Re-imagining the future state of the ventricular assist device controller interface through human-centered design.

BACKGROUND: Ventricular assist devices (VADs) are effective therapy for patients with end-stage heart failure. Current VAD controllers offer improved interactivity, yet limitations of the visual, tactile, and auditory interface persist that impact patient experience and quality of life (QoL). This study explores how VAD controllers can be redesigned using a human-centered design approach to enhance the emotional and functional experience of the device for patients. METHODS: VAD patients (n = 21), caregivers (n = 4) and healthcare practitioners (n = 24) were interviewed to uncover design opportunities. From this, a series of realistic scenarios to design for emerged. A "design by analogy" method took inspiration from existing consumer products to ideate new functionality for the VAD wearable system, creating concepts for a controller interface and paired wearable device. An additional 15 patients and 2 caregivers were engaged to explore current VAD controller experiences and evaluate the future-state concepts. RESULTS: This research validated the need for increased automation and emergency functionality in VAD controllers, including remote monitoring of data, accurate communication of battery status, and automated medical alerts for critical device alarms. "Manage my health," "Feeling normal," "Social belonging," "Feeling safe," and "Sense of control" emerged as key patient concerns to be met by future VAD controller designs. CONCLUSIONS: The study demonstrated an innovative and relevant approach to improve usability of future VAD peripherals. By considering both emotional and functional perspectives in the design of lifesaving medical devices such as VADs, device manufacturers can uncover new opportunities to improve patient QoL through improved user experiences.

COVID-19 vaccine confidence, concerns, and uptake in children aged 5 and older in Calgary, Alberta: a longitudinal cohort study.

Objectives: Beginning early in the pandemic, there was a worldwide effort to develop effective vaccines against the SARS-CoV-2 virus. Before and after the approval and implementation of vaccines, there were concerns about their need as well as their safety and rapid development. We explored child demographic characteristics and parental concerns to identify factors associated with the decision to vaccinate. Methods: A cohort of 1035 children from Calgary was assembled in 2020 to participate in 5 visits every 6 months for survey completion and blood sampling for SARS-CoV-2 antibodies. Visits 1 to 2 occurred before approval of vaccines for children; Visits 3 to 5 occurred after vaccine approval for different age groups. We described vaccine concerns and utilized logistic regression to examine factors associated with the decision to vaccinate in children ≥5 years of age. Results: Children ≥12 years of age, of non-white or non-black ethnicity, and who had received previous influenza vaccines had higher odds of being vaccinated against SARS-CoV-2. Children with previous SARS-CoV-2 infection had lower odds of being vaccinated. The most common concerns in early 2021 were about vaccine safety. By summer 2022, the most common concern was a belief that vaccines were not necessary. Through the study 88% of children were vaccinated. Conclusions: Age, ethnicity, previous infections, and vaccine attitudes were associated with parental decision to vaccinate against SARS-CoV-2. For children who remained unvaccinated, parents continued to have safety concerns and questioned the necessity of the vaccine. Complacency about the need for vaccination may be more challenging to address and overcome than concerns about safety alone.

Substrate Electronics Dominate the Rate of Reductive Dehalogenation Promoted by the Flavin-Dependent Iodotyrosine Deiodinase.

Iodotyrosine deiodinase (IYD) is unusual in its reliance on flavin to promote reductive dehalogenation of halotyrosines under aerobic conditions. Applications of this activity can be envisioned for bioremediation, but expansion of its specificity requires an understanding of the mechanistic steps that limit the rate of turnover. Key processes capable of controlling steady-state turnover have now been evaluated and described in this study. While proton transfer is necessary for converting the electron-rich substrate into an electrophilic intermediate suitable for reduction, kinetic solvent deuterium isotope effects suggest that this process does not contribute to the overall efficiency of catalysis under neutral conditions. Similarly, reconstituting IYD with flavin analogues demonstrates that a change in reduction potential by as much as 132 mV affects kcat by less than 3-fold. Furthermore, kcat/Km does not correlate with reduction potential and indicates that electron transfer is also not rate determining. Catalytic efficiency is most sensitive to the electronic nature of its substrates. Electron-donating substituents on the ortho position of iodotyrosine stimulate catalysis and conversely electron-withdrawing substituents suppress catalysis. Effects on kcat and kcat/Km range from 22- to 100-fold and fit a linear free-energy correlation with a ρ ranging from -2.1 to -2.8 for human and bacterial IYD. These values are consistent with a rate-determining process of stabilizing the electrophilic and nonaromatic intermediate poised for reduction. Future engineering can now focus on efforts to stabilize this electrophilic intermediate over a broad series of phenolic substrates that are targeted for removal from our environment.

Developments and Applications of Functional Protein Microarrays.

Protein microarrays are crucial tools in the study of proteins in an unbiased, high-throughput manner, as they allow for characterization of up to thousands of individually purified proteins in parallel. The adaptability of this technology has enabled its use in a wide variety of applications, including the study of proteome-wide molecular interactions, analysis of post-translational modifications, identification of novel drug targets, and examination of pathogen-host interactions. In addition, the technology has also been shown to be useful in profiling antibody specificity, as well as in the discovery of novel biomarkers, especially for autoimmune diseases and cancers. In this review, we will summarize the developments that have been made in protein microarray technology in both in basic and translational research over the past decade. We will also introduce a novel membrane protein array, the GPCR-VirD array, and discuss the future directions of functional protein microarrays.

Dynamic thermal imaging confirms local but not fast systemic ABA responses.

Abscisic acid (ABA) signals regulating stomatal aperture and water loss are usually studied in detached leaves or isolated epidermal peels and at infrequent timepoints. Measuring stomatal ABA responses in attached leaves across a time course enables the study of stomatal behaviour in the physiological context of the plant. Infrared thermal imaging is often used to characterize steady-state stomatal conductance via comparisons of leaf surface temperature but is rarely used to capture stomatal responses over time or across different leaf surfaces. We used dynamic thermal imaging as a robust, but sensitive, tool to observe stomatal ABA responses in a whole plant context. We detected stomatal responses to low levels of ABA in both monocots and dicots and identified differences between the responses of different leaves. Using whole plant thermal imaging, stomata did not always behave as described previously for detached samples: in Arabidopsis, we found no evidence for fast systemic ABA-induced stomatal closure, and in barley, we observed no requirement for exogenous nitrate during ABA-induced stomatal closure. Thus, we recommend dynamic thermal imaging as a useful approach to complement detached sample assays for the study of local and systemic stomatal responses and molecular mechanisms underlying stomatal responses to ABA in the whole plant context.

Circularity of Lithium-Ion Battery Materials in Electric Vehicles.

Batteries have the potential to significantly reduce greenhouse gas emissions from on-road transportation. However, environmental and social impacts of producing lithium-ion batteries, particularly cathode materials, and concerns over material criticality are frequently highlighted as barriers to widespread electric vehicle adoption. Circular economy strategies, like reuse and recycling, can reduce impacts and secure regional supplies. To understand the potential for circularity, we undertake a dynamic global material flow analysis of pack-level materials that includes scenario analysis for changing battery cathode chemistries and electric vehicle demand. Results are produced regionwise and through the year 2040 to estimate the potential global and regional circularity of lithium, cobalt, nickel, manganese, iron, aluminum, copper, and graphite, although the analysis is focused on the cathode materials. Under idealized conditions, retired batteries could supply 60% of cobalt, 53% of lithium, 57% of manganese, and 53% of nickel globally in 2040. If the current mix of cathode chemistries evolves to a market dominated by NMC 811, a low cobalt chemistry, there is potential for 85% global circularity of cobalt in 2040. If the market steers away from cathodes containing cobalt, to an LFP-dominated market, cobalt, manganese, and nickel become less relevant and reach circularity before 2040. For each market to benefit from the recovery of secondary materials, recycling and manufacturing infrastructure must be developed in each region.

Bingeing, Purging, and Suicidal Ideation in Clinical and Non-Clinical Samples of Youth.

Suicidal ideation is a serious mental health concern reported by adolescents. Despite understanding of increased suicidal ideation in patients with eating disorders (EDs) and obesity, few studies have compared how disordered eating (bingeing, vomiting and over exercising) is associated with suicidal ideation in clinical and non-clinical samples of youth across the ED and weight spectrum. The present study aimed to 1) comparatively examine rates of suicidal ideation and disordered eating behaviors in clinical samples of youth with EDs, complex obesity, or from the community, and 2) examine whether disordered eating was associated with suicidal ideation above and beyond age, body mass index, diagnosis, treatment-seeking status, and depressive symptoms in large samples of males vs. females in an attempt to understand whether these behaviors should lead to concern regarding suicidal ideation. Data from charts on treatment-seeking adolescents diagnosed with either an ED (N = 315), severe complex obesity (N = 212), and from the community (N = 3036) were pooled together for comparative purposes. Results showed that suicidal ideation was higher in youth seeking treatment for an ED (50.2%) and obesity (23.7%) as compared to youth from the community (13%). Binary logistic regression analyses revealed that vomiting (OR = 1.73 for females, 8.17 for males) and over-exercising (OR = 1.47 for females, 1.68 for males) was significantly associated with suicidal ideation in both males and females. Findings underscore the importance of screening for suicidal ideation in youth who report vomiting or over-exercising despite diagnostic presentation, age, weight, or treatment setting.

Implementation Science: Incorporating Obstructive Sleep Apnea Screening and Capnography Into Everyday Practice.

PURPOSE: This article describes the implementation and maintenance of obstructive sleep apnea (OSA) screening and capnography monitoring. DESIGN: A quality improvement project. METHODS: A multidisciplinary team provided staff education to three perianesthesia care units. Using the STOP-Bang screening tool, five or more positive responses indicated high risk for OSA. A postanesthesia care unit audit tool tracked STOP-Bang scores, capnography use, hypoventilation events, nursing interventions, and respiratory complications. FINDINGS: Among 314 patients with OSA, 36% were identified as high risk. Nurses used capnography on 76% of OSA patients and were able to readily identify hypoventilation and intervene. Respiratory complications occurred in 10.8% (n = 34) requiring a higher level of care. Postimplementation, all six postanesthesia care units employ this best practice. CONCLUSIONS: Perianesthesia nurses found OSA screening and capnography easy to incorporate into nursing practice. This process can reduce respiratory complications in the surgical patient with OSA. An Evidence-Based Practice Fellowship Program facilitated this practice change.

Reduced stomatal density in bread wheat leads to increased water-use efficiency.

Wheat is a staple crop, frequently cultivated in water-restricted environments. Improving crop water-use efficiency would be desirable if grain yield can be maintained. We investigated whether a decrease in wheat stomatal density via the manipulation of epidermal patterning factor (EPF) gene expression could improve water-use efficiency. Our results show that severe reductions in stomatal density in EPF-overexpressing wheat plants have a detrimental outcome on yields. However, wheat plants with a more moderate reduction in stomatal density (i.e. <50% reduction in stomatal density on leaves prior to tillering) had yields indistinguishable from controls, coupled with an increase in intrinsic water-use efficiency. Yields of these moderately reduced stomatal density plants were also comparable with those of control plants under conditions of drought and elevated CO2. Our data demonstrate that EPF-mediated control of wheat stomatal development follows that observed in other grasses, and we identify the potential of stomatal density as a tool for breeding wheat plants that are better able to withstand water-restricted environments without yield loss.

Reducing Stomatal Density in Barley Improves Drought Tolerance without Impacting on Yield.

The epidermal patterning factor (EPF) family of secreted signaling peptides regulate the frequency of stomatal development in model dicot and basal land plant species. Here, we identify and manipulate the expression of a barley (Hordeum vulgare) ortholog and demonstrate that when overexpressed HvEPF1 limits entry to, and progression through, the stomatal development pathway. Despite substantial reductions in leaf gas exchange, barley plants with significantly reduced stomatal density show no reductions in grain yield. In addition, HvEPF1OE barley lines exhibit significantly enhanced water use efficiency, drought tolerance, and soil water conservation properties. Our results demonstrate the potential of manipulating stomatal frequency for the protection and optimization of cereal crop yields under future drier environments.

Effectiveness of a Multifaceted Delirium Screening, Prevention, and Treatment Initiative on the Rate of Delirium Falls in the Acute Care Setting.

Delirium is a potentially modifiable fall risk factor, but few studies address the effects of delirium programs on falls. Beginning in 2011, we implemented a nursing-driven hospitalwide delirium program targeting improvements in risk identification, prevention, detection, and treatment. Over the course of the program, delirium falls decreased from 0.91 to 0.50 per patient day (P = .0002). A decrease in overall falls was also noted (P = .0007).

Implications of Parasites Lacking Plasmodium falciparum Histidine-Rich Protein 2 on Malaria Morbidity and Control When Rapid Diagnostic Tests Are Used for Diagnosis.

Background: Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most using antibodies against Plasmodium falciparum histidine-rich protein 2 (PfHRP2). Reports of P. falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality-assured microscopy. Methods: An agent-based stochastic simulation model of P. falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases. The model considered parasites with normal, reduced, or no PfHRP2, and diagnosis using PfHRP2-only or combination RDTs. Results: Use of PfHRP2-only RDTs in communities where a PfHRP2-negative parasite was introduced during the simulation resulted in transmission of the parasite in >80% of cases, compared with <30% for normal or PfHRP2-reduced parasites. Using PfHRP2-only RDTs in the presence of PfHRP2-negative parasites caused an increase in prevalence, reduced RDT positivity within symptomatic patients but no change in the number of antimalarial treatments due to false-negative RDT results. Diagnosis with PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs did not select for PfHRP2-negative parasites. Conclusions: The use of PfHRP2-only RDTs is sufficient to select P. falciparum parasites lacking this protein, thus posing a significant public health problem, which could be moderated by using PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs.

Charting the electric vehicle battery reuse and recycling network in North America.

As electric vehicle (EV) sales grow across the world, a common question arises: "what happens to the batteries?" Using expert elicitation, this study identifies the current pathways for retired EV batteries in the United States and Canada and anticipates how the network might evolve in the future. The majority of end-of-life (EOL) EVs are currently managed within the manufacturer and dealership network, but more will enter the independent afterlife market as growing volumes reach EOL out-of-warranty. The interviews indicate that safety, transportation, and accessible information about battery composition and remaining capacity are critical issues across sectors. Participants demonstrated a strong commitment to creating a closed-loop value chain, motivating novel partnerships between recyclers and producers. At the same time, the value of EOL batteries as a material supply source may create competition between recycling and repurposing in the short term. State and federal governments are implementing policies to facilitate access to information and incentivize domestic manufacturing, but compared to other countries, the US lacks a mechanism to ensure that batteries will be collected and recycled. In addition, there is no national tracking system that would provide more robust data on LIB management. Multiple participants noted that the network handles the majority of EOL batteries without significant policy intervention. However, at present, the system depends the economics of reuse and recycling when accounting for the cost of collection and processing, which creates a risk of stranded batteries and/or wasted materials for packs that are lower-value or difficult to access.

Increased Elastase and Matrix Metalloproteinase Levels in the Pulmonary Arteries of Infants With Congenital Diaphragmatic Hernia.

BACKGROUND: Pulmonary vascular disease (PVD) complicated with pulmonary hypertension (PH) is a leading cause of mortality in congenital diaphragmatic hernia (CDH). Unfortunately, CDH patients are often resistant to PH therapy. Using the nitrogen CDH rat model, we previously demonstrated that CDH-associated PVD involves an induction of elastase and matrix metalloproteinase (MMP) activities, increased osteopontin and epidermal growth factor (EGF) levels, and enhanced smooth muscle cell (SMC) proliferation. Here, we aimed to determine whether the levels of the key members of this proteinase-induced pathway are also elevated in the pulmonary arteries (PAs) of CDH patients. METHODS: Neutrophil elastase (NE), matrix metalloproteinase-2 (MMP-2), epidermal growth factor (EGF), tenascin-C, and osteopontin levels were assessed by immunohistochemistry in the PAs from the lungs of 11 CDH patients and 5 normal age-matched controls. Markers of proliferation (proliferating cell nuclear antigen (PCNA)) and apoptosis (cleaved (active) caspase-3) were also used. RESULTS: While expressed by both control and CDH lungs, the levels of NE, MMP-2, EGF, as well as tenascin-C and osteopontin were significantly increased in the PAs from CDH patients. The percentage of PCNA-positive PA SMCs were also enhanced, while those positive for caspase-3 were slightly decreased. CONCLUSIONS: These results suggest that increased elastase and MMPs, together with elevated tenascin-C and osteopontin levels in an EGF-rich environment may contribute to the PVD in CDH infants. The next step of this study is to expand our analysis to a larger cohort, and determine the potential of targeting this pathway for the treatment of CDH-associated PVD and PH. TYPE OF STUDY: Therapeutic. LEVEL OF EVIDENCE: LEVEL III.

Optimizing Crop Plant Stomatal Density to Mitigate and Adapt to Climate Change.

Plants take up carbon dioxide, and lose water, through pores on their leaf surfaces called stomata. We have a good understanding of the biochemical signals that control the production of stomata, and over the past decade, these have been manipulated to produce crops with fewer stomata. Crops with abnormally low stomatal densities require less water to produce the same yield and have enhanced drought tolerance. These "water-saver" crops also have improved salinity tolerance and are expected to have increased resistance to some diseases. We calculate that the widespread adoption of water-saver crops could lead to reductions in greenhouse gas emissions equivalent to a maximum of 0.5 GtCO2/yr and thus could help to mitigate the impacts of climate change on agriculture and food security through protecting yields in stressful environments and requiring fewer inputs.

An Artificial Neural Network for Nasogastric Tube Position Decision Support.

Purpose: To develop and validate a deep learning model for detection of nasogastric tube (NGT) malposition on chest radiographs and assess model impact as a clinical decision support tool for junior physicians to help determine whether feeding can be safely performed in patients (feed/do not feed). Materials and Methods: A neural network ensemble was pretrained on 1 132 142 retrospectively collected (June 2007-August 2019) frontal chest radiographs and further fine-tuned on 7081 chest radiographs labeled by three radiologists. Clinical relevance was assessed on an independent set of 335 images. Five junior emergency medicine physicians assessed chest radiographs and made feed/do not feed decisions without and with artificial intelligence (AI)-generated NGT malposition probabilities placed above chest radiographs. Decisions from the radiologists served as ground truths. Model performance was evaluated using receiver operating characteristic analysis. Agreement between junior physician and radiologist decision was determined using the Cohen κ coefficient. Results: In the testing set, the ensemble achieved area under the receiver operating characteristic curve values of 0.82 (95% CI: 0.78, 0.86), 0.77 (95% CI: 0.71, 0.83), and 0.98 (95% CI: 0.96, 1.00) for satisfactory, malpositioned, and bronchial positions, respectively. In the clinical evaluation set, mean interreader agreement for feed/do not feed decisions among junior physicians was 0.65 ± 0.03 (SD) and 0.77 ± 0.13 without and with AI support, respectively. Mean agreement between junior physicians and radiologists was 0.53 ± 0.05 (unaided) and 0.65 ± 0.09 (AI-aided). Conclusion: A simple classifier for NGT malposition may help junior physicians determine the safety of feeding in patients with NGTs.Keywords: Neural Networks, Feature Detection, Supervised Learning, Machine Learning Supplemental material is available for this article. Published under a CC BY 4.0 license.

A longitudinal seroepidemiology study to evaluate antibody response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Canada from July 2020 to April 2022: Alberta COVID-19 Childhood Cohort (AB3C) Study.

BACKGROUND: Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. This study aimed to estimate the serologic response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Alberta over a two-year period. METHODS: Children with or without prior SARS-CoV-2 infections, were enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records. RESULTS: 1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrolment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% of all infected children after more than 200 days post diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated infected children after more than 200 days post diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children. CONCLUSIONS: In our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children, but just over one-half of unvaccinated children, had SARS-CoV-2 spike antibodies indicating infection and/or vaccination, highlighting the benefit of vaccination. It is not yet known whether a high proportion of seropositivity at the present time predicts sustained population-level protection against future SARS-CoV-2 transmission, infection or severe COVID-19 outcomes in children.

Congenital SARS-CoV-2 Infection in Two Neonates with Confirmation by Viral Culture of the Placenta in One Case.

Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.

Enhancing climate change resilience in agricultural crops.

Climate change threatens global food and nutritional security through negative effects on crop growth and agricultural productivity. Many countries have adopted ambitious climate change mitigation and adaptation targets that will exacerbate the problem, as they require significant changes in current agri-food systems. In this review, we provide a roadmap for improved crop production that encompasses the effective transfer of current knowledge into plant breeding and crop management strategies that will underpin sustainable agriculture intensification and climate resilience. We identify the main problem areas and highlight outstanding questions and potential solutions that can be applied to mitigate the impacts of climate change on crop growth and productivity. Although translation of scientific advances into crop production lags far behind current scientific knowledge and technology, we consider that a holistic approach, combining disciplines in collaborative efforts, can drive better connections between research, policy, and the needs of society.