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We document that children growing up in places left behind by todays economy experience lower levels of social mobility as adults. Using a longitudinal database that tracks over 20,000 places in the USA from 1980 to 2018, we identify two kinds of left behind places: the long-term left behind that have struggled over long periods of history; and recently left-behind places where conditions have deteriorated. Compared to children of similar baseline household income levels, we find that exposure to left behind places is associated with a 4-percentile reduction in adult income rank. Children fare considerably better when exposed to places where conditions are improving. These outcomes vary across prominent social and spatial categories and are compounded when nearby places are also experiencing hardship. Based on these findings, we argue that left behind places are having scarring effects on children that could manifest long into the future, exacerbating the intergenerational challenges faced by low-income households and communities. Improvements in local economic conditions and outmigration to more prosperous places are, therefore, unlikely to be full remedies for the problems created by left behind places.

Current customer segmentations in omnichannel retail are based on channel usage and tend to be rather descriptive. In comparison, this research focuses on the role of “need for touch” (NFT) and channel preferences (attractiveness, appropriateness, satisfactoriness) introduced as antecedents to channel choice. The aim of this research was to develop a predictive model of omnichannel purchase behaviour and use its results to identify customer segments in the so far under-researched sports and leisure category, where the key decision factor of NFT seems to dominate when considering information and purchase options. We have examined its role and incorporated it as an exogenous variable and channel preferences as mediating variables in a SEM model to predict omnichannel purchase behaviour. Using the latent scores of channel preferences, we performed a cluster analysis and introduced various segments. In the proposed structural model preferences towards the information channel and the purchase channel serve as key mediators. Webrooming behaviour is negatively related to offline search channel preference, but showrooming is positively related to it. Meanwhile, webrooming behaviour is positively related to offline shopping channel preference, but showrooming is negatively related to it. Competitive mediation results indicate cross-channel synergies and complementary mediation results point out lock-in effects. Six customer segments were identified, and we found significant differences in their shopping behaviour. Lock-in effect arises in the case of online information enthusiasts and online shopping enthusiasts. While in the case of the webrooming-oriented cluster, offline shopping was more appropriate and satisfactory, and positive cross-channel synergies appeared to be prevalent.

The characterization accuracy of damage indices in massive and porous composite biomaterials under complex osmotic conditions has long been a challenge in engineering materials science. Establishing correlations between damage indices calculated using different methodologies is crucial to validate and improve defects characterizations. In this study, we investigated the damage index correlation of cylindrical massive granite-porous backfill structural composites under both dry and seepage conditions. A series of triaxial cyclic loading and unloading tests were conducted on specimens under hydromechanical conditions with varying osmotic pressures (0, 1, 3, 5, 7, and 9 MPa) and a confining pressure of 9 MPa involving acoustic emission monitoring and phase-based 3D nondestructive CT scanning. The results revealed the AE energy was lower under osmotic conditions compared to dry conditions. The AE Damage Index (DAE), defined by separating tensile and shear microcracking signals, significantly increased from 0.32 to 0.55 with rising osmotic pressure. 3D mesoscopic fracture visualization provided detailed insights into the fractures in granite and backfill interfaces. The number of small-angle cracks increased with osmotic pressure, and the crack inclination distribution range expanded from 63°- 85° to 49°–80°. The average crack angle showed a significant monotonic decrease with increasing osmotic pressure. An Energy Dissipation Damage Index (DED) was defined, and its correlation with the DAE under dry conditions was modeled using a reciprocal function DED=a/(DAE+bσ3)+c. This novel approach offers insights into the transition points between tensile and shear-dominated failure stages. Furthermore, an exponential function DV=aDAEb(b

IntroductionThe COVID-19 pandemic has become a global health crisis, eliciting varying severity in infected individuals. This study aimed to explore the immune profiles between moderate and severe COVID-19 patients experiencing a cytokine storm and their association with mortality. This study highlights the role of PD-1/PD-L1 and the TIGIT/CD226/CD155/CD112 pathways in COVID-19 patients.MethodsWe performed a study using flow cytometry to compare the phenotypic and functional characteristics of peripheral blood mononuclear cells in patients with moderate or severe disease and healthy individuals. Soluble immune checkpoint molecule and ligand levels were measured by Luminex.ResultsSevere patients show reduced CD8+ T cell frequency, hyperactivation of CD8+ T, NK and NKT cells with concurrent upregulation of immune checkpoint ligands in monocytes. TIGIT expression by CD8+ T and NK cells and PD-1 by NKT cells suggest a spectrum of immune dysfunction, encompassing both hyperactivation and features of exhaustion. This dual phenomenon likely contributes to the impaired viral clearance and the exacerbation of inflammation characteristic of severe disease. Additionally, the study suggests that increased activation and cytotoxicity of NK cells may be associated with fatal outcomes in severe COVID-19 infection.ConclusionThese findings shed light on the intricate immune response regulation in COVID-19, emphasizing the importance of immune checkpoint pathways and activation signatures in disease severity. A novel aspect of this study is that it includes only COVID-19 patients experiencing cytokine storms, allowing for a focused analysis of immune dysregulation during this critical phase of the disease.

Abstract: Whether permafrost systematically alters the rate of riverbank erosion is a fundamental geomorphic question with significant importance to infrastructure, water quality, and biogeochemistry of high‐latitude watersheds. For over four decades, this question has remained unanswered due to a lack of data. Using remotely sensed imagery, we addressed this knowledge gap by quantifying riverbank erosion rates across the Arctic and subarctic. To compare these rates to non‐permafrost rivers, we assembled a global data set of published riverbank erosion rates. We found that erosion rates in rivers influenced by permafrost are on average nine times lower than non‐permafrost systems; erosion rate differences increase up to 40 times for the largest rivers. To test alternative hypotheses for the observed erosion rate difference, we examined differences in total water yield and erosional efficiency between these rivers and non‐permafrost rivers. Neither of these factors nor differences in river sediment loads provided compelling alternative explanations, leading us to conclude that permafrost limits riverbank erosion rates. This conclusion was supported by field investigations of rates and patterns of erosion along three rivers flowing through discontinuous permafrost in Alaska. Our results show that permafrost limits maximum bank erosion rates on rivers with stream powers greater than 900 Wm−1. On smaller rivers, however, hydrology rather than thaw rate may be the dominant control on bank erosion. Our findings suggest that Arctic warming and hydrological changes should increase bank erosion rates on large rivers but may reduce rates on rivers with drainage areas less than a few thousand km2.

Abstract Permafrost influences 25% of land in the Northern Hemisphere, where it stabilizes the ground beneath communities and infrastructure and sequesters carbon. However, the coevolution of permafrost, river dynamics, and vegetation in Arctic environments remains poorly understood. As rivers meander, they erode the floodplain at cutbanks and build new land through bar deposition, creating sequences of landforms with distinct formation ages. Here we mapped these sequences along the Koyukuk River floodplain, Alaska, analyzing permafrost occurrence, and landform and vegetation types. We used radiocarbon and optically stimulated luminescence (OSL) dating to develop a floodplain age map. Deposit ages ranged from modern to 10 ka, with more younger deposits near the modern channel. Permafrost rapidly reached 50% areal extent in all deposits older than 200 years then gradually increased up to ∼85% extent for deposits greater than 4 Kyr old. Permafrost extent correlated with increases in black spruce and wetland abundance, as well as increases in permafrost extent within wetland, and shrub and scrub vegetation classes. We developed an inverse model to constrain permafrost formation rate as a function of air temperature. Permafrost extent initially increased by ∼25% per century, in pace with vegetation succession, before decelerating to

Rock-encased-backfill (RB) structures are common in underground mining, for example in the cut-and-fill and stoping methods. To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures, a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens (rock on outside, backfill on inside) with different volume fractions of rock (VF = 0.48, 0.61, 0.73, and 0.84), confining pressures (0, 6, 9, and 12 MPa), and cyclic loading rates (200, 300, 400, and 500 N/s). The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops, acoustic emission events, and post-failure X-ray 3D fracture morphology. The results showed significant differences between cyclic and monotonic loadings of RB specimens, particularly with regard to the generation of shear microcracks, the development of stress memory and strain hardening, and the contact forces and associated friction that develops along the rock-backfill interface. One important finding is that as a function of the number of cycles, the elastic strain increases linearly and the dissipated energy increases exponentially. Also, compared with monotonic loading, the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage. Another finding is that compared with monotonic loading, more shear microcracks are generated during every reloading stage, but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation. The transition from elastic to plastic behavior varies depending on the parameters of each test (confinement, volume fraction, and cyclic rate), and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction, 400 N/s cyclic loading rate, and 9 MPa confinement. All the findings have important practical implications on the ability of backfill to support underground excavations.

Resumen: Introducción: El shock séptico continúa siendo una de las principales causas de mortalidad en las unidades de cuidados intensivos. Recientemente han surgido terapias de hemoadsorción como una herramienta adicional para abordar esta patología, contribuyendo a restablecer la homeostasis inmune del paciente. Sin embargo, aún existen dudas sobre la efectividad de estas intervenciones y es necesario mejorar el conocimiento sobre su aplicación en la práctica clínica. Objetivo: Evaluar el impacto de la combinación de terapia hemoadsorptiva y hemofiltración de alto volumen en el tratamiento del shock séptico refractario en una cohorte no concurrente de pacientes, analizando parámetros clínicos y de laboratorio. Métodos: Se realizó una revisión no concurrente de pacientes ingresados en la unidad de cuidados intensivos con shock séptico refractario que recibieron terapia hemoadsorptiva asociado a hemofiltración de alto volumen (HFAV) durante un periodo de cinco años (2016-2020). Se analizaron variables clínicas, como la edad y género, puntajes APACHE II y SOFA, requerimientos de vasopresores y los parámetros de laboratorio, así como la mortalidad hospitalaria y la mortalidad a los 30 y 90 días. Se calcularon estadísticas descriptivas, y se compararon las variables pre y post terapia utilizando la prueba de Mann-Whitney. Resultados: La edad media de la cohorte fue de 54,57 años, y consistió en 14 pacientes. La terapia hemoadsorptiva se asoció con una reducción en los requerimientos de vasopresores, con un requerimiento inicial mediano de noradrenalina de 0,7 μg/kg/min (RIC 0,45-0,8875) que disminuyó a 0,12 μg/kg/min (RIC 0-0,225) después de la terapia. El requerimiento total normalizado de vasopresores a noradrenalina al inicio de la terapia fue de 0,8125 μg/kg/min (RIC 0,56-1,08), y después de la terapia fue de 0,175 μg/kg/min (RIC 0,01-0,29). El 100% recibió noradrenalina como agente vasopresor primario. Un 71,4% tuvo un tratamiento adicional con adrenalina, el 28,6% con vasopresina, y tan solo el 7,1% fue complementado con dobutamina.Las puntuaciones APACHE II medianas pre y post terapia fueron de 30,5 y 20,5, respectivamente, mientras que las puntuaciones SOFA fueron de 13,5 y 11,5. Los niveles medios de lactato disminuyeron en un 60%, de 7,47 mmol/l pre-terapia a 2,97 mmol/l post terapia. Los parámetros inflamatorios, como la proteína C reactiva, disminuyeron de un promedio de 206 mg/dL a 180 mg/dl y la procalcitonina disminuyó de un promedio de 58 a 8,91 ng/ml. La mortalidad hospitalaria fue del 57%, aumentando a un 64% a los 90 días de seguimiento. Conclusión: En nuestra cohorte no concurrente de 14 pacientes, la terapia hemoadsorptiva combinado con hemofiltración de alto volumen demostró resultados alentadores en el tratamiento del shock séptico refractario, mejorando significativamente los outcomes intermedios como los requerimientos de vasopresores, niveles de lactato y parámetros inflamatorios. Sin embargo, nuestros resultados en outcomes duros, como la mortalidad, fueron similares a los reportados en casos de shock séptico refractario sin el uso de terapia hemoadsortiva. Estos datos publicados nos sirven como punto de partida para conformar una base de datos comparativa. Los resultados son prometedores y justifican la necesidad de estudios de cohorte más grandes para evaluar el impacto de la terapia hemoadsorptiva en la mortalidad a largo plazo y explorar su papel potencial como opción de tratamiento estándar para el shock séptico refractario. Abstract: Introduction: Septic shock continues to be one of the main causes of mortality in intensive care units. Recently, hemoadsorption therapies have emerged as an additional tool to address this pathology, contributing to reestablishing the patient's immune homeostasis. However, there are still doubts about the effectiveness of these interventions and it is necessary to improve knowledge about their application in clinical practice. Objective: Assess the impact of combined hemoadsorptive therapy and high-volume hemofiltration in the treatment of refractory septic shock in a non-concurrent patient cohort, analyzing clinical and laboratory parameters. Methods: A non-concurrent review of patients admitted to the intensive care unit with refractory septic shock who received hemoadsorptive associated with high-volume hemofiltration therapy over a period of five years (2016-2020) was conducted. Clinical variables, including age and gender, APACHE II and SOFA scores, vasopressor requirements, laboratory parameters, as well as in-hospital mortality and mortality at 30 and 90 days, were analyzed. Descriptive statistics were calculated, and pre- and post-therapy variables were compared using the Mann-Whitney test. Results: The mean age of the cohort was 54.57 years and consisted of 14 patients. Hemoadsorptive therapy was associated with a reduction in vasopressor requirements, with a median initial requirement of noradrenaline of 0.7 μg/kg/min (IQR 0.45-0.8875) that decreased to 0.12 μg/kg/min (IQR 0-0.225) after therapy. The total normalized vasopressor requirement to noradrenaline at the start of therapy was 0.8125 μg/kg/min (IQR 0.56-1.08), and after therapy, it was 0.175 μg/kg/min (IQR 0.01-0.29). All patients received norepinephrine as the primary vasopressor agent. 71.4% had additional treatment with adrenaline, 28.6% with vasopressin, and only 7.1% were supplemented with dobutamine.The median APACHE II scores pre- and post-therapy were 30.5 and 20.5, respectively, while the SOFA scores were 13.5 and 11.5. Mean lactate levels decreased by 60%, from 7.47 mmol/l pre-therapy to 2.97 mmol/l post-therapy. Inflammatory parameters, such as C-reactive protein, mean procalcitonin levels decreased from 206 mg/dl to 180 mg/dl, mean level of procalcitonin decreased from 58 to 8.91 ng/ml. Hospital mortality was 57%, increasing to 64% at 90-day follow-up. Conclusion: In our non-concurrent cohort of 14 patients, hemoadsorptive therapy combined with high-volume hemofiltration demonstrated encouraging results in the treatment of refractory septic shock, significantly improving intermediate outcomes such as vasopressor requirements, lactate levels, and inflammatory parameters. However, our results in hard outcomes, such as mortality, were similar to those reported in cases of refractory septic shock without the use of this therapy, which allows us to consider them as a historical control group. These results are promising and justify the need for larger cohort studies to evaluate the impact of hemoadsorptive therapy on long-term mortality and explore its potential role as a standard treatment option for refractory septic shock.

Objective: Metastatic spinal tumors represent a rare but concerning complication of primary thyroid carcinoma. We identified demographics, metastatic features, outcomes, and treatment strategies for these tumors in our institutional cohort. Materials and Methods: We retrospectively reviewed patients surgically treated for spinal metastases of primary thyroid carcinoma. Demographics, tumor characteristics, and treatment modalities were collected. The functional outcomes were quantified using Nurik, Modified Rankin, and Karnofsky Scores. Results: Twelve patients were identified who underwent 17 surgeries for resection of spinal metastases. The primary thyroid tumor pathologies included papillary (4/12), follicular (6/12), and Hurthle cell (2/12) subtypes. The average number of spinal metastases was 2.5. Of the primary tumor subtypes, follicular tumors averaged 2.8 metastases at the highest and Hurthle cell tumors averaged 2.0 spinal metastases at the lowest. Five patients (41.7%) underwent preoperative embolization for their spinal metastases. Seven patients (58.3%) received postoperative radiation. There was no significant difference in progression-free survival between patients receiving surgery with adjuvant radiation and surgery alone (P = 0.0773). Five patients (41.7%) experienced postoperative complications. Two patients (16.7%) succumbed to disease progression and two patients (16.7%) experienced tumor recurrence following resection. Postsurgical mean Nurik scores decreased 0.54 points, mean Modified Rankin scores decreased 0.48 points, and mean Karnofsky scores increased 4.8 points. Conclusion: Surgery presents as an important treatment modality in the management of spinal metastases from thyroid cancer. Further work is needed to understand the predictive factors for survival and outcomes following treatment.