Blast injuries in children: a mixed-methods narrative review.

Background and significance. Blast injuries arising from high explosive weaponry is common in conflict areas. While blast injury characteristics are well recognised in the adults, there is a lack of consensus as to whether these characteristics translate to the paediatric population. Understanding blast injury patterns in this cohort is essential for providing appropriate provision of services and care for this vulnerable cohort. Methods. In this mixed-method review, original papers were screened for data pertaining to paediatric injuries following blasts. Information on demographics, morbidity and mortality and service requirements were evaluated. The papers were written and published in English from a range of international specialists in the field. Patient and public involvement statement: No patients or members of the public were involved in this review. Results. Children affected by blast injuries are predominantly male and their injuries arise from explosive remnants of war, particularly unexploded ordinance. Blasts show increased morbidity and mortality in younger children, while older children have injury patterns similar to adults. Head and burn injuries represent a significant cause of mortality in young children, while lower limb morbidity is reduced compared to adults. Children have a disproportionate requirement for both operative and non-operative service resources, and provisions for this burden are essential. Conclusions. Certain characteristics of paediatric injuries arising from blasts are distinct from that of the adult cohort, while the intensive demands on services highlights the importance of understanding the diverse injury patterns in order to optimise future service provisions in caring for this the child blast survivor

Multimorbidity patterns and risk of hospitalisation in children: A population cohort study of 3.6 million children in England, with illustrative examples from childhood cancer survivors

Background: Population-level estimates of hospitalisation risk in children are currently limited. The study aims to characterise morbidity patterns in all children, focusing on childhood cancer survivors versus children without cancer. Methods: Employing hospital records of children aged <19 years between 1997 to 2018 in England, we characterised morbidity patterns in childhood cancer survivors compared with children without cancer. The follow-up began on the 5th anniversary of the index hospitalisation and the primary outcome was the incidence of comorbidities. Findings: We identified 3,559,439 eligible participants having 12,740,666 hospital admissions, with a mean age at study entry of 11.2 years. We identified 32,221 patients who survived for at least 5 years since their initial cancer diagnosis. During the follow-up period and within the whole population of 3.6 million children, the leading conditions for admission were (i) metabolic, endocrine, digestive renal and genitourinary conditions (84,749, 2.5%), (ii) neurological (35,833, 1.0%) and (iii) musculoskeletal or skin conditions (23,574, 0.7%), fever, acute respiratory and sepsis (22,604, 0.7%). Stratified analyses revealed that females and children from socioeconomically deprived areas had a higher cumulative incidence for morbidities requiring hospitalisation (p < 0.001). At baseline (5 years after the initial cancer diagnosis or initial hospitalisation for survivors and population comparisons, respectively), cancer survivors experienced a higher prevalence of individual conditions and multimorbidity (≥ 2 morbidities) compared with children without cancer. Cox regression analyses showed that survivors had at least a 4-fold increase in the risk of hospitalisation for conditions such as chronic eye conditions (hazard ration (HR):4.0, 95% confidence interval (CI): 3.5-4.7), fever requiring hospitalisation (HR: 4.4, 95% CI: 3.8-5.0), subsequent neoplasms (HR: 5.7, 95% CI:5.0-6.5), immunological disorders (HR: 6.5, 95% CI:4.5-9.3) and metabolic conditions (HR: 7.1, 95% CI:5.9-8.5). Interpretation: The overall morbidity burden among children was low in general; however, childhood cancer survivors experienced a higher prevalence and subsequent risk of hospitalisation for a range of morbidities. Targeted policies may be required to promote awareness on health vulnerabilities and gender disparity and to improve advocacy for healthcare in deprived communities. Funding: Wellcome Trust, National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre and Academy of Medical Sciences. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report

First characterization of a superconducting filter-bank spectrometer for hyper-spectral microwave atmospheric sounding with transition edge sensor readout

We describe the design, fabrication, integration and characterization of a prototype superconducting filter bank with transition edge sensor readout designed to explore millimetre-wave detection at frequencies in the range 40 to 65 GHz. Results indicate highly uniform filter channel placement in frequency and high overall detection efficiency. The route to a full atmospheric sounding instrument in this frequency range is discussed.Centre for Earth Observing Instrumentation UK (CEOI

Alcohol-abuse drug disulfiram targets pediatric glioma via MLL degradation

Pediatric gliomas comprise a broad range of brain tumors derived from glial cells. While high-grade gliomas are often resistant to therapy and associated with a poor outcome, children with low-grade gliomas face a better prognosis. However, the treatment of low-grade gliomas is often associated with severe long-term adverse effects. This shows that there is a strong need for improved treatment approaches. Here, we highlight the potential for repurposing disulfiram to treat pediatric gliomas. Disulfiram is a drug used to support the treatment of chronic alcoholism and was found to be effective against diverse cancer types in preclinical studies. Our results show that disulfiram efficiently kills pediatric glioma cell lines as well as patient-derived glioma stem cells. We propose a novel mechanism of action to explain disulfiram’s anti-oncogenic activities by providing evidence that disulfiram induces the degradation of the oncoprotein MLL. Our results further reveal that disulfiram treatment and MLL downregulation induce similar responses at the level of histone modifications and gene expression, further strengthening that MLL is a key target of the drug and explaining its anti-oncogenic properties

A Chandra X-ray Study of Cygnus A - II. The Nucleus

We report Chandra ACIS and quasi-simultaneous RXTE observations of the nearby, powerful radio galaxy Cygnus A, with the present paper focusing on the properties of the active nucleus. In the Chandra observation, the hard (> a few keV) X-ray emission is spatially unresolved with a size \approxlt 1 arcsec (1.5 kpc, H_0 = 50 km s^-1 Mpc^-1) and coincides with the radio and near infrared nuclei. In contrast, the soft (< 2 keV) emission exhibits a bi-polar nebulosity that aligns with the optical bi-polar continuum and emission-line structures and approximately with the radio jet. In particular, the soft X-ray emission corresponds very well with the [O III] \lambda 5007 and H\alpha + [N II] \lambda\lambda 6548, 6583 nebulosity imaged with HST. At the location of the nucleus there is only weak soft X-ray emission, an effect that may be intrinsic or result from a dust lane that crosses the nucleus perpendicular to the source axis. The spectra of the various X-ray components have been obtained by simultaneous fits to the 6 detectors. The compact nucleus is detected to 100 keV and is well described by a heavily absorbed power law spectrum with \Gamma_h = 1.52^{+0.12}_{-0.12} (similar to other narrow line radio galaxies) and equivalent hydrogen column N_H (nuc) = 2.0^{+0.1}_{-0.2} \times 10^{23} cm^-2. (Abstract truncated).Comment: To be published in the Astrophysical Journal, v564 January 1, 2002 issue; 34 pages, 11 figures (1 color

A 40-Year Cohort Study of Evolving Hypothalamic Dysfunction in Infants and Young Children (<3 years) with Optic Pathway Gliomas

Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.5 years (range 0.5–25.0). A total of 52 (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) of whom had hypothalamic involvement (H+) and lower endocrine event-free survival (EEFS) rates. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs. 46%, p = 0.001)), H+ (OR 6.1 95% CI 1.7–21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7–158.6, p = 0.017) and surgery (OR 4.8 95% CI 1.3–17.2, p = 0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and was clustered with the endocrinopathies. Neurobehavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1–5.9, p = 0.043) and radiotherapy (OR 23.1 C.I. 2.9–182, p = 0.003). Very young children with OPHG carry a high risk of endo-metabolic and neurobehavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in complex, hierarchical patterns over time whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies

Evaluating preclinical evidence for clinical translation in childhood brain tumours: Guidelines from the CONNECT, PNOC, and ITCC brain networks

Clinical outcomes for many childhood brain tumours remain poor, despite our increasing understanding of the underlying disease biology. Advances in molecular diagnostics have refined our ability to classify tumour types and subtypes, and efforts are underway across multiple international paediatric neuro-oncology consortia to take novel biological insights in the worst prognosis entities into innovative clinical trials. Whilst for the first time we are designing such studies on the basis of disease-specific biological data, the levels of preclincial evidence in appropriate model systems on which these trials are initiated is still widely variable. We have considered these issues between CONNECT, PNOC and ITCC-Brain, and developed a framework in which we can assess novel concepts being brought forward for possible clinical translation. Whilst not intended to be proscriptive for every possible circumstance, these criteria provide a basis for self-assessment of evidence by laboratory scientists, and a platform for discussion and rational decision-making prior to moving forward clinically