Individual Variation In Response Research Articles

503 - Visualizing 3-year treatment outcome trajectories of dupilumab in adults with moderate-to-severe atopic dermatitis in real world practice

Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with high global prevalence and profound negative impact on the quality of life of children and adults. RELIEVE-AD, a prospective, longitudinal cohort study, included adults with moderate-to-severe AD who initiated dupilumab in real-world clinical practice. Results from RELIEVE-AD showed significant improvements in patient-reported disease control, quality of life, and treatment satisfaction in the overall study population that were sustained through 3 years of dupilumab treatment. Objective To report on response to dupilumab treatment over time at the individual patient-level in adults with moderate-to-­severe AD, using 3-year data from RELIEVE-AD. Methods RELIEVE-AD is a single-arm, prospective, observational study of adults with moderate-to-severe AD prescribed dupilumab and enrolled in the US dupilumab patient support program, who agreed to participate in online surveys at baseline and Months 1, 2, 3, 6, 9, 12, and 30–36. Post hoc analysis of the RELIEVE-AD 3yr data, describing changes from baseline through all post-dupilumab initiation time points at individual patient level, using Sankey plots to assess variability of individual patient response over time for the following patient-reported outcomes: Atopic Dermatitis Control Tool (ADCT) total score-based disease control status, AD-related health status, and AD treatment satisfaction. Results Of 698 patients who completed the baseline survey, 425 completed the Months 30–36 survey. Disease control (as measured by the ADCT) increased rapidly from 5.9% at baseline to 61.0% at Month 1, further increasing to 80.7% at Months 30–36. Patients reported improved AD-related health status at Month 30–36, with 70.9% reporting “Excellent” or “Very Good”, compared to 2.8% at baseline. At Months 30–36, 86.8% of patients reported being “Extremely Satisfied/Very Satisfied/Somewhat Satisfied” with their AD treatment, compared to 17.7% at baseline. All endpoints were significant vs baseline (P < 0.001). Sankey plots of the three outcomes indicated that the majority of patients maintained response over time after achieving the initial response. Conclusion The majority of patients who completed the survey reported benefits of dupilumab, such as AD control, treatment satisfaction, and health status, which remained stable or significantly improved during long-term treatment up to 36 months.

PATIENT-SPECIFIC ADAPTIVE DYNAMIC CYCLING IS ASSOCIATED WITH IMPROVED PD SYMPTOMS

https://youtu.be/b2S2VPwRthE BACKGROUND High-cadence dynamic cycling is an effective therapy for improving motor symptoms in individuals with Parkinson’s Disease (PD), as measured by the Unified Disease Parkinson’s Rating Scale-Motor III (UPDRS-III). However, there is significant variability in individual responses to this therapy. Our lab developed a patient-specific adaptive dynamic cycling (PSADC) paradigm that manipulates entropy of cadence to optimize exercise prescriptions for individuals at various stages of disease progression. The purpose of this study is to evaluate the effectiveness of 12 sessions of PSADC on motor symptom improvement (UPDRS-III score) in individuals with PD. METHODS Twenty-three individuals with idiopathic PD (were randomized into two groups: PSADC (n=13) or active control (n=10). All individuals completed 12 sessions (3 sessions per week for 4 weeks) of dynamic cycling on a SMART (Speed Manipulated Adaptive Rehabilitation Therapy) bicycle. Each session consisted of a 5-minute warm-up at 60 revolutions per minute (rpm), 30-minute exercise session (80 rpm), and 5-minute cool-down (60 rpm). Individuals in the PSADC group followed an adaptive exercise prescription in which resistance level was optimized on a weekly basis, based on the individual’s entropy of cadence, and cycling effort. Individuals in the active control group remained at a constant resistance level for the entirety of the intervention. UPDRS-III was assessed in all participants prior to and following the 12-session intervention. Two-way analysis of variance (ANOVA) and paired samples t-tests were performed to detect statistical differences in UPDRS-III score between the groups. RESULTS There was a significant group by time interaction (F= 18.746, p <0.001). The PSADC group showed a significant reduction (improvement) in UPDRS-III score (Pre: 32.8, Post: 27.5; p<0.001), while the active control group showed no significant change in UPDRS-III score (Pre: 28.2, Post: 32.4, p=0.08). CONCLUSIONS 12 sessions of PSADC significantly improved UPDRS-III score, compared to non-adaptive high-cadence dynamic cycling. These results suggest that optimizing entropy of cadence is valuable for motor symptom improvement. Future studies will develop machine learning algorithms designed to predict appropriate clinical exercise prescriptions for individuals with PD.

High variability in short and long-term recovery kinetic of blood cell count and blood chemistry in a partial body irradiation mouse model

Purpose In the aftermath of a nuclear disaster or accident, survivors will suffer from radiation-induced normal tissue damage. Recovery after radiation exposure is dictated by several factors, one of which is degree of shielding at time of exposure. This study aims to characterize the short and late term changes in kinetics and magnitude of pancytopenia and blood chemistry in a model of heterogeneous radiation exposure, or partial body irradiation (PBI), compared to whole body irradiation (WBI). Materials and methods Male C57BL/6 mice, 8-10 weeks of age, were WBI at 6 different doses (6, 6.1. 6.15, 6.2, 6.5, and 7.5 Gy) to establish the LD50. To determine the effect of shielding on blood cell counts and chemistry, animals were either WBI at 6 Gy (LD2230) or 6 Gy PBI with one leg shielding (LD030). Complete blood counts and chemistry were measured at 1, 5-, 10-, 20-, 30- and 120-days post-irradiation. Results and conclusions Irradiated animals had significant depletion of white blood cells, red blood cells and platelets up to 10 days post-irradiation. Separation between PBI and WBI were observed at 10- and 20-days post-irradiation at which point PBI animals showed sign of recovery while overall cell count remains depleted in WBI animals up to 30 days post-irradiation. In addition, significant changes were found in parameters indicative of hematopoietic injury including hemoglobin count, hematocrit count and white blood cell population. Significant changes were observed in kidney function with changes to blood urea nitrogen and calcium concentration at 5-days post-irradiation. At 10-days post-irradiation. liver function changes differentiated WBI from PBI animals. Long-term, irradiated animal’s chemistry values and many blood counts were not significantly different from Sham. In conclusion, partial shielding ensured complete survival and demonstrated a different recovery kinetics of blood and chemistry parameters after irradiation compared to survivors of whole body irradiation and no single hemopoietic parameter was able to consistently differentiate irradiated from Sham animals. This seems to indicate that there is no single robust hemopoietic parameter to differentiate those exposed from those who were not due to the inherent variability in individual responses. Furthermore, there were no significant long-term effects on these blood parameters between survivors of WBI and PBI except that shielding accelerated recovery.

The Role of the FODMAP Diet in IBS.

The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel syndrome (IBS). However, how the low FODMAP diet works is still not completely understood. These mechanisms encompass not only traditionally known factors such as luminal distension induced by gas and water but also recent evidence on the role of FOMAPs in the modulation of visceral hypersensitivity, increases in intestinal permeability, the induction of microbiota changes, and the production of short-chain fatty acids (SCFAs), as well as metabolomics and alterations in motility. Although most of the supporting evidence is of low quality, recent trials have confirmed its effectiveness, even though the majority of the evidence pertains only to the restriction phase and its effectiveness in relieving abdominal bloating and pain. This review examines potential pathophysiological mechanisms and provides an overview of the existing evidence on the effectiveness of the low FODMAP diet across various IBS subtypes. Key considerations for its use include the challenges and disadvantages associated with its practical implementation, including the need for professional guidance, variations in individual responses, concerns related to microbiota, nutritional deficiencies, the development of constipation, the necessity of excluding an eating disorder before commencing the diet, and the scarcity of long-term data. Despite its recognized efficacy in symptom management, acknowledging these limitations becomes imperative for a nuanced comprehension of the role of a low FODMAP diet in managing IBS. By investigating its potential mechanisms and evidence across IBS subtypes and addressing emerging modulations alongside limitations, this review aims to serve as a valuable resource for healthcare practitioners, researchers, and patients navigating the intricate landscape of IBS.

The effectiveness of warning statements in reducing careless responding in crowdsourced online surveys.

Carelessness or insufficient effort responding is a widespread problem in online research, with estimates ranging from 3% to almost 50% of participants in online surveys being inattentive. While detecting carelessness has been subject to multiple studies, the factors that reduce or prevent carelessness are not as well understood. Initial evidence suggests that warning statements prior to study participation may reduce carelessness, but there is a lack of conclusive high-powered studies. This preregistered randomized controlled experiment aimed to test the effectiveness of a warning statement and an improved implementation of a warning statement in reducing participant inattention. A study with 812 participants recruited on Amazon Mechanical Turk was conducted. Results suggest that presenting a warning statement is not effective in reducing carelessness. However, requiring participants to actively type the warning statement statistically significantly reduced carelessness as measured with self-reported diligence, even-odd consistency, psychometric synonyms and antonyms, and individual response variability. The active warning statements also led to statistically significantly more attrition and potentially deterred those who were likely to be careless from even participating in this study. We show that the current standard practice of implementing warning statements is ineffective and novel methods to prevent and deter carelessness are needed.

Understanding risk and causal mechanisms for developing obesity in infants and young children: A National Institutes of Health workshop.

Obesity in children remains a major public health problem, with the current prevalence in youth ages 2-19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29-30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.

Effects of Individualized Exercise on Risk Factors of Metabolic Syndrome: A Scoping Review.

Exercise intervention is effective in alleviating the severity of metabolic syndrome (MetS). However, the results of previous studies on the effect of exercise on MetS have demonstrated considerable individual variability in response to a specific dose of exercise, which was attributed to the lack of a personalized approach to exercise prescription. It is essential to consider individual factors to enhance the effectiveness of exercise in addressing MetS. This scoping review assesses the effectiveness of individualized exercise on the risk factors associated with MetS. Various databases and articles were examined based on eligibility criteria and nine studies were chosen for this review. Personal and adjusted factors were predominantly analyzed to tailor exercise prescriptions to individual needs. This review proposes that personal factors can be classified into three categories: fixed factors, adaptation factors, and response factors, considering both clinical and exercise science perspectives. It also suggests that a two-way communication approach between specialists and individuals is more effective for prescribing exercise to address MetS compared to a one-way method. A one-way communication approach relies solely on an expert's decision, even whether or not he or she fully considers a client's lifestyle and preferences. If the individualized selection of exercise prescriptions is achieved through two-way communication between specialists and subjects, significant improvements can be expected in terms of both MetS severity and exercise adherence.

Incorporating life history diversity in an integrated population model to inform viability analysis

Life history diversity can significantly affect population dynamics and effects of management actions. For instance, variation in individual responses to environmental variability can reduce extirpation risk to populations, as the portfolio effect dampens temporal variability in abundance. Moreover, differences in habitat use may cause individuals to respond differently to habitat management and climate variability. To explore the role of life history diversity in population trajectories, population models need to incorporate within-population variation. Integrated population modeling (IPM) is a population modeling approach that offers several advantages for sharing information and propagating uncertainty across datasets. In this study, we developed an IPM for an endangered population of Chinook salmon ( Oncorhynchus tshawytscha) in the Wenatchee River, Washington, USA, that accounts for diversity in juvenile life histories, spawning location, and return age. Our analysis revealed that diversity in the age of juvenile emigration from natal streams had a portfolio effect, resulting in a 20% reduction in year-to-year variability in adult abundance in population projections. Our population viability analysis suggests that management interventions may be necessary to meet recovery goals, and our model should be useful for simulating the outcomes of proposed actions.

Synergistic effects of transcutaneous spinal stimulation and neuromuscular electrical stimulation on lower limb force production: Time to deliver.

Transcutaneous spinal stimulation (TSS) and neuromuscular electrical stimulation (NMES) can facilitate self-assisted standing in individuals with paralysis. However, individual variability in responses to each modality may limit their effectiveness in generating the necessary leg extension force for full body weight standing. To address this challenge, we proposed combining TSS and NMES to enhance leg extensor muscle activation, with optimizing timing adjustment to maximize the interaction between the two modalities. To assess the effects of TSS and NMES on knee extension and plantarflexion force, ten neurologically intact participants underwent three conditions: (1) TSS control, (2) NMES control, and (3) TSS + NMES. TSS was delivered between the T10 and L2 vertebrae, while NMES was delivered to the skin over the right knee extensors and plantarflexors. TSS and NMES were administered using a 15 Hz train of three 0.5 ms biphasic pulses. During the TSS + NMES condition, the timing between modalities was adjusted in increments of ¼ the interval within a 15 Hz frequency, i.e., 66, 49.5, 33, 16.5, and 1 ms. NMES combined with TSS, produced synergistic effects even on non-targeted muscle groups, thereby promoting leg extension across multiple joints in the kinematic chain. The sequence of NMES or TSS trains relative to each other did not significantly impact motor output. Notably, a delay of 16.5 to 49.5 ms between interleaved TSS and NMES pulses, each delivered at 15 Hz, results in more robust and synergistic responses in knee extensors and plantarflexors. By adjusting the timing between TSS and NMES, we can optimize the combined use of these modalities for functional restoration. Our findings highlight the potential of integrated TSS and NMES protocols to enhance motor function, suggesting promising avenues for therapeutic applications, particularly in the rehabilitation of individuals with SCI.

The Effects of Low-Load Squat Jump and Maximal Isometric Priming Exercise on Muscular Performance and Perceptual State.

Harrison, PW, James, LP, Jenkins, DG, McGuigan, MR, Holmberg, PM, and Kelly, VG. The effects of low-load squat jump and maximal isometric priming exercise on muscular performance and perceptual state. J Strength Cond Res 38(1): 1-9, 2024-The aim of this study was to examine responses at 3 and 27 hours after low-load jump squat (LL) and maximal isometric half-squat (ISO) priming stimuli. Fifteen resistance-trained males performed LL (4 × 3 at 20% 1 repetition maximum [1RM]), ISO (4 × 3 seconds), and control (CON) activities (standardized warm-up) in a randomized and counterbalanced order. Countermovement jump (CMJ) and isometric midthigh pull tests were conducted to assess performance changes after priming and CON activities. No clear changes in CMJ measures were found after priming activities compared with CON. However, small effect size improvements were found after priming stimuli completed on the same day. A 2.9% decrease in concentric phase duration (CI = 0.3-5.9, p = 0.333, Cliff's delta = -0.156) and a 9.1% increase in RSImod (CI = 0.2-12.3, p = 0.151, Cliff's delta = -0.218) occurred at 3 hours after LL compared with CON. Braking phase duration (CI = 0.8-10.6, p = 0.333, Cliff's delta = -0.213) was 2.9% shorter at 3 hours after ISO compared with CON. No clear changes in isometric peak force occurred after priming activities compared with CON. Additionally, questionnaires were completed to assess perceptual state and perceived effectiveness of the priming stimulus to influence performance. An increase in the "effect of activity" was perceived at 3 hours after LL and ISO (p = 0.013-0.044, Cliff's delta = 0.578-0.6) and at 27 hours after ISO (p = 0.99, Cliff's delta = 0.173) compared with CON. An increase in "muscular heaviness" was also reported at 3 hours after ISO compared with CON (p = 0.199, Cliff's delta = 0.320). The collective findings suggest limited benefits over the day after LL and ISO priming stimuli. However, as there was substantial variation in individual responses, the relative nature of priming responses should be considered when prescribing similar strategies in practical environments.

Genetic determinants of IgG antibody response to COVID-19 vaccination

Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial inter-individual variability and have been linked to vaccine efficacy. To elucidate the underlying mechanism behind this variability, we conducted a genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK Biobank participants who were previously uninfected by SARS-CoV-2 and had received either the first dose (n= 54,066) or the second dose (n= 46,232) of COVID-19 vaccines. Our analysis revealed significant genome-wide associations between the IgG antibody serostatus following the initial vaccine and human leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1∗13:02 allele (MAF= 4.0%, OR= 0.75, p= 2.34e-16) demonstrated the most statistically significant protective effect against IgG seronegativity. This protective effect was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at position 71 on HLA-DRβ1 (p= 1.88e-25), leading to a change in the electrostatic potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA alleles on IgG responses was cell type specific, and we observed a shared genetic predisposition between IgG status and susceptibility/severity of COVID-19. These results were replicated within independent cohorts where IgG serostatus was assayed by two different antibody serology tests. Our findings provide insights into the biological mechanism underlying individual variation in responses to COVID-19 vaccines and highlight the need to consider the influence of constitutive genetics when designing vaccination strategies for optimizing protection and control of infectious disease across diverse populations.

Islamic Mindfulness-Based Play Activities: Enhancing Child Mental Health in the Post-Pandemic Era

This research focuses on developing Islamic mindfulness-based play activities to mitigate child mental health issues in the post-pandemic context. The study was conducted in Jakarta-Depok kindergartens using a modified Research and development (R&D) approach tailored for educational settings, as per Borg and Gall. The primary aim was to create and evaluate educational tools to foster Islamic mindfulness among young learners. The research involved identifying children's learning challenges post-pandemic and developing and refining educational games and teaching methods. Data collection encompassed observational studies, educator feedback, and direct interaction with children using the developed tools. The analysis evaluated these tools' usability, engagement level, and educational impact. The results highlighted the development of a physical model comprising a 14-chapter guidebook for tea. Still, it is a procedural model that condenses the original ten stages into seven. Essential components include yoga based on prayer movements, activities for enhancing food relationships, self-body awareness exercises, sensory training, gratitude journal writing, and positive affirmations based on Asmaul Husna. Evaluations by material and learning design experts and one-to-one teacher tests affirmed the model's quality. A field trial with 20 children showed enjoyment and preference for gratitude journal writing. Conclusively, the research effectively developed a model for Islamic mindfulness-based play activities, demonstrating the potential to enhance children's mental health post-pandemic. However, limitations such as geographic confinement and individual response variability suggest the need for broader application and further research to assess long-term impacts. This study contributes significantly to educational and psychological interventions, offering a culturally sensitive, holistic child development approach integrating mental health, spirituality, and education.

Meta-Analysis of the Causality of Deformations in Marine Fish Larvae Culture

The development of deformities in farmed fish is largely the result of abiotic, biotic, and xenobiotic factors, information deficiencies in optimizing nutrition, and the genetic background to which the fish are exposed in their early life stages. In general, skeletal anomalies are considered to have significant adverse effects on animal welfare, biological performance of farmed fish, product quality, and production costs. In the data obtained by the meta-analysis method, the presence of negative effects on the formal structures of fish was found, regardless of the region, duration, stage, factor, stock density, and method used to detect deformation. In this regard, in the studies considered within the deformation region/type, 46% of deformities were found in the spine, 37% in the head, and 16% in the total skeleton. In turn, the results of the meta-analysis showed that the percentages of the apparent value were 35.82% in the spine, 33.12% in the skeleton, and 31.06% in the head. The deformation rate had an overall negative effect on the functional characteristics of the fish, regardless of the variables considered. In addition, all statistically significant individual response variables had a negative effect size. In the future, advanced statistical tools such as Bayesian meta-analysis, network meta-analysis, and meta-regression analysis can be used to explore more complex data structures. The rapid development of artificial intelligence techniques will increase the efficiency of data collection and the robustness of results for meta-analysis studies in aquaculture and other fields.

High-Quality Brain and Bone Marrow Nuclei Preparation for Single Nuclei Multiome Assays.

Single-cell analysis has become the approach of choice for unraveling the complexity of biological processes that require assessing the variability of individual cellular responses to treatment or infection with single-cell resolution. Many techniques for single-cell molecular profiling have been developed over the past 10 years, and several dedicated technologies have been commercialized. The 10X Genomics droplet-based single-cell profiling is a widespread technology that offers ready-to-use reagents for transcriptomic and multi-omic single-cell profiling. The technology includes workflows for single-cell and single-nuclei RNA sequencing (scRNA-Seq and snRNA-Seq, respectively), scATAC-Seq, single-cell immune profiling (BCR/TCR sequencing), and multiome. The latter combines transcriptional (scRNA-Seq) and epigenetic information (scATAC-Seq) coming from the same cell. The quality (viability, integrity, purity) of single-cell or single-nuclei suspensions isolated from tissues and analyzed by any of these approaches is critical for generating high-quality data. Therefore, the sample preparation protocols should be adapted to the particularities of each biological tissue and ensure the generation of high-quality cell and nuclei suspensions. This article describes two protocols for preparing brain and bone marrow samples for the downstream multiome 10X Genomics pipeline. The protocols are performed stepwise and cover tissue dissociation, cell sorting, nuclei isolation, and quality control of prepared nuclei suspension that is used as starting material for cell partitioning and barcoding, library preparation, and sequencing. These standardized protocols produce high-quality nuclei libraries and robust and reliable data.

Averaged versus individualized: pragmatic N-of-1 design as a method to investigate individual treatment response

Heterogeneous treatment effects represent a major issue for medicine as they undermine reliable inference and clinical decision-making. To overcome the issue, the current vision of precision and personalized medicine acknowledges the need to control individual variability in response to treatment. In this paper, we argue that gene-treatment-environment interactions (G × T × E) undermine inferences about individual treatment effects from the results of both genomics-based methodologies—such as genome-wide association studies (GWAS) and genome-wide interaction studies (GWIS)—and randomized controlled trials (RCTs). Then, we argue that N-of-1 trials can be a solution to overcome difficulties in handling individual variability in treatment response. Although this type of trial has been suggested as a promising strategy to assess individual treatment effects, it nonetheless has limitations that limit its use in everyday clinical practice. We analyze the existing variability within the designs of N-of-1 trials in terms of a continuum where each design prioritizes epistemic and pragmatic considerations. We then support wider use of the designs located at the pragmatic end of the explanatory-pragmatic continuum.

Role of Genetic Polymorphisms in the Development of Complications in Patients with Implanted Left Ventricular Assist Devices: HeartWare, HeartMate II, and HeartMate 3

Left ventricular assist device (LVAD) implantation is one of the mechanical circulatory support (MCS) treatments for advanced heart failure (HF) patients. MCS has emerged as a lifesaving therapy that improves patients’ quality of life. However, MCS remains limited by a paradoxical coagulopathy accompanied by thrombosis and bleeding. The mechanisms of MCS thrombosis are increasingly being defined, but MCS-related bleeding, which is related to shear-mediated alteration of platelet function, remains poorly understood. Complications might develop due to the high non-physiological shear stress in the device and as a consequence of individual variability in response to the antithrombotic therapy. Thromboelastography (TEG) and genotyping of gene polymorphisms that are involved in the coagulation cascade and in the metabolism of the antithrombotic therapy might be valuable sources of information for the reduction of complication development. The aim of the study was to identify genetic factors related to the development of device complications according to the implanted LVAD type. We compared the clinical and genetic data of HF patients (n = 98) with/without complications with three types of implanted devices: HeartWare HVAD (HW), HeartMate II (HMII), and HeartMate 3 (HM3). rs9923231 in VKORC1 (95%CI −6.28–0.22, p = 0.04) and rs5918 in ITGB3 genes (95%CI 0.003–4.36, p = 0.05) showed significant association with the TEG coagulation index parameter, which identified hyper- and hypo-coagulation states. The wild genotype of rs5918 in the ITGB3 gene prevailed in patients implanted with HM3 devices, which developed fewer complications than with HMII (p = 0.04). Individual genetic information could be useful in the management of patients with HF and the implantation of MCS to reduce the development of complications.

Highlighting the impacts of ciguatera poisoning on fishers and fish consumers in Hawaiʻi to inform future management strategies

Ciguatera poisoning (CP) occurs as a result of consuming seafood that has bioaccumulated toxins produced by dinoflagellates (primarily Gambierdiscus) in tropical, coastal ecosystems. The impacts of CP can be long-lasting for affected individuals and communities, especially in places like the Hawaiian Islands, where fish provide sustenance and have important financial and cultural value. This study used anonymous online surveys (n = 106) and targeted interviews (n = 20) to address data gaps on the prevalence, distribution, and impacts of CP among fishers and fish consumers in Hawaiʻi. Survey results indicated that few individuals (22%) reported their CP cases to the Department of Health, despite the fact that most impacted respondents (67%) experienced symptoms lasting more than a week and some (10%) were affected for more than a year. Certain locations (e.g., north shore of Kauaʻi) and species (e.g., uku - Aprion virescens and knifejaw - Oplegnathus punctatus) emerged as being highly problematic, though they have received little research, monitoring, or management attention historically. Interview data revealed common interests and themes among affected individuals, including a desire for more data on the environmental drivers, factors affecting individual CP response variability, and increased education and awareness, particularly for vulnerable populations. This study offers essential information for managers crafting policy and outreach materials to mitigate the risk of CP in Hawaiʻi and provides baseline information that can be used to inform future studies in Hawaiʻi and throughout the region.

Vocal Cues to Assess Arousal State of Bottlenose Dolphins (Tursiops spp.) Involved in Public Presentations

Emotions in animals may be expressed by arousal and understanding this often relies upon the monitoring of their behaviour. Under human care, animals’ arousal states may be linked to husbandry decisions, whereby animals may display arousal responses to scheduled events such as feeding and human interaction. Here, we investigate vocal correlates of arousal associated with public presentations of bottlenose dolphins (Tursiops spp.) in human care by comparing vocal production rates and characteristics between high and low arousal contexts. Elevated arousal during the day compared with overnight was characterised by increased signature and non-signature whistle production. High intensity broadband crack vocalisations were produced less than whistles during the day and did not correlate with increased arousal around presentation times. Three of ten dolphins increased signature whistle production before and/or after presentation sessions, indicating elevated arousal and variation in individual responses. Many individuals elevated minimum frequency and suppressed maximum frequency of signature whistles in a way that correlated with higher arousal contexts, indicating that these may therefore be good indicators of changes in arousal state. Overall, our study demonstrates that passive acoustic monitoring can provide a useful indication of arousal linked to husbandry decisions, and that individual variation in vocal responses, likely linked to personality, is important to consider.

Bailout inclisiran-based triple lipid-lowering therapy reduces plaque lipid content in stable coronary artery disease patients

Abstract Background Low-density lipoprotein cholesterol (LDL-C) has a causal role in atherosclerotic cardiovascular disease. Genetic studies and variability in individual response to lipid-lowering therapies suggest combining hypolipidaemic medications with different mechanisms of action. Purpose The aim of this study was to evaluate the effect of triple inclisiran-based hypolipidaemic therapy in patients not reaching LDL-C target on maximum statin/ezetimibe treatment. Methods This prospective study enrolled 37 stable coronary artery disease patients admitted for elective percutaneous coronary intervention after 4-6 weeks on maximum tolerated statin and/or ezetimibe therapy during run-in period. Afterwards, patients with LDL-C level >1.8 mmol/l at the time of inclusion were assigned to receive add-on inclisiran (triple therapy group). In all participants near-infrared spectroscopy (NIRS) was performed at baseline and after 15 months for atherosclerotic plaque evaluation in the segment of interest, defined as 20-50% lesion in the proximal or middle third of a coronary artery. Statistical analysis was carried out with SPSS Statistics software. Results Average LDL-C level among screened patients was 2.81 (±1.17) mmol/l. In 19 patients LDL-C level remained >1.8 mmol/l on maximally tolerated statin and/or ezetimibe treatment, and after 15 months of triple therapy mean LDL-C reached 1.81 (±1.02) mmol/l with a significant LDL-C percentage change of 35.59% (95%CI -47.31 to -9.18, P=0.006) in this group. 17 patients continued statin/ezetimibe as mono or dual treatment and at 15-month follow-up mean LDL-C level comprised 1.67 (±0.61) mmol/l among these participants. According to NIRS data, maximum lipid-core burden index within 4 mm (maxLCBI4 mm) was significantly reduced by 28.85 (95%CI -189.39 to 17.64, P=0.041) in triple therapy group and by 114.72 in mono or dual therapy group (-194.76 to 23.01, P=0.004), with no statistically significant difference established between both groups (P=0.494). Conclusions Triple therapy demonstrated significant atherosclerotic plaque lipid content reduction along with LDL-C level lowering in patients with insufficient effectiveness of statin/ezetimibe treatment.

Cognition mediates response to anthropogenic noise in wild Western Australian magpies (Gmynorhina tibicen dorsalis).

Anthropogenic noise is a pollutant of growing concern, with wide-ranging effects on taxa across ecosystems. Until recently, studies investigating the effects of anthropogenic noise on animals focused primarily on population-level consequences, rather than individual-level impacts. Individual variation in response to anthropogenic noise may result from extrinsic or intrinsic factors. One such intrinsic factor, cognitive performance, varies between individuals and is hypothesised to aid behavioural response to novel stressors. Here, we combine cognitive testing, behavioural focals and playback experiments to investigate how anthropogenic noise affects the behaviour and anti-predator response of Western Australian magpies (Gymnorhina tibicen dorsalis), and to determine whether this response is linked to cognitive performance. We found a significant population-level effect of anthropogenic noise on the foraging effort, foraging efficiency, vigilance, vocalisation rate and anti-predator response of magpies, with birds decreasing their foraging, vocalisation behaviours and anti-predator response, and increasing vigilance when loud anthropogenic noise was present. We also found that individuals varied in their response to playbacks depending on their cognitive performance, with individuals that performed better in an associative learning task maintaining their anti-predator response when an alarm call was played in anthropogenic noise. Our results add to the growing body of literature documenting the adverse effects of anthropogenic noise on wildlife and provide the first evidence for an association between individual cognitive performance and behavioural responses to anthropogenic noise.