Accurate prediction of neurologic changes in critically ill infants using pose AI.

Infant alertness and neurologic changes can reflect life-threatening pathology but are assessed by exam, which can be intermittent and subjective. Reliable, continuous methods are needed. We hypothesized that our computer vision method to track movement, pose AI, could predict neurologic changes in the neonatal intensive care unit (NICU). We collected 4,705 hours of video linked to electroencephalograms (EEG) from 115 infants. We trained a deep learning pose algorithm that accurately predicted anatomic landmarks in three evaluation sets (ROC-AUCs 0.83-0.94), showing feasibility of applying pose AI in an ICU. We then trained classifiers on landmarks from pose AI and observed high performance for sedation (ROC-AUCs 0.87-0.91) and cerebral dysfunction (ROC-AUCs 0.76-0.91), demonstrating that an EEG diagnosis can be predicted from video data alone. Taken together, deep learning with pose AI may offer a scalable, minimally invasive method for neuro-telemetry in the NICU.

Natural language syntax complies with the free-energy principle.

Natural language syntax yields an unbounded array of hierarchically structured expressions. We claim that these are used in the service of active inference in accord with the free-energy principle (FEP). While conceptual advances alongside modelling and simulation work have attempted to connect speech segmentation and linguistic communication with the FEP, we extend this program to the underlying computations responsible for generating syntactic objects. We argue that recently proposed principles of economy in language design-such as "minimal search" criteria from theoretical syntax-adhere to the FEP. This affords a greater degree of explanatory power to the FEP-with respect to higher language functions-and offers linguistics a grounding in first principles with respect to computability. While we mostly focus on building new principled conceptual relations between syntax and the FEP, we also show through a sample of preliminary examples how both tree-geometric depth and a Kolmogorov complexity estimate (recruiting a Lempel-Ziv compression algorithm) can be used to accurately predict legal operations on syntactic workspaces, directly in line with formulations of variational free energy minimization. This is used to motivate a general principle of language design that we term Turing-Chomsky Compression (TCC). We use TCC to align concerns of linguists with the normative account of self-organization furnished by the FEP, by marshalling evidence from theoretical linguistics and psycholinguistics to ground core principles of efficient syntactic computation within active inference.

Genotypic analysis of a localised hotspot of Pestivirus A (BVDV-1) infections in Northern Ireland.

BACKGROUND: Bovine viral diarrhoea (BVD) is caused by Pestivirus A and Pestivirus B. Northern Ireland (NI) embarked on a compulsory BVD eradication scheme in 2016, which continues to this day, so an understanding of the composition of the pestivirus genotypes in the cattle population of NI is required. METHODS: This molecular epidemiology study employed 5' untranslated region (5'UTR) genetic sequencing to examine the pestivirus genotypes circulating in samples taken from a hotspot of BVD outbreaks in the Enniskillen area in 2019. RESULTS: Bovine viral diarrhoea virus (BVDV)-1e (Pestivirus A) was detected for the first time in Northern Ireland, and at a high frequency, in an infection hotspot in Enniskillen in 2019. There was no evidence of infection with BVDV-2 (Pestivirus B), Border disease virus (pestivirus D) or HoBi-like virus/BVDV-3 (pestivirus H). LIMITATIONS: Only 5'UTR sequencing was used, so supplementary sequencing, along with phylogenetic trees that include all BVDV-1 genotype reference strains, would improve accuracy. Examination of farm locations and animal movement/trade is also required. CONCLUSIONS: Genotype BVDV-1e was found for the first time in Northern Ireland, indicating an increase in the genetic diversity of BVDV-1, which could have implications for vaccine design and highlights the need for continued pestivirus genotypic surveillance.

Large granular lymphocyte lymphoma in 65 dogs (2005-2023).

Large granular lymphocyte lymphoma (LGLL) is a rare form of lymphoma in dogs. Limited information exists regarding presentation, treatment response, and outcome. The aim of this single-institute, retrospective study was to characterise clinical presentation, biologic behaviour, outcomes, and prognostic factors for dogs with LGLL. Cytologic review was also performed. Sixty-five dogs were included. The most common breed was the Labrador retriever (29.2%), and the most common presenting signs were lethargy (60.0%) and hyporexia (55.4%). The most common primary anatomic forms were hepatosplenic (32.8%) and gastrointestinal (20.7%). Twenty dogs (30.8%) had peripheral blood or bone marrow involvement. Thirty-two dogs were treated with maximum tolerated dose chemotherapy (MTDC) with a response documented in 74.1% of dogs. Dogs ≥7 years, and those with neutropenia or thrombocytopenia at diagnosis had the reduced likelihood of response to treatment. For dogs treated with MTDC median progression-free interval (PFI) was 17 days (range, 0-481), the median overall survival time (OST) 28 days (range, 3-421), and the 6-month and 1-year survival rates were 9.4% and 3.1%, respectively. On multivariable analysis, monocytosis and peripheral blood involvement were significantly associated with shorter PFI and OST. Long-term survival (≥100 days) was significantly associated with intermediate lymphocyte size on cytology. Dogs with LGLL have moderate response rates to chemotherapy but poor overall survival. Additional studies are needed to further evaluate prognostic factors and guide optimum treatment recommendations.

Diagnostic quality of ultrasound-guided fine-needle aspirates samples from the canine liver and spleen is not significantly affected by using 22-, 23-, and 25-gauge needles.

Ultrasound-guided fine-needle aspirates (FNA) of the liver and spleen for cytological analysis are a commonly performed procedure in canine veterinary practice. Based on our review of the literature, this is the first published study investigating whether needle size affects the diagnostic quality of hepatic and splenic samples. The aim of this prospective analytical study was to compare the diagnostic quality of ultrasound-guided FNA cytological samples of canine liver and spleen based on cellularity, blood contamination, and overall cell preservation between three different needle sizes (22-, 23-, and 25-gauge). A total of 282 splenic aspirates from 94 dogs and 348 hepatic aspirates from 116 dogs were enrolled in the study and examined by two board-certified veterinary clinical pathologists. In this study, no significant differences in diagnostic quality were identified between different needle gauge sizes when sampling canine liver and spleen. Blood contamination was higher using 22-gauge needles compared with 25-gauge needles (P = 0.024) when sampling the liver.

Olfactory neuroblastoma in a domestic cat and review of the literature.

Nasal tumors account for less than 10% of all feline neoplasms, with lymphoma, followed by adenocarcinoma, and squamous cell carcinoma, the most commonly reported. Nasal neuroectodermal tumors, including olfactory neuroblastoma (ONB), are scarcely described, and their tumorigenesis is largely unknown. Here we report the cytological, histological, and immunohistochemical features of a feline ONB. We also provide a pathological review of nasal neuroendocrine neoplasms in cats. A 7-year-old Burmese cat was evaluated for sneezing, occasional epistaxis, and upper respiratory noise for 8 months. Computed tomography (CT) imaging revealed a 7 × 5 × 3 mm irregular mass effacing and expanding the nasal cavity, which extended to the nasopharynx. Cytologically, neoplastic cells were round to polygonal and had a round nucleus with finely stippled chromatin, a single small nucleolus, and abundant pale blue cytoplasm, which contained abundant fine pale pink granules. They exhibited mild cellular atypia, anisocytosis, and mild to occasionally moderate anisokaryosis. Rhinoscopic biopsies revealed a densely cellular, malignant neuroepithelial neoplasm. Cells were arranged in densely packed trabeculae and formed Homer Wright and Flexner-Wintersteiner-like rosettes, with rare mitotic figures and scant supportive fibrovascular stroma. Immunohistochemically, neoplastic cells were positive for vimentin, cytokeratin AE1/AE3, COX-2, and beta-tubulin and negative for S-100, chromogranin A, CD117, and epithelial membrane antigen (EMA). An ONB was diagnosed based on histological and immunohistochemical findings. Interestingly, and similar to nasal carcinomas, neoplastic cells diffusely neo-expressed COX-2. To the authors' knowledge, there is no previous evidence of COX-2 in feline ONB. Histopathology and immunohistochemistry are required for a definitive diagnosis of ONB.

Toxicity and Patient-Reported Quality-of-Life Outcomes After Prostate Stereotactic Body Radiation Therapy With Focal Boost to Magnetic Resonance Imaging-Identified Prostate Cancer Lesions: Results of a Phase 2 Trial.

PURPOSE: In this prospective phase 2 trial, we investigated the toxicity and patient-reported quality-of-life outcomes in patients treated with stereotactic body radiation therapy (SBRT) to the prostate gland and a simultaneous focal boost to magnetic resonance imaging (MRI)-identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk. METHODS AND MATERIALS: Eligible patients included low- or intermediate-risk prostate cancer (Gleason score ≤7, prostate specific antigen ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with any areas of high disease burden (MRI-identified prostate imaging reporting and data system 4 or 5 lesions) simultaneously escalated to 42.5 to 45 Gy and areas overlapping organs at risk (within 2 mm of urethra, rectum, and bladder) constrained to 36.25 Gy (n = 100). Patients without a pretreatment MRI or without MRI-identified lesions were treated to dose of 37.5 Gy with no focal boost (n = 14). RESULTS: From 2015 to 2022, a total of 114 patients were enrolled with a median follow-up of 42 months. No acute or late grade 3+ gastrointestinal (GI) toxicity was observed. One patient developed late grade 3 genitourinary (GU) toxicity at 16 months. In patients treated with focal boost (n = 100), acute grade 2 GU and GI toxicity was seen in 38% and 4% of patients, respectively. Cumulative late grade 2+ GU and GI toxicities at 24 months were 13% and 5% respectively. Patient-reported outcomes showed no significant long-term change from baseline in urinary, bowel, hormonal, or sexual quality-of-life scores after treatment. CONCLUSIONS: SBRT to a dose of 40 Gy to the prostate gland with a simultaneous focal boost up to 45 Gy is well tolerated with similar rates of acute and late grade 2+ GI and GU toxicity as seen in other SBRT regimens without intraprostatic boost. Moreover, no significant long-term changes were seen in patient-reported urinary, bowel, or sexual outcomes from pretreatment baseline.

Cognitive effort and active inference.

This paper aims to integrate some key constructs in the cognitive neuroscience of cognitive control and executive function by formalising the notion of cognitive (or mental) effort in terms of active inference. To do so, we call upon a task used in neuropsychology to assess impulse inhibition-a Stroop task. In this task, participants must suppress the impulse to read a colour word and instead report the colour of the text of the word. The Stroop task is characteristically effortful, and we unpack a theory of mental effort in which, to perform this task accurately, participants must overcome prior beliefs about how they would normally act. However, our interest here is not in overt action, but in covert (mental) action. Mental actions change our beliefs but have no (direct) effect on the outside world-much like deploying covert attention. This account of effort as mental action lets us generate multimodal (choice, reaction time, and electrophysiological) data of the sort we might expect from a human participant engaging in this task. We analyse how parameters determining cognitive effort influence simulated responses and demonstrate that-when provided only with performance data-these parameters can be recovered, provided they are within a certain range.

Clinical and clinicopathological features and outcomes of cats with suspected dietary induced pancytopenia.

BACKGROUND: After a strong epidemiological link to diet was established in an outbreak of pancytopenia in cats in spring 2021 in the United Kingdom, 3 dry diets were recalled. Concentrations of the hemato- and myelotoxic mycotoxins T-2, HT-2 and diacetoxyscirpenol (DAS) greater than the European Commission guidance for dry cat foods were detected in the recalled diets. OBJECTIVES: To describe clinical and clinicopathological findings in cats diagnosed with suspected diet induced pancytopenia. ANIMALS: Fifty cats presenting with pancytopenia after exposure to a recalled diet. METHODS: Multicenter retrospective case series study. Cats with known exposure to 1 of the recalled diets were included if presented with bi- or pancytopenia and underwent bone marrow examination. RESULTS: Case fatality rate was 78%. Bone marrow aspirates and biopsy examination results were available in 23 cats; 19 cats had a bone marrow aspirate, and 8 cats had a biopsy core, available for examination. Bone marrow hypo to aplasia-often affecting all cell lines-was the main feature in all 31 available core specimens. A disproportionately pronounced effect on myeloid and megakaryocytic cells was observed in 19 cats. Myelofibrosis or bone marrow necrosis was not a feature. CONCLUSION AND CLINICAL IMPORTANCE: Mycotoxin induced pancytopenia should be considered as differential diagnosis in otherwise healthy cats presenting with bi- or pancytopenia and bone marrow hypo- to aplasia.

Intelligibility benefit for familiar voices is not accompanied by better discrimination of fundamental frequency or vocal tract length.

Speech is more intelligible when it is spoken by familiar than unfamiliar people. If this benefit arises because key voice characteristics like perceptual correlates of fundamental frequency or vocal tract length (VTL) are more accurately represented for familiar voices, listeners may be able to discriminate smaller manipulations to such characteristics for familiar than unfamiliar voices. We measured participants' (N = 17) thresholds for discriminating pitch (correlate of fundamental frequency, or glottal pulse rate) and formant spacing (correlate of VTL; 'VTL-timbre') for voices that were familiar (participants' friends) and unfamiliar (other participants' friends). As expected, familiar voices were more intelligible. However, discrimination thresholds were no smaller for the same familiar voices. The size of the intelligibility benefit for a familiar over an unfamiliar voice did not relate to the difference in discrimination thresholds for the same voices. Also, the familiar-voice intelligibility benefit was just as large following perceptible manipulations to pitch and VTL-timbre. These results are more consistent with cognitive accounts of speech perception than traditional accounts that predict better discrimination.

Pitch discrimination is better for synthetic timbre than natural musical instrument timbres despite familiarity.

Pitch discrimination is better for complex tones than pure tones, but how pitch discrimination differs between natural and artificial sounds is not fully understood. This study compared pitch discrimination thresholds for flat-spectrum harmonic complex tones with those for natural sounds played by musical instruments of three different timbres (violin, trumpet, and flute). To investigate whether natural familiarity with sounds of particular timbres affects pitch discrimination thresholds, this study recruited non-musicians and musicians who were trained on one of the three instruments. We found that flautists and trumpeters could discriminate smaller differences in pitch for artificial flat-spectrum tones, despite their unfamiliar timbre, than for sounds played by musical instruments, which are regularly heard in everyday life (particularly by musicians who play those instruments). Furthermore, thresholds were no better for the instrument a musician was trained to play than for other instruments, suggesting that even extensive experience listening to and producing sounds of particular timbres does not reliably improve pitch discrimination thresholds for those timbres. The results show that timbre familiarity provides minimal improvements to auditory acuity, and physical acoustics (e.g., the presence of equal-amplitude harmonics) determine pitch discrimination thresholds more than does experience with natural sounds and timbre-specific training.

Medical and surgical management of pancreatic fluid accumulations in dogs: A retrospective study of 15 cases.

BACKGROUND: Limited data exist on the diagnosis and successful medical management of suspected pancreatic abscessation, and the appropriate terminology of this condition. HYPOTHESIS/OBJECTIVES: To describe the diagnosis and management of pancreatic fluid accumulations in dogs where pancreatic fluid cytology results were available, to describe those medically and surgically managed at the same institution, and reconsider the terminology describing acute pancreatitis with pancreatic fluid accumulation. ANIMALS: Fifteen dogs treated for suspected pancreatic abscessation at a university teaching hospital between January 2010 and March 2020. METHODS: Retrospective descriptive study. RESULTS: Ultrasonographic findings described pancreatic fluid accumulations as hypoechoic in 10/15 and anechoic in 2/15 cases, ranging between 1.6 and 7 cm in diameter (median, 3.5 cm). No complications were documented after ultrasound guided fine-needle aspiration. Cytologically, all samples revealed a predominantly neutrophilic inflammation. 11/15 samples yielded a negative culture (9/11 received antimicrobials before sampling) and in 4 cases culture was positive. 7/15 were initially managed surgically including all 4 infected cases. 4/7 surgically managed cases were discharged, including 2 infected cases. The remaining 3/7 surgically managed cases were euthanized due poor quality of life. 8/15 cases were managed medically; 7/8 were discharged, 1 died. 3/7 then represented, and underwent successful surgical intervention after recrudescence of clinical signs, and all were discharged. The remaining 4 medically managed cases did not require further therapeutic intervention, with no clinical deterioration on reassessment. CONCLUSIONS AND CLINICAL IMPORTANCE: Medical management is a viable treatment option for some dogs with pancreatic fluid accumulation, or as a prequel to surgical management. Subclassifications of pancreatic fluid accumulations using diagnostic findings could enable more tailored management approaches and accurate prognostication.

Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma.

INTRODUCTION: Recurrent glioblastoma (rGBM) prognosis is dismal. In the absence of effective adjuvant treatments for rGBM, re-resections remain prominent in our arsenal. This study evaluates the impact of reoperation on post-progression survival (PPS) considering rGBM genetic makeup. METHODS: To assess the genetic heterogeneity and treatment-related changes (TRC) roles in re-operated or medically managed rGBMs, we compiled demographic, clinical, histopathological, and next-generation genetic sequencing (NGS) characteristics of these tumors from 01/2005 to 10/2019. Survival data and reoperation were analyzed using conventional and random survival forest analysis (RSF). RESULTS: Patients harboring CDKN2A/B loss (p = 0.017) and KDR mutations (p = 0.031) had notably shorter survival. Reoperation or bevacizumab were associated with longer PPS (11.2 vs. 7.4-months, p = 0.006; 13.1 vs 6.2, p < 0.001). Reoperated patients were younger, had better performance status and greater initial resection. In 136/273 (49%) rGBMs undergoing re-operation, CDKN2A/B loss (p = 0.03) and KDR mutations (p = 0.02) were associated with shorter survival. In IDH-WT rGBMs with NGS data (n = 166), reoperation resulted in 7.0-month longer survival (p = 0.004) than those managed medically. This reoperation benefit was independently identified by RSF analysis. Stratification analysis revealed that EGFR-mutant, CDKN2A/B-mutant, NF1-WT, and TP53-WT rGBM IDH-WT subgroups benefit most from reoperation (p = 0.03). Lastly, whether or not TRC was prominent at re-operation does not have any significant impact on PPS (10.5 vs. 11.5-months, p = 0.77). CONCLUSIONS: Maximal safe re-resection significantly lengthens PPS regardless of genetic makeup, but reoperations are especially beneficial for IDH-WT rGBMs with EGFR and CDKN2A/B mutations with TP53-WT, and NF1-WT. Histopathology at recurrence may be an imperfect gauge of disease severity at progression and the imaging progression may be more reflective of the prognosis.

Active inference, selective attention, and the cocktail party problem.

In this paper, we introduce a new generative model for an active inference account of preparatory and selective attention, in the context of a classic 'cocktail party' paradigm. In this setup, pairs of words are presented simultaneously to the left and right ears and an instructive spatial cue directs attention to the left or right. We use this generative model to test competing hypotheses about the way that human listeners direct preparatory and selective attention. We show that assigning low precision to words at attended-relative to unattended-locations can explain why a listener reports words from a competing sentence. Under this model, temporal changes in sensory precision were not needed to account for faster reaction times with longer cue-target intervals, but were necessary to explain ramping effects on event-related potentials (ERPs)-resembling the contingent negative variation (CNV)-during the preparatory interval. These simulations reveal that different processes are likely to underlie the improvement in reaction times and the ramping of ERPs that are associated with spatial cueing.

Musicianship and melodic predictability enhance neural gain in auditory cortex during pitch deviance detection.

When listening to music, pitch deviations are more salient and elicit stronger prediction error responses when the melodic context is predictable and when the listener is a musician. Yet, the neuronal dynamics and changes in connectivity underlying such effects remain unclear. Here, we employed dynamic causal modeling (DCM) to investigate whether the magnetic mismatch negativity response (MMNm)-and its modulation by context predictability and musical expertise-are associated with enhanced neural gain of auditory areas, as a plausible mechanism for encoding precision-weighted prediction errors. Using Bayesian model comparison, we asked whether models with intrinsic connections within primary auditory cortex (A1) and superior temporal gyrus (STG)-typically related to gain control-or extrinsic connections between A1 and STG-typically related to propagation of prediction and error signals-better explained magnetoencephalography responses. We found that, compared to regular sounds, out-of-tune pitch deviations were associated with lower intrinsic (inhibitory) connectivity in A1 and STG, and lower backward (inhibitory) connectivity from STG to A1, consistent with disinhibition and enhanced neural gain in these auditory areas. More predictable melodies were associated with disinhibition in right A1, while musicianship was associated with disinhibition in left A1 and reduced connectivity from STG to left A1. These results indicate that musicianship and melodic predictability, as well as pitch deviations themselves, enhance neural gain in auditory cortex during deviance detection. Our findings are consistent with predictive processing theories suggesting that precise and informative error signals are selected by the brain for subsequent hierarchical processing.

How Long Does It Take for a Voice to Become Familiar? Speech Intelligibility and Voice Recognition Are Differentially Sensitive to Voice Training.

When people listen to speech in noisy places, they can understand more words spoken by someone familiar, such as a friend or partner, than someone unfamiliar. Yet we know little about how voice familiarity develops over time. We exposed participants (N = 50) to three voices for different lengths of time (speaking 88, 166, or 478 sentences during familiarization and training). These previously heard voices were recognizable and more intelligible when presented with a competing talker than novel voices-even the voice previously heard for the shortest duration. However, recognition and intelligibility improved at different rates with longer exposures. Whereas recognition was similar for all previously heard voices, intelligibility was best for the voice that had been heard most extensively. The speech-intelligibility benefit for the most extensively heard voice (10%-15%) is as large as that reported for voices that are naturally very familiar (friends and spouses)-demonstrating that the intelligibility of a voice can be improved substantially after only an hour of training.

Speech-evoked brain activity is more robust to competing speech when it is spoken by someone familiar.

When speech is masked by competing sound, people are better at understanding what is said if the talker is familiar compared to unfamiliar. The benefit is robust, but how does processing of familiar voices facilitate intelligibility? We combined high-resolution fMRI with representational similarity analysis to quantify the difference in distributed activity between clear and masked speech. We demonstrate that brain representations of spoken sentences are less affected by a competing sentence when they are spoken by a friend or partner than by someone unfamiliar-effectively, showing a cortical signal-to-noise ratio (SNR) enhancement for familiar voices. This effect correlated with the familiar-voice intelligibility benefit. We functionally parcellated auditory cortex, and found that the most prominent familiar-voice advantage was manifest along the posterior superior and middle temporal gyri. Overall, our results demonstrate that experience-driven improvements in intelligibility are associated with enhanced multivariate pattern activity in posterior temporal cortex.