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There is limited information regarding COVID-19 in long-term blood or marrow transplant (BMT) survivors. We leveraged the BMT Survivor Study (BMTSS) to address this gap. BMTSS included patients who underwent BMT at one of three US sites between 1974 and 2014 and survived ≥2 years after BMT. A sibling cohort serves as a non-BMT comparison group. Participants (2,430 BMT survivors; 780 non-BMT participants) completed the BMTSS survey between 10/2020 and 11/2021 about COVID-19 testing, risk mitigation behaviors, morbidity, and healthcare utilization. Median age at BMT was 46 years (range: 0-78 years) and median follow up since BMT was 14 years (6-46 years); 76% were non-Hispanic white, 54% had received allogeneic BMT. The risk of COVID-19 infection was comparable for BMT survivors vs non-BMT participants (15-month cumulative incidence: 6.5% vs. 8.1%; adjusted odd ratio [aOR]=0.93, 95%CI=0.65-1.33, p=0.68). Among survivors, being unemployed (aOR=1.90, 95%CI=1.12-3.23, p=0.02; reference: retired) increased the odds of infection; always wearing a mask in public was protective (aOR=0.49, 95%CI=0.31-0.77. p=0.002; reference: not always masking). When compared with COVID positive non-BMT participants, COVID positive BMT survivors had higher odds of hospitalization (aOR=2.23, 95%CI=0.99-5.05, p=0.05); however, the odds of emergency department visits were comparable (aOR=1.60, 95%CI=0.71-3.58, p=0.25). COVID-19 infection status did not increase the odds of hospitalization among BMT survivors (aOR=1.32, 95%CI=0.89-1.95, p=0.17, but did increase the odds of ED visits (aOR=2.63, 95%CI=1.74-3.98, p=

PURPOSE The financial burden experienced by blood or marrow transplant (BMT) survivors during the COVID-19 pandemic remains unstudied. We evaluated the risk for high out-of-pocket medical costs and associated financial burden experienced by BMT survivors and a sibling comparison group during the COVID-19 pandemic. METHODS This study included 2,370 BMT survivors and 750 siblings who completed the BMT Survivor Study survey during the pandemic. Participants reported employment status, out-of-pocket medical costs, and financial burden. Medical expenses ≥ 10% of the annual household income constituted high out-of-pocket medical costs. Logistic regression identified factors associated with high out-of-pocket medical costs and financial burden. RESULTS BMT survivors were more likely to incur high out-of-pocket medical costs (11.3% v 3.1%; adjusted odds ratio [aOR], 2.88; 95% CI, 1.84 to 4.50) than the siblings. Survivor characteristics associated with high out-of-pocket medical costs included younger age at study (aORper_year_younger_age, 1.02; 95% CI, 1.00 to 1.03), lower prepandemic annual household income and/or education (< $50,000 US dollars and/or < college graduate: aOR, 1.96; 95% CI, 1.42 to 2.69; reference: ≥ $50,000 in US dollars and ≥ college graduate), > 1 chronic health condition (aOR, 2.82; 95% CI, 2.00 to 3.98), ≥ 1 hospitalization during the pandemic (aOR, 2.11; 95% CI, 1.53 to 2.89), and being unemployed during the pandemic (aOR, 1.52; 95% CI, 1.06 to 2.17). Among BMT survivors, high out-of-pocket medical costs were significantly associated with problems in paying medical bills (aOR, 10.57; 95% CI, 7.39 to 15.11), deferring medical care (aOR, 4.93; 95% CI, 3.71 to 6.55), taking a smaller dose of medication than prescribed (aOR, 4.99; 95% CI, 3.23 to 7.70), and considering filing for bankruptcy (aOR, 3.80; 95% CI, 2.14 to 6.73). CONCLUSION BMT survivors report high out-of-pocket medical costs, which jeopardizes their health care and may affect health outcomes. Policies aimed at reducing financial burden in BMT survivors, such as expanding access to patient assistance programs, may mitigate the negative health consequences.

Living in a disadvantaged neighborhood is associated with poor health outcomes. Blood or Marrow Transplant (BMT) survivors remain at risk of chronic health conditions requiring anticipatory management. We hypothesized that among BMT survivors, neighborhood disadvantage was associated with poor self-reported routine health care utilization and health. We leveraged data from BMTSS – a retrospective cohort study examining long-term outcomes among individuals surviving ≥2 y following BMT at three institutions between 1974 and 2014. Participants in this analysis completed the BMTSS survey (sociodemographics; chronic health conditions; time since routine check-up; self-reported health). The Area Deprivation Index (ADI) represented neighborhood disadvantage; this composite indicator of 17 census measures is a percentile rank (0 = least deprived to 100 = most deprived). Multivariable ordered logit regression adjusted for clinical factors and individual-level sociodemographics, modeling associations between ADI, time since routine check-up, and self-reported health. Among 2,857 survivors, median ADI was 24 (interquartile range: 10-46). Adjusting for self-reported individual-level socioeconomic indicators and chronic health conditions, patients in more disadvantaged neighborhoods had higher odds of reporting longer intervals since routine check-up (ORADI_continuous = 1.007, P < .001) and poorer health status (controlling for time since check-up; ORADI_continuous = 1.005, P = .003). Compared with patients living in the least disadvantaged neighborhood (ADI = 1), patients in the most disadvantaged neighborhood (ADI = 100), had twice the odds (ORADI = 1.007^99 = 2.06) of reporting no routine visits and 1.65-times the odds of reporting poor health (ORADI = 1.005^99 = 1.65). In BMT survivors, access to health care and health status are associated with area disadvantage. These findings may inform strategies to address long-term care coordination and retention for vulnerable survivors.

An Autonomous Structural Health Monitoring (SHM) System for Fixed Offshore Structures is a tool used to monitor the state or the health of a structure in terms of its integrity and strength in an automated manner. An SHM system framework comprises of software and hardware integration equipped with IoT capability to collect raw data, online data transmittal to onshore, a back-end engine to process data into useful engineering information and display the monitoring results through engineering parameters and digital twinning, which emulates the real condition of the structure offshore. The prominent monitoring method for a structure's strength is through global monitoring, using structural modal properties as the measuring parameter to indentify a certain structure's global integrity, specifically using its natural frequency. This paper aims to layout the framework of an autonomous SHM system for global monitoring which is implemented onto a seismically vulnerable fixed offshore structure.

PURPOSE We determined trends in life expectancy and cause-specific late mortality after autologous blood or marrow transplantation (BMT) performed over a 30-year period, using the BMT Survivor Study. METHODS We constructed a cohort of 4,702 individuals with hematologic neoplasms who lived ≥ 2 years after autologous BMT performed between 1981 and 2014 at three transplant centers. The end of follow-up was April 19, 2021. The primary exposure variable was autologous BMT performed in four eras: 1981-1999; 2000-2005; 2006-2010; and 2011-2014. Vital status and cause of death were obtained from National Death Index Plus program and Accurinct databases. RESULTS The median age at BMT was 53 years (range, 0-78 years), 58.7% were male, 67.8% were non-Hispanic White, and 28.3% had undergone transplantation between 2011 and 2014. Autologous BMT recipients experienced a 7-year reduction in life expectancy. The adjusted hazard of 5-year all-cause mortality declined over the four eras (reference: 1981-1999; hazard ratio [HR]2000-2005 = 0.77; 95% CI, 0.62 to 0.94; HR2006-2010 = 0.64; 95% CI, 0.51 to 0.79; HR2011-2014 = 0.56; 95% CI, 0.45 to 0.71; Ptrend < .001), as did years of life lost (5.0 years to 1.6 years). The reduction in all-cause mortality was most pronounced among those transplanted for Hodgkin lymphoma or plasma cell dyscrasias, but was not observed among those transplanted for non-Hodgkin lymphoma or those conditioned with total-body irradiation. We also observed a decline in late deaths because of infection ( Ptrend < .0001; primarily for BMTs before 2006) and subsequent neoplasms ( Ptrend = .03; confined to decline in therapy-related myeloid neoplasm–related mortality) but not because of cardiovascular or renal disease. CONCLUSION Late mortality among autologous BMT recipients has declined over a 30-year period. However, ongoing efforts are needed to mitigate development of infections, subsequent neoplasms, and cardiovascular and renal disease to further reduce late mortality.

Background Urban pollution is correlated with an increased prevalence of skin pigmentation disorders, however the physiological processes underlying this association are unclear. Objectives To delineate the relationship between polycyclic aromatic hydrocarbons (PAHs), a key constituent of atmospheric pollution, and immunity/skin pigmentation pathways. Methods We exposed peripheral blood mononuclear cells (PBMC) to PAHs and performed cytokines/chemokine profiling. We then examined the effect of immune activation on pigmentation by co-culturing PBMC and Benzo(a)pyrene (BaP) with reconstructed human pigmented epidermis (RHPE). To study the mechanism, we treated keratinocytes with conditioned medium from BaP-exposed PBMC and studied DNA damage responses, aryl hydrocarbon receptor (AhR) activation and pro-pigmentation factor, proopiomelanocortin (POMC) secretion. Results PAHs induced up-regulation of inflammatory cytokines/chemokine in PBMC. Co-culturing of RHPE with PBMC+BaP resulted in increased melanin content and localization. BaP conditioned medium significantly increased DNA damage, p53 stabilization, AhR activation and POMC secretion in keratinocytes. We found that IFNγ induced DNA damage while TNFα and IL-8 potentiated POMC secretion in keratinocytes. Importantly, BaP conditioned medium-induced DNA damage and POMC secretion is prevented by antioxidants vitamin E, vitamin C and sulforaphane, as well as the prototypical corticosteroid dexamethasone. Finally, vitamin C and sulforaphane enhanced the genome protective and depigmentation effects of dexamethasone, providing proof-of-concept for a combinatorial approach for the prevention and/or correction of PAH-induced pigment spots formation. Conclusion Our study reveals the importance of systemic immunity in regulating PAH-induced skin pigmentation, and provide a new keratinocytes DNA damage response mechanistic target for the prevention or reversal of pollution-associated skin pigmentation.

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)–mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3s as potential promoters of inflammation in PSO.

Offshore structures are susceptible to damages due to hurricane. The main subject of this research, free standing drilling riser (FSDR), is an innovation to the drilling riser that enables rapid disconnection prior to hurricane conditions. This allows the offshore drilling rig and operator to move away from hurricane path prior to hurricane landing. Yet, currently, the emergency disconnection decision of FSDR is decided by a rig manager. Past incidents have shown that human error can cause catastrophic damage. Studies on FSDR operations under hurricane condition are scarcely available. The most relevant studies, free standing riser (FSR) behaves differently. With the increase in hurricane intensity over the past 50 years, this increases the risk in FSDR operations. In this work, the hydrodynamic response of FSDR under hurricane conditions was investigated. Four simulation studies were conducted in Orcaflex finite element modeling (FEM) software. These studies were conducted to determine the effect of emergency disconnection location, the optimum emergency disconnection location, the effect of various Saffir Simpson maximum significant wave height and hurricane generated swell on the hydrodynamic response of FSDR. Hurricane generated wave spectrum was used to replicate hurricane conditions. The simulation study shows that the lateral displacement of FSDR decreases in a 3rd order polynomial function with the emergency disconnection location, LD = −6e−6d3 + 0.0024d2 − 0.3348d + 19.179. In addition, the optimum emergency disconnection location along drilling riser line is at 87.50% of the original water depth. The lateral displacement of FSDR increases exponentially with Saffir Simpson scale storm intensity, y = 1.7537e0.0386x. Lastly, the stronger the swell component of hurricane generated swell, the higher the hydrodynamic responses. Wind wave component of hurricane generated swell did not influence FSDR as the riser was in the free standing mode. The limitation of this research is the findings are applicable for this simulation setup only. Further validations are required with experimental setup and various types of offshore structure.

Cole disease is a genodermatosis of pigmentation following a strict dominant mode of inheritance. In this study, we investigated eight patients affected with an overlapping genodermatosis after recessive inheritance. The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients. We found that this mutation, like those causing dominant Cole disease, impairs homodimerization of the ENPP1 enzyme that is mediated by its two somatomedin-B-like domains. Histological analysis revealed structural and molecular changes in affected skin that were likely to originate from defective melanocytes because keratinocytes do not express ENPP1. Consistently, RNA-sequencing analysis of patient-derived primary melanocytes revealed alterations in melanocyte development and in pigmentation signaling pathways. We therefore conclude that germline ENPP1 cysteine-specific mutations, primarily affecting the melanocyte lineage, cause a clinical spectrum of dyschromatosis, in which the p.Cys120Arg allele represents a recessive and more severe form of Cole disease.

Herrigbone structures are identified on the chitins of the Mantis shrimp. Bio-inspired helicoidal arrangement of composite layers can mimic these herringbone structures. First, the carbon composite samples are fabricated using the hand lay-up method, followed by a curing process using a hot press system. The impact absorption properties of these samples will be analyzed through a series of impact tests. The samples will also be tested for its tensile properties to compare the effect of plies arranged in helicoidal [0,45,90], [0,30,60,90] and Cross-ply orientations to form the laminate structure. The results showed that helicoidal samples have higher penetration tolerance and toughness as compared to Cross-ply samples during impact tests. It is found that the specimen with helicoidal stacking sequence has better debonding resistance and improved damage tolerance. The 6-ply helicoidal samples exhibits higher tensile strength as compared to 6-ply Cross-ply samples due to better fiber to matrix adhesion for helicoidal structure in the direction of pulling force.

Co-regulation of Epidermal Permeability Barrier and Cutaneous Immunity The epidermal permeability barrier is no longer viewed solely as a physical barrier against molecules and microorganisms passing through skin. In addition to regulating epidermal proliferation and lipid production, epidermal permeability barrier function and cutaneous immune functions are also co-regulated. A compromised epidermal permeability barrier upregulates a wide range of cutaneous immune responses, including the expression of cytokines, antimicrobial peptides, and Toll-like receptors. Moreover, perturbation of the epidermal permeability barrier stimulates T cell proliferation, Langerhans cell infiltration and maturation, and mast-cell infiltration. Furthermore, barrier disruption enhances Staphylococcus aureus colonization and certain Candida invasions. Certain cytokines, Toll-like receptors, and antimicrobial peptides benefit the epidermal permeability barrier. Clinically, improvement of epidermal permeability barrier function is a valuable approach to prevent and treat certain immune-mediated dermatoses.

In this paper, we present a new system of non-photorealistic rendering which allows landscape photographs to be automatically converted to look like Oriental paintings. Using various computer vision and image processing techniques, we can generate images with the rules and features commonly found in Oriental paintings. With such a system, anyone can create realistic Oriental paintings easily, without the years of practice that are usually required by Oriental artists.

Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.

We have developed a 2-D multiplexed cantilever array platform for high-throughput nanomechanical chemical sensing and analysis. After coating the cantilevers with alkane thiols having different functional end groups, we have performed vapor phase chemical sensing experiments with toluene and water vapor as targets. To overcome non-uniform responses caused by fabrication and imaging issues, the chemical response of each cantilever is self-calibrated using the thermal response of each cantilever. From these experiments, we could observe chemically induced nanoscale motion of cantilevers for various humidity or vapor concentration levels, and response differentiation with different functional end groups of thiols.

Summary Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.

Understanding the interactions between aromatic gas molecules and various simple aromatic receptor molecules is important in developing selective receptors for volatile organic compounds (VOCs). Here, five benzene thiols with different functional end groups were used to investigate the weak binding of aromatic vapors such as dinitrotolouene (DNT) and toluene. A multiplexed microcantilever array in conjunction with a very low concentration vapor generation system was developed to study multiple receptor-target interactions simultaneously. Differential nanomechanical responses of such devices provided insight into the influence of various chemical and structural features of such molecules.

Microcantilever (MC) sensors can detect the presence of chemical vapors at very low concentrations based on the surface stress changes generated by the interactions between probe and target molecules on their surfaces [1-2]. The magnitude of the surface stress change depends on the type of interaction taking place which include hydrogen bonding, electrostatic, van der Waals forces, etc. Pinnaduwage et al [2] demonstrated detection of explosive materials at ultra low concentrations (10-30 ppt) using single MC AFM tip coated with a thiol (-SH) self assembled monolayer (SAM). They were able to get highly sensitive and reproducible signals from their MC sensor while detecting chemicals like PETN, RDX, etc. However, they did not demonstrate the specificity of the coating material to explosive materials. Most types of chemical sensors (metal oxide, conductive polymer, carbon nano tube or belt sensors) are known to respond to interfering chemical agents in a similar manner as the target. Bietsch et al [3] used a set of MC’s (1D array) coated with different types of polymers as chemical sensing layers to try and identify unique deflection signatures for each target chemical. The performance of such sensors is expected to degrade during long term usage as the binding force between the polymer coating and the silicon cantilever structure is weak. Furthermore, polymer coating layers are in general not selective to specific target vapors since they have limited chemical and structural information due to the simple repetition of same chemical structure. To increase the selectivity for a particular target vapor, it is necessary to develop coating materials, which have enough chemical/structural information and long term stability specifically for that target. To expedite the screening process for testing several coating materials in parallel, we need a high throughput sensor array platform.Copyright © 2005 by ASME

To increase the sensitivity of a micromechanical structure to temperature (in thermal sensing) and surface stress (in biochemical sensing) change, a novel Flip-Over-Bimorph (FOB) structure has been proposed. For detecting physically induced nanoscale motion, the operation of a piston motion optomechanical sensor using the FOB design has been demonstrated. The piston motion opto-mechanical sensor has a symmetric structure such that the structural deflection is converted into a linear displacement of a reflecting surface, which is used for optical interferometry. Through the optical measurement setup using the He-Ne laser and CCD, light intensity changes for chip temperature changes are measured, and the thermo-mechanical sensitivity of the designed sensor is 180 nm/K.Copyright © 2005 by ASME