Machine Learning Approaches to Determine Feature Importance for Predicting Infant Autopsy Outcome

Introduction: Sudden unexpected death in infancy (SUDI) represents the commonest presentation of postneonatal death. We explored whether machine learning could be used to derive data driven insights for prediction of infant autopsy outcome. Methods: A paediatric autopsy database containing >7,000 cases, with >300 variables, was analysed by examination stage and autopsy outcome classified as ‘explained (medical cause of death identified)’ or ‘unexplained’. Decision tree, random forest, and gradient boosting models were iteratively trained and evaluated. Results: Data from 3,100 infant and young child (<2 years) autopsies were included. Naïve decision tree using external examination data had performance of 68% for predicting an explained death. Core data items were identified using model feature importance. The most effective model was XG Boost, with overall predictive performance of 80%, demonstrating age at death, and cardiovascular and respiratory histological findings as the most important variables associated with determining medical cause of death. Conclusion: This study demonstrates feasibility of using machine-learning to evaluate component importance of complex medical procedures (paediatric autopsy) and highlights value of collecting routine clinical data according to defined standards. This approach can be applied to a range of clinical and operational healthcare scenario

Intraoperative anti-A/B immunoadsorption is associated with significantly reduced blood product utilization with similar outcomes in pediatric ABO-incompatible heart transplantation

BACKGROUND: Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible heart transplantation. Here we report the first case series of patients transplanted with ABO-IA, and compare outcomes with those undergoing plasma exchange facilitated ABO-incompatible heart transplantation (ABO-PE). METHODS: Data were retrospectively analysed on all ABO-incompatible heart transplants undertaken at a single centre between January 1, 2000 and June 1, 2020. Data included all routine laboratory tests, demographics and pre-operative characteristics, intraoperative details and post-operative outcomes. Primary outcome measures were volume of blood product transfusions, maximum post-transplant isohaemagglutinin titres, occurrence of rejection and graft survival. Secondary outcome measures were length of intensive care and hospital stay. Demographic and survival data were also obtained for ABO-compatible transplants during the same time period for comparison. RESULTS: Thirty-seven patients underwent ABO-incompatible heart transplantation, with 27 (73%) using ABO-PE and 10 (27%) using ABO-IA. ABO-IA patients were significantly older than ABO-PE patients (p < 0.001) and the total volume of blood products transfused during the hospital admission was significantly lower (164 [126-212] ml/kg vs 323 [268-379] ml/kg, p < 0.001). No significant differences were noted between methods in either pre or post-transplant maximum isohaemagglutinin titres, incidence of rejection, length of intensive care or total hospital stay. Survival comparison showed no significant difference between antibody reduction methods, or indeed ABO-compatible transplants (p = 0.6). CONCLUSIONS: This novel technique appears to allow a significantly older population than typical to undergo ABO-incompatible heart transplantation, as well as significantly reducing blood product utilization. Furthermore, intraoperative anti-A/B immunoadsorption does not demonstrate increased early post-transplant isohaemagglutinin accumulation or rates of rejection compared to ABO-PE. Early survival is equivalent between ABO-IA, ABO-PE and ABO-compatible heart transplantation

Fourth ventricle tumors in children: complications and influence of surgical approach

OBJECTIVES: The goal of this study was to characterize the complications and morbidity related to the surgical management of pediatric fourth ventricle tumors. / METHODS: All patients referred to the authors’ institution with posterior fossa tumors from 2002 to 2018 inclusive were screened to include only true fourth ventricle tumors. Preoperative imaging and clinical notes were reviewed to extract data on presenting symptoms; surgical episodes, techniques, and adjuncts; tumor histology; and postoperative complications. / RESULTS: Three hundred fifty-four children with posterior fossa tumors were treated during the study period; of these, 185 tumors were in the fourth ventricle, and 167 fourth ventricle tumors with full data sets were included in this analysis. One hundred patients were male (mean age ± SD, 5.98 ± 4.12 years). The most common presenting symptom was vomiting (63.5%). The most common tumor types, in order, were medulloblastoma (94 cases) > pilocytic astrocytoma (30 cases) > ependymoma (30 cases) > choroid plexus neoplasms (5 cases) > atypical teratoid/rhabdoid tumor (4 cases), with 4 miscellaneous lesions. Of the 67.1% of patients who presented with hydrocephalus, 45.5% had an external ventricular drain inserted (66.7% of these prior to tumor surgery, 56.9% frontal); these patients were more likely to undergo ventriculoperitoneal shunt (VPS) placement at a later date (p = 0.00673). Twenty-two had an endoscopic third ventriculostomy, of whom 8 later underwent VPS placement. Overall, 19.7% of patients had a VPS sited during treatment. Across the whole series, the transvermian approach was more frequent than the telovelar approach (64.1% vs 33.0%); however, the telovelar approach was significantly more common in the latter half of the series (p < 0.001). Gross-total resection was achieved in 70.7%. The most common postoperative deficit was cerebellar mutism syndrome (CMS; 28.7%), followed by new weakness (24.0%), cranial neuropathy (18.0%), and new gait abnormality/ataxia (12.6%). Use of intraoperative ultrasonography significantly reduced the incidence of CMS (p = 0.0365). There was no significant difference in the rate of CMS between telovelar or transvermian approaches (p = 0.745), and multivariate logistic regression modeling did not reveal any statistically significant relationships between CMS and surgical approach. / CONCLUSIONS: Surgical management of pediatric fourth ventricle tumors continues to evolve, and resection is increasingly performed through the telovelar route. CMS is enduringly the major postoperative complication in this patient population

Rapid desensitization through immunoadsorption during cardiopulmonary bypass. A novel method to facilitate human leukocyte antigen incompatible heart transplantation

Background: Anti-human leukocyte antigen (HLA)-antibody production represents a major barrier to heart transplantation, limiting recipient compatibility with potential donors and increasing the risk of complications with poor waiting-list outcomes. Currently there is no consensus to when desensitization should take place, and through what mechanism, meaning that sensitized patients must wait for a compatible donor for many months, if not years. We aimed to determine if intraoperative immunoadsorption could provide a potential desensitization methodology. Methods: Anti-HLA antibody-containing whole blood was added to a Cardiopulmonary bypass (CPB) circuit set up to mimic a 20 kg patient undergoing heart transplantation. Plasma was separated and diverted to a standalone, secondary immunoadsorption system, with antibody-depleted plasma returned to the CPB circuit. Samples for anti-HLA antibody definition were taken at baseline, when combined with the CPB prime (on bypass), and then every 20 min for the duration of treatment (total 180 min). Results: A reduction in individual allele median fluorescence intensity (MFI) to below clinically relevant levels (4000 was demonstrated. Reduction occurred in all cases within 120 min, demonstrating efficacy in a time period usual for heart transplantation. Flowcytometric crossmatching of suitable pseudo-donor lymphocytes demonstrated a change from T cell and B cell positive channel shifts to negative, demonstrating a reduction in binding capacity. Conclusions: Intraoperative immunoadsorption in an ex vivo setting demonstrates clinically relevant reductions in anti-HLA antibodies within the normal timeframe for heart transplantation. This method represents a potential desensitization technique that could enable sensitized children to accept a donor organ earlier, even in the presence of donor-specific anti-HLA antibodies

Impact of Scottish vocational qualifications on residential child care : have they fulfilled the promise?

This article will present findings from a doctoral study exploring the impact of 'SVQ Care: Promoting Independence (level III)' within children's homes. The study focuses on the extent to which SVQs enhance practice and their function within a 'learning society'. A total of 30 staff were selected from seven children's homes in two different local authority social work departments in Scotland. Each member of staff was interviewed on four separate occasions over a period of 9 months. Interviews were structured using a combination of repertory grids and questions. Particular focus was given to the assessment process, the extent to which SVQs enhance practice and the learning experiences of staff. The findings suggest that there are considerable deficiencies both in terms of the SVQ format and the way in which children's homes are structured for the assessment of competence. Rather than address the history of failure within residential care, it appears that SVQs have enabled the status quo to be maintained whilst creating an 'illusion' of change within a learning society

What is evidence required for and who generates that evidence in the Finnish Educational System?

Peer reviewe

Structural analysis of the Ss sialoglycoprotein specific for Henshaw blood group from human erythrocyte membranes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66122/1/j.1432-1033.1984.tb08155.x.pd

Population Genetics of GYPB and Association Study between GYPB*S/s Polymorphism and Susceptibility to P. falciparum Infection in the Brazilian Amazon

Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil.Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection.GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity.Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population

International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality

Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach

Scientific publishing and the reading of science in nineteenth-century Britain: a historiographical survey and guide to sources

[FIRST PARAGRAPH] It is now generally accepted that both the conception and practices of natural enquiry in the Western tradition underwent a series of profound developments in the late eighteenth and early nineteenth century—developments which have been variously characterized as a ‘second scientific revolution’ and, much more tellingly, as the ‘invention of science’. As several authors have argued, moreover, a crucial aspect of this change consisted in the distinctive audience relations of the new sciences. While eighteenth-century natural philosophy was distinguished by an audience relation in which, as William Whewell put it, ‘a large and popular circle of spectators and amateurs [felt] themselves nearly upon a level, in the value of their trials and speculations, with more profound thinkers’, the science which was invented in the late eighteenth and early nineteenth century was, as Simon Schaffer has argued, marked by the ‘emergence of disciplined, trained cadres of research scientists’ clearly distinguished from a wider, exoteric public. Similarly, Jan Golinski argues that the ‘emergence of new instrumentation and a more consolidated social structure for the specialist community’ for early nineteenth-century chemistry was intimately connected with the transformation in the role of its public audience to a condition of relative passivity. These moves were underpinned by crucial epistemological and rhetorical shifts—from a logic of discovery, theoretically open to all, to a more restrictive notion of discovery as the preserve of scientific ‘genius’, and from an open-ended philosophy of ‘experience’ to a far more restrictive notion of disciplined ‘expertise’. Both of these moves were intended to do boundary work, restricting the community active in creating and validating scientific knowledge, and producing a passive public