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The interpretation and reuse of previous design solutions, or precedents, is central to design. This paper describes qualitative research conducted over three years at two institutions, aimed at investigating the role of design knowledge re-use in project-based mechanical design courses. Research data were collected through participant observation, student interviews, anonymous questionnaires, and website analytics. The paper identifies challenges that must be addressed in order to support novice engineers in rehearsing the types of knowledge required to successfully reason about and engage with design precedents. Two categories of design precedents are identified: concept precedents and detail precedents. Providing students with access to the latter is identified as a particular challenge, as is providing students with access to engineering communities of practice. Approaches to addressing these challenges are discussed.

Abstract During pregnancy the immune system needs to maintain immune tolerance of the foetus while also responding to infection, which can cause premature activation of the inflammatory pathways leading to the onset of labour and preterm birth. The vaginal microbiome is an important modifier of preterm birth risk, with Lactobacillus dominance during pregnancy associated with term delivery while high microbial diversity is associated with an increased risk of preterm birth. Glycans on glycoproteins along the lower female reproductive tract are fundamental to microbiota-host interactions and the mediation of inflammatory responses. However, the specific glycan epitopes involved in these processes are not well understood. To address this, we conducted glycomic analyses of cervicovaginal fluid (CVF) from 36 pregnant women at high risk of preterm birth and 4 non-pregnant women. Our analysis of N- and O-glycans revealed a rich CVF glycome. While O-glycans were shown to be the main carriers of ABO blood group epitopes, the main features of N-glycans were the presence of abundant paucimannose and high mannose glycans, and a remarkable diversity of complex bi-, tri-, and tetra-antennary glycans decorated with fucose and sialic acid. We identified immuno-regulatory epitopes, such as Lewis antigens, and found that fucosylation was negatively correlated to pro-inflammatory factors, such as IL-1β, MMP-8, C3a and C5a, while glycans with only sialylated antennae were mainly positively correlated to those. Similarly, paucimannose glycans showed a positive correlation to pro-inflammatory factors. We revealed a high abundance of glycans which have previously been identified as hallmarks of cancer and viral glycosylation, such as Man8 and Man9 high mannose glycans. Although each pregnant woman had a unique glycomic profile, longitudinal studies showed that the main glycosylation features were consistent throughout pregnancy in women who delivered at term, whereas women who experienced extreme preterm birth exhibited sharp changes in the CVF glycome shortly before delivery. These findings shed light on the processes underlying the role of glycosylation in maintaining a healthy vaginal microbiome and associated host immune responses. In addition, these discoveries facilitate our understanding of the lower female reproductive tract which has broad implications for women’s health.

Abstract Inferring the 3D structure and conformation of disordered biomolecules, e.g., single stranded nucleic acids (ssNAs), remains challenging due to their conformational heterogeneity in solution. Here, we use escape-time electrometry (ETe) to measure with sub elementary-charge precision the effective electrical charge in solution of short to medium chain length ssNAs in the range of 5–60 bases. We compare measurements of molecular effective charge with theoretically calculated values for simulated molecular conformations obtained from Molecular Dynamics simulations using a variety of forcefield descriptions. We demonstrate that the measured effective charge captures subtle differences in molecular structure in various nucleic acid homopolymers of identical length, and also that the experimental measurements can find agreement with computed values derived from coarse-grained molecular structure descriptions such as oxDNA, as well next generation ssNA force fields. We further show that comparing the measured effective charge with calculations for a rigid, charged rod—the simplest model of a nucleic acid—yields estimates of molecular structural dimensions such as linear charge spacings that capture molecular structural trends observed using high resolution structural analysis methods such as X-ray scattering. By sensitively probing the effective charge of a molecule, electrometry provides a powerful dimension supporting inferences of molecular structural and conformational properties, as well as the validation of biomolecular structural models. The overall approach holds promise for a high throughput, microscopy-based biomolecular analytical approach offering rapid screening and inference of molecular 3D conformation, and operating at the single molecule level in solution.

Abstract The use of targeted agents in the treatment of pediatric low-grade gliomas (pLGGs) relies on the determination of molecular status. It has been shown that genetic alterations in pLGG can be identified non-invasively using MRI-based radiomic features or convolutional neural networks (CNNs). We aimed to build and assess a combined radiomics and CNN non-invasive pLGG molecular status identification model. This retrospective study used the tumor regions, manually segmented from T2-FLAIR MR images, of 336 patients treated for pLGG between 1999 and 2018. We designed a CNN and Random Forest radiomics model, along with a model relying on a combination of CNN and radiomic features, to predict the genetic status of pLGG. Additionally, we investigated whether CNNs could predict radiomic feature values from MR images. The combined model (mean AUC: 0.824) outperformed the radiomics model (0.802) and CNN (0.764). The differences in model performance were statistically significant (p-values

Abstract A whiplash injury can alter neck muscle function, which remains years after the injury and may explain why symptoms such as persistent pain and disability occur. There is currently limited knowledge about dynamic neck muscle function in chronic whiplash-associated disorders (WAD), and about the extent to which altered muscle function can improve after rehabilitation. Ultrasound can detect mechanical neck muscle function by measuring real-time deformation and deformation rate in the muscles. This method was used for five dorsal neck muscles in participants with chronic WAD versus matched controls in resistant neck rotation. We obtained real-time, non-invasive ultrasound measurements using speckle tracking, multivariate analyses, and mixed-design ANOVA analyses. The results showed altered deformation in the three deepest neck muscle layers, with less deformation area in the WAD group compared to controls in rotation to the most painful side at baseline. Participants in the WAD group performed three months of neck-specific exercises, resulting in improved deformation in the deep neck muscles in WAD and with a similar deformation pattern to controls, and the significant group differences ceased. We reveal new and important insights into the capability of ultrasound to diagnose altered neck muscle function and evaluate an exercise intervention.

Abstract Background Significant recent efforts have facilitated increased access to clinical genetics assessment and genomic sequencing for children with rare diseases in many centres, but there remains a service gap for adults. The Austin Health Adult Undiagnosed Disease Program (AHA-UDP) was designed to complement existing UDP programs that focus on paediatric rare diseases and address an area of unmet diagnostic need for adults with undiagnosed rare conditions in Victoria, Australia. It was conducted at a large Victorian hospital to demonstrate the benefits of bringing genomic techniques currently used predominantly in a research setting into hospital clinical practice, and identify the benefits of enrolling adults with undiagnosed rare diseases into a UDP program. The main objectives were to identify the causal mutation for a variety of diseases of individuals and families enrolled, and to discover novel disease genes. Methods Unsolved patients in whom standard genomic diagnostic techniques such as targeted gene panel, exome-wide next generation sequencing, and/or chromosomal microarray, had already been performed were recruited. Genome sequencing and enhanced genomic analysis from the research setting were applied to aid novel gene discovery. Results In total, 16/50 (32%) families/cases were solved. One or more candidate variants of uncertain significance were detected in 18/50 (36%) families. No candidate variants were identified in 16/50 (32%) families. Two novel disease genes (TOP3B, PRKACB) and two novel genotype–phenotype correlations (NARS, and KMT2C genes) were identified. Three out of eight patients with suspected mosaic tuberous sclerosis complex had their diagnosis confirmed which provided reproductive options for two patients. The utility of confirming diagnoses for patients with mosaic conditions (using high read depth sequencing and ddPCR) was not specifically envisaged at the onset of the project, but the flexibility to offer recruitment and analyses on an as-needed basis proved to be a strength of the AHA-UDP. Conclusion AHA-UDP demonstrates the utility of a UDP approach applying genome sequencing approaches in diagnosing adults with rare diseases who have had uninformative conventional genetic analysis, informing clinical management, recurrence risk, and recommendations for relatives.

Abstract About 20% of patients with diabetes suffer from chronic pain with neuropathic characteristics. We investigated the multivariate associations between 92 neurology-related proteins measured in serum from 190 patients with painful and painless diabetic neuropathy. Participants were recruited from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the exploration cohort, two groups were defined by hierarchical cluster analyses of protein data. The proportion of painless vs painful neuropathy did not differ between the two groups, but one group had a significantly higher grade of neuropathy as measured by the Toronto Clinical Scoring System (TCSS). This finding was replicated in the replication cohort. Analyzing both groups together, we found that a group of 11 inter-correlated proteins (TNFRSF12A, SCARB2, N2DL-2, SKR3, EFNA4, LAYN, CLM-1, CD38, UNC5C, GFR-alpha-1, and JAM-B) were positively associated with TCSS values. Notably, EFNA4 and UNC5C are known to be part of axon guidance pathways. To conclude, although cluster analysis of 92 neurology-related proteins did not distinguish painful from painless diabetic neuropathy, we identified 11 proteins which positively correlated to neuropathy severity and warrant further investigation as potential biomarkers.

Abstract Background This overview of reviews aims to identify evidence on the benefits (i.e. tobacco use abstinence and reduction in smoking frequency) and harms (i.e. possible adverse events/outcomes) of smoking cessation interventions among adults aged 18 years and older. Methods We searched Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the CADTH Health Technology Assessment Database and several other websites for grey literature. Searches were conducted on November 12, 2018, updated on September 24, 2020, with publication years 2008 to 2020. Two reviewers independently performed title-abstract and full-text screening considering pre-determined inclusion criteria. Data extraction and quality assessments were initially completed by two reviewers independently (i.e. 73% of included studies (n = 22)) using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR 2), and the remainder done by one reviewer and verified by another due to resources and feasibility. The application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) was performed by one independent reviewer and verified by another. Results A total of 22 Cochrane systematic reviews evaluating the impact of smoking cessation interventions on outcomes such as tobacco use abstinence, reduction in smoking frequency, quality of life and possible adverse events were included. Pharmaceutical (i.e. varenicline, cytisine, nicotine replacement therapy (NRT), bupropion) and behavioural interventions (i.e. physician advice, non-tailored print-based self-help materials, stage-based individual counselling, etc.) showed to have increased smoking cessation; whereas, data for mobile phone-based interventions including text messaging, hypnotherapy, acupuncture, continuous auricular stimulation, laser therapy, electrostimulation, acupressure, St John’s wort, S-adenosyl-L-methionine (SAMe), interactive voice response systems and other combination treatments were unclear. Considering harms related to smoking cessation interventions, small/mild harms (i.e. increased palpitations, chest pain, nausea, insomnia, headache) were observed following NRT, varenicline and cytisine use. There were no data on harms related to behavioural therapies (i.e. individual or group counselling self-help materials, internet interventions), combination therapies or other therapies (i.e. laser therapy, electrostimulation, acupressure, St John’s wort, SAMe). Conclusion Results suggest that pharmacological and behavioural interventions may help the general smoking population quit smoking with observed small/mild harms following NRT or varenicline. Consequently, evidence regarding ideal intervention strategies and the long-term impact of these interventions for preventing smoking was unclear. Systematic review registration PROSPERO CRD42018099691

Abstract Computational models and eye-tracking research suggest that encoding variability accounts for the reduced recognition of targets (A) when paired with non-corresponding lures (B′) relative to corresponding lures (A′). The current study examined whether neural activity during learning coincided with subsequent performance on the forced-choice Mnemonic Similarity Task (MST). Event-related potential responses were collected during encoding while young adults completed A–B′ and A–A′ trials of the forced-choice MST. Consistent with previous research, performance was lower on A–B′ trials than A–A′ trials. The subsequent memory effect was not significant for the A–A′ test format. However, for A–B′ trials, we observed a significant Accuracy × Stimulus interaction 1000–1200 ms poststimulus onset across frontal and fronto-central electrodes. As hypothesized, subsequently correct A–B′ trials were associated with a larger amplitude response at encoding to the target (A) than the original version of the non-corresponding lure (B). However, subsequently incorrect trials were associated with a larger amplitude response to the non-corresponding lure (B) than the target stimulus (A). These findings provide additional support for the effect of encoding variability on mnemonic discrimination.

Abstract Neurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task. Results revealed significantly larger differences between younger and older adults for maximum than average magnetization transfer-weighted contrast (MTC), axial than mean or radial single-tensor diffusivity (DTI), and free than restricted multi-compartment diffusion (NODDI) metrics in the locus coeruleus; with maximum MTC being the best predictor of age group. Age effects for all imaging modalities interacted with sex, with larger age group differences in males than females for MTC and NODDI metrics. Age group differences also varied across locus coeruleus subdivision for DTI and NODDI metrics, and across locus coeruleus hemispheres for MTC. Within older adults, however, there were no significant effects of age on MTC or DTI metrics, only an interaction between age and sex for free diffusion. Finally, independent of age and sex, higher restricted diffusion in the locus coeruleus was significantly related to better (lower) recall variability, but not mean recall. Whereas MTC has been widely used in the literature, our comparison between the average and maximum MTC metrics, inclusion of DTI and NODDI metrics, and breakdowns by locus coeruleus subdivision and hemisphere make important and novel contributions to our understanding of the aging of locus coeruleus structure.

Abstract Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids.

Abstract Background This systematic review aims to identify the benefits and harms of electronic cigarettes (e-cigarettes) as a smoking cessation aid in adults (aged ≥ 18 years) and to inform the development of the Canadian Task Force on Preventive Health Care’s (CTFPHC) clinical practice guidelines on e-cigarettes. Methods We searched Ovid MEDLINE®, Ovid MEDLINE® Epub Ahead of Print, In-Process & Other Non-Indexed Citations, PsycINFO, Embase Classic + Embase, and the Cochrane Library on Wiley. Searches were conducted from January 2016 to July 2019 and updated on 24 September 2020 and 25 January 2024. Two reviewers independently performed title-abstract and full-text screening according to the pre-determined inclusion criteria. Data extraction, quality assessments, and the application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) were performed by one independent reviewer and verified by another. Results We identified 18 studies on 17 randomized controlled trials that compared e-cigarettes with nicotine to e-cigarettes without nicotine and e-cigarettes (with or without nicotine) to other interventions (i.e., no intervention, waitlist, standard/usual care, quit advice, or behavioral support). Considering the benefits of e-cigarettes in terms of smoking abstinence and smoking frequency reduction, 14 studies showed small or moderate benefits of e-cigarettes with or without nicotine compared to other interventions; although, with low, very low or moderate evidence certainty. With a focus on e-cigarettes with nicotine specifically, 12 studies showed benefits in terms of smoking abstinence when compared with usual care or non-nicotine e-cigarettes. In terms of harms following nicotine or non-nicotine e-cigarette use, 15 studies reported mild adverse events with little to no difference between groups and low to very low evidence certainty. Conclusion The evidence synthesis on the e-cigarette’s effectiveness shows data surrounding benefits having low to moderate evidence certainty for some comparisons and very low certainty for others, indicating that e-cigarettes may or probably increase smoking cessation, whereas, for harms, there is low to very low evidence certainty. Since the duration for outcome measurement varied among different studies, it may not be long-term enough for Adverse Events (AEs) to emerge, and there is a need for more research to understand the long-term benefits and potential harms of e-cigarettes. Systematic review registration PROSPERO CRD42018099692

Abstract There are two known mechanisms by which natural killer (NK) cells recognize and kill diseased targets: (i) direct killing and (ii) antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated an indirect NK cell activation strategy for the enhancement of human NK cell killing function. We did this by leveraging the fact that toll-like receptor 9 (TLR9) agonism within pools of human peripheral blood mononuclear cells (PBMCs) results in a robust interferon signaling cascade that leads to NK cell activation. After TLR9 agonist stimulation, NK cells were enriched and incorporated into assays to assess their ability to kill tumor cell line targets. Notably, differential impacts of TLR9 agonism were observed—direct killing was enhanced while ADCC was not increased. To ensure that the observed differential effects were not attributable to differences between human donors, we recapitulated the observation using our Natural Killer—Simultaneous ADCC and Direct Killing Assay (NK-SADKA) that controls for human-to-human differences. Next, we observed a treatment-induced decrease in NK cell surface CD16—known to be shed by NK cells post-activation. Given the essential role of CD16 in ADCC, such shedding could account for the observed differential impact of TLR9 agonism on NK cell-mediated killing capacity.

Abstract The benefits of breastfeeding for the health and wellbeing of both infants and mothers are well documented, yet global breastfeeding rates are low. One factor associated with low breast feeding is maternal body mass index (BMI), which is used as a measure of obesity. The negative relationship between maternal obesity and breastfeeding is likely caused by a variety of social, psychological, and physiological factors. Maternal obesity may also have a direct biological association with breastfeeding through changes in maternal DNA methylation. Here, we investigate this potential biological association using data from a UK-based cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). We find that pre-pregnancy body mass index (BMI) is associated with lower initiation to breastfeed and shorter breastfeeding duration. We conduct epigenome-wide association studies (EWAS) of pre-pregnancy BMI and breastfeeding outcomes, and run candidate-gene analysis of methylation sites associated with BMI identified via previous meta-EWAS. We find that DNA methylation at cg11453712, annotated to PHTP1, is associated with pre-pregnancy BMI. From our results, neither this association nor those at candidate-gene sites are likely to mediate the link between pre-pregnancy BMI and breastfeeding.

Major dengue epidemics throughout Nicaragua’s history have been dominated by 1 of 4 dengue virus serotypes (DENV-1–4). To examine serotypes during the dengue epidemic in Nicaragua in 2022, we performed real-time genomic surveillance in-country and documented cocirculation of all 4 serotypes. We observed a shift toward co-dominance of DENV-1 and DENV-4 over previously dominant DENV-2. By analyzing 135 new full-length DENV sequences, we found that introductions underlay the resurgence: DENV-1 clustered with viruses from Ecuador in 2014 rather than those previously seen in Nicaragua; DENV-3, which last circulated locally in 2014, grouped instead with Southeast Asia strains expanding into Florida and Cuba in 2022; and new DENV-4 strains clustered within a South America lineage spreading to Florida in 2022. In contrast, DENV-2 persisted from the formerly dominant Nicaragua clade. We posit that the resurgence emerged from travel after the COVID-19 pandemic and that the resultant intensifying hyperendemicity could affect future dengue immunity and severity.

Abstract AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom was designed to establish the relationship between AGuIX concentration and longitudinal ( $${T}_{1}$$ T 1 ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient $${T}_{1}$$ T 1 maps. AGuIX uptake in tumors was determined based on longitudinal relaxivity. AGuIX (or placebo) was administered to 23 patients intravenously at 100 mg/kg 1–5 hours pre-imaging. Each of 129 brain metastases across 23 patients were captured in $${T}_{1}$$ T 1 maps and examined for AGuIX uptake and distribution. Inferred AGuIX recipients had average tumor uptakes between 0.012 and 0.17 mg/ml, with a mean of 0.055 mg/ml. Suspected placebo recipients appeared to have no appreciable uptake. Tumors presented with varying spatial AGuIX uptake distributions, suspected to be related to differences in accumulation time and patient-specific bioaccumulation factors. This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via $${T}_{1}$$ T 1 mapping. Future analyses will extend these methods to complete clinical trial data (~ 134 patients) to evaluate the potential relationship between nanoparticle uptake and possible tumor response following radiotherapy. Clinical Trial Registration Number: NCT04899908. Clinical Trial Registration Date: 25/05/2021.

Abstract This study assessed the association between arthritis, functional impairment, and nutritional risk (NR). Cross-sectional data were from the Canadian Longitudinal Study on Aging, a nationally representative sample of 45–85-year-old community-dwelling Canadians (n = 41,153). The abbreviated Seniors in the Community: Risk Evaluating for Eating and Nutrition II (SCREEN II-AB) Questionnaire determined NR scores (continuous), and high NR (score

Abstract Tracking a moving object with the eyes seems like a simple task but involves areas of prefrontal cortex (PFC) associated with attention, working memory and prediction. Increasing the demand on these processes with secondary tasks can affect eye movements and/or perceptual judgments. This is particularly evident in chronic or acute neurological conditions such as Alzheimer’s disease or mild traumatic brain injury. Here, we combined near infrared spectroscopy and video-oculography to examine the effects of concurrent upper limb movement, which provides additional afference and efference that facilitates tracking of a moving object, in a novel dual-task pursuit protocol. We confirmed the expected effects on judgement accuracy in the primary and secondary tasks, as well as a reduction in eye velocity when the moving object was occluded. Although there was limited evidence of oculo-manual facilitation on behavioural measures, performing concurrent upper limb movement did result in lower activity in left medial PFC, as well as a change in PFC network organisation, which was shown by Graph analysis to be locally and globally more efficient. These findings extend upon previous work by showing how PFC is functionally organised to support eye-hand coordination when task demands more closely replicate daily activities.

Abstract The Mini-Mental State Examination (MMSE) is a widely employed screening tool for the severity of cognitive impairment. Among the MMSE items, the pentagon copying test (PCT) requires participants to accurately replicate a sample of two interlocking pentagons. While the PCT is traditionally scored on a binary scale, there have been limited developments of granular scoring scale to assess task performance. In this paper, we present a novel three-stage algorithm, called Quantification of Interlocking Pentagons (QIP) which quantifies PCT performance by computing the areas of individual pentagons and their intersection areas, and a balance ratio between the areas of the two individual pentagons. The three stages of the QIP algorithm include: (1) detection of line segments, (2) unraveling of the interlocking pentagons, and (3) quantification of areas. A set of 497 PCTs from 84 participants including their baseline and follow-up PCTs from the Rush Memory and Aging Project was selected blinded about their cognitive and clinical status. Analysis of the quantified data revealed a significant inverse relationship between age and balance ratio (beta = − 0.49, p = 0.0033), indicating that older age was associated with a smaller balance ratio. In addition, balance ratio was associated with perceptual speed (r = 0.71, p = 0.0135), vascular risk factors (beta = − 3.96, p = 0.0269), and medical conditions (beta = − 2.78, p = 0.0389). The QIP algorithm can serve as a useful tool for enhancing the scoring of performance in the PCT.

Abstract Roots are crucial in plant adaptation through the exudation of various compounds which are influenced and modified by environmental factors. Buckwheat root exudate and root system response to neighbouring plants (buckwheat or redroot pigweed) and how these exudates affect redroot pigweed was investigated. Characterising root exudates in plant–plant interactions presents challenges, therefore a split-root system which enabled the application of differential treatments to parts of a single root system and non-destructive sampling was developed. Non-targeted metabolome profiling revealed that neighbour presence and identity induces systemic changes. Buckwheat and redroot pigweed neighbour presence upregulated 64 and 46 metabolites, respectively, with an overlap of only 7 metabolites. Root morphology analysis showed that, while the presence of redroot pigweed decreased the number of root tips in buckwheat, buckwheat decreased total root length and volume, surface area, number of root tips, and forks of redroot pigweed. Treatment with exudates (from the roots of buckwheat and redroot pigweed closely interacting) on redroot pigweed decreased the total root length and number of forks of redroot pigweed seedlings when compared to controls. These findings provide understanding of how plants modify their root exudate composition in the presence of neighbours and how this impacts each other’s root systems.

Abstract Many gregarious insect species use aggregation and alarm pheromones. The bed bug, Cimex lectularius L., emits an alarm pheromone (AP), a 70/30 blend of (E)-2-hexenal and (E)-2-octenal, when threatened. Bed bugs avoid temperatures above 43 °C, which are lethal to bugs and used commercially as spatial heat treatments to manage infestations. However, the interaction of bed bug AP in heat avoidance has not been investigated. The goal of this research was to: 1) determine if bed bugs emit AP as an alarm response to heat exposure, and 2) quantify the behavioral responses of conspecifics to AP emitted by heat-exposed bed bugs. Using a selected ion flow tube mass spectrometer, we found that bed bugs responded to lethal and sublethal heat exposure by emitting AP. The Harlan laboratory population emitted more pheromone than a laboratory adapted field population from Florida (McCall). Harlan females emitted the most AP, followed by Harlan males, McCall females and males. In separate behavioral experiments, we showed that conspecifics (i.e., recipients) reacted to AP released by heat exposed bed bugs (i.e., emitters) by frantically moving within 50 mm and 100 mm test arenas. The Harlan recipients reacted to AP in 100 mm areas, whereas the McCall strain did not, indicating a short area of effectiveness of the AP. Synthetic AP components tested in behavioral experiments caused identical effects as the natural AP blend released by heat-exposed bed bugs.

Abstract Despite the significant advances in understanding the genetic architecture of epilepsy, many patients do not receive a molecular diagnosis after genomic testing. Re-analysing existing genomic data has emerged as a potent method to increase diagnostic yields—providing the benefits of genomic-enabled medicine to more individuals afflicted with a range of different conditions. The primary drivers for these new diagnoses are the discovery of novel gene-disease and variants-disease relationships; however, most decisions to trigger re-analysis are based on the passage of time rather than the accumulation of new knowledge. To explore how our understanding of a specific condition changes and how this impacts re-analysis of genomic data from epilepsy patients, we developed Vigelint. This approach combines the information from PanelApp and ClinVar to characterise how the clinically relevant genes and causative variants available to laboratories change over time, and this approach to five clinical-grade epilepsy panels. Applying the Vigelint pipeline to these panels revealed highly variable patterns in new, clinically relevant knowledge becoming publicly available. This variability indicates that a more dynamic approach to re-analysis may benefit the diagnosis and treatment of epilepsy patients. Moreover, this work suggests that Vigelint can provide empirical data to guide more nuanced, condition-specific approaches to re-analysis.

Purpose: Our quality improvement study aimed to determine whether application of a neonatal early-onset sepsis calculator (NSC) among well-appearing infants born at ≥ 35 weeks’ gestation to mothers with chorioamnionitis decreases the number of lab evaluations (LEs) and antibiotic treatments (Abxs) without missing early-onset sepsis. Methods: We compared 2 years (January 1, 2019–January 3, 2021) of data from a historical-control group before implementation of the NSC to 1 year (January 4, 2021–December 31, 2021) of data from a calculator group after implementation of the NSC to evaluate whether LE and Abx decreased following implementation of the NSC on January 4, 2021. A P-value of < 0.05 was considered statistically significant for the chi-squared test, Fisher’s exact test, Student’s t-test, and Mann-Whitney U test used for the analyses. Results: In the historical-control group, 94% of infants received LE and Abx. Retrospective application of the NSC in the historical-control group decreased LE from 94% to 21% and Abx from 94% to 13%. In the calculator group, 14% and 5% of infants received LE and Abx, respectively, and none of the blood culture was positive. Median time from birth to antibiotic initiation was significantly longer (14.5 vs 3.8 hours; P = 0.0037) with no increase in median length of stay (2.3 vs 2.4 days; P = 0.02) after NSC implementation. No significant difference in neonatal intensive care unit admission was identified between groups (4% vs 1%; P = 0.15). Conclusions: There was a significant decrease in LE and Abx among well-appearing infants born at ≥ 35 weeks’ gestation to mothers with chorioamnionitis after implementation of the NSC without missing early-onset sepsis. There was no increase in neonatal intensive care unit admission or length of hospital stay in infants who received antibiotics later after they appeared equivocal or clinically ill in the calculator group. Larger prospective studies that include follow ups are needed to confirm that early-onset sepsis is not missed. (J Patient Cent Res Rev. 2024;11:29-35.)

Preexposure prophylaxis (PrEP) is underused in persons who use drugs and justice-involved persons. In an ongoing randomized controlled trial in 4 US locations comparing patient navigation versus mobile health unit on time to initiation of HIV medication or PrEP for justice-involved persons who use stimulants or opioids and who are at risk for or living with HIV, we assessed HIV risk factors, perceived HIV risk, and interest in PrEP. Participants without HIV (n = 195) were 77% men, 65% White, 23% Black, and 26% Hispanic; 73% reported a recent history of condomless sex, mainly with partners of unknown HIV status. Of 34% (67/195) reporting injection drug use, 43% reported sharing equipment. Despite risk factors, many persons reported their risk for acquiring HIV as low (47%) or no (43%) risk, although 51/93 (55%) with PrEP indications reported interest in PrEP. Justice-involved persons who use drugs underestimated their HIV risk and might benefit from increased PrEP education efforts.

Low-intensity shockwave therapy (LiSWT) for erectile dysfunction (ED) continues to gain popularity in both clinical practice and the academic literature. The majority of trials and meta-analysis studies have shown LiSWT to be low risk with a trend toward positive improvements in International Index of Erectile Function (IIEF) scores. However, there is still debate over the clinical utility of LiSWT and there is no agreed upon optimal treatment protocol. In this review article we summarize published meta-analysis studies of LiSWT for ED, and review the treatment protocols from randomized sham-control trials published in the last 10 years. We found the most common device settings were an energy of 0.09 mJ/mm2 and a frequency of 5 Hz. Shock number and location varied, but the most common protocol was 1,500 shocks per session, with 900 shocks to the penis (shaft, base, or hilum) and 600 shocks to the proximal corpora/crura. Protocols ranged from 4 to 12 treatment sessions. We also describe our institutional experience with LiSWT, including patient counseling and treatment protocol.

Background: Musculoskeletal changes occur during pregnancy; one-half of pregnant women experienced low back pain and/or pelvic pain during pregnancy. Prescription opioid use for Medicaid enrolled pregnant women has increased dramatically due to severe low back pain/pelvic pain. Objectives: This study aimed to explore the prevalence of low back pain/pelvic pain and related risk factors among a broader population. Design: This is a retrospective cohort study. Methods: This study utilized de-identified Medicaid claims data provided by the South Carolina Revenue and Fiscal Affairs Office, including individuals who gave birth between 2016 and 2021 during pregnancy. Low back pain/pelvic pain and a group of musculoskeletal risk factors were identified with International Classification of Diseases v10. Comparisons were made for the prevalence of low back pain and pelvic pain between those with pregnancy-related musculoskeletal risk and those without. Results: Among 167,396 pregnancies, 65.6% were affected by musculoskeletal risk factors. The overall prevalence of low back pain was 15.6%, and of pregnancy-related pelvic pain was 25.2%. The overall prevalence for either low back pain or pelvic pain was 33.3% (increased from 29.5% in 2016 to 35.3% in 2021), with 24.6% being pregnancy-induced. Pregnancies with musculoskeletal risk factors were more likely to be diagnosed with low back pain (20.7% versus 5.7%, p

Objective The chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample.Design Cross-sectional study.Setting Community-dwelling cohort.Participants Twins from the TwinsUK cohortPrimary and secondary outcome measures We compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing.Results In N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance.Conclusion Our findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS.

Aim: Online food delivery services (OFDS) are popular for purchasing meals prepared outside home, increasing access to energy-dense and nutrient-poor foods. This adversely impacts dietary choices and health outcomes. Our study examined trends in OFDS use in Australia, Canada, Mexico, the United Kingdom (UK), and the United States (US) from 2018 to 2021. Methods: Repeated annual cross-sectional data was sourced from the International Food Policy Study for five countries among adults over 18 years (N = 83,337). Weighted estimates for trends in i) the proportion of the respondent’s purchasing meals per week using OFDS, and ii) average number (and standard deviation (SD)) of meals purchased per week using OFDS were assessed. Logistic regression models were fitted. Findings: OFDS use increased among adults between 2018–2021 (Australia: 17 % of respondents purchased at least one meal in the last 7 days using OFDS in 2018 to 25 % in 2021, Canada: 12 % to 19 %, Mexico: 28 % to 38 %, UK: 19 % to 28 %, and US: 17 % to 21 %). Average number of meals purchased per week outside home remained consistent for all countries over time (e.g., in Australia, 2.70 (SD 0.06) meals in 2018 and 2.63 (SD 0.06) in 2021). However, average number of meals purchased using OFDS nearly doubled between 2018 and 2021 (e.g., in Australia, 0.45 (SD 0.03) meals in 2018 to 0.81 (SD 0.04) in 2021). Conclusion: OFDS use is increasing and are substituting the conventional forms of purchasing meals outside home. Nutritional quality of foods sold, marketing practices and purchasing patterns on OFDS deserve further attention.

Background: Women with cardiometabolic pregnancy complications are at increased risk of future diabetes and heart disease which can be reduced through lifestyle management postpartum. Objectives: This study aimed to explore preferred intervention characteristics and behaviour change needs of women with or without prior cardiometabolic pregnancy complications for engaging in postpartum lifestyle interventions. Design: Quantitative cross-sectional study. Methods: Online survey. Results: Overall, 473 women were included, 207 (gestational diabetes (n = 105), gestational hypertension (n = 39), preeclampsia (n = 35), preterm birth (n = 65) and small for gestational age (n = 23)) with and 266 without prior cardiometabolic pregnancy complications. Women with and without complications had similar intervention preferences, with delivery ideally by a healthcare professional with expertise in women’s health, occurring during maternal child health nurse visits or online, commencing 7 weeks to 3 months post birth, with 15- to 30-min monthly sessions, lasting 1 year and including monitoring of progress and social support. Women with prior complications preferred intervention content on women’s health, mental health, exercise, mother’s diet and their children’s health and needed to know more about how to change behaviour, have more time to do it and feel they want to do it enough to participate. There were significant differences between groups, with more women with prior cardiometabolic pregnancy complications wanting content on women’s health (87.9% vs 80.8%, p = 0.037), mother’s diet (72.5% vs 60.5%, p = 0.007), preventing diabetes or heart disease (43.5% vs 27.4%, p

BackgroundOverdose deaths continue to reach new records in New York City and nationwide, largely driven by adulterants such as fentanyl and xylazine in the illicit drug supply. Unknowingly consuming adulterated substances dramatically increases risks of overdose and other health problems, especially when individuals consume multiple adulterants and are exposed to a combination of drugs they did not intend to take. Although test strips and more sophisticated devices enable people to check drugs for adulterants including fentanyl and xylazine prior to consumption and are often available free of charge, many people who use drugs decline to use them. ObjectiveWe sought to better understand why people in the New York City area do or do not check drugs before use. We plan to use study findings to inform the development of technology-based interventions to encourage consistent drug checking. MethodsIn summer 2023, team members who have experience working with people who use drugs conducted 22 semistructured qualitative interviews with a convenience sample of people who reported illicit drug use within the past 90 days. An interview guide examined participants’ knowledge of and experience with adulterants including fentanyl, xylazine, and benzodiazepines; using drug testing strips; and whether they had ever received harm reduction services. All interviews were audio recorded, transcribed, and analyzed for emerging themes. ResultsMost participants lacked knowledge of adulterants, and only a few reported regularly checking drugs. Reasons for not checking included lacking convenient access to test supplies, or a place to check samples out of the public’s view, as well as time considerations. Some participants also reported a strong belief that they were not at risk from fentanyl, xylazine, or other adulterants because they exclusively used cocaine or crack, or that they were confident the people they bought drugs from would not sell them adulterated substances. Those who did report testing their drugs described positive interactions with harm reduction agency staff. ConclusionsNew forms of outreach are needed not only to increase people’s knowledge of adulterated substances and awareness of the increasing risks they pose but also to encourage people who use drugs to regularly check their substances prior to use. This includes new intervention messages that highlight the importance of drug checking in the context of a rapidly changing and volatile drug supply. This messaging can potentially help normalize drug checking as an easily enacted behavior that benefits public health. To increase effectiveness, messages can be developed with, and outreach can be conducted by, trusted community members including people who use drugs and, potentially, people who sell drugs. Pairing this messaging with access to no-cost drug-checking supplies and equipment may help address the ongoing spiral of increased overdose deaths nationwide.

Abstract Typical differential single-nucleus gene expression (snRNA-seq) analyses in Alzheimer’s disease (AD) provide fixed snapshots of cellular alterations, making the accurate detection of temporal cell changes challenging. To characterize the dynamic cellular and transcriptomic differences in AD neuropathology, we apply the novel concept of RNA velocity to the study of single-nucleus RNA from the cortex of 60 subjects with varied levels of AD pathology. RNA velocity captures the rate of change of gene expression by comparing intronic and exonic sequence counts. We performed differential analyses to find the significant genes driving both cell type-specific RNA velocity and expression differences in AD, extensively compared these two transcriptomic metrics, and clarified their associations with multiple neuropathologic traits. The results were cross-validated in an independent dataset. Comparison of AD pathology-associated RNA velocity with parallel gene expression differences reveals sets of genes and molecular pathways that underlie the dynamic and static regimes of cell type-specific dysregulations underlying the disease. Differential RNA velocity and its linked progressive neuropathology point to significant dysregulations in synaptic organization and cell development across cell types. Notably, most of the genes underlying this synaptic dysregulation showed increased RNA velocity in AD subjects compared to controls. Accelerated cell changes were also observed in the AD subjects, suggesting that the precocious depletion of precursor cell pools might be associated with neurodegeneration. Overall, this study uncovers active molecular drivers of the spatiotemporal alterations in AD and offers novel insights towards gene- and cell-centric therapeutic strategies accounting for dynamic cell perturbations and synaptic disruptions.

Abstract Cattle herders and agricultural workers have been identified has key high-risk populations for malaria in northern Namibia. Population size estimates for these groups are lacking but are important for planning, monitoring and evaluating the effectiveness of targeted strategies towards malaria elimination in the region. In this analysis, we extend population size estimation methods routinely used in HIV research, specifically social mapping and multiple source capture-recapture, to the context of malaria to estimate how many cattle herders and agricultural workers lived in two regions of northern Namibia over the course of the 2019–2020 malaria season. Both methods estimated two to three times more agricultural workers than cattle herders but size estimates based on the multiple source capture-recapture method were two to three times greater than the mapping-based, highlighting important methodological considerations to apply such methods to these highly mobile populations. In particular, we compared open versus closed populations assumptions for the capture-recapture method and assessed the impact of sensitivity analyses on the procedure to link records across multiple data sources on population size estimates. Our results are important for national control programs to target their resources and consider integrating routine population size estimation of high risk populations in their surveillance activities.

Abstract Mucin protein glycosylation is important in determining biological properties of mucus gels, which form protective barriers at mucosal surfaces of the body such as the intestine. Ecological factors including: age, sex, and diet can change mucus barrier properties by modulating mucin glycosylation. However, as our understanding stems from controlled laboratory studies in house mice, the combined influence of ecological factors on mucin glycosylation in real-world contexts remains limited. In this study, we used histological staining with ‘Alcian Blue, Periodic Acid, Schiff’s’ and ‘High-Iron diamine’ to assess the acidic nature of mucins stored within goblet cells of the intestine, in a wild mouse population (Mus musculus). Using statistical models, we identified sex as among the most influential ecological factors determining the acidity of intestinal mucin glycans in wild mice. Our data from wild mice and experiments using laboratory mice suggest estrogen signalling associates with an increase in the relative abundance of sialylated mucins. Thus, estrogen signalling may underpin sex differences observed in the colonic mucus of wild and laboratory mice. These findings highlight the significant influence of ecological parameters on mucosal barrier sites and the complementary role of wild populations in augmenting standard laboratory studies in the advancement of mucus biology.

Abstract A proportion of people with fibromyalgia demonstrate small fibre pathology (SFP). However, it is unclear how SFP directly relates to pain phenomenology. Thirty-three individuals with FMS and ten healthy volunteers underwent assessment of SFP and sensory phenotyping using corneal confocal microscopy, validated questionnaires and quantitative sensory testing (QST). Corneal nerve fibre length was used to stratify participants with fibromyalgia into with SFP [SFP+] and without SFP [SFP−]. SFP was detected in 50% of the fibromyalgia cohort. Current pain score and QST parameters did not differ between SFP+ and SFP−. Mechanical pain sensitivity (MPS) demonstrated a significant gain-of-function in the SFP− cohort compared to healthy-volunteers (p = 0.014, F = 4.806, η2 = 0.22). Further stratification revealed a cohort without structural SFP but with symptoms compatible with small fibre neuropathy symptoms and a significant gain in function in MPS (p = 0.020 Chi-square). Additionally, this cohort reported higher scores for both depression (p = 0.039, H = 8.483, η2 = 0.312) and anxiety (p = 0.022, F = 3.587, η2 = 0.293). This study confirms that SFP is present in a proportion of people with fibromyalgia. We also show that in a proportion of people with fibromyalgia, small fibre neuropathy symptoms are present in the absence of structural SFP. Greater mechanical pain sensitivity, depression and anxiety are seen in these individuals.

Abstract Purpose To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews. Methods To evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case–control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes. Discussion The results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older. Systematic review registration This protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).

Abstract Background The transition from childhood to adolescence is associated with an increase in rates of some psychiatric disorders, including major depressive disorder, a debilitating mood disorder. The aim of this systematic review is to update the evidence on the benefits and harms of screening for depression in primary care and non-mental health clinic settings among children and adolescents. Methods This review is an update of a previous systematic review, for which the last search was conducted in 2017. We searched Ovid MEDLINE® ALL, Embase Classic+Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and CINAHL on November 4, 2019, and updated on February 19, 2021. If no randomized controlled trials were found, we planned to conduct an additional search for non-randomized trials with a comparator group. For non-randomized trials, we applied a non-randomized controlled trial filter and searched the same databases except for Cochrane Central Register of Controlled Trials from January 2015 to February 2021. We also conducted a targeted search of the gray literature for unpublished documents. Title and abstract, and full-text screening were completed independently by pairs of reviewers. Results In this review update, we were unable to find any randomized controlled studies that satisfied our eligibility criteria and evaluated the potential benefits and harms of screening for depression in children and adolescents. Additionally, a search for non-randomized trials yielded no studies that met the inclusion criteria. Conclusions The findings of this review indicate a lack of available evidence regarding the potential benefits and harms of screening for depression in children and adolescents. This absence of evidence emphasizes the necessity for well-conducted clinical trials to evaluate the effectiveness of depression screening among children and adolescents in primary care and non-mental health clinic settings. Systematic review registration PROSPERO CRD42020150373 .

Abstract Anoxia halts oxidative phosphorylation (OXPHOS) causing an accumulation of reduced compounds in the mitochondrial matrix which impedes dehydrogenases. By simultaneously measuring oxygen concentration, NADH autofluorescence, mitochondrial membrane potential and ubiquinone reduction extent in isolated mitochondria in real-time, we demonstrate that Complex I utilized endogenous quinones to oxidize NADH under acute anoxia. 13C metabolic tracing or untargeted analysis of metabolites extracted during anoxia in the presence or absence of site-specific inhibitors of the electron transfer system showed that NAD+ regenerated by Complex I is reduced by the 2-oxoglutarate dehydrogenase Complex yielding succinyl-CoA supporting mitochondrial substrate-level phosphorylation (mtSLP), releasing succinate. Complex II operated amphidirectionally during the anoxic event, providing quinones to Complex I and reducing fumarate to succinate. Our results highlight the importance of quinone provision to Complex I oxidizing NADH maintaining glutamate catabolism and mtSLP in the absence of OXPHOS.

Changes in the profession of medicine are creating the demand for a substantive reexamination of current practices in medical education. Many of the major issues in addressing this challenge are structural and political rather than scientific; here we address one critical scientific issue that will be important to (though not by itself adequate for) guiding such changes. The factor we address is the development of a global performance assessment: a standardized mechanism to assess individual skills and abilities that can be used to evaluate alternative educational interventions. We discuss the issues involved in developing such a system, and describe a set of principles for defining desired outcomes and developing assessment tools, including (a) wide clinical scope, (b) direct relationship to actual clinical performance, (c) reliability and repeatability, and (d) non-longitudinal measurement. We discuss the role of simulation, reflective practice, and portfolios of work in developing such a system, and argue that whatever form such metrics take, a system of global performance assessment will develop from close collaboration between clinicians and educators with innovative ways of thinking about performance and expertise.

Background Gluteal tendinopathy (GT) is a degenerative tendon condition characterised by pain over the greater trochanter of the hip. A randomised controlled trial (RCT) in Australia found that 14 sessions of EDucation on load management plus eXercise (EDX) delivered over 8 weeks resulted in greater improvements in global rating of change and pain outcomes at 8 and 52 weeks, compared with corticosteroid injection or ‘wait and see’. Typically, 5-6 physiotherapy sessions are provided in public and private physiotherapy settings in Ireland, therefore, the aim of this study is to examine the feasibility of conducting a future definitive RCT to investigate effectiveness of 6 sessions of the EDX programme compared to usual care. Methods We will randomly allocate 64 participants with GT to physiotherapist-administered EDX or usual care. The EDX intervention (EDX-Ireland) will be delivered in 6 sessions over 8 weeks. To determine feasibility of an RCT, we will assess recruitment and retention and outcome measure completion. The health status outcomes to be assessed at baseline, 8 weeks and 3 months include: Global Rating of Change, pain severity, the Victorian Institute of Sport Assessment-Gluteal Questionnaire (VISA-G), the Patient-Specific Functional Scale, the Pain Catastrophizing Scale, Patient Health Questionnaire (PHQ), Pain Self-Efficacy Questionnaire, the EQ-5D-5L, the Central Sensitisation Inventory and hip abductor muscle strength. We will explore acceptability of the EDX-Ireland intervention from the perspective of patients and treatment providers, and the perspective of referrers to the trial. A Study Within A Trial will be also applied to compare recording of exercise adherence using app-based technology to paper diaries. Discussion There is a need to establish effective treatments for GT that potentially can be implemented into existing health systems. The findings of this feasibility trial will inform development of a future definitive RCT. Registration The trial is registered prospectively on ClinicalTrials.gov (NCT05516563, 27/10/2022).

Background Secondary use of health data provides opportunities to drive improvements in healthcare provision, personalised medicine, comparative effectiveness research, health services innovation, and policy and practice. However, secondary data use requires compliance with relevant legislation, implementation of technical safeguards, ethical data management, and respect for data sharers. Existing evidence suggests widespread support for secondary use of health data among the public, which co-exists with concerns about privacy, confidentiality and misuse of data. Balancing the protection of individuals’ rights against the use of their health data for societal benefits is of vital importance, and trust underpins this process. The study protocol explores how to build public trust and confidence in the secondary use of health data through all key stakeholder groups in Ireland, towards developing a culture that promotes a safe and trustworthy use of data. Methods This study will adopt a qualitative cross-sectional approach conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research COREQ guidelines. Participants in the study will include academics and researchers; healthcare professionals, data protection, ethics and privacy experts and data controllers; pharmaceutical industry and patients and public. Purposive and convenience sampling techniques will be utilised to recruit the participants, and data will be collected utilizing focus groups that may be supplemented with semi-structured interviews. Data will be coded by themes using reflexive thematic analysis (TA) and collective intelligence (CI) will be convened post-analysis to explore the preliminary findings with the participants. Ethics and Dissemination Ethical approval was obtained from the Royal College of Surgeons in Ireland Research Ethics Committee (REC202208013). Final data analysis and dissemination is expected by Q1 2024. Findings will be disseminated through peer-reviewed journal publications, presentations at relevant conferences, and other academic, public and policy channels. Lay summaries will be designed for Public and Patient Involvement (PPI) contributors and general public.

Objective We aimed to evaluate the feasibility and utility of an unsupervised testing mechanism, in which participants pick up a swab kit, self-test (unsupervised) and return the kit to an on-campus drop box, as compared with supervised self-testing at staffed locations.Design University SARS-CoV-2 testing cohort.Setting Husky Coronavirus Testing provided voluntary SARS-CoV-2 testing at a university in Seattle, USA.Outcome measures We computed descriptive statistics to describe the characteristics of the study sample. Adjusted logistic regression implemented via generalised estimating equations was used to estimate the odds of a self-swab being conducted through unsupervised versus supervised testing mechanisms by participant characteristics, including year of study enrolment, pre-Omicron versus post-Omicron time period, age, sex, race, ethnicity, affiliation and symptom status.Results From September 2021 to July 2022, we received 92 499 supervised and 26 800 unsupervised self-swabs. Among swabs received by the laboratory, the overall error rate for supervised versus unsupervised swabs was 0.3% vs 4%, although this declined to 2% for unsupervised swabs by the spring of the academic year. Results were returned for 92 407 supervised (5% positive) and 25 836 unsupervised (4%) swabs from 26 359 participants. The majority were students (79%), 61% were female and most identified as white (49%) or Asian (34%). The use of unsupervised testing increased during the Omicron wave when testing demand was high and stayed constant in spring 2022 even when testing demand fell. We estimated the odds of using unsupervised versus supervised testing to be significantly greater among those

BackgroundFood insecurity continues to be a risk for college students in the United States. It is associated with numerous problems, such as chronic health conditions, increased stress and anxiety, and a lower grade point average. After COVID-19, the Supplemental Nutrition Assistance Program (SNAP) benefits were extended to college-aged students; however, there were some barriers to participation, which persisted such as lack of perceived food insecurity risk, lack of knowledge regarding the SNAP application process, the complexity of determining eligibility, and stigma associated with needing social assistance. A technology-enhanced tool was developed to address these barriers to SNAP enrollment and encourage at-risk college students to apply for SNAP. ObjectiveThe purpose of this study was to test the usability and acceptability of a web-based SNAP screening tool designed for college-aged students. MethodsCollege students aged 18-25 years were recruited to participate in 2 rounds of usability testing during fall 2022. Participants tested the prototype of a web-based SNAP screener tool using a standardized think-aloud method. The usability and acceptability of the tool were assessed using a semistructured interview and a 10-item validated System Usability Scale questionnaire. Audio recordings and field notes were systematically reviewed by extracting and sorting feedback as positive or negative comments. System Usability Scale questionnaire data were analyzed using the Wilcoxon signed rank test and sign test. ResultsA total of 12 students (mean age 21.8, SD 2.8 years; n=6, 50% undergraduate; n=11, 92% female; n=7, 58% Hispanic or Black or African American; n=9, 78% low or very low food security) participated in both rounds of user testing. Round 1 testing highlighted overall positive experiences with the tool, with most participants (10/12) stating that the website fulfills its primary objective as a support tool to encourage college students to apply for SNAP. However, issues related to user interface design, navigation, and wording of some questions in the screening tool were noted. Key changes after round 1 reflected these concerns, including improved design of response buttons and tool logo and improved clarity of screening questions. The overall system usability showed slight, but not statistically significant, improvement between round 1 and round 2 (91.25 vs 92.50; P=.10, respectively). ConclusionsOverall usability findings suggest that this web-based tool was highly usable and acceptable to urban college students and could be an effective and appealing approach as a support tool to introduce college students to the SNAP application process. The findings from this study will inform further development of the tool, which could eventually be disseminated publicly among various college campuses.

Introduction One in 10 patients are harmed in healthcare, more than three million deaths occur annually worldwide due to patient safety incidents, and the economic burden of patient safety incidents accounts for 15% of hospital expenditure. Poor communication between patients and practitioners is a significant contributor to patient safety incidents. This study aims to evaluate the extent to which patient safety is affected by communication and to provide a logic model that illustrates how communication impacts patient safety.Methods and analysis We will conduct a systematic review of randomised and non-randomised studies, reported in any language, that quantify the effects of practitioner and patient communication on patient safety. We will search MEDLINE, CINAHL, APA PsychINfo, CENTRAL, Scopus and ProQuest theses and dissertations from 2013 to 7 February 2024. We will also hand-search references of included studies. Screening, data extraction and risk of bias assessment will be conducted by two independent reviewers. Risk of bias will be assessed using the Cochrane Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) for non-randomised studies, and the Cochrane Risk of Bias V.2 (RoB2) for randomised controlled trials. If appropriate, results will be pooled with summary estimates and 95% confidence intervals (CIs); otherwise, we will conduct a narrative synthesis. We will organise our findings by healthcare discipline, type of communication and type of patient safety incident. We will produce a logic model to illustrate how communication impacts patient safety.Ethics and dissemination This systematic review does not require formal ethics approval. Findings will be disseminated through international conferences, news and peer-reviewed journals.PROSPERO registration number CRD42024507578.

A series of 12 contiguous caudal vertebrae of an ichthyodectiform fish from the Smoky Hill Chalk Member of the Niobrara Formation is described. The vertebral centra exhibit extensive overgrowth of pathological bone and there is additional pathological bone within the centra and intervertebral spaces, which together resulted in the coossification of most centra. The extent of the pathology is greatest on preural vertebrae 1-3 and decreases anteriorly, which suggests that the pathology began posteriorly and progressed anteriorly. In addition to the pathological overgrowth on bones, the specimen preserves features interpreted as calcified and/or ossified soft tissues associated with the neural and haemal canals. The pathologies are unlike previously described examples of bony pathologies in fish, and it is suggested that they resulted from combined bacterial and fungal infections. As the pathologies developed, they would have adversely impacted the fish’s swimming and feeding abilities, and presumably eventually led to the fish’s death.

Objective To conduct an overview of systematic reviews that explore the effectiveness of interventions to enhance medical student well-being.Design Overview of systematic reviews.Data sources The Cochrane Library of Systematic Reviews, MEDLINE, APA PsychInfo, CINAHL and Scopus were searched from database inception until 31 May 2023 to identify systematic reviews of interventions to enhance medical student well-being. Ancestry searching and citation chasing were also conducted.Data extraction and synthesis The Assessing the Methodological Quality of Systematic Reviews V.2 tool was used to appraise the quality of the included reviews. A narrative synthesis was conducted, and the evidence of effectiveness for each intervention was rated.Results 13 reviews (with 94 independent studies and 17 616 students) were included. The reviews covered individual-level and curriculum-level interventions. Individual interventions included mindfulness (n=12), hypnosis (n=6), mental health programmes (n=7), yoga (n=4), cognitive and behavioural interventions (n=1), mind-sound technology (n=1), music-based interventions (n=1), omega-3 supplementation (n=1), electroacupuncture (n=1) and osteopathic manipulative treatment (n=1). The curriculum-level interventions included pass/fail grading (n=4), problem-based curriculum (n=2) and multicomponent curriculum reform (n=2). Most interventions were not supported by sufficient evidence to establish effectiveness. Eleven reviews were rated as having ‘critically low’ quality, and two reviews were rated as having ‘low’ quality.Conclusions Individual-level interventions (mindfulness and mental health programmes) and curriculum-level interventions (pass/fail grading) can improve medical student well-being. These conclusions should be tempered by the low quality of the evidence. Further high-quality research is required to explore additional effective interventions to enhance medical student well-being and the most efficient ways to implement and combine these for maximum benefit.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Introduction The developmentally variable nature of autism poses challenges in providing timely services tailored to a child’s needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child’s day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the Pediatric Autism Research Cohort (PARC) Study. In young children (

Key Clinical Message Acute aortic dissection in unusual/rare circumstances may become chronic and multi lumen. A high clinical acumen, examination and investigations in the acute setting, may help reduce late/misdiagnosis and complications in low resource settings.