Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to Fio2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/Fio2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.

Monoamine oxidase B activatable red fluorescence probe for bioimaging in cells and zebrafish.

A real-time and specific for the detection of Monoamine Oxidase B (MAO-B) to investigate the MAO-B-relevant disease development and treatment process is urgently desirable. Here, we utilized MAO-B to catalyze the conversion of propylamino groups to aldehyde groups, which was then quickly followed by a ß-elimination process to produce fluorescent probes (FNJP) that may be used to detect MAO-B in vitro and in vivo. The FNJP probe possesses unique properties, including favorable reactivity (Km = 10.8 µM), high cell permeability, and NIR characteristics (λem = 610 nm). Moreover, the FNJP probe showed high selectivity for MAO-B and was able to detect endogenous MAO-B levels from a mixed population of NIH-3 T3 and HepG2 cells. MAO-B expression was found to be increased in cells under lipopolysaccharide-stimulated cellular oxidative stress in neuronal-like SH-SY5Y cells. In addition, the visualization of FNJP for MAO-B activity in zebrafish can be an effective tool for exploring the biofunctions of MAO-B. Considering these excellent properties, the FNJP probe may be a powerful tool for detecting MAO-B levels in living organisms and can be used for accurate clinical diagnoses of related diseases.

Through the lens: A qualitative exploration of nurses' experiences of smart glasses in urgent care.

AIM: To investigate the real-world experiences of nurses' using smart glasses to triage patients in an urgent care centre. DESIGN: A parallel convergent mixed-method design. METHODS: We collected data through twelve in-depth interviews with nurses using the device and a survey. Recruitment continued until no new themes emerged. We coded the data using a deductive-thematic approach. Qualitative and survey data were coded and then mapped to the most dominant dimension of the sociotechnical framework. Both the qualitative and quantitative findings were triangulated within each dimension of the framework to gain a comprehensive understanding of user experiences. RESULTS: Overall, nurses were satisfied with using smart glasses in urgent care and would recommend them to others. Nurses rated the device highly on ease of use, facilitation of training and development, nursing empowerment and communication. Qualitatively, nurses generally felt the device improved workflows and saved staff time. Conversely, technological challenges limited its use, and users questioned its sustainability if inadequate staffing could not be resolved. CONCLUSION: Smart glasses enhanced urgent care practices by improving workflows, fostering staff communication, and empowering healthcare professionals, notably providing development opportunities for nurses. While smart glasses offered transformative benefits in the urgent care setting, challenges, including technological constraints and insufficient organisational support, were barriers to sustained integration. IMPLICATIONS FOR PRACTICE: These real-world insights encompass both the benefits and challenges of smart glass utilisation in the context of urgent care. The findings will help inform greater workflow optimisation and future technological developments. Moreover, by sharing these experiences, other healthcare institutions looking to implement smart glass technology can learn from the successes and barriers encountered, facilitating smoother adoption, and maximising the potential benefits for patient care. REPORTING METHOD: COREQ checklist (consolidated criteria for reporting qualitative research). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Natural clues to danger: attachment behavior in threatening situations.

A fundamental principle of attachment theory is that threatening situations give rise to individual differences in the extent to which people seek proximity to close others. The current research examines the way in which attachment styles predict individual differences in attachment-relevant behavior during threatening events. We tested alternative theoretical perspectives concerning the association between adult attachment (specifically, attachment avoidance) and attachment behavior in the presence of natural clues to danger by observing couples (N = 204) when they were watching horror vs. control film excerpts. Results suggest that highly avoidant people engaged in less attachment behavior across both threatening and non-threatening situations. These findings have implications for the understanding of attachment-related processes and how working models of the self and others facilitate (or inhibit) the expression of attachment behavior.

Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants.

BACKGROUND: Existing pharmacogenetic algorithms cannot fully explain warfarin dose variability in all patients. CYP2C9*13 is an important allelic variant in the Han Chinese population. However, adjustment of warfarin dosing in CYP2C9*13 variant carriers remains unclear. To the best of our knowledge, this study is the first to assess the effects of adjusting warfarin dosages in Han Chinese patients harbouring CYP2C9*13 variants. METHODS: In total, 971 warfarin-treated Han Chinese patients with atrial fibrillation were enrolled in this study. Clinical data were collected, and CYP2C9*2, *3, *13 and VKORC1-1639 G > A variants were genotyped. We quantitatively analysed the effect of CYP2C9*13 on warfarin maintenance dose and provided multiplicative adjustments for CYP2C9*13 using validated pharmacogenetic algorithms. RESULTS: Approximately 0.6% of the Han Chinese population carried CYP2C9*13 variant, and the genotype frequency was between those of CYP2C9*2 and CYP2C9*3. The warfarin maintenance doses were significantly reduced in CYP2C9*13 carriers. When CYP2C9*13 variants were not considered, the pharmacogenetic algorithms overestimated warfarin maintenance doses by 1.03-1.16 mg/d on average. The actual warfarin dose in CYP2C9*13 variant carriers was approximately 40% lower than the algorithm-predicted dose. Adjusting the warfarin-dosing algorithm according to the CYP2C9*13 allele could reduce the dose prediction error. CONCLUSION: Our study showed that the algorithm-predicted doses should be lowered for CYP2C9*13 carriers. Inclusion of the CYP2C9*13 variant in the warfarin-dosing algorithm tends to predict the warfarin maintenance dose more accurately and improves the efficacy and safety of warfarin administration in Han Chinese patients.

Implementation of a Real-Time Object Pick-and-Place System Based on a Changing Strategy for Rapidly-Exploring Random Tree.

An object pick-and-place system with a camera, a six-degree-of-freedom (DOF) robot manipulator, and a two-finger gripper is implemented based on the robot operating system (ROS) in this paper. A collision-free path planning method is one of the most fundamental problems that has to be solved before the robot manipulator can autonomously pick-and-place objects in complex environments. In the implementation of the real-time pick-and-place system, the success rate and computing time of path planning by a six-DOF robot manipulator are two essential key factors. Therefore, an improved rapidly-exploring random tree (RRT) algorithm, named changing strategy RRT (CS-RRT), is proposed. Based on the method of gradually changing the sampling area based on RRT (CSA-RRT), two mechanisms are used in the proposed CS-RRT to improve the success rate and computing time. The proposed CS-RRT algorithm adopts a sampling-radius limitation mechanism, which enables the random tree to approach the goal area more efficiently each time the environment is explored. It can avoid spending a lot of time looking for valid points when it is close to the goal point, thus reducing the computing time of the improved RRT algorithm. In addition, the CS-RRT algorithm adopts a node counting mechanism, which enables the algorithm to switch to an appropriate sampling method in complex environments. It can avoid the search path being trapped in some constrained areas due to excessive exploration in the direction of the goal point, thus improving the adaptability of the proposed algorithm to various environments and increasing the success rate. Finally, an environment with four object pick-and-place tasks is established, and four simulation results are given to illustrate that the proposed CS-RRT-based collision-free path planning method has the best performance compared with the other two RRT algorithms. A practical experiment is also provided to verify that the robot manipulator can indeed complete the specified four object pick-and-place tasks successfully and effectively.

Supply chain optimisation for recycling and remanufacturing sustainable management in end-of-life vehicles: A mini-review and classification.

End-of-life vehicles (ELV) management is becoming a global concern in the automotive industry. However, there is still limited study on supply chain optimisation that focusses on specific ELV treatments. Therefore, this mini-review article analyses the supply chain optimisation for recycling and remanufacturing sustainable management in ELV. A total of 51 papers were reviewed from the year 2016 to 2021. The key topics in each article were assessed and classified into various themes, followed by the content analysis. The percentage breakdown for the six main themes are ELV recovery management system (37.25%), reverse logistic network design (29.41%), ELV economy analysis (15.69%), government regulation or subsidies (7.84%), ELV quantity forecast (5.88%) and ELV part design (3.92%). It can be concluded that ELV recovery management and reverse logistic network design are the top two key focusses of supply chain optimisation priorities that have been extensively applied to improve ELV development. The literature gap has shown that the study on remanufacturing in the ELV supply chain is minimal compared to recycling. The classification of ELV recycling and remanufacturing supply chain optimisation in this study will be beneficial in supporting real-life problem-solving for industrial applications. This study serves as a valuable reference guide to identifying more sustainable solutions in ELV management and promoting the critical focus area for academicians and industry players.

End-of-life vehicles research development in Malaysia: a comprehensive review with the integrated conceptual model of innovative sustainable manufacturing elements.

The end-of-life vehicles (ELV) issue has become an essential topic in the fast-growing automotive industry. This study utilizes comprehensive content analysis to critically review the recent ELV research developments and underpinning issues in Malaysia. Fifty relevant ELV studies in Malaysia from the year 2006 to 2021 are selected and categorized based on three innovative sub-elements (product, process, system) of sustainable manufacturing. The literature review findings show that sustainable product recovery and recyclability issues in ELV treatments are still a major concern. Current studies overlook specific research on sustainable and integrated processes for ELV treatment. There is still lack of detailed ELV implementation framework equipped with the documented procedures and appropriate industrial practices in the ELV ecosystem to optimize the ELV supply chain. ELV policy is yet to be enacted in Malaysia, and public awareness of ELV is still low. There is inadequate alignment in ELV research developments with the current National Automotive Policy 2020 in Malaysia. The proposed integrated conceptual model will provide an extensive overview for scholars, policy-makers, and ELV stakeholders to implement appropriate actions to improve present ELV businesses in line with the public readiness to enact the potential ELV directives or legislation in Malaysia.

Ethylene glycol metabolism in the poly(ethylene terephthalate)-degrading bacterium Ideonella sakaiensis.

Poly(ethylene terephthalate) (PET)-degrading bacterium Ideonella sakaiensis produces hydrolytic enzymes that convert PET, via mono(2-hydroxyethyl) terephthalate (MHET), into the monomeric compounds, terephthalic acid (TPA), and ethylene glycol (EG). Understanding PET metabolism is critical if this bacterium is to be engineered for bioremediation and biorecycling. TPA uptake and catabolism in I. sakaiensis have previously been studied, but EG metabolism remains largely unexplored despite its importance. First, we identified two alcohol dehydrogenases (IsPedE and IsPedH) and one aldehyde dehydrogenase (IsPedI) in I. sakaiensis as the homologs of EG metabolic enzymes in Pseudomonas putida KT2440. IsPedE and IsPedH exhibited EG dehydrogenase activities with Ca2+ and a rare earth element (REE) Pr3+, respectively. We further found an upregulated dehydrogenase gene when the bacterium was grown on EG, whose gene product (IsXoxF) displays a minor EG dehydrogenase activity with Pr3+. IsPedE displayed a similar level of activity toward various alcohols. In contrast, IsPedH was more active toward small alcohols, whereas IsXoxF was the opposite. Structural analysis with homology models revealed that IsXoxF had a larger catalytic pocket than IsPedE and IsPedH, which could accommodate relatively bulkier substrates. Pr3+ regulated the protein expression of IsPedE negatively; IsPedH and IsXoxF were positively regulated. Taken together, these results indicated that the combination of IsPedH and IsXoxF complements the function of IsPedE in the presence of REEs. IsPedI exhibited dehydrogenase activity toward various aldehydes with the highest activity toward glycolaldehyde. This study demonstrated a unique alcohol oxidation pathway of I. sakaiensis, which could be efficient in EG utilization. KEY POINTS: • IsPedH and IsXoxF complement IsPedE function in the presence of REEs. • IsPedI displayed the highest dehydrogenase activity toward glycolaldehyde. • Unique alcohol oxidation pathway of I. sakaiensis identified for EG utilization.

Neurodevelopmental outcomes in neonatal extracorporeal membrane oxygenation survivors: An institutional perspective.

AIM: To describe the neurodevelopmental outcomes following extracorporeal membrane oxygenation (ECMO) in early infancy. METHODS: Thirty-seven patients who had survived following ECMO support from 2008 to 2018 had their neurodevelopmental outcomes assessed and analysed using the Bayley Scales of Infant and Toddler Development. Developmental outcome was defined as impairment in any of the developmental domains of motor function, cognition and language with mild impairment being 1-2 standard deviations below the test mean, moderate being 2-3 standard deviations below and severe being greater than 3 standard deviations below. RESULTS: Of these 37 patients, the median age at admission to Paediatric Intensive Care Unit was 0.4 months (interquartile range 2.8 months) with all of the study patients having an underlying diagnosis of congenital cardiac disease and 37/40 (92.5%) ECMO runs occurring in the immediate post-operative period. Of the 29 patients who had had follow-up at 12 months of age or older, 3 (10.3%) had severe impairment, 4 (13.8%) had moderate impairment, 12 (41.3%) had mild impairment and 10 (34.5%) had no impairment. Gross motor function was most significantly impacted in 18/29 (62.1%) patients, of which 7/18 (38.9%) had severe impairment. This was followed by impairment of receptive language in 8/29 (27.6%) patients and expressive language in 6/29 (20.1%) patients. CONCLUSIONS: One in four infants undergoing ECMO treatment in early infancy has moderate to severe neurodevelopmental impairment. Gross motor and language are the most affected developmental domains.

Population Segmentation Based on Healthcare Needs: Validation of a Brief Clinician-Administered Tool.

BACKGROUND: As populations age with increasingly complex chronic conditions, segmenting populations into clinically meaningful categories of healthcare and related service needs can provide healthcare planners with crucial information to optimally meet needs. However, while conventional approaches typically involve electronic medical records (EMRs), such records do not always capture information reliably or accurately. OBJECTIVE: We describe the inter-rater reliability and predictive validity of a clinician-administered tool, the Simple Segmentation Tool (SST) for categorizing older individuals into one of six Global Impression (GI) segments and eight complicating factors (CFs) indicative of healthcare and related social needs. DESIGN: Observational study ( ClinicalTrials.gov , number NCT02663037). PARTICIPANTS: Patients aged 55 years and above. MAIN MEASURES: Emergency department (ED) subjects (between May and June 2016) had baseline SST assessment by two physicians and a nurse concurrently seeing the same individual. General medical (GM) ward subjects (February 2017) had a SST assessment by their principal physician. Adverse events (ED visits, hospitalizations, and mortality over 90 days from baseline) were determined by a blinded reviewer. Inter-rater reliability was measured using Cohen's kappa. Predictive validity was evaluated using Cox hazard ratios based on time to first adverse event. KEY RESULTS: Cohen's kappa between physician-physician, service physician-nurse, and physician-nurse pairs for GI were 0.60, 0.71, and 0.68, respectively. Cox analyses demonstrated significant predictive validity of GI and CFs for adverse outcomes. CONCLUSIONS: With modest training, clinicians can complete a brief instrument to segment their patient into clinically meaningful categories of healthcare and related service needs. This approach can complement and overcome current limitations of EMR-based instruments, particularly with respect to whole-patient care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02663037.

Enhancing mentoring experiences through e-mentoring: a systematic scoping review of e-mentoring programs between 2000 and 2017.

Mentoring is suffering from a shortage of trained mentors which compromise the efficacy of novice mentoring or mentoring between a senior clinician and a junior clinician. E-mentoring is proposed as a means of supplementing this dominant form of mentoring in medicine by providing accessible, timely and longitudinal support for mentees. However, with little is known about e-mentoring nor its role in a blended mentoring approach, a systematic scoping review is proposed to evaluate these gaps in understanding in order to better understand e-mentoring and assess the viability of employing e-mentoring practice to support novice mentoring. Using Arksey and O'Malley's (Int J Soc Res Methodol 8(1):19-32, 2005) approach, 5 reviewers carried out independent literature reviews of e-mentoring as an adjuvant to novice mentoring in PubMed, Embase, PsycINFO, ERIC, Cochrane Database of Systematic Reviews, Google Scholar, Scopus, GreyLit, OpenGrey, and Web of Science databases. Braun and Clarke's (Qual Res Psychol 3(2):77-101, 2006) thematic analysis approach was used to thematically analyse accounts of e-mentoring across different settings. 6557 abstracts were identified, 109 full text articles were reviewed, and 18 articles were included and thematically analysed. The themes identified include definitions, role, stages, processes, platforms, evaluation, and relationships in e-mentoring. The themes identified provide a clinically relevant definition of e-mentoring, and in highlighting the similarities in the phases of novice and e-mentoring reaffirms the validity of a blended approach as a means of addressing shortfalls in mentoring in medicine.

Do healthcare needs-based population segments predict outcomes among the elderly? Findings from a prospective cohort study in an urbanized low-income community.

BACKGROUND: A rapidly ageing population with increasing prevalence of chronic disease presents policymakers the urgent task of tailoring healthcare services to optimally meet changing needs. While healthcare needs-based segmentation is a promising approach to efficiently assessing and responding to healthcare needs at the population level, it is not clear how available schemes perform in the context of community-based surveys administered by non-medically trained personnel. The aim of this prospective cohort, community setting study is to evaluate 4 segmentation schemes in terms of practicality and predictive validity for future health outcomes and service utilization. METHODS: A cohort was identified from a cross-sectional health and social characteristics survey of Singapore public rental housing residents aged 60 years and above. Baseline survey data was used to assign individuals into segments as defined by 4 predefined population segmentation schemes developed in Singapore, Delaware, Lombardy and North-West London. From electronic data records, mortality, hospital admissions, emergency department visits, and specialist outpatient clinic visits were assessed for 180 days after baseline segment assignment and compared to segment membership for each segmentation scheme. RESULTS: Of 1324 residents contacted, 928 agreed to participate in the survey (70% response). All subjects could be assigned an exclusive segment for each segmentation scheme. Individuals in more severe segments tended to have lower quality of life as assessed by the EQ-5D Index for health utility. All population segmentation schemes were observed to exhibit an ability to differentiate different levels of mortality and healthcare utilization. CONCLUSIONS: It is practical to assign individuals to healthcare needs-based population segments through community surveys by non-medically trained personnel. The resulting segments for all 4 schemes evaluated in this way have an ability to predict health outcomes and utilization over the medium term (180 days), with significant overlap for some segments. Healthcare needs-based segmentation schemes which are designed to guide action hold particular promise for promoting efficient allocation of services to meet the needs of salient population groups. Further evaluation is needed to determine if these schemes also predict responsiveness to interventions to meet needs implied by segment membership.

Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats.

CONTEXT: Rivaroxaban and ticagrelor are two common drugs for the treatment of atrial fibrillation and acute coronary syndrome. However, the drug-drug interaction between them is still unknown. OBJECTIVE: To investigate the effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats both in vivo and in vitro. MATERIALS AND METHODS: A sensitive and reliable UPLC-MS/MS method was developed for the determination of rivaroxaban in rat plasma. Ten Sprague-Dawley rats were randomly divided into ticagrelor pre-treated group (10 mg/kg/day for 14 days) and control group. The pharmacokinetics of orally administered rivaroxaban (10 mg/kg, single dose) with or without ticagrelor pre-treatment was investigated with developed UPLC-MS/MS method. Additionally, Sprague-Dawley rat liver microsomes were also used to investigate the drug-drug interaction between these two drugs in vitro. RESULTS: The C max (221.34 ± 53.33 vs. 691.18 ± 238.31 ng/mL) and the AUC(0-t) (1060.97 ± 291.21 vs. 3483.03 ± 753.83 µg·h/L) of rivaroxaban increased significantly (p < 0.05) with ticagrelor pre-treatment. The MRT(0-∞) of rivaroxaban increased from 4.41 ± 0.79 to 5.97 ± 1.11 h, while the intrinsic clearance decreased from 9.93 ± 2.55 to 2.89 ± 0.63 L/h/kg (both p < 0.05) after pre-treated with ticagrelor. Enzyme kinetic study indicated that ticagrelor decreased rivaroxaban metabolic clearance with the IC50 value of 14.04 µmol/L. CONCLUSIONS: Our in vivo and in vitro results demonstrated that there is a drug-drug interaction between ticagrelor and rivaroxaban in rats. Further studies need to be carried out to verify whether similar interactions truly apply in humans and whether these interactions have clinical significance.

Educational roles as a continuum of mentoring's role in medicine - a systematic review and thematic analysis of educational studies from 2000 to 2018.

BACKGROUND: Recent studies have gone to great lengths to differentiate mentoring from teaching, tutoring, role modelling, coaching and supervision in efforts to better understand mentoring processes. This review seeks to evaluate the notion that teaching, tutoring, role modelling, coaching and supervision may in fact all be part of the mentoring process. To evaluate this theory, this review scrutinizes current literature on teaching, tutoring, role modelling, coaching and supervision to evaluate their commonalities with prevailing concepts of novice mentoring. METHODS: A three staged approach is adopted to evaluate this premise. Stage one involves four systematic reviews on one-to-one learning interactions in teaching, tutoring, role modelling, coaching and supervision within Internal Medicine, published between 1st January 2000 and 31st December 2018. Braun and Clarke's (2006) approach to thematic analysis was used to identify key elements within these approaches and facilitate comparisons between them. Stage two provides an updated view of one-to-one mentoring between a senior physician and a medical student or junior doctor to contextualise the discussion. Stage three infuses mentoring into the findings delineated in stage one. RESULTS: Seventeen thousand four hundred ninety-nine citations were reviewed, 235 full-text articles were reviewed, and 104 articles were thematically analysed. Four themes were identified - characteristics, processes, nature of relationship, and problems faced in each of the four educational roles. CONCLUSIONS: Role modelling, teaching and tutoring, coaching and supervision lie within a mentoring spectrum of increasingly structured interactions, assisted by assessments, feedback and personalised support that culminate with a mentoring approach. Still requiring validation, these findings necessitate a reconceptualization of mentoring and changes to mentor training programs and how mentoring is assessed and supported.