Individual Response Patterns Research Articles

Effects of α-olefin sulfonate (AOS) on Tubifex tubifex: toxicodynamic-toxicokinetic inferences from the general unified threshold (GUTS) model, biomarker responses and molecular docking predictions.

We investigated the potential ecological risks and harm to aquatic organisms posed by anionic surfactants such as α-olefin sulfonate (AOS), which are commonly found in industrial and consumer products, including detergents. This study assessed acute (96-h) and subchronic (14-day) responses using antioxidant activity, protein levels, and histopathological changes in Tubifex tubifex exposed to different AOS concentrations (10% of the LC50, 20% of the LC50, and a control). Molecular docking was used to investigate the potential interactions between the key stress biomarker enzymes (superoxide dismutase, catalase, and cytochrome c oxidase) of Tubifex tubifex. Acute AOS exposure showed a concentration-dependent decrease in survival, and the general unified threshold (GUTS) model revealed that survivorship is linked to individual response patterns rather than random (stochastic) fluctuations. The GUTS model also revealed dose-dependent toxicity patterns in Tubifex tubifex exposed to α-olefin sulfonate (AOS), with adaptive mechanisms at lower concentrations but significant increases in mortality beyond a certain threshold, emphasizing the role of the AOS concentration in shaping its toxicological impact. Exposure to AOS disrupted antioxidant activity, inducing oxidative stress, with GST and GPx showing positive associations with surfactant concentration and increased lipid peroxidation (elevated MDA levels); moreover, AOS exposure decreased protein concentration, signifying disturbances in vital cellular processes. Histopathological examinations revealed various tissue-level alterations, including cellular vacuolation, cytoplasmic swelling, inflammation, necrosis, and apoptosis. Molecular docking analysis demonstrated interactions between AOS and enzymes (-catalase, superoxide dismutase, and cytochrome c oxidase) in Tubifex tubifex, including hydrophobic and hydrogen bond interactions, with the potential to disrupt enzyme structures and activities, leading to cellular process disruptions, oxidative stress, and tissue damage. According to the species sensitivity distribution (SSD), the difference in toxicity between Tilapia melanopleura (higher sensitivity) and Daphnia magna (low sensitivity) to AOS suggests distinct toxicokinetic and toxicodynamic mechanisms attributable to more complex physiology in Tilapia and efficient detoxification in Daphnia due to its smaller size.

Item response theory validation of the Oxford knee score and Activity and Participation Questionnaire: a step toward a common metric

ObjectivesThe Oxford knee score (OKS) and OKS Activity and Participation Questionnaire (OKS-APQ) are patient-reported outcome measures used to assess people undergoing knee replacement surgery. They have not explicitly been tested for unidimensionality (whether they measure one underlying trait such as ‘knee health’). This study applied item response theory (IRT) to improve the validity of the instruments to optimize for ongoing use. Study Design and SettingParticipants undergoing primary total knee replacement (TKR) provided preoperative and postoperative responses for OKS and OKS-APQ. Confirmatory factor analysis (CFA) were performed on the OKS and OKS-APQ separately and then on both when pooled into one. An IRT model was fitted to the data. Results2972 individual response patterns were analyzed. CFA demonstrated that when combining OKS and OKS-APQ as one instrument, they measure one latent health trait. A user-friendly, free-to-use, web app has been developed to allow clinicians to upload raw data and instantly receive IRT scores. ConclusionsThe OKS and OKS-APQ can be combined to use effectively as a single instrument (producing a single score). For the separate OKS and OKS-APQ the original items and response options can continue to be posed to patients, and this study has confirmed the suitability of IRT-weighted scoring. Applying IRT to existing responses converts traditional sum scores into continuous measurements with greater granularity, including individual measurement error.

Inhibition of muscle sympathetic nerve activity in premenopausal women: responses to sudden sensory stimuli predict responses to mental stress.

Muscle sympathetic nerve responses to sudden sensory stimuli have been elucidated in several studies on young healthy men, showing reproducible interindividual differences ranging from varying degrees of inhibition to no significant change, with very few subjects showing significant excitation. These individual response patterns have been shown to predict the neural response to mental stress and coupled blood pressure responses. The aim of this study was to investigate whether premenopausal healthy women show similar neural and blood pressure responses. Muscle sympathetic nerve recordings from the peroneal nerve were performed in 34 healthy women (mean age 27 ± 8 yr) during sudden sensory stimuli (electrical stimuli to a finger) and 3 min of mental stress (forced arithmetics). After sensory stimuli, 18 women showed varying degrees of inhibition of muscle sympathetic nerve activity (burst amplitude mean reduction 60%, range 34-100%). The remaining 16 showed no inhibition (mean 5%, range -31 to 28%; one subject exhibiting excitation). During 3 min of mental stress, the normalized change in burst incidence for muscle sympathetic nerve activity correlated with the percentage change of muscle sympathetic nerve activity induced by the sensory stimulation protocol (r = 0.64, P = 0.0042). In contrast to men, the neural responses did not predict changes in blood pressure. Thus, premenopausal females show a similar range of individual differences in defense-related muscle sympathetic neural responses as men, but no associated differences in blood pressure responses. Whether these patterns are unchanged after menopause remains to be investigated.NEW & NOTEWORTHY Muscle sympathetic neural responses to sudden sensory stimuli in premenopausal women showed interindividual differences and the distribution of sympathetic responses was similar to that previously found in men. Despite this similarity, the associated differences in transient blood pressure responses seen in men were not found in women. The increased risk of developing hypertension in postmenopausal women warrants an investigation of whether these response patterns are altered after menopause.

Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures

Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking. We screened fourteen patient-derived PDAC cultures which reflect the intra- and intertumoural heterogeneity of PDAC for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H-1PV. Live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays and titration of viral progeny were conducted. Transcriptome profiling was employed to identify potential predictive biomarkers for response to OV treatment. Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the classical molecular subtype, the quasi-mesenchymal or basal-like subtype of PDAC was found to be more sensitive to H-1PV, jin-3, and T-VEC. Generally, expression of viral entry receptors did not correlate with sensitivity to OV treatment, with one exception: Expression of Galectin-1 (LGALS1), a factor involved in H-1PV entry, positively correlated with H-1PV induced cell killing. Rather, cellular pathways controlling immunological, metabolic and proliferative signaling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas low cyclic GMP-AMP synthase (cGAS) expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures and cells overexpressing cGAS were found to be less sensitive to MV oncolysis. Considering the heterogeneity of PDAC and the complexity of biological therapies such as OVs, no single biomarker can explain the spectrum of response patterns. For selection of a particular OV, PDAC molecular subtype, ISG expression as well as activation of distinct signaling and metabolic pathways should be considered. Combination therapies can overcome resistance in specific constellations. Overall, oncolytic virotherapy is a viable treatment option for PDAC, which warrants further development. This study highlights the need for personalised treatment in OVT. By providing all primary data, this study provides a rich source and guidance for ongoing developments. German National Science Foundation (Deutsche Forschungsgemeinschaft, DFG), German Cancer Aid (Deutsche Krebshilfe), German National Academic Scholarship Foundation (Studienstiftung des deutschen Volkes), Survival with Pancreatic Cancer Foundation.

A Bayesian hierarchical model for the analysis of visual analogue scaling tasks.

In psychophysics and psychometrics, an integral method to the discipline involves charting how a person's response pattern changes according to a continuum of stimuli. For instance, in hearing science, Visual Analog Scaling tasks are experiments in which listeners hear sounds across a speech continuum and give a numeric rating between 0 and 100 conveying whether the sound they heard was more like word "a" or more like word "b" (i.e. each participant is giving a continuous categorization response). By taking all the continuous categorization responses across the speech continuum, a parametric curve model can be fit to the data and used to analyze any individual's response pattern by speech continuum. Standard statistical modeling techniques are not able to accommodate all of the specific requirements needed to analyze these data. Thus, Bayesian hierarchical modeling techniques are employed to accommodate group-level non-linear curves, individual-specific non-linear curves, continuum-level random effects, and a subject-specific variance that is predicted by other model parameters. In this paper, a Bayesian hierarchical model is constructed to model the data from a Visual Analog Scaling task study of mono-lingual and bi-lingual participants. Any nonlinear curve function could be used and we demonstrate the technique using the 4-parameter logistic function. Overall, the model was found to fit particularly well to the data from the study and results suggested that the magnitude of the slope was what most defined the differences in response patterns between continua.

Cyanobacterial harmful bloom lipopolysaccharides: pro-inflammatory effects on epithelial and immune cells in vitro

Cyanobacterial harmful blooms (CyanoHABs) pose a global ecological problem, and their lipopolysaccharides (LPS) are among the bioactive compounds they release. Previous studies on CyanoHAB-LPS from single cyanobacterial species have shown varying bioactivities in different in vitro cell models. In this study, we isolated LPS from 19 CyanoHAB samples collected at 18 water bodies in the Czech Republic over two consecutive seasons. The proportions of cyanobacteria, Gram-negative bacteria (G-), and other bacteria in the biomass were determined by qPCR, while the cyanobacterial genera were identified using light microscopy. In vitro models of keratinocytes (HaCaT), the intestinal epithelium (co-culture of differentiated Caco-2 cells and peripheral blood mononuclear cells — PBMC), and PBMC alone were treated with isolated LPS at concentrations of 50, 100, and 1 µg/ml, respectively. The endotoxin activities of these concentrations were within the range measured in the aquatic environment. Approximately 85–90% of the samples displayed biological activity. However, the potency of individual LPS effects and response patterns varied across the different in vitro models. Furthermore, the observed activities did not exhibit a clear correlation with the taxonomic composition of the phytoplankton community, the relative share of microbial groups in the biomass, endotoxin activity of the LPS, or LPS migration and staining pattern in SDS-PAGE. These findings suggest that the effects of CyanoHAB-LPS depend on the specific composition and abundance of various LPS structures within the complex environmental sample and their interactions with cellular receptors.

(HIIT-The Track) High-Intensity Interval Training for People with Parkinson's Disease: Individual Response Patterns of (Non-)Motor Symptoms and Blood-Based Biomarkers-A Crossover Single-Case Experimental Design.

Physical exercise is receiving increasing interest as an augmentative non-pharmacological intervention in Parkinson's disease (PD). This pilot study primarily aimed to quantify individual response patterns of motor symptoms to alternating exercise modalities, along with non-motor functioning and blood biomarkers of neuroplasticity and neurodegeneration. People with PD performed high-intensity interval training (HIIT) and continuous aerobic exercise (CAE) using a crossover single-case experimental design. A repeated assessment of outcome measures was conducted. The trajectories of outcome measures were visualized in time series plots and interpreted relative to the minimal clinically important difference (MCID) and smallest detectable change (SDC) or as a change in the positive or negative direction using trend lines. Data of three participants were analyzed and engaging in physical exercise seemed beneficial for reducing motor symptoms. Participant 1 demonstrated improvement in motor function, independent of exercise modality; while for participant 2, such a clinically relevant (positive) change in motor function was only observed in response to CAE. Participant 3 showed improved motor function after HIIT, but no comparison could be made with CAE because of drop-out. Heterogeneous responses on secondary outcome measures were found, not only between exercise modalities but also among participants. Though this study underpins the positive impact of physical exercise in the management of PD, large variability in individual response patterns to the interventions among participants makes it difficult to identify clear exercise-induced adaptations in functioning and blood biomarkers. Further research is needed to overcome methodological challenges in measuring individual response patterns.

Interindividual variability and individual stability of pain- and touch-related neuronal gamma oscillations.

Brief painful laser and innocuous tactile stimuli have been associated with an increase of neuronal oscillations in the gamma range. Although it is indicated that event-related gamma oscillations may be highly variable across individuals, to date no study has systematically investigated interindividual variability and individual stability of induced gamma synchronization. Here, we addressed this question using two EEG datasets. The first dataset contains two repeated sessions of tactile and painful stimulation from 22 participants. The second dataset contains a single session of painful stimulation from 48 participants. In the first dataset, we observed gamma responses in the majority of the included participants. We found a broad interindividual variety of gamma magnitudes, time-frequency (TF) response patterns, and scalp topographies. Some participants showed a gamma response with individually unique time-frequency patterns, others did not exhibit any gamma response. This was reproducible and therefore stable; subjects with a large gamma magnitude in the first session showed a large gamma magnitude and a similar response pattern in the follow-up session. The second dataset confirmed the large between-subject variability, but only a fraction of the included participants exhibited laser-induced gamma synchronization. Our results indicate that current EEG measures do not reflect the complex reality of the diverse individual response patterns to brief pain and touch experiences. The present findings question whether a similar phenomenon would be observed in other neuroscience domains. Group results may be replicable, but could be driven by a subgroup of the sample.NEW & NOTEWORTHY The interpretation of gamma activity in response to noxious and innocuous somatosensory stimuli has sparked controversy. Here, we show that participants' gamma oscillations measured through electroencephalography vary. Although some participants do not show a distinct gamma response, others exhibit stable and reliable response patterns in terms of time, frequency, and magnitude.

New insights into the treatment of meningoencephalomyelitis of unknown origin since 2009: A review of 671 cases.

"Meningoencephalomyelitis of unknown origin" (MUO)-a collective term for a group of clinically-indistinguishable (but pathologically distinct) autoimmune diseases of the CNS-has become increasingly commonly recognized throughout the world. In the 1960s-1980s the focus was primarily on the pathological description of these conditions and, largely anecdotally, their response to glucocorticoids. The subsequent availability of magnetic resonance imaging for companion animals led to a focus on imaging characteristics and response of MUO to various immunosuppressive medications. Previous reviews have not found clear evidence of superiority of any specific treatment regimen. Here, we review outcomes in a further 671 dogs treated with various combinations of glucocorticoids and immunosuppressive drugs and reported since 2009, aiming to determine whether recommendations can be drawn from the material published during more recent decades. We observe that: (i) there is more complete information on outcome of MUO-affected dogs solely receiving glucocorticoids and these reports provide evidence to undermine the dogma that MUO inevitably requires treatment with glucocorticoids plus an immunosuppressive drug; (ii) there is far more information on the pharmacokinetics of cytarabine delivered by a variety of routes, revealing that previous dosing and duration of administration in dogs with MUO may not have been optimal; and, (iii) there is a large number of cases that could be available for entry into multi-institutional randomized controlled trials. Finally, we suggest new research avenues that might aid future clinical trials in MUO through improved understanding of etiological triggers and individual patterns of immune response, such as the impact of the gut microbiome, the potential of CSF flow cytometry, and the establishment of robust clinical scores for evaluation of treatment success.

Twenty-Seven Year Response of South Carolina Coastal Plain Forests Affected by Hurricane Hugo.

In 1989, Hurricane Hugo inflicted catastrophic damage on approximately 1.8 million ha of forested land in South Carolina. The purpose of this study was to monitor species compositional shifts and structural changes in several forest types following the hurricane's disturbance. The immediate consequences of hurricane damage are well documented, but there are few studies based on the long-term compositional and structural changes that may result from hurricane disturbance, especially in temperate forest ecosystems. Forty-two forested plots were monitored within four study areas that received varying degrees of hurricane damage. Inventories included species, damage class, tree diameter, and regeneration. The objectives of this study were (1) to compare the recovery speed of wetland forests (e.g., bottomland hardwood swamps and cypress-tupelo swamps) to that of upland pine and hardwood forests; (2) to discover how the degree of hurricane damage can affect the timing and the pattern of forest recovery in the coastal plain; and (3) to compare individual species response patterns across different forest types and at different levels of initial damage. Over the 27-year period following the hurricane, successional pathways have been variable among plots of different forest types and intensity of initial disturbance. We have observed an expected increase in basal area (BA) following the disturbance. Sapling populations in many species have increased dramatically, and some of these populations have begun to thin in recent years. In several forest types, loblolly pine (Pinus taeda L.-not a predominant species in these sites prior to the hurricane) responded quickly and overtook some dominant species in BA and tree/sapling abundance. Several other species that were not a major component of the tree strata (wax myrtle [Morella cerifera (L.) Small], green ash [Fraxinus pennsylvanica Marsh.], and the invasive Chinese tallow [Triadica sebifera (L.) Small]) showed a large increase in sapling population. Overall, recovery speed and species resilience were specific to forest types and damage severity. The intensity and frequency of hurricanes may increase in the future as sea surface temperatures rise. Understanding how coastal forests respond to major hurricanes in the short-term and the long-term will aid us in preparing for future hurricanes and for potential changes in disturbance regimes.

The effectiveness of a cognitive-plus-motivational reading intervention: A multiple-baseline study with four pupils at-risk for reading difficulties

AimsWe aimed to examine the impact of supplementing cognitive reading intervention with supports for reading motivation on the reading motivation (reading interest and self-efficacy) and reading fluency of four Year four pupils at-risk for reading difficulties.Method/rationaleCase studies of four pupils at-risk for reading difficulties were conducted using a multiple-baseline across-participants design. The effects of a combined Cognitive-plus-Motivational intervention (experimental phase) were compared to those of a Cognitive-Only intervention (baseline phase) using probes for reading fluency, interest, and self-efficacy. Scores on each probe were plotted and analysed by combining visual analysis and the Process Control Chart method of analysis.FindingsResults suggest that compared to a Cognitive-Only intervention, the Cognitive-plus-Motivational intervention improved the fluency of three participants, and the interest and self-efficacy of two out of four participants. Findings provided insight into individual patterns of response to the intervention, with the greatest impact on fluency observed for students with the lowest initial reading skills.LimitationsCaution is needed in generalising findings due to the study’s small sample size, the lack of a control group and the potential presence of experimenter bias.ConclusionsThe findings presented here provide preliminary support for the benefits of supplementing reading intervention with instruction to foster reading motivation on the outcomes of pupils at-risk for reading difficulties and provide insight into patterns of individual response to motivational intervention.

Differential responses of canonical nitrifiers and comammox Nitrospira to long-term fertilization in an Alfisol of Northeast China.

The newly identified complete ammonia oxidizer (comammox) that converts ammonia directly into nitrate has redefined the long-held paradigm of two-step nitrification mediated by two distinct groups of nitrifiers. However, exploration of the niche differentiation of canonical nitrifiers and comammox Nitrospira and their ecological importance in agroecosystems is still limited. Here, we adopted quantitative PCR (qPCR) and Illumina MiSeq sequencing to investigate the effects of five long-term fertilization regimes in the variations of ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA), nitrite-oxidizing bacteria (NOB), and comammox Nitrospira abundances and comammox community composition in two soil layers (0-20 cm, topsoil; 20-40 cm, subsoil) in an Alfisol in Northeast China. The fertilization treatments included no fertilizer (CK); chemical nitrogen (N) fertilizer; chemical N; phosphorus (P) and potassium (K) fertilizers (NPK); recycled organic manure (M) and chemical N, P, K plus recycled manure (MNPK). Compared with CK, manure and/or chemical fertilizer significantly increased the AOB amoA gene abundance. Long-term recycled manure increased soil organic matter (SOM) contents and maintained the soil pH, but decreased the NH4 +-N concentrations, which markedly promoted the nxrA and nxrB gene abundances of NOB and the amoA gene abundances of comammox Nitrospira clade A and AOA. Although the comammox Nitrospira clade B abundance tended to decrease after fertilization, the structural equation modeling analysis showed that comammox clade B had direct positive impacts on soil potential ammonia oxidation (PAO; λ = 0.59, p < 0.001). The long-term fertilization regime altered the community composition of comammox Nitrospira. Additionally, comammox Nitrospira clades A and B had individual response patterns to the soil layer. The relative abundance of clade A was predominant in the topsoil in the N (86.5%) and MNPK (76.4%) treatments, while clade B appeared to be dominant in the subsoil (from 78.7 to 88.1%) with lower ammonium contents, implying niche separation between these clades. Soil pH, NH4 +-N and SOM content were crucial factors shaping the soil nitrifying microbial abundances and the comammox Nitrospira community. Together, these findings expand the current understanding of the niche specialization and the important role of comammox Nitrospira in terrestrial ecosystems.

Patients Experience Significant and Meaningful Changes in Self-Report of Function During the First 2 Weeks After an Ankle Sprain Injury: A Report From the Athletic Training Practice-Based Research Network.

Ankle sprains are common during sport participation and associated with long-term deficits in self-report of function. However, little is known of short-term changes in self-report of function following injury. The authors aimed to assess statistical and clinically meaningful changes in self-report of function, as measured by the Foot and Ankle Ability Measure (FAAM), during the first 2weeks after an ankle sprain injury. A retrospective analysis of electronic medical records. Eighty-eight patients, who were diagnosed with an ankle sprain injury by an athletic trainer, received usual care from an athletic trainer, and completed the FAAM during treatment at weeks 1 and 2 postinjury. The authors calculated the percentage of patients who reported clinically meaningful changes and used Wilcoxon signed-rank tests to compare differences in FAAM scores between time points. Between weeks 1 and 2, significant differences were noted for the FAAM Activities of Daily Living (FAAM-ADL) (P < .001) and FAAM Sport (FAAM-Sport) (P < .001). At the patient level, 86.5% (64/74) and 85.2% (69/81) of patients reported changes that exceeded the minimal clinically important difference value for the FAAM-ADL and FAAM-Sport, respectively, between weeks 1 and 2. At week 2, 31.8% (28/88) and 47.7% (42/88) of patients reported a score below 90% on the FAAM-ADL and below 80% on the FAAM-Sport subscale, respectively. Also, 36.4% (32/88) and 25.0% (22/88) of patients reported a score of 100% on the FAAM-ADL and FAAM-Sport subscales, respectively, at week 2. Patients report statistically significant and meaningful improvements in self-report of function during the first 2weeks following ankle sprain injury. However, almost half of patients still report deficits in sport function at 2weeks postinjury. Patient-reported outcome measures such as the FAAM, can help capture the patient's perception of function and inform patient care decisions. Research efforts should explore individual response patterns to treatment.

Effect of PD-1 inhibition on macrophage population in human tissue cultures.

463 Background: Moderate response rates of PD-1 inhibition in gastric and esophagogastric junction cancers (GC/EGJC) urge for reliable biomarkers. To further improve treatment outcomes, patients need targeted therapy based on clinically relevant biomarkers and predictive test systems for assessing individual drug susceptibility. We have previously established patient derived tissue cultures (PDTC) as a comprehensive ex-vivo drug testing system for GC/EGJC patients. Methods: The standardized PDTC) model was developed using tissue from surgical resection specimens to investigate response to the PD-1 inhibitor Nivolumab and the macrophage depriving bisphosphonates clodronate and zoledronic acid. Resident macrophage population (CD68, CD163), tumor proliferation (Ki67) and apoptosis (cPARP), as well as bulk gene expression data (nanoString technology) were analysed after 72 hours of PD-1 inhibition. Additionally, supernatants were collected, and cytokine concentrations are measured based on Luminex technology. Results: Macrophage depletion could lead to enhanced anti-tumoral effects in PDTCs after PD-1 inhibition. Gene signatures for Interferon γ-mediated inflammation and myeloid cell activity were identified and found to be relevant indicators for tissue response upon immune checkpoint inhibition. We observed alterations in cytokine and soluble surface marker concentrations, such as IL-8, IL-17A and IL-23 or PD-L2, LAG3 and CTLA4. Conclusions: Yielding an organotypic cell composition, we were able to demonstrate individual response patterns and immunological characteristics to identify responsiveness to PD-1 inhibition in GC and EGJC tissue. PDTCs are potent to define biological marker sets ex vivo and to differentiate and predict clinical patient response as well as their inherent immune cell capacity and plasticity.

“Life-changing”: the experience of super-responders to biologics in severe asthma

BackgroundThere is limited information on the patient’s perspective of how biologic treatments impact their lives. We conducted a qualitative study to explore the patient’s experience of being considered a super-responder from a quality of life perspective.MethodsPatients with severe asthma identified as super-responders were invited to semi-structured interviews conducted online. Participants could bring a family member/friend to the interview. The interviews explored experiences of biologic treatment, were transcribed and underwent thematic analysis.ResultsTwenty-five participants took part in this study. Themes emerged on the impact of biologic treatment for participants and for their friends/family: (i) Words used to describe their often life-changing experiences and (ii) the positive changes noted. Biologic treatment stopped the disruption of family life and social life caused by exacerbations. Improvements in mental health were also noted. Marked individual variations in the way it affected their lives were noted. Most participants noticed improvements 2–3 months after starting their biologic, but some noticed improvement within a few days and others after 6 months.ConclusionsSuper-responders reported profound but heterogeneous improvements following biologic treatment beyond asthma symptoms and exacerbations including important benefits to social and family life. Improvements may be underestimated as social and family benefits are not reliably measured in current studies with implications for health economic evaluations. Not all patients are super-responders, and excellent responses may be lost in group mean data in trials. Individual time course and response patterns need further elucidation to identify who will respond best to biologics.

On the evolution of concepts of causal and preventive interdependence in epidemiology in the late 20th century.

The 1970s and 1980s saw the appearance of many papers on the topics of synergy, antagonism, and similar concepts of causal interactions and interdependence of effects, with a special emphasis on distinguishing these concepts from that of statistical interaction - the need for a product term in a model. As an example, Miettinen defined "synergism" as "the existence of instances in which both risk factors are needed for the effect", whereas "antagonism" is where "at least one [factor] can block the solo effect of the other". In response, Greenland and Poole constructed a systematic analysis of 16 possible individual response patterns in a deterministic causal model for two binary exposure variables, and showed how these patterns can be mapped onto nine types of sufficient causes, which in turn can be simplified into four intuitive categories. Although these and other papers recognized that epidemiology cannot directly study biological mechanisms underlying interaction, they showed how it can usefully study causal and preventive interdependence - which, despite its mechanistic agnosticism, has important implications for clinical decision making as well as for public health.

An ecological approach for investigations of the anticipatory cortisol stress response

Real-world anticipatory stressors account for rising rates of chronic psychophysiological stress and adverse health outcomes, yet the literature lacks an effective approach to study the anticipatory cortisol stress response. An extended pre-stressor period to capture peak anticipatory cortisol is not conducive to laboratory stress manipulations but is inherent to naturalistic stressors. Naturalistic approaches have been frequently utilized, but few studies included valid baseline and temporally proximate pre-post cortisol measures to operationalize the anticipatory cortisol stress response, and none have differentiated anticipatory from reactive response types. To address these gaps, this study sought to establish an effective and easy-to-implement protocol to investigate the anticipatory cortisol stress response. Saliva was sampled from 78 healthy college students (69 % female) before and after a 50-minute class period on a day of a lecture (baseline) and day of a scheduled written exam (stressor). The overall sample displayed an anticipatory stress response, operationalized as peak pre-exam cortisol and post-exam levels that returned to baseline, while individual response patterns were also detected and subsequently differentiated into anticipatory (37 %), reactive (9 %), anticipatory-reactive (13 %), and non- (41 %) response groups. These responses are consistent with those previously differentiated in a controlled laboratory setting with an exhaustive sampling schedule; yet this study captured a larger number of pre-stressor (anticipatory) cortisol peaks. Subjective measures of psychological stress were also examined. Findings demonstrate the effectiveness of a college written exam and validity of a baseline-pre-post sampling design for operationalizing the anticipatory cortisol stress response and differentiating within-sample response variability.

Distinct Kinematic and Neuromuscular Activation Strategies During Quiet Stance and in Response to Postural Perturbations in Healthy Individuals Fitted With and Without a Lower-Limb Exoskeleton.

Many individuals with disabling conditions have difficulty with gait and balance control that may result in a fall. Exoskeletons are becoming an increasingly popular technology to aid in walking. Despite being a significant aid in increasing mobility, little attention has been paid to exoskeleton features to mitigate falls. To develop improved exoskeleton stability, quantitative information regarding how a user reacts to postural challenges while wearing the exoskeleton is needed. Assessing the unique responses of individuals to postural perturbations while wearing an exoskeleton provides critical information necessary to effectively accommodate a variety of individual response patterns. This report provides kinematic and neuromuscular data obtained from seven healthy, college-aged individuals during posterior support surface translations with and without wearing a lower limb exoskeleton. A 2-min, static baseline standing trial was also obtained. Outcome measures included a variety of 0 dimensional (OD) measures such as center of pressure (COP) RMS, peak amplitude, velocities, pathlength, and electromyographic (EMG) RMS, and peak amplitudes. These measures were obtained during epochs associated with the response to the perturbations: baseline, response, and recovery. T-tests were used to explore potential statistical differences between the exoskeleton and no exoskeleton conditions. Time series waveforms (1D) of the COP and EMG data were also analyzed. Statistical parametric mapping (SPM) was used to evaluate the 1D COP and EMG waveforms obtained during the epochs with and without wearing the exoskeleton. The results indicated that during quiet stance, COP velocity was increased while wearing the exoskeleton, but the magnitude of sway was unchanged. The OD COP measures revealed that wearing the exoskeleton significantly reduced the sway magnitude and velocity in response to the perturbations. There were no systematic effects of wearing the exoskeleton on EMG. SPM analysis revealed that there was a range of individual responses; both behaviorally (COP) and among neuromuscular activation patterns (EMG). Using both the OD and 1D measures provided a more comprehensive representation of how wearing the exoskeleton impacts the responses to posterior perturbations. This study supports a growing body of evidence that exoskeletons must be personalized to meet the specific capabilities and needs of each individual end-user.

Dwarfs on the Shoulders of Giants: Bayesian Analysis With Informative Priors in Elite Sports Research and Decision Making.

While sample sizes in elite sports are necessarily small, so are the effects that may be relevant. This conundrum is complicated by an understandable reluctance of athletes to comply with extensive study requirements. In Bayesian analyses, pre-existing knowledge (e.g., from sub-elite trials) can be formally included to supplement scarce data. Moreover, some design specifics for small sample research extend to the extreme case of a single subject. This provides the basis for actionable feedback (e.g., about individual responses) thereby incentivising participation. As a proof-of-concept, we conducted a replicated cross-over trial on the effect of cold-water immersion (CWI) on sprint performance recovery in soccer players. Times for 30 m linear sprint and the initial 5 m section, respectively, were measured by light gates before and 24 h after induction of fatigue. Data were analysed by Bayesian and by standard frequentist methods. Informative priors are based on a published metaanalysis. Seven players completed the trial. Sprint performance was 4.156 ± 0.193 s for 30 m linear sprint and 0.978 ± 0.064 s for the initial 5 m section. CWI improved recovery of sprint time for the initial 5 m section (difference to control: −0.060 ± 0.060 s, p = 0.004) but not for the full 30 m sprint (0.002 ± 0.115 s, p = 0.959), with general agreement between Bayesian and frequentist interval estimates. On the individual level, relevant differences between analytical approaches were present for most players. Changes in the two performance measures are correlated (p = 0.009) with a fairly good reproducibility of individual response patterns. Bayesian analyses with informative priors may be a practicable and meaningful option particularly for very small samples and when the analytical aim is decision making (use / don't use in the specific setting) rather than generalizable inference.

Autonomic Nervous System Response Patterns of Test-Anxious Individuals to Evaluative Stress.

Test anxiety is a widespread and primarily detrimental emotion in learning and achievement settings. This research aimed to explore the autonomic nervous system (ANS) response patterns of test-anxious individuals in response to evaluative stress. By presenting a standard interview task, an evaluative scenario was effectively induced. Heart rate variability (HRV), a biomarker that can accurately reflect the ANS activity, was used to reflect the physiological responses of 48 high test-anxious subjects and 49 low test-anxious subjects. Results indicate that: (1) both groups show a significantly increased emotional arousal in the evaluative scenario; (2) high test-anxious individuals show a significantly decreased emotional pleasantness in the evaluative scenario, whereas low test-anxious individuals show no significant changes; (3) both groups show a significantly increased low-frequency HRV; (4) high test-anxious individuals show a significantly decreased high-frequency HRV and root mean square of successive heartbeat interval differences (RMSSD), whereas low test-anxious individuals remain stable. These findings suggest that high test-anxious individuals display an increased sympathetic nervous system (SNS) activity and a decreased parasympathetic nervous system (PNS) activity in response to evaluative stress, while low-anxious individuals display an increased SNS activity and a stable PNS activity in response to evaluative stress.