National Trends in PSA Cancer Screening With Parallel Investigation of Colorectal Cancer Screening: An Analysis of the CDC Behavioral Risk Factor Surveillance System From 2012 to 2022.

INTRODUCTION/BACKGROUND: From 2012 to 2022 there have been numerous revisions in the United States Preventative Task Force guidelines for prostate cancer screening, including advising against PSA testing to allowing shared-decision making for men aged 55 to 69. We sought to observe trends in PSA testing rates in relation to the changing guidelines. Conversely, colorectal cancer screening recommendations remained consistent for patients aged 50-75 and we sought to use this as a comparison to observe the effect of differing guidelines. METHODS: The Centers for Disease Control Behavioral Risk Factor Surveillance System is a national database of surveys on health-related behaviors and preventive medical services. We extracted responses from 2012 to 2022 regarding both prostate and colorectal cancer screening. Our primary variable of interest was prostate cancer screening while colorectal cancer screening served as a positive control. RESULTS: Prostate cancer screening decreased among respondents from 70.1% in 2012 to 59.7% in 2022. However, there was a significant rebound in prostate cancer screening prevalence in 2022. In contrast, colorectal cancer screening rates steadily increased from 70.7% in 2012 to 78% in 2022. The annual percentage of men who had received prostate cancer screening was statistically different year to year. CONCLUSIONS: Trends in the rate of screening for prostate and colorectal cancer appeared to adapt to the updated recommendations. However, further investigation regarding lower income levels, minority groups, and uninsured men are essential to address the social and racial disparities seen in prostate cancer screening. Efforts to promote shared-decision making may improve effective cancer screening.

Preventing Site-Specific Calpain Proteolysis of Junctophilin-2 Protects Against Stress-Induced Excitation-Contraction Uncoupling and Heart Failure Development.

BACKGROUND: Excitation-contraction (E-C) coupling processes become disrupted in heart failure (HF), resulting in abnormal Ca2+ homeostasis, maladaptive structural and transcriptional remodeling, and cardiac dysfunction. Junctophilin-2 (JP2) is an essential component of the E-C coupling apparatus but becomes site-specifically cleaved by calpain, leading to disruption of E-C coupling, plasmalemmal transverse tubule degeneration, abnormal Ca2+ homeostasis, and HF. However, it is not clear whether preventing site-specific calpain cleavage of JP2 is sufficient to protect the heart against stress-induced pathological cardiac remodeling in vivo. METHODS: Calpain-resistant JP2 knock-in mice (JP2CR) were generated by deleting the primary JP2 calpain cleavage site. Stress-dependent JP2 cleavage was assessed through in vitro cleavage assays and in isolated cardiomyocytes treated with 1 µmol/L isoproterenol by immunofluorescence. Cardiac outcomes were assessed in wild-type and JP2CR mice 5 weeks after transverse aortic constriction compared with sham surgery using echocardiography, histology, and RNA-sequencing methods. E-C coupling efficiency was measured by in situ confocal microscopy. E-C coupling proteins were evaluated by calpain assays and Western blotting. The effectiveness of adeno-associated virus gene therapy with JP2CR, JP2, or green fluorescent protein to slow HF progression was evaluated in mice with established cardiac dysfunction. RESULTS: JP2 proteolysis by calpain and in response to transverse aortic constriction and isoproterenol was blocked in JP2CR cardiomyocytes. JP2CR hearts are more resistant to pressure-overload stress, having significantly improved Ca2+ homeostasis and transverse tubule organization with significantly attenuated cardiac dysfunction, hypertrophy, lung edema, fibrosis, and gene expression changes relative to wild-type mice. JP2CR preserves the integrity of calpain-sensitive E-C coupling-related proteins, including ryanodine receptor 2, CaV1.2, and sarcoplasmic reticulum calcium ATPase 2a, by attenuating transverse aortic constriction-induced increases in calpain activity. Furthermore, JP2CR gene therapy after the onset of cardiac dysfunction was found to be effective at slowing the progression of HF and superior to wild-type JP2. CONCLUSIONS: The data presented here demonstrate that preserving JP2-dependent E-C coupling by prohibiting the site-specific calpain cleavage of JP2 offers multifaceted beneficial effects, conferring cardiac protection against stress-induced proteolysis, hypertrophy, and HF. Our data also indicate that specifically targeting the primary calpain cleavage site of JP2 by gene therapy approaches holds great therapeutic potential as a novel precision medicine for treating HF.

Soccer and Vocational Training are Ineffective Delivery Strategies to Prevent HIV and Substance Abuse by Young, South African Men: A Cluster Randomized Controlled Trial.

HIV and substance abuse are common among young men, associated with a cluster of risk behaviors. Yet, most services addressing these challenges are delivered in setting underutilized by men and are often inconsistent with male identity. This cluster randomized controlled trial aimed to reduce multiple risk behaviors found among young men township areas on the outskirts of Cape Town, South Africa. Young men aged 18-29 years (N = 1193) across 27 neighborhoods were randomized by area to receive HIV-related skills training during either: (1) a 12-month soccer league (SL) intervention; (2) 6-month SL followed by 6 months of vocational training (VT) intervention (SL/VT, n = 9); or 3) a control condition (CC). Bayesian longitudinal mixture models were used to evaluate behaviors over time. Because we targeted multiple outcomes as our primary outcome, we analyzed if the number of significantly different outcomes between conditions exceeded chance for 13 measures over 18 months (with 83%, 76%, and 61% follow-up). Only if there were three significant benefits favoring the SL/VT over the SL would benefits be significant. Outcome measures included substance use, HIV-testing, protective sexual behaviors, violence, community engagement and mental health. Consistent participation in the SL was typically around 45% over time across conditions, however, only 17% of men completed SL/VT. There were no significant differences between conditions over time based on the number of study outcomes. These structural interventions were ineffective in addressing young men's substance abuse and risk for HIV.Clinical Trial Registration: This trial was prospectively registered on 24 November 2014 with ClinicalTrials.gov (NCT02358226).

Resist and recover: Introducing a spring theory for modeling disaster resilience.

This paper presents a new approach for quantitatively modeling the resilience of a system that has been disrupted by a sudden-impact event. It introduces a new theoretical model that explicitly incorporates representations of the enabling and inhibiting forces that are inherent within postdisruption recovery behavior. Based on a new, more comprehensive measure of resilience that is able to capture both negative and positive deviations in performance, a generic mass-spring system is then used to illustrate the applicability of the theoretical model. The interplay between the enabling and inhibiting forces that is revealed by the new model provides a new theoretical basis for understanding the complexity of resilience and disaster recovery. With the addition of the new resilience measure, it lends support for defining and characterizing a new type of resilient behavior: unstable resilience.

Comparison of Retinal Nerve Fiber Layer and Ganglion Cell Complex Rates of Change in Patients With Moderate to Advanced Glaucoma.

PURPOSE: To compare ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) rates of change (RoC) in eyes with central or moderate to advanced glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 918 matched macular and RNFL OCT scan pairs from 109 eyes (109 patients) enrolled in the Advanced Glaucoma Progression Study with ≥2 years of follow-up and ≥4 OCT scans. METHODS: We exported GCC and RNFL thickness measurements in 49 central macular superpixels and 12 RNFL clock-hour sectors, respectively. We applied our latest Bayesian hierarchical longitudinal model to estimate population and subject-specific baseline thickness (intercepts) and rates of change (RoC) in macular superpixels and RNFL sectors. Global RNFL and GCC RoC were analyzed in a single bivariate longitudinal model to properly compare them accounting for the correlation between their RoC. MAIN OUTCOME MEASURES: Proportion of significant negative (deteriorating) and positive (improving) RoC expressed in µm/year. Standardized RoC were calculated by dividing RoC by the corresponding population SD. Analyses were repeated in eyes with visual field mean deviation (MD) ≤-6 and > -6 dB. RESULTS: Average (SD) 24-2 visual field MD and follow-up length were -8.6 (6.3) dB and 4.2 (0.5) years, respectively. Global RNFL RoC (-0.70 µm/year) were faster than GCC (-0.44 µm/year) (P < .001); corresponding normalized RoC were not significantly different (P = .052). In bivariate analysis, patients with a significant negative global RNFL RoC (n = 63, 57%) or GCC (n = 56, 51%) frequently did so for both outcomes (n = 49, 45%). The average proportion of significantly decreasing RNFL sectors within an eye was 30.7% in eyes with MD > -6 dB compared to 20.5% in those with MD ≤ -6 dB (P = .014); the proportions for GCC superpixels were 21.1% versus 18.7%, respectively (P = .63). CONCLUSIONS: Both GCC and RNFL measures can detect structural progression in glaucoma patients with central damage or moderate to advanced glaucoma. The clinical utility of RNFL imaging decreases with worsening severity of glaucoma.

Dimethylene-Cyclopropanide Units as Building Blocks for Fluorescence Dyes.

Many organic dyes are fluorescent in solution. In the solid state, however, quenching processes often dominate, hampering material science applications such as light filters, light-emitting devices, or coding tags. We show that the dimethylene-cyclopropanide scaffold can be used to form two structurally different types of chromophores, which feature fluorescence quantum yields up to 0.65 in dimethyl sulfoxide and 0.53 in solids. The increased fluorescence in the solid state for compounds bearing malonate substituents instead of dicyanomethid ones is rationalized by the induced twist between the planes of the cyclopropanide core and a pyridine ligand.

Predisposing Anatomy for Thoracic Outlet Syndrome and Functional Outcomes after Supraclavicular Thoracic Outlet Decompression in Athletes.

Purpose: This study aims to examine predisposing anatomic factors and subsequent post-decompression functional outcomes among high-intensity athletes with thoracic outlet syndrome (TOS). Materials and Methods: A single-institution retrospective review was performed on a prospective database of patients with TOS from 2018 to 2023 who had undergone operative decompression for TOS. Demographics, TOS characteristics, predisposing anatomy, operative details, and postoperative outcomes were examined. The primary outcome was postoperative return to sport. Secondary outcomes included vascular patency. Results: A total of 13 patients who were engaged in high-demand athletic activity at the time of their diagnosis were included. Diagnoses included 8 (62%) patients with venous TOS, 4 (31%) patients with neurogenic TOS, and 1 (8%) patient with arterial TOS. Mixed vascular and neurogenic TOS was observed in 3 (23%) patients. The mean age of the cohort was 30 years. Abnormal scalene structure was observed in 12 (92%) patients, and abnormal bone structures were noted in 4 (27%) patients; 2 (15%) with cervical ribs and 3 (23%) patients with clavicular abnormalities. Prior ipsilateral upper extremity trauma was reported in 4 (27%) patients. Significant joint hypermobility was observed in 8 (62%) patients with a median Beighton score of 6. Supraclavicular cervical and/or first rib resection with scalenectomy was performed in all patients. One case of postoperative pneumothorax was treated non-operatively. Ten (77%) patients returned to sport. Duplex ultrasonography showed subclavian vein patency in all 8 patients with venous TOS and wide patency with no drop in perfusion indices in the patient with arterial TOS. Conclusion: Athletes with TOS who required operative intervention had a high incidence of musculoskeletal aberrations and joint hypermobility. Supraclavicular decompression was associated with a high success rate, with overall good functional outcomes and good likelihood of patients returning to preoperative high-intensity athletics.

Stochasticity, determinism, and contingency shape genome evolution of endosymbiotic bacteria.

Evolution results from the interaction of stochastic and deterministic processes that create a web of historical contingency, shaping gene content and organismal function. To understand the scope of this interaction, we examine the relative contributions of stochasticity, determinism, and contingency in shaping gene inactivation in 34 lineages of endosymbiotic bacteria, Sodalis, found in parasitic lice, Columbicola, that are independently undergoing genome degeneration. Here we show that the process of genome degeneration in this system is largely deterministic: genes involved in amino acid biosynthesis are lost while those involved in providing B-vitamins to the host are retained. In contrast, many genes encoding redundant functions, including components of the respiratory chain and DNA repair pathways, are subject to stochastic loss, yielding historical contingencies that constrain subsequent losses. Thus, while selection results in functional convergence between symbiont lineages, stochastic mutations initiate distinct evolutionary trajectories, generating diverse gene inventories that lack the functional redundancy typically found in free-living relatives.

Matriglycan maintains t-tubule structural integrity in cardiac muscle.

Maintaining the structure of cardiac membranes and membrane organelles is essential for heart function. A critical cardiac membrane organelle is the transverse tubule system (called the t-tubule system) which is an invagination of the surface membrane. A unique structural characteristic of the cardiac muscle t-tubule system is the extension of the extracellular matrix (ECM) from the surface membrane into the t-tubule lumen. However, the importance of the ECM extending into the cardiac t-tubule lumen is not well understood. Dystroglycan (DG) is an ECM receptor in the surface membrane of many cells, and it is also expressed in t-tubules in cardiac muscle. Extensive posttranslational processing and O-glycosylation are required for DG to bind ECM proteins and the binding is mediated by a glycan structure known as matriglycan. Genetic disruption resulting in defective O-glycosylation of DG results in muscular dystrophy with cardiorespiratory pathophysiology. Here, we show that DG is essential for maintaining cardiac t-tubule structural integrity. Mice with defects in O-glycosylation of DG developed normal t-tubules but were susceptible to stress-induced t-tubule loss or severing that contributed to cardiac dysfunction and disease progression. Finally, we observed similar stress-induced cardiac t-tubule disruption in a cohort of mice that solely lacked matriglycan. Collectively, our data indicate that DG in t-tubules anchors the luminal ECM to the t-tubule membrane via the polysaccharide matriglycan, which is critical to transmitting structural strength of the ECM to the t-tubules and provides resistance to mechanical stress, ultimately preventing disruptions in cardiac t-tubule integrity.

"Efficacy and Safety of OnabotulinumtoxinA for the Treatment of Platysma Prominence: A Randomized Phase 2 Dose-Ranging Study".

BACKGROUND: With aging, repetitive contraction of the platysma leads to an increase in platysma prominence (PP) characterized by the accentuation of vertical neck bands and blunting of the jawline's contour. METHODS: This multicenter, double-blind, phase 2 study evaluated onabotulinumtoxinA (onabotA) treatment in adults with Moderate to Severe PP. Participants were randomized to receive 1 treatment of onabotA low dose (LD), onabotA high dose (HD), or placebo, and were followed for 4 months. Efficacy endpoints were the achievement of a ≥ 1-grade improvement on both the left and right sides at Day 14 at maximum contraction as assessed by the investigator (primary) or by participants (secondary) using validated scales. Safety was evaluated throughout. RESULTS: Participants in the modified intent-to-treat population (N = 164) had a mean age of 50 years; 95.1% were female and 93.9% were White. The primary endpoint was met for both onabotA groups, with investigator-assessed ≥ 1-grade improvement in 77.8% (LD) and 88.2% (HD) vs 12.0% (placebo) of participants on Day 14 (P < 0.0001 vs placebo). Based on participant self-assessment, 75.9% (LD) and 88.2% (HD) vs 18.0% (placebo) achieved ≥ 1-grade improvement on Day 14 (P < 0.0001 vs placebo). Most treatment-related adverse events (AEs) were procedure-related, transient, and mild in severity. The most frequent onabotA-related AE was neck muscle weakness, reported in the HD group. CONCLUSIONS: OnabotA was effective in improving the appearance of PP based on both investigators' and participants' ratings. Treatment was well tolerated.

A TOPBP1 allele causing male infertility uncouples XY silencing dynamics from sex body formation.

Meiotic sex chromosome inactivation (MSCI) is a critical feature of meiotic prophase I progression in males. While the ATR kinase and its activator TOPBP1 are key drivers of MSCI within the specialized sex body (SB) domain of the nucleus, how they promote silencing remains unclear given their multifaceted meiotic functions that also include DNA repair, chromosome synapsis, and SB formation. Here we report a novel mutant mouse harboring mutations in the TOPBP1-BRCT5 domain. Topbp1B5/B5 males are infertile, with impaired MSCI despite displaying grossly normal events of early prophase I, including synapsis and SB formation. Specific ATR-dependent events are disrupted, including phosphorylation and localization of the RNA:DNA helicase Senataxin. Topbp1B5/B5 spermatocytes initiate, but cannot maintain ongoing, MSCI. These findings reveal a non-canonical role for the ATR-TOPBP1 signaling axis in MSCI dynamics at advanced stages in pachynema and establish the first mouse mutant that separates ATR signaling and MSCI from SB formation.

Directional atherectomy for retained valves in a femoropopliteal saphenous vein bypass graft.

We describe the case of a 62-year-old man presenting 2 months after a reversed great saphenous vein femoropopliteal bypass performed for critical limb ischemia. He was found to have early, high-grade bypass graft stenosis on duplex ultrasound. Subsequent angiography demonstrated flow limitations secondary to two areas of retained venous valves in the proximal and mid-portions of the vein graft. The culprit valve lesions were successfully lysed endovascularly with a HawkOne (Medtronic) directional atherectomy device. This case demonstrates a safe, novel use of a directional atherectomy device for treatment of remnant valves causing hemodynamically significant flow problems in peripheral vein grafts.

Acylspermidines are conserved mitochondrial sirtuin-dependent metabolites.

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent protein lysine deacylases regulating metabolism and stress responses; however, characterization of the removed acyl groups and their downstream metabolic fates remains incomplete. Here we employed untargeted comparative metabolomics to reinvestigate mitochondrial sirtuin biochemistry. First, we identified N-glutarylspermidines as metabolites downstream of the mitochondrial sirtuin SIR-2.3 in Caenorhabditis elegans and demonstrated that SIR-2.3 functions as a lysine deglutarylase and that N-glutarylspermidines can be derived from O-glutaryl-ADP-ribose. Subsequent targeted analysis of C. elegans, mouse and human metabolomes revealed a chemically diverse range of N-acylspermidines, and formation of N-succinylspermidines and/or N-glutarylspermidines was observed downstream of mammalian mitochondrial sirtuin SIRT5 in two cell lines, consistent with annotated functions of SIRT5. Finally, N-glutarylspermidines were found to adversely affect C. elegans lifespan and mammalian cell proliferation. Our results indicate that N-acylspermidines are conserved metabolites downstream of mitochondrial sirtuins that facilitate annotation of sirtuin enzymatic activities in vivo and may contribute to sirtuin-dependent phenotypes.

Detecting Fast Progressors: Comparing a Bayesian Longitudinal Model to Linear Regression for Detecting Structural Changes in Glaucoma.

PURPOSE: Demonstrate that a novel Bayesian hierarchical spatial longitudinal (HSL) model identifies macular superpixels with rapidly deteriorating ganglion cell complex (GCC) thickness more efficiently than simple linear regression (SLR). DESIGN: Prospective cohort study. SETTING: Tertiary Glaucoma Center. SUBJECTS: One hundred eleven eyes (111 patients) with moderate to severe glaucoma at baseline and ≥4 macular optical coherence tomography scans and ≥2 years of follow-up. OBSERVATION PROCEDURE: Superpixel-patient-specific GCC slopes and their posterior variances in 49 superpixels were derived from our latest Bayesian HSL model and Bayesian SLR. A simulation cohort was created with known intercepts, slopes, and residual variances in individual superpixels. MAIN OUTCOME MEASURES: We compared HSL and SLR in the fastest progressing deciles on (1) proportion of superpixels identified as significantly progressing in the simulation study and compared to SLR slopes in cohort data; (2) root mean square error (RMSE), and SLR/HSL RMSE ratios. RESULTS: Cohort- In the fastest decile of slopes per SLR, 77% and 80% of superpixels progressed significantly according to SLR and HSL, respectively. The SLR/HSL posterior SD ratio had a median of 1.83, with 90% of ratios favoring HSL. Simulation- HSL identified 89% significant negative slopes in the fastest progressing decile vs 64% for SLR. SLR/HSL RMSE ratio was 1.36 for the fastest decile of slopes, with 83% of RMSE ratios favoring HSL. CONCLUSION: The Bayesian HSL model improves the estimation efficiency of local GCC rates of change regardless of underlying true rates of change, particularly in fast progressors.

Validating the Reliability and Clinical Relevance of a Nasolabial Fold Photonumeric Scale.

BACKGROUND: The use of tissue fillers to treat age-related deepening of the nasolabial fold (NLF) has increased and become the standard clinical approach, creating a need for evidence-based, objective evaluation for pre- and post-procedure assessment of the NLF. METHODS: A 5-point rating scale was developed to assess the NLF, specifically the presence of depression and shadowing. Live validation of the scale was performed with a total of 73 participants representing the full range of NLF severities. Physicians board-certified in a core aesthetic specialty (3 trained raters) performed the scale validation over 2 rounds, 2 weeks apart. Training was carried out, and test-retest reliability was quantitated through the determination of intra- and inter-rater reliability by percentage of agreement, weighted kappa statistic with 95% confidence interval (CI), and intraclass correlation coefficient with 95% CI. To evaluate the clinical relevance of a 1-grade difference, rater assessments of 90 photo pairs were compared with previous designations of clinically different or not clinically different. RESULTS: The NLF scale achieved near-perfect intra- and inter-rater reliability when utilized by trained raters to assess a diverse group of live participants. Furthermore, clinically relevant differences between grades were established, and a 1-point difference was detectable by trained evaluators using the NLF scale. CONCLUSION: The clinically relevant and highly reliable validated NLF scale provides a standardized grading system with a user-friendly design for objectively assessing NLF in clinical practice and as a research tool for clinical approval studies of new aesthetic products and technologies. J Drugs Dermatol. 2024;23(1):1284-1291.   doi:10.36849/JDD.7316.

Interleukin 17A Contributes to Blood-Brain Barrier Disruption of Hypothalamic Paraventricular Nucleus in Rats With Myocardial Infarction.

BACKGROUND: Elevated inflammatory cytokines in the periphery have been identified as active contributors to neuroinflammation and sympathetic overactivity in heart failure (HF). Yet, the exact mechanisms by which these cytokines breach the blood-brain barrier (BBB) to exert their effects on the brain remain elusive. Interleukin 17A has been linked to BBB disruption in various neurologic disorders, and its levels were significantly augmented in circulation and the brain in HF. The present study aimed to determine whether the BBB integrity was compromised within the hypothalamic paraventricular nucleus (PVN), and if so, whether interleukin 17A contributes to BBB disruption in myocardial infarction-induced HF. METHODS AND RESULTS: Male Sprague-Dawley rats underwent coronary artery ligation to induce HF or sham surgery. Some HF rats received bilateral PVN microinjections of an interleukin 17 receptor A small interfering RNA or a scrambled small interfering RNA adeno-associated virus. Four weeks after coronary artery ligation, the permeability of the BBB was evaluated by intracarotid injection of fluorescent dyes (fluorescein isothiocyanate-dextran 10 kDa+rhodamine-dextran 70 kDa). Compared with sham-operated rats, HF rats exhibited an elevated extravasation of fluorescein isothiocyanate-dextran 10 kDa within the PVN but not in the brain cortex. The plasma interleukin 17A levels were positively correlated with fluorescein isothiocyanate 10 kDa extravasation in the PVN. The expression of caveolin-1, a transcytosis marker, was augmented, whereas the expression of tight junction proteins was diminished in HF rats. Interleukin 17 receptor A was identified within the endothelium of PVN microvessels. Treatment with interleukin 17 receptor A small interfering RNA led to a significant attenuation of fluorescein isothiocyanate 10 kDa extravasation in the PVN and reversed expression of caveolin-1 and tight junction-associated proteins in the PVN. CONCLUSIONS: Collectively, these data indicate that BBB permeability within the PVN is enhanced in HF and is likely attributable to increased interleukin 17A/interleukin 17 receptor A signaling in the BBB endothelium, by promoting caveolar transcytosis and degradation of tight junction complexes.

A Bayesian Hierarchical Spatial Longitudinal Model Improves Estimation of Local Macular Rates of Change in Glaucomatous Eyes.

Purpose: Demonstrate that a novel Bayesian hierarchical spatial longitudinal (HSL) model improves estimation of local macular ganglion cell complex (GCC) rates of change compared to simple linear regression (SLR) and a conditional autoregressive (CAR) model. Methods: We analyzed GCC thickness measurements within 49 macular superpixels in 111 eyes (111 patients) with four or more macular optical coherence tomography scans and two or more years of follow-up. We compared superpixel-patient-specific estimates and their posterior variances derived from the latest version of a recently developed Bayesian HSL model, CAR, and SLR. We performed a simulation study to compare the accuracy of intercept and slope estimates in individual superpixels. Results: HSL identified a significantly higher proportion of significant negative slopes in 13/49 superpixels and a significantly lower proportion of significant positive slopes in 21/49 superpixels than SLR. In the simulation study, the median (tenth, ninetieth percentile) ratio of mean squared error of SLR [CAR] over HSL for intercepts and slopes were 1.91 (1.23, 2.75) [1.51 (1.05, 2.20)] and 3.25 (1.40, 10.14) [2.36 (1.17, 5.56)], respectively. Conclusions: A novel Bayesian HSL model improves estimation accuracy of patient-specific local GCC rates of change. The proposed model is more than twice as efficient as SLR for estimating superpixel-patient slopes and identifies a higher proportion of deteriorating superpixels than SLR while minimizing false-positive detection rates. Translational Relevance: The proposed HSL model can be used to model macular structural measurements to detect individual glaucoma progression earlier and more efficiently in clinical and research settings.