Controlling Chaos: Periodic Defect Braiding in Active Nematics Confined to a Cardioid.

This work examines self-mixing in active nematics, a class of fluids in which mobile topological defects drive chaotic flows in a system comprised of biological filaments and molecular motors. We present experiments that demonstrate how geometrical confinement can influence the braiding dynamics of the defects. Notably, we show that confinement in cardioid-shaped wells leads to realization of the golden braid, a maximally efficient mixing state of exactly three defects with no defect creation or annihilation. We characterize the golden braid state using different measures of topological entropy and the Lyapunov exponent. In particular, topological entropy measured from the stretching rate of material lines agrees well with an analytical computation from braid theory. Increasing the size of the confining cardioid produces a transition from the golden braid, to the fully chaotic active turbulent state.

The speed of sight: Individual variation in critical flicker fusion thresholds.

The critical flicker fusion threshold is a psychophysical measure commonly used to quantify visual temporal resolution; the fastest rate at which a visual system can discriminate visual signals. Critical flicker fusion thresholds vary substantially among species, reflecting different ecological niches and demands. However, it is unclear how much variation exists in flicker fusion thresholds between healthy individuals of the same species, or how stable this attribute is over time within individuals. In this study, we assessed both inter- and intra-individual variation in critical flicker fusion thresholds in a cohort of healthy human participants within a specific age range, using two common psychophysical methods and three different measurements during each session. The resulting thresholds for each method were highly correlated. We found a between-participant maximum difference of roughly 30 Hz in flicker fusion thresholds and we estimated a 95% prediction interval of 21 Hz. We used random-effects models to compare between- and within-participant variance and found that approximately 80% of variance was due to between-individual differences, and about 10% of the variance originated from within-individual differences over three sessions. Within-individual thresholds did not differ significantly between the three sessions in males, but did in females (P<0.001 for two methods and P<0.05 for one method), indicating that critical flicker fusion thresholds may be more variable in females than in males.

Maximally mixing active nematics.

Active nematics are an important new paradigm in soft condensed matter systems. They consist of rodlike components with an internal driving force pushing them out of equilibrium. The resulting fluid motion exhibits chaotic advection, in which a small patch of fluid is stretched exponentially in length. Using simulation, this paper shows that this system can exhibit stable periodic motion when confined to a sufficiently small square with periodic boundary conditions. Moreover, employing tools from braid theory, we show that this motion is maximally mixing, in that it optimizes the (dimensionless) "topological entropy"-the exponential stretching rate of a material line advected by the fluid. That is, this periodic motion of the defects, counterintuitively, produces more chaotic mixing than chaotic motion of the defects. We also explore the stability of the periodic state. Importantly, we show how to stabilize this orbit into a larger periodic tiling, a critical necessity for it to be seen in future experiments.

Variability in Neural Circuit Formation.

The study of neural development is usually concerned with the question of how nervous systems get put together. Variation in these processes is usually of interest as a means of revealing these normative mechanisms. However, variation itself can be an object of study and is of interest from multiple angles. First, the nature of variation in both the processes and the outcomes of neural development is relevant to our understanding of how these processes and outcomes are encoded in the genome. Second, variation in the wiring of the brain in humans may underlie variation in all kinds of psychological and behavioral traits, as well as neurodevelopmental disorders. And third, genetic variation that affects circuit development provides the raw material for evolutionary change. Here, I examine these different aspects of variation in circuit development and consider what they may tell us about these larger questions.

Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases.

Protein-truncating variants (PTVs) near the 3' end of genes may escape nonsense-mediated decay (NMD). PTVs in the NMD-escape region (PTVescs) can cause Mendelian disease but are difficult to interpret given their varying impact on protein function. Previously, PTVesc burden was assessed in an epilepsy cohort, but no large-scale analysis has systematically evaluated these variants in rare disease. We performed a retrospective analysis of 29,031 neurodevelopmental disorder (NDD) parent-offspring trios referred for clinical exome sequencing to identify PTVesc de novo mutations (DNMs). We identified 1,376 PTVesc DNMs and 133 genes that were significantly enriched (binomial p < 0.001). The PTVesc-enriched genes included those with PTVescs previously described to cause dominant Mendelian disease (e.g., SEMA6B, PPM1D, and DAGLA). We annotated ClinVar variants for PTVescs and identified 948 genes with at least one high-confidence pathogenic variant. Twenty-two known Mendelian PTVesc-enriched genes had no prior evidence of PTVesc-associated disease. We found 22 additional PTVesc-enriched genes that are not well established to be associated with Mendelian disease, several of which showed phenotypic similarity between individuals harboring PTVesc variants in the same gene. Four individuals with PTVesc mutations in RAB1A had similar phenotypes including NDD and spasticity. PTVesc mutations in IRF2BP1 were found in two individuals who each had severe immunodeficiency manifesting in NDD. Three individuals with PTVesc mutations in LDB1 all had NDD and multiple congenital anomalies. Using a large-scale, systematic analysis of DNMs, we extend the mutation spectrum for known Mendelian disease-associated genes and identify potentially novel disease-associated genes.

Management of penetrating thoracic wounds from a dog attack in a Nigerian dwarf goat: A case report.

Pet goat ownership has gradually increased in popularity and veterinarians are expected to provide gold-standard treatments for these animals. As in small-animal practice, decision-making regarding thoracic bite injuries is challenging because of the variability in clinical, radiographic, and surgical findings. Mortality rates from dog bite wounds in small animals range between 15.3 and 17.7%, and these cases represent 10% of all traumatic injuries referred to an emergency service; such information is not available regarding pet goats. The aim of this report is to describe a thoracic dog bite wound in a goat. It details the clinical, radiographic, and surgical findings and the repair, and reports the successful outcome, all to provide information to small-ruminant practitioners for treatment or referral. Future retrospective studies will help to determine prognostic factors for outcomes in goats with thoracic dog bite wounds. Key clinical message: Thoracic bite wounds are a challenge to manage, considering the potential severe underlying pathology and the absence of clear external injuries or clinical signs. Referring veterinarians and owners should be advised that goats with the presence of flail chest, pneumothorax, or rib fractures may require a higher level of intervention.

Prise en charge des plaies thoraciques pénétrantes consécutives à une attaque de chien chez une chèvre naine nigériane : rapport de cas. La possession de chèvres de compagnie a progressivement gagné en popularité et les vétérinaires devraient fournir des traitements de référence pour ces animaux. Tout comme dans la pratique des petits animaux, la prise de décision concernant les morsures thoraciques est difficile en raison de la variabilité des résultats cliniques, radiographiques et chirurgicaux. Les taux de mortalité par morsure de chien chez les petits animaux varient entre 15,3 et 17,7 %, et ces cas représentent 10 % de toutes les blessures traumatiques référées à un service d'urgence; ces informations ne sont pas disponibles concernant les chèvres de compagnie. Le but de ce rapport est de décrire une morsure thoracique de chien chez une chèvre. Il détaille les résultats cliniques, radiographiques et chirurgicaux ainsi que la réparation, et rend compte du résultat positif, le tout dans le but de fournir des informations aux praticiens des petits ruminants pour un traitement ou une référence. De futures études rétrospectives aideront à déterminer les facteurs pronostiques des résultats chez les chèvres présentant des morsures thoraciques de chien.Message clinique clé :Les morsures thoraciques sont un défi à gérer, compte tenu de la pathologie sous-jacente potentiellement grave et de l'absence de blessures externes ou de signes cliniques évidents. Les vétérinaires référents et les propriétaires doivent être informés que les chèvres présentant un volet thoracique, un pneumothorax ou des fractures des côtes peuvent nécessiter un niveau d'intervention plus élevé.(Traduit par Dr Serge Messier).

Noninvasive diagnosis of secondary infections in COVID-19 by sequencing of plasma microbial cell-free DNA.

Secondary infection (SI) diagnosis in severe COVID-19 remains challenging. We correlated metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) with clinical SI assessment, immune response, and outcomes. We classified 42 COVID-19 inpatients as microbiologically confirmed-SI (Micro-SI, n = 8), clinically diagnosed-SI (Clinical-SI, n = 13, i.e., empiric antimicrobials), or no-clinical-suspicion-for-SI (No-Suspected-SI, n = 21). McfDNA-Seq was successful in 73% of samples. McfDNA detection was higher in Micro-SI (94%) compared to Clinical-SI (57%, p = 0.03), and unexpectedly high in No-Suspected-SI (83%), similar to Micro-SI. We detected culture-concordant mcfDNA species in 81% of Micro-SI samples. McfDNA correlated with LRT 16S rRNA bacterial burden (r = 0.74, p = 0.02), and biomarkers (white blood cell count, IL-6, IL-8, SPD, all p < 0.05). McfDNA levels were predictive of worse 90-day survival (hazard ratio 1.30 [1.02-1.64] for each log10 mcfDNA, p = 0.03). High mcfDNA levels in COVID-19 patients without clinical SI suspicion may suggest SI under-diagnosis. McfDNA-Seq offers a non-invasive diagnostic tool for pathogen identification, with prognostic value on clinical outcomes.

Identification and characterization of protein interactions with the major Niemann-Pick type C disease protein in yeast reveals pathways of therapeutic potential.

Niemann-Pick type C (NP-C) disease is a rare lysosomal storage disease caused by mutations in NPC1 (95% cases) or NPC2 (5% cases). These proteins function together in cholesterol egress from the lysosome, whereby upon mutation, cholesterol and other lipids accumulate causing major pathologies. However, it is not fully understood how cholesterol is transported from NPC1 residing at the lysosomal membrane to the endoplasmic reticulum (ER) and plasma membrane. The yeast ortholog of NPC1, Niemann-Pick type C-related protein-1 (Ncr1), functions similarly to NPC1; when transfected into a mammalian cell lacking NPC1, Ncr1 rescues the diagnostic hallmarks of cholesterol and sphingolipid accumulation. Here, we aimed to identify and characterize protein-protein interactions (PPIs) with the yeast Ncr1 protein. A genome-wide split-ubiquitin membrane yeast two-hybrid (MYTH) protein interaction screen identified 11 ER membrane-localized, full-length proteins interacting with Ncr1 at the lysosomal/vacuolar membrane. These highlight the importance of ER-vacuole membrane interface and include PPIs with the Cyb5/Cbr1 electron transfer system, the ceramide synthase complex, and the Sec61/Sbh1 protein translocation complex. These PPIs were not detected in a sterol auxotrophy condition and thus depend on normal sterol metabolism. To provide biological context for the Ncr1-Cyb5 PPI, a yeast strain lacking this PPI (via gene deletions) exhibited altered levels of sterols and sphingolipids including increased levels of glucosylceramide that mimic NP-C disease. Overall, the results herein provide new physical and genetic interaction models to further use the yeast model of NP-C disease to better understand human NP-C disease.

Development and Narrow Validation of Computer Vision Approach to Facilitate Assessment of Change in Pigmented Cutaneous Lesions.

The documentation of the change in the number and appearance of pigmented cutaneous lesions over time is critical to the early detection of skin cancers and may provide preliminary signals of efficacy in early-phase therapeutic prevention trials for melanoma. Despite substantial progress in computer-aided diagnosis of melanoma, automated methods to assess the evolution of lesions are relatively undeveloped. This report describes the development and narrow validation of mathematical algorithms to register nevi between sequential digital photographs of large areas of skin and to align images for improved detection and quantification of changes. Serial posterior truncal photographs from a pre-existing database were processed and analyzed by the software, and the results were evaluated by a panel of clinicians using a separate Extensible Markup Language‒based application. The software had a high sensitivity for the detection of cutaneous lesions as small as 2 mm. The software registered lesions accurately, with occasional errors at the edges of the images. In one pilot study with 17 patients, the use of the software enabled clinicians to identify new and/or enlarged lesions in 3‒11 additional patients versus the unregistered images. Automated quantification of size change performed similarly to that of human raters. These results support the further development and broader validation of this technique.

Inter-rater reliability and prognostic value of baseline Radiographic Assessment of Lung Edema (RALE) scores in observational cohort studies of inpatients with COVID-19.

OBJECTIVES: To reliably quantify the radiographic severity of COVID-19 pneumonia with the Radiographic Assessment of Lung Edema (RALE) score on clinical chest X-rays among inpatients and examine the prognostic value of baseline RALE scores on COVID-19 clinical outcomes. SETTING: Hospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems. PARTICIPANTS: 425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set. PRIMARY AND SECONDARY OUTCOMES: We measured inter-rater reliability for RALE score annotations by different reviewers and examined for associations of consensus RALE scores with the level of respiratory support, demographics, physiologic variables, applied therapies, plasma host-response biomarkers, SARS-CoV-2 RNA load and clinical outcomes. RESULTS: Inter-rater agreement for RALE scores improved from fair to excellent following reviewer training and feedback (intraclass correlation coefficient of 0.85 vs 0.93, respectively). In the discovery cohort, the required level of respiratory support at the time of CXR acquisition (supplemental oxygen or non-invasive ventilation (n=178); invasive-mechanical ventilation (n=234), extracorporeal membrane oxygenation (n=13)) was significantly associated with RALE scores (median (IQR): 20.0 (14.1-26.7), 26.0 (20.5-34.0) and 44.5 (34.5-48.0), respectively, p<0.0001). Among invasively ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, soluble receptor of advanced glycation end-products and soluble tumour necrosis factor receptor 1 (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted HR 1.04 (1.02-1.07), p=0.002). We replicated the significant associations of RALE scores with baseline disease severity and mortality in the independent validation data set. CONCLUSIONS: With a reproducible method to measure radiographic severity in COVID-19, we found significant associations with clinical and physiologic severity, host inflammation and clinical outcomes. The incorporation of radiographic severity assessments in clinical decision-making may provide important guidance for prognostication and treatment allocation in COVID-19.

Effect of a Biopsychosocial Intervention or Postural Therapy on Disability and Health Care Spending Among Patients With Acute and Subacute Spine Pain: The SPINE CARE Randomized Clinical Trial.

Importance: Low back and neck pain are often self-limited, but health care spending remains high. Objective: To evaluate the effects of 2 interventions that emphasize noninvasive care for spine pain. Design, Setting, and Participants: Pragmatic, cluster, randomized clinical trial conducted at 33 centers in the US that enrolled 2971 participants with neck or back pain of 3 months' duration or less (enrollment, June 2017 to March 2020; final follow-up, March 2021). Interventions: Participants were randomized at the clinic-level to (1) usual care (n = 992); (2) a risk-stratified, multidisciplinary intervention (the identify, coordinate, and enhance [ICE] care model that combines physical therapy, health coach counseling, and consultation from a specialist in pain medicine or rehabilitation) (n = 829); or (3) individualized postural therapy (IPT), a postural therapy approach that combines physical therapy with building self-efficacy and self-management (n = 1150). Main Outcomes and Measures: The primary outcomes were change in Oswestry Disability Index (ODI) score at 3 months (range, 0 [best] to 100 [worst]; minimal clinically important difference, 6) and spine-related health care spending at 1 year. A 2-sided significance threshold of .025 was used to define statistical significance. Results: Among 2971 participants randomized (mean age, 51.7 years; 1792 women [60.3%]), 2733 (92%) finished the trial. Between baseline and 3-month follow-up, mean ODI scores changed from 31.2 to 15.4 for ICE, from 29.3 to 15.4 for IPT, and from 28.9 to 19.5 for usual care. At 3-month follow-up, absolute differences compared with usual care were -5.8 (95% CI, -7.7 to -3.9; P < .001) for ICE and -4.3 (95% CI, -5.9 to -2.6; P < .001) for IPT. Mean 12-month spending was $1448, $2528, and $1587 in the ICE, IPT, and usual care groups, respectively. Differences in spending compared with usual care were -$139 (risk ratio, 0.93 [95% CI, 0.87 to 0.997]; P = .04) for ICE and $941 (risk ratio, 1.40 [95% CI, 1.35 to 1.45]; P < .001) for IPT. Conclusions and Relevance: Among patients with acute or subacute spine pain, a multidisciplinary biopsychosocial intervention or an individualized postural therapy intervention, each compared with usual care, resulted in small but statistically significant reductions in pain-related disability at 3 months. However, compared with usual care, the biopsychosocial intervention resulted in no significant difference in spine-related health care spending and the postural therapy intervention resulted in significantly greater spine-related health care spending at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT03083886.

Real-Time Scene Monitoring for Deaf-Blind People.

It is estimated that at least 15 million people worldwide live with severe deaf-blindness, with many more experiencing varying degrees of deaf-blindness. The existing options of assistance are mostly limited to walking canes, guide dogs and human care. We propose a wearable device which harnesses a multi-antenna mmWave radar transceiver and a haptic feedback array for real time detection of a person moving within a scene. We present our findings from a series of workshops with participants classed with multi-sensory impairments (MSI), to demonstrate the relative success of this approach and its potential for integration into existing assistance for the MSI of the future.

Developmental noise is an overlooked contributor to innate variation in psychological traits.

Stochastic developmental variation is an additional important source of variance - beyond genes and environment - that should be included in considering how our innate psychological predispositions may interact with environment and experience, in a culture-dependent manner, to ultimately shape patterns of human behaviour.

Radiographic Assessment of Lung Edema (RALE) Scores are Highly Reproducible and Prognostic of Clinical Outcomes for Inpatients with COVID-19.

INTRODUCTION: Chest imaging is necessary for diagnosis of COVID-19 pneumonia, but current risk stratification tools do not consider radiographic severity. We quantified radiographic heterogeneity among inpatients with COVID-19 with the Radiographic Assessment of Lung Edema (RALE) score on Chest X-rays (CXRs). METHODS: We performed independent RALE scoring by ≥2 reviewers on baseline CXRs from 425 inpatients with COVID-19 (discovery dataset), we recorded clinical variables and outcomes, and measured plasma host-response biomarkers and SARS-CoV-2 RNA load from subjects with available biospecimens. RESULTS: We found excellent inter-rater agreement for RALE scores (intraclass correlation co-efficient=0.93). The required level of respiratory support at the time of baseline CXRs (supplemental oxygen or non-invasive ventilation [n=178]; invasive-mechanical ventilation [n=234], extracorporeal membrane oxygenation [n=13]) was significantly associated with RALE scores (median [interquartile range]: 20.0[14.1-26.7], 26.0[20.5-34.0] and 44.5[34.5-48.0], respectively, p<0.0001). Among invasively-ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, sRAGE and TNFR1 levels (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.04[1.02-1.07], p=0.002). We validated significant associations of RALE scores with baseline severity and mortality in an independent dataset of 415 COVID-19 inpatients. CONCLUSION: Reproducible assessment of radiographic severity revealed significant associations with clinical and physiologic severity, host-response biomarkers and clinical outcome in COVID-19 pneumonia. Incorporation of radiographic severity assessments may provide prognostic and treatment allocation guidance in patients hospitalized with COVID-19.

Naturalising Agent Causation.

The idea of agent causation-that a system such as a living organism can be a cause of things in the world-is often seen as mysterious and deemed to be at odds with the physicalist thesis that is now commonly embraced in science and philosophy. Instead, the causal power of organisms is attributed to mechanistic components within the system or derived from the causal activity at the lowest level of physical description. In either case, the 'agent' itself (i.e., the system as a whole) is left out of the picture entirely, and agent causation is explained away. We argue that this is not the right way to think about causation in biology or in systems more generally. We present a framework of eight criteria that we argue, collectively, describe a system that overcomes the challenges concerning agent causality in an entirely naturalistic and non-mysterious way. They are: (1) thermodynamic autonomy, (2) persistence, (3) endogenous activity, (4) holistic integration, (5) low-level indeterminacy, (6) multiple realisability, (7) historicity, (8) agent-level normativity. Each criterion is taken to be dimensional rather than categorical, and thus we conclude with a short discussion on how researchers working on quantifying agency may use this multidimensional framework to situate and guide their research.

The effect of laparoscopy on intracranial pressure as measured by optic nerve sheath diameter: A review.

Laparoscopic surgery has many benefits over open surgery including lower complication rates, and shorter duration and lower cost of hospitalization. However, recent human literature suggests laparoscopy and carbon dioxide insufflation can result in intracranial hypertension. Invasive monitoring of intracranial pressure is not routinely performed in veterinary medicine, and ultrasonographic evaluation of the optic nerve sheath has been employed as an indirect measure of intracranial pressure in many species. The optic nerve sheath is continuous with the meninges of the brain and becomes distended with intracranial hypertension. Optic nerve sheath diameter is a reliable and consistent measure of intracranial pressure and has been utilized in humans to evaluate patients for intracranial hypertension secondary to laparoscopy and capnoperitoneum. No thorough evaluation of the effects of laparoscopy on intracranial pressure has been performed in dogs. Ultrasonographic evaluation of the optic nerve sheath is a safe, non-invasive, and inexpensive procedure that may allow for the evaluation of intracranial pressure without the need for invasive monitoring systems. As laparoscopic procedures are performed increasingly often, this review aims to inform the reader on the effects of capnoperitoneum and to facilitate appropriate patient selection, anesthetic considerations, and surgical planning.

L'effet de la laparoscopie sur la pression intracrânienne mesurée par le diamètre de la gaine du nerf optique : une revue. La chirurgie laparoscopique présente de nombreux avantages par rapport à la chirurgie ouverte, notamment des taux de complications plus faibles, une durée d'hospitalisation plus courte et un coût moindre. Cependant, la littérature humaine récente suggère que la laparoscopie et l'insufflation de dioxyde de carbone peuvent entraîner une hypertension intracrânienne. La surveillance invasive de la pression intracrânienne n'est pas systématiquement effectuée en médecine vétérinaire, et l'évaluation échographique de la gaine du nerf optique a été utilisée comme mesure indirecte de la pression intracrânienne chez de nombreuses espèces. La gaine du nerf optique est continue avec les méninges du cerveau et se distend avec l'hypertension intracrânienne. Le diamètre de la gaine du nerf optique est une mesure fiable et cohérente de la pression intracrânienne et a été utilisé chez l'homme pour évaluer les patients atteints d'hypertension intracrânienne secondaire à la laparoscopie et au capnopéritoine. Aucune évaluation approfondie des effets de la laparoscopie sur la pression intracrânienne n'a été réalisée chez le chien. L'évaluation échographique de la gaine du nerf optique est une procédure sûre, non invasive et peu coûteuse qui peut permettre l'évaluation de la pression intracrânienne sans avoir besoin de systèmes de surveillance invasifs. Les procédures laparoscopiques étant de plus en plus pratiquées, cette revue vise à informer le lecteur sur les effets du pneumopéritoine et à faciliter la sélection appropriée des patients, les considérations anesthésiques et la planification chirurgicale.(Traduit par Dr Serge Messier).

Reference intervals and values for fecal cortisol, aldosterone, and the ratio of cortisol to dehydroepiandrosterone metabolites in four species of cetaceans.

The goal of the current study was to create reference intervals and values for several common and one potential novel physiological indicators of animal welfare for four species of cetaceans. The subjects included 189 bottlenose dolphins (Tursiops truncatus), 27 Indo-Pacific bottlenose dolphins (Tursiops aduncus), eight Pacific white-sided dolphins (Lagenorhynchus obliquidens), and 13 beluga whales (Delphinapterus leucas) at Alliance of Marine Mammal Parks and Aquariums and/or Association of Zoos and Aquariums accredited facilities. During two sampling time periods between July and November of 2018 and between January and April of 2019, fecal samples were collected weekly for five weeks from all animals. Samples were processed and analyzed using enzyme immunoassay for fecal cortisol, aldosterone, and dehydroepiandrosterone (DHEA) metabolites. Linear mixed models were used to examine demographic and time factors impacting hormone metabolite concentrations. Age, sex, and time of year were all significant predictors for some of the models (p < 0.01). An iOS mobile application ZooPhysioTrak was created for easy access to species-specific reference intervals and values accounting for significant predictors. For facilities without access to this application, additional reference intervals and values were constructed without accounting for significant predictors. Information gained from this study and the use of the application can provide reference intervals and values to make informed management decisions for cetaceans in zoological facilities.

Health reference intervals and values for common bottlenose dolphins (Tursiops truncatus), Indo-Pacific bottlenose dolphins (Tursiops aduncus), Pacific white-sided dolphins (Lagenorhynchus obliquidens), and beluga whales (Delphinapterus leucas).

This study reports comprehensive clinical pathology data for hematology, serum, and plasma biochemistry reference intervals for 174 apparently healthy common bottlenose dolphins (Tursiops truncatus) and reference values for 27 Indo-Pacific bottlenose dolphins (Tursiops aduncus), 13 beluga whales (Delphinapterus leucas), and 6 Pacific white-sided dolphins (Lagenorhynchus obliquidens) in zoos and aquariums accredited by the Alliance for Marine Mammal Parks and Aquariums and the Association of Zoos & Aquariums. Blood samples were collected as part of a larger study titled "Towards understanding the welfare of cetaceans in zoos and aquariums" (colloquially called the Cetacean Welfare Study). Two blood samples were collected following a standardized protocol, and two veterinarian examinations were conducted approximately six months apart between July to November 2018 and January to April 2019. Least square means, standard deviations, and 95% confidence intervals were calculated for hematology, serum, and plasma biochemical variables. Comparisons by age, gender, and month revealed statistically significant differences (p < 0.01) for several variables. Reference intervals and values were generated for samples tested at two laboratories for up to 56 hematologic, serum, and plasma biochemical variables. To apply these data, ZooPhysioTrak, an iOS mobile software application, was developed to provide a new resource for cetacean management. ZooPhysioTrak provides species-specific reference intervals and values based on user inputs of individual demographic and sample information. These data provide a baseline from which to compare hematological, serum, and plasma biochemical values in cetaceans in zoos and aquariums.

Fractal generation in a two-dimensional active-nematic fluid.

Active fluids, composed of individual self-propelled agents, can generate complex large-scale coherent flows. A particularly important laboratory realization of such an active fluid is a system composed of microtubules, aligned in a quasi-two-dimensional (2D) nematic phase and driven by adenosine-triphosphate-fueled kinesin motor proteins. This system exhibits robust chaotic advection and gives rise to a pronounced fractal structure in the nematic contours. We characterize such experimentally derived fractals using the power spectrum and discover that the power spectrum decays as k-ß for large wavenumbers k. The parameter ß is measured for several experimental realizations. Though ß is effectively constant in time, it does vary with experimental parameters, indicating differences in the scale-free behavior of the microtubule-based active nematic. Though the fractal patterns generated in this active system are reminiscent of passively advected dye in 2D chaotic flows, the underlying mechanism for fractal generation is more subtle. We provide a simple, physically inspired mathematical model of fractal generation in this system that relies on the material being locally compressible, though the total area of the material is conserved globally. The model also requires that large-scale density variations are injected into the material periodically. The model reproduces the power-spectrum decay k-ß seen in experiments. Linearizing the model of fractal generation about the equilibrium density, we derive an analytic relationship between ß and a single dimensionless quantity r, which characterizes the compressibility.

The cumulative effects and clinical safety of repeat magnetic resonance imaging on an MRI-conditional pacemaker system at 1.5 tesla.

BACKGROUND: Studies have demonstrated magnetic resonance imaging (MRI) safety in the presence of MRI-conditional permanent pacemakers (PPM). However, since patients' care may require serial MRIs, it is necessary to evaluate device safety and performance after multiple scans. OBJECTIVES: We evaluated safety and performance of MRI-conditional PPMs after serial MRIs over various anatomic regions performed during a multicenter, prospective, single-arm study (ProMRI). METHODS: ProMRI was a multiphase observational study designed to evaluate PPM performance after MRI scans. Our study evaluated PPM function in a cohort of patients who underwent multiple 1.5-T MRI scans. Selected patients underwent separate head, chest, and lumbar spine MRIs. Pacing capture threshold (PCT), lead impedance (LI), sensing amplitude, and battery capacity were collected before and after scanning. Freedom from serious adverse device effects (SADE) through 1 month post MRI served as a primary endpoint. Changes in PPM function parameters, including threshold success rate and sensing attenuation, were analyzed for statistical significance and clinical relevance. RESULTS: In 81 patients no adverse events or SADE occurred. Statistically significant changes in ventricular PCT (0.034 ± 0.15 V) immediately after, ventricular LI immediately after (-18.7 ± 44.2 Ω) and 1 month post phase B (-19.8 ± 44.9 Ω), and atrial sensing attenuation immediately after (-0.27 ± 0.92 mV) and 1 month post phase B (-0.22 ± 0.92 mV) were noted. However, these changes were not clinically relevant in degree. CONCLUSION: These results demonstrate the safety and performance of the ProMRI PPM in patients undergoing 3 serial MRIs over various anatomic regions.