Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

Maternal and perinatal outcomes of SARS-CoV-2 infection in unvaccinated pregnancies during Delta and Omicron waves.

OBJECTIVE: There is little evidence related to the effects of the Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant on pregnancy outcomes, particularly in unvaccinated women. This study aimed to compare pregnancy outcomes of unvaccinated women infected with SARS-CoV-2 during the pre-Delta, Delta and Omicron waves. METHODS: This was a retrospective cohort study conducted at two tertiary care facilities: Sancaktepe Training and Research Hospital, Istanbul, Turkey, and St George's University Hospitals NHS Foundation Trust, London, UK. Included were women who tested positive for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (RT-PCR) during pregnancy, between 1 April 2020 and 14 February 2022. The cohort was divided into three periods according to the date of their positive RT-PCR test: (i) pre-Delta (1 April 2020 to 8 June 2021 in Turkey, and 1 April 2020 to 31 July 2021 in the UK), (ii) Delta (9 June 2021 to 27 December 2021 in Turkey, and 1 August 2021 to 27 December 2021 in the UK) and (iii) Omicron (after 27 December 2021 in both Turkey and the UK). Baseline data collected included maternal age, parity, body mass index, gestational age at diagnosis and comorbidities. The primary outcome was the need for oxygen supplementation, classified as oxygen support via nasal cannula or breather mask, non-invasive mechanical ventilation with continuous positive airway pressure (CPAP) or high-flow oxygen, mechanical ventilation with intubation, or extracorporeal membrane oxygenation (ECMO). Inferences were made after balancing of confounders, using an evolutionary search algorithm. Selected confounders were maternal age, body mass index and gestational age at diagnosis of infection. RESULTS: During the study period, 1286 unvaccinated pregnant women with RT-PCR-proven SARS-CoV-2 infection were identified, comprising 870 cases during the pre-Delta period, 339 during the Delta wave and 77 during the Omicron wave. In the confounder-balanced cohort, infection during the Delta wave vs during the pre-Delta period was associated with increased need for nasal oxygen support (risk ratio (RR), 2.53 (95% CI, 1.75-3.65); P < 0.001), CPAP or high-flow oxygen (RR, 2.50 (95% CI, 1.37-4.56); P = 0.002), mechanical ventilation (RR, 4.20 (95% CI, 1.60-11.0); P = 0.003) and ECMO (RR, 11.0 (95% CI, 1.43-84.7); P = 0.021). The maternal mortality rate was 3.6-fold higher during the Delta wave compared to the pre-Delta period (5.3% vs 1.5%, P = 0.010). Infection during the Omicron wave was associated with a similar need for nasal oxygen support (RR, 0.62 (95% CI, 0.25-1.55); P = 0.251), CPAP or high-flow oxygen (RR, 1.07 (95% CI, 0.36-3.12); P = 0.906) and mechanical ventilation (RR, 0.44 (95% CI, 0.06-3.45); P = 0.438) with that in the pre-Delta period. The maternal mortality rate was similar during the Omicron wave and the pre-Delta period (1.3% vs 1.3%, P = 0.999). The need for nasal oxygen support during the Omicron wave was significantly lower compared to the Delta wave (RR, 0.26 (95% CI, 0.11-0.64); P = 0.003). Perinatal outcomes were available for a subset of the confounder-balanced cohort. Preterm birth before 34 weeks' gestation was significantly increased during the Delta wave compared with the pre-Delta period (15.4% vs 4.9%, P < 0.001). CONCLUSIONS: Among unvaccinated pregnant women, SARS-CoV-2 infection during the Delta wave, in comparison to the pre-Delta period, was associated with increased requirement for oxygen support (including ECMO) and higher maternal mortality. Disease severity and pregnancy complications were similar between the Omicron wave and pre-Delta period. SARS-CoV-2 infection of unvaccinated pregnant women carries considerable risks of morbidity and mortality regardless of variant, and vaccination remains key. Miscommunication of the risks of Omicron infection may impact adversely vaccination uptake among pregnant women, who are at increased risk of complications related to SARS-CoV-2. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

An Ambulatory Pathway for the Investigation of Patients with Suspected Pulmonary Embolism.

Aims The aim of this project was to provide an ambulatory pathway for diagnosis and management of patients with suspected Pulmonary Embolism (PE) with "low-risk" features. Methods A structured algorithm for the management of suspected PE was designed and implemented in April 2021. This involved the development of local guidelines to identify those "low-risk" patients with suspected PE, through the use of modified sPESI and Hestia criteria. This pathway was audited monthly to establish effect on admission and hospital length of stay. Results 51 CT PAs were performed by the Emergency Department in April 2021. Total number of CT confirmed PEs in April was 7(11%). 12 "low-risk" patients with suspected PE were identified and placed on the "Ambulatory Suspected Pulmonary Embolism Pathway". One (8.3%) patient on this pathway had a confirmed PE. Patients placed on this pathway spent significantly less time in the Emergency Department and in hospital with greater satisfaction by physicians using this pathway. Conclusion This pathway has succeeded in significantly decreasing length of stay both in the ED and in hospital for patients with suspected and confirmed PE.

Acute fasciolosis in an alpaca: a case report.

BACKGROUND: The popularity of new world camelids, particularly alpacas, is growing rapidly in Ireland, presenting a clinical challenge to veterinary practitioners who may not have worked with these species previously. To the authors' knowledge, the clinical course of a case of acute fasciolosis in an alpaca has not previously been reported, and fasciolosis has not been reported at all in alpacas in Ireland, making this case report a valuable addition to the current literature. CASE PRESENTATION: A three-year-old male castrated huacaya alpaca was admitted to UCD Veterinary Hospital with a two-day history of colic and tenesmus. He had been treated with albendazole, dexamethasone and potentiated amoxycillin by the referring veterinary practitioner with no response. On initial clinical exam, sensitivity to abdominal palpation was the only abnormality. However, the alpaca proceeded to show abnormal lying positions, tenesmus and reduced faecal output over the next 24 h. A general blood panel demonstrated moderate anaemia, marked hyperglobulinaemia and moderately increased hepatocellular and hepatobiliary enzyme activity. Abdominal radiography revealed enlargement of the first forestomach compartment without evidence of gastrointestinal obstruction or peritonitis. An abdominal ultrasound exam revealed an elongated, heterogenous mass in the caudoventral abdomen that appeared to be contiguous with the liver. FNA of this mass revealed that it was in fact a liver lobe with biliary stasis and inflammation. Faecal sedimentation demonstrated Fasciola hepatica eggs. In spite of treatment with triclabendazole and supportive treatment including blood transfusion, the alpaca's condition continued to deteriorate and he was euthanised. On post-mortem exam, acute fasciolosis was diagnosed. CONCLUSIONS: The clinical presentation and course of a case of acute fasciolosis in an individual alpaca is described, including the results of a range of diagnostic tests that were carried out. The final diagnosis is supported by a description of post-mortem findings. This information will serve as a resource for veterinary practitioners involved in the diagnosis and treatment of similar cases.

Suicidality in women with Premenstrual Dysphoric Disorder: a systematic literature review.

Previous research has identified how menstruation is an important factor in both attempted and completed suicides for women. The purpose of this review was to outline (a) the risk profile for suicidality in women who were identified to experience Premenstrual Dysphoric Disorder (PMDD), a condition characterized by severe physical and psychological changes that occur during the luteal menstrual phase, and (b) the implications of these findings for clinical practice. A systematic literature review was conducted using five databases to identify any peer-reviewed articles published between 1989 and 2019. Ten papers eligible for inclusion were identified: three pertaining to suicide cognitions, five to suicide attempts and two to both cognitions and attempts. Findings showed that suicidal thoughts, ideation, plans and attempts were strongly associated with experiences of PMDD and that these findings were independent of psychiatric co-morbidities. However, women with PMDD did not present with more severe risk profiles for suicide attempts (in terms of frequency, impulsivity and lethality) or make more frequent attempts during the luteal menstrual phase compared with suicide attempters without PMDD. Women with PMDD should be considered a high risk group for suicidality; thus, identifying and treating symptoms are vital in reducing suicide attempts. Implications for clinical practice are outlined in the discussion.

Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

Anthracycline-induced cardiotoxicity in patients with early-stage breast cancer: the Canadian Cancer Trials Group (CCTG) MA.21 experience.

PURPOSE: Anthracyclines are frequently used in adjuvant treatment for early-stage breast cancer (ESBC). The purpose of this study was to evaluate cardiotoxic effects in the first five years after treatment with different anthracycline-based regimens. METHODS: CCTG MA.21 (NCT000142) was a phase III trial in ESBC that compared cyclophosphamide (75 mg/m2) orally for 14 days, epirubicin (60 mg/m2) and fluorouracil, IV days one and eight (CEF) for six cycles; dose-dense epirubicin (120 mg/m2) and cyclophosphamide, IV every 2 weeks for six cycles with concurrent G-CSF then paclitaxel every 2 weeks for four cycles (ddEC/T); doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for four cycles then four cycles q3 weekly paclitaxel (175 mg/m2) (AC/T). ENDPOINTS: LVEF decline; LV function changes (heart failure), or Grade 3-4 cardiac ischemia/infarction. A competing risk analysis was performed with endpoints of cardiotoxicity or recurrence in first 5 years after completion of chemotherapy. RESULTS: 2104 women were randomized. Compliance with cardiac LVEF assessments was 70% at 5 years in all arms. The 5-year cumulative risks of any cardiac event for CEF, ddECT, and AC/T were 22.3% (95%CI 18.9 to 25.7), 14.2% (95%CI 11.0 to 17.3), and 8.1% (95%CI 5.8 to 10.4), respectively, p < 0.0001. At 5 years, women in the ddEC/T and AC/T group had significantly lower risk of cardiotoxicity than those given CEF (HR 0.599 and 0.371, respectively). Most events were asymptomatic drop in LVEF. CONCLUSIONS: Asymptomatic changes in LVEF accounted for most of the cardiotoxicity. The majority of cardiac events occurred in year one although occurrence of cardiotoxicity over time highlights the need for improved risk stratification to guide cardiac surveillance strategies.

Coronavirus in pregnancy and delivery: rapid review.

OBJECTIVES: There are limited case series reporting the impact on women affected by coronavirus during pregnancy. In women affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the case fatality rate appears higher in those affected in pregnancy compared with non-pregnant women. We conducted a rapid review to guide health policy and management of women affected by COVID-19 during pregnancy, which was used to develop the Royal College of Obstetricians and Gynaecologists' (RCOG) guidelines on COVID-19 infection in pregnancy. METHODS: Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies and randomized controlled trials describing women affected by coronavirus in pregnancy. Data were extracted from relevant papers. This review has been used to develop guidelines with representatives of the Royal College of Paediatrics and Child Health (RCPCH) and RCOG who provided expert consensus on areas in which data were lacking. RESULTS: From 9965 search results in PubMed and 600 in MedRxiv, 21 relevant studies, all of which were case reports or case series, were identified. From reports of 32 women to date affected by COVID-19 in pregnancy, delivering 30 babies (one set of twins, three ongoing pregnancies), seven (22%) were asymptomatic and two (6%) were admitted to the intensive care unit (ICU), one of whom remained on extracorporeal membrane oxygenation. No maternal deaths have been reported to date. Delivery was by Cesarean section in 27 cases and by vaginal delivery in two, and 15 (47%) delivered preterm. There was one stillbirth and one neonatal death. In 25 babies, no cases of vertical transmission were reported; 15 were reported as being tested with reverse transcription polymerase chain reaction after delivery. Case fatality rates for SARS and MERS were 15% and 27%, respectively. SARS was associated with miscarriage or intrauterine death in five cases, and fetal growth restriction was noted in two ongoing pregnancies affected by SARS in the third trimester. CONCLUSIONS: Serious morbidity occurred in 2/32 women with COVID-19, both of whom required ICU care. Compared with SARS and MERS, COVID-19 appears less lethal, acknowledging the limited number of cases reported to date and that one woman remains in a critical condition. Preterm delivery affected 47% of women hospitalized with COVID-19, which may put considerable pressure on neonatal services if the UK's reasonable worst-case scenario of 80% of the population being affected is realized. Based on this review, RCOG, in consultation with RCPCH, developed guidance for delivery and neonatal care in pregnancies affected by COVID-19, which recommends that delivery mode be determined primarily by obstetric indication and recommends against routine separation of affected mothers and their babies. We hope that this review will be helpful for maternity and neonatal services planning their response to COVID-19. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Circular polarization in the optical afterglow of GRB 121024A.

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

Women's experiences of receiving a diagnosis of premenstrual dysphoric disorder: a qualitative investigation.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a complex and disabling condition that affects women of reproductive age, characterised by severe physical and psychological symptoms that occur cyclically and remit following the onset of menses. As the psychological nature and consequences of PMDD often seem indistinguishable from symptoms of other mental health difficulties, this condition presents distinct diagnostic challenges for healthcare professionals. Therefore, this study aimed to explore women's experiences of both having PMDD and of receiving this diagnosis. METHODS: Participant recruitment took place in the United Kingdom during 2018. Seventeen women who had been diagnosed with PMDD by a medical specialist and met the clinical criteria for PMDD on the premenstrual symptoms screening tool were interviewed. The data from these semi-structured interviews were audio-recorded, transcribed and inductively analysed using reflexive thematic analysis. RESULTS: Twelve subthemes were identified and organised around four main themes: (1) A broken woman, (2) Misdiagnosis and the lost decades, (3) A life transformed and (4) Negotiating the aftermath. CONCLUSIONS: The findings of this study highlight the critical importance of the accurate and timely detection of PMDD, with the aim of preventing women from experiencing severe and prolonged psychological distress. In order to achieve this, there needs to be a greater understanding and awareness of PMDD within both the medical and lay communities, alongside training for healthcare practitioners in PMDD assessment.

Karyotype, evolution and phylogenetic reconstruction in Micronycterinae bats with implications for the ancestral karyotype of Phyllostomidae.

BACKGROUND: The Micronycterinae form a subfamily of leaf-nosed bats (Phyllostomidae) that contains the genera Lampronycteris Sanborn, 1949, and Micronycteris Gray, 1866 (stricto sensu), and is characterized by marked karyotypic variability and discrepancies in the phylogenetic relationships suggested by the molecular versus morphological data. In the present study, we investigated the chromosomal evolution of the Micronycterinae using classical cytogenetics and multidirectional chromosome painting with whole-chromosomes probes of Phyllostomus hastatus and Carollia brevicauda. Our goal was to perform comparative chromosome mapping between the genera of this subfamily and explore the potential for using chromosomal rearrangements as phylogenetic markers. RESULTS: The Micronycterinae exhibit great inter- and intraspecific karyotype diversity, with large blocks of telomere-like sequences inserted within or adjacent to constitutive heterochromatin regions. The phylogenetic results generated from our chromosomal data revealed that the Micronycterinae hold a basal position in the phylogenetic tree of the Phyllostomidae. Molecular cytogenetic data confirmed that there is a low degree of karyotype similarity between Lampronycteris and Micronycteris specimens analyzed, indicating an absence of synapomorphic associations in Micronycterinae. CONCLUSIONS: We herein confirm that karyotypic variability is present in subfamily Micronycterinae. We further report intraspecific variation and describe a new cytotype in M. megalotis. The cytogenetic data show that this group typically has large blocks of interstitial telomeric sequences that do not appear to be correlated with chromosomal rearrangement events. Phylogenetic analysis using chromosome data recovered the basal position for Micronycterinae, but did not demonstrate that it is a monophyletic lineage, due to the absence of common chromosomal synapomorphy between the genera. These findings may be related to an increase in the rate of chromosomal evolution during the time period that separates Lampronycteris from Micronycteris.

A quantitative analysis of CT angiography, large vessel occlusion, and thrombectomy rates in acute ischaemic stroke.

AIMS: To determine the workload of acute computed tomography angiography (CTA) in patients presenting with suspected acute ischaemic stroke (AIS) and rate of large vessel occlusion (LVO) and thrombectomy relative to suspected and confirmed stroke diagnoses across three stroke centres within the Republic of Ireland. MATERIALS AND METHODS: A retrospective review of data from three stroke centres, one of which provides a 24-hour thrombectomy service was undertaken. The number of CTA studies performed from January 2015 to December 2017 for suspected AIS was quantified using the national PACS in addition to occlusion location, collateral status, and rates of LVO and thrombectomy. The hospital inpatient enquiry (HIPE) system was searched for all patients with a primary discharge diagnosis of stroke and then correlated with patients who underwent CTA on admission. RESULTS: A total of 2,358 CTA studies were performed for suspected AIS during the study period across three stroke centres. LVO was demonstrated in 18.4% of suspected AIS, 18.4% of primary discharge stroke diagnoses, and 40.2% of confirmed AIS who underwent CTA. A total of 283 thrombectomies were performed of which 64.6% were LVO. Thrombectomy was performed in 12% of suspected AIS, 12% of overall primary discharge diagnoses of stroke cases, and 26% of confirmed stroke who underwent CTA. CONCLUSION: Establishing the volume of acute CTAs and rates of LVO and thrombectomy when compared to suspected AIS on admission, confirmed stroke diagnoses who underwent CTA and primary discharge diagnosis of stroke is essential for the planning and provision of stroke services worldwide.

A consensus statement on how to conduct inclusive health research.

BACKGROUND: The active involvement of people with intellectual disabilities in research, or inclusive research, is relatively common. However, inclusive health research is less common, even though it is expected to lead to appropriate healthcare and increased quality of life. Inclusive health research can build upon lessons learned from inclusive research. METHOD: A total of 17 experts on inclusive (health) research without intellectual disabilities and 40 experts with intellectual disabilities collaborated in this consensus statement. The consensus statement was developed in three consecutive rounds: (1) an initial feedback round; (2) a roundtable discussion at the 2016 International Association for the Scientific Study of Intellectual and Developmental Disabilities World Congress; and (3) a final feedback round. RESULTS: This consensus statement provides researchers with guidelines, agreed upon by experts in the field, regarding attributes, potential outcomes, reporting and publishing, and future research directions, for designing and conducting inclusive health research. CONCLUSIONS: Consensus was reached on how to design and conduct inclusive health research. However, this statement should be continuously adapted to incorporate recent knowledge. The focus of this consensus statement is largely on inclusive health research, but the principles can also be applied to other areas.

New insights into sex chromosome evolution in anole lizards (Reptilia, Dactyloidae).

Anoles are a clade of iguanian lizards that underwent an extensive radiation between 125 and 65 million years ago. Their karyotypes show wide variation in diploid number spanning from 26 (Anolis evermanni) to 44 (A. insolitus). This chromosomal variation involves their sex chromosomes, ranging from simple systems (XX/XY), with heterochromosomes represented by either micro- or macrochromosomes, to multiple systems (X1X1X2X2/X1X2Y). Here, for the first time, the homology relationships of sex chromosomes have been investigated in nine anole lizards at the whole chromosome level. Cross-species chromosome painting using sex chromosome paints from A. carolinensis, Ctenonotus pogus and Norops sagrei and gene mapping of X-linked genes demonstrated that the anole ancestral sex chromosome system constituted by microchromosomes is retained in all the species with the ancestral karyotype (2n = 36, 12 macro- and 24 microchromosomes). On the contrary, species with a derived karyotype, namely those belonging to genera Ctenonotus and Norops, show a series of rearrangements (fusions/fissions) involving autosomes/microchromosomes that led to the formation of their current sex chromosome systems. These results demonstrate that different autosomes were involved in translocations with sex chromosomes in closely related lineages of anole lizards and that several sequential microautosome/sex chromosome fusions lead to a remarkable increase in size of Norops sagrei sex chromosomes.

Municipal Wastewater as a Microbial Surveillance Platform for Enteric Diseases: A Case Study for Salmonella and Salmonellosis.

Municipal wastewater (MW) contains a conglomeration of human enteric microbiota from a community and, hence, represents a potential surveillance tool for gastrointestinal infectious disease burden at the community level. To evaluate this, the concentration of Salmonella in MW samples from Honolulu, Hawaii, was monitored over a 54-week period, which showed positive and significant linear and rank correlation with clinical salmonellosis case numbers over the same period. Salmonella isolates were obtained from the MW samples and then compared with clinical isolates obtained by the Hawaii Department of Health State Laboratories over the same period. The MW isolate collection contained 34 serotypes, and the clinical isolate collection contained 47 serotypes, 21 of which were shared between the two isolate collections, including nine of the 12 most commonly detected clinical serotypes. Most notably, nine Salmonella strains, including one outbreak-associated Paratyphi B strain and eight other clinically rare strains, were shared and concurrently detected between the MW and the clinical isolate collections, indicating the feasibility of using enteric pathogens in the MW as a timely indication of community enteric disease activity.

High-energy astrophysics and the search for sources of gravitational waves.

The dawn of the gravitational-wave (GW) era has sparked a greatly renewed interest into possible links between sources of high-energy radiation and GWs. The most luminous high-energy sources-gamma-ray bursts (GRBs)-have long been considered as very likely sources of GWs, particularly from short-duration GRBs, which are thought to originate from the merger of two compact objects such as binary neutron stars and a neutron star-black hole binary. In this paper, we discuss: (i) the high-energy emission from short-duration GRBs; (ii) what other sources of high-energy radiation may be observed from binary mergers; and (iii) how searches for high-energy electromagnetic counterparts to GW events are performed with current space facilities. While current high-energy facilities, such as Swift and Fermi, play a crucial role in the search for electromagnetic counterparts, new space missions will greatly enhance our capabilities for joint observations. We discuss why such facilities, which incorporate new technology that enables very wide-field X-ray imaging, are required if we are to truly exploit the multi-messenger era.This article is part of a discussion meeting issue 'The promises of gravitational-wave astronomy'.

Outcomes of endovascular treatment for acute large-vessel ischaemic stroke more than 6 h after symptom onset.

BACKGROUND AND OBJECTIVES: Benefit from endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) is well demonstrated. Furthermore, emerging evidence supports efficacy in appropriately selected patients treated beyond current recommendations of 6 h. We evaluated clinical outcomes in patients undergoing late EVT at our institution. METHODS: Retrospective review of prospectively collected clinical database on 355 patients who underwent EVT for LVO AIS. Data collected consisted of patient demographics, radiological findings and outcome details. Outcomes, including 90-day functional status, recanalization, symptomatic intracranial haemorrhage (sICH) and 90-day mortality, for patients undergoing EVT <6 h, >6 h, and >7.3 h, were compared. RESULTS: A total of 355 patients underwent EVT for LVO AIS at our institution during the review period, with 74 (21%) patients treated ≥6 h from symptom onset. Successful recanalization was achieved in 285 (80%) patients, with 228 (81%) achieving a mTICI ≥2b in the <6 h group, and 57 (77%) in the >6 h group (P = 0.429). Ninety-day functional independence (mRS 0-2) was achieved in 162 (46%) patients, with 130 (46%) achieving a mRS of 0-2 in the <6 h group, and 32 (43%) in the >6 h group (P = 0.643). No significant differences were found in rates of sICH or 90-day mortality. No significant differences in functional independence, recanalization rates, sICH or mortality were identified in patients treated with EVT >7.3 h compared to <7.3 h. CONCLUSIONS: In appropriately selected patients, EVT >6 h was associated with comparable outcomes to those treated <6 h. These data support a physiological approach to patient selection.

Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release.

BACKGROUND: Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli. METHODS: Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli, and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization. RESULTS: Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity. CONCLUSIONS: IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.

Weight loss after laparoscopic adjustable gastric band and resolution of the metabolic syndrome and its components.

BACKGROUND: Substantial weight loss in the setting of obesity has considerable metabolic benefits. Yet some studies have shown improvements in obesity-related metabolic comorbidities with more modest weight loss. By closely monitoring patients undergoing bariatric surgery, we aimed to determine the effects of weight loss on the metabolic syndrome and its components and determine the weight loss required for their resolution. METHODS: We performed a prospective observational study of obese participants with metabolic syndrome (Adult Treatment Panel III criteria) who underwent laparoscopic adjustable gastric banding. Participants were assessed for all criteria of the metabolic syndrome monthly for the first 9 months, then 3-monthly until 24 months. RESULTS: There were 89 participants with adequate longitudinal data. Baseline body mass index was 42.4±6.2 kg m-2 with an average age was 48.2±10.7 years. There were 56 (63%) women. Resolution of the metabolic syndrome occurred in 60 of the 89 participants (67%) at 12 months and 60 of the 75 participants (80%) at 24 months. The mean weight loss when metabolic syndrome resolved was 10.9±7.7% total body weight loss (TBWL). The median weight loss at which prevalence of disease halved was 7.0% TBWL (17.5% excess weight loss (EWL)) for hypertriglyceridaemia; 11% TBWL (26.1-28% EWL) for high-density lipoprotein cholesterol and hyperglycaemia; 20% TBWL (59.5% EWL) for hypertension and 29% TBWL (73.3% EWL) for waist circumference. The odds ratio for resolution of the metabolic syndrome with 10-12.5% TBWL was 2.09 (P=0.025), with increasing probability of resolution with more substantial weight loss. CONCLUSIONS: In obese participants with metabolic syndrome, a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits. If minimal improvements are seen with this initial target, additional weight loss substantially increases the probability of resolution.