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Evaluating the Association of Widefield Swept-Source Optical Coherence Tomography Angiography with Visual Function in Common Retinal Diseases
No full textBackground: The clinical evaluation, diagnosis, and treatment of ophthalmic diseases relies on both a structural evaluation and a visual function assessment. Wide-field swept source optical coherence tomography (WF SS-OCTA) is a novel imaging technique that acquires fast, non-invasive, high-resolution images of the retinal microvasculature. Visual acuity (VA) is the most common measure of visual function. Contrast sensitivity (CS) is an adjunct functional metric that studies suggest is better associated with vision related quality of life and affected earlier in retinal disease. Yet few studies have evaluated WF SS-OCTA and CS associations. We aim to evaluate the association of WF SS-OCTA with visual function, including CS, for a variety of common retinal diseases.
Methods: Patients were prospectively-recruited from retina clinics at Massachusetts Eye and Ear. The cohorts included diabetic retinopathy (DR, n = 140), diabetic macular edema (DME, n = 61), retinal vein occlusion (RVO, n = 63), retinal detachment (RD, n = 57), age-related macular degeneration (AMD, n = 72), and healthy eyes (n = 57). WF SS-OCTA (PLEX® Elite 9000, Carl Zeiss Meditec) 3x3, 6x6, and 12x12 mm images were acquired, from which vessel density (VD) and vessel skeletonized density (VSD) in the superficial (SCP) and deep (DCP) capillary plexus, and whole retina (WR), foveal avascular zone (FAZ) parameters, and non-perfusion area were calculated. VA was measured on Snellen charts. CS was measured using the quantitative contrast sensitivity function (qCSF) device (Adaptive Sensory Technology), resulting in the following qCSF metrics: Area under the Log CSF (AULCSF), contrast acuity (CA), and contrast sensitivity (CS) thresholds at 1 to 18 cycles per degree (cpd). Mixed effects multivariable linear regression models were used to evaluate for associations between WF SS-OCTA vascular metrics and visual function.
Results: Across all the diseases evaluated OCTA vascular metrics demonstrated significant associations with both VA and CS. Further, the effect size of OCTA vascular metrics was consistently larger on CS compared to VA on nearly all associations. For example, in DME the standardized beta coefficients for VSD and CS at 3 cpd (βSCP = 0.76, βDCP = 0.71, βWR = 0.72, p 0.001) were larger than those for VA (βSCP = -0.55, p 0.001; βDCP = -0.43, p = 0.004; βWR = -0.50, p 0.001). Across each disease there were instances where VA failed to demonstrate significant associations with the vascular metrics, unlike CS. For example among the RD cohort, CS had multiple significant associations with VD and VSD on all three image sizes, unlike VA. In AMD, nearly every single CS metric showed significant associations with VD and VSD on 3x3 mm images, even though VA did not. Each disease cohort revealed unique structure-function associations, for example, in RVO and RD the vascular metrics appeared to have the largest effect size on AULCSF, in DR and healthy eyes the largest effect size was on CS at 12-18 cpd, while in DME and AMD it was on CS at 3-6 cpd.
Conclusion: Multiple structure-function studies across various retinal diseases demonstrated that WF SS-OCTA vascular metrics were significantly associated with both CS and VA. However, the effect size of OCTA was larger on CS, compared to VA, suggesting that CS likely better reflects the microvascular changes found in WF SS-OCTA. Integrating WF SS-OCTA and CS into the clinical workflow of retina clinics and utilizing these measures in clinical trials may positively impact the management and outcomes among various ophthalmic diseases.Honors Progra
Architectures of Relation: A Rhizomatic Pedagogy for Heartland Brazil
No full textThis thesis is a proposition for a new turn in the architectural pedagogy of Brazil, with a focus on addressing the curricula found in schools in the country’s heartland. The prevailing educational model is the continuation of a colonial project, reflecting its xenocentric premise — the devaluation of local culture in favor of foreign values. As a result, the dominant current pedagogical frameworks are misaligned with the specific demands and disciplinary realities of Brazil, especially its mid-sized cities, its heartlands.
This project introduces the concept of Architectures of Relation, developed after Édouard Glissant’s epistemology. Glissant defines Relation as a break from models of alterity, offering a way to understand cultural identity as “not made up of things that are foreign, but of shared knowledge” (Glissant, 1997). While the Western worldview tends to impose transparency, Relation embraces opacities: the untranslatable and culturally specific.
This proposition is informed by a study of the professional context of architecture in Brazil’s mid-sized cities, which are currently the fastest-growing urban centers in the country. To further the studies of pedagogical realities, Escola da Cidade, an independent architecture school in São Paulo, serves as a case study for its pedagogical model tailored to the city it operates within.
Building on the insights from the case study and field analysis, the thesis interprets the parameters of the UNESCO-UIA Charter for Architectural Education under the lens of Glissant’s thought, addressing core architectural realities such as labor, materials, cultural elements, spatial occupation, and climate-responsive design. The final proposed framework is based on pedagogical devices meant to be merged with the core curriculum of schools, aiming to educate architects and urbanists capable of designing cities that are culturally, socially, and ecologically sustainable.Department of Architectur
Predicting Non-Surgical Root Canal Therapy Outcomes Using Machine Learning
No full textDespite the high success rate of nonsurgical root canal treatment (NSRCT), some cases fail, making outcome prediction challenging. Artificial intelligence (AI), particularly machine learning (ML), has shown promise in dentistry for diagnosing various conditions. However, precise AI tools for predicting endodontic outcomes remains limited. This study evaluates the ability of ML models to predict NSRCT prognosis, compare their effectiveness, and identify key factors influencing treatment outcomes. Specifically, it assesses and compares the performances of three ML algorithms: Decision Tree (DT), Gradient Boosting Machine (GBM), and Random Forest (RF). From 2009 to 2022, 11,232 primary NSRCT and recall cases were performed at the Harvard Dental Clinic Faculty Group Practice by residents and faculty. A total of 700 charts were randomly selected and manually screened, with 120 cases meeting the inclusion and exclusion criteria for ML analysis. The Chi-Squared p-value matrix identified “Satisfactory Coronal Restoration” as significantly correlated with NSRCT “Success vs. Failure” (p = 0.0107). To enhance model performance, features with p-values greater than 0.9 were removed prior to ML analysis to minimize noise. Feature importance rankings across all three ML models identified “Follow-up Time (Months)”, “Age During Treatment”, “Satisfactory Coronal Restoration”, and “Sealer Puff” as top influential factor in predicting NSRCT outcomes. Among the models, RF demonstrated the highest performance, as reflected by its slightly superior F1 score and AUC value. F1 sores ranked as follows: RF (F1 = 0.789), GBM (F1 = 0.707), and DT (F1 = 0.693). For AUC values, DT did slightly better than GBM with the following ranking: RF (AUC = 0.617), DT (AUC = 0.582), GBM (AUC = 0.501). With the current selection of naïve hyperparameters and features selected, cross validation scoring and accuracy metrics indicate a slight preference of the RF classifier over the other two models. Further hyperparameter tuning and improved feature selection may provide marginal improvements. The primary limitation of this study is the small sample size, which affects the reliability of the ML model predictions. However, with a larger dataset, ML could serve as a valuable tool for assessing NSRCT outcomes and guiding clinical decision-making in endodontics.Endodontic
FL* theory of the pseudogap, d-wave superconductivity, and charge order in the cuprates
No full textPhysicsAuthor's Origina
Mosaic nucleic acids that bind purine nucleotides
No full textModels for the origin of life have maintained that the first cells relied upon a single biopolymer for both genotype and phenotype. RNA may have provided these activities through its ability to transfer information via base-pairing and its ability to fold into functional structures. It follows that a comprehensive account of abiogenesis would include an understanding of prebiotic ribonucleotide synthesis. However, studies along these lines have shown that, depending on conditions, prebiotic chemistry may yield diverse nucleotides; some of which are based on sugars other than ribose. This monomer pool would likely support the polymerization of nucleic acid molecules characterized by a heterogeneous sugar-phosphate backbone. Copies of such mosaic nucleic acid (MNA) would conserve sequence information, but not the order and content of sugars in the sugar-phosphate backbone. Might MNA represent a possible source of early biological activity? The answer to this question largely depends on whether the structural heterogeneity of the sugar-phosphate backbone would allow for the emergence of selectable function. To test this possibility, we used in vitro selection to isolate purine nucleotide-binding MNA aptamers from a large library of random MNA sequences (containing an ∼1:1 mixed assignment of deoxy- and ribonucleotides). We report two MNA aptamers that bind either ATP or GTP with weak affinity (apparent KDs = ∼350 µM each) and moderate to high specificity. We conclude that variations in nucleic acid backbone content, perhaps introduced by imprecise synthesis, may not have posed an insurmountable barrier for the emergence of simple biological function.Medical SciencesMedical Science
Evaluation of Resveratrol and BioDendrimer-Resveratrol in Models of Dental Pulp Inflammation – In-vitro
No full textVital pulp therapy (VPT) aims to preserve dental pulp tissues and maintain tooth function, while alleviating dental pain. However, persistent pain may necessitate more invasive treatments like root canal therapy (RCT). Current clinical VPT protocols lack options for treatments that might enhance tissue healing and improve post-operative pain outcomes. Resveratrol (RESV), a naturally occurring bioactive compounds, that exists in 72 plant species such as grapevines, blueberries, and others. RESV is known for its anti-inflammatory, antimicrobial, and neuroprotective effects, and it holds promise for VPT. Our aim is to determine the effects of two formulations of resveratrol (resveratrol (RESV) and biodendrimer- resveratrol (BD- RESV) on cytokine expression, mineralization and migration of dental pulp stem cells (DPSCs) challenged with LPS as an in-vitro model of pulpitis.
Commercially available (Lansa) DPSCs from healthy adult teeth were grown using a-Minimum Essential Medium (Sigma-Aldrich, St Louis, MO) supplemented with other agents. Cells were maintained at 37 °C / 5% CO2 and plated for experiments at passage 2 or 3. Cells were treated for 2 to 7 days with varying doses of RESV (0.001-100µM), BD-RESV (0.001-100µM) and challenged with LPS or vehicle control (0.001-100µg/ml). Cell viability was assessed using the MTT assay on day 7, cell migration and cytokine expression (qRT-PCR) were evaluated on day 2 and mineralization was evaluated with alizarin red staining on day 28. We found that BD-RESV decreased LPS -induced DPSC cytotoxicity with statistically significant effect on LPS dose of 1µg/ml (p 0.05), while RESV had no effect. However, both RESV and BD-RESV significantly prevented LPS induced upregulation of IL1-β, IL-6, IL-8 mRNA (p 0.05). RESV and BD-RESV also induced the formation of calcium nodules (alizarin Staining) with the most significant effect observed at RESV 5µM and BD-10 µM (p 0.05) and significantly increased DPSC migration (p 0.05). Resv and Biodendrimer demonstrated a similar ability to mitigate LPS-induced cytokine upregulation and induce mineralization and DPSC migration suggesting its properties are particularly relevant to improve tissue healing in dental pulpas an inflammatory response modulator. However, further in-vivo research that incorporates RESV and BD-RESV as a direct pulp capping material in pulp exposure model of pulpitis is necessary to confirm that RESV's would be useful as a VPT supplementary component.Oral Biolog
The Forced Migration of German-Speaking Neuroscientists in North America, 1933 to 1989
No full textAuthor's Origina
Implant Stability: A Prospective Clinical Study with a 2-year Follow-up
No full textAbstract
Purpose:
This prospective cohort study investigated the relationship between interproximal contact loss (ICL) and tactile sensitivity around implant-supported single-tooth restorations over an 18-month period.
Materials and Methods:
Twenty partially edentulous participants received posterior single-tooth implants restored with screw-retained monolithic zirconia crowns on custom titanium abutments. Interproximal contact tightness was quantitatively measured using a digital force gauge, and occlusal tactile sensitivity (osseoperception) was evaluated using progressively thicker occlusal foils. Contralateral natural teeth served as controls. Clinical assessments, including peri-implant plaque index, probing depths, and bleeding on probing, were performed at baseline and follow-up visits at 1, 3, 6, 12, and 18 months.
Results:
Only two of 20 implant sites (10%) developed open interproximal contacts, both within six months of crown delivery. Most contacts remained functionally closed, with only modest decreases in contact force over time. Tactile sensitivity thresholds were consistently higher for implant sites compared to control teeth, though differences were not statistically significant (p > 0.05). Peri-implant soft tissue health remained stable across all time points.
Conclusions:
The incidence of interproximal contact loss in this cohort was low, with no adverse effects on peri-implant health. Although implant restorations demonstrated higher tactile thresholds than natural teeth, perceptual function improved over time. These findings highlight the need for continued monitoring of contact stability, particularly in the mandible, and support the potential for limited osseoperception in implant-supported crowns.Prosthodontic
The Mixed Blessing/Curse of the Meyer-Pierce Legacy
No full textThe Supreme Court decisions in Meyer v. Nebraska and Pierce v. Society of Sisters left us a mixed legacy, one part blessing and one part curse. Many would agree on this but differ on which part is blessing and which part curse. In my view the blessing is the doctrine of substantive due process protecting personal liberty. The Court did not use this language in these cases, but it did rule that the states’ attempts to interfere with parent rights in those cases violated the 14th Amendment to the U.S. Constitution, and the Court made it clear that in future cases the state would bear a heavy burden to justify any such attempts. In later cases, the Court looked back to Meyer and Pierce as the foundational law when it created important reproductive freedom and relationship rights—the right to contraception and abortion, the rights to sex and marriage for same-sex couples. In my view the curse is the doctrine of parent rights, given the Court’s failure to create any comparable rights for children. More on this later, but first a word on legacy.Version of Recor