A luminous fast radio burst that probes the Universe at redshift 1.

Fast radio bursts (FRBs) are millisecond-duration pulses of radio emission originating from extragalactic distances. Radio dispersion is imparted on each burst by intervening plasma, mostly located in the intergalactic medium. In this work, we observe the burst FRB 20220610A and localize it to a morphologically complex host galaxy system at redshift 1.016 ± 0.002. The burst redshift and dispersion measure are consistent with passage through a substantial column of plasma in the intergalactic medium and extend the relationship between those quantities measured at lower redshift. The burst shows evidence for passage through additional turbulent magnetized plasma, potentially associated with the host galaxy. We use the burst energy of 2 × 1042 erg to revise the empirical maximum energy of an FRB.

Use of radiological information system data in Clinical Portal database to screen for missed abdominal aortic aneurysms.

INTRODUCTION: New Zealand lacks a formal abdominal aortic aneurysm screening programme and owing to its rural nature, many patients have limited access to vascular surgery. Patients with vascular emergencies often have limited treatment options locally, especially if they present perimortem. In our small hospital in Whanganui, with the nearest vascular centre more than 150km away, there are cases of aneurysms diagnosed incidentally on radiology reporting but lost to follow-up. METHODS: Clinical Portal (CP) is a widely used patient-centred dashboard for viewing health information that is managed by Orion Health. A search strategy utilising the CP common database was devised that aimed to find aneurysms which were not followed up. This search was performed retrospectively for all imaging within a 5-month period. RESULTS: Some 294 scans were flagged and 53 patients with aneurysms were found. Of these patients, 36 had follow-up by the ordering provider and 17 (32%) were found to have been lost to follow-up. CONCLUSIONS: Our pilot study demonstrated high rates of loss to follow-up and a lack of communication of important health information across multiple health disciplines in the region, and represents a potential method for identifying 'lost' aneurysms. For patients in rural communities, this may be critical to preventing future complications from aneurysmal disease.

Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial.

PURPOSE: Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . METHODS: We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . RESULTS: Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (- 1, 21) vs 10 (- 1, to 21) in subphenotype-2; 1.5 (- 1, 21) vs 12 (- 1, to 21) in suphenotype-3, and 0 (- 1, 21) vs 0 (- 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). CONCLUSIONS: We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.

Long-term outcomes of laparoscopic large hiatus hernia repair with nonabsorbable mesh.

The use of mesh to augment suture repair of large hiatus hernias remains controversial. Repair with mesh may help reduce the recurrence rate of primary repair, but concerns about the potential for serious complications, such as mesh erosion or stricturing, continue to limit its use. We aim to evaluate the long-term outcome of primary hiatus hernia repair with lightweight polypropylene mesh (TiMesh) specifically looking at rates of clinical recurrence, dysphagia, and mesh-related complications. From a prospectively maintained database, 50 consecutive patients who underwent elective primary laparoscopic hiatal hernia repair with TiMesh between January 2005 and December 2007 were identified. Case notes and postoperative endoscopy reports were reviewed. Clinical outcomes were evaluated using a structured questionnaire, including a validated dysphagia score. Of the 50 patients identified, 36 (72%) were contactable for follow-up. At a median follow-up of 9 years, the majority of patients (97%) regarded their surgery as successful. Twelve patients (33%) reported a recurrence of their symptoms, but only 4 (11%) reported that their symptoms were as severe as prior to the surgery. There was no significant difference between pre- and postoperative dysphagia scores. Postoperative endoscopy reports were available for 32 patients at a median time point of 4 years postoperatively, none of which revealed any mesh-related complications. One patient had undergone a revision procedure for a recurrent hernia at another institution. In this series, primary repair of large hiatus hernia with nonabsorbable mesh was not associated with any adverse effects over time. Patient satisfaction with symptomatic outcome remained high in the long term.

Delivering precision antimicrobial therapy through closed-loop control systems.

Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients.

General paediatric surgery for patients aged under 5 years: a 5-year experience at a district general hospital.

Introduction The gradual shift of general paediatric surgery (GPS) provision from district general hospitals (DGH) to specialised units is well recognised in the UK. The consequences of centralisation include a reduction in exposure to GPS for current surgical trainees. The GPS practice of a DGH is examined here. Methods All operations performed on children aged under 5 years over a 5-year period were identified using the local electronic operation database. Electronic hospital records and clinic letters were accessed to collect data on demographics, operations performed and outcome measures. Results 472 GPS operations were performed on children between the age of 22 days and 5 years between 2009 and 2014, of which 43 were on an emergency basis and 105 were performed on patients aged less than 1 year. Three patients were admitted following day case surgery. Six patients were readmitted within 30 days. Complication rates for all procedures and the four most common procedures were similar to those found in published literature. Conclusions GPS for patients aged less than 5 years is comparatively safe in the DGH setting. The training opportunities available at DGHs are invaluable to surgical trainees and vital for sustaining the future provision of GPS by such hospitals.

Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation.

Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (≤1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.

Patients with faecal peritonitis admitted to European intensive care units: an epidemiological survey of the GenOSept cohort.

INTRODUCTION: Faecal peritonitis (FP) is a common cause of sepsis and admission to the intensive care unit (ICU). The Genetics of Sepsis and Septic Shock in Europe (GenOSept) project is investigating the influence of genetic variation on the host response and outcomes in a large cohort of patients with sepsis admitted to ICUs across Europe. Here we report an epidemiological survey of the subset of patients with FP. OBJECTIVES: To define the clinical characteristics, outcomes and risk factors for mortality in patients with FP admitted to ICUs across Europe. METHODS: Data was extracted from electronic case report forms. Phenotypic data was recorded using a detailed, quality-assured clinical database. The primary outcome measure was 6-month mortality. Patients were followed for 6 months. Kaplan-Meier analysis was used to determine mortality rates. Cox proportional hazards regression analysis was employed to identify independent risk factors for mortality. RESULTS: Data for 977 FP patients admitted to 102 centres across 16 countries between 29 September 2005 and 5 January 2011 was extracted. The median age was 69.2 years (IQR 58.3-77.1), with a male preponderance (54.3%). The most common causes of FP were perforated diverticular disease (32.1%) and surgical anastomotic breakdown (31.1%). The ICU mortality rate at 28 days was 19.1%, increasing to 31.6% at 6 months. The cause of FP, pre-existing co-morbidities and time from estimated onset of symptoms to surgery did not impact on survival. The strongest independent risk factors associated with an increased rate of death at 6 months included age, higher APACHE II score, acute renal and cardiovascular dysfunction within 1 week of admission to ICU, hypothermia, lower haematocrit and bradycardia on day 1 of ICU stay. CONCLUSIONS: In this large cohort of patients admitted to European ICUs with FP the 6 month mortality was 31.6%. The most consistent predictors of mortality across all time points were increased age, development of acute renal dysfunction during the first week of admission, lower haematocrit and hypothermia on day 1 of ICU admission.

Levosimendan: current data, clinical use and future development.

Levosimendan is an inodilator indicated for the short-term treatment of acutely decompensated severe chronic heart failure, and in situations where conventional therapy is not considered adequate. The principal pharmacological effects of levosimendan are (a) increased cardiac contractility by calcium sensitisation of troponin C, (b) vasodilation, and (c) cardioprotection. These last two effects are related to the opening of sarcolemmal and mitochondrial potassium-ATP channels, respectively. Data from clinical trials indicate that levosimendan improves haemodynamics with no attendant significant increase in cardiac oxygen consumption and relieves symptoms of acute heart failure; these effects are not impaired or attenuated by the concomitant use of beta-blockers. Levosimendan also has favourable effects on neurohormone levels in heart failure patients. Levosimendan is generally well tolerated in acute heart failure patients: the most common adverse events encountered in this setting are hypotension, headache, atrial fibrillation, hypokalaemia and tachycardia. Levosimendan has also been studied in other therapeutic applications, particularly cardiac surgery - in which it has shown a range of beneficial haemodynamic and cardioprotective effects, and a favourable influence on clinical outcomes - and has been evaluated in repetitive dosing protocols in patients with advanced chronic heart failure. Levosimendan has shown preliminary positive effects in a range of conditions requiring inotropic support, including right ventricular failure, cardiogenic shock, septic shock, and Takotsubo cardiomyopathy.

Incidence and outcome of critical illness amongst hospitalised patients with haematological malignancy: a prospective observational study of ward and intensive care unit based care.

To determine the incidence and outcome of critical illness amongst the total population of hospital patients with haematological malignancy (including patients treated on the ward as well as those admitted to the intensive care unit), consecutive patients with haematological malignancy were prospectively studied. One hundred and one of the 1437 haemato-oncology admissions (7%) in 2001 were complicated by critical illness (26% of all new referrals). Fifty-four (53%) of these critically ill patients survived to leave hospital and 33 (34%) were still alive after 6 months. The majority (77/101) were not admitted to the intensive care unit but were managed on the ward, often with the assistance of the intensive care team. Independent risk factors for dying in hospital included hepatic failure (odds ratio 5.3, 95% confidence intervals 1.3-21.2) and central nervous system failure (odds ratio 14.5, 95% confidence intervals 1.7-120.5). No patient with four or more organ failures or a Simplified Acute Physiology Score II >/= 65 survived to leave hospital. There was close agreement between actual and predicted mortality with increasing Simplified Acute Physiology Score II for all patients, including those not admitted to intensive care.

TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.

Tumour necrosis factor (TNF) is an important pro-inflammatory cytokine produced in sepsis. Studies examining the association of individual TNF single nucleotide polymorphisms with sepsis have produced conflicting results. This study investigated whether common polymorphisms of the TNF locus and the two receptor genes, TNFRSF1A and TNFRSF1B, influence circulating levels of encoded proteins, and whether individual polymorphisms or extended haplotypes of these genes are associated with susceptibility, severity of illness or outcome in adult patients with severe sepsis or septic shock. A total of 213 Caucasian patients were recruited from eight intensive care units (ICU) in the UK and Australia. Plasma levels of TNF (P = 0.02), sTNFRSF1A (P = 0.005) and sTNFRSF1B (P = 0.01) were significantly higher in those who died on ICU compared to those who survived. There was a positive correlation between increasing soluble receptor levels and organ dysfunction (increasing SOFA score) (sTNFRSF1A R = 0.51, P < 0.001; sTNFRSF1B R = 0.53, P < 0.001), and in particular with the degree of renal dysfunction. In this study, there were no significant associations between the selected candidate TNF or TNF receptor polymorphisms, or their haplotypes, and susceptibility to sepsis, illness severity or outcome. The influence of polymorphisms of the TNF locus on susceptibility to, and outcome from sepsis remains uncertain.

A randomized prospective assessor-blind evaluation of luteinizing hormone dosage and in vitro fertilization outcome.

OBJECTIVE: To determine the effect of exogenous LH dosage on IVF outcome. DESIGN: Single-blinded (assessor-blinded) study with random assignment of treatment groups. SETTING: Human Assisted Reproduction Unit, Rotunda Hospital, Dublin, Ireland. PATIENT(S): Infertile normogonadotropic women undergoing their first cycle of IVF were studied. INTERVENTION(S): Patients were randomized to gonadotropin drugs with varying doses of LH per ampule: recombinant FSH containing no LH (group 0, n = 39), urinary FSH containing <1 IU of LH per ampule (group 1, n = 30), hMG containing 25 IU of LH per ampule (group 25, n = 30), and hMG containing 75 IU of LH per ampule (group 75, n = 29). The FSH dose was kept constant at 75 IU per ampule. A long-protocol GnRH-analog regimen was used. MAIN OUTCOME MEASURE(S): Dose and duration of gonadotropin stimulation, follicle and oocyte numbers, implantation rate, and pregnancy rate. RESULT(S): The median duration of ovarian stimulation; median number of gonadotropin ampules used; serum E2 levels; and numbers of follicles, oocytes, and embryos were similar among the four groups. Median LH levels on the day of hCG administration, however, differed significantly. Live birth rates per cycle differed markedly, but statistical significance was not achieved (23%, 7%, 20%, and 31% for groups 0, 1, 25, and 75, respectively). A significant trend in implantation rates was noted with increasing LH dosage of the urinary preparations (19%, 10%, 18%, and 28% for groups 0, 1, 25, and 75, respectively). CONCLUSION(S): In the present study, although the residual endogenous LH after down-regulation was adequate for ovarian response and E2 synthesis, the addition of exogenous LH improved implantation. An FSH/LH ratio of 75/75 IU per ampule appeared to be the optimum dose.

Image-guided central venous catheters for apheresis.

Apheresis is an increasingly important procedure in the treatment of a variety of conditions, sometimes performed via peripheral access because of concern over major complications associated with central venous catheter (CVC) placement. This study sought to determine the safety and success for ultrasound and fluoroscopically guided, non-tunneled dual lumen CVCs placed for apheresis. Prospective data collection was made of 200 attempted CVC placements in the radiology department utilizing real time sonographic guidance. The complications relating to placement were noted in all and the number of passes required for venepuncture and whether a single wall puncture was achieved was recorded in 185 cases. Duration of catheterization and reason for line removal were recorded in all. Our study group included 71 donors providing peripheral blood stem cells for allogeneic transplant. CVCs were successfully placed in all patients, 191 lines in the internal jugular and seven in the femoral vein. 86.5% required only a single pass and 80.5% with only anterior wall puncture. Inadvertent but clinically insignificant arterial puncture occurred in six (3%) cases. In no case did this prevent line placement. There were no other procedure-related complications. 173 (87.4%) catheters were removed the same day. No catheters were removed prematurely. There was one case of prolonged venous bleeding. Our study demonstrates the safety of central venous catheters for apheresis provided that duration of catheterization is short and real-time sonographic guidance is used for the puncture, and guide wire and catheter placement are confirmed fluoroscopically.

Acute exacerbation of vasculitis during interferon-alpha therapy for hepatitis C-associated cryoglobulinaemia.

A significant, previously unreported, adverse reaction to interferon-alpha therapy is reported. Immediately after the commencement of low dose therapy a man with hepatitis-C associated cryoglobulinaemia developed a purpuric rash and a severe, reversible impairment of renal function. This observation may elucidate the immunopathogenesis of vasculitis.

The relation between acquisition of a theory of mind and the capacity to hold in mind.

Building on earlier work by Pascual-Leone (1970) and Case (1985), Olson (1989; 1993) set out a theory showing how a series of incremental changes in capacity for "holding in mind" could account, in part, for children's acquisition of a theory of mind. Following Piaget (1951) infants were said to employ schemata for maintaining relations with objects and events in the presence of those events. At about 18 months children became capable of holding in mind an object so as to free the perceptual system to perceive a second object and form a relation between the two, allowing for what Piaget called the "symbolic function" and what Olson described as predication. At around 4 years, the period examined in the present study, children were said to acquire the ability to represent that predicative relation as a belief or as true or false. That was the stage at which children were said to possess a theory of mind. The present study tested the hypothesized relation between development of a theory of mind and increasing computational resources. Three-, four-, and five-year-old children's performance on a pair of theory of mind tasks was compared with that on a pair of dual processing tasks designed on the basis of Baddeley's (1986) model of working memory. The resulting correlations, as high as r = .64 between the tasks, suggest that changes in capacity to hold in mind allow the expression of, and arguably the formation of, a theory of mind.

US-guided puncture of the internal jugular vein: complications and anatomic considerations.

PURPOSE: To examine success and complication rates for ultrasound (US)-guided cannulation of the internal jugular vein (IJV) in comparison with blind techniques and to present the variations in anatomy of the IJV. MATERIALS AND METHODS: Data were prospectively collected for 869 cases of sonographically guided cannulation of the IJV. In all cases, the side of the puncture, procedural success or failure, and any immediate complications were recorded. In 764 (88%) cases, the number of passes required and whether a single- or double-wall puncture was used were recorded. In 690 (79%) cases, IJV diameter and depth were recorded, while its relationship to the common carotid artery (CCA) was noted in 659 (76%) cases. RESULTS: Cannulation was successful in 868 (99.9%) cases. Complications occurred in 20 (2.3%) cases. Eighty-seven percent of cannulations were achieved with one pass and 83% with a single-wall puncture. Success at first pass was significantly correlated with right-sided puncture and the diameter of the IJV. In 5.5% of cases, the IJV lay medial to the CCA, making successful cannulation with use of the landmark technique unlikely. CONCLUSIONS: US-guided cannulation of the IJV is superior to blind techniques, increasing the success rate and incidence of first pass cannulation and reducing the incidence of complications.