Patterns of prescribing in the management of gastro-oesophageal reflux in infants in Scotland.

The aim of this study was to determine trends over time and geographical differences in prescribing for gastro-oesophageal reflux (GOR) and gastro-oesophageal reflux disease (GORD) in infants aged 0–1 year in Scotland. National prescribing data obtained from the Information Services Division of NHS Scotland (ISD Scotland) was quantitatively analysed using the software tool Minitab16. Prescribing of the three key medicines, alginate, omeprazole and ranitidine, used in the management of GOR and GORD in infants aged 0–1 year increased in Scotland over the 7 years between 2010 and 2016. The rise in the prescribing rates of alginate, omeprazole and ranitidine is a cause for concern given the uncertainty regarding the efficacy of these medicines in this age group, and that omeprazole and ranitidine are not licensed for use in infants under 1 year of age in the UK. While the data suggest that the prescribing rate of alginate may have stabilised, the increasing trends for omeprazole and ranitidine show no sign of abating and this may have financial implications for the NHS, as well as potential ethical and health implications for young infants

Orientation and structure of the Ndc80 complex on the microtubule lattice

The four-subunit Ndc80 complex, comprised of Ndc80/Nuf2 and Spc24/Spc25 dimers, directly connects kinetochores to spindle microtubules. The complex is anchored to the kinetochore at the Spc24/25 end, and the Ndc80/Nuf2 dimer projects outward to bind to microtubules. Here, we use cryoelectron microscopy and helical image analysis to visualize the interaction of the Ndc80/Nuf2 dimer with microtubules. Our results, when combined with crystallography data, suggest that the globular domain of the Ndc80 subunit binds strongly at the interface between tubulin dimers and weakly at the adjacent intradimer interface along the protofilament axis. Such a binding mode, in which the Ndc80 complex interacts with sequential α/β-tubulin heterodimers, may be important for stabilizing kinetochore-bound microtubules. Additionally, we define the binding of the Ndc80 complex relative to microtubule polarity, which reveals that the microtubule interaction surface is at a considerable distance from the opposite kinetochore-anchored end; this binding geometry may facilitate polymerization and depolymerization at kinetochore-attached microtubule ends

Air and surface sampling for monkeypox virus in a UK hospital: an observational study

Background An outbreak of monkeypox virus infections in non-endemic countries was recognised on May 12, 2022. As of September 29, more than 67 000 infections have been reported globally, with more than 3400 confirmed cases in the UK by September 26. Monkeypox virus is believed to be predominantly transmitted through direct contact with lesions or infected body fluids, with possible involvement of fomites and large respiratory droplets. A case of monkeypox in a health-care worker in the UK in 2018 was suspected to be due to virus exposure while changing bedding. We aimed to measure the extent of environmental contamination in the isolation rooms of patients with symptomatic monkeypox. Methods We investigated environmental contamination with monkeypox virus from infected patients admitted to isolation rooms at the Royal Free Hospital (London, UK) between May 24 and June 17, 2022. Surface swabs of high-touch areas in five isolation rooms, of the personal protective equipment (PPE) of health-care workers in doffing areas in three rooms, and from air samples collected before and during bedding changes in five rooms were analysed using quantitative PCR to assess monkeypox virus contamination levels. Virus isolation was performed to confirm presence of infectious virus in selected positive samples. Findings We identified widespread surface contamination (56 [93%] of 60 samples were positive) in occupied patient rooms (monkeypox DNA cycle threshold [Ct] values 24·7–37·4), on health-care worker PPE after use (Ct 26·1–35·6), and in PPE doffing areas (Ct 26·3–36·8). Of 20 air samples taken, five (25%) were positive. Three (75%) of four air samples collected before and during a bedding change in one patient's room were positive (Ct 32·7–36·2). Replication-competent virus was identified in two (50%) of four samples selected for viral isolation, including from air samples collected during bedding change. Interpretation These data show contamination in isolation facilities and potential for suspension of monkeypox virus into the air during specific activities. PPE contamination was observed after clinical contact and changing of bedding. Contamination of hard surfaces in doffing areas supports the importance of cleaning protocols, PPE use, and doffing procedures. Fundin

A multinational case series describing successful treatment of persistent SARS-CoV-2 infection caused by Omicron sublineages with prolonged courses of nirmatrelvir/ritonavir.

The optimum treatment for persistent infection with SARS-CoV-2 is not known. Our case series, across 5 hospitals in 3 countries, describes 11 cases where persistent SARS-CoV-2 infection was successfully treated with prolonged courses (median 10 days, range 10-18) of nirmatrelvir/ritonavir (Paxlovid). Most cases (9/11) had haematological malignancy and ten (10/11) had received CD20 depleting therapy. The median duration of infection was 103 days (IQR 85-138). The majority (10/11) were hospitalised, and seven (7/11) had severe/critical disease. All survived and 9/11 demonstrated viral clearance, almost half (4/9) of whom received nirmatrelvir/ritonavir as monotherapy. This case series suggests prolonged nirmatrelvir/ritonavir has a role in treating persistent infection

Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination : a nested case-control within the SIREN study

Funding: This study was supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grant from the UK Medical Research Council (grant number MR/W02067X/1). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2087, CC1283), the UK Medical Research Council (CC2087, CC1283), and the Wellcome Trust (CC2087, CC1283).Objectives To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. Methods We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. Results We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001–0·31) and LV-N Alpha (OR 0·07, CI 0·009–0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03–0·64) and Alpha (0·06, CI 0·008–0·40). Conclusions Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. Trial registration number ISRCTN11041050Publisher PDFPeer reviewe

The need for focused, hard X-ray investigations of the Sun

Understanding accelerated particles at the Sun is one of the most important problems in heliophysics. Flare-accelerated particles have huge energies; are an important source of particles in the heliosphere; and are the most important corollary to other areas of high-energy astrophysics. This paper describes the scientific motivation for X-ray studies of particle acceleration at the Sun

Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA.

Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA (lncRNA), a heterogeneous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA (miRNA) pathways. lncRNA has been shown to act as both a source and an inhibitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying complexes by directing them to specific loci

The need for focused, hard X-ray investigations of the Sun

Understanding the nature of energetic particles in the solar atmosphere is one of the most important outstanding problems in heliophysics. Flare-accelerated particles compose a huge fraction of the flare energy budget; they have large influences on how events develop; they are an important source of high-energy particles found in the heliosphere; and they are the single most important corollary to other areas of high-energy astrophysics. Despite the importance of this area of study, this topic has in the past decade received only a small fraction of the resources necessary for a full investigation. For example, NASA has selected no new Explorer-class instrument in the past two decades that is capable of examining this topic. The advances that are currently being made in understanding flare-accelerated electrons are largely undertaken with data from EOVSA (NSF), STIX (ESA), and NuSTAR (NASA Astrophysics). This is despite the inclusion in the previous Heliophysics decadal survey of the FOXSI concept as part of the SEE2020 mission, and also despite NASA's having invested heavily in readying the technology for such an instrument via four flights of the FOXSI sounding rocket experiment. Due to that investment, the instrumentation stands ready to implement a hard X-ray mission to investigate flare-accelerated electrons. This white paper describes the scientific motivation for why this venture should be undertaken soon.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 15 pages, 5 figure