Vehicle Position Detection Based on Machine Learning Algorithms in Dynamic Wireless Charging.

Dynamic wireless charging (DWC) has emerged as a viable approach to mitigate range anxiety by ensuring continuous and uninterrupted charging for electric vehicles in motion. DWC systems rely on the length of the transmitter, which can be categorized into long-track transmitters and segmented coil arrays. The segmented coil array, favored for its heightened efficiency and reduced electromagnetic interference, stands out as the preferred option. However, in such DWC systems, the need arises to detect the vehicle's position, specifically to activate the transmitter coils aligned with the receiver pad and de-energize uncoupled transmitter coils. This paper introduces various machine learning algorithms for precise vehicle position determination, accommodating diverse ground clearances of electric vehicles and various speeds. Through testing eight different machine learning algorithms and comparing the results, the random forest algorithm emerged as superior, displaying the lowest error in predicting the actual position.

The ATM Ser49Cys Variant Effects ATM Function as a Regulator of Oncogene-Induced Senescence.

An apical component of the cell cycle checkpoint and DNA damage repair response is the ataxia-telangiectasia mutated (ATM) Ser/Thr protein kinase. A variant of ATM, Ser49Cys (rs1800054; minor allele frequency = 0.011), has been associated with an elevated risk of melanoma development; however, the functional consequence of this variant is not defined. ATM-dependent signalling in response to DNA damage has been assessed in a panel of patient-derived lymphoblastoid lines and primary human melanocytic cell strains heterozygous for the ATM Ser49Cys variant allele. The ATM Ser49Cys allele appears functional for acute p53-dependent signalling in response to DNA damage. Expression of the variant allele did reduce the efficacy of oncogene expression in inducing senescence. These findings demonstrate that the ATM 146C>G Ser49Cys allele has little discernible effect on the acute response to DNA damage but has reduced function observed in the chronic response to oncogene over-expression. Analysis of melanoma, naevus and skin colour genomics and GWAS analyses have demonstrated no association of this variant with any of these outcomes. The modest loss of function detected suggest that the variant may act as a modifier of other variants of ATM/p53-dependent signalling.

Mammary mechanobiology - investigating roles for mechanically activated ion channels in lactation and involution.

The ability of a mother to produce a nutritionally complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by mammary epithelial cells is adaptive, its release is exquisitely timed, and its own glandular stagnation with the permanent cessation of suckling triggers the cell death and tissue remodeling that enables female mammals to nurse successive progeny. Chemical and mechanical signals both play a role in this process. However, despite this duality of input, much remains unknown about the nature and function of mechanical forces in this organ. Here, we characterize the force landscape in the functionally mature gland and the capacity of luminal and basal cells to experience and exert force. We explore molecular instruments for force-sensing, in particular channel-mediated mechanotransduction, revealing increased expression of Piezo1 in mammary tissue in lactation and confirming functional expression in luminal cells. We also reveal, however, that lactation and involution proceed normally in mice with luminal-specific Piezo1 deletion. These findings support a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.

Multiscale imaging of basal cell dynamics in the functionally mature mammary gland.

The mammary epithelium is indispensable for the continued survival of more than 5,000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate the ejection of milk from alveolar units and its passage along the mammary ductal network. Using quantitative, multidimensional imaging of mammary cell ensembles from GCaMP6 transgenic mice, we reveal how stimulus evoked Ca2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca2+-dependent contractions generate the requisite force to physically deform the innermost layer of luminal cells, compelling them to discharge the fluid that they produced and housed. Through the collective action of thousands of these biological positive-displacement pumps, each linked to a contractile ductal network, milk begins its passage toward the dependent neonate, seconds after the command.

Intravenous prostanoids in systemic sclerosis-associated pulmonary arterial hypertension: a single-centre experience.

OBJECTIVES: The current study evaluates survival rates among SSc-associated pulmonary arterial hypertension (SSc-PAH) patients on i.v. prostanoids, and short-term impact of i.v. prostanoids on clinical and haemodynamic parameters. METHODS: Baseline demographics, invasive and non-invasive data, European Society of Cardiology (ESC) score and REVEAL score of 81 SSc-PAH patients (median age 61 years, interquartile range 54-67 years, 84% females) were prospectively recorded, from November 2006 till November 2020, before initiation of i.v. prostanoids, and at first formal reassessment. Survival data were retrieved from National Health Service Spine and hospital databases. RESULTS: Significant improvements in clinical and haemodynamic parameters in response to i.v. prostanoid therapy were documented. Functional class (FC) (16.6% improved by 1FC, P =0.041), mean pulmonary arterial pressure (-6.5 mmHg, P =0.036), pulmonary vascular resistance (-2.6 WU, P =0.012), cardiac index (Q/m2) (+0.7 l/min/m2, P =0.003) and mixed venous oxygen saturation (SvO2) (+3%, P =0.036) improved. Estimated survival for CTD-PAH patients on i.v. prostanoids was 64%, 31% and 18%, at 1 year, 3 years and 5 years, respectively. Independent baseline predictors of mortality were older age (HR: 1.043, 95% CI: 1.011-1.075, P =0.007), higher N-terminal pro-brain natriuretic peptide levels (HR: 2.191, 95% CI: 1.131-4.243, P =0.020), and lower SvO2 levels (HR: 0.962, 95% CI: 0.926-0.998, P =0.039). High ESC risk or high and very high REVEAL score was associated with significantly worse survival compared with patients with lower risk scores, both at baseline and when reassessed after a median of 6.5 months. CONCLUSIONS: Survival among SSc-PAH patients on i.v. prostanoids remains poor, risk scoring at baseline and after 6.5 months of therapy improves prognostication.

Limited resources restrict the provision of adequate neonatal respiratory care in the countries of Africa.

AIM: Over two thirds of newborn deaths occur in Africa and South Asia, and respiratory failure is a major contributor of these deaths. The exact availability of continuous positive airway pressure (CPAP) and surfactant in Africa is unknown. The aim of this study was to describe the availability of newborn respiratory care treatments in the countries of Africa. METHODS: Surveys, in English, French and Portuguese, were sent to neonatal leaders in all 48 continental countries and the two islands with populations over 1 million. RESULTS: Forty-nine (98%) countries responded. Twenty-one countries reported less than 50 paediatricians, and 12 countries had no neonatologists. Speciality neonatal nursing was recognised in 57% of countries. Most units were able to provide supplemental oxygen. CPAP was available in 63% and 67% of the most well-equipped government and private hospitals. Surfactant was available in 33% and 39% of the most well-equipped public and private hospitals, respectively. Availability of CPAP and surfactant was greatly reduced in smaller cities. Continuous oxygen saturation monitoring was only available in 33% of countries. CONCLUSION: The availability of proven life-saving interventions in Africa is inadequate. There is a need to sustainably improve availability and use of these interventions.

Anthropogenic habitat alteration leads to rapid loss of adaptive variation and restoration potential in wild salmon populations.

Phenotypic variation is critical for the long-term persistence of species and populations. Anthropogenic activities have caused substantial shifts and reductions in phenotypic variation across diverse taxa, but the underlying mechanism(s) (i.e., phenotypic plasticity and/or genetic evolution) and long-term consequences (e.g., ability to recover phenotypic variation) are unclear. Here we investigate the widespread and dramatic changes in adult migration characteristics of wild Chinook salmon caused by dam construction and other anthropogenic activities. Strikingly, we find an extremely robust association between migration phenotype (i.e., spring-run or fall-run) and a single locus, and that the rapid phenotypic shift observed after a recent dam construction is explained by dramatic allele frequency change at this locus. Furthermore, modeling demonstrates that continued selection against the spring-run phenotype could rapidly lead to complete loss of the spring-run allele, and an empirical analysis of populations that have already lost the spring-run phenotype reveals they are not acting as sustainable reservoirs of the allele. Finally, ancient DNA analysis suggests the spring-run allele was abundant in historical habitat that will soon become accessible through a large-scale restoration (i.e., dam removal) project, but our findings suggest that widespread declines and extirpation of the spring-run phenotype and allele will challenge reestablishment of the spring-run phenotype in this and future restoration projects. These results reveal the mechanisms and consequences of human-induced phenotypic change and highlight the need to conserve and restore critical adaptive variation before the potential for recovery is lost.

Melanoma mutations modify melanocyte dynamics in co-culture with keratinocytes or fibroblasts.

Melanocytic cell interactions are integral to skin homeostasis, and affect the outcome of multiple diseases, including cutaneous pigmentation disorders and melanoma. By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R/R variant strain and by NRAS.Q61K and BRAF.V600E expression, while expression of CDK4.R24C and RAC1.P29S had no detectable effect. Time-lapse tracking of melanocytes in co-culture revealed dynamic interaction phenotypes and hyper-motile cell states that indicated that, in addition to the known role in activating mitogenic signalling, MEK-pathway-activating mutations may also allow melanocytes to escape keratinocyte control and increase their invasive potential. Expanding this combinatorial platform will identify other therapeutic target mutations and melanocyte genetic variants, as well as increase understanding of skin cell interactions.

A Comparison of the Accuracy of Various Methods of Postnatal Gestational Age Estimation; Including Ballard Score, Foot Length, Vascularity of the Anterior Lens, Last Menstrual Period and Also a Clinician's Non-Structured Assessment.

INTRODUCTION: Gestational age is a strong determinant of neonatal mortality and morbidity. Early obstetric ultrasound is the clinical reference standard, but is not widely available in many developing countries. METHODS: A prospectively designed diagnostic accuracy study in a tertiary referral hospital in a developing country. Early ultrasound (<20 weeks) was the clinical reference standard. Methods evaluated included anthropometric measurements (including foot length), vascularity of the anterior lens, the New Ballard Score and last menstrual period. Clinicians' non-structured global impression 'End of Bed' Assessment was also evaluated. RESULTS: 106 babies were included in the study. Median age at birth was 34 weeks (interquartile range 29-36). Ballard Score and 'End of Bed' Assessment had a mean bias of -0.14 and 0.06 weeks respectively but wide 95% limits of agreement. The physical component of the Ballard score, the total Ballard score and Foot length's ability to discriminate between term and preterm infants gave an area under the receiver operating characteristics curve of 0.97, 0.96 and 0.95, respectively. DISCUSSION: Although 'End of Bed' Assessment and Ballard score had small mean biases, the wide confidence intervals render the methods irrelevant in clinical practice. Foot length was particularly poor in Small for Gestational Age infants. None of the methods studied were superior to a non-structured clinician's informal 'End of Bed' Assessment. CONCLUSION: None of the methods studied met the a priori definition of clinical usefulness. Improving access to early ultrasound remains a priority. Instead of focusing on chronological accuracy, future research should compare the ability of early ultrasound and Ballard score to predict morbidity and mortality. Lay summary. BACKGROUND: Gestational age describes the time interval between conception and the delivery of the baby. Babies born before 37 weeks of gestation (preterm) or after 42 weeks of gestation (post-dates) have an increased risk of death and specific illnesses. The best way to estimate the gestational age is to perform an ultrasound scan on the mother before 20 weeks. However, this is not widely available in many developing countries. Methods to estimate gestational age after birth include calculating the time from the last period, various measurements of the child (such as weight, foot length or head circumference) physical and neurological markers of maturity and examination of the blood vessels on the lens in the eye. METHODS: In this study, we assessed how accurate these methods were when compared with the best available method; early ultrasound. We also analyzed the clinicians own personal feeling of what the most likely gestation was, based on an informal 'end of bed' assessment. If a method was to be deemed clinically useful it was agreed that it would have to confidently identify the gestation to within 1 week of the true gestation. RESULTS: None of the methods studied could confidently predict the gestational age of individual babies within 1 week. Ballard scoring and the clinician's informal 'End of Bed' Assessment were the most accurate and also had the smallest inter-operator variability when the results of two separate researchers were compared. Foot length performed particularly badly with babies who were small for their gestational age. CONCLUSION: None of the methods studied confidently predicted gestational age within a week, so have little use in clinical practice. Access to early ultrasound should be improved. Further research into the relationship between maturity markers such as the Ballard score and the rates of death and specific premature related illnesses is warranted.

Patients' views about parathyroid transplantation for post-thyroidectomy hypoparathyroidism.

BACKGROUND: Permanent hypoparathyroidism (hypoPT) represents the most common postoperative complication associated with total thyroidectomy. Current treatment relies on high-dose calcium and/or vitamin D supplementation, but often this is insufficient and some patients remain symptomatic. Parathyroid allotransplantation is a new therapeutic option described recently in the literature. This study aims to investigate the patients' acceptability of parathyroid transplantation as a potential new treatment for hypoPT. METHOD: Online survey of members of HypoParaUK, a support group for individuals affected by hypoPT. RESULTS: Responses were received from 252 hypoPT patients. Majority declared to experience severe symptoms despite regular medical treatment. On a severity scale of 0-5, symptoms that were most troublesome were fatigue (3.8), low sense of well-being (3.5), and numbness/tingling (2.9). On a scale of 0-10, on average, their current quality of life (QoL) was 5 ± 3 and they expected this would improve to 7 ± 2 with correction of their hypoPT. Forty-four percent of patients were extremely interested in a potential technique involving intramuscular injection of parathyroid cell suspension compared to just 14% who were interested in the more invasive procedure of implantation of a parathyroid allograft into the forearm. The main concerns expressed were related to the possible need for immunosuppressive therapy. CONCLUSION: Patients with severe symptomatic hypoPT seem interested to consider participation in a clinical trial exploring the feasibility and success rate of parathyroid transplantation.

Self-Renewal and High Proliferative Colony Forming Capacity of Late-Outgrowth Endothelial Progenitors Is Regulated by Cyclin-Dependent Kinase Inhibitors Driven by Notch Signaling.

Since the discovery of endothelial colony forming cells (ECFC), there has been significant interest in their therapeutic potential to treat vascular injuries. ECFC cultures display significant heterogeneity and a hierarchy among cells able to give rise to high proliferative versus low proliferative colonies. Here we aimed to define molecularly this in vitro hierarchy. Based on flow cytometry, CD34 expression levels distinguished two populations. Only CD34 + ECFC had the capacity to reproduce high proliferative potential (HPP) colonies on replating, whereas CD34- ECFCs formed only small clusters. CD34 + ECFCs were the only ones to self-renew in stringent single-cell cultures and gave rise to both CD34 + and CD34- cells. Upon replating, CD34 + ECFCs were always found at the centre of HPP colonies and were more likely in G0/1 phase of cell cycling. Functionally, CD34 + ECFC were superior at restoring perfusion and better engrafted when injected into ischemic hind limbs. Transcriptomic analysis identified cyclin-dependent kinase (CDK) cell cycle inhibiting genes (p16, p21, and p57), the Notch signaling pathway (dll1, dll4, hes1, and hey1), and the endothelial cytokine il33 as highly expressed in CD34 + ECFC. Blocking the Notch pathway using a γ-secretase inhibitor (DAPT) led to reduced expression of cell cycle inhibitors, increased cell proliferation followed by a loss of self-renewal, and HPP colony formation capacity reflecting progenitor exhaustion. Similarly shRNA knockdown of p57 strongly affected self-renewal of ECFC colonies. ECFC hierarchy is defined by Notch signalling driving cell cycle regulators, progenitor quiescence and self-renewal potential.

Routine Antenatal Echocardiography in High-Prevalence Areas of Rheumatic Heart Disease: A WHO-Guideline Systematic Review.

Background: Rheumatic Heart Disease (RHD) is the most common cause of valvular heart disease worldwide. Undiagnosed or untreated RHD can complicate pregnancy and lead to poor maternal and fetal outcomes and is a significant factor in non-obstetric morbidity. Echocardiography has an emerging role in screening for RHD. We aimed to critically analyse the evidence on the use of echocardiography for screening pregnant women for RHD in high-prevalence areas. Methods: We searched MEDLINE and Embase to identify the relevant reports. Two independent reviewers assessed the reports against the eligibility criteria in a double-blind process. Results: The searches (date: 4 April 2023) identified 432 records for screening. Ten non-controlled observational studies were identified, five using portable or handheld echocardiography, comprising data from 23,166 women. Prevalence of RHD varied across the studies, ranging from 0.4 to 6.6% (I2, heterogeneity >90%). Other cardiac abnormalities (e.g., congenital heart disease and left ventricular systolic dysfunction) were also detected <1% to 2% of cases. Certainty of evidence was very low. Conclusion: Echocardiography as part of antenatal care in high-prevalence areas may detect RHD or other cardiac abnormalities in asymptomatic pregnant women, potentially reducing the rates of disease progression and adverse labor-associated outcomes. However, this evidence is affected by the low certainty of evidence, and lack of studies comparing echocardiography versus standard antenatal care. Prospective Registration: PROSPERO 2022 July 4; CRD42022344081 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=344081. Research question: 'In areas with a high prevalence of rheumatic heart disease, should handheld echocardiography be added to routine antenatal care?'

Prognostic Value of Late Gadolinium Enhancement Detected on Cardiac Magnetic Resonance in Cardiac Sarcoidosis.

BACKGROUND: Sarcoidosis is a complex multisystem inflammatory disorder, with approximately 5% of patients having overt cardiac involvement. Patients with cardiac sarcoidosis are at an increased risk of both ventricular arrhythmias and sudden cardiac death. Previous studies have shown that the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with an increased risk of mortality and ventricular arrhythmias and may be useful in predicting prognosis. OBJECTIVES: This systematic review and meta-analysis assessed the value of LGE on CMR imaging in predicting prognosis for patients with known or suspected cardiac sarcoidosis. METHODS: The authors searched the Embase and MEDLINE databases from inception to March 2022 for studies reporting individuals with known or suspected cardiac sarcoidosis referred for CMR with LGE. Outcomes were defined as all-cause mortality, ventricular arrhythmia, or a composite outcome of either death or ventricular arrhythmias. The primary analysis evaluated these outcomes according to the presence of LGE. A secondary analysis evaluated outcomes specifically according to the presence of biventricular LGE. RESULTS: Thirteen studies were included (1,318 participants) in the analysis, with an average participant age of 52.0 years and LGE prevalence of 13% to 70% over a follow-up of 3.1 years. Patients with LGE on CMR vs those without had higher odds of ventricular arrhythmias (odds ratio [OR]: 20.3; 95% CI: 8.1-51.0), all-cause mortality (OR: 3.45; 95% CI: 1.6-7.3), and the composite of both (OR: 9.2; 95% CI: 5.1-16.7). Right ventricular LGE is invariably accompanied by left ventricular LGE. Biventricular LGE is also associated with markedly increased odds of ventricular arrhythmias (OR: 43.6; 95% CI: 16.2-117.2). CONCLUSIONS: Patients with known or suspected cardiac sarcoidosis with LGE on CMR have significantly increased odds of both ventricular arrhythmias and all-cause mortality. The presence of biventricular LGE may confer additional prognostic information regarding arrhythmogenic risk.

Robotic-Assisted PCI: The Future of Coronary Intervention?

Robotic percutaneous coronary intervention (R-PCI) is a novel approach to performing percutaneous coronary intervention (PCI) whereby the operator can utilise remotely controlled technology to manipulate guidewires and catheter devices. This enables the procedure to be undertaken from within a radiation-shielded cockpit. Success in early trials has led to the release of commercially available robotic platforms which have now received regulatory approval and are available for use in clinical practice. Recent trials evaluating R-PCI have demonstrated high technical success rates with low complication rates. Despite this, a significant number of cases, particularly those with complex anatomy, still require at least partial conversion to a manual procedure. Advantages of R-PCI include accurate stent placement, reduced operator radiation exposure and a presumed reduction in orthopedic injuries. Limitations include current incompatibility with certain intravascular imaging catheters and the inability to manipulate multiple guidewires and stents simultaneously. Patients presenting with ST-elevation myocardial infarction requiring primary-PCI have also largely been excluded from existing R-PCI studies. Given these caveats, R-PCI remains a novel technology and has yet to become commonplace in cardiac catheterisation laboratories, however with increasing safety and feasibility data emerging, it is possible that R-PCI may form part of standard practice in the future.

Bedside and laboratory diagnostic testing in myasthenia.

Myasthenia gravis (MG) and congenital myasthenic syndromes (CMS) are a group of disorders with a well characterised autoimmune or genetic and neurophysiological basis. We reviewed the literature from the last 20 years assessing the utility of various neurophysiological, immunological, provocative and genetic tests in MG and CMS. Diagnostic sensitivity of repetitive nerve stimulation test ranges between 14 and 94% and specificity between 73 and 100%; sensitivity of single-fibre EMG (SFEMG) test ranges between 64 and 100% and specificity between 22 and 100%; anti-acetylcholine receptor (AChR) antibody sensitivity ranges from 13 to 97% and specificity ranges from 95 to 100%. Overall, SFEMG has the highest sensitivity while positive anti-AChR antibodies have the highest specificity. Newer testing strategies that have been investigated over the last couple of decades include ocular vestibular-evoked myogenic potentials, otoacoustic emissions and disease-specific circulating miRNAs in serum for autoimmune myasthenia, as well as next-generation sequencing for genetic testing of CMS. While there has been significant progress in developing newer testing strategies for diagnosing MG and CMS over the last couple of decades, more research is needed to assess the utility of these newer tools regarding their sensitivity and specificity.

Protocol for an intervention development and pilot implementation evaluation study of an e-health solution to improve newborn care quality and survival in two low-resource settings, Malawi and Zimbabwe: Neotree.

INTRODUCTION: Every year 2.4 million deaths occur worldwide in babies younger than 28 days. Approximately 70% of these deaths occur in low-resource settings because of failure to implement evidence-based interventions. Digital health technologies may offer an implementation solution. Since 2014, we have worked in Bangladesh, Malawi, Zimbabwe and the UK to develop and pilot Neotree: an android app with accompanying data visualisation, linkage and export. Its low-cost hardware and state-of-the-art software are used to improve bedside postnatal care and to provide insights into population health trends, to impact wider policy and practice. METHODS AND ANALYSIS: This is a mixed methods (1) intervention codevelopment and optimisation and (2) pilot implementation evaluation (including economic evaluation) study. Neotree will be implemented in two hospitals in Zimbabwe, and one in Malawi. Over the 2-year study period clinical and demographic newborn data will be collected via Neotree, in addition to behavioural science informed qualitative and quantitative implementation evaluation and measures of cost, newborn care quality and usability. Neotree clinical decision support algorithms will be optimised according to best available evidence and clinical validation studies. ETHICS AND DISSEMINATION: This is a Wellcome Trust funded project (215742_Z_19_Z). Research ethics approvals have been obtained: Malawi College of Medicine Research and Ethics Committee (P.01/20/2909; P.02/19/2613); UCL (17123/001, 6681/001, 5019/004); Medical Research Council Zimbabwe (MRCZ/A/2570), BRTI and JREC institutional review boards (AP155/2020; JREC/327/19), Sally Mugabe Hospital Ethics Committee (071119/64; 250418/48). Results will be disseminated via academic publications and public and policy engagement activities. In this study, the care for an estimated 15 000 babies across three sites will be impacted. TRIAL REGISTRATION NUMBER: NCT0512707; Pre-results.

Supervision--growing and building a sustainable general practice supervisor system.

This article explores various models and ideas for future sustainable general practice vocational training supervision in Australia. The general practitioner supervisor in the clinical practice setting is currently central to training the future general practice workforce. Finding ways to recruit, retain and motivate both new and experienced GP teachers is discussed, as is the creation of career paths for such teachers. Some of the newer methods of practice-based teaching are considered for further development, including vertically integrated teaching, e-learning, wave consulting and teaching on the run, teaching teams and remote teaching. Approaches to supporting and resourcing teaching and the required infrastructure are also considered. Further research into sustaining the practice-based general practice supervision model will be required.

The use of data in resource limited settings to improve quality of care.

Quality improvement is driven by benchmarking between and within institutions over time and the collaborative improvement efforts that stem from these comparisons. Benchmarking requires systematic collection and use of standardized data. Low- and middle-income countries (LMIC) have great potential for improvements in newborn outcomes but serious obstacles to data collection, analysis, and implementation of robust improvement methodologies exist. We review the importance of data collection, internationally recommended neonatal metrics, selected methods of data collection, and reporting. The transformation from data collection to data use is illustrated by several select data system examples from LMIC. Key features include aims and measures important to neonatal team members, co-development with local providers, immediate access to data for review, and multidisciplinary team involvement. The future of neonatal care, use of data, and the trajectory to reach global neonatal improvement targets in resource-limited settings will be dependent on initiatives led by LMIC clinicians and experts.

Dysregulated G2 phase checkpoint recovery pathway reduces DNA repair efficiency and increases chromosomal instability in a wide range of tumours.

Defective DNA repair is being demonstrated to be a useful target in cancer treatment. Currently, defective repair is identified by specific gene mutations, however defective repair is a common feature of cancers without these mutations. DNA damage triggers cell cycle checkpoints that are responsible for co-ordinating cell cycle arrest and DNA repair. Defects in checkpoint signalling components such as ataxia telangiectasia mutated (ATM) occur in a low proportion of cancers and are responsible for reduced DNA repair and increased genomic instability. Here we have investigated the AURKA-PLK1 cell cycle checkpoint recovery pathway that is responsible for exit from the G2 phase cell cycle checkpoint arrest. We demonstrate that dysregulation of PP6 and AURKA maintained elevated PLK1 activation to promote premature exit from only ATM, and not ATR-dependent checkpoint arrest. Surprisingly, depletion of the B55α subunit of PP2A that negatively regulates PLK1 was capable of overcoming ATM and ATR checkpoint arrests. Dysregulation of the checkpoint recovery pathway reduced S/G2 phase DNA repair efficiency and increased genomic instability. We found a strong correlation between dysregulation of the PP6-AURKA-PLK1-B55α checkpoint recovery pathway with signatures of defective homologous recombination and increased chromosomal instability in several cancer types. This work has identified an unrealised source of G2 phase DNA repair defects and chromosomal instability that are likely to be sensitive to treatments targeting defective repair.