Background Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. MethodsIn this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 434 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0•32 [95% CI 0•27-0•37]) and 82% at 8 weeks (0•18 [0•14-0•23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

Absolute oscillator strengths in the region of carbon and fluorine K-shell excitation have been derived for CH~CH2, CH2CHF, eis-CHFCHF, CH2CF2, CHFCF2, CFqCF2, 1,3-C4H6, and 1,3-C4F6 from electron-energy-loss spectra recorded under dipole-dominated conditions. The methods used to derive absolute oscillator strengths from relative energy-loss intensities are discussed in detail. The accuracy of the procedures is tested through comparisons with literature results for Nz, CO, and CO&. The total C 1s~~* and C 1s~o.*(C-F) intensities increase systematically as the degree of fluorination increases. The spectra are discussed in terms of bond-length correlation and potential barrier concepts.

Public Health England, GlaxoSmithKline.

Summary We have demonstrated the feasibility of an endoscopic ultrasound-guided injectable hydrogel separation technique using a cadaveric model to increase the space between the head of the pancreas and duodenum. Using modeling studies, we identified the minimum distance of this separation for optimal sparing of the duodenum, setting the foundation for future clinical trials using this technique to enable dose escalation with either stereotactic or intensity-modulated radiation therapy for patients with unresectable pancreatic cancer. Purpose We assessed the feasibility and theoretical dosimetric advantages of an injectable hydrogel to increase the space between the head of the pancreas (HOP) and duodenum in a human cadaveric model. Methods and Materials Using 3 human cadaveric specimens, an absorbable radiopaque hydrogel was injected between the HOP and duodenum by way of open laparotomy in 1 case and endoscopic ultrasound (EUS) guidance in 2 cases. The cadavers were subsequently imaged using computed tomography and dissected for histologic confirmation of hydrogel placement. The duodenal dose reduction and planning target volume (PTV) coverage were characterized using pre- and postspacer injection stereotactic body radiation therapy (SBRT) plans for the 2 cadavers with EUS-guided placement, the delivery method that appeared the most clinically desirable. Modeling studies were performed using 60 SBRT plans consisting of 10 previously treated patients with unresectable pancreatic cancer, each with 6 different HOP–duodenum separation distances. The duodenal volume receiving 15 Gy (V15), 20 Gy (V20), and 33 Gy (V33) was assessed for each iteration. Results In the 3 cadaveric studies, an average of 0.9 cm, 1.1 cm, and 0.9 cm HOP–duodenum separation was achieved. In the 2 EUS cases, the V20 decreased from 3.86 cm3 to 0.36 cm3 and 3.75 cm3 to 1.08 cm3 (treatment constraint <3 cm3), and the V15 decreased from 7.07 cm3 to 2.02 cm3 and 9.12 cm3 to 3.91 cm3 (treatment constraint <9 cm3). The PTV coverage improved or was comparable between the pre- and postinjection studies. Modeling studies demonstrated that a separation of 8 mm was sufficient to consistently reduce the V15, V20, and V33 to acceptable clinical constraints. Conclusions Currently, dose escalation has been limited owing to radiosensitive structures adjacent to the pancreas. We demonstrated the feasibility of hydrogel separation of the HOP and duodenum. Future studies will evaluate the safety and efficacy of this technique with the potential for more effective dose escalation using SBRT or intensity-modulated radiation therapy to improve the outcomes in patients with unresectable pancreatic cancer.

BACKGROUND 4CMenB is a protein-based meningococcal group B vaccine but the vaccine antigens may also be present on non-group B meningococci. In September 2015, the UK implemented 4CMenB into the national infant immunisation programme, alongside an emergency adolescent meningococcal ACWY (MenACWY) programme to control a national outbreak of group W (MenW) disease caused by a hypervirulent strain belonging to the ST11 clonal complex. The adolescent programme aimed to provide direct protection for adolescents and, over time, indirect (herd) protection across the population. METHODS Public Health England conducts meningococcal disease surveillance in England. MenW cases confirmed during four years before and four years after implementation of both vaccines were analysed. Poisson models were constructed to estimate direct protection against MenW disease offered by the infant 4CMenB programme on top of the indirect impact of the adolescent MenACWY programme in children eligible for 4CMenB but not MenACWY. RESULTS Model estimates showed 69% (adjusted incidence rate ratio (IRR) 0.31, 95%CI, 0.20-0.67) and 52% (aIRR 0.48, 95%CI 0.28-0.81) fewer MenW cases than predicted among age-cohorts that were fully-eligible and partly-eligible for 4CMenB, respectively. There were 138 MenW cases in &5 year-olds. 4CMenB directly prevented 98 (95%CI, 34-201) cases, while the MenACWY programme indirectly prevented an additional 114 (conservative) to 899 (extreme) cases over four years. Disease severity was similar in 4CMenB-immunised and unimmunised children. CONCLUSIONS Our results provide the first real-world evidence of the direct protection afforded by 4CMenB against MenW:cc11 disease. 4CMenB has the potential to provide some protection against all meningococcal serogroups.

An electron momentum spectrometer has been constructed which measures electron binding energies and momenta by fully determining the kinematics of the incident, scattered, and ejected electrons resulting from (e,2e) ionizing collisions in a thin solid foil. The spectrometer operates with incident beam energies of 20–30 keV in an asymmetric, non-coplanar scattering geometry. Bethe ridge kinematics are used which for 20 keV incident energy has scattered electron energies of 18.8 keV at a polar angle of θs=14°and azimuthal angles φs in the range from −18° to +18° and ejected electrons of 1.2 keV and θe=76°with φe=π±6°. The technique uses transmission through the target foil, but it is most sensitive to the surface from which the 1.2 keV electrons emerge, to a depth of about 2 nm. Scattered and ejected electron energies and azimuthal angles are detected in parallel using position sensitive detection, yielding true coincidence count rates of 6 Hz from a 5.5 nm thick evaporated carbon target and an incident beam current of around 100 nA. The energy resolution is approximately 1.3 eV and momentum resolution approximately 0.15 a0−1. The energy resolution could readily be improved by monochromating the incident electron beam.

Background To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. Methods Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008–2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. Results A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y. Conclusions In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.

In England and Wales, approximately one half of all laboratory-confirmed meningococcal disease cases fail to yield a viable invasive isolate, primarily due to the use of antibiotics. Characterisation of non-culture meningococci has been restricted to the detection or sequencing of specific gene targets within clinical specimens. In this study we investigated the ability of the Agilent SureSelectXT kit to facilitate DNA enrichment and genome sequencing of meningococcal DNA within a small panel of blood and CSF specimens. A target-specific RNA oligonucleotide bait library was used to capture and enrich the bacterial DNA prior to next generation sequencing. A positive correlation between meningococcal DNA amount and genome coverage was observed with eight of the ten specimens producing genomes of acceptable quality. All commonly-used typing information derived from each acceptable non-culture genome matched those of an isolate from the same patient and the paired genomes showed a high level of congruence across indexed loci. We estimate that this technique could be used to perform whole genome sequencing on up to ∼45% of the positive specimens received by the Public Health England's Meningococcal Reference Unit. Further optimisation of the extraction and/or enrichment processes may, however, increase the proportion of non-culture cases from which quality genomes can be obtained.