Dynamic mortality prediction in critically Ill children during interhospital transports to PICUs using explainable AI.

Critically ill children who require inter-hospital transfers to paediatric intensive care units are sicker than other admissions and have higher mortality rates. Current transport practice primarily relies on early clinical assessments within the initial hours of transport. Real-time mortality risk during transport is lacking due to the absence of data-driven assessment tools.

Estrogen and testosterone secretion from the mouse brain.

Estrogen and testosterone are typically thought of as gonadal or adrenal derived steroids that cross the blood brain barrier to signal via both rapid nongenomic and slower genomic signalling pathways. Estrogen and testosterone signalling has been shown to drive interlinked behaviours such as social behaviours and cognition by binding to their cognate receptors in hypothalamic and forebrain nuclei. So far, acute brain slices have been used to study short-term actions of 17β-estradiol, typically using electrophysiological measures.

Can critical care transport be safely reduced in children intubated during emergency management of status epilepticus in the United Kingdom: a national audit with case-control analysis.

Objective: This study describes the baseline clinical characteristics, predictors of successful extubation at referring hospitals and short-term outcomes of children intubated for status epilepticus and referred to United Kingdom (UK) paediatric critical care transport teams (PCCTs).

Design: Multicentre audit with case-control analysis, conducted between 1 September 2018 and 1 September 2020.

Setting: This study involved 10 UK PCCTs.

Does kisspeptin exert a local modulatory effect on bovine ovarian steroidogenesis?

Kisspeptin, a hypothalamic neuropeptide encoded by the KISS1 gene, has a pivotal role in promoting GnRH secretion in mammals. Kisspeptin and its receptor (KISS1R) are also expressed in certain peripheral tissues including gonads, suggesting intra-gonadal roles. Such actions at the level of the bovine ovary have not been explored previously.

COVID-19: trainee perspectives from unprecedented changes on the Paediatric Intensive Care Unit (PICU).

During the coronavirus disease 2019 (COVID-19) global pandemic, there has been a need to develop surge capacity. Since the disease is uncommon in children, working on a paediatric intensive care unit (PICU) has required an expansion of roles and responsibilities outside established confines. The most drastic change in practice involved having to care for both critically ill adults and children side by side on the PICU.

A Hybrid Model of Pediatric and Adult Critical Care During the Coronavirus Disease 2019 Surge: The Experience of Two Tertiary Hospitals in London and New York.

Objectives: The current novel severe acute respiratory syndrome coronavirus 2 outbreak has caused an unprecedented demand on global adult critical care services. As adult patients have been disproportionately affected by the coronavirus disease 2019 pandemic, pediatric practitioners world-wide have stepped forward to support their adult colleagues. In general, standalone pediatric hospitals expanded their capacity to centralize pediatric critical care, decanting patients from other institutions.

Mitigating Latent Threats Identified through an Embedded Simulation Program and Their Comparison to Patient Safety Incidents: A Retrospective Review.

Objective: To assess the impact of service improvements implemented because of latent threats (LTs) detected during simulation.

Design: Retrospective review from April 2008 to April 2015.

Setting: Paediatric Intensive Care Unit in a specialist tertiary hospital.

Transcriptomal profiling of bovine ovarian granulosa and theca interna cells in primary culture in comparison with their in vivo counterparts.

In vitro culture of ovarian granulosa cells and theca cells has been very important for our understanding of their function and regulation. One of the most eagerly sought attributes of cell culture is the use of chemically-defined conditions. However, even under such in vitro conditions cell behaviour could differ from the in vivo situation because of differences in oxygen tension, nutrients, adhesion matrix and other factors.

Factors associated with high heterogeneity of malaria at fine spatial scale in the Western Kenyan highlands.

Background: The East African highlands are fringe regions between stable and unstable malaria transmission. What factors contribute to the heterogeneity of malaria exposure on different spatial scales within larger foci has not been extensively studied. In a comprehensive, community-based cross-sectional survey an attempt was made to identify factors that drive the macro- and micro epidemiology of malaria in a fringe region using parasitological and serological outcomes.

The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial.

Background: Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities.

Spatial Patterns of Plasmodium falciparum Clinical Incidence, Asymptomatic Parasite Carriage and Anopheles Density in Two Villages in Mali.

Heterogeneity in malaria exposure is most readily recognized in areas with low-transmission patterns. By comparison, little research has been done on spatial patterns in malaria exposure in high-endemic settings. We determined the spatial clustering of clinical malaria incidence, asymptomatic parasite carriage, and Anopheles density in two villages in Mali exposed to low- and mesoendemic-malaria transmission.

The global effect of follicle-stimulating hormone and tumour necrosis factor α on gene expression in cultured bovine ovarian granulosa cells.

Background: Oocytes mature in ovarian follicles surrounded by granulosa cells. During follicle growth, granulosa cells replicate and secrete hormones, particularly steroids close to ovulation. However, most follicles cease growing and undergo atresia or regression instead of ovulating.

Ovarian expression of insulin-like peptide 3 (INSL3) and its receptor (RXFP2) during development of bovine antral follicles and corpora lutea and measurement of circulating INSL3 levels during synchronized estrous cycles.

Insulin-like peptide 3 (INSL3), a major product of testicular Leydig cells, is also expressed by the ovary, but its functional role remains poorly understood. Here, we quantified expression of INSL3 and its receptor RXFP2 in theca interna cell (TIC) and granulosa cell compartments of developing bovine antral follicles and in corpora lutea (CL). INSL3 and RXFP2 mRNA levels were much higher in TIC than granulosa cell and increased progressively during follicle maturation with INSL3 peaking in large (11-18 mm) estrogen-active follicles and RXFP2 peaking in 9- to 10-mm follicles before declining in larger (11-18 mm) follicles.

Functional link between bone morphogenetic proteins and insulin-like peptide 3 signaling in modulating ovarian androgen production.

Bone morphogenetic proteins (BMPs) are firmly implicated as intra-ovarian regulators of follicle development and steroidogenesis. Here we report a microarray analysis showing that treatment of cultured bovine theca cells (TC) with BMP6 significantly (>twofold; P < 0.01) up- or down-regulated expression of 445 genes.

The anti-epileptic drug valproic acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro.

Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells maintained under conditions that preserve their 'follicular' phenotype.

Bak-Sneppen-type models and rank-driven processes.

The Bak-Sneppen model is a well-known stochastic model of evolution that exhibits self-organized criticality; only a few analytical results have been established for it so far. We report a surprising connection between Bak-Sneppen-type models and more tractable Markov processes that evolve without any reference to an underlying topology. Specifically, we show that in the case of a large number of species, the long time behavior of the fitness profile in the Bak-Sneppen model can be replicated by a model with a purely rank-based update rule whose asymptotics can be studied rigorously.

Changes in expression of bone morphogenetic proteins (BMPs), their receptors and inhibin co-receptor betaglycan during bovine antral follicle development: inhibin can antagonize the suppressive effect of BMPs on thecal androgen production.

We reported previously that bone morphogenetic proteins (BMPs) potently suppress CYP17 expression and androgen production by bovine theca interna cells (TC) in vitro. In this study, real-time PCR was used to analyse gene expression in TC and granulosa cell (GC) layers from developing bovine antral follicles (1-18 mm). Abundance of mRNA transcripts for four BMPs (BMP2, BMP4, BMP6, and BMP7) and associated type I (BMPR1A, BMPR1B, ACVR1 and ACVR1B) and type II (BMPR2, ACVR2A and ACVR2B) receptors showed relatively modest, though significant, changes during follicle development.

Evidence for an inhibitory role of bone morphogenetic protein(s) in the follicular-luteal transition in cattle.

Bone morphogenetic proteins (BMPs) and their receptors are expressed in ovarian theca cells (TC) and granulosa cells (GC) and BMPs have been implicated in the regulation of several aspects of follicle development including thecal androgen production and granulosal oestrogen production. Their potential involvement in luteal function has received less attention. In this study, we first compared relative abundance of mRNA transcripts for BMPs, activin-betaA and BMP/activin receptors in bovine corpus luteum (CL) and follicular theca and granulosa layers before undertaking functional in vitro experiments to test the effect of selected ligands (BMP6 and activin A) on luteinizing bovine TC and GC.

Bone morphogenetic protein-6 enhances gonadotrophin-dependent progesterone and inhibin secretion and expression of mRNA transcripts encoding gonadotrophin receptors and inhibin/activin subunits in chicken granulosa cells.

The aims were to examine ovarian expression of bone morphogenetic protein (BMP) ligands/receptor mRNAs in the chicken and to test the hypothesis that theca-derived BMP(s) modulates granulosa cell function in a paracrine manner. RT-PCR revealed expression of multiple BMPs in granulosa and theca cells from pre hierarchical and preovulatory follicles with greater expression in theca cells; both cell types expressed BMP receptors-IA, -IB and -II consistent with tissue responsiveness. Preovulatory granulosa cells (F1, F2 and F3/4) were cultured with BMP-6 (expressed by theca but not granulosa) in the presence/absence of LH, FSH or 8-Br-cAMP.

Gonadotrophins modulate hormone secretion and steady-state mRNA levels for activin receptors (type I, IIA, IIB) and inhibin co-receptor (betaglycan) in granulosa and theca cells from chicken prehierarchical and preovulatory follicles.

Ovarian follicle development is regulated through endocrine and local mechanisms. Increasing evidence indicates roles for transforming growth factor beta superfamily members, including inhibins and activins. We recently identified divergent expression of mRNAs encoding activin receptors (ActR) and inhibin co-receptor betaglycan in chicken follicles at different stages of maturation.

Precocious puberty because of a pancreatic neuroectodermal tumor.

Primitive neuroectodermal tumors (PNETs) are uncommon, representing approximately 1% of all sarcomas. Pancreatic PNETs have been reported only 12 times in the literature. This report presents the first case of a patient with a PNET exhibiting precocious puberty.

Bovine follicle development is associated with divergent changes in activin-A, inhibin-A and follistatin and the relative abundance of different follistatin isoforms in follicular fluid.

The aim was to determine whether follicle growth in cattle is accompanied by changes in levels of inhibin-A (inh-A), activin-A (act-A) and different Mr isoforms of follistatin (FS) in bovine follicular fluid (bFF), reflecting differential roles of these proteins during folliculogenesis. Follicles (n = 146) from 2-20 mm diameter were dissected from ovaries of approximately 40 cattle. Immunoassays were used to measure total FS, act-A, inh-A, oestradiol (E) and progesterone (P) levels; immunoblotting was used to quantify the relative abundance of different FS isoforms.

Bone morphogenetic proteins (BMP) -4, -6, and -7 potently suppress basal and luteinizing hormone-induced androgen production by bovine theca interna cells in primary culture: could ovarian hyperandrogenic dysfunction be caused by a defect in thecal BMP signaling?

We reported recently that bovine theca interna cells in primary culture express several type-I and type-II receptors for bone morphogenetic proteins (BMPs). The same cells express at least two potential ligands for these receptors (BMP-4 and -7), whereas bovine granulosa cells and oocytes express BMP-6. Therefore, BMPs of intrafollicular origin may exert autocrine/paracrine actions to modulate theca cell function.