John Gill Technology (United Kingdom)

Objective: This study examined sex differences in subacute plasma biomarkers in adolescents post-concussion and their associations with post-concussion symptom (PCS) burden. We hypothesized that biomarker levels would differ by sex and relate to PCS severity. Setting: Participants were recruited from outpatient settings as part of the Concussion Assessment, Research, and Education for Kids (CARE4Kids) multi-site observational study. Participants: Adolescents 11 to 17.99 years with a concussion based on Concussion In Sport Group criteria were eligible. Participants were assessed 7 to 35 days post-injury and required to report at least one PCS exceeding pre-injury baseline. A total of 339 participants (174 females, 145 males) with both blood biomarkers and PCS data were analyzed. Design: Plasma levels of glial fibrillary acidic protein, neurofilament light chain (NFL), ubiquitin C-terminal hydrolase (UCH-L1), tau, and phosphorylated tau at threonine 181 (p-tau181) were measured and compared between sexes. PCS severity was assessed using the Post-Concussion Symptom Inventory, 2nd Ed (PCSI-2) Retrospective Adjusted Post-Injury Difference (RAPID) scoring system. Main Measures: Primary outcomes were sex differences in biomarker levels and their associations with RAPID scores. Results: Females had significantly higher tau (females: M = 6.18, SD = 8.02; males: M = 4.55, SD = 5.53; P = .012) and lower p-tau181/tau ratios (females: M = 6.18, SD = 8.02; males: M = 4.55, SD = 5.53; P = .002) after adjusting for age, BMI, and days post-injury. In both sexes, cognitive symptoms were associated with higher p-tau181. In females, emotional symptoms were associated with elevated NFL and UCH-L1. In males, physical and overall symptoms were associated with lower NFL, UCH-L1, and p-tau181. Conclusion: This study highlights sex-specific biomarker differences during adolescent concussion recovery and the importance of understanding how sex differences may influence symptom burden and recovery trajectories. Future research should examine hormonal influences on biomarker profiles and prolonged symptomatology.

PurposePatient Public Involvement (PPI) is integral within health research. This abstract presents how involving families and other stakeholders has directly guided a forthcoming research project; which intends to understand families’ and young peoples’ experiences of selective dorsal rhizotomy (SDR), including rehabilitation.AimsTo demonstrate how PPI influenced protocol design for the forthcoming study exploring SDRTo highlight the benefits PPI had on protocol designMethodAn active PPI group was convened for this project, building on previous PPI work. The group comprises 2 parents, 2 CYP’s and 2 clinicians active in the field of neurodisability, to provide direction to:Prioritise and refine the research questions and design (including recruitment)Develop relevant topic guideDevelop accessible information sheets‘Sense check’ future findingsCritically evaluate research outputs that include family informationThe initial PPI focus group used participatory methods for equal member contributions. It covered points 1-3 with some reference for point 4. Further open PPI work at an SDR family event day provided steering for point 5.ResultsPPI has demonstrably influenced protocol development, which is now undergoing NHS ethical review. The project is focused upon stakeholders’ priorities with tangible outputs, whilst filling a research gap. The title represents this priority and associated methodology;‘Supporting family decision making around Selective Dorsal Rhizotomy – A family participatory research project to co-design pre-operative counselling information’.Refined protocol qualitative interviews, now includes creative methods, to meet agreed objectives, to:Understand experiences and expectations families consider most important relating to SDR operation, physiotherapy treatment and outcomes (Phase1).Explore findings with families and clinical experts to direct child and family–centred information development, supporting their SDR journey (Phase 2).ConclusionCollaboration with young people and families was essential to driving a relevant participatory research project including meaningful outputs.

Abstract BackgroundInfections with helminths cause an enormous disease burden in billions of animals and plants worldwide. Large scale use of anthelmintics has driven the evolution of resistance in a number of species that infect livestock and companion animals, and there are growing concerns regarding the reduced efficacy in some human-infective helminths. Understanding the mechanisms by which resistance evolves is the focus of increasing interest; robust genetic analysis of helminths is challenging, and although many candidate genes have been proposed, the genetic basis of resistance remains poorly resolved.ResultsHere, we present a genome-wide analysis of two genetic crosses between ivermectin resistant and sensitive isolates of the parasitic nematode Haemonchus contortus, an economically important gastrointestinal parasite of small ruminants and a model for anthelmintic research. Whole genome sequencing of parental populations, and key stages throughout the crosses, identified extensive genomic diversity that differentiates populations, but after backcrossing and selection, a single genomic quantitative trait locus (QTL) localised on chromosome V was revealed to be associated with ivermectin resistance. This QTL was common between the two geographically and genetically divergent resistant populations and did not include any leading candidate genes, suggestive of a previously uncharacterised mechanism and/or driver of resistance. Despite limited resolution due to low recombination in this region, population genetic analyses and novel evolutionary models supported strong selection at this Q.TL, driven by at least partial dominance of the resistant allele, and that large resistance-associated haplotype blocks were enriched in response to selection.ConclusionsWe have described the genetic architecture and mode of ivermectin selection, revealing a major genomic locus associated with ivermectin resistance, the most conclusive evidence to date in any parasitic nematode. This study highlights a novel genome-wide approach to the analysis of a genetic cross in non-model organisms with extreme genetic diversity, and the importance of a high quality reference genome in interpreting the signals of selection so identified.

This article presents the initial results from the first road-mapping event organised on the theme technology-transfer in the field of assistive and ICT products by the FP7 Coordination Action CARDIAC (Coordination Action in R&D in Accessible and

Background and objective Insertion of the laryngeal mask airway in the anaesthetized patient can sometimes be difficult and propofol has been advocated as the anaesthetic induction agent of choice because of its depressant effect on laryngeal reflexes compared with other intravenous anaesthetics. However, when used as the sole induction agent, relatively large doses of propofol are required to achieve successful laryngeal mask insertion. This has cost implications and may produce unwanted cardiorespiratory depression. Methods One hundred and forty-two patients were randomized to receive either: fentanyl 1 µg kg−1 and lidocaine 1.5 mg kg−1 (group 1), or fentanyl 1 µg kg−1 and midazolam 0.04 mg kg−1 (group 2), or fentanyl 1 µg kg−1, midazolam 0.04 mg kg−1 and lidocaine 1.5 mg kg−1 (group 3) or fentanyl 1 µg kg−1 (group 4) 2 min before induction of anaesthesia. Anaesthesia was established with propofol infused at 33.3 mg min−1. Results Patients who were given midazolam required significantly less propofol to achieve satisfactory laryngeal mask insertion, median propofol doses: group 1, 1.63 mg kg−1; group 2, 1.16 mg kg−1; group 3, 1.01 mg kg−1; group 4, 1.9 mg kg−1, P < 0.0001 (analysis of variance). Patients given midazolam reported less pain on injection with propofol 13% and 3% groups (2 and 3) compared with 37.5% and 77% (groups 1 and 4) P = 0.002 (χ2). Conclusions Midazolam reduces the dose of propofol required for induction of anaesthesia and successful insertion of the laryngeal mask airway. There was no clinical benefit to be gained from the addition of lidocaine.

We studied 1035 consecutive postinfarction patients to determine the feasibility of altering type A behavior and the effect such alteration might have on subsequent rates of infarction and cardiovascular death. Approximately 300 subjects were enrolled in small groups and primarily received cardiologic counseling on the usually accepted coronary risk factors. Six hundred subjects received, in addition to cardiologic counseling, advice and instructions designed to diminish the intensity of their type A behavior. The remaining subjects, serving as controls, received no counseling, but were examined and interviewed annually, as were those who dropped out of counseling groups. More than 98% of the 1035 subjects exhibited moderate-to-severe type A behavior during a videotaped structured interview. After the first year of this 5-year study, the rates of infarction and cardiovascular death were lower (p less than 0.01 and p less than 0.05, respectively) among subjects who received both cardiologic and behavioral counseling than among the control subjects. The rate of nonfatal infarction was lower (p less than 0.05) among subjects who received behavioral counseling than among those who received only cardiologic counseling or those who dropped out of either counseling group. The circumstances that most often preceded recurrent infarction or cardiovascular death were emotional crisis, excess physical activity, ingestion of a single fatty meal or a combination of these phenomena.