Real-world learnings for digital health industry-NHS collaboration: Life sciences vision in action.

Several publications have indicated potential benefit from collaboration with industry regarding wider use of anonymised routine NHS healthcare data. However, there is limited guidance regarding exactly how such collaborations between NHS hospitals and industry partners should best be carried out, and specific issues that need to be addressed at an individual project or collaboration level to achieve desired benefit. Specifically, routine health data are complex, not collected in a format optimised for secondary use, and often require interpretation based on clinical understanding of the medical conditions or patients. In order to address these issues, a formal partnership collaboration was established between an NHS organisation (Great Ormond Street Hospital for Children) and a pharmaceutical company (Roche Products Limited), to jointly understand the problems that require solving in order to maximise such use of NHS data to support improved patient outcomes and other patient/NHS benefit in a more sustainable way. We present the learnings from the first 2 years of the 5-year collaboration addressing aspects such as complexities of NHS Electronic Patient Record (EPR), data engineering and use of modern technology to optimise such data. Plus, the development of appropriate technology and data infrastructure within the NHS to support interoperability and prepare the NHS for wider application of artificial intelligence. We also highlight the staff skills and training needed to support such systems in the NHS, governance structures and processes needed to ensure appropriate use of tools and data and how best to co-design with patients, their families, and clinical teams. It is hoped that this review may provide useful information for both healthcare organisations and industry partners working towards the future of optimal use of data and technology for healthcare benefit.

Experiences with Negative Behavior and Incivility: Perspectives of Unlicensed Assistive Personnel and Registered Nurses.

Healthcare professionals experience negative behaviors such as incivility from various sources within the hospital environment. However, little is known regarding the experience of unlicensed assistive personnel with these behaviors. Using a cross-sectional survey design, the research team aimed to examine the presence, sources, and impact of negative behaviors among registered nurses and unlicensed assistive personnel within a US hospital. Descriptive and inferential statistics were used to analyze quantitative data, while thematic analysis was used to analyze the qualitative responses. A total of 309 participants completed the survey, and 135 participants responded to three qualitative questions. Most respondents identified inadequate staffing/resources to handle workload (87%) and job stress leading to loss of control over behavior as contributing factors to lateral/vertical aggression in the work environment (71%). Impacts of negative behavior on job performance were related to both personal well-being and the work environment. Demoralization was identified as a common consequence of negative behaviors for individuals and within the work environment. The results suggested that registered nurses, unlicensed assistive personnel, and nursing leadership may benefit from system-wide approaches addressing negative behaviors such as incivility within the clinical environment. Specifically, efforts and policies aimed at aiding clinicians in responding to negative behaviors could potentially improve the clinical environment.

Communicating exploratory unsupervised machine learning analysis in age clustering for paediatric disease.

BACKGROUND: Despite the increasing availability of electronic healthcare record (EHR) data and wide availability of plug-and-play machine learning (ML) Application Programming Interfaces, the adoption of data-driven decision-making within routine hospital workflows thus far, has remained limited. Through the lens of deriving clusters of diagnoses by age, this study investigated the type of ML analysis that can be performed using EHR data and how results could be communicated to lay stakeholders. METHODS: Observational EHR data from a tertiary paediatric hospital, containing 61 522 unique patients and 3315 unique ICD-10 diagnosis codes was used, after preprocessing. K-means clustering was applied to identify age distributions of patient diagnoses. The final model was selected using quantitative metrics and expert assessment of the clinical validity of the clusters. Additionally, uncertainty over preprocessing decisions was analysed. FINDINGS: Four age clusters of diseases were identified, broadly aligning to ages between: 0 and 1; 1 and 5; 5 and 13; 13 and 18. Diagnoses, within the clusters, aligned to existing knowledge regarding the propensity of presentation at different ages, and sequential clusters presented known disease progressions. The results validated similar methodologies within the literature. The impact of uncertainty induced by preprocessing decisions was large at the individual diagnoses but not at a population level. Strategies for mitigating, or communicating, this uncertainty were successfully demonstrated. CONCLUSION: Unsupervised ML applied to EHR data identifies clinically relevant age distributions of diagnoses which can augment existing decision making. However, biases within healthcare datasets dramatically impact results if not appropriately mitigated or communicated.

A patient-centered model of mental health care for trauma and minority stress in transgender and gender diverse people: A bottom-up network analysis.

Transgender and gender diverse (TGD) individuals are disproportionately exposed to traumatic and high-impact minority stressors which can produce an array of transdiagnostic symptoms. Some clinical presentations align well with established evidence-based treatments, but others may require patient-centered modifications or combined approaches to address treatment needs. In this study, we employed a novel, bottom-up approach to derive insights into preferred intervention strategies for a broad range of trauma- and TGD-minority stress-related expressions of clinical distress. Participants (18 TGD individuals, 16 providers) completed a q-sort task by first sorting cards featuring traumatic experiences and/or minority stressors and transdiagnostic psychiatric symptoms into groups based on perceived similarity. Next, participants sorted interventions they believed to be most relevant for addressing these concerns/symptoms. We overlayed networks of stressors and symptoms with intervention networks to evaluate preferred intervention strategies. TGD networks revealed transdiagnostic clustering of intervention strategies and uniquely positioned the expectancy of future harm as a traumatic stressor. Provider networks were more granular in structure; both groups surprisingly emphasized the role of self-defense as intervention. While both networks had high overlap, their discrepancies highlight patient perspectives that practical, material, and structural changes should occur alongside traditional clinical interventions.

Neurological diagnoses in hospitalized COVID-19 patients associated with adverse outcomes: A multinational cohort study.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.

John L. McNulty (1955-2023).

Dr. John L. McNulty, born on January 25, 1955, in Bartlesville, Oklahoma, passed away on October 31, 2023, in Tulsa, Oklahoma, at the age of 68 years. Ever the pragmatist and always bringing a critical mindset to test use, Dr. McNulty coauthored seminal articles demonstrating the absence of predictive bias among African Americans. His commitment to diversity more recently focused on contemporary assessment with transgender and gender-diverse individuals. While Dr. McNulty's empirical work advanced the field of personality and psychopathology, his relationships with colleagues and mentees are his most lasting legacy. Dr. McNulty inspired many while he was here, and his memory will inspire many into the future. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Exploring the Minnesota Multiphasic Personality Inventory (MMPI)-3 in a transgender and gender diverse sample.

Comparisons of transgender and gender diverse (TGD) individuals' mental health functioning with that of cisgender individuals rely almost exclusively on screening measures. The limited research with TGD individuals and omnibus assessment measures has primarily used previous iterations of the Minnesota Multiphasic Personality Inventories (MMPIs). This study sought to examine the psychometric functioning of the MMPI-3 with a TGD community sample (n = 97) and compare mean scores across TGD and cisgender subsamples. We expected MMPI-3 substantive scale reliability to be comparable across all samples and subsamples. Individual MMPI-3 scales were expected to demonstrate appropriate convergent and discriminant validity with relevant criterion measures in the TGD sample. Results generally supported MMPI-3 scale score reliability and validity with TGD individuals. Next, three sets of mean score comparisons were conducted across all MMPI-3 substantive scales: (a) TGD individuals not currently in mental health treatment and the MMPI-3 normative sample, (b) TGD individuals not currently in mental health treatment and TGD individuals currently in mental health treatment, and (c) TGD individuals currently in mental health treatment and an outpatient mental health sample. Fewer differences were found between TGD individuals in our sample who were not currently in mental health treatment and the MMPI-3 normative sample compared to previous work. This initial study indicates that MMPI-3 scales largely have appropriate psychometric properties when administered to a TGD sample and that the test may be helpful in identifying mental health needs of TGD individuals. Needs and directions for further research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

microRNA Expression Dynamics in Culicoides sonorensis Biting Midges Following Blood-Feeding.

Culicoides sonorensis midges vector multiple livestock arboviruses, resulting in significant economic losses worldwide. Due to the tight association between virus transmission, blood feeding, and egg development, understanding midge physiology is paramount to limiting pathogen transmission. Previous studies have demonstrated the importance of small non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), in multiple aspects of vector physiology. These small ncRNAs regulate gene expression at the post-transcriptional level and display differential expression during pathogen infection. Due to the lack of annotated miRNAs in the biting midge and associated expression profiles, we used small RNA-Seq and miRDeep2 analyses to determine the Culicoides miRNAs in whole females and midgut tissues in response to blood feeding. Our analyses revealed 76 miRNAs within C. sonorensis composed of 73 orthologous and three candidate novel miRNAs, as well as conserved miRNA clusters. miRNA conservation suggests an interesting evolutionary relationship between miRNA expression and hematophagy in the infraorder Culicomorpha. We also identified multiple blood meal-regulated and tissue-enriched miRNAs. Lastly, we further identified miRNAs with expression patterns potentially associated with virus infection by probing publicly available datasets. Together, our data provide a foundation for future ncRNA work to untangle the dynamics of gene regulation associated with midge physiology.

INKILN is a Novel Long Noncoding RNA Promoting Vascular Smooth Muscle Inflammation via Scaffolding MKL1 and USP10.

BACKGROUND: Activation of vascular smooth muscle cell (VSMC) inflammation is vital to initiate vascular disease. The role of human-specific long noncoding RNAs in VSMC inflammation is poorly understood. METHODS: Bulk RNA sequencing in differentiated human VSMCs revealed a novel human-specific long noncoding RNA called inflammatory MKL1 (megakaryoblastic leukemia 1) interacting long noncoding RNA (INKILN). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation as well as human atherosclerosis and abdominal aortic aneurysm. The transcriptional regulation of INKILN was verified through luciferase reporter and chromatin immunoprecipitation assays. Loss-of-function and gain-of-function studies and multiple RNA-protein and protein-protein interaction assays were used to uncover a mechanistic role of INKILN in the VSMC proinflammatory gene program. Bacterial artificial chromosome transgenic mice were used to study INKILN expression and function in ligation injury-induced neointimal formation. RESULTS: INKILN expression is downregulated in contractile VSMCs and induced in human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-κB (nuclear factor kappa B) site within its proximal promoter. INKILN activates proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway. INKILN depletion blocks interleukin-1ß-induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1 and the luciferase activity of an NF-κB reporter. Furthermore, INKILN knockdown enhances MKL1 ubiquitination through reduced physical interaction with the deubiquitinating enzyme USP10 (ubiquitin-specific peptidase 10). INKILN is induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in bacterial artificial chromosome transgenic mice. CONCLUSIONS: These findings elucidate an important pathway of VSMC inflammation involving an INKILN/MKL1/USP10 regulatory axis. Human bacterial artificial chromosome transgenic mice offer a novel and physiologically relevant approach for investigating human-specific long noncoding RNAs under vascular disease conditions.

Removal of polyvinylidene fluoride binder and other organics for enhancing the leaching efficiency of lithium and cobalt from black mass.

The agglomeration and encapsulation of recoverable materials of interest (e.g. metals and graphite) as a result of the presence of polyvinylidene fluoride (PVDF) in spent lithium-ion batteries (LIBs) with mixed chemistries (black mass) lower the extraction efficiency of metals. In this study, organic solvents and alkaline solutions were used as non-toxic reagents to investigate the removal of a PVDF binder from a black mass. The results demonstrated that 33.1%, 31.4%, and 31.4% of the PVDF were removed using dimethylformamide (DMF), dimethylacetamide (DMAc), and dimethyl sulfoxide (DMSO) at 150, 160, and 180 °C, respectively. Under these conditions, the peel-off efficiencies for DMF, DMAc, and DMSO were 92.9%, 85.3%, and approximately 92.9%, respectively. Using tetrabutylammonium bromide (TBAB) as a catalyst and 5 M sodium hydroxide (NaOH) at room temperature (RT- 21 °C-23 °C), 50.3% of PVDF and other organic compounds were eliminated. The removal efficiency was enhanced to approximately 60.5% when the temperature was raised to 80 °C using NaOH. Using 5 M potassium hydroxide at RT in a TBAB-containing solution, ca. 32.8% removal efficiency was obtained; raising the temperature to 80 °C further enhanced the removal efficiency to almost 52.7%. The peel-off efficiency was 100% for both alkaline solutions. Lithium extraction increased from 47.2% to 78.7% following treatment with DMSO and to 90.1% following treatment with NaOH via leaching black mass (2 M sulfuric acid, solid-to-liquid ratio (S/L): 100 g L-1 at 50 °C, for 1 h without a reducing agent) before and after removal of the PVDF binder. Cobalt's recovery went from 28.5% to 61.3% with DMSO treatment to 74.4% with NaOH treatment.

INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10.

Background: Activation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood. Methods: Bulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA called IN flammatory M K L1 I nteracting L ong N oncoding RNA ( INKILN ). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation of INKILN was determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role of INKILN in VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to study INKLIN expression and function in ligation injury-induced neointimal formation. Results: INKILN expression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-κB site within its proximal promoter. INKILN activates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically, INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway. INKILN depletion blocks ILIß-induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-κB reporter. Further, INKILN knockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10. INKILN is induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice. Conclusions: These findings elucidate an important pathway of VSMC inflammation involving an INKILN /MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.

A bottom-up approach to developing a unified trauma-minority stress model for transgender and gender diverse people.

OBJECTIVE: Transgender and gender diverse (TGD) people are at heightened risk of both Criterion A trauma exposure and other bias-related minority stressors (e.g., discrimination, rejection). In the absence of a unified trauma-minority stress theory, it remains unclear how to best conceptualize psychopathology for people who experience both trauma and minority stress. METHOD: Using a participant-driven q-sort methodology and network analytic approach, we analyzed card sort data from 18 TGD people and 16 providers with expertise in TGD care to derive thematic networks of trauma and minority stress experiences, as they connected to transdiagnostic symptoms (e.g., hyperarousal, avoidance). RESULTS: The TGD participants' resulting network illustrates conceptualizations of identity- and nonidentity-based Criterion A traumas as similar and only related to psychiatric symptoms via the shared connection through other minority stressors. The provider network was more granular, although the general pattern was consistent with TGD participants, demonstrating similar perceptions of how these experiences are associated. CONCLUSIONS: Evidence of inextricable links between trauma and psychiatric symptoms through the conduit of minority stressors lays the groundwork for novel, integrated models of trauma, minority stress, and their transdiagnostic symptom sequelae. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Generation and Comparative Analysis of an Itga8-CreER T2 Mouse with Preferential Activity in Vascular Smooth Muscle Cells.

All current smooth muscle cell (SMC) Cre mice similarly recombine floxed alleles in vascular and visceral SMCs. Here, we present an Itga8-CreER T2 knock-in mouse and compare its activity with a Myh11-CreER T2 mouse. Both Cre drivers demonstrate equivalent recombination in vascular SMCs. However, Myh11-CreER T2 mice, but not Itga8-CreER T2 mice, display high activity in visceral SMC-containing tissues such as intestine, show early tamoxifen-independent activity, and produce high levels of CreERT2 protein. Whereas Myh11-CreER T2 -mediated knockout of serum response factor (Srf) causes a lethal intestinal phenotype precluding analysis of the vasculature, loss of Srf with Itga8-CreER T2 (Srf Itga8 ) yields viable mice with no evidence of intestinal pathology. Male and female Srf Itga8 mice exhibit vascular contractile incompetence, and angiotensin II causes elevated blood pressure in wild type, but not Srf Itga8 , male mice. These findings establish the Itga8-CreER T2 mouse as an alternative to existing SMC Cre mice for unfettered phenotyping of vascular SMCs following selective gene loss.

Machine learning forecasting for COVID-19 pandemic-associated effects on paediatric respiratory infections.

OBJECTIVE: The COVID-19 pandemic and subsequent government restrictions have had a major impact on healthcare services and disease transmission, particularly those associated with acute respiratory infection. This study examined non-identifiable routine electronic patient record data from a specialist children's hospital in England, UK, examining the effect of pandemic mitigation measures on seasonal respiratory infection rates compared with forecasts based on open-source, transferable machine learning models. METHODS: We performed a retrospective longitudinal study of respiratory disorder diagnoses between January 2010 and February 2022. All diagnoses were extracted from routine healthcare activity data and diagnosis rates were calculated for several diagnosis groups. To study changes in diagnoses, seasonal forecast models were fit to prerestriction period data and extrapolated. RESULTS: Based on 144 704 diagnoses from 31 002 patients, all but two diagnosis groups saw a marked reduction in diagnosis rates during restrictions. We observed 91%, 89%, 72% and 63% reductions in peak diagnoses of 'respiratory syncytial virus', 'influenza', 'acute nasopharyngitis' and 'acute bronchiolitis', respectively. The machine learning predictive model calculated that total diagnoses were reduced by up to 73% (z-score: -26) versus expected during restrictions and increased by up to 27% (z-score: 8) postrestrictions. CONCLUSIONS: We demonstrate the association between COVID-19 related restrictions and significant reductions in paediatric seasonal respiratory infections. Moreover, while many infection rates have returned to expected levels postrestrictions, others remain supressed or followed atypical winter trends. This study further demonstrates the applicability and efficacy of routine electronic record data and cross-domain time-series forecasting to model, monitor, analyse and address clinically important issues.

Real-time associations between discrimination, cannabis use, and mood among sexual and gender minority individuals.

OBJECTIVE: Sexual and gender minority (SGM) individuals experience high rates of discrimination, which is associated with increased cannabis use. Studies have also linked daily SGM discrimination to event-based mood states, but none have examined the degree to which cannabis buffers or potentially exacerbates mood in response to discrimination in real time. METHOD: Fifty SGM individuals participated in a 2-week ecological momentary assessment study. Participants completed a baseline assessment and then received six daily prompts assessing SGM discrimination, cannabis use, and current mood. We investigated the immediate associations between SGM discrimination and mood, and how cannabis use differentially moderated these associations. RESULTS: SGM discrimination was associated with increased negative mood and decreased positive mood. Among those who experienced discrimination, individuals who used cannabis reported feeling less anxious and depressed, and happier and more relaxed, in the 2 hr following an SGM discrimination experience compared to those that did not use cannabis. CONCLUSIONS: These findings uncover some of the acute within-day effects of both daily SGM discrimination and cannabis use on mood. These findings build on the current understanding of minority stress, in real time, and suggest avenues for prevention, and intervention efforts to offset risk for psychological distress and cannabis use among SGM individuals who experience minority stress. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO).

INTRODUCTION: Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians' concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid-base abnormalities in children following kidney transplantation compared with current practice.The aim of the Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO) trial was to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte 148 compared with intravenous fluid currently administered. METHODS AND ANALYSIS: PLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of <135 mmol/L. Secondary outcomes include symptoms of acute hyponatraemia, other electrolyte and acid-base imbalances and transplant kidney function.The primary outcome will be analysed using a logistic regression model adjusting for donor type (living vs deceased donor), patient weight (<20 kg vs ≥20 kg pretransplant) and transplant centre as a random effect. ETHICS AND DISSEMINATION: The trial received Health Research Authority approval on 20 January 2020. Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain. TRIAL REGISTRATION NUMBERS: 2019-003025-22 and 16586164.

Classification Performance of Neural Networks Versus Logistic Regression Models: Evidence From Healthcare Practice.

Machine learning encompasses statistical approaches such as logistic regression (LR) through to more computationally complex models such as neural networks (NN). The aim of this study is to review current published evidence for performance from studies directly comparing logistic regression, and neural network classification approaches in medicine. A literature review was carried out to identify primary research studies which provided information regarding comparative area under the curve (AUC) values for the overall performance of both LR and NN for a defined clinical healthcare-related problem. Following an initial search, articles were reviewed to remove those that did not meet the criteria and performance metrics were extracted from the included articles. Teh initial search revealed 114 articles; 21 studies were included in the study. In 13/21 (62%) of cases, NN had a greater AUC compared to LR, but in most the difference was small and unlikely to be of clinical significance; (unweighted mean difference in AUC 0.03 (95% CI 0-0.06) in favour of NN versus LR. In the majority of cases examined across a range of clinical settings, LR models provide reasonable performance that is only marginally improved using more complex methods such as NN. In many circumstances, the use of a relatively simple LR model is likely to be adequate for real-world needs but in specific circumstances in which large amounts of data are available, and where even small increases in performance would provide significant management value, the application of advanced analytic tools such as NNs may be indicated.

Of mice and human-specific long noncoding RNAs.

The number of human LncRNAs has now exceeded all known protein-coding genes. Most studies of human LncRNAs have been conducted in cell culture systems where various mechanisms of action have been worked out. On the other hand, efforts to elucidate the function of human LncRNAs in an in vivo setting have been limited. In this brief review, we highlight some strengths and weaknesses of studying human LncRNAs in the mouse. Special consideration is given to bacterial artificial chromosome transgenesis and genome editing. The integration of these technical innovations offers an unprecedented opportunity to complement and extend the expansive literature of cell culture models for the study of human LncRNAs. Two different examples of how BAC transgenesis and genome editing can be leveraged to gain insight into human LncRNA regulation and function in mice are presented: the random integration of a vascular cell-enriched LncRNA and a targeted approach for a new LncRNA immediately upstream of the ACE2 gene, which encodes the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent underlying the coronavirus disease-19 (COVID-19) pandemic.