Search

Modern cities pay particular attention to upscale their infrastructure systems in order to improve the every-day life of their citizens and lead the way towards a more sustainable environment. As part of this, they invest extensive funds in large infrastructure projects which are challenging to deliver as they require an e efficient communication among different professions, in order to share information efficiently throughout the lifecycle of the project, thus highlighting the importance of standardization to maintain consistency and integrity during data exchange. Building Information Modelling (BIM) aims to facilitate the above-mentioned requirements by describing the life-cycle of the project and Industry Foundation Classes (IFC) is the Standard for BIM that enables an efficient storage, management, exchange and visualization of information. However, there are two important challenges that need to be addressed: (i) IFC focuses particularly on buildings and provides limited support for infrastructure elements and (ii) the information exchange aims to describe mostly the construction phase; highlighting the lack of classes that refer to the operation and maintenance phase. Within this context, this paper proposes the extension of Industry Foundation Classes (IFC) for Asset Management in Infrastructure. A method is developed based on a case study of three highway entities: (i) retaining wall, (ii) gantry and (iii) bridge and a conceptual extension is presented. The results are further discussed and recommendations regarding future research fields are proposed.

Background: This study aims to characterize the types of procedures performed on patients previously diagnosed with Ehlers-Danlos syndrome (EDS)/hypermobility spectrum disorder (HSD) and investigate rates of revision surgery following open, arthroscopic, or bony stabilization procedures in patients with and without a preoperative diagnosis of EDS/HSD. Methods: This is a retrospective comparative study utilizing a large nationwide claims database. Records were queried between January 2011 and December 2021 for patients undergoing surgical management for glenohumeral instability using Current Procedural Terminology codes. Patients with preoperative diagnoses of EDS/HSD were identified using International Classifications of Disease, ninth revision and tenth revision billing codes. Multivariable logistic regression was used to analyze the distribution of surgical techniques performed for patients with HSD and compare rates of revision operation following open, arthroscopic, and/or bony procedures. Unadjusted and adjusted odds ratios (aOR) and 95% confidence intervals are reported for each comparison. A P value of .05 was used to signify statistical significance. Results: Patients with preoperative diagnoses of EDS/HSD were significantly more likely to undergo open posterior (aOR = 3.47, 95% CI [2.13, 5.31]), open capsulorrhaphy (aOR = 5.04, 95% CI [3.97, 6.32]), and Latarjet (aOR = 1.84, 95% CI [1.33, 2.48]) procedures than patients without EDS/HSD. In contrast, these patients were significantly less likely to undergo arthroscopic Bankart repair (aOR = 0.48, 95% CI [0.40, 0.58]). Preoperative EDS/HSD was also associated with increased rates of secondary shoulder surgery (aOR = 2.63, 95% CI [2.01, 3.39]), but not necessarily ipsilateral revision shoulder surgery (aOR = 1.64, 95% CI [0.89, 2.77], P = .87). Conclusions: The present study demonstrates that EDS/HSD results in greater likelihood of shoulder instability being surgically managed through open procedures as opposed to arthroscopic procedures, as well as greater likelihood of requiring subsequent surgical procedures. These findings provide critical insights to patients with EDS/HSD and their clinical providers for developing treatment plans for shoulder instability. Providers should educate patients with known hyperlaxity to make them aware of their increased odds of future reoperation. Surgeons should also prioritize assessment of ligamentous laxity in all patients and adjust individual treatment protocols accordingly.

Abstract Background Policymaking is quickly gaining focus in the field of implementation science as a potential opportunity for aligning cross-sector systems and introducing incentives to promote population health, including substance use disorders (SUD) and their prevention in adolescents. Policymakers are seen as holding the necessary levers for realigning service infrastructure to more rapidly and effectively address adolescent behavioral health across the continuum of need (prevention through crisis care, mental health, and SUD) and in multiple locations (schools, primary care, community settings). The difficulty of aligning policy intent, policy design, and successful policy implementation is a well-known challenge in the broader public policy and public administration literature that also affects local behavioral health policymaking. This study will examine a blended approach of coproduction and codesign (i.e., Policy Codesign), iteratively developed over multiple years to address problems in policy formation that often lead to poor implementation outcomes. The current study evaluates this scalable approach using reproducible measures to grow the knowledge base in this field of study. Methods This is a single-arm, longitudinal, staggered implementation study to examine the acceptability and short-term impacts of Policy Codesign in resolving critical challenges in behavioral health policy formation. The aims are to (1) examine the acceptability, feasibility, and reach of Policy Codesign within two geographically distinct counties in Washington state, USA; (2) examine the impact of Policy Codesign on multisector policy development within these counties using social network analysis; and (3) assess the perceived replicability of Policy Codesign among leaders and other staff of policy-oriented state behavioral health intermediary organizations across the USA. Discussion This study will assess the feasibility of a specific approach to collaborative policy development, Policy Codesign, in two diverse regions. Results will inform a subsequent multi-state study measuring the impact and effectiveness of this approach for achieving multi-sector and evidence informed policy development in adolescent SUD prevention and treatment.

Wind-borne dust supply of iron (Fe) to the oceans plays a crucial role in Earth’s biogeochemical cycles. Iron, a limiting micronutrient for phytoplankton growth, is fundamental in regulating ocean primary productivity and in turn the global carbon cycle. The flux of bioavailable Fe to the open ocean affects oscillations in atmospheric CO2 due to its control on inorganic carbon fixation into organic matter that is eventually exported to the sediments. However, the nature of dust-delivered Fe to the ocean and controls on its bioavailability remain poorly constrained. To evaluate the supply of wind-borne bioavailable Fe and its potential impact on Fe-based climate feedbacks over the last 120,000 years, we examine sediment profiles from four localities that define a proximal to distal transect relative to Saharan dust inputs. Bulk δ56Fe isotope compositions (average = -0.05‰) and FeT/Al ratios suggest crustal values, thus pointing to a dominant dust origin for the sediments at all four sites. We observed no variability in grain size distribution or in bioavailable Fe supply at individual sites as a function of glacial-versus-interglacial deposition. Importantly, there is no correlation between sediment grain size and Fe bioavailability. Spatial trends do, however, suggest increasing Fe bioavailability with increasing distance of atmospheric transport, and our sediments also indicate the loss of this Fe and thus potential bioavailability utilization once deposited in the ocean. Our study underscores the significance of Fe dynamics in oceanic environments using refined speciation techniques to elucidate patterns in Fe reactivity. Such insights are crucial for understanding nutrient availability and productivity in various ocean regions, including the Southern Ocean, where wind-delivered Fe may play a pivotal role. It is expected that dust delivery on glacial-interglacial timescales would be more pronounced in these high-latitude regions. Our findings suggest that studies linking Fe availability to marine productivity should benefit significantly from refined Fe speciation approaches, which provide insights into the patterns and controls on Fe reactivity, including atmospheric processing. These insights are essential for understanding the impacts on primary production and thus carbon cycling in the oceans and consequences for the atmosphere.

Background: This study aims to determine the effect of time and imaging modality (three-dimensional (3D) CT vs. 3D magnetic resonance imaging (MRI)) on the surgical procedure indicated for shoulder instability. The hypothesis is there will be no clinical difference in procedure selection between time and imaging modality. Methods: Eleven shoulder surgeons were surveyed with the same ten shoulder instability clinical scenarios at three time points. All time points included history of present illness, musculoskeletal exam, radiographs, and standard two-dimensional MRI. To assess the effect of imaging modality, survey 1 included 3D MRI while survey 2 included a two-dimensional and 3D CT scan. To assess the effect of time, a retest was performed with survey 3 which was identical to survey 2. The outcome measured was whether surgeons made a “major” or “minor” surgical change between surveys. Results: The average major change rate was 14.1% (standard deviation: 7.6%). The average minor change rate was 12.6% (standard deviation: 7.5%). Between survey 1 to the survey 2, the major change rate was 15.2%, compared to 13.1% when going from the second to the third survey (P = .68). The minior change rate between the first and second surveys was 12.1% and between the second to third interview was 13.1% (P = .8). Discussion: The findings suggest that the major factor related to procedural changes was time between reviewing patient information. Furthermore, this study demonstrates that there remains significant intrasurgeon variability in selecting surgical procedures for shoulder instability. Lastly, the findings in this study suggest that 3D MRI is clinically equivalent to 3D CT in guiding shoulder instability surgical management. Conclusion: This study demonstrates that there is significant variability in surgical procedure selection driven by time alone in shoulder instability. Surgical decision making with 3D MRI was similar to 3D CT scans and may be used by surgeons for preoperative planning.

Abstract Impaired cerebrovascular function contributes to the genesis of age‐related cognitive decline. In this study, the hypothesis is tested that impairments in neurovascular coupling (NVC) responses and brain network function predict cognitive dysfunction in older adults. Cerebromicrovascular and working memory function of healthy young (n = 21, 33.2±7.0 years) and aged (n = 30, 75.9±6.9 years) participants are assessed. To determine NVC responses and functional connectivity (FC) during a working memory (n‐back) paradigm, oxy‐ and deoxyhemoglobin concentration changes from the frontal cortex using functional near‐infrared spectroscopy are recorded. NVC responses are significantly impaired during the 2‐back task in aged participants, while the frontal networks are characterized by higher local and global connection strength, and dynamic FC (p < 0.05). Both impaired NVC and increased FC correlate with age‐related decline in accuracy during the 2‐back task. These findings suggest that task‐related brain states in older adults require stronger functional connections to compensate for the attenuated NVC responses associated with working memory load.

Chondrocyte-based cell therapy has been used for more than 30 years and is still considered to be a promising method of cartilage repair despite some limitations. This review introduces the latest developments of four generations of autologous chondrocyte implantation and current autologous chondrocyte products. The regeneration of cartilage from adult chondrocytes is limited by culture-induced dedifferentiation and patient age. Cartibeads is an innovative three-step method to produce high-quality hyaline cartilage microtissues, and it is developed from adult dedifferentiated chondrocytes with a high number of cell passages. In addition, allogeneic chondrocyte therapies using the Quantum hollow-fiber bioreactor and several signaling pathways involved in chondrocyte-based cartilage repair are mentioned, such as WNT signaling, the BMP-2/WISP1 pathway, and the FGF19 pathway.

Background: We investigate epidemiological models, their parameters, and the models’ predictive performance of daily new cases during the first three weeks of the SARS-CoV-2 outbreak in a southwest Georgia hotspot. Methods: We fit stochastic versions of the classical SIR, a network-based SIR, an SEIR model with two different priors on the latent period rate parameter, and a simple doubling time model to SARS-CoV-2 patients’ date of hospital admission and length of symptoms data from the Phoebe Putney Health System. Results: The estimated basic reproductive numbers and 95% Bayesian credible intervals for each of the models were: 1.98 (1.63, 2.45) for the SIR model, 1.99 (1.62, 2.48) for the network-based SIR model, 2.04 (1.64, 2.68) for the SEIR model with noninformative prior, and 3.37 (2.42, 4.68) for the SEIR model with informative prior. The SIR and network-based SIR models performed similarly in terms of predicting new cases each day, with median absolute error (MAE) of 3 cases. They had better predictive performance compared to the SEIR (MAE=13) with noninformative prior and doubling time models (MAE=42). The SEIR with informative prior on the incubation rate had an MAE of 4. Conclusions: These results indicate a herd immunity of between 50% and 70% were necessary to prevent further spread. The simple doubling time model consistently overpredicts daily new cases. Using duration of symptoms data from the severe cases with SIR-type models led to improved real-time predictions of cumulative daily cases compared to the doubling time and SEIR model with noninformative prior. The latent period parameter for the SEIR model was not identifiable from the data, but good predictions were achieved with an informative prior on this parameter using results from the literature.

Abstract Background Opioid use disorder (OUD) is a serious health condition that is effectively treated with buprenorphine. However, only a minority of people with OUD are able to access buprenorphine. Many access points for buprenorphine have high barriers for initiation and retention. Health care and drug treatment systems have not been able to provide services to all—let alone the majority—who need it, and many with OUD report extreme challenges starting and staying on buprenorphine in those care settings. We describe the design and protocol for a study of a rapid access buprenorphine program model in six Washington State communities at existing sites serving people who are unhoused and/or using syringe services programs. This study aimed to test the effectiveness of a Community-Based Medication-First Program model. Methods We are conducting a hybrid effectiveness-implementation study of a rapid access buprenorphine model of care staffed by prescribers, nurse care managers, and care navigators. The Community-Based Medication-First model of care was designed as a 6-month, induction-stabilization-transition model to be delivered between 2019 and 2022. Effectiveness outcomes will be tested by comparing the intervention group with a comparison group derived from state records of people who had OUD. Construction of the comparison group will align characteristics such as geography, demographics, historical rates of arrests, OUD medication, and health care utilization, using restriction and propensity score techniques. Outcomes will include arrests, emergency and inpatient health care utilization, and mortality rates. Descriptive statistics for buprenorphine utilization patterns during the intervention period will be documented with the prescription drug monitoring program. Discussion Results of this study will help determine the effectiveness of the intervention. Given the serious population-level and individual-level impacts of OUD, it is essential that services be readily available to all people with OUD, including those who cannot readily access care due to their circumstances, capacity, preferences, and related systems barriers.

Abstract Bruton’s tyrosine kinase (BTK), expressed in B cells and cells of innate immunity, including microglia, is an essential signaling element downstream of the B‐cell receptor and Fc‐receptors. Tolebrutinib (PRN2246, SAR442168) is a potent BTK inhibitor that covalently binds the kinase, resulting in durable inhibition with the potential to target inflammation in the periphery and central nervous system (CNS). Tolebrutinib crosses the blood‐brain barrier and potently inhibits BTK in microglial cells isolated from the CNS. A first‐in‐human randomized, double‐blind, placebo‐controlled study of tolebrutinib was conducted. The trial design consisted of five single ascending dose arms with oral administration of a single dose of 5, 15, 30, 60, and 120 mg (n = 6 per arm, n = 2 placebo), five multiple ascending dose arms with oral administration of 7.5, 15, 30, 60, and 90 mg (n = 8 per arm, n = 2 placebo) over 10 days, and one arm (n = 4) in which cerebral spinal fluid (CSF) exposure was measured 2 h after a single 120 mg dose. Tolebrutinib was well‐tolerated in the study and all treatment‐related treatment emergent adverse events were mild. Tolebrutinib was rapidly absorbed following oral administration with a rapid half‐life of ~ 2 h. Peripheral BTK occupancy was assessed at various timepoints by an enzyme‐linked immunosorbent assay‐based readout using an irreversible probe. Assessments demonstrated extensive and prolonged peripheral BTK occupancy at steady‐state with once daily doses as low as 7.5 mg. Further, CSF exposure was demonstrated 2 h after administration at 120 mg.

IntroductionMild cognitive impairment (MCI) is a prodromal stage to dementia, affecting up to 20% of the aging population worldwide. Patients with MCI have an annual conversion rate to dementia of 15-20%. Thus, conditions that increase the conversion from MCI to dementia are of the utmost public health concern. The COVID-19 pandemic poses a significant impact on our aging population with cognitive decline as one of the leading complications following recovery from acute infection. Recent findings suggest that COVID-19 increases the conversion rate from MCI to dementia in older adults. Hence, we aim to uncover a mechanism for COVID-19 induced cognitive impairment and progression to dementia to pave the way for future therapeutic targets that may mitigate COVID-19 induced cognitive decline.MethodologyA prospective longitudinal study is conducted at the University of Oklahoma Health Sciences Center. Patients are screened in the Department of Neurology and must have a formal diagnosis of MCI, and MRI imaging prior to study enrollment. Patients who meet the inclusion criteria are enrolled and followed-up at 18-months after their first visit. Visit one and 18-month follow-up will include an integrated and cohesive battery of vascular and cognitive measurements, including peripheral endothelial function (flow-mediated dilation, laser speckle contrast imaging), retinal and cerebrovascular hemodynamics (dynamic vessel retinal analysis, functional near-infrared spectroscopy), and fluid and crystalized intelligence (NIH-Toolbox, n-back). Multiple logistic regression will be used for primary longitudinal data analysis to determine whether COVID-19 related impairment in neurovascular coupling and increases in white matter hyperintensity burden contribute to progression to dementia.

Abstract Many metals present in trace concentrations in the oceans are sensitive to reduction and oxidation reactions (termed redox‐sensitive trace metals or RSTMs) and can therefore be affected during intervals of expanded oceanic anoxia and euxinia (anoxic and sulfidic waters). These RSTMs are important micronutrients; and their availability plays a significant role in controlling metabolic pathways and therefore ecosystem structure. Understanding the links to ecosystem restructuring and potential collapse is important since past deoxygenation events are associated with biological turnover. The Early Jurassic Toarcian Oceanic Anoxic Event (T‐OAE) was one such event. We focus on the RSTM molybdenum (Mo), important in the nitrogen cycle, from a basin transect where local redox conditions permit the tracking of the marine reservoir of Mo. Mo enrichments start to decline in the Pliensbachian, continue to decline in the early Toarcian, drop precipitously during the T‐OAE interval, and remain low afterward before a protracted increase toward the initial values seen in the Pliensbachian. From a compilation of available data, we estimate that ∼41 Gt of Mo was buried during the T‐OAE using a range of possible flux estimates. Given the known correlations of Mo with total organic carbon, the estimated burial of organic carbon during the T‐OAE interval was ∼244,000 Gt. This requires a minimum of 3.25% of the ocean floor to be covered by euxinic waters. Finally, we suggest that the intervals traditionally classified as OAEs are associated with the greatest extent of euxinia.

IntroductionAdvanced methods of gait research, including approaches to quantify variability, and orderliness/regularity/predictability, are increasingly used to identify patients at risk for the development of cognitive impairment. Cerebral small vessel disease (CSVD) is highly prevalent in older adults and is known to contribute to the development of vascular cognitive impairment and dementia (VCID). Studies in preclinical models demonstrate that subclinical alterations precede CSVD-related cognitive impairment in gait coordination. In humans, CSVD also associates with gait abnormalities. The present study was designed to test the hypothesis that increased gait variability and gait asymmetry predict a decline in cognitive performance in older adults with CSVD.MethodsTo test this hypothesis, we compared cognitive performance and gait function in patients with CSVD (age: 69.8 ± 5.3 years; n = 11) and age- and sex-matched control participants (age: 70.7 ± 5.8 years; n = 11). Based on imaging findings, patients with CSVD were identified [presence of white matter hyperintensities plus silent brain infarcts and/or microhemorrhages on magnetic resonance imaging (MRI) assessment]. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Gait parameters were measured during the single and dual tasks, during which participants, in addition to the motor task, completed a series of mental arithmetic calculations. Spatial and temporal parameters of gait variability, symmetry, and permutation entropy were determined using a pressure-sensitive gait mat during single and dual cognitive task conditions.ResultsPatients with CSVD exhibited lower performance in a visual learning test (p = 0.030) and in a sustained attention test (p = 0.007). CSVD also affected step time variability (p = 0.009) and step length variability (p = 0.017). Step lengths of CSVD participants were more asymmetric (p = 0.043) than that of controls, while the two groups were statistically similar regarding step time symmetry and entropy of step time and length. Gait variability was inversely associated with sustained attention, especially among CSVD patients, and this relationship was significantly different between the two groups. The association of sustained attention with gait symmetry was also significantly different between the two groups.DiscussionOur findings provide additional evidence in support of the concept that increased gait variability and asymmetry may predict cognitive impairment in older adults with CSVD.

Meniscal tearing in the knee increases the risk of post-traumatic osteoarthritis (OA) in patients. The therapeutic application of tissue-specific mesenchymal progenitor cells is currently being investigated as an emerging biologic strategy to help improve healing of musculoskeletal tissues like meniscal fibrocartilage and articular hyaline cartilage. However, many of these approaches involve isolating cells from healthy tissues, and the low yield of rare progenitor populations (< 1% of total cells residing in tissues) can make finding a readily available cell source for therapeutic use a significant logistical challenge. In the present study, we investigated the therapeutic efficacy of using expanded cartilage-derived and bone marrow-derived progenitor cell lines, which were stabilized using retroviral SV40, for repair of meniscus injury in a rodent model. Our findings indicate that these cell lines express the same cell surface marker phenotype of primary cells (CD54+, CD90+, CD105+, CD166+), and that they exhibit improved proliferative capacity that is suitable for extensive expansion. Skeletally mature male athymic rats treated with 3.2 million cartilage-derived progenitor cell line exhibited approximately 79% greater meniscal tear reintegration/healing, compared to injured animals that left untreated, and 76% greater compared to animals treated with the same number of marrow-derived stromal cells. Histological analysis of articular surfaces also showed that cartilage-derived progenitor cell line treated animals exhibited reduced post-traumatic OA associated articular cartilage degeneration. Stable cell line treatment did not cause tumor formation or off-target engraftment in animals. Taken together, we present a proof-of-concept study demonstrating, for the first time, that intra-articular injection of a stable human cartilage-derived progenitor cell line stimulates meniscus tear healing and provide chondroprotection in an animal model. These outcomes suggest that the use of stable cell lines may help overcome cell source limitations for cell-based medicine.

Abstract Background Detection of urinary casts is difficult due to their intermittent presence and deterioration in urine samples. Objective To compare the performance of the IDEXX SediVue Dx® Urine Sediment Analyzer (SediVue) with manual microscopy for the detection of urinary casts. We hypothesized that the SediVue analyzer would perform similarly to manual microscopy in cast detection. Animals Four hundred forty‐three samples from 420 dogs from a hospital population. Methods This is a prospective, cross‐sectional study. For SediVue analysis (software version [SW] 1.0.1.3), uncentrifuged urine was pipetted into a disposable cartridge. Seventy images were captured and processed by an onboard algorithm. For manual microscopy, urine was centrifuged to obtain sediment. Any cast identified by either method was considered a positive result (>0/low‐power field [LPF]). SediVue images were evaluated if casts were detected by either methodology. A revised sensitivity and specificity were calculated after image review and when using a threshold of >1 cast/LPF. Results The sensitivity of the SediVue analysis for the detection of urinary casts was 53.7% (43.85%‐63.35%), and specificity was 86.0% (81.78%‐89.51%). After image review, the revised sensitivity/specificity was 52.0% (42.89%‐61.02%) and 90.6% (86.81%‐93.54%), respectively. When using a more clinically relevant threshold of >1/LPF, the sensitivity was 52.6% (35.82%‐69.02%) and specificity was 99.3% (97.85%‐99.85%). Conclusions and Clinical Importance The SediVue provides moderate agreement to manual methodology for detection of casts in urine.

Current clinical strategies for restoring cartilage defects do not adequately consider taking the necessary steps to prevent the formation of hypertrophic tissue at injury sites. Chondrocyte hypertrophy inevitably causes both macroscopic and microscopic level changes in cartilage, resulting in adverse long-term outcomes following attempted restoration. Repairing/restoring articular cartilage while minimizing the risk of hypertrophic neo tissue formation represents an unmet clinical challenge. Previous investigations have extensively identified and characterized the biological mechanisms that regulate cartilage hypertrophy with preclinical studies now beginning to leverage this knowledge to help build better cartilage. In this comprehensive article, we will provide a summary of these biological mechanisms and systematically review the most cutting-edge strategies for circumventing this pathological hallmark of osteoarthritis.

Background: Stigma is a barrier to the treatment of opioid use disorder (OUD) in the criminal legal system. Staff sometimes have negative attitudes about medications for OUD (i.e., MOUD), but there is little research on what drives these attitudes. How staff think about criminal involvement and addiction may explain their attitudes toward MOUD. Methods: A convenience sample of U.S. criminal legal staff (e.g., correctional/probation officers, nurses, psychologists, court personnel) were recruited via online methods (N = 152). Participants completed an online survey of their attitudes about justice-involved people and addiction, and these were entered as predictors of an adapted version of the Opinions about Medication Assisted Treatment survey (OAMAT) in a linear regression, controlling for sociodemographics (cross-sectional design). Results: At the bivariate level, measures capturing more stigmatizing attitudes toward justice-involved people, believing addiction represents a moral weakness, and believing people with addiction are responsible for their actions and their recovery were related to more negative attitudes about MOUD, whereas higher educational attainment and believing addiction has a genetic basis were related to more positive attitudes about MOUD. In a linear regression, only stigma toward justice-involved people significantly predicted negative attitudes about MOUD (B = -.27, p = .010). Conclusion: Criminal legal staff's stigmatizing attitudes about justice-involved people, such as believing they are untrustworthy and cannot be rehabilitated, contributed significantly to negative attitudes about MOUD, above their beliefs about addiction. The stigma tied to criminal involvement needs to be addressed in attempts to increase MOUD adoption in the criminal legal system.

Abstract The Ordovician (Hirnantian; 445 Ma) hosts the second most severe mass extinction in Earth history, coinciding with Gondwanan glaciation and increased geochemical evidence for marine anoxia. It remains unclear whether cooling, expanded oxygen deficiency, or a combination drove the Late Ordovician Mass Extinction (LOME). Here, we present combined iodine and sulfur isotope geochemical data from three globally distributed carbonate successions to constrain changes in local and global marine redox conditions. Iodine records suggest locally anoxic conditions were potentially pervasive on shallow carbonate shelves, while sulfur isotopes suggest a reduction in global euxinic (anoxic and sulfidic) conditions. Late Katian sulfate‐sulfur isotope data show a large negative excursion that initiated during elevated sea level and continued through peak Hirnantian glaciation. Geochemical box modeling suggests a combination of decreasing pyrite burial and increasing weathering are required to drive the observed negative excursion suggesting a ∼3% decrease of global seafloor euxinia during the Late Ordovician. The sulfur datasets provide further evidence that this trend was followed by increases in euxinia which coincided with eustatic sea‐level rise during subsequent deglaciation in the late Hirnantian. A persistence of shelf anoxia against a backdrop of waning then waxing global euxinia was linked to the two LOME pulses. These results place important constraints on local and global marine redox conditions throughout the Late Ordovician and suggest that non‐sulfidic shelfal anoxia—along with glacioeustatic sea level and climatic cooling—were important environmental stressors that worsened conditions for marine fauna, resulting in the second‐largest mass extinction in Earth history and the only example during an icehouse climate.