A fast radio burst associated with a Galactic magnetar.

Since their discovery in 20071, much effort has been devoted to uncovering the sources of the extragalactic, millisecond-duration fast radio bursts (FRBs)2. A class of neutron stars known as magnetars is a leading candidate source of FRBs3,4. Magnetars have surface magnetic fields in excess of 1014 gauss, the decay of which powers a range of high-energy phenomena5. Here we report observations of a millisecond-duration radio burst from the Galactic magnetar SGR 1935+2154, with a fluence of 1.5 ± 0.3 megajansky milliseconds. This event, FRB 200428 (ST 200428A), was detected on 28 April 2020 by the STARE2 radio array6 in the 1,281-1,468 megahertz band. The isotropic-equivalent energy released in FRB 200428 is 4 × 103 times greater than that of any radio pulse from the Crab pulsar-previously the source of the brightest Galactic radio bursts observed on similar timescales7. FRB 200428 is just 30 times less energetic than the weakest extragalactic FRB observed so far8, and is drawn from the same population as the observed FRB sample. The coincidence of FRB 200428 with an X-ray burst9-11 favours emission models that describe synchrotron masers or electromagnetic pulses powered by magnetar bursts and giant flares3,4,12,13. The discovery of FRB 200428 implies that active magnetars such as SGR 1935+2154 can produce FRBs at extragalactic distances.

Improved adherence to hip fracture standards reduces mortality after hip fractures.

BACKGROUND: Hip fractures are increasing in incidence due to increasing life expectancy. Mortality continues to improve but it is important to explore which factors are responsible for driving improvements. METHODS: A cohort of hip fracture patients predating SARS-CoV-2 was examined to determine the predictors of adherence to the six Irish Hip Fracture Standards (IHFS) and the impact of adherence on short (30 day) and long term (1 year) mortality. Our primary aim was assess the impact of a single HFS and cumulative number of HFS on mortality after hip fracture. Our secondary aim was to determine the impact of the HFS which are intrinsically linked to specialist Geriatric care. RESULTS: Across 962 patients, over 5 years, the factors which were associated with adherence to HFS were female gender, increasing ASA grade and being nursed on an orthopaedic ward. Patients with increasing ASA were more likely to have met HFS 4-6 (Geriatrician review HFS4, bone health HFS5 & specialist falls assessment HFS6), less likely to have surgery within 48 h are more likely to develop a pressure ulcer. If the patient was not nursed on an orthopaedic ward all HFS were less likely to be met. At 30 days HFS 4-6 were associated with a statistically significant odds ratio (OR) of being alive, while at one year HFS 1 (admitted to an orthopaedic ward within 4 h), 5 and 6 were associated with a statistically significant OR of being alive. As increasing numbers of hip fracture standards were met patients were more likely to be alive at 30 days and one year. CONCLUSION: This study has identified that improved adherence to hip fracture standards are associated with improved mortality at 30 days and one year.

Phylogenomics illuminates the phylogeny of flower weevils (Curculioninae) and reveals ten independent origins of brood-site pollination mutualism in true weevils.

Weevils are an unusually species-rich group of phytophagous insects for which there is increasing evidence of frequent involvement in brood-site pollination. This study examines phylogenetic patterns in the emergence of brood-site pollination mutualism among one of the most speciose beetle groups, the flower weevils (subfamily Curculioninae). We analysed a novel phylogenomic dataset consisting of 214 nuclear loci for 202 weevil species, with a sampling that mainly includes flower weevils as well as representatives of all major lineages of true weevils (Curculionidae). Our phylogenomic analyses establish a uniquely comprehensive phylogenetic framework for Curculioninae and provide new insights into the relationships among lineages of true weevils. Based on this phylogeny, statistical reconstruction of ancestral character states revealed at least 10 independent origins of brood-site pollination in higher weevils through transitions from ancestral associations with reproductive structures in the larval stage. Broadly, our results illuminate the unexpected frequency with which true weevils-typically specialized phytophages and hence antagonists of plants-have evolved mutualistic interactions of ecological significance that are key to both weevil and plant evolutionary fitness and thus a component of their deeply intertwined macroevolutionary success.

The diversity and evolution of odorant receptors in beetles (Coleoptera).

The insect odorant receptors (ORs) are amongst the largest gene families in insect genomes and the primary means by which insects recognize volatile compounds. The evolution of ORs is thus instrumental in explaining the chemical ecology of insects and as a model of evolutionary biology. However, although ORs have been described from numerous insect species, their analysis within and amongst the insect orders has been hindered by a combination of limited genomic information and a tendency of the OR family toward rapid divergence, gain, and loss. We addressed these issues in the insect order Coleoptera through a targeted genomic annotation effort that included 1181 ORs from one species of the sister order Strepsiptera and 10 species representing the four coleopteran suborders. The numbers of ORs in each species varied from hundreds to fewer than 10, but coleopteran ORs could nevertheless be represented within a scheme of nine monophyletic subfamilies. We observed many radiations and losses of genes amongst OR subfamilies, and the diversity of ORs appeared to parallel the host breadth of the study species. However, some small lineages of ORs persisted amongst many coleopteran families, suggesting receptors of key function that underlie the olfactory ecology of beetles.

A re-evaluation of teenage sunbed use following the introduction of banning legislation for under 18-year-olds.

BACKGROUND: There is little information on the effectiveness of introducing age restriction legislation alone to reduce the rate of sunbed usage by teenagers. Prior to the Public Health (Sunbed) Act of 2014 prohibiting the use of sunbeds in under 18-year-olds in Ireland we reported the rate of sunbed use at 7.5%. OBJECTIVES: The aim of the study was to compare the rate of sunbed usage among Irish teenagers before and after the introduction of banning legislation to determine if it had the desired effect of reducing its rate of use. METHODS: In a cross-sectional survey, students from the same schools as in our previous study completed an anonymous, written questionnaire pertaining to sunbed usage. RESULTS: In total, 783 questionnaires, from 13 schools across Ireland, were completed. The rate of sunbed use in the current study was 7.2%, compared to 7.5% in the pre-ban study, (P = 0.76). A higher rate of sunbed use was observed in Dublin schools and female public students. CONCLUSION: Our study suggests that legislation alone is ineffective at reducing sunbed usage in a teenage population. A multifaceted approach is required that includes enforcement of the legislation together with targeted public education and awareness campaigns using all aspects of the media.

Experience of skin disease and relationships with healthcare providers: a qualitative study of Traveller women in Ireland.

BACKGROUND: Significant health disparities exist between members of the Travelling community and those of the general population. Barriers to Traveller engagement with health services include the experience or perception of discrimination, and cultural and health literacy barriers. Experience of skin disease and interactions with healthcare providers has not been widely explored in this ethnic minority. The formation of positive relationships between the Travelling community and healthcare providers is important in the promotion of treatment adherence and improving health outcomes. OBJECTIVES: To investigate Travellers' experience of skin disease and their relationships with healthcare providers. METHODS: Focus groups were conducted with a purposive sample of female members of the Irish Travelling community with experience of skin health issues, between January 2018 and April 2018. Three focus groups were conducted at three separate locations with 10 participants in each group. Themes were identified from the focus group transcripts using an inductive thematic analysis framework. RESULTS: Emergent themes surrounding relationships between Travellers and healthcare providers included health literacy, discrimination, information inconsistency, trust and communication. Factors that were valued in the creation of positive relationships included an appreciation of varying degrees of health literacy, the provision of sufficient information tailored to an individual's needs and a demonstration of cultural competence. CONCLUSIONS: Dermatologists are well placed to provide practical, customized, treatment guidance and engage patients while integrating their culturally based beliefs.

Artificial intelligence and amniotic fluid multiomics: prediction of perinatal outcome in asymptomatic women with short cervix.

OBJECTIVE: To evaluate the application of artificial intelligence (AI), i.e. deep learning and other machine-learning techniques, to amniotic fluid (AF) metabolomics and proteomics, alone and in combination with sonographic, clinical and demographic factors, in the prediction of perinatal outcome in asymptomatic pregnant women with short cervical length (CL). METHODS: AF samples, which had been obtained in the second trimester from asymptomatic women with short CL (< 15 mm) identified on transvaginal ultrasound, were analyzed. CL, funneling and the presence of AF 'sludge' were assessed in all cases close to the time of amniocentesis. A combination of liquid chromatography coupled with mass spectrometry and proton nuclear magnetic resonance spectroscopy-based metabolomics, as well as targeted proteomics analysis, including chemokines, cytokines and growth factors, was performed on the AF samples. To determine the robustness of the markers, we used six different machine-learning techniques, including deep learning, to predict preterm delivery < 34 weeks, latency period prior to delivery < 28 days after amniocentesis and requirement for admission to a neonatal intensive care unit (NICU). Omics biomarkers were evaluated alone and in combination with standard sonographic, clinical and demographic factors to predict outcome. Predictive accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) with 95% CI, sensitivity and specificity. RESULTS: Of the 32 patients included in the study, complete omics, demographic and clinical data and outcome information were available for 26. Of these, 11 (42.3%) patients delivered ≥ 34 weeks, while 15 (57.7%) delivered < 34 weeks. There was no statistically significant difference in CL between these two groups (mean ± SD, 11.2 ± 4.4 mm vs 8.9 ± 5.3 mm, P = 0.31). Using combined omics, demographic and clinical data, deep learning displayed good to excellent performance, with an AUC (95% CI) of 0.890 (0.810-0.970) for delivery < 34 weeks' gestation, 0.890 (0.790-0.990) for delivery < 28 days post-amniocentesis and 0.792 (0.689-0.894) for NICU admission. These values were higher overall than for the other five machine-learning methods, although each individual machine-learning technique yielded statistically significant prediction of the different perinatal outcomes. CONCLUSIONS: This is the first study to report use of AI with AF proteomics and metabolomics and ultrasound assessment in pregnancy. Machine learning, particularly deep learning, achieved good to excellent prediction of perinatal outcome in asymptomatic pregnant women with short CL in the second trimester. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

The molecular characterisation of Cryptosporidium species in relinquished dogs in Great Britain: a novel zoonotic risk?

Surveillance was conducted to investigate the occurrence of protozoan parasites of the genus Cryptosporidium in dogs newly admitted to a dog rehoming charity in London, Great Britain. Voided faecal samples were collected from all new admissions between 2011 and 2012 during six separate 4-week sampling periods. Information on host signalment, including age, breed and reason for submission and faecal consistency, was collected. Polymerase Chain Reaction (PCR) targeting the 18S ribosomal RNA gene, confirmed by sequencing, was conducted on the faecal samples to detect Cryptosporidium genomic DNA and determine Cryptosporidium identity. In total, 677 dogs were included in the study. The prevalence of Cryptosporidium-positive faecal samples was 4.6% (31/676). There were positive samples in all of the six sampling periods. Cryptosporidium canis (n = 28), C. parvum (n = 2) and C. andersoni (n = 1) were identified. Sixty KDa glycoprotein (gp60) gene amplicon sequencing of the C. parvum samples identified genotypes IIaA17G1R1 and IIaA15G2R1 for the first time from a dog. There were no significant associations between signalment data and Cryptosporidium status. While this was a study of one rehoming shelter, the presence of the potentially zoonotic C. parvum and C. canis in dogs highlights a public health concern. Further research is needed to better understand the epidemiology and potential impacts of Cryptosporidium infection in dogs.

Hydrogen-poor superluminous stellar explosions.

Supernovae are stellar explosions driven by gravitational or thermonuclear energy that is observed as electromagnetic radiation emitted over weeks or more. In all known supernovae, this radiation comes from internal energy deposited in the outflowing ejecta by one or more of the following processes: radioactive decay of freshly synthesized elements (typically (56)Ni), the explosion shock in the envelope of a supergiant star, and interaction between the debris and slowly moving, hydrogen-rich circumstellar material. Here we report observations of a class of luminous supernovae whose properties cannot be explained by any of these processes. The class includes four new supernovae that we have discovered and two previously unexplained events (SN 2005ap and SCP 06F6) that we can now identify as members of the same class. These supernovae are all about ten times brighter than most type Ia supernova, do not show any trace of hydrogen, emit significant ultraviolet flux for extended periods of time and have late-time decay rates that are inconsistent with radioactivity. Our data require that the observed radiation be emitted by hydrogen-free material distributed over a large radius (∼10(15) centimetres) and expanding at high speeds (>10(4) kilometres per second). These long-lived, ultraviolet-luminous events can be observed out to redshifts z > 4.

Androgen deprivation in LNCaP prostate tumour xenografts induces vascular changes and hypoxic stress, resulting in promotion of epithelial-to-mesenchymal transition.

BACKGROUND: When single-agent androgen deprivation therapy (ADT) is administered for locally advanced prostate cancer, men usually relapse within 1-2 years with more malignant castrate-resistant disease. The reason for this is currently unknown. We now hypothesise that an initial treatment response that increases tumour hypoxia drives selection of more malignant tumours. METHODS: The LNCaP prostate tumour xenografts were analysed for physiological (oxygen and vasculature) and genetic (PCR array) changes during longitudinal treatment with ADT (bicalutamide, 6 or 2 mg kg⁻¹ daily for 28 days). RESULTS: Bicalutamide caused an immediate (within 24 h) dose-dependent fall in oxygenation in LNCaP-luc prostate tumours with a nadir of ≤ 0.1% oxygen within 3-7 days; this was attributed to a significant loss of tumour microvessels (window chamber study). The hypoxic nadir persisted for 10-14 days. During the next 7 days, tumours regrew, oxygenation improved and the vasculature recovered; this was inhibited by the VEGF inhibitor B20.4.1.1. Gene expression over 28 days showed marked fluctuations consistent with the physiological changes. Accompanying the angiogenic burst (day 21) was a particularly striking increase in expression of genes associated with epithelial-to-mesenchymal transition (EMT). In particular, insulin-like growth factor 1 (IGF-1) showed increases in mRNA and protein expression. CONCLUSIONS: Hypoxic stress caused by ADT promotes EMT, providing a mechanism for the cause of malignant progression in prostate cancer.

Clinical grade allogeneic human mesenchymal stem cells restore alveolar fluid clearance in human lungs rejected for transplantation.

The lack of suitable donors for all solid-organ transplant programs is exacerbated in lung transplantation by the low utilization of potential donor lungs, due primarily to donor lung injury and dysfunction, including pulmonary edema. The current studies were designed to determine if intravenous clinical-grade human mesenchymal stem (stromal) cells (hMSCs) would be effective in restoring alveolar fluid clearance (AFC) in the human ex vivo lung perfusion model, using lungs that had been deemed unsuitable for transplantation and had been subjected to prolonged ischemic time. The human lungs were perfused with 5% albumin in a balanced electrolyte solution and oxygenated with continuous positive airway pressure. Baseline AFC was measured in the control lobe and if AFC was impaired (defined as <10%/h), the lungs received either hMSC (5 × 10(6) cells) added to the perfusate or perfusion only as a control. AFC was measured in a different lung lobe at 4 h. Intravenous hMSC restored AFC in the injured lungs to a normal level. In contrast, perfusion only did not increase AFC. This positive effect on AFC was reduced by intrabronchial administration of a neutralizing antibody to keratinocyte growth factor (KGF). Thus, intravenous allogeneic hMSCs are effective in restoring the capacity of the alveolar epithelium to remove alveolar fluid at a normal rate, suggesting that this therapy may be effective in enhancing the resolution of pulmonary edema in human lungs deemed clinically unsuitable for transplantation.

Toxic effect of chemotherapy dosing using actual body weight in obese versus normal-weight patients: a systematic review and meta-analysis.

BACKGROUND: Many oncologists reduce chemotherapy doses in obese patients due to fear of excess toxic effect from very large weight-based calculations. While recent guidelines advise against this practice, quantitative summarization of the supporting evidence is not available. MATERIALS AND METHODS: We systematically identified studies that compared toxic effect or survival outcomes between obese and normal-weight adults receiving chemotherapy dosed by actual body weight (ABW). We pooled odds ratios (OR) and 95% confidence intervals (CI) using random-effects models. RESULTS: Of 5490 records screened, 12 studies representing 9314 relevant patients met inclusion criteria. The large majority of reported toxic effect and survival outcomes did not statistically differ between obese and normal-weight subjects. Exceptions included five studies in which one or more toxic effect or survival outcomes statistically favored obese patients, and one study that statistically favored normal-weight patients. Pooling usable data, rates of toxic effects were similar or lower in obese patients (grade 3/4 hematologic toxic effect: OR 0.73, CI 0.55-0.98, 4 studies; grade 3/4 nonhematologic toxic effect: OR 0.98, CI 0.76-1.26, 3 subgroups; any grade 3/4 toxic effect: OR 0.75, CI 0.65-0.87, three studies). CONCLUSIONS: Obese patients receiving chemotherapy based on ABW experience similar or lower rates of toxic effects compared with normal-weight patients, and survival outcomes do not differ.

Systemic juvenile idiopathic arthritis: The Great Ormond Street Hospital experience (2005-2021).

Systemic juvenile idiopathic arthritis (sJIA) is a complex, systemic inflammatory disorder driven by both innate and adaptive immunity. Improved understanding of sJIA pathophysiology has led to recent therapeutic advances including a growing evidence base for the earlier use of IL-1 or IL-6 blockade as first-line treatment. We conducted a retrospective case notes review of patients diagnosed with sJIA over a 16-year period (October 2005-October 2021) at Great Ormond Street Hospital for Children. We describe the clinical presentation, therapeutic interventions, complications, and remission rates at different timepoints over the disease course. We examined our data, which spanned a period of changing therapeutic landscape, to try and identify potential therapeutic signals in patients who received biologic treatment early in the disease course compared to those who did not. A total of 76-children (female n = 40, 53%) were diagnosed with sJIA, median age 4.5 years (range 0.6-14.1); 36% (27/76) presented with suspected or confirmed macrophage activation syndrome. A biologic disease-modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3 months of diagnosis compared to those who did not (90% vs. 53%, p = 0.002). Based on an ever-increasing evidence base for the earlier use of bDMARD in sJIA and our experience of the largest UK single-centre case series described to date, we now propose a new therapeutic pathway for children diagnosed with sJIA in the UK based on early use of bDMARDs. Reappraisal of the current National Health Service commissioning pathway for sJIA is now urgently required.