Burlington College

Wear debris is a known contributor to orthopaedic implant failure, particularly in joint arthroplasty. The wear characteristics of spinal total disc replacement (TDR) remain under-investigated. Spinal TDRs have been shown to produce wear particles that elicit strong inflammatory reactions. Submicron debris, in particular, is associated with osteolysis and implant loosening. Viscoelastic TDR (VTDR) devices have emerged to address these risks. Five AxioMed Freedom Lumbar Disc (FLD) devices underwent 30 million cycles (10 million each in flexion-extension, lateral bending, and axial rotation) of wear testing in phosphate-buffered saline solution at 37°C using an MTS servohydraulic system. Wear fluid samples were collected every 5 million cycles and analyzed using scanning electron microscopy and laser diffraction. A 30-million device cycle count simulates 240 years of lumbar bending. Wear rates were calculated in milligrams per million cycles (mg/MC). Comparative data for CHARITÉ (DePuy Synthes) and prodisc L (Centinel Spine) discs were obtained from the United States Food and Drug Administration (FDA) Summary of Safety and Effectiveness Data. The AxioMed device showed a mean wear rate of 1.7 mg/MC, in comparison to 5.7 mg/MC for the prodisc L. The number-average particle diameter was 1.9 μm, with a mass-average particle diameter of 49 μm, which was notably larger than those reportedly produced by the CHARITÉ (0.2 μm) and prodisc L (0.4 μm) devices, which is promising because larger particles (>1.0 μm) are less likely to induce inflammatory responses. No mechanical failures were observed during the 30 million cycles. The AxioMed 1-piece VTDR device demonstrated a lower wear rate and larger, less biologically reactive, particles compared with articulating TDRs, suggesting a reduced risk of osteolysis and longer implant lifespan. No mechanical failures were observed, even after each 10-million-cycle interval, which simulates approximately 80 years of lumbar-bending motions. This study focused on particle size; further work is warranted to characterize composition and particle burden. This 1-piece VTDR may offer a safer and more durable alternative for motion-preserving lumbar spine surgery. Further clinical and retrieval studies are warranted.

ABSTRACTBackgroundAlthough prenatal imaging advancements have increased isolated right aortic arch (iRAA) detection, optimal postnatal vascular ring management remains uncertain. Whereas early postnatal imaging and surgical management may be clinically warranted for some infants, long‐term data are not yet available to justify an identical approach for all prenatal iRAA diagnoses.MethodsChildren with prenatally diagnosed iRAA and left ductus arteriosus were included in a retrospective cohort study at a rural academic center. Fetal echocardiograms (2014–2024) were reviewed to exclude complex congenital heart disease. Joint postnatal cardiopulmonary care was standardized. Clinical data were ascertained using aerodigestive symptom checklists. Fisher's exact test was used to examine associations between symptoms and surgical referral. Growth was assessed by z‐score rates of change from birth weight until last clinic weight.Results3,458 fetal echocardiograms were performed yielding 31 distinct cases meeting inclusion criteria, with postnatal data available for 25. Twenty were managed medically (25% asymptomatic, 75% intermittently symptomatic) with median follow up of 14 (11.5, 17.5) months; five underwent surgery (80% progressively symptomatic) with median follow up of 36 (18, 37) months). Choking/dysphagia (p = 0.04), recurrent emesis (p = 0.03), and the combination of both digestive symptoms and noisy breathing (p = 0.01) were associated with surgical referral. Weight outcomes were similar (p = 0.98) between medical and surgical patients.ConclusionsAlthough aerodigestive symptoms were common, most were not progressive and weight profiles were not adversely affected. Isolated digestive symptoms or in combination with respiratory symptoms may prompt greater concern. A collaborative cardiopulmonary approach to clinical evaluation may help with short‐term risk stratification.

Abstract Many regional aquifer systems undergoing depletion contain “fossil” groundwater recharged under different climate conditions, raising questions on groundwater renewability. We examine the spatial distribution in groundwater ages estimated with multiple tracers covering different timescales, along with differences in paleoclimate and water table depths (WTD) in the Tucson Basin, Arizona, USA, to constrain recharge history. The presence of 3 H and 85 Kr in upgradient wells indicates modern recharge, while 39 Ar, 14 C, and 4 He values show components of water several hundred to tens of thousands of years old in downgradient wells. In some wells, apparent ages on the orders of decades, centuries, and millennia are simultaneously indicated by 85 Kr, 39 Ar, and 14 C activities, indicating that the flow system cannot be explained by a simple piston‐flow model. To disentangle mixing and recharge history signals, we apply an inverse modeling technique that couples lumped parameter modeling of residence times with (stable) noble gas reconstructions of recharge temperature and WTD. A mid‐Holocene maximum in WTD, reconstructed from Kr and Xe isotopes, suggests enhanced aridity associated with a reduction of wintertime precipitation, inferred from a shift in δ 18 O and δD. Colder temperatures were present during the Last Glacial Maximum, reflecting both climatic cooling and cold mountain front recharge. Recharge to the Tucson Basin has been continuous since the LGM, albeit with a likely reduction during the mid‐Holocene. Natural fluctuations in groundwater recharge have been small compared to those associated with groundwater extraction, indicating that pumping poses a larger threat to groundwater resources than climate change.

Introduction and Objective: Glucagon-like peptide 1 (GLP-1) is an incretin that signals satiety and regulates islet hormone secretion. GLP-1 drugs manage diabetes and promote weight loss, but most patients discontinue, leading to weight regain and metabolic decline. We developed a novel pancreatic gene therapy (PGTx) for sustained meal-regulated GLP-1 production from beta cells. Here, we assessed the potential for PGTx to prevent metabolic disease progression in lean and diet-induced obesity (DIO) mice. Methods: We created an AAV vector encoding Exendin-4 with an insulin promoter for beta-cell-specific expression. Four groups were studied for 5 weeks (n=8 per group): 1) started on 60% high-fat diet (HFD), treated with single-dose IP PGTx (8.3e11 VGs), and maintained on HFD (DIO PGTx) 2) started on chow diet (CD), given PGTx, and switched to HFD at week (wk) 3 (Lean PGTx+HFD) 3) started and maintained on CD (Lean) 4) started on CD and switched to HFD at wk 3 (Lean+HFD). Body weight (BW) and blood glucose (BG) were evaluated as disease markers. Data are reported as mean percent change from baseline (BL) or wk 3. Results: PGTx was well-tolerated. In the DIO PGTx cohort, PGTx reduced BW by 20% at wk 3 and maintained weight loss through wk 5 on HFD (-17%). BW at wk 5 increased by 25% in the Lean+HFD cohort when switched to HFD. However, in the Lean PGTx+HFD group, BW was reduced by 6% at wk 3, and did not rise above BL after the HFD switch. In parallel, PGTx reduced BG by 38% at wk 3 and maintained BG reduction through wk 5 on HFD (-32%). In the Lean+HFD group, BG at wk 5 increased by 20% when switched to HFD. In the Lean PGTx+HFD group, PGTx induced a BG reduction of 15% at wk 3 and prevented HFD-induced hyperglycemia as evidenced by a BG level 9% below BL at wk 5. Conclusion: These data suggest that PGTx can durably reduce weight and glycemia in DIO and prevent weight gain and hyperglycemia when treatment is initiated before HFD. Lean mice receiving PGTx exhibited less weight loss than their DIO counterparts, suggesting a self-limiting mechanism that could enhance the PGTx safety profile. Disclosure T.J. Kieffer: Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. C. Hutch: None. S. Kernodle: None. A.L. Fitzpatrick: Employee; Fractyl Health, Inc. E. Cozzi: Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. S. Slomovic: Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. J. Caplan: Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. H. Rajagopalan: Board Member; Fractyl Health, Inc. Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. R.J. Seeley: Advisory Panel; Amgen Inc. Research Support; Amgen Inc, Eli Lilly and Company, AstraZeneca. Consultant; AstraZeneca. Research Support; Glyscend Therapeutics. Advisory Panel; Structure Therapeutics, Inc, CinRx, Eccogene. Consultant; Juvena.

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The project investigates the incorporation of ground motions into traffic-light protocols (TLPs) for induced seismicity oversight with a focus on applications in the Kiskatinaw area. The objectives of the study are twofold:1. The development of regional ground motion models for induced events, which can be used for the assessment of associated hazard in future, and2. the review of the existing magnitude thresholds of traffic-light protocols (TLPs) on the basis of ground motions for effective induced seismicity risk management.The project is conducted in three phases: ground motion prediction, definition of perception and potential damage thresholds, and review of traffic light protocol (TLP) magnitude thresholds on the basis of ground motions.

Material extrusion additive manufacturing enables the production of complex objects fabricated from sinterable materials embedded in an extrudable feedstock. Here, we describe the fundamental aspects of the fabrication process with specific attention to the hierarchy of printed objects, including the various length scales of objects fabricated. Using the hierarchy as a guide, we detail various physical and chemical attributes which contribute to overall print and object performance. We illustrate the interplay between the length scales using specific examples of extrusion performance and the effect of toolpathing on printing accuracy and part strength.

In response to the global rise in chronic diseases among aging populations, healthcare systems are transitioning from acute care models to community‐based interventions tailored to the diverse needs of older adults. This study aimed to explore the role of champions in implementing community‐based interventions for older adults with chronic conditions to address the gap in understanding the specific functions and impact of champions in these contexts. A scoping review methodology used a six‐stage process aligned with the Arksey and O’Malley framework. After searching across 8 databases, a total of 10 studies met all inclusion criteria. The included studies were predominantly from the United States (n = 6/10, 60%) and the United Kingdom (n = 2/10, 20%). Most studies employed quantitative methodologies (n = 6/10, 60%), describing and evaluating healthcare champion programs or investigating the quality of care for older adults. Community interventions targeted various chronic conditions (e.g., dementia) and health outcomes (e.g., medication reconciliation). Champions, ranging from 17 to 106 individuals, played diverse roles as professional healthcare providers or lay volunteers. They facilitated intervention delivery, advocated for change, participated in evaluation, and fostered collaboration within multidisciplinary teams, contributing significantly to program implementation and health information dissemination. Recognizing champions’ diverse roles, researchers and practitioners can tailor interventions to leverage their strengths and maximize their impact. Additionally, the review highlights the importance of clear definitions and operationalization of champions to ensure consistency across studies and interventions. Practitioners can use this knowledge to identify, train effectively, and support champions within their communities, ultimately enhancing the sustainability and success of interventions for older adults with chronic conditions.

Reports of pembrolizumab-induced lichen planus and eruptive keratoacanthomas are limited in the literature. Here, we describe the unique concurrence of both lichen planus and eruptive keratoacanthomas in a patient who received pembrolizumab for non-small cell lung cancer (NSCLC). Although several therapies have been proposed, we show that pembrolizumab-induced lichen planus and keratoacanthomas can be controlled with the conservative management of topical corticosteroids and intralesional corticosteroids, respectively, allowing patients to continue pembrolizumab therapy.

Hierarchical Test (HT) is a partitioned-test method designed to improve performance and decrease resources costs in both DFT and test. Specifically, this methodology eases computing resources and run times required for automatic test pattern generation. It also presents unique challenges and opportunities for diagnosis. Physically aware volume diagnostics greatly improves callout resolution, enabling diagnosis of new fault types, but presents scalability and deployability issues for hierarchical core-based designs. This paper highlights solutions needed to create an efficient high-volume physical diagnosis pipeline for hierarchical core-based designs. Results of the proposed system are demonstrated on 7nm processor designs.