Notch signaling enhances bone regeneration in the zebrafish mandible.

Loss or damage to the mandible caused by trauma, treatment of oral malignancies, and other diseases is treated using bone-grafting techniques that suffer from numerous shortcomings and contraindications. Zebrafish naturally heal large injuries to mandibular bone, offering an opportunity to understand how to boost intrinsic healing potential. Using a novel her6:mCherry Notch reporter, we show that canonical Notch signaling is induced during the initial stages of cartilage callus formation in both mesenchymal cells and chondrocytes following surgical mandibulectomy. We also show that modulation of Notch signaling during the initial post-operative period results in lasting changes to regenerate bone quantity one month later. Pharmacological inhibition of Notch signaling reduces the size of the cartilage callus and delays its conversion into bone, resulting in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates conversion of the cartilage callus into bone, improving bone healing. Given the conserved functions of this pathway in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing in mammals may both augment the size of the initial callus and boost its ossification into reparative bone.

Power of Sequential Protocols in Hidden Quantum Channel Discrimination.

In many natural and engineered systems, unknown quantum channels act on a subsystem that cannot be directly controlled and measured, but is instead learned through a controllable subsystem that weakly interacts with it. We study quantum channel discrimination (QCD) under these restrictions, which we call hidden system QCD. We find sequential protocols achieve perfect discrimination and saturate the Heisenberg limit. In contrast, depth-1 parallel and multishot protocols cannot solve hidden system QCD. This suggests sequential protocols are superior in experimentally realistic situations.

An introduction to machine learning and generative artificial intelligence for otolaryngologists-head and neck surgeons: a narrative review.

PURPOSE: Despite the robust expansion of research surrounding artificial intelligence (AI) and machine learning (ML) and their applications to medicine, these methodologies often remain opaque and inaccessible to many otolaryngologists. Especially, with the increasing ubiquity of large-language models (LLMs), such as ChatGPT and their potential implementation in clinical practice, clinicians may benefit from a baseline understanding of some aspects of AI. In this narrative review, we seek to clarify underlying concepts, illustrate applications to otolaryngology, and highlight future directions and limitations of these tools. METHODS: Recent literature regarding AI principles and otolaryngologic applications of ML and LLMs was reviewed via search in PubMed and Google Scholar. RESULTS: Significant recent strides have been made in otolaryngology research utilizing AI and ML, across all subspecialties, including neurotology, head and neck oncology, laryngology, rhinology, and sleep surgery. Potential applications suggested by recent publications include screening and diagnosis, predictive tools, clinical decision support, and clinical workflow improvement via LLMs. Ongoing concerns regarding AI in medicine include ethical concerns around bias and data sharing, as well as the "black box" problem and limitations in explainability. CONCLUSIONS: Potential implementations of AI in otolaryngology are rapidly expanding. While implementation in clinical practice remains theoretical for most of these tools, their potential power to influence the practice of otolaryngology is substantial.

Accuracy and effort costs together lead to temporal asynchrony of multiple motor commands.

The timing of motor commands is critical for task performance. A well-known example is rapidly raising the arm while standing upright. Here, reaction forces from the arm movement to the body are countered by leg and trunk muscle activity starting before any sensory feedback from the perturbation and often before the onset of arm muscle activity. Despite decades of research on the patterns, modifiability, and neural basis of these "anticipatory postural adjustments," it remains unclear why asynchronous motor commands occur. Simple accuracy considerations appear unlikely since temporally advanced motor commands displace the body from its initial position. Effort is a credible and overlooked factor that has successfully explained coordination patterns of many behaviors including gait and reaching. We provide the first use of optimal control to address this question. Feedforward commands were applied to a body mass mechanically linked to a rapidly moving limb mass. We determined the feedforward actions with the lowest cost according to an explicit criterion, accuracy alone versus accuracy + effort. Accuracy costs alone led to synchronous activation of the body and limb controllers. Adding effort to the cost resulted in body commands preceding limb commands. This sequence takes advantage of the body's momentum in one direction to counter the limb's reaction force in the opposite direction, allowing a lower peak command and lower integral. With a combined accuracy + effort cost, temporal advancement was further impacted by various task goals and plant dynamics, replicating previous findings and suggesting further studies using optimal control principles.NEW & NOTEWORTHY An important goal in the fields of sensorimotor neuroscience and biomechanics is to explain the timing of different muscles during behavior. Here, we propose that energy and accuracy considerations underlie the asynchronous onset of postural and arm muscles during rapid movement. Our novel model-based framework replicates a broad range of observations across varying task demands and plant dynamics and offers a new perspective to study motor timing.

Experimental Quantum Channel Discrimination Using Metastable States of a Trapped Ion.

We present experimental demonstrations of accurate and unambiguous single-shot discrimination between three quantum channels using a single trapped ^{40}Ca^{+} ion. The three channels cannot be distinguished unambiguously using repeated single channel queries, the natural classical analogue. We develop techniques for using the six-dimensional D_{5/2} state space for quantum information processing, and we implement protocols to discriminate quantum channel analogues of phase shift keying and amplitude shift keying data encodings used in classical radio communication. The demonstrations achieve discrimination accuracy exceeding 99% in each case, limited entirely by known experimental imperfections.

Evaluating a treatment selection approach for online single-session interventions for adolescent depression.

BACKGROUND: The question 'what works for whom' is essential to mental health research, as matching individuals to the treatment best suited to their needs has the potential to maximize the effectiveness of existing approaches. Digitally administered single-session interventions (SSIs) are effective means of reducing depressive symptoms in adolescence, with potential for rapid, large-scale implementation. However, little is known about which SSIs work best for different adolescents. OBJECTIVE: We created and tested a treatment selection algorithm for use with two SSIs targeting depression in high-symptom adolescents from across the United States. METHODS: Using data from a large-scale RCT comparing two evidence-based SSIs (N = 996; ClinicalTrials.gov: NCT04634903), we utilized a Personalized Advantage Index approach to create and evaluate a treatment-matching algorithm for these interventions. The two interventions were Project Personality (PP; N = 482), an intervention teaching that traits and symptoms are malleable (a 'growth mindset'), and the Action Brings Change Project (ABC; N = 514), a behavioral activation intervention. RESULTS: Results indicated no significant difference in 3-month depression outcomes between participants assigned to their matched intervention and those assigned to their nonmatched intervention. The relationship between predicted response to intervention (RTI) and observed RTI was weak for both interventions (r = .39 for PP, r = .24 for ABC). Moreover, the correlation between a participants' predicted RTI for PP and their predicted RTI for ABC was very high (r = .79). CONCLUSIONS: The utility of treatment selection approaches for SSIs targeting adolescent depression appears limited. Results suggest that both (a) predicting RTI for SSIs is relatively challenging, and (b) the factors that predict RTI for SSIs are similar regardless of the content of the intervention. Given their overall effectiveness and their low-intensity, low-cost nature, increasing youths' access to both digital SSIs may carry more public health utility than additional treatment-matching efforts.

Ursolic acid-rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease.

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 µg/mL; LC50 26.73 ± 1.2 µg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity.

Modification of N-hydroxycytidine yields a novel lead compound exhibiting activity against the Venezuelan equine encephalitis virus.

Nucleoside and nucleobase analogs capable of interfering with nucleic acid synthesis have played essential roles in fighting infectious diseases. However, many of these agents are associated with important and potentially lethal off-target intracellular effects that limit their use. Based on the previous discovery of base-modified 2'-deoxyuridines, which showed high anticancer activity while exhibiting lower toxicity toward rapidly dividing normal human cells compared to antimetabolite chemotherapeutics, we hypothesized that a similar modification of the N4-hydroxycytidine (NHC) molecule would provide novel antiviral compounds with diminished side effects. This presumption is due to the substantial structural difference with natural cytidine leading to less recognizability by host cell enzymes. Among the 42 antimetabolite species that have been synthesized and screened against VEEV, one hit compound was identified. The structural features of the modifying moiety were similar to those of the anticancer lead 2'-deoxyuridine derivative reported previously, providing an opportunity to pursue further structure-activity relationship (SAR) studies directed to lead improvement, and obtain insight into the mechanism of action, which can lead to identifying drug candidates against a broad spectrum of RNA viral infections.

Efficient fully-coherent quantum signal processing algorithms for real-time dynamics simulation.

Simulating the unitary dynamics of a quantum system is a fundamental problem of quantum mechanics, in which quantum computers are believed to have significant advantage over their classical counterparts. One prominent such instance is the simulation of electronic dynamics, which plays an essential role in chemical reactions, non-equilibrium dynamics, and material design. These systems are time-dependent, which requires that the corresponding simulation algorithm can be successfully concatenated with itself over different time intervals to reproduce the overall coherent quantum dynamics of the system. In this paper, we quantify such simulation algorithms by the property of being fully-coherent: the algorithm succeeds with arbitrarily high success probability 1 - δ while only requiring a single copy of the initial state. We subsequently develop fully-coherent simulation algorithms based on quantum signal processing (QSP), including a novel algorithm that circumvents the use of amplitude amplification while also achieving a query complexity additive in time t, ln(1/δ), and ln(1/ϵ) for error tolerance ϵ: Θ‖H‖|t|+ln(1/ϵ)+ln(1/δ). Furthermore, we numerically analyze these algorithms by applying them to the simulation of the spin dynamics of the Heisenberg model and the correlated electronic dynamics of an H2 molecule. Since any electronic Hamiltonian can be mapped to a spin Hamiltonian, our algorithm can efficiently simulate time-dependent ab initio electronic dynamics in the circuit model of quantum computation. Accordingly, it is also our hope that the present work serves as a bridge between QSP-based quantum algorithms and chemical dynamics, stimulating a cross-fertilization between these exciting fields.

The Prone Lateral Approach for Lumbar Fusion-A Review of the Literature and Case Series.

Lateral lumbar interbody fusion is an evolving procedure in spine surgery allowing for the placement of large interbody devices to achieve indirect decompression of segmental stenosis, deformity correction and high fusion rates through a minimally invasive approach. Traditionally, this technique has been performed in the lateral decubitus position. Many surgeons have adopted simultaneous posterior instrumentation in the lateral position to avoid patient repositioning; however, this technique presents several challenges and limitations. Recently, lateral interbody fusion in the prone position has been gaining in popularity due to the surgeon's ability to perform simultaneous posterior instrumentation as well as decompression procedures and corrective osteotomies. Furthermore, the prone position allows improved correction of sagittal plane imbalance due to increased lumbar lordosis when prone on most operative tables used for spinal surgery. In this paper, we describe the evolution of the prone lateral approach for interbody fusion and present our experience with this technique. Case examples are included for illustration.

Current Trends in Recombinant Human Bone Morphogenetic Protein 2 (rhBMP2) Usage for Spinal Fusion Surgery.

(1) Background: Since first approved by the FDA, on-label and off-label usage of recombinant human bone morphogenetic protein 2 (rhBMP2) for spinal fusion surgeries has become widespread. While many studies have investigated the safety and efficacy of its use, as well as its economic impact, few have looked at the current trends in its on- and off-label use. The goal of this study is to evaluate the current trends of on- and off-label rhBMP2 use for spinal fusion surgery. (2) Methods: A deidentified survey was created and electronically distributed to members of two international spine societies. Surgeons were asked to report their demographic information, surgical experience, and current usage of rhBMP2. They were then presented with five spinal fusion procedures and asked to report if they use rhBMP2 for these indications in their current practice. Responses were stratified between rhBMP2 users vs. non-users and on-label vs. off-label use. Data were analyzed using chi-square with Fisher's exact test for categorical data. (3) Results: A total of 146 respondents completed the survey with a response rate of 20.5%. There was no difference in overall rhBMP2 usage based on specialty, experience, or number of cases per year. Fellowship-trained surgeons and those who practice in the United States were more likely to use rhBMP2. Surgeons who were trained in the Southeast and Midwest regions reported the highest usage rates. rhBMP2 use was more common among fellowship-trained and US surgeons for ALIFs; non-US surgeons for multilevel anterior cervical discectomy and fusions; and fellowship-trained and orthopedic spine surgeons for lateral lumbar interbody fusions. Non-US surgeons were more likely to use rhBMP2 for off-label indications compared to surgeons from the US. (4) Conclusions: While various demographics of surgeons report different rates of rhBMP2 use, off-label use remains relatively commonplace amongst practicing spine surgeons.

Inflamed Ulcerative Colitis Regions Associated With MRGPRX2-Mediated Mast Cell Degranulation and Cell Activation Modules, Defining a New Therapeutic Target.

BACKGROUND & AIMS: Recent literature has implicated a key role for mast cells in murine models of colonic inflammation, but their role in human ulcerative colitis (UC) is not well established. A major advance has been the identification of mrgprb2 (human orthologue, MRGPX2) as mediating IgE-independent mast cell activation. We sought to define mechanisms of mast cell activation and MRGPRX2 in human UC. METHODS: Colon tissues were collected from patients with UC for bulk RNA sequencing and lamina propria cells were isolated for MRGPRX2 activation studies and single-cell RNA sequencing. Genetic association of all protein-altering G-protein coupled receptor single-nucleotide polymorphism was performed in an Ashkenazi Jewish UC case-control cohort. Variants of MRGPRX2 were transfected into Chinese hamster ovary (CHO) and human mast cell (HMC) 1.1 cells to detect genotype-dependent effects on ß-arrestin recruitment, IP-1 accumulation, and phosphorylated extracellular signal-regulated kinase. RESULTS: Mast cell-specific mediators and adrenomedullin (proteolytic precursor of PAMP-12, an MRGPRX2 agonist) are up-regulated in inflamed compared to uninflamed UC. MRGPRX2 stimulation induces carboxypeptidase secretion from inflamed UC. Of all protein-altering GPCR alleles, a unique variant of MRGPRX2, Asn62Ser, was most associated with and was bioinformatically predicted to alter arrestin recruitment. We validated that the UC protective serine allele enhances ß-arrestin recruitment, decreases IP-1, and increases phosphorylated extracellular signal-regulated kinase with MRGPRX2 agonists. Single-cell RNA sequencing defines that adrenomedullin is expressed by activated fibroblasts and epithelial cells and that interferon gamma is a key upstream regulator of mast cell gene expression. CONCLUSION: Inflamed UC regions are distinguished by MRGPRX2-mediated activation of mast cells, with decreased activation observed with a UC-protective genetic variant. These results define cell modules of UC activation and a new therapeutic target.

Multimodal magnetic resonance neuroimaging measures characteristic of early cART-treated pediatric HIV: A feature selection approach.

Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV-related brain alterations can be investigated separately using proton magnetic resonance spectroscopy (1 H-MRS), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI), a set of multimodal MRI measures characteristic of children on cART has not been previously identified. We used the embedded feature selection of a logistic elastic-net (EN) regularization to select neuroimaging measures that distinguish CPHIV from controls and measured their classification performance via the area under the receiver operating characteristic curve (AUC) using repeated cross validation. We also wished to establish whether combining MRI modalities improved the models. In single modality analysis, sMRI volumes performed best followed by DTI, whereas individual EN models on spectroscopic, gyrification, and cortical thickness measures showed no class discrimination capability. Adding DTI and 1 H-MRS in basal measures to sMRI volumes produced the highest classification performance validation accuracy = 85 % AUC = 0.80 . The best multimodal MRI set consisted of 22 DTI and sMRI volume features, which included reduced volumes of the bilateral globus pallidus and amygdala, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the right corticospinal tract in cART-treated CPHIV. Consistent with previous studies of CPHIV, select subcortical volumes obtained from sMRI provide reasonable discrimination between CPHIV and controls. This may give insight into neuroimaging measures that are relevant in understanding the effects of HIV on the brain, thereby providing a starting point for evaluating their link with cognitive performance in CPHIV.

Pareto-Optimal Clustering with the Primal Deterministic Information Bottleneck.

At the heart of both lossy compression and clustering is a trade-off between the fidelity and size of the learned representation. Our goal is to map out and study the Pareto frontier that quantifies this trade-off. We focus on the optimization of the Deterministic Information Bottleneck (DIB) objective over the space of hard clusterings. To this end, we introduce the primal DIB problem, which we show results in a much richer frontier than its previously studied Lagrangian relaxation when optimized over discrete search spaces. We present an algorithm for mapping out the Pareto frontier of the primal DIB trade-off that is also applicable to other two-objective clustering problems. We study general properties of the Pareto frontier, and we give both analytic and numerical evidence for logarithmic sparsity of the frontier in general. We provide evidence that our algorithm has polynomial scaling despite the super-exponential search space, and additionally, we propose a modification to the algorithm that can be used where sampling noise is expected to be significant. Finally, we use our algorithm to map the DIB frontier of three different tasks: compressing the English alphabet, extracting informative color classes from natural images, and compressing a group theory-inspired dataset, revealing interesting features of frontier, and demonstrating how the structure of the frontier can be used for model selection with a focus on points previously hidden by the cloak of the convex hull.

Intensive Care Unit-Like Care of Nonhuman Primates with Ebola Virus Disease.

BACKGROUND: Ebola virus disease (EVD) supportive care strategies are largely guided by retrospective observational research. This study investigated the effect of EVD supportive care algorithms on duration of survival in a controlled nonhuman primate (NHP) model. METHODS: Fourteen rhesus macaques were challenged intramuscularly with a target dose of Ebola virus (1000 plaque-forming units; Kikwit). NHPs were allocated to intensive care unit (ICU)-like algorithms (n = 7), intravenous fluids plus levofloxacin (n = 2), or a control group (n = 5). The primary outcome measure was duration of survival, and secondary outcomes included changes in clinical laboratory values. RESULTS: Duration of survival was not significantly different between the pooled ICU-like algorithm and control groups (8.2 vs 6.9 days of survival; hazard ratio; 0.50; P = .25). Norepinephrine was effective in transiently maintaining baseline blood pressure. NHPs treated with ICU-like algorithms had delayed onset of liver and kidney injury. CONCLUSIONS: While an obvious survival difference was not observed with ICU-like care, clinical observations from this model may aid in EVD supportive care NHP model refinement.

Age-related deficits in rapid visuomotor decision-making.

Many goal-directed actions that require rapid visuomotor planning and perceptual decision-making are affected in older adults, causing difficulties in execution of many functional activities of daily living. Visuomotor planning and perceptual identification are mediated by the dorsal and ventral visual streams, respectively, but it is unclear how age-induced changes in sensory processing in these streams contribute to declines in visuomotor decision-making performance. Previously, we showed that in young adults, task demands influenced movement strategies during visuomotor decision-making, reflecting differential integration of sensory information between the two streams. Here, we asked the question if older adults would exhibit deficits in interactions between the two streams during demanding motor tasks. Older adults (n = 15) and young controls (n = 26) performed reaching or interception movements toward virtual objects. In some blocks of trials, participants also had to select an appropriate movement goal based on the shape of the object. Our results showed that older adults corrected fewer initial decision errors during both reaching and interception movements. During the interception decision task, older adults made more decision- and execution-related errors than young adults, which were related to early initiation of their movements. Together, these results suggest that older adults have a reduced ability to integrate new perceptual information to guide online action, which may reflect impaired ventral-dorsal stream interactions.NEW & NOTEWORTHY Older adults show declines in vision, decision-making, and motor control, which can lead to functional limitations. We used a rapid visuomotor decision task to examine how these deficits may interact to affect task performance. Compared with healthy young adults, older adults made more errors in both decision-making and motor execution, especially when the task required intercepting moving targets. This suggests that age-related declines in integrating perceptual and motor information may contribute to functional deficits.

Comparison of Urologist- vs Gastroenterologist-Directed Extracorporeal Shock Wave Lithotripsy for Pancreaticolithiasis.

BACKGROUND & AIMS: Extracorporeal shock wave lithotripsy (ESWL) for pancreaticolithiasis is most commonly performed by urologists. We investigated the effects of transitioning from urologist- to gastroenterologist-directed ESWL on case complexity, process measures, and duct clearance. METHODS: We performed a retrospective study of patients who underwent ESWL for pancreaticolithiasis from 2014 through 2019 at a single center. We collected demographic, clinical, radiographic, and procedural data in duplicate and compared case complexity and process measures between the periods the procedure was performed by urologists (January 2014 through February 2017; 18 patients, 0.47 patients/month) vs gastroenterologists (March 2017 through December 2019; 61 patients; 1.79 patients/month). We also compared data on pancreatic duct stone characteristics and technical success (duct clearance, determined by imaging analysis). RESULTS: There were no differences in patient demographics, comorbidities, pancreatic stone morphology, or time from referral to ESWL during the period the procedure was performed by urologists vs gastroenterologists. Patients received a higher mean number of ESWL shocks per session during the gastroenterology period (4341) than during the urology period (3117) (P < .001). A higher proportion of patients underwent same-session endoscopic retrograde cholangiopancreatography during the gastroenterology time period (66%) than the urology time period (6%) (P < .001). A higher proportion of patients had partial or complete duct clearance during the gastroenterology period (71%) than during the urology period (44%) (P = .04). During the urology period, a higher proportion of patients were hospitalized following ESWL, although there was no difference in captured adverse events between the periods. CONCLUSIONS: Transition from urologist- to gastroenterologist-directed ESWL did not affect case complexity or wait times for ESWL. However, the transition did result in increased procedure volume, more shocks per ESWL session, and improved duct clearance.

The role of CT and endoscopy in the evaluation of patients referred for intranasal Cryoablation.

BACKGROUND: Cryoablation (CA) of the posterior nasal nerves has garnered increasing interest as an office-based procedure for chronic rhinitis (CR). Standardized preoperative evaluation, specifically the role of computed tomography (CT) and nasal endoscopy, has yet to be defined. We report a series of patients who underwent CT and endoscopy as part of CR work-up in patients referred for CA. OBJECTIVE: Highlight the importance of both nasal endoscopy and CT scan in the evaluation of CR given significant overlap of symptoms and common occurrence of related sinonasal conditions. METHODS: Retrospective analysis of all patients referred to a single tertiary rhinology practice for CA was performed. RESULTS: Fifteen patients were sent for CA by medical allergists. Five patients were deemed CA candidates, and 1 patient received only medical CR treatment. Four patients had evidence of incomplete prior sinus surgery and/or continued chronic rhinosinusitis on endoscopic exam. These 4 patients received a combination of medical and surgical management with either complete resolution or improvement in CR symptoms. In 3 patients, CT confirmed chronic rhinosinusitis that was not apparent on endoscopy, and received a combination of medical and surgical management with symptom improvement. In the last two patients, final diagnoses were nasal valve collapse and recurrent acute rhinosinusitis. CONCLUSIONS: Referrals for CA are becoming more common and the optimal preoperative work up remains unclear. In this limited retrospective review, 67% of patients had diagnoses other than CR and thus were not deemed candidates for CA. Both CT and endoscopy are complementary to a detailed history and physical examination and can aid in CA candidate selection.

Reaching movements are automatically redirected to nearby options during target split.

Motor behavior often occurs in environments with multiple goal options that can vary during the ongoing action. We explored this situation by requiring subjects to select between different target options during an ongoing reach. During split trials the original target was replaced with a left and a right flanking target, and participants had to select between them. This contrasted with the standard jump trials, where the original target would be replaced with a single flanking target, left or right. When participants were instructed to follow their natural tendency, they all tended to select the split target nearest the original. The near-target preference was more prominent with increased spatial disparity between the options and when participants could preview the potential options. Moreover, explicit instruction to obtain the "far" target during split trials resulted many errors compared with a "near" instruction, ~50% vs. ~15%. Online reaction times to target change were delayed in split trials compared with jump trials, ~200 ms vs. ~150 ms, but also highly automatic. Trials in which the instructed far target was correctly obtained were delayed by a further ~50 ms, unlike those in which the near target was incorrectly obtained. We also observed nonspecific responses from arm muscles at the jump trial latency during split trials. Taken together, our results indicate that online selection of reach targets is automatically linked to the spatial distribution of the options, though at greater delays than redirecting to a single target.NEW & NOTEWORTHY This work demonstrates that target selection during an ongoing reach is automatically linked to the option nearest a voided target. Online reaction times for two options are longer than redirection to a single option. Attempts to override the near-target tendency result in a high number of errors at the normal delay and further delays when the attempt is successful.

Investigating child self-report capacity: a systematic review and utility analysis.

PURPOSE: To identify and evaluate methods for assessing pediatric patient-reported outcome (PRO) data quality at the individual level. METHODS: We conducted a systematic literature review to identify methods for detecting invalid responses to PRO measures. Eight data quality indicators were applied to child-report data collected from 1780 children ages 8-11 years. We grouped children with similar data quality patterns and tested for between-group differences in factors hypothesized to influence self-report capacity. RESULTS: We identified 126 articles that described 494 instances in which special measures or statistical techniques were applied to evaluate data quality at the individual level. We identified 22 data quality indicator subtypes: 9 direct methods (require administration of special items) and 13 archival techniques (statistical procedures applied to PRO data post hoc). Application of archival techniques to child-report PRO data revealed 3 distinct patterns (or classes) of the data quality indicators. Compared to class 1 (56%), classes 2 (36%) and 3 (8%) had greater variation in their PRO item responses. Three archival indicators were especially useful for differentiating plausible item response variation (class 2) from statistically unlikely response patterns (class 3). Neurodevelopmental conditions, which are associated with a range of cognitive processing challenges, were more common among children in class 3. CONCLUSION: A multi-indicator approach is needed to identify invalid PRO responses. Once identified, assessment environments and measurement tools should be adapted to best support these individuals' self-report capacity. Individual-level data quality indicators can be used to gauge the effectiveness of these accommodations.