and modulating factors. Spearman’s rank correlation assessed the relationship between aspects of induction and supervision, and overall volunteering rating. Follow up interviews were carried out with students to check back findings and co-create conclusions. Results Modulating factors identified through thematic analysis include altruistic motivation, engaged induction and supervision, feeling valued, having responsibility and freedom from the formal curriculum. Statistically significant positive correlations are identified between volunteers overall rating and being a year 1 or 2 student, ability to discuss role and ask questions during induction, being male, and having regular meetings and role support from supervisors. Qualitatively reported impacts include improved wellbeing, valuable contribution to service and transformative learning. Transformative learning effects included reframing of role within the multidisciplinary team, view of effective learning and view of themselves as competent clinicians. The number of weeks, number of shifts per week, and the role the volunteers performed, did not significantly impact experiences. Conclusions While acknowledging the uniqueness of the situation presented by the first wave COVID-19, we suggest the features of a successful service-learning programme include: a learner-centred induction, engaged and appreciative supervisors, and the entrustment of students with meaningful work with reciprocal benefits to services. Programmes in similar settings may find that 1) volunteering is best appreciated in years 1 or 2, 2) students with altruistic motivations and meaningful work may flourish without formal outcomes and assessments, and 3) that female volunteers may experience emergency learning differently to men

Understanding the Correlation between Tomographic and Biomechanical Severity of Keratoconic Corneas

Purpose. To evaluate correlation between tomographic gradation of keratoconus (KC) and its corresponding air-puff induced biomechanical response. Methods. Corneal tomography and biomechanics were measured with Scheimpflug imaging in 44 normal and 92 KC corneas. Deformation waveform was also analyzed with Fourier series. A custom KC severity scale was used from 1 to 3 with 3 as the most severe grade. Tomographic and biomechanical variables were assessed among the grades. Sensitivity and specificity of the variables were assessed using receiver operating characteristics (ROC). Results. Curvature variables were significantly different between normal and disease (P0.05). All variables had an area under the ROC curve greater than 0.5. The root mean square of the Fourier cosine coefficients had the best ROC (0.92, cut-off: 0.027, sensitivity: 83%, specificity: 88.6%). Spearman correlation coefficient was significant between most variables (P<0.05). However, tomographic segregation of keratoconus did not result in concomitant biomechanical segregation of the grades. Conclusions. There was lack of significant biomechanical difference between mild disease grades, despite progressive corneal thinning. Mathematical models that estimate corneal modulus from air-puff deformation may be more useful