Faculty Bibliography

BACKGROUND:Oral pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) provision via online pharmacies (henceforth online PrEP and PEP) offers promise in increasing biomedical HIV prevention coverage. In this study, we aimed to estimate the cost-effectiveness of online PrEP and PEP scale-up in western Kenya. METHODS:We adapted a network-based model, EMOD-HIV, to simulate online PrEP and PEP implementation from 2026 to 2036; costs and use of online PrEP and PEP and client characteristics were informed by the ePrEP Kenya pilot study, which evaluated online PrEP and PEP provision in Nairobi and Mombasa, Kenya. Other parameters were obtained from surveillance data and published literature. Eligible clients were aged 15-49 years reporting condomless sex with non-marital partners. We assumed online PrEP and PEP provision was implemented through public-private partnership, with the Kenya Ministry of Health providing PrEP and PEP drugs and service delivery costs paid by the online pharmacy (and charged to clients). We estimated HIV infections, HIV-related deaths, and disability-adjusted life-years (DALYs) averted compared with the baseline scenario of background oral PrEP only. We calculated incremental cost-effectiveness ratios (ICERs) assessing only costs incurred by the Kenya Ministry of Health over 35 years and used a supply-side threshold of US$500 per DALY averted. We calculated 95% uncertainty intervals (UIs) across 100 parameter sets. FINDINGS/RESULTS:Online PrEP and PEP was projected to reach population coverage of 0·7% (95% UI 0·7-0·8) for PEP and 0·3% (0·2-0·3) for PrEP and avert 13·9% (10·1-17·1) of HIV infections over 10 years. HIV-related deaths were reduced by 4·3% (95% UI 2·0-6·9) over the 35-year time horizon. The intervention was cost-effective from the Kenya Ministry of Health perspective (ICER $212 [95% UI 15-1409] per DALY averted). In a scenario assuming only online PEP availability (to isolate the effect of PEP), 11·6% (95% UI 8·6-15·2) of HIV infections were averted (ICER $210 [95% UI 41-3798] per DALY averted). The intervention remained cost-effective when varying PrEP and PEP effectiveness and assuming HIV testing and treatment disruptions. INTERPRETATION/CONCLUSIONS:Online PrEP and PEP can avert substantial HIV infections, even with low population coverage. PEP was responsible for most intervention health benefits, likely due to high observed demand for PEP compared with PrEP in the pilot study. Leveraging private retailers can be efficient for scaling up HIV prevention in an era of shrinking donor funding. FUNDING/BACKGROUND:Gates Foundation.

Parallel imaging techniques reduce magnetic resonance imaging (MRI) scan time but image quality degrades as the acceleration factor increases. In clinical practice, conservative acceleration factors are chosen because no mechanism exists to automatically assess the diagnostic quality of undersampled reconstructions. This work introduces a general framework for pixel-wise uncertainty quantification in parallel MRI reconstructions, enabling automatic identification of unreliable regions without access to any ground-truth reference image. Our method integrates conformal quantile regression with image reconstruction methods to estimate statistically rigorous pixelwise uncertainty intervals. We trained and evaluated our model on Cartesian undersampled brain and knee data obtained from the fastMRI dataset using acceleration factors ranging from 2 to 10. An end-to-end Variational Network was used for image reconstruction. Quantitative experiments demonstrate strong agreement between predicted uncertainty maps and true reconstruction error. Using our method, the corresponding Pearson correlation coefficient was higher than 90% at acceleration levels at and above four-fold; whereas it dropped to less than 70% when the uncertainty was computed using a simpler a heuristic notion (magnitude of the residual). Qualitative examples further show the uncertainty maps based on quantile regression capture the magnitude and spatial distribution of reconstruction errors across acceleration factors, with regions of elevated uncertainty aligning with pathologies and artifacts. The proposed framework enables evaluation of reconstruction quality without access to fully-sampled ground-truth reference images. It represents a step toward adaptive MRI acquisition protocols that may be able to dynamically balance scan time and diagnostic reliability.

INTRODUCTION/BACKGROUND:Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss due to immune dysregulation. Despite advances, its precise molecular mechanisms remain unclear. This study investigates plasma microRNA (miRNA) expression profiles in patients with AA to identify biological pathways influenced by miRNAs and potential therapeutic targets. METHODS:A total of 50 patients with AA were categorized as severe or mild on the basis of Severity of Alopecia Tool (SALT) scores. Plasma miRNA levels were compared with those of healthy controls and individuals with other immune-mediated skin diseases. In the discovery phase, 754 miRNAs were analyzed in 20 participants (5 severe AA, 5 mild AA, and 10 controls). Key miRNAs identified were then validated in a second cohort of 90 participants, including patients with AA, non-segmental vitiligo, atopic dermatitis (AD), psoriasis (PsO), and healthy controls, using real-time polymerase chain reaction (RT-PCR). Machine learning was used to classify patients on the basis of their miRNA profiles, and pathway enrichment analysis and drug targeting were conducted to explore therapeutic opportunities. RESULTS:In total, 19 miRNAs were significantly downregulated in AA, with 9 technically and clinically validated for both mild and severe forms. The top four miRNAs with the highest classification potential were miR-130b-3p, miR-296-5p, miR-424-5p, and miR-195-5p. Distinct upregulation patterns were identified in vitiligo, AD, and PsO. Machine learning models showed vital classification accuracy for AA (AUC = 0.94) and PsO (AUC = 0.88), with moderate performance for non-segmental vitiligo and AD. Pathway enrichment analysis highlighted immune-related pathways, including the interferon-gamma and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. Drug repositioning identified kinase inhibitors showing the most significant promise for reversing miRNA dysregulation. CONCLUSIONS:This study identifies distinct plasma miRNA profiles in AA, with potential applications for both diagnosis and therapy. Machine learning validated its solid predictive accuracy, and pathway analysis highlighted key immune pathways in AA. These findings should be interpreted as exploratory and hypothesis-generating, pending further functional validation of candidate miRNAs.

This video demonstrates a repeat bleb revision for over filtration following a trabeculectomy in a 69-year-old male with severe pigmentary glaucoma.