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Lopinavir–ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir–ritonavir improves outcomes in patients admitted to hospital with COVID-19. In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir–ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir–ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir–ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91–1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91–1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99–1·20; p=0·092). In patients admitted to hospital with COVID-19, lopinavir–ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir–ritonavir for treatment of patients admitted to hospital with COVID-19. Medical Research Council and National Institute for Health Research.

Leafy greens contaminated with Shiga toxin-producing Escherichia coli have continued to cause foodborne illness outbreaks in recent years and present a threat to public health. An important component of foodborne illness outbreak investigations is determining the source of the outbreak vehicle through traceback investigations. The U.S. Food and Drug Administration is home to traceback investigation experts who use a standardized process to initiate, execute, and interpret the results of traceback investigations in collaboration with the Centers for Disease Control and Prevention and state and local partners. Traceback investigations of three outbreaks of Shiga toxin-producing E. coli infections linked to romaine lettuce in 2018 and 2019 were examined to demonstrate challenges, limitations, and opportunities for improvement. The three outbreaks resulted in a total of 474 illnesses, 215 hospitalizations, and 5 deaths. These illnesses were linked to the consumption of romaine lettuce from three distinct growing regions in Arizona and California. Some of the challenges encountered included the time it took to initiate a traceback, limited product-identifying information throughout the supply chain, lack of interoperability in record-keeping systems, and comingling of product from multiple suppliers. These challenges led to time delays in the identification of the farm source of the leafy greens and the inability to identify the root cause of contamination. Implementation of technology-enabled traceability systems, testing of these systems, and future regulations to incentivize adoption of traceability systems are some of the initiatives that will help address these challenges by improving traceback investigations and ultimately preventing foodborne illnesses and future outbreaks from occurring.

The light-absorbing organic aerosol (OA) commonly referred to as “brown carbon” (BrC) has attracted considerable attention in recent years because of its potential to affect atmospheric radiation balance, especially in the ultraviolet region and thus impact photochemical processes. A growing amount of data has indicated that BrC is prevalent in the atmosphere, which has motivated numerous laboratory and field studies; however, our understanding of the relationship between the chemical composition and optical properties of BrC remains limited. We conducted chamber experiments to investigate the effect of various volatile organic carbon (VOC) precursors, NOx concentrations, photolysis time, and relative humidity (RH) on the light absorption of selected secondary organic aerosols (SOA). Light absorption of chamber-generated SOA samples, especially aromatic SOA, was found to increase with NOx concentration, at moderate RH, and for the shortest photolysis aging times. The highest mass absorption coefficient (MAC) value is observed from toluene SOA products formed under high-NOx conditions at moderate RH, in which nitro-aromatics were previously identified as the major light-absorbing compounds. BrC light absorption is observed to decrease with photolysis time, correlated with a decline of the organic nitrate fraction of SOA. SOA formed from mixtures of aromatics and isoprene absorb less visible (Vis) and ultraviolet (UV) light than SOA formed from aromatic precursors alone on a mass basis. However, the mixed SOA absorption was underestimated when optical properties were predicted using a two-product SOA formation model, as done in many current climate models. Further investigation, including analysis on detailed mechanisms, are required to explain the discrepancy.

Plough marks in Pine Island Bay, West Antarctica, left by the keels of drifting icebergs 12,000 years ago provide evidence that marine ice-cliff instability can drive rapid ice-sheet retreat. MICI evidence beneath the sheets In a recent Nature paper, Rob DeConto and David Pollard proposed that a mechanism called marine ice-cliff instability (MICI) could have an important role in the rapid retreat of ice sheets and, potentially, in their collapse. Observational confirmation of MICI has been missing, and the glaciological community has questioned the realism and likelihood of such a mechanism. Now, Matthew Wise and colleagues present an analysis of some plough marks that are approximately 12,000 years old, left by the keels of icebergs in Pine Island Bay—the epicentre of modern-day glacial retreat in Antarctica. The authors show that the characteristics of these plough marks are probably explained by MICI, thereby providing an initial confirmation that the mechanism operated in the past, and at a scale that is likely to be relevant to present and future ice-sheet behaviour. Marine ice-cliff instability (MICI) processes could accelerate future retreat of the Antarctic Ice Sheet if ice shelves that buttress grounding lines more than 800 metres below sea level are lost 1 , 2 . The present-day grounding zones of the Pine Island and Thwaites glaciers in West Antarctica need to retreat only short distances before they reach extensive retrograde slopes 3 , 4 . When grounding zones of glaciers retreat onto such slopes, theoretical considerations and modelling results indicate that the retreat becomes unstable (marine ice-sheet instability) and thus accelerates 5 . It is thought 1 , 2 that MICI is triggered when this retreat produces ice cliffs above the water line with heights approaching about 90 metres. However, observational evidence confirming the action of MICI has not previously been reported. Here we present observational evidence that rapid deglacial ice-sheet retreat into Pine Island Bay proceeded in a similar manner to that simulated in a recent modelling study 1 , driven by MICI. Iceberg-keel plough marks on the sea-floor provide geological evidence of past and present iceberg morphology, keel depth 6 and drift direction 7 . From the planform shape and cross-sectional morphologies of iceberg-keel plough marks, we find that iceberg calving during the most recent deglaciation was not characterized by small numbers of large, tabular icebergs as is observed today 8 , 9 , which would produce wide, flat-based plough marks 10 or toothcomb-like multi-keeled plough marks 11 , 12 . Instead, it was characterized by large numbers of smaller icebergs with V-shaped keels. Geological evidence of the form and water-depth distribution of the plough marks indicates calving-margin thicknesses equivalent to the threshold that is predicted to trigger ice-cliff structural collapse as a result of MICI 13 . We infer rapid and sustained ice-sheet retreat driven by MICI, commencing around 12,300 years ago and terminating before about 11,200 years ago, which produced large numbers of icebergs smaller than the typical tabular icebergs produced today. Our findings demonstrate the effective operation of MICI in the past, and highlight its potential contribution to accelerated future retreat of the Antarctic Ice Sheet.

Acinetobacter baumannii is recognized as an emerging bacterial pathogen because of traits such as prolonged survival in a desiccated state, effective nosocomial transmission, and an inherent ability to acquire antibiotic resistance genes. A pressing need in the field of A. baumannii research is a suitable model strain that is representative of current clinical isolates, is highly virulent in established animal models, and can be genetically manipulated. To identify a suitable strain, a genetically diverse set of recent U.S. military clinical isolates was assessed. Pulsed-field gel electrophoresis and multiplex PCR determined the genetic diversity of 33 A. baumannii isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain, AB5075, were considerably more severe in both animal models than those with other isolates, as there was a significant decrease in survival rates. AB5075 also caused osteomyelitis in a rat open fracture model, while another isolate did not. Additionally, a Tn 5 transposon library was successfully generated in AB5075, and the insertion of exogenous genes into the AB5075 chromosome via Tn 7 was completed, suggesting that this isolate may be genetically amenable for research purposes. Finally, proof-of-concept experiments with the antibiotic rifampin showed that this strain can be used in animal models to assess therapies under numerous parameters, including survival rates and lung bacterial burden. We propose that AB5075 can serve as a model strain for A. baumannii pathogenesis due to its relatively recent isolation, multidrug resistance, reproducible virulence in animal models, and genetic tractability. IMPORTANCE The incidence of A. baumannii infections has increased over the last decade, and unfortunately, so has antibiotic resistance in this bacterial species. A. baumannii is now responsible for more than 10% of all hospital-acquired infections in the United States and has a >50% mortality rate in patients with sepsis and pneumonia. Most research on the pathogenicity of A. baumannii focused on isolates that are not truly representative of current multidrug-resistant strains isolated from patients. After screening of a panel of isolates in different in vitro and in vivo assays, the strain AB5075 was selected as more suitable for research because of its antibiotic resistance profile and increased virulence in animal models. Moreover, AB5075 is susceptible to tetracycline and hygromycin, which makes it amenable to genetic manipulation. Taken together, these traits make AB5075 a good candidate for use in studying virulence and pathogenicity of this species and testing novel antimicrobials. The incidence of A. baumannii infections has increased over the last decade, and unfortunately, so has antibiotic resistance in this bacterial species. A. baumannii is now responsible for more than 10% of all hospital-acquired infections in the United States and has a >50% mortality rate in patients with sepsis and pneumonia. Most research on the pathogenicity of A. baumannii focused on isolates that are not truly representative of current multidrug-resistant strains isolated from patients. After screening of a panel of isolates in different in vitro and in vivo assays, the strain AB5075 was selected as more suitable for research because of its antibiotic resistance profile and increased virulence in animal models. Moreover, AB5075 is susceptible to tetracycline and hygromycin, which makes it amenable to genetic manipulation. Taken together, these traits make AB5075 a good candidate for use in studying virulence and pathogenicity of this species and testing novel antimicrobials.

Known foodborne disease agents are estimated to cause approximately 9.4 million illnesses each year in the United States. Although only a small subset of illnesses are associated with recognized outbreaks, data from outbreak investigations provide insight into the foods and pathogens that cause illnesses and the settings and conditions in which they occur. 2009-2015 DESCRIPTION OF SYSTEM: The Foodborne Disease Outbreak Surveillance System (FDOSS) collects data on foodborne disease outbreaks, which are defined as the occurrence of two or more cases of a similar illness resulting from the ingestion of a common food. Since the early 1960s, foodborne outbreaks have been reported voluntarily to CDC by state, local, and territorial health departments using a standard form. Beginning in 2009, FDOSS reporting was made through the National Outbreak Reporting System, a web-based platform launched that year. During 2009-2015, FDOSS received reports of 5,760 outbreaks that resulted in 100,939 illnesses, 5,699 hospitalizations, and 145 deaths. All 50 states, the District of Columbia, Puerto Rico, and CDC reported outbreaks. Among 2,953 outbreaks with a single confirmed etiology, norovirus was the most common cause of outbreaks (1,130 outbreaks [38%]) and outbreak-associated illnesses (27,623 illnesses [41%]), followed by Salmonella with 896 outbreaks (30%) and 23,662 illnesses (35%). Outbreaks caused by Listeria, Salmonella, and Shiga toxin-producing Escherichia coli (STEC) were responsible for 82% of all hospitalizations and 82% of deaths reported. Among 1,281 outbreaks in which the food reported could be classified into a single food category, fish were the most commonly implicated category (222 outbreaks [17%]), followed by dairy (136 [11%]) and chicken (123 [10%]). The food categories responsible for the most outbreak-associated illnesses were chicken (3,114 illnesses [12%]), pork (2,670 [10%]), and seeded vegetables (2,572 [10%]). Multistate outbreaks comprised only 3% of all outbreaks reported but accounted for 11% of illnesses, 34% of hospitalizations, and 54% of deaths. Foodborne disease outbreaks provide information about the pathogens and foods responsible for illness. Norovirus remains the leading cause of foodborne disease outbreaks, highlighting the continued need for food safety improvements targeting worker health and hygiene in food service settings. Outbreaks caused by Listeria, Salmonella, and STEC are important targets for public health intervention efforts, and improving the safety of chicken, pork, and seeded vegetables should be a priority. The causes of foodborne illness should continue to be tracked and analyzed to inform disease prevention policies and initiatives. Strengthening the capacity of state and local health departments to investigate and report outbreaks will assist with these efforts through identification of the foods, etiologies, and settings linked to these outbreaks.

Shiga toxin-producing Escherichia coli (STEC) cause substantial and costly illnesses. Leafy greens are the second most common source of foodborne STEC O157 outbreaks. We examined STEC outbreaks linked to leafy greens during 2009-2018 in the United States and Canada. We identified 40 outbreaks, 1,212 illnesses, 77 cases of hemolytic uremic syndrome, and 8 deaths. More outbreaks were linked to romaine lettuce (54%) than to any other type of leafy green. More outbreaks occurred in the fall (45%) and spring (28%) than in other seasons. Barriers in epidemiologic and traceback investigations complicated identification of the ultimate outbreak source. Research on the seasonality of leafy green outbreaks and vulnerability to STEC contamination and bacterial survival dynamics by leafy green type are warranted. Improvements in traceability of leafy greens are also needed. Federal and state health partners, researchers, the leafy green industry, and retailers can work together on interventions to reduce STEC contamination.

Population incidence of Guillain-Barré syndrome (GBS) is required to assess changes in GBS epidemiology, but published estimates of GBS incidence vary greatly depending on case ascertainment, definitions, and sample size. We performed a meta-analysis of articles on GBS incidence by searching Medline (1966–2009), Embase (1988–2009), Cinahl (1981–2009) and CABI (1973–2009) as well as article bibliographies. We included studies from North America and Europe with at least 20 cases, and used population-based data, subject matter experts to confirm GBS diagnosis, and an accepted GBS case definition. With these data, we fitted a random-effects negative binomial regression model to estimate age-specific GBS incidence. Of 1,683 nonduplicate citations, 16 met the inclusion criteria, which produced 1,643 cases and 152.7 million person-years of follow-up. GBS incidence increased by 20% for every 10-year increase in age; the risk of GBS was higher for males than females. The regression equation for calculating the average GBS rate per 100,000 person-years as a function of age in years was exp[–12.0771 + 0.01813(age in years)] × 100,000. Our findings provide a robust estimate of background GBS incidence in Western countries. Our regression model may be used in comparable populations to estimate the background age-specific rate of GBS incidence for future studies.

Background Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA. Methods This was a prospective case–control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. Results Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z -score ≤ − 1 (at least borderline–mild impairment) in ≥ 2 cognitive domains, 14% performed z -score ≤ − 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = − 0.37, 95% confidence intervals [− 0.61, − 0.12]), verbal (MD = − 0.34 [− 0.62, − 0.07]), and visual/constructive functions (MD = − 0.26 [− 0.47, − 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = − 0.44 [− 0.82, − 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance. Conclusions In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue. Trial registration ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.