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Joseph Mermelstein,1 Alanna Chait Mermelstein,2 Maxwell M Chait3 1Gasteroenterology and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist. Keywords: PPI failure, resistant GERD, acid-related diseases, gastroesophageal reflux disease, acid reflux, proton pump inhibitors

Joseph Mermelstein,1 Alanna Chait Mermelstein,2 Maxwell M Chait,3 1Department of Medicine, Mount Sinai Beth Israel/Icahn School of Medicine, 2Department of Psychiatry, New York Presbyterian Hospital/Weill Cornell Medicine, 3Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: Gastroesophageal reflux disease is the most common upper gastroenterology disorder in the US. It is associated with a variety of complications and significantly impacts quality of life. Proton pump inhibitors are the most effective treatment. Dexlansoprazole modified release (MR) is a proton pump inhibitor that employs a novel release formulation that prolongs its absorption and allows for more flexibility in dosing. Dexlansoprazole MR can be dosed without regard to food intake or time of day, and once-daily dosing may replace twice-daily dosing of other agents. Dexlansoprazole MR is effective for healing and maintenance of erosive esophagitis, and for the treatment of nonerosive disease, including nocturnal gastroesophageal reflux disease. Dexlansoprazole MR is safe and well tolerated, and can improve quality of life. Keywords: dexlansoprazole, proton pump inhibitors, gastroesophageal reflux disease, erosive esophagitis

Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention. Strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech. Combining simultaneously recorded eye tracking and magnetoencephalographic data with temporal response functions, we show that gaze tracks attended speech, a phenomenon we termed ocular speech tracking. Ocular speech tracking even differentiates a target from a distractor in a multi-speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition., (© 2024. The Author(s).)

Human listeners possess an innate capacity to discern patterns within rapidly unfolding sensory input. Core questions, guiding ongoing research, focus on the mechanisms through which these representations are acquired and whether the brain prioritizes or suppresses predictable sensory signals. Previous work, using fast auditory sequences (tone-pips presented at a rate of 20 Hz), revealed sustained response effects that appear to track the dynamic predictability of the sequence. Here, we extend the investigation to slower sequences (4 Hz), permitting the isolation of responses to individual tones. Stimuli were 50 ms tone-pips, ordered into random (RND) and regular (REG; a repeating pattern of 10 frequencies) sequences; Two timing profiles were created: in "fast" sequences, tone-pips were presented in direct succession (20 Hz); in "slow" sequences, tone-pips were separated by a 200 ms silent gap (4 Hz). Naive participants ( N  = 22; both sexes) passively listened to these sequences, while brain responses were recorded using magnetoencephalography (MEG). Results unveiled a heightened magnitude of sustained brain responses in REG when compared to RND patterns. This manifested from three tones after the onset of the pattern repetition, even in the context of slower sequences characterized by extended pattern durations (2,500 ms). This observation underscores the remarkable implicit sensitivity of the auditory brain to acoustic regularities. Importantly, brain responses evoked by single tones exhibited the opposite pattern-stronger responses to tones in RND than REG sequences. The demonstration of simultaneous but opposing sustained and evoked response effects reveals concurrent processes that shape the representation of unfolding auditory patterns., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Hu et al.)

Microsaccades are small, involuntary eye movements that occur during fixation. Their role is debated with recent hypotheses proposing a contribution to automatic scene sampling. Microsaccadic inhibition (MSI) refers to the abrupt suppression of microsaccades, typically evoked within 0.1 s after new stimulus onset. The functional significance and neural underpinnings of MSI are subjects of ongoing research. It has been suggested that MSI is a component of the brain's attentional re-orienting network which facilitates the allocation of attention to new environmental occurrences by reducing disruptions or shifts in gaze that could interfere with processing. The extent to which MSI is reflexive or influenced by top-down mechanisms remains debated. We developed a task that examines the impact of auditory top-down attention on MSI, allowing us to disentangle ocular dynamics from visual sensory processing. Participants ( N  = 24 and 27; both sexes) listened to two simultaneous streams of tones and were instructed to attend to one stream while detecting specific task "targets." We quantified MSI in response to occasional task-irrelevant events presented in both the attended and unattended streams (frequency steps in Experiment 1, omissions in Experiment 2). The results show that initial stages of MSI are not affected by auditory attention. However, later stages (∼0.25 s postevent onset), affecting the extent and duration of the inhibition, are enhanced for sounds in the attended stream compared to the unattended stream. These findings provide converging evidence for the reflexive nature of early MSI stages and robustly demonstrate the involvement of auditory attention in modulating the later stages., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Zhao et al.)

From auditory perception to general cognition, the ability to play a musical instrument has been associated with skills both related and unrelated to music. However, it is unclear if these effects are bound to the specific characteristics of musical instrument training, as little attention has been paid to other populations such as audio engineers and designers whose auditory expertise may match or surpass that of musicians in specific auditory tasks or more naturalistic acoustic scenarios. We explored this possibility by comparing students of audio engineering (n = 20) to matched conservatory-trained instrumentalists (n = 24) and to naive controls (n = 20) on measures of auditory discrimination, auditory scene analysis, and speech in noise perception. We found that audio engineers and performing musicians had generally lower psychophysical thresholds than controls, with pitch perception showing the largest effect size. Compared to controls, audio engineers could better memorise and recall auditory scenes composed of non-musical sounds, whereas instrumental musicians performed best in a sustained selective attention task with two competing streams of tones. Finally, in a diotic speech-in-babble task, musicians showed lower signal-to-noise-ratio thresholds than both controls and engineers; however, a follow-up online study did not replicate this musician advantage. We also observed differences in personality that might account for group-based self-selection biases. Overall, we showed that investigating a wider range of forms of auditory expertise can help us corroborate (or challenge) the specificity of the advantages previously associated with musical instrument training., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Any listening task, from sound recognition to sound-based communication, rests on auditory memory which is known to decline in healthy ageing. However, how this decline maps onto multiple components and stages of auditory memory remains poorly characterised. In an online unsupervised longitudinal study, we tested ageing effects on implicit auditory memory for rapid tone patterns. The test required participants (younger, aged 20-30, and older adults aged 60-70) to quickly respond to rapid regularly repeating patterns emerging from random sequences. Patterns were novel in most trials (REGn), but unbeknownst to the participants, a few distinct patterns reoccurred identically throughout the sessions (REGr). After correcting for processing speed, the response times (RT) to REGn should reflect the information held in echoic and short-term memory before detecting the pattern; long-term memory formation and retention should be reflected by the RT advantage (RTA) to REGr vs REGn which is expected to grow with exposure. Older participants were slower than younger adults in detecting REGn and exhibited a smaller RTA to REGr. Computational simulations using a model of auditory sequence memory indicated that these effects reflect age-related limitations both in early and long-term memory stages. In contrast to ageing-related accelerated forgetting of verbal material, here older adults maintained stable memory traces for REGr patterns up to 6 months after the first exposure. The results demonstrate that ageing is associated with reduced short-term memory and long-term memory formation for tone patterns, but not with forgetting, even over surprisingly long timescales., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

Listeners often operate in complex acoustic environments, consisting of many concurrent sounds. Accurately encoding and maintaining such auditory objects in short-term memory is crucial for communication and scene analysis. Yet, the neural underpinnings of successful auditory short-term memory (ASTM) performance are currently not well understood. To elucidate this issue, we presented a novel, challenging auditory delayed match-to-sample task while recording MEG. Human participants listened to 'scenes' comprising three concurrent tone pip streams. The task was to indicate, after a delay, whether a probe stream was present in the just-heard scene. We present three key findings: First, behavioural performance revealed faster responses in correct versus incorrect trials as well as in 'probe present' versus 'probe absent' trials, consistent with ASTM search. Second, successful compared with unsuccessful ASTM performance was associated with a significant enhancement of event-related fields and oscillatory activity in the theta, alpha and beta frequency ranges. This extends previous findings of an overall increase of persistent activity during short-term memory performance. Third, using distributed source modelling, we found these effects to be confined mostly to sensory areas during encoding, presumably related to ASTM contents per se. Parietal and frontal sources then became relevant during the maintenance stage, indicating that effective STM operation also relies on ongoing inhibitory processes suppressing task-irrelevant information. In summary, our results deliver a detailed account of the neural patterns that differentiate successful from unsuccessful ASTM performance in the context of a complex, multi-object auditory scene., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Listening in noisy environments requires effort- the active engagement of attention and other cognitive abilities- as well as increased arousal. The ability to separately quantify the contribution of these components is key to understanding the dynamics of effort and how it may change across listening situations and in certain populations. We concurrently measured two types of ocular data in young participants (both sexes): pupil dilation (PD; thought to index arousal aspects of effort) and microsaccades (MS; hypothesized to reflect automatic visual exploratory sampling), while they performed a speech-in-noise task under high- (HL) and low- (LL) listening load conditions. Sentences were manipulated so that the behaviorally relevant information (keywords) appeared at the end (Experiment 1) or beginning (Experiment 2) of the sentence, resulting in different temporal demands on focused attention. In line with previous reports, PD effects were associated with increased dilation under load. We observed a sustained difference between HL and LL conditions, consistent with increased phasic and tonic arousal. Importantly we show that MS rate was also modulated by listening load. This was manifested as a reduced MS rate in HL relative to LL. Critically, in contrast to the sustained difference seen for PD, MS effects were localized in time, specifically during periods when demands on auditory attention were greatest. These results demonstrate that auditory selective attention interfaces with the mechanisms controlling MS generation, establishing MS as an informative measure, complementary to PD, with which to quantify the temporal dynamics of auditory attentional processing under effortful listening conditions. SIGNIFICANCE STATEMENT Listening effort, reflecting the "cognitive bandwidth" deployed to effectively process sound in adverse environments, contributes critically to listening success. Understanding listening effort and the processes involved in its allocation is a major challenge in auditory neuroscience. Here, we demonstrate that microsaccade rate can be used to index a specific subcomponent of listening effort, the allocation of instantaneous auditory attention, that is distinct from the modulation of arousal indexed by pupil dilation (currently the dominant measure of listening effort). These results reveal the push-pull process through which auditory attention interfaces with the (visual) attention network that controls microsaccades, establishing microsaccades as a powerful tool for measuring auditory attention and its deficits., (Copyright © 2023 Contadini-Wright et al.)

A growing literature is demonstrating a link between working memory (WM) and speech-in-noise (SiN) perception. However, the nature of this correlation and which components of WM might underlie it, are being debated. We investigated how SiN reception links with auditory sensory memory (aSM) - the low-level processes that support the short-term maintenance of temporally unfolding sounds. A large sample of old ( N  = 199, 60-79 yo) and young ( N  = 149, 20-35 yo) participants was recruited online and performed a coordinate response measure-based speech-in-babble task that taps listeners' ability to track a speech target in background noise. We used two tasks to investigate implicit and explicit aSM. Both were based on tone patterns overlapping in processing time scales with speech (presentation rate of tones 20 Hz; of patterns 2 Hz). We hypothesised that a link between SiN and aSM may be particularly apparent in older listeners due to age-related reduction in both SiN reception and aSM. We confirmed impaired SiN reception in the older cohort and demonstrated reduced aSM performance in those listeners. However, SiN and aSM did not share variability. Across the two age groups, SiN performance was predicted by a binaural processing test and age. The results suggest that previously observed links between WM and SiN may relate to the executive components and other cognitive demands of the used tasks. This finding helps to constrain the search for the perceptual and cognitive factors that explain individual variability in SiN performance., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Respiratory failure in COVID-19 is characterized by widespread disruption of the lung's alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18-92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19-mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.

Online experimental platforms can be used as an alternative to, or complement, lab-based research. However, when conducting auditory experiments via online methods, the researcher has limited control over the participants' listening environment. We offer a new method to probe one aspect of that environment, headphone use. Headphones not only provide better control of sound presentation but can also "shield" the listener from background noise. Here we present a rapid (< 3 min) headphone screening test based on Huggins Pitch (HP), a perceptual phenomenon that can only be detected when stimuli are presented dichotically. We validate this test using a cohort of "Trusted" online participants who completed the test using both headphones and loudspeakers. The same participants were also used to test an existing headphone test (AP test; Woods et al., 2017, Attention Perception Psychophysics). We demonstrate that compared to the AP test, the HP test has a higher selectivity for headphone users, rendering it as a compelling alternative to existing methods. Overall, the new HP test correctly detects 80% of headphone users and has a false-positive rate of 20%. Moreover, we demonstrate that combining the HP test with an additional test-either the AP test or an alternative based on a beat test (BT)-can lower the false-positive rate to ~ 7%. This should be useful in situations where headphone use is particularly critical (e.g., dichotic or spatial manipulations). Code for implementing the new tests is publicly available in JavaScript and through Gorilla (gorilla.sc)., (© 2020. The Author(s).)

The brain is highly sensitive to auditory regularities and exploits the predictable order of sounds in many situations, from parsing complex auditory scenes, to the acquisition of language. To understand the impact of stimulus predictability on perception, it is important to determine how the detection of predictable structure influences processing and attention. Here, we use pupillometry to gain insight into the effect of sensory regularity on arousal. Pupillometry is a commonly used measure of salience and processing effort, with more perceptually salient or perceptually demanding stimuli consistently associated with larger pupil diameters. In two experiments we tracked human listeners' pupil dynamics while they listened to sequences of 50-ms tone pips of different frequencies. The order of the tone pips was either random, contained deterministic (fully predictable) regularities (experiment 1, n = 18, 11 female) or had a probabilistic regularity structure (experiment 2, n = 20, 17 female). The sequences were rapid, preventing conscious tracking of sequence structure thus allowing us to focus on the automatic extraction of different types of regularities. We hypothesized that if regularity facilitates processing by reducing processing demands, a smaller pupil diameter would be seen in response to regular relative to random patterns. Conversely, if regularity is associated with heightened arousal and attention (i.e., engages processing resources) the opposite pattern would be expected. In both experiments we observed a smaller sustained (tonic) pupil diameter for regular compared with random sequences, consistent with the former hypothesis and confirming that predictability facilitates sequence processing. SIGNIFICANCE STATEMENT The brain is highly sensitive to auditory regularities. To appreciate the impact that the presence of predictability has on perception, we need to better understand how a predictable structure influences processing and attention. We recorded listeners' pupil responses to sequences of tones that followed either a predictable or unpredictable pattern, as the pupil can be used to implicitly tap into these different cognitive processes. We found that the pupil showed a smaller sustained diameter to predictable sequences, indicating that predictability eased processing rather than boosted attention. The findings suggest that the pupil response can be used to study the automatic extraction of regularities, and that the effects are most consistent with predictability helping the listener to efficiently process upcoming sounds., (Copyright © 2021 Milne et al.)

Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyperinflammatory signatures, and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163 + monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract., Competing Interests: Declaration of interests J.Z., M.S., and S.M. have competing interests with IsoPlexis. The remaining authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The notion that sensitivity to the statistical structure of the environment is pivotal to perception has recently garnered considerable attention. Here we investigated this issue in the context of hearing. Building on previous work (Sohoglu and Chait, 2016a; elife), stimuli were artificial 'soundscapes' populated by multiple (up to 14) simultaneous streams ('auditory objects') comprised of tone-pip sequences, each with a distinct frequency and pattern of amplitude modulation. Sequences were either temporally regular or random. We show that listeners' ability to detect abrupt appearance or disappearance of a stream is facilitated when scene streams were characterized by a temporally regular fluctuation pattern. The regularity of the changing stream as well as that of the background (non-changing) streams contribute independently to this effect. Remarkably, listeners benefit from regularity even when they are not consciously aware of it. These findings establish that perception of complex acoustic scenes relies on the availability of detailed representations of the regularities automatically extracted from multiple concurrent streams., (Copyright © 2020. Published by Elsevier B.V.)

Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age 1,2 . Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C) 3-5 . Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.

Online recruitment platforms are increasingly used for experimental research. Crowdsourcing is associated with numerous benefits but also notable constraints, including lack of control over participants' environment and engagement. In the context of auditory experiments, these limitations may be particularly detrimental to threshold-based tasks that require effortful listening. Here, we ask whether incorporating a performance-based monetary bonus improves speech reception performance of online participants. In two experiments, participants performed an adaptive matrix-type speech-in-noise task (where listeners select two key words out of closed sets). In Experiment 1, our results revealed worse performance in online ( N  = 49) compared with in-lab ( N  = 81) groups. Specifically, relative to the in-lab cohort, significantly fewer participants in the online group achieved very low thresholds. In Experiment 2 ( N  = 200), we show that a monetary reward improved listeners' thresholds to levels similar to those observed in the lab setting. Overall, the results suggest that providing a small performance-based bonus increases participants' task engagement, facilitating a more accurate estimation of auditory ability under challenging listening conditions.

The auditory system plays a critical role in supporting our ability to detect abrupt changes in our surroundings. Here we study how this capacity is affected in the course of healthy ageing. Artifical acoustic 'scenes', populated by multiple concurrent streams of pure tones ('sources') were used to capture the challenges of listening in complex acoustic environments. Two scene conditions were included: REG scenes consisted of sources characterized by a regular temporal structure. Matched RAND scenes contained sources which were temporally random. Changes, manifested as the abrupt disappearance of one of the sources, were introduced to a subset of the trials and participants ('young' group N = 41, age 20-38 years; 'older' group N = 41, age 60-82 years) were instructed to monitor the scenes for these events. Previous work demonstrated that young listeners exhibit better change detection performance in REG scenes, reflecting sensitivity to temporal structure. Here we sought to determine: (1) Whether 'baseline' change detection ability (i.e. in RAND scenes) is affected by age. (2) Whether aging affects listeners' sensitivity to temporal regularity. (3) How change detection capacity relates to listeners' hearing and cognitive profile (a battery of tests that capture hearing and cognitive abilities hypothesized to be affected by aging). The results demonstrated that healthy aging is associated with reduced sensitivity to abrupt scene changes in RAND scenes but that performance does not correlate with age or standard audiological measures such as pure tone audiometry or speech in noise performance. Remarkably older listeners' change detection performance improved substantially (up to the level exhibited by young listeners) in REG relative to RAND scenes. This suggests that the ability to extract and track the regularity associated with scene sources, even in crowded acoustic environments, is relatively preserved in older listeners., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Statistical learning and probabilistic prediction are fundamental processes in auditory cognition. A prominent computational model of these processes is Prediction by Partial Matching (PPM), a variable-order Markov model that learns by internalizing n-grams from training sequences. However, PPM has limitations as a cognitive model: in particular, it has a perfect memory that weights all historic observations equally, which is inconsistent with memory capacity constraints and recency effects observed in human cognition. We address these limitations with PPM-Decay, a new variant of PPM that introduces a customizable memory decay kernel. In three studies-one with artificially generated sequences, one with chord sequences from Western music, and one with new behavioral data from an auditory pattern detection experiment-we show how this decay kernel improves the model's predictive performance for sequences whose underlying statistics change over time, and enables the model to capture effects of memory constraints on auditory pattern detection. The resulting model is available in our new open-source R package, ppm (https://github.com/pmcharrison/ppm)., Competing Interests: The authors have declared that no competing interests exist.

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder in the United States. Although proton pump inhibitors (PPIs) are the mainstay of therapy for GERD and its complications, they have several limitations, including incomplete symptom resolution. Potassium-competitive acid blockers (P-CABs) were developed to address the limitations of PPIs as well as the need for improved antisecretory effects. Tegoprazan, the newest P-CAB, was approved in 2018 in South Korea for the treatment of erosive esophagitis (EE) and nonerosive reflux disease (NERD). A highly selective inhibitor of the H+/K+-ATPase, tegoprazan is also safe and effective for nocturnal acid breakthrough (NAB) and motility. Further studies of tegoprazan are warranted to define its potential role in the treatment of acid-related disorders., (Copyright 2020 Clarivate Analytics.)

Introduction: Percutaneous nephrolithotomy is a procedure used for management of refractory renal calculi. Oral and parenteral opioids, along with local anesthetic infiltration, neuraxial anesthesia, and paravertebral blocks are the most common methods of managing intra-operative and post-operative pain for these patients. The erector spinae plane block with catheter (ESPC) is a newer interfascial regional anesthetic technique that can be used to manage peri-operative pain in these patients., Clinical Findings: Three patients complained of significant flank pain were scheduled for percutaneous nephrolithotomy under general anesthesia in the prone position., Diagnoses: Patients were diagnosed with large renal calculi., Therapeutic Interventions: Patients received ESPC in the pre-operative holding area at the level of the T7 transverse process. The ESPCS were bolused with a solution of 30 mL 0.25% bupivacaine with 4 mg dexamethasone prior to surgery. Patients also received oral tramadol 50 mg and acetaminophen 1 g as part of the multimodal pain protocol prior to surgery. After the procedure, the patients were bolused with 0.25% bupivacaine or started on an infusion of 0.25% bupivacaine to manage their pain., Outcomes: No opioid or other pain medications, other than the local anesthetic solution given in the ESPCs, were used during the intra-operative or post-operative period for management of pain in these patients. Visual analogue scale (VAS) scores were below 4 for all patients in the post-operative period, and patients did not report any issues with post-operative nausea or vomiting., Conclusion: These patients were compared to 3 prior patients who had undergone percutaneous nephrolithotomy without ESPC. The 3 patients without ESPC placement reported increased VAS scores, had increased opioid/pain medication consumption intraoperatively and postoperatively, and had increased incidence of perioperative nausea when compared to our ESPC patients. Our report shows that ESPC, in combination with a multimodal pain protocol, can be a good option for management of patients undergoing percutaneous nephrolithotomy.

Using fMRI and multivariate pattern analysis, we determined whether spectral and temporal acoustic features are represented by independent or integrated multivoxel codes in human cortex. Listeners heard band-pass noise varying in frequency (spectral) and amplitude-modulation (AM) rate (temporal) features. In the superior temporal plane, changes in multivoxel activity due to frequency were largely invariant with respect to AM rate (and vice versa), consistent with an independent representation. In contrast, in posterior parietal cortex, multivoxel representation was exclusively integrated and tuned to specific conjunctions of frequency and AM features (albeit weakly). Direct between-region comparisons show that whereas independent coding of frequency weakened with increasing levels of the hierarchy, such a progression for AM and integrated coding was less fine-grained and only evident in the higher hierarchical levels from non-core to parietal cortex (with AM coding weakening and integrated coding strengthening). Our findings support the notion that primary auditory cortex can represent spectral and temporal acoustic features in an independent fashion and suggest a role for parietal cortex in feature integration and the structuring of sensory input., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

A study by Tóth, Kocsis, Háden, Szerafin, Shinn-Cunningham, and Winkler [Neuroimage 141, 108 - 119 (2016)] reported that spatial cues (such as interaural differences or ITDs) that differentiate the perceived sound source directions of a target tone sequence (figure) from simultaneous distracting tones (background) did not improve the ability of participants to detect the target sequence. The present study aims to investigate more systematically whether spatially separating a complex auditory "figure" from the background auditory stream may enhance the detection of a target in a cluttered auditory scene. Results of the presented experiment suggest that the previous negative results arose because of the specific experimental conditions tested. Here the authors find that ITDs provide a clear benefit for detecting a target tone sequence amid a mixture of other simultaneous tone bursts.

Memory, on multiple timescales, is critical to our ability to discover the structure of our surroundings, and efficiently interact with the environment. We combined behavioural manipulation and modelling to investigate the dynamics of memory formation for rarely reoccurring acoustic patterns. In a series of experiments, participants detected the emergence of regularly repeating patterns within rapid tone-pip sequences. Unbeknownst to them, a few patterns reoccurred every ~3 min. All sequences consisted of the same 20 frequencies and were distinguishable only by the order of tone-pips. Despite this, reoccurring patterns were associated with a rapidly growing detection-time advantage over novel patterns. This effect was implicit, robust to interference, and persisted for 7 weeks. The results implicate an interplay between short (a few seconds) and long-term (over many minutes) integration in memory formation and demonstrate the remarkable sensitivity of the human auditory system to sporadically reoccurring structure within the acoustic environment., Competing Interests: RB, PH, MH, CB, SP, MP, MC No competing interests declared, (© 2020, Bianco et al.)

Non-recirculating tissue-resident memory T cells (TRMs) are the predominant T cell subset in diverse tissue sites, where they mediate protective immune responses in situ. Here, we reveal a role for TRM in maintaining immune homeostasis in the human pancreas through interactions with resident macrophages and the PD-1/PD-L1 inhibitory pathway. Using tissues obtained from organ donors, we identify that pancreas T cells comprise CD8 + PD-1 hi TRMs, which are phenotypically, functionally, and transcriptionally distinct compared to TRMs in neighboring jejunum and lymph node sites. Pancreas TRMs cluster with resident macrophages throughout the exocrine areas; TRM effector functions are enhanced by macrophage-derived co-stimulation and attenuated by the PD-1/PD-L1 pathways. Conversely, in samples from chronic pancreatitis, TRMs exhibit reduced PD-1 expression and reduced interactions with macrophages. These findings suggest important roles for PD-1 and TRM-macrophage interactions in controlling tissue homeostasis and immune dysfunctions underlying inflammatory disease, with important implications for PD-1-based immunotherapies., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)