Healthcare-prescribed opioids are a known contributor to the opioid epidemic. Locally, there was an identified opportunity to improve opioid prescribing practices in cardiac surgical patients. The cardiac surgical team sought to standardise prescribing practices in postoperative patients and reduce opioid prescriptions at discharge. The improvement was undertaken at a large midwestern freestanding children’s hospital with over 400 beds and 120 cardiac surgeries annually. A multidisciplinary team was formed, using the model for Improvement to guide the improvement work. The key improvement interventions included standardised evidence-based prescribing guidelines based patient age and surgical approach, enhanced pain management with non-opioid medications, and integration of prescribing guidelines into the electronic health record. The primary outcome measure was rate of compliance with the prescribing guidelines and secondary measures included morphine equivalent dosing at discharge, opioid-free discharge, and length of stay. A balancing measure of opioid re-prescriptions was tracked. There were 289 patients included in the primary study period (January 2019 through December 2021). Sustainability of key outcomes was tracked though December 2022. The guideline compliance increased from 24% to 100%. The morphine equivalent dosing decreased to 22.5 in 2021 then 0 in 2022, from baseline of 36.25 in 2019. Opioid-free discharges decreased from 8% (2019) to 1.5% (2021) and 0% in 2022. Establishment and compliance with standardised guidelines for post-operative cardiac surgical pain management yielded a reduction in morphine equivalent dosing, an increase opioid-free discharges, and no increase in length of stay or opioid re-prescriptions.

Although radiocarbon-accelerator mass spectrometry (14C-AMS) is an important tool for the establishment of soil chronology, its application is challenging due to the complex nature of soil samples. In the present study, chemical extraction methodologies were tested to obtain the most representative age of Amazonian soil deposition by 14C-AMS. We performed acid hydrolysis with different numbers of extractions, as well as treatments combining acid and bases and quartered and non-quartered samples. The ages of the soil organic matter (SOM) fractions were compared to the ages of naturally buried charcoal samples at similar depths. The results showed that the age of the non-hydrolyzable inert fraction of soil was closer to the age of charcoal and older than the ages of humin. It was also observed that the quartering process can influence the results, since the dating of the humin fraction showed variability in the results. Our results are important to provide information about the most suitable method for the 14C-AMS dating of soil samples for paleoenvironment reconstruction studies.

The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration and dose needed to elicit gut microbial changes and whether these changes also influence microbial metabolites remain unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)) on the stool microbiota and microbial metabolite concentrations in plasma, stool and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study. The DISC study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma and urine by high-performance liquid chromatography. A total of fifty-eight participants with paired samples available were included. After 50 d, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention. The gut microbiota and fecal, plasma and urinary microbial metabolites were stable in response to a 50-d fibre intervention in middle-aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome and host health.

The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.

To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25–1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22–1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22–1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.

Several recent studies conclude that an increase in the pathogenicity of SARS-CoV-2 cannot be ruled out. However, it should be noted that SARS-CoV-2 is a ‘direct’ respiratory virus – meaning it is usually spread by the respiratory route but does not routinely pass through the lymphatics like measles and smallpox. Providing its tropism does not change, it will be unique if its pathogenicity does not decrease until it becomes similar to common cold viruses. Ewald noted in the 1980s that respiratory viruses may evolve mildness because their spread benefits from the mobility of their hosts. This review examines factors that usually lower respiratory viruses’ severity, including heat sensitivity (which limits replication in the warmer lungs) and changes to the virus’s surface proteins. Other factors may, however, increase pathogenicity, such as replication in the lymphatic system and spreading via solid surfaces or faecal matter. Furthermore, human activities and political events could increase the harmfulness of SARS-CoV-2, including the following: large-scale testing, especially when the results are delayed; transmission in settings where people are close together and not free to move around; poor hygiene facilities; and social, political, or cultural influences that encourage sick individuals to remain active, including crises such as wars. If we can avoid these eventualities, SARS-CoV-2 is likely to evolve to be milder, although the timescale is uncertain. Observations of influenza-like pandemics suggest it may take around two decades for COVID-19 to become as mild as seasonal colds.

With the growing global population and climate change, achieving food security is a pressing challenge(1). Vertical farming has the potential to support local food production and security. In the UK population females and younger adults appear to be particularly vulnerable to micronutrient shortfalls from food sources alone. Levels of micronutrient intakes including zinc and iron are below the recommended daily intake(2). As a Total Controlled Environment Agriculture (TCEA) system, vertical farming employs hydroponics using a nutrient solution which offers opportunities to modulate nutrient uptake, and thus influence plant mineral and vitamin composition(3).

In this study we aimed to determine the suitability of different crop types for soilless agronomic biofortification with zinc and iron to achieve biofortified crops.

In this study, we investigated the effect of the addition of 20ppm (+20 mg L−1) of zinc (ZnSO4) or iron (Fe-EDTA) to the nutrient solution on the growth and nutritional components in pea microgreens, kale microgreens and kale baby leaf plants. The growth conditions were kept identical throughout the treatments with photoperiod 18 h d-1, temperature 20-22°C and relative humidity at 70-80%. Plant growth, mineral composition, glucosinolate content and protein content were evaluated. Results were analysed using ANOVA (p<0.05, Tukey’s test).

It was determined that higher amounts of zinc in the nutrient solution resulted in significantly higher levels of zinc in all three crops (p<0.05), with increases of 205% in pea microgreens, 264% in babyleaf kale and 217% in kale microgreens compared to the control plants. Higher amounts of iron in the nutrient solution resulted in significantly higher levels of iron only in pea microgreens, with an increase of 38% (p<0.05). Neither dosing regimen negatively influenced the overall crop performance.

These results suggest that the three different crops are suitable for soilless biofortification with zinc and iron, although pea microgreens were the only crop that had a significant increase in iron upon iron-dosing.

Background: Continuous spike and waves during slow-wave sleep (CSWS) is a childhood-onset epileptic encephalopathy that is characterized by clinical seizures, electrical status epilepticus during sleep (ESES), and neurocognitive regression. Early intervention can preserve neurocognitive development, and vagus nerve stimulator (VNS) therapy had positive outcomes in the few previously reported case reports. We present three patients with intractable CSWS unresponsive to medications, who had a positive response to VNS therapy. Methods: Review of clinical records of three pediatric patients diagnosed with CSWS were compared for selected clinical outcomes and electrographic data both prior to and in the years following the initiation of VNS therapy. Results: Three patients now aged 13, 16 and 20 years, were treated with VNS following intolerance and a lack of response to multiple medications (5-9) for CSWS. The ketogenic diet was not an option. The CSWS resolved in all three patients, resulting in improved cognitive function. Patient 3 had resurgence of CSWS on EEG when the VNS settings inadvertently reset to the factory settings and improved with adjustment in the cycling. Conclusions: In patients who are unresponsive to medication, VNS provides an alternative option for resolving CSWS to preserve and, in some cases, potentially restore neurocognitive function.

Lithofacies and biostratigraphical analysis has enabled the establishment of a stratigraphic event framework for Ludfordian and Pridoli strata in south Wales and the Welsh Borderland. In SW Wales, the Golden Grove Axis acted as a structural hinge separating the shallow marine storm-influenced Cae’r mynach Seaway from a pediment surface above which Ludfordian colluvium (Abercyfor Formation) was deposited. The Axis seeded four NW-derived river-influenced delta progrades of Leintwardinian to early Pridoli age (Tilestones Formation). A NE-sourced early Pridoli wave-influenced delta deposited the Downton Castle Sandstone Formation (DCSF), coeval to the youngest Tilestones prograde, with a lateral interface existing between Mynydd Epynt and the Clun Forest area. Except for the Malverns area, the DCSF is no longer recognized south of the Neath Disturbance. Early Pridoli forced regression promoted widespread subaerial exposure north of the Neath Disturbance, with incision into tracts close to the Welsh Borderland Fault System. The basinward-shift in facies belts resulted in marine erosion and deposition of a phosphatic ravinement pebble lag. The wave-influenced Clifford’s Mesne Sandstone Formation delta subsequently seeded on the Gorsley Axis with tidally influenced Rushall Formation accumulating in a back-barrier setting. The Pwll-Mawr Formation records the easterly advance of coeval coastal deposits on the western side of the remnant Cae’r mynach Seaway. Behind migrating delta coastlines, green muds accumulated on coastal plains (Temeside Mudstone Formation) with better drained red dryland alluvium (Moor Cliffs Formation) charting expansion of Old Red Sandstone lithofacies. Mid-Pridoli incision preserves the Pont ar Llechau Formation estuarine valley fill.

Melting icebergs provide nearly half of the total freshwater flux from ice shelves to the ocean, but the availability of accurate, data-constrained melting rate parametrisations limits the correct representation of this process in ocean models. Here, we investigate the melting of a vertical ice face in a warm, salt-stratified environment in a laboratory setting. Observations of the depth-dependent melting rates ${m}$ and boundary layer flow speed $U$ are reported for a range of initially uniform far-field ambient temperatures $T_a$ above ${10}\,^{\circ }{\rm C}$. Ice scallops are characteristic features observed in all experiments, with the width of the scallops consistent with the theory of double-diffusive layers. The morphology of the scallops changes from symmetric about the scallop centre in the colder experiments to asymmetric in the warmer experiments. Observed melting rates are consistent with a melting rate scaling of the form ${m}\propto U\,\Delta T_a$ proposed by previous work in less extreme parameter regimes, where $\Delta T_a$ is the magnitude of thermal driving between the ambient and ice–fluid interface. Our results indicate that ice scalloping is closely linked to the naturally convecting flow of the ambient fluid. Depth-averaged melting rates depend on the buoyancy frequency in the ambient fluid, and double-diffusive convection promotes a turbulent-flux regime distinct from that explained previously in an unstratified regime. These findings have implications for parametrising melting rates of icebergs and glaciers in numerical models or potential freshwater harvesting operations, and provide insights into the interplay between stratification and ice melting.