A microwave study of 3,5 difluoropyridine…CO2: the effect of meta-fluorination on intermolecular interactions of pyridine

The rotational spectrum of the weakly bound complex 3,5-difluoropyridine$\cdots$CO$_{2}$ has been observed using pulsed-nozzle Fourier transform microwave spectroscopy. Spectroscopic constants are reported for the parent and the $^{13}$CO$_{2}$ isotopologues. The data indicate a structure in which the nitrogen approaches the carbon of the CO$_{2}$ with the \textit{C$_{2}$} axis of the difluoropyridine perpendicular to the CO$_{2}$. The N$\cdots$C van der Waals bond distance is 2.827(17) \AA\, and the oxygen$\cdots$ortho-hydrogen distance is 3.045(3) \AA. The amplitude of the zero point bending vibrational motion of the difluoropyridine moiety away from the \textit{C$_{2}$} axis of the complex is estimated from $^{14}$N nuclear hyperfine structure to be $8.8^{\circ}$. The N$\cdots$C van der Waals bond length is 0.029 \AA \, longer than that previously determined for pyridine-CO$_{2}$, but is still considerably shorter than the 2.997(1) \AA \, distance in HCN$\cdots$CO$_{2}$. Density functional theory calculations place the binding energy of the complex at 3.2 kcal/mol

Predicting molecular vibronic spectra using time-domain analog quantum simulation

Spectroscopy is one of the most accurate probes of the molecular world. However, predicting molecular spectra accurately is computationally difficult because of the presence of entanglement between electronic and nuclear degrees of freedom. Although quantum computers promise to reduce this computational cost, existing quantum approaches rely on combining signals from individual eigenstates, an approach that is difficult to scale because the number of eigenstates grows exponentially with molecule size. Here, we introduce a method for scalable analog quantum simulation of molecular spectroscopy, by performing simulations in the time domain. Our approach can treat more complicated molecular models than previous ones, requires fewer approximations, and can be extended to open quantum systems with minimal overhead. We present a direct mapping of the underlying problem of time-domain simulation of molecular spectra to the degrees of freedom and control fields available in a trapped-ion quantum simulator. We experimentally demonstrate our algorithm on a trapped-ion device, exploiting both intrinsic electronic and motional degrees of freedom, showing excellent quantitative agreement for a single-mode vibronic photoelectron spectrum of SO$_2$.Comment: 13 pages, 8 figure

Insignificant Change in Antarctic Snowfall Since the International Geophysical Year

Antarctic snowfall exhibits substantial variability over a range of timescales, with consequent impacts on global sea level and the mass balance of the ice sheets. To assess how snowfall has affected the thickness of the ice sheets in Antarctica and to provide an extended perspective, we derived a 50-year time series of snowfall accumulation over the continent is derived by combining model simulations and observations primilarly from ice cores. There has been no statistically significant change in snowfall since the 1950s indicating that Antarctic precipitation is not mitigating global sea level rise as expected, despite recent winter warming of the overlying atmosphere

Molecular identification of adenoviruses associated with respiratory infection in Egypt from 2003 to 2010.

BACKGROUND: Human adenoviruses of species B, C, and E (HAdV-B, -C, -E) are frequent causative agents of acute respiratory infections worldwide. As part of a surveillance program aimed at identifying the etiology of influenza-like illness (ILI) in Egypt, we characterized 105 adenovirus isolates from clinical samples collected between 2003 and 2010. METHODS: Identification of the isolates as HAdV was accomplished by an immunofluorescence assay (IFA) and confirmed by a set of species and type specific polymerase chain reactions (PCR). RESULTS: Of the 105 isolates, 42% were identified as belonging to HAdV-B, 60% as HAdV-C, and 1% as HAdV-E. We identified a total of six co-infections by PCR, of which five were HAdV-B/HAdV-C co-infections, and one was a co-infection of two HAdV-C types: HAdV-5/HAdV-6. Molecular typing by PCR enabled the identification of eight genotypes of human adenoviruses; HAdV-3 (n = 22), HAdV-7 (n = 14), HAdV-11 (n = 8), HAdV-1 (n = 22), HAdV-2 (20), HAdV-5 (n = 15), HAdV-6 (n = 3) and HAdV-4 (n = 1). The most abundant species in the characterized collection of isolates was HAdV-C, which is concordant with existing data for worldwide epidemiology of HAdV respiratory infections. CONCLUSIONS: We identified three species, HAdV-B, -C and -E, among patients with ILI over the course of 7 years in Egypt, with at least eight diverse types circulating

The Rise of Adaptive Platform Trials in Critical Care

As durable learning research systems, adaptive platform trials represent a transformative new approach to accelerating clinical evaluation and discovery in critical care. This Perspective provides a brief introduction to the concept of adaptive platform trials, describes several established and emerging platforms in critical care, and surveys some opportunities and challenges for their implementation and impact.<br/

Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

Background: To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods: Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [ 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results: Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion: During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two staged, adaptive placebo controlled trial (APRICOT)

Background Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease affecting the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. Objective To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit for PPP. Methods A randomised (1:1), double-blind, two-staged, adaptive, UK multi-centre, placebo-controlled trial. Participants had a diagnosis of PPP (>6 months) requiring systemic therapy. Treatment was eight weeks of anakinra or placebo via daily self-administered subcutaneous injections. The primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Results A total of 374 patients were screened and 64 were enrolled (31 anakinra, 33 placebo) with mean baseline PPPASI 17.8 (SD=10.5); PPP investigator’s global assessment severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in intention-to-treat analysis, -1.65, 95% CI [-4.77 to 1.47], p=0.300. Secondary objective measures including fresh pustule count (2.94, 95% CI [-26.44 to 32.33] favouring anakinra), total pustule count (-30.08, 95% CI [-83.20 to 23.05] favouring placebo), and patient-reported outcomes, similarly did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect (CACE) for an individual who receives ≥90% total treatment (48% anakinra group), was -3.80, 95% CI [-10.76 to 3.16], p=0.285. No serious adverse events occurred. Conclusions No evidence for superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP