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Research regarding self-maintenance of pool-riffle river morphology has focused on hydraulics within individual pool-riffle couplets. Here, we make a scientific leap from one site on river to 702 pool-riffle couplets across northern California to understand the frequency of the foundational velocity-reversal hypothesis. A geometrical, mass and energy conservation-based velocity reversal criterion was used to predict the occurrence of a velocity reversal. Only 18% of all couplets met the established criteria indicating a velocity reversal. At locations with riffle-to-pool bankfull width ratios greater than 1.2, more than 50% of couplets met velocity-reversal conditions. Velocity reversal pools were almost always (89%) associated with channel constrictions while riffles were typically (71%) associated with channel expansions, albeit less often. Therefore, across landscapes, it appears channel constrictions propagate velocity reversal maintenance. Phasing between width and depth variability is central to fluvial morphodynamics and ecology and must be considered in sustainable river eco-engineering.

© 2020 John Wiley & Sons, Ltd. Reach-scale morphological channel classifications are underpinned by the theory that each channel type is related to an assemblage of reach- and catchment-scale hydrologic, topographic, and sediment supply drivers. However, the relative importance of each driver on reach morphology is unclear, as is the possibility that different driver assemblages yield the same reach morphology. Reach-scale classifications have never needed to be predicated on hydrology, yet hydrology controls discharge and thus sediment transport capacity. The scientific question is: do two or more regions with quantifiable differences in hydrologic setting end up with different reach-scale channel types, or do channel types transcend hydrologic setting because hydrologic setting is not a dominant control at the reach scale? This study answered this question by isolating hydrologic metrics as potential dominant controls of channel type. Three steps were applied in a large test basin with diverse hydrologic settings (Sacramento River, California) to: (1) create a reach-scale channel classification based on local site surveys, (2) categorize sites by flood magnitude, dimensionless flood magnitude, and annual hydrologic regime type, and (3) statistically analyze two hydrogeomorphic linkages. Statistical tests assessed the spatial distribution of channel types and the dependence of channel type morphological attributes by hydrologic setting. Results yielded 10 channel types. Nearly all types existed across all hydrologic settings, which is perhaps a surprising development for hydrogeomorphology. Downstream hydraulic geometry relationships were statistically significant. In addition, cobble-dominated uniform streams showed a consistent inverse relationship between slope and dimensionless flood magnitude, an indication of dynamic equilibrium between transport capacity and sediment supply. However, most morphological attributes showed no sorting by hydrologic setting. This study suggests that median hydraulic geometry relations persist across basins and within channel types, but hydrologic influence on geomorphic variability is likely due to local influences rather than catchment-scale drivers. © 2020 John Wiley & Sons, Ltd.

© 2020 Elsevier B.V. Seasonal flow transitions between wet and dry conditions are a primary control on river conditions, including biogeochemical processes and aquatic life-history strategies. In regions like California with highly seasonal flow patterns and immense interannual variability, a rigorous approach is needed to accurately identify and quantify seasonal flow transitions from the annual flow regime. Drawing on signal processing theory, this study develops a transferable approach to detect the timing of seasonal flow transitions from daily streamflow time series using an iterative smoothing, feature detection, and windowing methodology. The approach is shown to accurately identify and characterize seasonal flows across highly variable natural flow regimes in California. A quantitative error assessment validated the accuracy of the approach, finding that inaccuracies in seasonal timing identification did not exceed 10%, with infrequent exceptions. Results for seasonal timing were also used to highlight the statistically distinct timing found across streams with varying climatic drivers in California. The proposed approach improves understanding of spatial and temporal trends in hydrologic processes and climate conditions across complex landscapes and informs environmental water management efforts by delineating timing of seasonal flows.

The extent and timing of many river ecosystem functions is controlled by the interplay of streamflow dynamics with the river corridor shape and structure. However, most river management studies evaluate the role of either flow or form without regard to their dynamic interactions. This study develops an integrated modelling approach to assess changes in ecosystem functions resulting from different river flow and form configurations. Moreover, it investigates the role of temporal variability in such flow–form–function trade-offs. The use of synthetic, archetypal channel forms in lieu of high-resolution topographic data reduces time and financial requirements, overcomes site-specific topographic features, and allows for evaluation of any morphological structure of interest. In an application to California's Mediterranean-montane streams, the interacting roles of channel form, water year type, and hydrologic impairment were evaluated across a suite of ecosystem functions related to hydrogeomorphic processes and aquatic habitat. Channel form acted as the dominant control on hydrogeomorphic processes, whereas water year type controlled salmonid habitat functions. Streamflow alteration for hydropower increased redd dewatering risk and altered aquatic habitat availability. Study results highlight critical trade-offs in ecosystem function performance and emphasize the significance of spatio-temporal diversity of flow and form at multiple scales for maintaining river ecosystem integrity. The proposed approach is broadly applicable and extensible to other systems and ecosystem functions, where findings can be used to inform river management and design testing.

To date, subreach-scale variations in flow width and bed elevation have rarely been included in channel classifications. Variability in topographic features of rivers, however, in conjunction with sediment supply and discharge produces a mosaic of channel forms that provides unique habitats for sensitive aquatic species. In this study we investigated the utility of topographic variability attributes (TVAs) in distinguishing channel types and dominant channel formation and maintenance processes in montane and lowland streams of the Sacramento River basin, California, USA. A stratified random survey of 161 stream sites was performed to ensure balanced sampling across groups of stream reaches with expected similar geomorphic settings. For each site surveyed, width and depth variability were measured at baseflow and bankfull stages, and then incorporated in a channel classification framework alongside traditional reach-averaged geomorphic attributes (e.g., channel slope, width-to-depth, confinement, and dominant substrate) to evaluate the significance of TVAs in differentiating channel types. In contrast to more traditional attributes such as slope and contributing area, which are often touted as the key indicators of hydrogeomorphic processes, bankfull width variance emerged as a first-order attribute for distinguishing channel types. A total of nine channel types were distinguished for the Sacramento Basin consisting of both previously identified and new channel types. The results indicate that incorporating TVAs in channel classification provides a quantitative basis for interpreting nonuniform as well as uniform geomorphic processes, which can improve our ability to distinguish linked channel forms and processes of geomorphic and ecological significance.

Today's water systems require integrated water resource management to improve the water supply for conflicting water uses. This research explores alternative policies to improve the water supply for two conflicting uses, hydropower and environmental, using the Leishui River basin and Dongjiang reservoir as a case study. First, the natural flow regime prior to reservoir construction (pre-1992) was estimated by performing a statistical analysis of 41years of daily streamflow data (March 1952-February 1993). This natural flow regime was used as a template for proposing environmental flow (e-flow) requirements. The post-reservoir flow regime (post-1992) (March 1993-February 2011) was analysed to estimate the streamflow alteration. Results show that the natural flow regime has been completely transformed; post-1992 winter normal flows are greater, and summer flows are smaller than pre-1992 conditions. Also, the occurrence of natural floods has been prevented. Second, a planning model was built of the current operation of the Dongjiang reservoir and used for comparison of four alternative water management policies that considered e-flow releases from the Dongjiang reservoir. The scenarios that considered combinations of the current operational policy and e-flow releases performed better in terms of hydropower generation than the current operation. Different volumes of e-flow requirements were tested, and an annual e-flow volume of 75% of the pre-1992 hydrograph was determined to generate the most hydropower while providing for environmental water needs. Trade-offs are essential to balance these two water management objectives, and compromises have to be made for both water uses to obtain benefits.

Background:. An estimated 0.6% of the U.S. population identifies as transgender and an increasing number of patients are presenting for gender-related medical and surgical services. Utilization of health care services, especially surgical services, by transgender patients is poorly understood beyond survey-based studies. In this article, our aim is 2-fold; first, we intend to demonstrate the utilization of datasets generated by insurance claims data as a means of analyzing gender-related health services, and second, we use this modality to provide basic demographic, utilization, and outcomes data about the insured transgender population. Methods:. The Truven MarketScan Database, containing data from 2009 to 2015, was utilized, and a sample set was created using the Gender Identity Disorder diagnosis code. Basic demographic information and utilization of gender-affirming procedures was tabulated. Results:. We identified 7,905 transgender patients, 1,047 of which underwent surgical procedures from 2009 to 2015. Our demographic results were consistent with previous survey-based studies, suggesting transgender patients are on average young adults (average age = 29.8), and geographically diverse. The most common procedure from 2009 to 2015 was mastectomy. Complications of all gender-affirming procedures was 5.8%, with the highest rate of complications occurring with phalloplasty. There was a marked year-by-year increase in utilization of surgical services. Conclusion:. Transgender care and gender confirming surgery are an increasing component of health care in the United States. The data contained in existing databases can provide demographic, utilization, and outcomes data relevant to providers caring for the transgender patient population.

Background: Increased posterior tibial slope is a strong predictor of anterior cruciate ligament (ACL) graft re-injury. A concomitant slope-reducing high tibial osteotomy (HTO) has been suggested to decrease re-tear risk in these cases although little is known regarding outcomes following ACL reconstruction with HTO, especially in elite athletic patients. Indications: A 19-year-old National Collegiate Athletics Association (NCAA) Division 1 running back presented with an ACL tear, lateral meniscus tear, and posterior tibial slope of 19° (case 1). A 19-year-old NCAA Division 1 soccer forward presented with an ACL graft re-tear and posterior tibial slope of 21° (case 2). Technique: Anterior closing wedge HTOs were performed along with a primary ACL reconstruction with quadriceps tendon autograft (case 1) and a revision ACL reconstruction with quadriceps tendon autograft (case 2). Following the arthroscopic procedures, an anterior approach was used to insert the first guide wire distal to the patellar tendon insertion from anterior to posterior aiming toward the posterior curve of the tibia. A second guide wire was placed at the previously templated distance. The osteotomy was then performed utilizing a saw and then osteotome. The reduction was performed by gently lifting the ankle anteriorly and applying axial pressure, and a new posterior tibial slope was calculated. After the osteotomy site was reduced, a preliminary reduction was performed by applying a clamp to both wires followed by placing a wire across the osteotomy site aiming from anterolateral to posteromedial. An anterolateral proximal tibial plate was applied, as well as a lag screw across the osteotomy site. Results: At 6 months after surgery, case 1 demonstrated >90% Limb Symmetry Indices (LSI) with quadriceps strength, single leg hop tests, and change of direction tests. At 12 months after surgery, case 2 demonstrated >90% LSI with all functional testing and competed in 17 games. Both patients returned to preinjury performance metrics including top speed and vertical jump height. No significant postoperative complications or instability was observed. Discussion/Conclusion: Primary or revision ACL reconstruction with HTO shows potential to assist athletes in returning to high-level sport while reducing posterior slope. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

# Background Despite the association between hip abduction weakness and non-contact anterior cruciate ligament (ACL) injury, hip abduction strength is rarely considered in return to sport decision-making following ACL reconstruction (ACLR). # Hypothesis/Purpose The purpose of this study was to compare self-reported function, objective functional test performance, and re-injury rates in patients with high (≥33%) versus low (

# Background Self-efficacy and fear of re-injury have been documented as factors related to an athlete’s ability to return-to-sport after anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare psychological readiness between athletes injured in their primary mode of sport versus those injured outside of their primary sport following ACL reconstruction. # Hypothesis Athletes sustaining ‘in-sport’ injuries will demonstrate poorer psychological readiness when compared their matched counterparts injured outside of their primary sport. # Study Design Case-Control Study # Methods A single-surgeon database of 638 patients following ACL reconstruction was used to conduct a matched case-control analysis. Psychological readiness was examined 16-weeks postoperatively using the ACL-Return to Sport after Injury (ACL-RSI) questionnaire with subgroup analyses for the ‘emotional’, ‘confidence’ and ‘injury-risk’ subscales. Subject matching was performed for baseline patient and surgical demographics. All statistical comparisons were performed using a one-way (group) analysis variance (ANOVA) at a significance level of α = .05. # Results Ninety-two matched patients (49 ‘in-sport’ injuries, 43 ‘out-of-sport’ injuries) were included in the final analysis. The ‘in-sport’ group exhibited significantly lower total ACL-RSI scores (55.3 ±12.9 versus 60.8 ±11.6, t = 2.747, P < .001) when compared to the ‘out-of-sport’ group. Subscale comparisons indicated lower ‘emotional’ (P < .016) and higher ‘injury risk’ (P < .001) psychological constructs for ‘in-sport’ athletes versus ‘out-of-sport’ athletes. No differences were found between groups for the ‘confidence’ subscale (P = .987). # Conclusions Athletes sustaining ‘in-sport’ ACL injuries demonstrated poorer psychological readiness when compared to athletes injured outside their primary sport when in preparation for return-to-sport activities following ACL reconstruction. # Clinical Relevance Clinicians should consider the potential impact of mode of injury on psychological readiness when returning athletes to sport after ACL reconstruction.

Background:. Effective medical record documentation is imperative for both patient care and reimbursement for care provided. The purpose of this study was to compare coding/billing patterns for plastic surgery consultations before and after implementation of a standardized documentation protocol. Methods:. Standardized hand, facial trauma, and general plastic surgery consult note templates were created. Following institutional approval, records were reviewed for all plastic surgery consultations from January to October 2019. Template notes were universally implemented in July 2019. Medical coding was performed by a certified professional coder using the 1995 Evaluation and Management Review Worksheet. Coding/billing patterns between groups were compared with and without standardized documentation using univariate analysis. Results:. Seventy-five consecutive preimplementation consult notes and 75 consecutive postimplementation consult notes were selected for review. Each group included 25 hand, 25 facial trauma, and 25 general plastic surgery consultation notes. The history and physical examination components of the visit code were more frequently coded as “comprehensive”postimplementation (P = 0.000). There was no significant difference in coding for medical decision making between the two groups (P = 0.340). The final visit code was significantly higher in the postimplementation group (45.3% 99254/99284 versus 2.7%, P = 0.000), and the charges were significantly higher post implementation—average charge per consult $250 versus $203 (P = 0.000) with a 22.8% increase in total charges generated. Conclusion:. Utilization of standardized consultation note templates increases the accuracy of coding and associated billing of inpatient and emergency department plastic surgery consultations through documentation and reflection of level of service provided.

Objective: A significant proportion of patients with advanced heart failure present with dilated left ventricles and functional mitral regurgitation. These patients currently have limited treatment options. The MitraClip device (Abbott) has benefited only patients with smaller left ventricles (end-diastolic dimension <70 mm), whereas those with larger left ventricles did not benefit. A possible explanation is correcting functional mitral regurgitation alone may not adequately reduce the wall stresses of a dilated left ventricle. We have developed a beating-heart device that not only approximates the papillary muscles to reduce functional mitral regurgitation but also modifies the left ventricle size and shape to reduce wall stress., Methods: Yorkshire swine (n = 16) had a myocardial infarction induced by permanent occlusion of the left circumflex with intracoronary ethanol. Three months later, the animals developed heart failure and moderate or greater functional mitral regurgitation. Through a transapical approach, the new device was implanted under echocardiography guidance to reshape the left ventricle and correct functional mitral regurgitation. The acute impact of this approach on the mitral valve and left ventricle was assessed with echocardiography and invasive hemodynamics., Results: After reshaping, echocardiography showed a decrease in end-diastolic volume by 36.3 ± 30.5 mL (P < .001), a decrease in sphericity index by 0.143 ± 0.087 (P < .001), and an increase in ejection fraction of 5.90% ± 6.38% (P < .01). Mitral valve tenting area was reduced by 39.29 ± 33.66 mm 2 (P < .001), coaptation length was increased by 2.12 ± 1.02 mm (P < .001), and posterior excursion angle was improved by 9.07° ± 9.14° (P < .01), resulting in functional mitral regurgitation reduction., Conclusions: Correction of functional mitral regurgitation with favorable changes in mitral valve geometry and reduction in left ventricle geometry is possible with the proposed device., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Wall shear stress (WSS) is a critically important physical factor contributing to atherosclerosis. Mapping the spatial distribution of local, oscillatory WSS can identify important mechanisms underlying the progression of coronary artery disease., Methods: In this study, blood flow velocity and time-varying WSS were estimated in the left anterior descending (LAD) coronary artery of an ex vivo beating porcine heart using ultrasound with an 18 MHz linear array transducer aligned with the LAD in a forward-viewing orientation. A pulsatile heart loop with physiologically-accurate flow was created using a pulsatile pump. The coronary artery wall motion was compensated using a local block matching technique. Next, 2D and 3D velocity magnitude and WSS maps in the LAD coronary artery were estimated at different time points in the cardiac cycle using an ultrafast Doppler approach. The blood flow velocity estimated using the presented approach was compared with a commercially-available, calibrated single element blood flow velocity measurement system., Results: The resulting root mean square error (RMSE) of 2D velocity magnitude acquired from a high frequency, linear array transducer was less than 8% of the maximum velocity estimated by the commercial system., Conclusion: When implemented in a forward-viewing intravascular ultrasound device, the presented approach will enable dynamic estimation of WSS, an indicator of plaque vulnerability in coronary arteries., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

The murine aorta is a complex, heterogeneous structure that undergoes large and sometimes asymmetrical deformations under loading. For analytical convenience, mechanical behavior is predominantly described using global quantities that fail to capture critical local information essential to elucidating aortopathic processes. Here, in our methodological study, we used stereo digital image correlation (StereoDIC) to measure the strain profiles of speckle-patterned healthy and elastase-infused, pathological mouse aortas submerged in a temperature-controlled liquid medium. Our unique device rotates two 15-degree stereo-angle cameras that gather sequential digital images while simultaneously performing conventional biaxial pressure-diameter and force-length testing. A StereoDIC Variable Ray Origin (VRO) camera system model is employed to correct for high-magnification image refraction through hydrating physiological media. The resultant Green-Lagrange surface strain tensor was quantified at different blood vessel inflation pressures, axial extension ratios, and after aneurysm-initiating elastase exposure. Quantified results capture large, heterogeneous, inflation-related, circumferential strains that are drastically reduced in elastase-infused tissues. Shear strains, however, were very small on the tissue's surface. Spatially averaged StereoDIC-based strains were generally more detailed than those determined using conventional edge detection techniques., Competing Interests: Declaration of competing interest Naren Vyavahare, John F. Eberth, and Susan M. Lessner reports financial support was provided by National Institutes of Health. Susan Lessner and John Eberth reports financial support was provided by National Science Foundation. Michael A. Sutton reports a relationship with Correlated Solutions, Incorporated that includes: board membership and equity or stocks. Michael A. Sutton is the Chief Scientific Officer for Correlated Solutions, Incorporated. No other authors have conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aortic dissection is a complex, intramural, and dynamic condition involving multiple mechanisms, hence, difficult to observe. In the present study, a controlled in vitro aortic dissection was performed using tension-inflation tests on notched rabbit aortic segments. The mechanical test was combined with conventional (cCT) and synchrotron (sCT) computed tomography for in situ imaging of the macro- and micro-structural morphological changes of the aortic wall during dissection. We demonstrate that the morphology of the notch and the aorta can be quantified in situ at different steps of the aortic dissection, and that the notch geometry correlates with the critical pressure. The phenomena prior to propagation of the notch are also described, for instance the presence of a bulge at the tip of the notch is identified, deforming the remaining wall. Finally, our method allows us to visualize for the first time the propagation of an aortic dissection in real-time with a resolution that has never previously been reached. STATEMENT OF SIGNIFICANCE: With the present study, we investigated the factors leading to the propagation of aortic dissection by reproducing this mechanical process in notched rabbit aortas. Synchrotron CT provided the first visualisation in real-time of an aortic dissection propagation with a resolution that has never previously been reached. The morphology of the intimal tear and aorta was quantified at different steps of the aortic dissection, demonstrating that the early notch geometry correlates with the critical pressure. This quantification is crucial for the development of better criteria identifying patients at risk. Phenomena prior to tear propagation were also described, such as the presence of a bulge at the tip of the notch, deforming the remaining wall., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Cardiac volume overload from mitral regurgitation (MR) is a trigger for left ventricular dilatation, remodeling, and ultimate failure. While the functional and structural adaptations to this overload are known, the adaptation of myocardial mechanical properties remains unknown. Using a rodent model of MR, in this study, we discern changes in the passive material properties of the intact and decellularized myocardium. Eighty Sprague-Dawley rats (350-400 g) were assigned to two groups: (1) MR (n = 40) and (2) control (n = 40). MR was induced in the beating heart by perforating the mitral leaflet with a 23G needle, and rats were terminated at 2, 10, 20, or 40 weeks (n = 10/time-point). Echocardiography was performed at baseline and termination, and explanted hearts were used for equibiaxial mechanical testing of the intact myocardium and after decellularization. Two weeks after inducing severe MR, the myocardium was more extensible compared to control, however, stiffness and extensibility of the extracellular matrix did not differ from control at this timepoint. By 20 weeks, the myocardium was stiffer with a higher elastic modulus of 1920 ± 246 kPa, and a parallel rise in extracellular matrix stiffness. Despite some matrix stiffening, it only contributed to 31% and 36% of the elastic modulus of the intact tissue in the circumferential and longitudinal directions. At 40 weeks, similar trends of increasing stiffness were observed, but the contribution of extracellular matrix remained relatively low. Chronic MR induces ventricular myocardial stiffening, which seems to be driven by the myocyte compartment of the muscle, and not the extracellular matrix., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: To investigate the feasibility of a hybrid material in which decellularized pericardial extracellular matrix is functionalized with polymeric nanofibers, for use as a cardiovascular tissue substitute., Background: A cardiovascular tissue substitute, which is gradually resorbed and is replaced by host's native tissue, has several advantages. Especially in children and young adults, a resorbable material can be useful in accommodating growth, but also enable rapid endothelialization that is necessary to avoid thrombotic complications. In this study, we report a hybrid material, wherein decellularized pericardial matrix is functionalized with a layer of polymeric nanofibers, to achieve the mechanical strength for implantation in the cardiovascular system, but also have enhanced cell honing capacity., Methods: Pericardial sacs were decellularized with sodium deoxycholate, and polycaprolactone-chitosan fibers were electrospun onto the matrix. Tissue-polymer interaction was evaluated using spectroscopic methods, and the mechanical properties of the individual components and the hybrid material were quantified. In-vitro blood flow loop studies were conducted to assess hemocompatibility and cell culture methods were used to assess biocompatibility., Results: Encapsulation of the decellularized matrix with 70 μm thick matrix of polycaprolactone-chitosan nanofibers, was feasible and reproducible. Spectroscopy of the cross-section depicted new amide bond formation and C-O-C stretch at the interface. An average peel strength of 56.13 ± 11.87 mN/mm 2 was measured, that is sufficient to withstand a high shear of 15 dynes/cm 2 without delamination. Mechanical strength and extensibility ratio of the decellularized matrix alone were 18,000 ± 4,200 KPa and 0.18 ± 0.03% whereas that of the hybrid was higher at 20,000 ± 6,600 KPa and 0.35 ± 0.20%. Anisotropy index and stiffness of the biohybrid were increased as well. Neither thrombus formation, nor platelet adhesion or hemolysis was measured in the in-vitro blood flow loop studies. Cellular adhesion and survival were adequate in the material., Conclusion: Encapsulating a decellularized matrix with a polymeric nanofiber coating, has favorable attributes for use as a cardiovascular tissue substitute., Competing Interests: JM and MP are co-inventors of a patent application relevant to this technology, whose rights are assigned to Emory University. MP owns stock in Nyra Medical, and is an officer of this company. This entity did not have any role in this study, nor did it sponsor or review it. MP has received personal consulting fees from Heart Repair Technologies, which again did not have any role in this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mudigonda, Xu, Amedi, Lane, Corporan, Wang and Padala.)

Transforming growth factor-beta (TGFβ-1, -2, -3) ligands act through a common receptor complex yet each is expressed in a unique and overlapping fashion throughout development. TGFβ plays a role in extra-cellular matrix composition with mutations to genes encoding TGFβ and TGFβ signaling molecules contributing to diverse and deadly thoracic aortopathies common in Loeys-Dietz syndrome (LDS). In this investigation, we studied the TGFβ ligand-specific mechanical phenotype of ascending thoracic aortas (ATA) taken from 4-to-6 months-old Tgfb1 +/- , Tgfb2 +/- , and Tgfb3 +/- mice, their wild-type (WT) controls, and an elastase infusion model representative of severe elastolysis. Heterozygous mice were studied at an age without dilation to elucidate potential pre-aortopathic mechanical cues. Our findings indicate that ATAs from Tgfb2 +/- mice demonstrated significant wall thickening, a corresponding decrease in biaxial stress, decreased biaxial stiffness, and a decrease in stored energy. These results were unlike the pathological elastase model where decreases in biaxial stretch were found along with increases in diameter, biaxial stress, and biaxial stiffness. ATAs from Tgfb1 +/- and Tgfb3 +/- , on the other hand, had few mechanical differences when compared to wild-type controls. Although aortopathy generally occurs later in development, our findings reveal that in 4-to-6 month-old animals, only Tgfb2 +/- mice demonstrate a significant phenotype that fails to model ubiquitous elastolysis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AAA, no safe and efficient pharmacotherapies exist for patients. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs, making it an ideal target for delivering drugs to the AAA site. In this research, we conjugated nanoparticles with an elastin antibody that only targets degraded elastin while sparing healthy elastin. After induction of aneurysm by 4-week infusion of angiotensin II (Ang II), two biweekly intravenous injections of pentagalloyl glucose (PGG)-loaded nanoparticles conjugated with elastin antibody delivered the drug to the aneurysm site. We show that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastic lamina, and improve the mechanical properties of the aorta at the AAA site. Therefore, simple iv therapy of PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to reverse disease progression and return the aorta to normal homeostasis.

The great saphenous vein (GSV) has served as a coronary artery bypass graft (CABG) conduit for over 50 years. Despite prevalent use, first-year failure rates remain high compared to arterial autograft options. Amongst other factors, vein graft failure can be attributed to material and mechanical mismatching that lead to apoptosis, inflammation, and intimal-medial hyperplasia. Through the implementation of the continuum mechanical-based theory of "stress-mediated growth and remodeling," we hypothesize that the mechanical properties of porcine GSV grafts can be favorably tuned for CABG applications prior to implantation using a prolonged but gradual transition from venous to arterial loading conditions in an inflammatory and thrombogenic deficient environment. To test this hypothesis, we used a hemodynamic-mimetic perfusion bioreactor to guide remodeling through stepwise incremental changes in pressure and flow over the course of 21-day cultures. Biaxial mechanical testing of vessels pre- and post-remodeling was performed, with results fit to structurally-motivated constitutive models using non-parametric bootstrapping. The theory of "small-on-large" was used to describe appropriate stiffness moduli, while histology and viability assays confirmed microstructural adaptations and vessel viability. Results suggest that stepwise transition from venous-to-arterial conditions results in a partial restoration of circumferential stretch and circumferential, but not axial, stress through vessel dilation and wall thickening in a primarily outward remodeling process. These remodeled tissues also exhibited decreased mechanical isotropy and circumferential, but not axial, stiffening. In contrast, only increases in axial stiffness were observed using culture under venous perfusion conditions and those tissues experienced moderate intimal resorption.

Background: Mouse models of abdominal aortic aneurysm (AAA) and dissection have proven to be invaluable in the advancement of diagnostics and therapeutics by providing a platform to decipher response variables that are elusive in human populations. One such model involves systemic Angiotensin II (Ang-II) infusion into low density-lipoprotein receptor-deficient (LDLr-/-) mice leading to intramural thrombus formation, inflammation, matrix degradation, dilation, and dissection. Despite its effectiveness, considerable experimental variability has been observed in AAAs taken from our Ang-II infused LDLr-/- mice (n=12) with obvious dissection occurring in 3 samples, outer bulge radii ranging from 0.73 to 2.12 mm, burst pressures ranging from 155 to 540 mmHg, and rupture location occurring 0.05 to 2.53 mm from the peak bulge location., Objective: We hypothesized that surface curvature, a fundamental measure of shape, could serve as a useful predictor of AAA failure at supra-physiological inflation pressures., Methods: To test this hypothesis, we fit well-known biquadratic surface patches to 360° micro-mechanical test data and used Spearman's rank correlation (rho) to identify relationships between failure metrics and curvature indices., Results: We found the strongest associations between burst pressure and the maximum value of the first principal curvature (rho=-0.591, p-val=0.061), the maximum value of Mean curvature (rho=-0.545, p-val=0.087), and local values of Mean curvature at the burst location (rho=-0.864, p-val=0.001) with only the latter significant after Bonferroni correction. Additionally, the surface profile at failure was predominantly convex and hyperbolic (saddle-shaped) as indicated by a negative sign in the Gaussian curvature. Findings reiterate the importance of shape in experimental models of AAA.

Elastin is a key structural protein and its pathological degradation deterministic in aortic aneurysm (AA) outcomes. Unfortunately, using current diagnostic and clinical surveillance techniques the integrity of the elastic fiber network can only be assessed invasively. To address this, we employed fragmented elastin-targeting gold nanoparticles (EL-AuNPs) as a diagnostic tool for the evaluation of unruptured AAs. Electron dense EL-AuNPs were visualized within AAs using micro-computed tomography (micro-CT) and the corresponding Gold-to-Tissue volume ratios quantified. The Gold-to-Tissue volume ratios correlated strongly with the concentration (0, 0.5, or 10 U/mL) of infused porcine pancreatic elastase and therefore the degree of elastin damage. Hyperspectral mapping confirmed the spatial targeting of the EL-AuNPs to the sites of damaged elastin. Nonparametric Spearman's rank correlation indicated that the micro-CT-based Gold-to-Tissue volume ratios had a strong correlation with loaded (ρ = 0.867, p-val = 0.015) and unloaded (ρ = 0.830, p-val = 0.005) vessel diameter, percent dilation (ρ = 0.976, p-val = 0.015), circumferential stress (ρ = 0.673, p-val = 0.007), loaded (ρ = - 0.673, p-val = 0.017) and unloaded (ρ = - 0.697, p-val = 0.031) wall thicknesses, circumferential stretch (ρ = - 0.7234, p-val = 0.018), and lumen area compliance (ρ = - 0.831, p-val = 0.003). Likewise, in terms of axial force and axial stress vs. stretch, the post-elastase vessels were stiffer. Collectively, these findings suggest that, when combined with CT imaging, EL-AuNPs can be used as a powerful tool in the non-destructive estimation of mechanical and geometric features of AAs.

To measure the inhomogeneous 3D-strain fields present during inflation-extension testing of physiologically submerged micro-aneurysms, a Stereo Digital Image Correlation (StereoDIC) microscopy system is developed that revolves 15 ° stereo-angle cameras around a centrally-mounted target. Calibration is performed using submerged dot patterns and system accuracy verified using strain and deformation analyses for rigid body motions of speckle-patterned, micro-aneurysmal surrogates. In terms of the Green-Lagrange strain tensor and the 3D displacement fields, the results are stable even after 120 minutes, with maxima in both strain bias and strain standard deviation less than 2E-03 for all components, and micron-level displacement standard deviation.

Objectives: Previously, we found that maximum ingested bite size (V b ), the largest piece of food an animal can consume without biting it into smaller pieces first, isometrically scales relative to body size in strepsirrhines and with negative allometry in anthropoids. In the current study, we rectify the omission of great apes from the earlier sample to now characterize the V b of the entire size-range of the order., Materials and Methods: Five gorillas (Gorilla gorilla gorilla-G. g. gorilla) were studied to ascertain V b in relation to the mechanical properties of five foods., Results: Gorilla V b ranged from 166.38 cm 3 (for the least obdurate food: watermelon) to 8 cm 3 (for the most obdurate food: turnip), with an average V b of 33.50 cm 3 across all food types., Conclusions: When these data were compared to those from our previous studies, we found that gorillas consumed relatively slightly smaller volumes of food compared to the trend found across primates. However, because the more frugivorous gorillas consumed relatively larger pieces of food than the large folivorous monkeys previously studied, including the gorilla data increased the slope of the linear regression between body mass and V b in anthropoids. Thus, the addition of the largest living primate brings the anthropoid V b trend closer to the V b trend of the order. Notwithstanding, there is still negative allometry in anthropoid V b , in contrast with the isometry in strepsirrhine V b . Future research should include species with body masses between the smaller anthropoids and gorillas by studying the V b of large papionids and the other great apes., (© 2020 Wiley Periodicals, Inc.)

Background : Abdominal aortic aneurysms (AAA) are characterized by a progressive disruption and weakening of the extracellular matrix (ECM) leading to dilation of the aorta which can be fatal if not treated. Current diagnostic imaging modalities provides little insight on the varying degree of ECM degeneration that precedes rupture in AAAs. Targeted delivery of contrast agents such as gold nanoparticles (GNPs) that bind to degraded matrix could prove useful when combined with computed tomography (CT) to provide a non-invasive surrogate marker of AAA rupture potential. Methods : AAAs were induced by chronic infusion of angiotensin II (AngII) into low density-lipoprotein receptor-deficient (LDLr -/-) mice in combination with a high-fat diet. Abdominal ultrasound was used to monitor disease progression and to assess the circumferential strain throughout the cardiac cycle. At six weeks, GNPs conjugated with an elastin antibody (EL-GNP) were injected retro-orbitally. Mice were euthanized 24 hours after EL-GNP injection, and aortas were explanted and scanned ex-vivo with a micro-CT system. Histological assessment and 3D models of the aneurysms with micro-CT were used to determine the EL-GNPs distribution. Isolated vessel burst pressure testing was performed on each aneurysmal aorta to quantify rupture strength and to assess rupture location. Results : Aneurysms were found along the suprarenal aorta in AngII infused mice. Darkfield microscopy indicated EL-GNPs accumulation around the site of degraded elastin while avoiding the healthy and intact elastin fibers. Using nonlinear regression, the micro-CT signal intensity of EL-GNPs along the suprarenal aortas correlated strongly with burst pressures (R 2 =0.9415) but not the dilation as assessed by ultrasound measurements. Conclusions : Using an established mouse model of AAA, we successfully demonstrated in vivo targeting of EL-GNPs to damaged aortic elastin and correlated micro-CT-based signal intensities with burst pressures. Thus, we show that this novel targeting technique can be used as a diagnostic tool to predict the degree of elastin damage and therefore rupture potential in AAAs better than the extent of dilation., Competing Interests: Competing Interests: NRV holds significant equity in Elastrin Therapeutics Inc., which has licensed this technology from Clemson University.

Balancing ecological and human water needs often requires characterizing key aspects of the natural flow regime and then predicting ecological response to flow alterations. Flow metrics are generally relied upon to characterize long-term average statistical properties of the natural flow regime (hydrologic baseline conditions). However, some key aspects of hydrologic baseline conditions may be better understood through more complete consideration of continuous patterns of daily, seasonal, and inter-annual variability than through summary metrics. Here we propose the additional use of high-resolution dimensionless archetypes of regional stream classes to improve understanding of baseline hydrologic conditions and inform regional environmental flows assessments. In an application to California, we describe the development and analysis of hydrologic baseline archetypes to characterize patterns of flow variability within and between stream classes. We then assess the utility of archetypes to provide context for common flow metrics and improve understanding of linkages between aquatic patterns and processes and their hydrologic controls. Results indicate that these archetypes may offer a distinct and complementary tool for researching mechanistic flow-ecology relationships, assessing regional patterns for streamflow management, or understanding impacts of changing climate.

The prevalence of diverse animal models as surrogates for human vascular pathologies necessitate a comprehensive understanding of the differences that exist between species. Comparative passive mechanics are presented here for the common carotid arteries taken from bovine, porcine, ovine, leporine, murine-rat, and murine-mouse specimens. Data is generated using a scalable biaxial mechanical testing device following consistent circumferential (pressure-diameter) and axial (force-length) testing protocols. The structural mechanical response of carotids under equivalent loading, quantified by the deformed inner radius, deformed wall thickness, lumen area compliance and axial force, varies significantly among species but generally follows allometric scaling. Conversely, descriptors of the local mechanical response within the deformed arterial wall, including mean circumferential stress, mid-wall circumferential stretch, and mean axial stress, are relatively consistent across species. Unlike the larger animals studied, the diameter distensibility curves of murine specimens are non-monotonic and have a significantly higher value at 100 mmHg. Taken together, our results provide baseline structural and mechanical information for carotid arteries across a broad range of common animal models., Competing Interests: The authors have declared that no competing interests exist.

Background: Biomedical devices are implanted into mammalian soft tissues to improve, monitor, or restore form or function. The utility of these implants is limited by the subsequent foreign body response (FBR), beginning with inflammation and terminating in a collagen envelope around the device, known as the capsule. This capsule then can contract and distort the shape of the device or limit its effectiveness in interacting with the surrounding host tissues. In the current study, we investigated the effect of therapeutic collagen-coated silicone discs in a rat model of the FBR., Methods: A 3-dimensional printed mold was used to fabricate collagen-coated silicone discs incorporating 3 therapeutic agents: colchicine, a function-blocking antibody against interleukin 8 (IL-8) receptor B, and a powerful anti-inflammatory steroid, dexamethasone. Discs were implanted submuscularly into a well-characterized rat model of the FBR and evaluated for inflammatory response, fibrotic development, and cytokine release., Results: Coated silicone discs exhibited reduced collagen deposition and little to no foreign body giant cells at the host-silicone interface when compared with the silicone-only group. Therapeutic hydrogels demonstrate a significant decrease in cellular infiltration into the coatings over the 2-week time point in contrast to therapeutic-free hydrogel coatings. Cytokine analysis revealed significant differences between therapeutic-free and therapeutic-containing coatings when compared with silicone-only controls. Levels of IL-1β, IL-6, monocyte chemotactic protein 1, and macrophage inflammatory protein 3α were affected 48 hours after implantation, while differences in IL-18, growth-regulated oncogene/keratinocyte chemoattractant, and macrophage inflammatory protein 3α were observed 1 week after implantation., Conclusions: By utilizing the host's innate immune response, our engineered hydrogel coatings delivered therapeutic moieties directly to the implant microenvironment, thus delaying the FBR up to 2 weeks.

Collagen hydrogels have been used ubiquitously as engineering biomaterials with a biphasic network of fibrillar collagen and aqueous-filled voids that contribute to a complex, compressible, and nonlinear mechanical behavior - not well captured within the infinitesimal strain theory. In this study, type-I collagen, processed from a bovine corium, was fabricated into disks at 2, 3, and 4% (w/w) and exposed to 0, 10 5 , 10 6 , and 10 7 microjoules of ultraviolet light or enzymatic degradation via matrix metalloproteinase-2. Fully hydrated gels were subjected to unconfined, aqueous, compression testing with experimental data modeled within a continuum mechanics framework by employing the uncommon Blatz-Ko material model for porous elastic materials and a nonlinear form of the Poisson's ratio. From the Generalized form, the Special Blatz-Ko, compressible Neo-Hookean, and incompressible Mooney-Rivlin models were derived and the best-fit material parameters reported for each. The average root-mean-squared (RMS) error for the General (RMS = 0.13 ± 0.07) and Special Blatz-Ko (RMS = 0.13 ± 0.07) were lower than the Neo-Hookean (RMS = 0.23 ± 0.10) and Mooney-Rivlin (RMS = 0.18 ± 0.08) models. We conclude that, with a single fitted-parameter, the Special Blatz-Ko sufficiently captured the salient features of collagen hydrogel compression over most examined formulations and treatments., (Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.)

Calibration in diagnosis and treatment planning is difficult to achieve due to variations that exist in clinical interpretation. To determine if dental faculty members are consistent in teaching how to diagnose and treat periodontal disease, variations among dental students can be evaluated. A previous study reported high variability in diagnoses and treatment plans of periodontal cases at Indiana University School of Dentistry. This study aimed to build on that one by extending the research to two additional schools: Marquette University School of Dentistry and West Virginia University School of Dentistry. Diagnosis and treatment planning by 40 third- and fourth-year dental students were assessed at each of the schools. Students were asked to select the diagnosis and treatment plans on a questionnaire pertaining to 11 cases. Their responses were compared using chi-square tests, and multirater kappa statistics were used to assess agreement between classes and between schools. Logistic regression models were used to evaluate the effects of school, class year, prior experience, and GPA/class rank on correct responses. One case had a statistically significant difference in responses between third- and fourth-year dental students. Kappas for school agreement and class agreement were low. The students from Indiana University had higher diagnosis and treatment agreements than the Marquette University students, and the Marquette students fared better than the West Virginia University students. This study can help restructure future periodontal courses for a better understanding of periodontal diagnosis and treatment planning.

Healthcare is now more challenged to provide excellent care, while also increasing efficiency with more limited resources. The recent introduction of Ontario's funding reform challenges hospitals to increase the efficiency of specific procedures by providing funding based on patient volumes. The cataract surgery program at Ross Memorial Hospital, in Lindsay, Ontario, is an example of how a program designed a few years ago with a focus on patient care and efficiency managed to become substantially more efficient by introducing a series of small changes.

Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.