Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China.

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China. Methods: A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome-assessed using the modified Barthel disability index-were recorded and compared. Findings: A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score ≥ 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (≥15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death. Conclusion: TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

Comparison of deep inspiration breath hold and free breathing intensity modulated proton therapy of locally advanced lung cancer.

Background and purpose: For locally advanced non-small cell lung cancer (LA-NSCLC), intensity-modulated proton therapy (IMPT) can reduce organ at risk (OAR) doses compared to intensity-modulated radiotherapy (IMRT). Deep inspiration breath hold (DIBH) reduces OAR doses compared to free breathing (FB) in IMRT. In IMPT, differences in dose distributions and robustness between DIBH and FB are unclear. In this study, we compare DIBH to FB in IMPT, and IMPT to IMRT. Materials and methods: Fortyone LA-NSCLC patients were prospectively included. 4D computed tomography images (4DCTs) and DIBH CTs were acquired for treatment planning and during weeks 1 and 3 of treatment. A new system for automated robust planning was developed and used to generate a FB and a DIBH IMPT plan for each patient. Plans were compared in terms of dose-volume parameters and normal tissue complication probabilities (NTCPs). Dose recalculations on repeat CTs were used to compare inter-fraction plan robustness. Results: In IMPT, DIBH reduced median lungs Dmean from 9.3 Gy(RBE) to 8.0 Gy(RBE) compared to FB, and radiation pneumonitis NTCP from 10.9 % to 9.4 % (p < 0.001). Inter-fraction plan robustness for DIBH and FB was similar. Median NTCPs for radiation pneumonitis and mortality were around 9 percentage points lower with IMPT than IMRT (p < 0.001). These differences were much larger than between FB and DIBH within each modality. Conclusion: DIBH IMPT resulted in reduced lung dose and radiation pneumonitis NTCP compared to FB IMPT. Inter-fraction robustness was comparable. OAR doses were far lower in IMPT than IMRT.

Population-wide active case finding as a strategy to end TB.

Tuberculosis (TB) is the leading infectious cause of morbidity and mortality globally. Despite available tools for preventing, finding, and treating TB, many people with TB remain undiagnosed. In high-incidence settings, TB transmission is ubiquitous within the community, affecting both high-risk groups and the general population. In fact, most people who develop TB come from the general population. To disrupt the chain of transmission that sustains the TB epidemic, we need to find and treat everyone with infectious TB as early as possible, including those with minimal symptoms or subclinical TB who are unlikely to present for care. Important elements of an effective active case-finding strategy include effective social mobilisation and community engagement, using sensitive screening tools that can be used at scale, and embracing population-wide screening in high-incidence ('hot spot') areas. We require a better description of feasible delivery models, 'real-life' impact and cost effectiveness to enable wider implementation.

Compartmentalised enzyme-induced phase transformations in self-assembling lipid systems.

HYPOTHESIS: Understanding the digestion of lipid-based pharmaceutical formulations and food systems is necessary for optimising drug and nutrient delivery and has been extensively studied in bulk emulsion systems using the pH-stat method [1]. However, this approach is not suitable for investigation of individual lipid droplets, in particular the interface where the lipase acts. Microfluidic approaches to study digestion at lipid-water interfaces using droplet trapping have been proposed, however the aqueous phase in that case washes over the interface presenting uncertainty over the stoichiometry of interactions [2]. The internal interface of a Janus-like droplet, containing distinct aqueous and lipid compartments, mimics the interface of a lipid droplet in aqueous solution with controlled stoichiometry [3]. Hence, it was hypothesised that the internal interface of Janus droplets can offer a precise way to study the enzymatic digestion of lipids formulations. EXPERIMENTS: Using microfluidic methods, Janus-like droplets were formed by coalescing emulsion droplets containing lipid formulation and pancreatic lipase. Polarised light microscopy (PLM) and in-situ small-angle X-ray scattering (SAXS) were used to investigate the droplets. FINDINGS: PLM revealed the growth of an aligned inverse hexagonal phase (H2), and with SAXS showed that this phase transformation and alignment resulted from enzymatic digestion. A subsequent partial transformation from H2 to inverse bicontinuous cubic phase occurred when simulated intestinal fluid was used instead of Tris buffer. Suggesting that phospholipids and bile salts could diffuse across the internal interface to locally affect their surroundings.

Effect of retirement on loneliness: a longitudinal comparative analysis across Australia, China and the USA.

BACKGROUND: There is evidence that the transition to retirement can bring social challenges and may increase loneliness. Few studies have examined the impact of retirement on loneliness; most have been conducted in Western countries. It is important to examine the differences in loneliness postretirement across countries to identify patterns and risk factors that might influence the health and well-being of older adults. We aimed to examine the effect of retirement on loneliness among older adults in Australia, China and the USA. METHODS: Longitudinal analysis of data from population-based samples of Australian, Chinese and American adults over 50. Lagged and fully lagged adjusted models were applied. Social engagement was examined as an effect modifier and a sensitivity analysis was conducted among urban participants. RESULTS: Retirees had a higher predicted prevalence of loneliness than non-retirees in Australia (19.4% (95% CI 18.0% to 20.9%) vs 17.0% (95% CI 15.7% to 18.4%)) and in the USA (19.3% (95% CI 17.5% to 21.1%) vs 15.7% (95% CI 14.3% to 17.3%)). These differences were significant only in the USA. In China, loneliness was significantly lower in those who had retired (10.0% (95% CI 7.9% to 12.5%) vs 17.1% (95% CI 15.7% to 18.5%)). In Australia and the USA, voluntary retirees had the lowest loneliness and involuntary retirees had the highest. Social engagement did not modify the association between retirement and loneliness. CONCLUSIONS: Our findings imply that the effect of retirement should be considered within a cultural context to inform suitable and effective strategies to alleviate loneliness.

Diagnostic yield as an important metric for the evaluation of novel tuberculosis tests: rationale and guidance for future research.

Better access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of molecular WHO-recommended rapid diagnostics to replace sputum smear microscopy over the past decade, a large diagnostic gap remains. Of the estimated 10·6 million people who developed tuberculosis globally in 2022, more than 3·1 million were not diagnosed. An exclusive focus on improving tuberculosis test accuracy alone will not be sufficient to close the diagnostic gap for tuberculosis. Diagnostic yield, which we define as the proportion of people in whom a diagnostic test identifies tuberculosis among all people we attempt to test for tuberculosis, is an important metric not adequately explored. Diagnostic yield is particularly relevant for subpopulations unable to produce sputum such as young children, people living with HIV, and people with subclinical tuberculosis. As more accessible non-sputum specimens (eg, urine, oral swabs, saliva, capillary blood, and breath) are being explored for point-of-care tuberculosis testing, the concept of yield will be of growing importance. Using the example of urine lipoarabinomannan testing, we illustrate how even tests with limited sensitivity can diagnose more people with tuberculosis if they enable increased diagnostic yield. Using tongue swab-based molecular tuberculosis testing as another example, we provide definitions and guidance for the design and conduct of pragmatic studies that assess diagnostic yield. Lastly, we show how diagnostic yield and other important test characteristics, such as cost and implementation feasibility, are essential for increased effective population coverage, which is required for optimal clinical care and transmission impact. We are calling for diagnostic yield to be incorporated into tuberculosis test evaluation processes, including the WHO Grading of Recommendations, Assessment, Development, and Evaluations process, providing a crucial real-life implementation metric that complements traditional accuracy measures.

Dissecting the MUC5AC/ANXA2 signaling axis: implications for brain metastasis in lung adenocarcinoma.

Non-small cell lung carcinoma (NSCLC) exhibits a heightened propensity for brain metastasis, posing a significant clinical challenge. Mucin 5ac (MUC5AC) plays a pivotal role in the development of lung adenocarcinoma (LUAD); however, its role in causing brain metastases remains unknown. In this study, we aimed to investigate the contribution of MUC5AC to brain metastasis in patients with LUAD utilizing various brain metastasis models. Our findings revealed a substantial increase in the MUC5AC level in LUAD brain metastases (LUAD-BrM) samples and brain-tropic cell lines compared to primary samples or parental control cell lines. Intriguingly, depletion of MUC5AC in brain-tropic cells led to significant reductions in intracranial metastasis and tumor growth, and improved survival following intracardiac injection, in contrast to the observations in the control groups. Proteomic analysis revealed that mechanistically, MUC5AC depletion resulted in decreased expression of metastasis-associated molecules. There were increases in epithelial-to-mesenchymal transition, tumor invasiveness, and metastasis phenotypes in tumors with high MUC5AC expression. Furthermore, immunoprecipitation and proteomic analysis revealed a novel interaction of MUC5AC with Annexin A2 (ANXA2), which activated downstream matrix metalloproteases and facilitated extracellular matrix degradation to promote metastasis. Disrupting MUC5AC-ANXA2 signaling with a peptide inhibitor effectively abrogated the metastatic process. Additionally, treatment of tumor cells with an astrocyte-conditioned medium or the chemokine CCL2 resulted in upregulation of MUC5AC expression and enhanced brain colonization. In summary, our study demonstrates that the MUC5AC/ANXA2 signaling axis promotes brain metastasis, suggesting a potential therapeutic paradigm for LUAD patients with high MUC5AC expression.

An amplicon panel for high-throughput and low-cost genotyping of Pacific oyster.

Maintaining genetic diversity in cultured shellfish can be challenging due to high variance in individual reproductive success, founder effects, and rapid genetic drift, but is important to retain adaptive potential and avoid inbreeding depression. To support broodstock management and selective breeding in cultured Pacific oysters (Crassostrea (Magallana) gigas), we developed an amplicon panel targeting 592 genomic regions and SNP variants with an average of 50 amplicons per chromosome. Target SNPs were selected based on elevated observed heterozygosity or differentiation in Pacific oyster populations in British Columbia, Canada. The use of the panel for parentage applications was evaluated using multiple generations of oysters from a breeding program on Vancouver Island, Canada (n = 181) and families selected for Ostreid herpesvirus-1 resistance from the Molluscan Broodstock Program in Oregon, USA (n = 136). Population characterization was evaluated using wild, naturalized, farmed, or hatchery oysters sampled throughout the Northern Hemisphere (n = 190). Technical replicates showed high genotype concordance (97.5%; n = 68 replicates). Parentage analysis found suspected pedigree and sample handling errors, demonstrating the panel's value for quality control in breeding programs. Suspected null alleles were identified and found to be largely population dependent, suggesting population-specific variation impacting target amplification. Null alleles were identified using existing data without the need for pedigree information, and once they were removed, assignment rates increased to 93.0% and 86.0% of possible assignments in the two breeding program datasets. A pipeline for analyzing the amplicon sequence data from sequencer output, amplitools, is also provided.

Genome-wide association and expression quantitative trait loci in cattle reveals common genes regulating mammalian fertility.

Most genetic variants associated with fertility in mammals fall in non-coding regions of the genome and it is unclear how these variants affect fertility. Here we use genome-wide association summary statistics for Heifer puberty (pubertal or not at 600 days) from 27,707 Bos indicus, Bos taurus and crossbred cattle; multi-trait GWAS signals from 2119 indicine cattle for four fertility traits, including days to calving, age at first calving, pregnancy status, and foetus age in weeks (assessed by rectal palpation of the foetus); and expression quantitative trait locus for whole blood from 489 indicine cattle, to identify 87 putatively functional genes affecting cattle fertility. Our analysis reveals a significant overlap between the set of cattle and previously reported human fertility-related genes, impling the existence of a shared pool of genes that regulate fertility in mammals. These findings are crucial for developing approaches to improve fertility in cattle and potentially other mammals.

Citizen science as a vehicle to address multiple policy objectives: Case studies from Australia.

ISSUE ADDRESSED: Despite increasing interest in citizen science as an approach to engage members of the public in research and decision making about health and wellbeing, there is a lack of practical evidence to guide policy and practice organisations to utilise these approaches. In this study we investigated how and why citizen science came to be incorporated into the work of two policy organisations. METHODS: We offer two in-depth case studies of Australian government organisations which have utilised citizen science in environmental and healthy ageing policy. Interviews with organisational informants and relevant documents were analysed inductively to explore how citizen science came to be adopted, legitimised and supported. RESULTS: Citizen science was utilised to address multiple organisational objectives, including increasing community participation in science; enhancing individuals' wellbeing, learning, and skills, and generating data to support research and policy in a relatively cost-effective manner. In both cases, grant funding was a mechanism to support citizen science, with project delivery facilitated through academic-policy partnerships and led by external academic or community partners. CONCLUSION: Although citizen science is relatively new in policy and practice settings, this study underscores the value of these approaches in realising co-benefits for organisations, academics, and community members. The support and advocacy of senior managers as 'champions', and a willingness to invest in trialling new approaches to address policy problems are necessary ingredients to foster acceptance and legitimacy of citizen science. SO WHAT?: Citizen science initiatives can be strategically utilised by health promotion organisations to enact priorities related to genuine community involvement, support research and innovation and facilitate collaboration and partnerships between academic, policy and community stakeholders.

Microbial polyphenol metabolism is part of the thawing permafrost carbon cycle.

With rising global temperatures, permafrost carbon stores are vulnerable to microbial degradation. The enzyme latch theory states that polyphenols should accumulate in saturated peatlands due to diminished phenol oxidase activity, inhibiting resident microbes and promoting carbon stabilization. Pairing microbiome and geochemical measurements along a permafrost thaw-induced saturation gradient in Stordalen Mire, a model Arctic peatland, we confirmed a negative relationship between phenol oxidase expression and saturation but failed to support other trends predicted by the enzyme latch. To inventory alternative polyphenol removal strategies, we built CAMPER, a gene annotation tool leveraging polyphenol enzyme knowledge gleaned across microbial ecosystems. Applying CAMPER to genome-resolved metatranscriptomes, we identified genes for diverse polyphenol-active enzymes expressed by various microbial lineages under a range of redox conditions. This shifts the paradigm that polyphenols stabilize carbon in saturated soils and highlights the need to consider both oxic and anoxic polyphenol metabolisms to understand carbon cycling in changing ecosystems.

Differential Effect of Consolidative Thoracic Radiation Therapy in Extensive-Stage Small Cell Lung Cancer Based on Sex.

Purpose: The landmark randomized trial on chest irradiation in extensive disease small cell lung cancer (CREST) demonstrated that consolidative thoracic radiation therapy (cTRT) improved overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer, with potentially increased benefit in women compared with men. It is unknown whether similar findings would apply after chemoimmunotherapy became the standard first-line treatment. In this analysis, we report national practice patterns and survival outcomes of cTRT according to patient sex. Methods and Materials: We included patients from de-identified electronic health record-derived database diagnosed with stage IV small cell lung cancer (2014-2021) who completed 4 to 6 cycles of first-line systemic therapy (platinum-doublet chemotherapy or chemoimmunotherapy). We evaluated OS and PFS using multivariable Cox proportional hazards regression with receipt of cTRT as an independent variable and stratified by sex. As a sensitivity analysis, we weighted the models by the inverse probability of receiving cTRT. Results: A total of 1227 patients were included (850 chemotherapy, 377 chemoimmunotherapy). There were no statistically significant differences in baseline characteristics between patients who did and did not receive cTRT. Among women, cTRT was associated with superior OS (adjusted hazard ratio [HR], 0.67; 95% CI, 0.52-0.87) and PFS (HR, 0.63; 95% CI, 0.49-0.82) compared with those not receiving cTRT. Conversely, no OS or PFS benefit with cTRT was observed in men (OS HR, 1.03; 95% CI, 0.80-1.31; PFS HR, 1.12; 95% CI, 0.85-1.47). Findings were similar in weighted analyses. Conclusions: The survival efficacy of cTRT may be moderated by sex, with female patients appearing more likely to benefit than male patients. These findings reflect sex-based survival trends with similar effect sizes to those observed in the CREST trial. Although the underpinnings of this association need to be elucidated, stratification by sex should be considered for randomized-controlled trials studying cTRT in extensive-stage small cell lung cancer.

Technical note: Dosimetry and FLASH potential of UHDR proton PBS for small lung tumors: Bragg-peak-based delivery versus transmission beam and IMPT.

BACKGROUND: High-energy transmission beams (TBs) are currently the main delivery method for proton pencil beam scanning ultrahigh dose-rate (UHDR) FLASH radiotherapy. TBs place the Bragg-peaks behind the target, outside the patient, making delivery practical and achievement of high dose-rates more likely. However, they lead to higher integral dose compared to conventional intensity-modulated proton therapy (IMPT), in which Bragg-peaks are placed within the tumor. It is hypothesized that, when energy changes are not required and high beam currents are possible, Bragg-peak-based beams can not only achieve more conformal dose distributions than TBs, but also have more FLASH-potential. PURPOSE: This works aims to verify this hypothesis by taking three different Bragg-peak-based delivery techniques and comparing them with TB and IMPT-plans in terms of dosimetry and FLASH-potential for single-fraction lung stereotactic body radiotherapy (SBRT). METHODS: For a peripherally located lung target of various sizes, five different proton plans were made using "matRad" and inhouse-developed algorithms for spot/energy-layer/beam reduction and minimum monitor unit maximization: (1) IMPT-plan, reference for dosimetry, (2) TB-plan, reference for FLASH-amount, (3) pristine Bragg-peak plan (non-depth-modulated Bragg-peaks), (4) Bragg-peak plan using generic ridge filter, and (5) Bragg-peak plan using 3D range-modulated ridge filter. RESULTS: Bragg-peak-based plans are able to achieve sufficient plan quality and high dose-rates. IMPT-plans resulted in lowest OAR-dose and integral dose (also after a FLASH sparing-effect of 30%) compared to both TB-plans and Bragg-peak-based plans. Bragg-peak-based plans vary only slightly between themselves and generally achieve lower integral dose than TB-plans. However, TB-plans nearly always resulted in lower mean lung dose than Bragg-peak-based plans and due to a higher amount of FLASH-dose for TB-plans, this difference increased after including a FLASH sparing-effect. CONCLUSION: This work indicates that there is no benefit in using Bragg-peak-based beams instead of TBs for peripherally located, UHDR stereotactic lung radiotherapy, if lung dose is the priority.

Evolutionary computing to assemble standing genetic diversity and achieve long-term genetic gain.

Loss of genetic diversity in elite crop breeding pools can severely limit long-term genetic gains and limit ability to make gains in new traits, like heat tolerance, that are becoming important as the climate changes. Here, we investigate and propose potential breeding program applications of optimal haplotype stacking (OHS), a selection method that retains useful diversity in the population. OHS selects sets of candidates containing, between them, haplotype segments with very high segment breeding values for the target trait. We compared the performance of OHS, a similar method called optimal population value (OPV), truncation selection on genomic estimated breeding values (GEBVs), and optimal contribution selection (OCS) in stochastic simulations of recurrent selection on founder wheat genotypes. After 100 generations of intercrossing and selection, OCS and truncation selection had exhausted the genetic diversity, while considerable diversity remained in the OHS population. Gain under OHS in these simulations ultimately exceeded that from truncation selection or OCS. OHS achieved faster gains when the population size was small, with many progeny per cross. A promising hybrid strategy, involving a single cycle of OHS in the first generation followed by recurrent truncation selection, substantially improved long-term gain compared with truncation selection and performed similarly to OCS. The results of this study provide initial insights into where OHS could be incorporated into breeding programs.

Ticks and tick-borne diseases from Mallorca Island, Spain.

Ixodid ticks are obligate blood-feeding arthropods and important vectors of pathogens. In Mallorca, almost no data on the tick fauna are available. Herein, we investigated ticks and tick-borne pathogens in ticks collected from dogs, a cat and humans in Mallorca as result of a citizen science project. A total of 91 ticks were received from German tourists and residents in Mallorca. Ticks were collected from March to October 2023 from dogs, cat and humans, morphologically and genetically identified and tested for pathogens by PCRs. Six tick species could be identified: Ixodes ricinus (n = 2), Ixodes ventalloi (n = 1), Hyalomma lusitanicum (n = 7), Hyalomma marginatum (n = 1), Rhipicephalus sanguineus s.l. (n = 71) and Rhipicephalus pusillus (n = 9). Rhipicephalus sanguineus s.l. adults were collected from dogs and four females from a cat and the 16S rDNA sequences identified it as Rh. sanguineus s.s. Hyalomma lusitanicum was collected from 1 human, 1 dog and 5 specimens were collected from the ground in the community of Santanyi, together with one H. marginatum male. This is the first report of Hyalomma marginatum in Mallorca. Both I. ricinus were collected from humans and I. ventalloi female was collected from a dog. All ticks tested negative for Anaplasma phagocytophilum, Coxiella spp., Francisella spp., and piroplasms. In 32/71 (45%) specimens of Rh. sanguineus s.s., Rickettsia spp. could be detected and in 18/32 (56.2%) sequenced tick DNAs R. massiliae was identified. Ixodes ventalloi female and both I. ricinus tested positive in the screening PCR, but the sequencing for the identification of the Rickettsia sp. failed.

Genetic influence on within-person longitudinal change in anthropometric traits in the UK Biobank.

The causes of temporal fluctuations in adult traits are poorly understood. Here, we investigate the genetic determinants of within-person trait variability of 8 repeatedly measured anthropometric traits in 50,117 individuals from the UK Biobank. We found that within-person (non-directional) variability had a SNP-based heritability of 2-5% for height, sitting height, body mass index (BMI) and weight (P ≤ 2.4 × 10-3). We also analysed longitudinal trait change and show a loss of both average height and weight beyond about 70 years of age. A variant tracking the Alzheimer's risk APOE- E 4 allele (rs429358) was significantly associated with weight loss ( ß = -0.047 kg per yr, s.e. 0.007, P = 2.2 × 10-11), and using 2-sample Mendelian Randomisation we detected a relationship consistent with causality between decreased lumbar spine bone mineral density and height loss (bxy = 0.011, s.e. 0.003, P = 3.5 × 10-4). Finally, population-level variance quantitative trait loci (vQTL) were consistent with within-person variability for several traits, indicating an overlap between trait variability assessed at the population or individual level. Our findings help elucidate the genetic influence on trait-change within an individual and highlight disease risks associated with these changes.

Infant formula as a solid lipid dose form for enhancement of the oral bioavailability of cannabidiol for paediatric patients.

Cannabinoids can save paediatric patients from harmful psychological conditions caused by epilepsy. However, the limited aqueous solubility of the drug presents a limitation to oral absorption and bioavailability. Previous studies have shown the enhancement of oral bioavailability for poorly water-soluble drugs using milk or milk-based products like infant formula as a novel lipid-based formulation, due to digestion of the lipids to enhance drug solubility that is particularly well suited to infants and in low economy settings. Therefore, this study has investigated the in vitro solubilisation enhancement of cannabidiol (CBD) in milk-based products during digestion using synchrotron small angle X-ray scattering, followed by pharmacokinetic studies to determine the relative oral bioavailability. The in vitro results, coupled with in vivo data, demonstrate a two-fold increase in the oral bioavailability of CBD in bovine milk as well as infant formula. The results of this study indicate the potential for infant formula to be considered as a novel formulation approach for CBD. Further study is encouraged for more drugs with infant formula to strengthen the correlation between the solubilisation of drug and their oral bioavailability.

Regurgitated skua pellets containing the remains of South Atlantic seabirds can be used as biomonitors of small buoyant plastics at sea.

Using seabirds as bioindicators of marine plastic pollution requires an understanding of how the plastic retained in each species compares with that found in their environment. We show that brown skua Catharacta antarctica regurgitated pellets can be used to characterise plastics in four seabird taxa breeding in the central South Atlantic, even though skua pellets might underrepresent the smallest plastic items in their prey. Fregetta storm petrels ingested more thread-like plastics and white-faced storm petrels Pelagodroma marina more industrial pellets than broad-billed prions Pachyptila vittata and great shearwaters Ardenna gravis. Ingested plastic composition (type, colour and polymer) was similar to floating plastics in the region sampled with a 200 µm net, but storm petrels were better indicators of the size of plastics than prions and shearwaters. Given this information, plastics in skua pellets containing the remains of seabirds can be used to track long-term changes in floating marine plastics.

Flexible circumferential bioelectronics to enable 360-degree recording and stimulation of the spinal cord.

The spinal cord is crucial for transmitting motor and sensory information between the brain and peripheral systems. Spinal cord injuries can lead to severe consequences, including paralysis and autonomic dysfunction. We introduce thin-film, flexible electronics for circumferential interfacing with the spinal cord. This method enables simultaneous recording and stimulation of dorsal, lateral, and ventral tracts with a single device. Our findings include successful motor and sensory signal capture and elicitation in anesthetized rats, a proof-of-concept closed-loop system for bridging complete spinal cord injuries, and device safety verification in freely moving rodents. Moreover, we demonstrate potential for human application through a cadaver model. This method sees a clear route to the clinic by using materials and surgical practices that mitigate risk during implantation and preserve cord integrity.