Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic Care on the Neuroendocrine-Immune System.

In this paper we synthesize an expansive body of literature examining the multifaceted influence of chiropractic care on processes within and modulators of the neuroendocrine-immune (NEI) system, for the purpose of generating an inductive hypothesis regarding the potential impacts of chiropractic care on integrated physiology. Taking a broad, interdisciplinary, and integrative view of two decades of research-documented outcomes of chiropractic care, inclusive of reports ranging from systematic and meta-analysis and randomized and observational trials to case and cohort studies, this review encapsulates a rigorous analysis of research and suggests the appropriateness of a more integrative perspective on the impact of chiropractic care on systemic physiology. A novel perspective on the salutogenic, health-promoting effects of chiropractic adjustment is presented, focused on the improvement of physical indicators of well-being and adaptability such as blood pressure, heart rate variability, and sleep, potential benefits that may be facilitated through multiple neurologically mediated pathways. Our findings support the biological plausibility of complex benefits from chiropractic intervention that is not limited to simple neuromusculoskeletal outcomes and open new avenues for future research, specifically the exploration and mapping of the precise neural pathways and networks influenced by chiropractic adjustment.

Towards sensory substitution and augmentation: Mapping visual distance to audio and tactile frequency.

Multimodal perception is the predominant means by which individuals experience and interact with the world. However, sensory dysfunction or loss can significantly impede this process. In such cases, cross-modality research offers valuable insight into how we can compensate for these sensory deficits through sensory substitution. Although sight and hearing are both used to estimate the distance to an object (e.g., by visual size and sound volume) and the perception of distance is an important element in navigation and guidance, it is not widely studied in cross-modal research. We investigate the relationship between audio and vibrotactile frequencies (in the ranges 47-2,764 Hz and 10-99 Hz, respectively) and distances uniformly distributed in the range 1-12 m. In our experiments participants mapped the distance (represented by an image of a model at that distance) to a frequency via adjusting a virtual tuning knob. The results revealed that the majority (more than 76%) of participants demonstrated a strong negative monotonic relationship between frequency and distance, across both vibrotactile (represented by a natural log function) and auditory domains (represented by an exponential function). However, a subgroup of participants showed the opposite positive linear relationship between frequency and distance. The strong cross-modal sensory correlation could contribute to the development of assistive robotic technologies and devices to augment human perception. This work provides the fundamental foundation for future assisted HRI applications where a mapping between distance and frequency is needed, for example for people with vision or hearing loss, drivers with loss of focus or response delay, doctors undertaking teleoperation surgery, and users in augmented reality (AR) or virtual reality (VR) environments.

Errorful learning improves recognition memory for new vocabulary for people living with memory and dysexecutive impairment following brain injury.

A widely accepted view is that errorless learning is essential for supporting new learning in people with anterograde amnesia, but findings are mixed for those with a broader range of memory impairments. People at a chronic stage of recovery from brain injury (BI) with impaired memory and executive function (N = 26) were compared with adults in a comparison group without any known risks to brain function (N = 25). Learning techniques were compared using a "Generate-and-correct" and "Read-only" condition when learning novel word pairs. At test, both groups scored above chance and showed benefits of Generate-and-correct (errorful learning). Poor learners in the BI group were classified from "flat" learning slopes extracted from an independent word-pair learning task. Critically, poor learners showed no benefit, but also no decrement to learning, using the Generate-and-correct method. No group was harmed by errorful learning; all, except the poorest learners, benefitted from errorful learning. This study indicates, that in some rehabilitation settings, encouraging clients to guess the meaning of unfamiliar material (e.g., from cards, magazines, newspapers) and then correct their errors, could have benefits for recognition memory. Determining when and how errorful learning benefits learning is a key aim for future research.

Subsecond lung cancer detection within a heterogeneous background of normal and benign tissue using single-point Raman spectroscopy.

Significance: Lung cancer is the most frequently diagnosed cancer overall and the deadliest cancer in North America. Early diagnosis through current bronchoscopy techniques is limited by poor diagnostic yield and low specificity, especially for lesions located in peripheral pulmonary locations. Even with the emergence of robotic-assisted platforms, bronchoscopy diagnostic yields remain below 80%. Aim: The aim of this study was to determine whether in situ single-point fingerprint (800 to 1700 cm-1) Raman spectroscopy coupled with machine learning could detect lung cancer within an otherwise heterogenous background composed of normal tissue and tissue associated with benign conditions, including emphysema and bronchiolitis. Approach: A Raman spectroscopy probe was used to measure the spectral fingerprint of normal, benign, and cancer lung tissue in 10 patients. Each interrogated specimen was characterized by histology to determine cancer type, i.e., small cell carcinoma or non-small cell carcinoma (adenocarcinoma and squamous cell carcinoma). Biomolecular information was extracted from the fingerprint spectra to identify biomolecular features that can be used for cancer detection. Results: Supervised machine learning models were trained using leave-one-patient-out cross-validation, showing lung cancer could be detected with a sensitivity of 94% and a specificity of 80%. Conclusions: This proof of concept demonstrates fingerprint Raman spectroscopy is a promising tool for the detection of lung cancer during diagnostic procedures and can capture biomolecular changes associated with the presence of cancer among a complex heterogeneous background within less than 1 s.

Graded prioritisation of targets in search: reward diminishes the low prevalence effect.

In many real-life contexts, observers are required to search for targets that are rarely present (e.g. tumours in X-rays; dangerous items in airport security screenings). Despite the rarity of these items, they are of enormous importance for the health and safety of the public, yet they are easily missed during visual search. This is referred to as the prevalence effect. In the current series of experiments, we investigate whether unequal reward can modulate the prevalence effect, in a multiple target search task. Having first established the impact of prevalence (Experiment 1) and reward (Experiment 2) on how efficiently participants can find one of several targets in the current paradigm, we then combined the two forms of priority to investigate their interaction. An unequal reward distribution (where lower prevalence items are more rewarded; Experiment 3) was found to diminish the effect of prevalence, compared to an equal reward distribution (Experiment 4) as indicated by faster response times and fewer misses. These findings suggest that when combined with an unequal reward distribution, the low prevalence effect can be diminished.

Retrieval-induced forgetting of spatial position depends on access to multiple shared features within categories.

Retrieval-induced forgetting (RIF) is typically observed in verbal memory tasks, although a few studies have observed RIF in visual spatial tasks. This leaves an open question as to whether RIF depends on semantic identity to link across semantic properties of objects, or whether RIF depends on access to the perceptual features of objects. To explore RIF of spatial positions, we report three experiments utilizing a continuous measure of the accessibility and precision for objects that were distinguished by their shape, color, and spatial region. After a study phase, half of the objects in a single-color category were selectively practiced for their spatial position, by requiring the object to be placed in the exact spatial position seen previously. Finally, all objects were probed for their spatial position at test. No RIF occurred for objects that shared only one color feature but were located within the same spatial region (in Experiment 1) or when objects shared the same color, but were located within different spatial regions (in Experiment 3). However, RIF did occur when objects shared the same spatial region and the same color (Experiment 2). Overall, the interim recall of the spatial positions of cue-objects impairs access to the position of other cue-objects within the same color category, but only when these groups had sufficient overlapping and competing features. The finding that RIF only occurs to the accessibility of spatial positions, not the precision of visual spatial memory, was interpreted as consistent with inhibitory theories of forgetting.

Progressive retrieval practice leads to greater memory for image-word pairs than standard retrieval practice.

The benefits of retrieval practice on learning are robust and have transferred from laboratory findings to many real-world educational settings. We report two experiments that investigated a novel retrieval practice technique for remembering arbitrary associations (image-word pairs), with and without reward as a motivator. As well as typical retrieval practice and restudy conditions, we added a third condition of graded retrieval practice in which the image cue was partially released in a progressive process. Experiment 1 found significant benefits of retrieval practice over restudy, with an additional benefit of graded retrieval practice compared with standard retrieval practice after a 48-hour delay between study and retrieval. Experiment 2 included a reward manipulation by giving participants money based on their memory performance. The findings replicated the retrieval practice effects observed in Experiment 1, including a robust advantage for graded retrieval practice. Reward neither changed the additive advantage of graded recall nor the benefit of retrieval practice. The present study adds to the literature indicating that retrieval with progressive retrieval cues can boost the benefit of retrieval practice by generating repeated retrieval attempts. This benefit occurs most for items that are neither too easy nor too challenging to retrieve.

Unequal allocation of overt and covert attention in Multiple Object Tracking.

In many real-life contexts, where objects are moving around, we are often required to allocate our attention unequally between targets or regions of different importance. However, typical multiple object tracking (MOT) tasks, primarily investigate equal attention allocation as the likelihood of each target being probed is the same. In two experiments, we investigated whether participants can allocate attention unequally across regions of the visual field, using a MOT task where two regions were probed with either a high and low or with equal priority. Experiment 1 showed that for high-priority regions, accuracy (for direction of heading judgments) improved, and participants had more frequent and longer fixations in that region compared with a low-priority region. Experiment 2 showed that eye movements were functional in that they slightly improved accuracy when participants could freely move their eyes compared with when they had to centrally fixate. Replicating Experiment 1, we found better tracking performance for high compared with low-priority regions, in both the free and fixed viewing conditions, but the benefit was greater for the free viewing condition. Although unequal attention allocation is possible without eye movements, eye movements seem to improve tracking ability, presumably by allowing participants to fixate more in the high-priority region and get a better, foveal view of the objects. These findings can help us better understand how observers in real-life settings (e.g., CCTV monitoring, driving) can use their limited attentional capacity to allocate their attention unequally in a demand-based manner across different tracking regions.

A calming hug: Design and validation of a tactile aid to ease anxiety.

Anxiety disorders affect approximately one third of people during their lifetimes and are the ninth leading cause of global disability. Current treatments focus on therapy and pharmacological interventions. However, therapy is costly and pharmacological interventions often have undesirable side-effects. Healthy people also regularly suffer periods of anxiety. Therefore, a non-pharmacological, intuitive, home intervention would be complementary to other treatments and beneficial for non-clinical groups. Existing at-home anxiety aids, such as guided meditations, typically employ visual and/or audio stimuli to guide the user into a calmer state. However, the tactile sense has the potential to be a more natural modality to target in an anxiety-calming device. The tactile domain is relatively under-explored, but we suggest that there are manifold physiological and affective qualities of touch that lend it to the task. In this study we demonstrate that haptic technology can offer an enjoyable, effective and widely accessible alternative for easing state anxiety. We describe a novel huggable haptic interface that pneumatically simulates slow breathing. We discuss the development of this interface through a focus group evaluating five prototypes with embedded behaviours ('breathing', 'purring', 'heartbeat' and 'illumination'). Ratings indicated that the 'breathing' prototype was most pleasant to interact with and participants described this prototype as 'calming' and 'soothing', reminding them of a person breathing. This prototype was developed into an ergonomic huggable cushion containing a pneumatic chamber powered by an external pump allowing the cushion to 'breathe'. A mixed-design experiment (n = 129) inducing anxiety through a group mathematics test found that the device was effective at reducing pre-test anxiety compared to a control (no intervention) condition and that this reduction in anxiety was indistinguishable from that of a guided meditation. Our findings highlight the efficacy of this interface, demonstrating that haptic technologies can be effective at easing anxiety. We suggest that the field should be explored in more depth to capture the nuances of different modalities in relation to specific situations and trait characteristics.

Self-protecting motivation, indexed by self-threat, modifies retrieval-induced-forgetting and confidence in employment decision bias against out-group targets.

Human memory is malleable by both social and motivational factors and holds information relevant to workplace decisions. Retrieval-induced forgetting (RIF) describes a phenomenon where retrieval practice impairs subsequent memory for related (unpracticed) information. We report two RIF experiments. Chinese participants received a mild self-threat manipulation (Experiment 2) or not (Experiment 1) before an ethnicity-RIF task that involved practicing negative traits of either in-group (Chinese) or an out-group (Japanese) target. After a subsequent memory test, participants selected their preferred applicant for employment. RIF scores correspond to forgetting of unpracticed positive traits of one target (Rp-) relative to the recall of practiced negative traits of the other target (Rp+). Enhanced forgetting of positive traits was found in both experiments for both targets. Across experiments, a significant target by threat interaction showed that target ethnicity modified RIF (an ethnicity-RIF effect). Inducing a self-protecting motivation enhanced RIF effects for the out-group (Japanese) target. In a subsequent employment decision, there was a strong bias to select the in-group target, with the confidence in these decisions being associated with RIF scores. This study suggests that rehearsing negative traits of minority applicants can affect metacognitive aspects of employment decisions, possibly by shaping the schemas available to the majority (in-group) employer. To disrupt systemic racism, recruitment practices should aim to offset a human motivation to protect one-self, when exposed to a relatively mild threat to self-esteem. Discussing the negative traits of minority applicants is a critical, and sensitive, aspect of decision-making that warrants careful practice. These data suggest that recruiting individuals should be reminded of their personal strengths in this context, not their vulnerabilities, to secure their decision-making for fairer recruitment practice.

Motion disrupts dynamic visual search for an orientation change.

Visual search in dynamic environments, for example lifeguarding or CCTV monitoring, has several fundamentally different properties to standard visual search tasks. The visual environment is constantly moving, a range of items could become targets and the task is to search for a certain event. We developed a novel task in which participants were required to search static and moving displays for an orientation change thus capturing components of visual search, multiple object tracking and change detection paradigms. In Experiment 1, we found that the addition of moving distractors slowed participants' response time to detect an orientation changes in a moving target, showing that the motion of distractors disrupts the rapid detection of orientation changes in a moving target. In Experiment 2 we found that, in displays of both moving and static objects, response time was slower if a moving object underwent a change than if a static object did, thus demonstrating that motion of the target itself also disrupts the detection of an orientation change. Our results could have implications for training in real-world occupations where the task is to search a dynamic environment for a critical event. Moreover, we add to the literature highlighting the need to develop lab-based tasks with high experimental control from any real-world tasks researchers may wish to investigate rather than extrapolating from static visual search tasks to more dynamic environments.

Transfer effects in auditory temporal preparation occur using an unfilled but not filled foreperiod.

How quickly participants respond to a "go" after a "warning" signal is partly determined by the time between the two signals (the foreperiod) and the distribution of foreperiods. According to Multiple Trace Theory of Temporal Preparation (MTP), participants use memory traces of previous foreperiods to prepare for the upcoming go signal. If the processes underlying temporal preparation reflect general encoding and memory principles, transfer effects (the carryover effect of a previous block's distribution of foreperiods to the current block) should be observed regardless of the sensory modality in which signals are presented. Despite convincing evidence for transfer effects in the visual domain, only weak evidence for transfer effects has been documented in the auditory domain. Three experiments were conducted to examine whether such differences in results are due to the modality of the stimulus or other procedural factors. In each experiment, two groups of participants were exposed to different foreperiod distributions in the acquisition phase and to the same foreperiod distribution in the transfer phase. Experiment 1 used a choice-reaction time (RT) task, and the warning signal remained on until the go signal, but there was no evidence for transfer effects. Experiments 2 and 3 used a simple- and choice-RT task, respectively, and there was silence between the warning and go signals. Both experiments revealed evidence for transfer effects, which suggests that transfer effects are most evident when there is no auditory stimulation between the warning and go signals.

Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression.

Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least one somatic mutation at a variant allele frequency (VAF) > 20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis could become a useful biomarker for early detection and monitoring of EC recurrence. However, further research is needed to confirm these findings and to explore their potential implications for patient management.

A 'no' with a trace of 'yes': A mouse-tracking study of negative sentence processing.

There is strong evidence that comprehenders can parse sentences in an incremental fashion. However, when the sentence contains a negation, the evidence is less clear. Previous work has shown that increasing the pragmatic felicity of a negative sentence reduces or eliminates any processing overhead relative to affirmative sentences. However, in previous work felicity has gone hand-in-hand with the predictability of critical material in a sentence. In three experiments reported here, we presented equally felicitous sentences with critical material of varying predictability (operationalised as the number of possible completions) to test whether this might be a critical factor determining the ease with which partial sentences containing a negation are interpreted. Participants completed a truth-value judgement task (Experiment 1) or a sentence completion task (Experiments 2 and 3) after viewing a visual environment that provided the context for a test sentence, which could differ in truth value (in Experiment 1 only), polarity (affirmative or negative), and number of possible completions (one, two, or three). In all three experiments, we recorded response times and accuracy, but also response dynamics via participants' computer mouse trajectories, allowing us to test specific hypotheses about the time course of comprehension. Across all experiments, in conditions with one or two possible targets, we observed consistent detrimental effects of negative polarity, suggesting that the difficulty in processing negation cannot be reduced to effects relating to predictability or pragmatic felicity. We discuss this finding in relation to incremental and two-stage models of processing and outline a new account of the processing difficulty arising from negation in terms of a conflict between what is locally activated on the basis of individual words and phrases and the global meaning of a negative sentence.

Visual spatial attention and spatial working memory do not draw on shared capacity-limited core processes.

The extent to which similar capacity limits in visual attention and visual working memory indicate a common shared underlying mechanism is currently still debated. In the spatial domain, the multiple object tracking (MOT) task has been used to assess the relationship between spatial attention and spatial working memory though existing results have been inconclusive. In three dual task experiments, we examined the extent of interference between attention to spatial positions and memory for spatial positions. When the position monitoring task required keeping track of target identities through colour-location binding, we found a moderate detrimental effect of position monitoring on spatial working memory and an ambiguous interaction effect. However, when this task requirement was removed, load increases in neither task were detrimental to the other. The only very moderate interference effect that remained resided in an interaction between load types but was not consistent with shared capacity between tasks-rather it was consistent with content-related crosstalk between spatial representations. Contrary to propositions that spatial attention and spatial working memory may draw on a common shared set of core processes, these findings indicate that for a purely spatial task, perceptual attention and working memory appear to recruit separate core capacity-limited processes.

Delayed-Onset Muscle Soreness and Topical Analgesic Alter Corticospinal Excitability of the Biceps Brachii.

INTRODUCTION: The interactive effect of delayed-onset muscle soreness (DOMS) and a topical analgesic on corticospinal excitability was investigated. METHODS: Thirty-two participants completed Experiments A (no DOMS) and B (DOMS). For each experiment, participants were randomly assigned to two groups: 1) topical analgesic gel (topical analgesic, n = 8), or 2) placebo gel (placebo, n = 8) group. Before the application of gel (pregel), as well as 5, 15, 30, and 45 min postgel, motor-evoked potential (MEP) area, latency, and silent period, as well as cervicomedullary MEP and maximal compound motor unit action potential areas and latencies were measured. In addition, pressure-pain threshold (PPT) was measured pre-DOMS and at the same timepoints in experiment B. RESULTS: In experiment A, neither group showed a significant change for any outcome measure. In experiment B, both groups exhibited a significant decrease in PPT from pre-DOMS to pregel. After the application of topical analgesic, but not placebo, there was a significant increase in PPT at 45 min postgel, respectively, compared with pregel and a main effect of time for the silent period to increase compared with pregel. Participants with DOMS had reduced MEP and cervicomedullary MEP areas and increased corticospinal silent periods compared with those who did not have DOMS. CONCLUSIONS: These findings suggest that DOMS reduced corticospinal excitability and after the administration of menthol-based topical analgesic, there was a reduction in pain, which was accompanied by increased corticospinal inhibition.

Evidence for short-term, but not long-term, transfer effects in the temporal preparation of auditory stimuli.

Starting procedures in racing sports consist of a warning (e.g., "Set") followed by a target (e.g., "Go") signal. During this interval (the foreperiod), athletes engage in temporal preparation whereby they prepare to respond to the target as quickly as possible. Despite a long history, the cognitive mechanisms underlying this process are debated. Recently, it has been suggested that traces of previous temporal durations drive temporal preparation performance rather than the traditional explanation that performance is related to the currently perceived hazard function. Los and colleagues used visual stimuli for the warning and target signals. As racing sports typically rely upon auditory stimuli, we investigated the role of memory on temporal preparation in the auditory domain. Experiment 1 investigated long-term transfer effects. In an acquisition phase, two groups of participants were exposed to different foreperiod distributions. One week later, during a transfer phase, both groups received the same distribution of foreperiods. There was no evidence for transfer effects. Therefore, Experiment 2 examined short-term transfer effects in which acquisition and transfer phases were completed in the same testing session. There was some evidence for transfer effects, but this was limited, suggesting that there may be modality-specific memory differences.