The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

The key to understanding core knowledge resides in the fetus.

What Babies Know outlines a compelling case for why infancy research is fundamental for conceptualizing what it is to be human. There is another period in human development that is relatively inaccessible, yet is more important. In order to truly understand the nature of core knowledge, perception, and cognition, we must start not with the infant, but with the fetus.

Indoor air quality improvement with filtration and UV-C on mitigation of particulate matter and airborne bacteria: Monitoring and modeling.

Indoor air, especially with suspended particulate matter (PM), can be a carrier of airborne infectious pathogens. Without sufficient ventilation, airborne infectious diseases can be transmitted from one person to another. Indoor air quality (IAQ) significantly impacts people's daily lives as people spend 90% of their time indoors. An industrial-grade air cleaner prototype (filtration + ultraviolet light) was previously upgraded to clean indoor air to improve IAQ on two metrics: particulate matter (PM) and viable airborne bacteria. Previous experiments were conducted to test its removal efficiency on PM and airborne bacteria between the inlet and treated air. However, the longer-term improvement on IAQ would be more informative. Therefore, this research focused on quantifying longer-term improvement in a testing environment (poultry facility) loaded with high and variable PM and airborne bacteria concentrations. A 25-day experiment was conducted to treat indoor air using an air cleaner prototype with intermittent ON and OFF days in which PM and viable airborne bacteria were measured to quantify the treatment effect. The results showed an average of 55% reduction of total suspended particulate (TSP) concentration between OFF days (110 µg/m3) and ON days (49 µg/m3). An average of 47% reduction of total airborne viable bacteria concentrations was achieved between OFF days (∼3200 CFU/m3) and ON days (∼2000 CFU/m3). A cross-validation (CV) model was established to predict PM concentrations with five input variables, including the status of the air cleaner, time (h), ambient temperature, indoor relative humidity, and day of the week to help simulate the air-cleaning effect of this prototype. The model can approximately predict the air quality trend, and future improvements may be made to improve its accuracy.

Resting EEG correlates of neurodevelopment in a socioeconomically and linguistically diverse sample of toddlers: Wave 1 of the Kia Timata Pai best start New Zealand study.

Development of communication and self-regulation skills is fundamental to psychosocial maturation in childhood. The Kia Timata Pai Best Start (KTP) longitudinal study aims to promote these skills through interventions delivered at early childcare centers across New Zealand. In addition to evaluating effects of the interventions on behavioral and cognitive outcomes, the study utilizes electroencephalography (EEG) to characterize cortical development in a subsample of participating children. Here, we present results of the baseline resting EEG assessment with 193 children aged 15 to 33 months. We identified EEG correlates of individual differences in demographics, communication abilities, and temperament. We obtained communication and behavior ratings from multiple informants, and we applied contemporary analytic methods to the EEG data. Periodic spectral power adjusted for aperiodic activity was most closely associated with demographic, language, and behavioral measures. As in previous studies, gamma power was positively associated with verbal language. Alpha power was positively associated with effortful control. Nonverbal and verbal language measures showed distinct associations with EEG indices, as did the three temperament domains. Our results identified a number of candidate EEG measurements for use as longitudinal markers of optimal cortical development and response to interventions in the KTP cohort.

A framework to improve retention of Black surgical trainees: A Society of Black Academic Surgeons white paper.

Attrition is high among surgical trainees, and six of ten trainees consider leaving their programs, with two ultimately leaving before completion of training. Given known historically and systemically rooted biases, Black surgical trainees are at high risk of attrition during residency training. With only 4.5% of all surgical trainees identifying as Black, underrepresentation among their peers can lend to misclassification of failure to assimilate as clinical incompetence. Furthermore, the disproportionate impact of ongoing socioeconomic crisis (e.g., COVID-19 pandemic, police brutality etc.) on Black trainees and their families confers additional challenges that may exacerbate attrition rates. Thus, attrition is a significant threat to medical workforce diversity and health equity. There is urgent need for surgical programs to develop proactive approaches to address attrition and the threat to the surgical workforce. In this Society of Black Academic Surgeons (SBAS) white paper, we provide a framework that promotes an open and inclusive environment conducive to the retention of Black surgical trainees, and continued progress towards attainment of health equity for racial and ethnic minorities in the United States.

Offline Calibration for Infant Gaze and Head Tracking across a Wide Horizontal Visual Field.

Most well-established eye-tracking research paradigms adopt remote systems, which typically feature regular flat screens of limited width. Limitations of current eye-tracking methods over a wide area include calibration, the significant loss of data due to head movements, and the reduction of data quality over the course of an experimental session. Here, we introduced a novel method of tracking gaze and head movements that combines the possibility of investigating a wide field of view and an offline calibration procedure to enhance the accuracy of measurements. A 4-camera Smart Eye Pro system was adapted for infant research to detect gaze movements across 126° of the horizontal meridian. To accurately track this visual area, an online system calibration was combined with a new offline gaze calibration procedure. Results revealed that the proposed system successfully tracked infants' head and gaze beyond the average screen size. The implementation of an offline calibration procedure improved the validity and spatial accuracy of measures by correcting a systematic top-right error (1.38° mean horizontal error and 1.46° mean vertical error). This approach could be critical for deriving accurate physiological measures from the eye and represents a substantial methodological advance for tracking looking behaviour across both central and peripheral regions. The offline calibration is particularly useful for work with developing populations, such as infants, and for people who may have difficulties in following instructions.

Should I follow your virtual gaze? Infants' gaze following over video call.

From 10 months of age, human infants start to understand the function of the eyes in the looking behavior of others to the point where they preferentially orient toward an object if the social partner has open eyes rather than closed eyes. Thus far, gaze following has been investigated in controlled laboratory paradigms. The current study investigated this early ability using a remote live testing procedure, testing infants in their everyday environment while manipulating whether the experimenter could or could not see some target objects. A total of 32 11- and 12-month-old infants' looking behavior was assessed, varying the experimenter's eye status condition (open eyes vs closed eyes) in a between-participant design. Results showed that infants followed the gaze of a virtual social partner and that they preferentially followed open eyes rather than closed eyes. These data generalize past laboratory findings to a noisier home environment and demonstrate gaze processing capacities of infants to a virtual partner interacting with the participants in a live setup.

Evaluation of an Air Cleaning Device Equipped with Filtration and UV: Comparison of Removal Efficiency on Particulate Matter and Viable Airborne Bacteria in the Inlet and Treated Air.

Since the COVID-19 pandemic, improving indoor air quality (IAQ) has become vital for the public as COVID-19 and other infectious diseases can transmit via inhalable aerosols. Air cleaning devices with filtration and targeted pollutant treatment capabilities can help improve IAQ. However, only a few filtration/UV devices have been formally tested for their effectiveness, and little data is publicly available and UV doses comparable. In this research, we upgraded a particulate matter (PM) air filtration prototype by adding UV-C (germicidal) light. We developed realistic UV dose metrics for fast-moving air and selected performance scenarios to quantify the mitigation effect on viable airborne bacteria and PM. The targeted PM included total suspended particulate (TSP) and a coarse-to-fine range sized at PM10, PM4, PM2.5, and PM1. The PM and viable airborne bacteria concentrations were compared between the inlet and outlet of the prototype at 0.5 and 1.0 m3/s (low and high) air flow modes. The upgraded prototype inactivated nearly 100% of viable airborne bacteria and removed up to 97% of TSP, 91% of PM10, 87% of PM4, 87% of PM2.5, and 88% of PM1. The performance in the low flow rate mode was generally better than in the high flow rate mode. The combination of filtration and UV-C treatment provided 'double-barrier' assurance for air purification and lowered the risk of spreading infectious micro-organisms.

Identifying the limits of peripheral visual processing in 9-month-old infants.

Most fundamental aspects of information processing in infancy have been primarily investigated using simplified images centrally presented on computer displays. This approach lacks ecological validity as in reality the majority of visual information is presented across the visual field, over a range of eccentricities. Limited studies are present, however, about the extent and the characteristics of infant peripheral vision after 7 months of age. The present work investigates the limits of infant (9-month-olds) and adult visual fields using a detection task. Gabor patches were presented at one of six eccentricities per hemifield, from 35° up to 60° in the left and right mid-peripheral visual fields. Detection rates at different eccentricities were measured from video recordings (infant sample) or key press responses (adult sample). Infant performance declined below chance level beyond 50°, whereas adults performed at ceiling level across all eccentricities. The performance of 9-month-olds was unequal even within 50°, suggesting regions of differential sensitivity to low-level visual information in the infant's periphery. These findings are key to understanding the limits of visual fields in the infant and, in turn, will inform the design of future infant studies.

The Detection of Face-like Stimuli at the Edge of the Infant Visual Field.

Human infants are highly sensitive to social information in their visual world. In laboratory settings, researchers have mainly studied the development of social information processing using faces presented on standard computer displays, in paradigms exploring face-to-face, direct eye contact social interactions. This is a simplification of a richer visual environment in which social information derives from the wider visual field and detection involves navigating the world with eyes, head and body movements. The present study measured 9-month-old infants' sensitivities to face-like configurations across mid-peripheral visual areas using a detection task. Upright and inverted face-like stimuli appeared at one of three eccentricities (50°, 55° or 60°) in the left and right hemifields. Detection rates at different eccentricities were measured from video recordings. Results indicated that infant performance was heterogeneous and dropped beyond 55°, with a marginal advantage for targets appearing in the left hemifield. Infants' orienting behaviour was not influenced by the orientation of the target stimulus. These findings are key to understanding how face stimuli are perceived outside foveal regions and are informative for the design of infant paradigms involving stimulus presentation across a wider field of view, in more naturalistic visual environments.

The role of social signals in segmenting observed actions in 18-month-old children.

Learning about actions requires children to identify the boundaries of an action and its units. Whereas some action units are easily identified, parents can support children's action learning by adjusting the presentation and using social signals. However, currently, little is understood regarding how children use these signals to learn actions. In the current study, we investigate the possibility that communicative signals are a particularly suitable cue for segmenting events. We investigated this hypothesis by presenting 18-month-old children (N = 60) with short action sequences consisting of toy animals either hopping or sliding across a board into a house, but interrupting this two-step sequence either (a) using an ostensive signal as a segmentation cue, (b) using a non-ostensive segmentation cue and (c) without additional segmentation information between the actions. Marking the boundary using communicative signals increased children's imitation of the less salient sliding action. Imitation of the hopping action remained unaffected. Crucially, marking the boundary of both actions using a non-communicative control condition did not increase imitation of either action. Communicative signals might be particularly suitable in segmenting non-salient actions that would otherwise be perceived as part of another action or as non-intentional. These results provide evidence of the importance of ostensive signals at event boundaries in scaffolding children's learning.

Understanding the causes and consequences of variability in infant ERP editing practices.

The current study examined the effects of variability on infant event-related potential (ERP) data editing methods. A widespread approach for analyzing infant ERPs is through a trial-by-trial editing process. Researchers identify electroencephalogram (EEG) channels containing artifacts and reject trials that are judged to contain excessive noise. This process can be performed manually by experienced researchers, partially automated by specialized software, or completely automated using an artifact-detection algorithm. Here, we compared the editing process from four different editors-three human experts and an automated algorithm-on the final ERP from an existing infant EEG dataset. Findings reveal that agreement between editors was low, for both the numbers of included trials and of interpolated channels. Critically, variability resulted in differences in the final ERP morphology and in the statistical results of the target ERP that each editor obtained. We also analyzed sources of disagreement by estimating the EEG characteristics that each human editor considered for accepting an ERP trial. In sum, our study reveals significant variability in ERP data editing pipelines, which has important consequences for the final ERP results. These findings represent an important step toward developing best practices for ERP editing methods in infancy research.

Minimizing re-excision after breast conserving surgery - a review of radiofrequency spectroscopy for real-time, intraoperative margin assessment.

INTRODUCTION: For early-stage breast cancer, breast-conserving surgery (BCS) plus radiation is standard-of-care. Nationwide, >20% of BCS patients require re-excision for positive margins, resulting in delayed adjuvant therapy, increased complications, emotional and financial stress for patients, and additional cost to the healthcare system. Although several methods may be employed to mitigate positive margins, no technique can fully address the need. MarginProbe® is an adjunctive tool for real-time intraoperative margin assessment and is shown to reduce positive margins by >50%. AREAS COVERED: Discussion of the impact of re-excision following BCS, a review of currently available methods for intraoperative margin management, followed by a technology and literature review of the MarginProbe® Radiofrequency Spectroscopy System. EXPERT OPINION: Re-excision significantly impacts patients, providers and payers. Limitations in the ability to assess margins at time of surgery warrant more advanced methods of residual disease detection. MarginProbe facilitates the most efficient pathway for breast cancer patients through the surgical phase of treatment. The device is well-suited for adoption as the healthcare focus shifts from volume to value and supports the three pillars of the US Department of Health and Human Services' 'Triple-Aim' strategy: improve population health, improve patient experience of care, and reduce per-capita costs.

Infants Oscillatory Frequencies change during Free-Play.

Social interactions are known to be an essential component of infant development. For this reason, exploring functional neural activity while infants are engaged in social interactions will enable a better understanding of the infant social brain. This in turn, will enable the beginning of disentangling the neural basis of social and non-social interactions as well as the influence that maternal engagement has on infant brain function. Maternal sensitivity serves as a model for socio-emotional development during infancy, which poses the question: do interactions between parents and their offspring present altered electrophysiological responses in comparison to the general population if said parents are at risk of mental health disorders? The current research aimed to observe the oscillatory activity of 6-month-old infants during spontaneous free-play interactions with their mother. A 5-minute unconstrained free-play session was recorded between infant-mother dyads with EEG recordings taken from the 6-month-old infants (n = 64). During the recording, social and non-social behaviours were coded and EEG assessed with these epochs. Results showed an increase in oscillatory activity both when an infant played independently or interacted with their mother and oscillatory power was greatest in the alpha and theta bands. In the present 6-month-old cohort, no hemispheric power differences were observed as oscillatory power in the corresponding neural regions (i.e. left and right temporal regions) appeared to mirror each other. Instead, temporal estimates were larger and different from all other regions, whilst the frontal and parietal regions bihemispherically displayed similar estimates, which were larger than those observed centrally, but smaller than those displayed in the temporal locations. The interactions observed between the behavioural events and frequency bands demonstrated a significant reduction in power comparative to the power observed in the gamma band during the baseline event. The present research sought to explore the obstacle of artificial play paradigms for neuroscience research, whereby researchers question how much these paradigms relate to reality. The present manuscript will discuss the strengths and limitations of taking an unconstrained free-play approach.

Circular DNA viruses identified in short-finned pilot whale and orca tissue samples.

Members of the Delphinidae family are widely distributed across the world's oceans. We used a viral metagenomic approach to identify viruses in orca (Orcinus orca) and short-finned pilot whale (Globicephala macrorhynchus) muscle, kidney, and liver samples from deceased animals. From orca tissue samples (muscle, kidney, and liver), we identified a novel polyomavirus (Polyomaviridae), three cressdnaviruses, and two genomoviruses (Genomoviridae). In the short-finned pilot whale we were able to identify one genomovirus in a kidney sample. The presence of unclassified cressdnavirus within two samples (muscle and kidney) of the same animal supports the possibility these viruses might be widespread within the animal. The orca polyomavirus identified here is the first of its species and is not closely related to the only other dolphin polyomavirus previously discovered. The identification and verification of these viruses expands the current knowledge of viruses that are associated with the Delphinidae family.

Fetal eye movements in response to a visual stimulus.

INTRODUCTION: In 2D ultrasound, the lens of the fetal eye can be distinguished as white circles within the hypoechoic eyeball, and eye movements can be visualized from about 15 weeks' gestation. It has been shown that from 31 weeks gestational age the fetal sensory system is capable of directed vision if enough light is available. METHODS: We have developed a light source for delivering visual stimuli to be seen by the fetal eye, using laser dot diodes emitting at 650 nm. The 2D component of 94 fetal ultrasound scans (mean gestational age 240 days), where the light stimulus was presented, was coded to determine whether the eyes moved in response to the stimuli independent of any head movement. RESULTS: The light stimulus significantly provoked head and eye movements, but after the light was withdrawn the head stopped moving, yet the eyes continued to move. CONCLUSION: This provides evidence for visual attention mechanisms that can be controlled through eye movements that are independent of head movements prior to birth.

Infants' conceptual representations of meaningful verbal and nonverbal sounds.

In adults, words are more effective than sounds at activating conceptual representations. We aimed to replicate these findings and extend them to infants. In a series of experiments using an eye tracker object recognition task, suitable for both adults and infants, participants heard either a word (e.g. cow) or an associated sound (e.g. mooing) followed by an image illustrating a target (e.g. cow) and a distracter (e.g. telephone). The results showed that adults reacted faster when the visual object matched the auditory stimulus and even faster in the word relative to the associated sound condition. Infants, however, did not show a similar pattern of eye-movements: only eighteen-month-olds, but not 9- or 12-month-olds, were equally fast at recognizing the target object in both conditions. Looking times, however, were longer for associated sounds, suggesting that processing sounds elicits greater allocation of attention. Our findings suggest that the advantage of words over associated sounds in activating conceptual representations emerges at a later stage during language development.

Speech Intonation Induces Enhanced Face Perception in Infants.

Infants' preference for faces with direct compared to averted eye gaze, and for infant-directed over adult-directed speech, reflects early sensitivity to social communication. Here, we studied whether infant-directed speech (IDS), could affect the processing of a face with direct gaze in 4-month-olds. In a new ERP paradigm, the word 'hello' was uttered either in IDS or adult-direct speech (ADS) followed by an upright or inverted face. We show that the face-specific N290 ERP component was larger when faces were preceded by IDS relative to ADS. Crucially, this effect is specific to upright faces, whereas inverted faces preceded by IDS elicited larger attention-related P1 and Nc. These results suggest that IDS generates communicative expectations in infants. When such expectations are met by a following social stimulus - an upright face - infants are already prepared to process it. When the stimulus is a non-social one -inverted face - IDS merely increases general attention.

Oncolytic Herpes Simplex Virus Prevents Premalignant Lesions from Progressing to Cancer.

Early detection and timely treatment of precancerous lesions are hallmarks of successful strategies to prevent deaths due to cancer. Oncolytic viruses are a group of promising anti-cancer agents with wide-ranging experimental and clinical efficacy against solid tumors. Previously, we have shown that NV1066, an oncolytic herpes simplex-1 virus encoding enhanced green fluorescent protein, selectively infects, replicates in, and kills various cancer types. In this study, we sought to determine whether this oncolytic agent can treat precancerous lesions to prevent cancer formation. Using an oral chemical carcinogenesis model in hamsters, we assessed the ability of NV1066 to infect precancerous and cancerous lesions. NV1066 consistently infected dysplastic cells, carcinoma in situ, and squamous cell carcinoma. Animals receiving an intramucosal injection of NV1066 for 7 weeks showed significantly fewer (3-fold) and smaller (4-fold) lesions compared to animals that did not receive viral treatment. Results indicate that infectivity might be dependent on the herpes simplex virus 1 receptor, nectin-1. This study demonstrates that not only can NV1066 treat oral squamous cell carcinoma, but it can also infect and treat premalignant lesions, thus delaying cancer progression. Overall, our study shows the potential of the oncolytic virus NV1066 as a cancer prevention tool.