Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

A Case-Based, Longitudinal Curriculum in Pediatric Behavioral and Mental Health.

Introduction: Pediatric behavioral and mental health (BMH) disorders are increasingly common, but most pediatricians feel inadequately trained to manage them. We implemented a case-based, longitudinal curriculum in BMH within a pediatric residency program to prepare trainees to diagnose and manage these conditions. Methods: The pediatric residency program at Wright State University/Wright-Patterson Medical Center implemented a new BMH curriculum in 2020-2021. The curriculum consisted of five simulated cases involving depression, anxiety, attention deficit disorder with hyperactivity (ADHD), developmental delays, behavioral concerns, and autism. To reflect follow-up within a continuity clinic, cases included initial encounters and multiple follow-up visits. Faculty facilitators led residents in monthly small-group meetings over the academic year, with each session consisting of two to three simulated patient encounters. Residents completed pre-post surveys regarding their confidence in diagnosing and managing BMH conditions and pre- and posttests to evaluate the impact of the curriculum on knowledge gains. Results: All 47 pediatric residents participated in the curriculum; 38 (81%) completed pre-post surveys. Upon completion of the curriculum, residents reported significantly increased confidence in managing ADHD, treating depression, creating safety plans for suicidality, recognizing autism, and counseling patients and families on special education services. Knowledge-based pre- and posttests completed by 25 residents (53%) also demonstrated significant improvement (M = 92.4, SD = 10.9, pre vs. M = 99.3, SD = 6.6, post, p = .009). Discussion: This case-based, longitudinal curriculum in pediatric BMH simulating patient continuity improved residents' confidence and knowledge in diagnosing and managing common BMH conditions.

Homophily, selection, and choice in segregation models.

Schelling's 1971 work on the dynamics of segregation showed that even a small degree of homophily, the desire to live among like neighbors, can lead to a starkly segregated population. One of the driving factors for this result is that the notion of homophily used is based on group identities that are exogenous and immutable. In contrast, we consider a homophily that arises from the desire to be with neighbors who are behaviorally similar, not necessarily those who have the same group identity. The distinction matters because behaviors are neither exogenous nor immutable but choices that can change as individuals adapt to their neighborhoods. We show that in such an environment, integration rather than segregation is the typical outcome. However, the tendency toward adaptation and integration can be impeded when economic frictions in the form of income inequality and housing cost are present.

Migration and sustainable development.

To understand the implications of migration for sustainable development requires a comprehensive consideration of a range of population movements and their feedback across space and time. This Perspective reviews emerging science at the interface of migration studies, demography, and sustainability, focusing on consequences of migration flows for nature-society interactions including on societal outcomes such as inequality; environmental causes and consequences of involuntary displacement; and processes of cultural convergence in sustainability practices in dynamic new populations. We advance a framework that demonstrates how migration outcomes result in identifiable consequences on resources, environmental burdens and well-being, and on innovation, adaptation, and challenges for sustainability governance. We elaborate the research frontiers of migration for sustainability science, explicitly integrating the full spectrum of regular migration decisions dominated by economic motives through to involuntary displacement due to social or environmental stresses. Migration can potentially contribute to sustainability transitions when it enhances well-being while not exacerbating structural inequalities or compound uneven burdens on environmental resources.

KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo.

Oncogenic KRAS mutations are well-described functionally and are known to drive tumorigenesis. Recent reports describe a significant prevalence of KRAS allelic imbalances or gene dosage changes in human cancers, including loss of the wild-type allele in KRAS mutant cancers. However, the role of wild-type KRAS in tumorigenesis and therapeutic response remains elusive. We report an in vivo murine model of colorectal cancer featuring deletion of wild-type Kras in the context of oncogenic Kras. Deletion of wild-type Kras exacerbates oncogenic KRAS signalling through MAPK and thus drives tumour initiation. Absence of wild-type Kras potentiates the oncogenic effect of KRASG12D, while incidentally inducing sensitivity to inhibition of MEK1/2. Importantly, loss of the wild-type allele in aggressive models of KRASG12D-driven CRC significantly alters tumour progression, and suppresses metastasis through modulation of the immune microenvironment. This study highlights the critical role for wild-type Kras upon tumour initiation, progression and therapeutic response in Kras mutant CRC.

Sustainable utilization of fruit and vegetable waste bioresources for bioplastics production.

Nowadays, rapidly increasing production, use and disposable of plastic products has become one of the utmost environmental issues. Our current circumstances in which the food supply chain is demonstrated as containing plastic particles and other plastic-based impurities, represents a significant health risk to humans, animals, and environmental alike. According to this point of view, biodegradable plastic material aims to produce a more sustainable and greener world with a lower ecological impact. Bioplastics are being investigated as an environmentally friendly candidate to address this problem and hence global bioplastic production has seen significant growth and expansion in recent years. This article focuses on a few critical issues that must be addressed for bioplastic production to become commercially viable. Although the reduction of fruit and vegetable waste biomass has an apparent value in terms of environmental benefits and sustainability, commercial success at industrial scale has remained flat. This is due to various factors, including biomass feedstocks, pretreatment technologies, enzymatic hydrolysis, and scale-up issues in the industry, all of which contribute to high capital and operating costs. This review paper summarizes the global overview of bioplastics derived from fruit and vegetable waste biomass. Furthermore, economic and technical challenges associated with industrialization and diverse applications of bioplastics in biomedical, agricultural, and food-packaging fields due to their excellent biocompatibility properties are reviewed.HighlightsReview of the diverse types and characteristics of sustainability of biobased plasticsImproved pretreatment technologies can develop to enhance greater yieldEnzyme hydrolysis process used for bioplastic extraction & hasten industrial scale-upFocus on technical challenges facing commercialized the bioplasticsDetailed discussion on the application for sustainability of biodegradable plastics.

Place Attachment and Aging in Place: Preferences and Disruptions.

This paper examines the links between place attachment and older persons' preferences to age in place, and factors that disrupt these preferences. We use data from the 2001-2021 Household, Income and Labour Dynamics in Australia Survey and panel-data modelling to confirm strong associations between several place attachment dimensions and aging-in-place preferences. Strong ties to children, strong social capital, residence in social housing, homeownership status, housing wealth, and home and neighborhood satisfaction are all positively linked to a stronger preference to age in place. Our findings reveal important differences between older homeowners and older non-owners. For owners, closeness to children is a strong predictor of aging-in-place preferences, although mortgage debt can trigger involuntary moves. For non-owners, tenure security achieved through longer durations at one's address of residence is linked to stronger aging-in-place preferences. However, private renters are more often exposed to involuntary moves. We discuss the policy implications of these disruptions.

A self calibrating, magnetic sensor approach accurately positions an aortic damage control stent in a porcine model.

Objectives: Non-compressible torso hemorrhage remains a high mortality injury, with difficulty mobilizing resources before exsanguination. Previous studies reported on a retrievable stent graft for damage control and morphometric algorithms for rapid placement, yet fluoroscopy is impractical for the austere environment. We hypothesized that magnetic sensors could be used to position stents relative to an external magnet placed on an anatomic landmark, whereas an electromagnet would allow self-calibration to account for environmental noise. Methods: A magnetic sensor alone (MSA) and with integrated stent (MSIS) were examined in a porcine model under anesthesia. A target electromagnet was placed on the xiphoid process (position 0 cm). Sensors were placed in the aorta and measurements obtained at positions 0 cm, +4 cm, and +12 cm from the magnet and compared with fluoroscopy. Sensors were examined under conditions of tachycardia/hypertension, hypotension, vibration, and metal shrapnel to simulate environmental factors that might impact accuracy. General linear models compared mean differences between fluoroscopy and sensor readings. Results: Both sensors were compatible with a 10 French catheter system and provided real-time assessment of the distance between the sensor and magnetic target in centimeters. Mean differences between fluoroscopy and both magnetic sensor readings demonstrated accuracy within ±0.5 cm for all but one condition at 0 cm and +4 cm, whereas accuracy decreased at +12 cm from the target. Using the control as a reference, there was no significant difference in mean differences between fluoroscopy and both MSA or MSIS readings at 0 cm and +4 cm for all conditions. The system retained effectiveness if the target was overshot. Conclusion: Magnetic sensors achieved the highest accuracy as sensors approached the target. Oscillation of the electromagnet on and off effectively accounts for environmental noise.This approach is promising for rapid and accurate placement of damage control retrievable stent grafts when fluoroscopy is impractical. Level of evidence: Not applicable.

Sustainability transitions in consumption-production systems.

The need for faster and deeper transitions toward more sustainable development pathways is now widely recognized. How to meet that need has been at the center of a growing body of academic research and real-world policy implementation. This paper presents our perspective on some of the most powerful insights that have emerged from this ongoing work. In particular, we highlight insights on how sustainability transitions can be usefully conceptualized, how they come about and evolve, and how they can be shaped and guided through deliberate policy interventions. Throughout the paper, we also highlight some of the many how questions that remain unresolved and on which progress would be especially helpful for the pursuit of sustainable development. Our approach to these "how" questions on sustainability transitions draws on two strands of solution-driven research and policy advice: one emerging from studies of how human societies interact with nature and the other emerging from studies of how those societies interact with their technologies. Consumption-production systems have been a focus of extensive work in both strands. To help build bridges between them, we recently brought together a cross-section of relevant scholars for a PNAS Special Feature on "Sustainability transitions in consumption-production systems." Their contributions are summarized in a companion paper we have written to introduce the Special Feature [F. W. Geels, F. Kern, W. C. Clark, Proc. Natl. Acad. Sci. U.S.A. (2023)]. We draw on that work in the Perspective we present here as well as our reading of the relevant literatures.

Progress in modeling dynamic systems for sustainable development.

This Perspective evaluates recent progress in modeling nature-society systems to inform sustainable development. We argue that recent work has begun to address longstanding and often-cited challenges in bringing modeling to bear on problems of sustainable development. For each of four stages of modeling practice-defining purpose, selecting components, analyzing interactions, and assessing interventions-we highlight examples of dynamical modeling methods and advances in their application that have improved understanding and begun to inform action. Because many of these methods and associated advances have focused on particular sectors and places, their potential to inform key open questions in the field of sustainability science is often underappreciated. We discuss how application of such methods helps researchers interested in harnessing insights into specific sectors and locations to address human well-being, focus on sustainability-relevant timescales, and attend to power differentials among actors. In parallel, application of these modeling methods is helping to advance theory of nature-society systems by enhancing the uptake and utility of frameworks, clarifying key concepts through more rigorous definitions, and informing development of archetypes that can assist hypothesis development and testing. We conclude by suggesting ways to further leverage emerging modeling methods in the context of sustainability science.

Evaluation of right ventricular diastolic function, systolic function, and circulating galectin-3 concentrations in dogs with pulmonary stenosis.

BACKGROUND: Cardiovascular diseases with increased right ventricular (RV) afterload induce RV diastolic and systolic dysfunction, and myocardial fibrosis in humans. Studies in dogs with pulmonary stenosis (PS) evaluating RV diastolic function and markers of myocardial fibrosis are lacking. HYPOTHESIS/OBJECTIVES: Dogs with PS have echocardiographic evidence of RV diastolic and systolic dysfunction and increased serum concentrations of galectin-3 (Gal-3), a surrogate biomarker for myocardial fibrosis. ANIMALS: Forty client-owned dogs (10 controls, 30 with PS). METHODS: Prospective study. All dogs had systemic blood pressure measurement, serum biochemical analysis, echocardiography, and measurement of serum Gal-3 concentration performed. RESULTS: Variables of RV diastolic function were obtained in 39/40 dogs. Trans-tricuspid flow velocity in early diastole to trans-tricuspid flow velocity in late diastole ratios (RV E/A) were lower (P < .001) in dogs with PS (median, 0.94; range, 0.62-2.04) compared to controls (1.78; 1.17-2.35). Trans-tricuspid flow velocity in early diastole to tricuspid annular myocardial velocity in early diastole ratios (RV E/e') were higher (P < .001) in dogs with PS (11.55; 4.69-28) compared to control (6.21; 5.16-7.21). Variables of RV systolic function were lower in dogs with PS (P = <.001). Serum Gal-3 concentration was higher (P = .002) in dogs with PS (285.1 pg/mL; 94.71-406.97) compared to control dogs (162.83 pg/mL; 52.3-232.82). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with PS have RV diastolic and systolic dysfunction, and increased Gal-3 concentrations. These findings suggest the presence of RV myocardial fibrosis in dogs with PS, which could impact clinical management.

Standardization of Nomenclature for the Mechanisms and Materials Utilized for Extracorporeal Blood Purification.

In order to develop a standardized nomenclature for the mechanisms and materials utilized during extracorporeal blood purification, a consensus expert conference was convened in November 2022. Standardized nomenclature serves as a common language for reporting research findings, new device development, and education. It is also critically important to support patient safety, allow comparisons between techniques, materials, and devices, and be essential for defining and naming innovative technologies and classifying devices for regulatory approval. The multidisciplinary conference developed detailed descriptions of the performance characteristics of devices (membranes, filters, and sorbents), solute and fluid transport mechanisms, flow parameters, and methods of treatment evaluation. In addition, nomenclature for adsorptive blood purification techniques was proposed. This report summarizes these activities and highlights the need for standardization of nomenclature in the future to harmonize research, education, and innovation in extracorporeal blood purification therapies.

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target.

The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues. By identifying ions that drive variation between normal and transformed tissues, we found dysregulation of the methionine cycle to be a hallmark of APC-deficient CRC. Loss of Apc in the mouse intestine was found to be sufficient to drive expression of one of its enzymes, adenosylhomocysteinase (AHCY), which was also found to be transcriptionally upregulated in human CRC. Targeting of AHCY function impaired growth of APC-deficient organoids in vitro, and prevented the characteristic hyperproliferative/crypt progenitor phenotype driven by acute deletion of Apc in vivo, even in the context of mutant Kras. Finally, pharmacological inhibition of AHCY reduced intestinal tumour burden in ApcMin/+ mice indicating its potential as a metabolic drug target in CRC.

The effects of chromium propionate supplementation to yearling steers in a commercial feedyard on growth performance, carcass characteristics, and health.

British crossbred steers (n = 3,072; initial body weight [BW] = 358 ±â€…37 kg) were used to evaluate the effects of chromium propionate supplementation to yearling steers in a commercial feedyard on growth performance, carcass characteristics, and health. Steers were blocked by initial BW; pens were assigned randomly to one of two dietary treatments within block. Treatments, replicated in 15 pens per treatment with 75 to 135 heads per pen, included 1) control, 0 mg supplemental Cr/kg dietary dry matter (DM) (CTL); 2) 0.50 mg supplemental Cr/kg diet DM (chromium propionate; KemTRACE Chromium 0.4%, Kemin Industries, Des Moines, IA) (chromium propionate, CR). Final BW (638 vs. 641 kg), average daily gain (1.81 vs. 1.82 kg), DM intake (11.02 vs. 11.02 kg), and gain efficiency (0.164 vs. 0.165) did not differ between CTL and CR, respectively (P ≥ 0.75). No differences among treatments for hot carcass weight (407 vs. 408 kg, CTL and CR, respectively), dressing percentage, longissimus muscle area, or yield grade were observed (P ≥ 0.15). Twelfth-rib fat thickness tended (P = 0.10) to be greater for CR vs. CTL (1.55 vs. 1.29 cm, respectively). A trend (P = 0.10) for marbling score to be higher for CR vs. CTL was detected (452 vs. 440, respectively). Distribution of quality grade was similar between CR and CTL; 1.52% of carcasses graded prime (P = 0.68), and 87.2% of carcasses graded choice (P = 0.68). Respiratory morbidity was low (1.93%) and not different among treatments (P = 0.20); likewise, there was no difference in respiratory treatment rates between treatments (P ≥ 0.18). Supplementing Cr to high-performing yearling steers did not alter growth performance, carcass characteristics, or health outcomes.

A System to Track Stent Location in the Human Body by Fusing Magnetometer and Accelerometer Measurements.

This paper will introduce a simple locating system to track a stent when it is deployed into a human artery. The stent is proposed to achieve hemostasis for bleeding soldiers on the battlefield, where common surgical imaging equipment such as fluoroscopy systems are not available. In the application of interest, the stent must be guided to the right location to avoid serious complications. The most important features are its relative accuracy and the ease by which it may be quickly set up and used in a trauma situation. The locating approach in this paper utilizes a magnet outside the human body as the reference and a magnetometer that will be deployed inside the artery with the stent. The sensor can detect its location in a coordinate system centered with the reference magnet. In practice, the main challenge is that the locating accuracy will be deteriorated by external magnetic interference, rotation of the sensor, and random noise. These causes of error are addressed in the paper to improve the locating accuracy and repeatability under various conditions. Finally, the system's locating performance will be validated in benchtop experiments, where the effects of the disturbance-eliminating procedures will be addressed.

ARAG, an Antioxidant-Rich Gel, Shows Superiority to Mepilex Ag in the Treatment of Deep Partial Thickness Burns without Sacrificing Antimicrobial Efficiency.

Current treatments for deep tissue burns are limited, and most serve only to enhance hydration or prevent bacterial growth. This leaves burn healing dependent on slow natural processes to debride the wound and reestablish the epidermal and dermal layers of the skin. Infections are well known to destabilize this process through a variety of mechanisms, most notably through increased inflammation and the resulting oxidative stress. In this study, we show that ARAG (an antioxidant-rich antimicrobial gel) can suppress the growth of multiple bacteria commonly found to infect burns (Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, and Staphylococcus aureus). This inhibition is comparable to that conferred by silver ion release from burn dressings such as Mepilex-Ag. We further show, using a porcine model for deep partial-thickness burns, that ARAG allows for enhanced wound healing over Mepilex-Ag, the current standard of care. Histological findings indicate this is likely due to increased wound debridement and dampening of late inflammatory processes, leading to more balanced physiologic healing. Taken together, these findings show promise for ARAG as a superior alternative to the current standard of care.

Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis.

BACKGROUND: In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil. METHODS: In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause. RESULTS: In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups. CONCLUSIONS: Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. (Funded by the National Heart, Lung, and Blood Institute and others; BMT CTN 1703 ClinicalTrials.gov number, NCT03959241.).

Use of the Revised Second Victim Experience and Support Tool to Examine Second Victim Experiences of Respiratory Therapists.

BACKGROUND: Respiratory therapists (RTs) work alongside allied health staff, nurses, and physicians during stressful and traumatic events that can be associated with emotional and physiological implications known as second victim (SV) experiences (SVEs). This study aimed to evaluate SVEs of RTs, including both positive and negative implications. METHODS: RTs within a large academic health care organization across Minnesota, Wisconsin, Florida, and Arizona were asked to participate in an anonymous survey that included the validated Second Victim Experience and Support Tool-Revised to assess SVEs as well as desired support services. RESULTS: Of the RTs invited to participate, 30.8% (171/555) completed the survey. Of the 171 survey respondents, 91.2% (156) reported that they had been part of a stressful or traumatic work-related event as an RT, student, or department support staff member. Emotional or physiologic implications experienced by respondents as SVs included anxiety 39.1% (61/156), reliving of the event 36.5% (57/156), sleeplessness 32.1% (50/156), and guilt 28.2% (44/156). Following a stressful clinical event, 14.8% (22/149) experienced psychological distress, 14.2% (21/148) experienced physical distress, 17.7% (26/147) indicated lack of institutional support, and 15.6% (23/147) indicated turnover intentions. Enhanced resilience and growth were reported by 9.5% (14/147). Clinical and non-clinical events were reported as possible triggers for SVEs. Nearly half of respondents 49.4% (77/156) indicated feeling like an SV due to events related to COVID-19. Peer support was the highest ranked form of desired support following an SVE by 57.7% (90/156). CONCLUSIONS: RTs are involved in stressful or traumatic clinical events, resulting in psychological/physical distress and turnover intentions. The COVID-19 pandemic has had a significant impact on RTs' SVEs, highlighting the importance of addressing the SV phenomenon among this population.