Implementation of national guidelines on antenatal magnesium sulfate for neonatal neuroprotection: extended evaluation of the effectiveness and cost-effectiveness of the National PReCePT Programme in England.

Background: Since 2015, the National Institute for Health and Care Excellence (NICE) guidelines have recommended antenatal magnesium sulfate (MgSO) for mothers in preterm labour (<30 weeks' gestation) to reduce the risk of cerebral palsy (CP) in the preterm baby. However, the implementation of this guideline in clinical practice was slow, and MgSO use varied between maternity units. In 2018, the PRrevention of Cerebral palsy in PreTerm labour (PReCePT) programme, an evidence-based quality improvement (QI) intervention to improve use of MgSO, was rolled out across England.

CountASAP: A Lightweight, Easy to Use Python Package for Processing ASAPseq Data.

Declining sequencing costs coupled with the increasing availability of easy-to-use kits for the isolation of DNA and RNA transcripts from single cells have driven a rapid proliferation of studies centered around genomic and transcriptomic data. Simultaneously, a wealth of new techniques have been developed that utilize single cell technologies to interrogate a broad range of cell-biological processes. One recently developed technique, transposase-accessible chromatin with sequencing (ATAC) with select antigen profiling by sequencing (ASAPseq), provides a combination of chromatin accessibility assessments with measurements of cell-surface marker expression levels.

Maternal preconception stress produces sex-specific effects at the maternal:fetal interface to impact offspring development and phenotypic outcomes†.

Entering pregnancy with a history of adversity, including adverse childhood experiences and racial discrimination stress, is a predictor of negative maternal and fetal health outcomes. Little is known about the biological mechanisms by which preconception adverse experiences are stored and impact future offspring health outcomes. In our maternal preconception stress (MPS) model, female mice underwent chronic stress from postnatal days 28-70 and were mated 2 weeks post-stress.

Quality improvement interventions to increase the uptake of magnesium sulphate in preterm deliveries for the prevention of cerebral palsy (PReCePT study): a cluster randomised controlled trial.

Objective: To compare two quality improvement (QI) interventions to improve antenatal magnesium sulphate (MgSO ) uptake in preterm births for the prevention of cerebral palsy.

Design: Unblinded cluster randomised controlled trial.

Setting: Academic Health Sciences Network, England, 2018.

Using the recommended summary plan for emergency care and treatment (ReSPECT) in care homes: a qualitative interview study.

Background: The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) is an advance care planning process designed to facilitate discussion and documentation of preferences for care in a medical emergency. Advance care planning is important in residential and nursing homes.

Aim: To explore the views and experiences of GPs and care home staff of the role of ReSPECT in: (i) supporting, and documenting, conversations about care home residents' preferences for emergency care situations, and (ii) supporting decision-making in clinical emergencies.

Dendritic cells Trigger IFN-γ secretion by NK cells independent of IL-12 and IL-18.

It is commonly believed that IL-12 produced by DCs in response to pathogens is the first signal that stimulates the production of IFN-γ by NK cells. However, IL-12 production by DCs in response to bacterial LPS depends on either engagement of CD40 by CD40L on activated T cells or IFN-γ from NK cells. This suggests that during the primary immune response, NK cells produce IFN-γ before IL-12 production by DCs.

Evaluating a pre-surgical health optimisation programme: a feasibility study.

Background: Health optimisation programmes are increasingly popular and aim to support patients to lose weight or stop smoking ahead of surgery, yet there is little published evidence about their impact. This study aimed to assess the feasibility of evaluating a programme introduced by a National Health Service (NHS) clinical commissioning group offering support to smokers/obese patients in an extra 3 months prior to the elective hip/knee surgery pathway.

Methods: Feasibility study mapping routinely collected data sources, availability and completeness for 502 patients referred to the hip/knee pathway in February-July 2018.

Prognostic value of National Early Warning Scores (NEWS2) and component physiology in hospitalised patients with COVID-19: a multicentre study.

Background: National Early Warning Scores (NEWS2) are used to detect all-cause deterioration. While studies have looked at NEWS2, the use of virtual consultation and remote monitoring of patients with COVID-19 mean there is a need to know which physiological observations are important.

Aim: To investigate the relationship between outcome and NEWS2, change in NEWS2 and component physiology in COVID-19 inpatients.

Broadband sum-frequency generation of spectrally incoherent pulses.

We study and demonstrate the nonlinear frequency conversion of broadband optical pulses from 1053 nm to 351 nm using sum-frequency generation with a narrowband pulse at 526.5 nm. The combination of angular dispersion and noncollinearity cancels out the wave-vector mismatch and its frequency derivative, yielding an order-of-magnitude increase in spectral acceptance compared to conventional tripling.

Perinatal exposure to tetracycline contributes to lasting developmental effects on offspring.

Background: For more than 30 years, the tetracycline on/off system of inducible gene expression has been leveraged to study disease mechanisms across many research areas, especially that of metabolism and neuroscience. This system requires acute or chronic exposure to tetracycline derivatives, such as doxycycline, to manipulate gene expression in a temporal and tissue-specific manner, with exposure often being restricted to gestational and early developmental windows. Despite evidence showing that early life antibiotic exposure has adverse effects on gut microbiota, metabolism, physiology, immunity and behavior, little is known regarding the lasting impact of doxycycline treatment on relevant outcomes in experimental offspring.

Commissioner, clinician, and patient experiences of a pre-surgical health optimisation programme - a qualitative study.

Background: Health optimisation programmes are an increasingly popular policy intervention that aim to support patients to lose weight or stop smoking ahead of surgery. There is little evidence about their impact and the experience of their use. The aim of this study was to investigate the experiences and perspectives of commissioners, clinicians and patients involved in a locality's health optimisation programme in the United Kingdom.

Evaluation of a standardized collection device for exhaled breath sampling onto thermal desorption tubes.

The Respiration Collector for In Vitro Analysis (ReCIVA) sampler, marketed by Owlstone Medical, provides a step forward in exhaled breath sampling through active sampling directly onto thermal desorption (TD) tubes. Although an improvement to the issues surrounding breath bag sampling, the ReCIVA device, first released in 2015, is a relatively new research and clinical tool that requires further exploration. Here, data are presented comparing two distinct ReCIVA devices.

Characterization of standardized breath sampling for off-line field use.

Due to several sources of potential variability associated with exhaled breath bag sampling procedures for off-line analysis, the Respiration Collector for in vitro Analysis (ReCIVA) sampler was developed. Although designed to improve upon several pitfalls of sampling with exhaled breath bags, the ReCIVA remains a minimally studied research tool. In this manuscript, several attributes of the ReCIVA sampler are investigated among three individual tests, such as background contamination, control software version, performance of different adsorbent tubes, duplicate sample production, and comparison to exhaled breath bags.

The potential of nanoflow liquid chromatography-nano electrospray ionisation-mass spectrometry for global profiling the faecal metabolome.

Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised.

Monitoring Neonicotinoid Exposure for Bees in Rural and Peri-urban Areas of the U.K. during the Transition from Pre- to Post-moratorium.

Concerns regarding the impact of neonicotinoid exposure on bee populations recently led to an EU-wide moratorium on the use of certain neonicotinoids on flowering crops. Currently, evidence regarding the impact, if any, the moratorium has had on bees' exposure is limited. We sampled pollen and nectar from bumblebee colonies in rural and peri-urban habitats in three U.

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

Importance: Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment.

Objective: To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality.

Design, Setting, And Participants: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom.

Arbuscular Mycorrhizal Fungi and Plant Chemical Defence: Effects of Colonisation on Aboveground and Belowground Metabolomes.

Arbuscular mycorrhizal fungal (AMF) colonisation of plant roots is one of the most ancient and widespread interactions in ecology, yet the systemic consequences for plant secondary chemistry remain unclear. We performed the first metabolomic investigation into the impact of AMF colonisation by Rhizophagus irregularis on the chemical defences, spanning above- and below-ground tissues, in its host-plant ragwort (Senecio jacobaea). We used a non-targeted metabolomics approach to profile, and where possible identify, compounds induced by AMF colonisation in both roots and shoots.

Concentrating mixtures of neuroactive pharmaceuticals and altered neurotransmitter levels in the brain of fish exposed to a wastewater effluent.

Fish can be exposed to a variety of neuroactive pharmaceuticals via the effluent discharges from wastewater treatment plants and concerns have arisen regarding their potential impacts on fish behaviour and ecology. In this study, we investigated the uptake of 14 neuroactive pharmaceuticals from a treated wastewater effluent into blood plasma and brain regions of roach (Rutilus rutilus) after exposure for 15days. We show that a complex mixture of pharmaceuticals including, 6 selective serotonin reuptake inhibitors, a serotonin-noradrenaline reuptake inhibitor, 3 atypical antipsychotics, 2 tricyclic antidepressants and a benzodiazepine, concentrate in different regions of the brain including the telencephalon, hypothalamus, optic tectum and hindbrain of effluent-exposed fish.

Quantifying exposure of wild bumblebees to mixtures of agrochemicals in agricultural and urban landscapes.

The increased use of pesticides has caused concern over the possible direct association of exposure to combinations of these compounds with bee health problems. There is growing proof that bees are regularly exposed to mixtures of agrochemicals, but most research has been focused on managed bees living in farmland, whereas little is known about exposure of wild bees, both in farmland and urban habitats. To determine exposure of wild bumblebees to pesticides in agricultural and urban environments through the season, specimens of five different species were collected from farms and ornamental urban gardens in three sampling periods.

Disruption of the Prostaglandin Metabolome and Characterization of the Pharmaceutical Exposome in Fish Exposed to Wastewater Treatment Works Effluent As Revealed by Nanoflow-Nanospray Mass Spectrometry-Based Metabolomics.

Fish can be exposed to a complex mixture of chemical contaminants, including pharmaceuticals, present in discharges of wastewater treatment works (WwTWs) effluents. There is little information on the effects of effluent exposure on fish metabolism, especially the small molecule signaling compounds which are the biological target of many pharmaceuticals. We applied a newly developed sensitive nanoflow-nanospray mass spectrometry nontargeted profiling technique to identify changes in the exposome and metabolome of roach (Rutilus rutilus) exposed to a final WwTWs effluent for 15 days.

The conceptualization and measurement of cognitive reserve using common proxy indicators: Testing some tenable reflective and formative models.

Introduction: The examination of cognitive reserve (CR) literature reveals a lack of consensus regarding conceptualization and pervasive problems with its measurement. This study aimed at examining the conceptual nature of CR through the analysis of reflective and formative models using eight proxies commonly employed in the CR literature. We hypothesized that all CR proxies would significantly contribute to a one-factor reflective model and that educational and occupational attainment would produce the strongest loadings on a single CR factor.

Nanoflow-Nanospray Mass Spectrometry Metabolomics Reveals Disruption of the Urinary Metabolite Profiles of HIV-Positive Patients on Combination Antiretroviral Therapy.

Background: The use of combination antiretroviral therapy (cART) has substantially improved the outlook for patients with HIV infection. However, lifelong exposure to cART is also associated with adverse metabolic changes and an enhanced risk of renal, hepatic, and cardiovascular dysfunction. This study investigated disruptions of the urinary metabolome of cART-exposed patients, thereby furthering our understanding of some of the side effects of pharmaceutical intervention.

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee.

Background: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes.

Methods: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015).

Results: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%).

Contamination of wild plants near neonicotinoid seed-treated crops, and implications for non-target insects.

Neonicotinoid insecticides are commonly-used as seed treatments on flowering crops such as oilseed rape. Their persistence and solubility in water increase the chances of environmental contamination via surface-runoff or drainage into areas adjacent to the crops. However, their uptake and fate into non-target vegetation remains poorly understood.