Pediatric tympanostomy tube assessment via deep learning.

PURPOSE: Tympanostomy tube (TT) placement is the most frequently performed ambulatory surgery in children under 15. After the procedure it is recommended that patients follow up regularly for "tube checks" until TT extrusion. Such visits incur direct and indirect costs to families in the form of days off from work, copays, and travel expenses. This pilot study aims to compare the efficacy of tympanic membrane (TM) evaluation by an artificial intelligence algorithm with that of clinical staff for determining presence or absence of a tympanostomy tube within the TM. METHODS: Using a digital otoscope, we performed a prospective study in children (ages 10 months-10 years) with a history of TTs who were being seen for follow up in a pediatric otolaryngology clinic. A smartphone otoscope was used by study personnel who were not physicians to take ear exam images, then through conventional otoscopic exam, ears were assessed by a clinician for tubes being in place or tubes having extruded from the TM. We trained and tested a deep learning (artificial intelligence) algorithm to assess the images and compared that with the clinician's assessment. RESULTS: A total of 123 images were obtained from 28 subjects. The algorithm classified images as TM with or without tube in place. Overall classification accuracy was 97.7 %. Recall and precision were 100 % and 96 %, respectively, for TM without a tube present, and 95 % and 100 %, respectively, for TM with a tube in place. DISCUSSION: This is a promising deep learning algorithm for classifying ear tube presence in the TM utilizing images obtained in awake children using an over-the-counter otoscope available to the lay population. We are continuing enrollment, with the goal of building an algorithm to assess tube patency and extrusion.

High-content phenotypic screening identifies novel chemistries that disrupt mosquito activity and development.

New classes of chemistries are needed to control insecticide resistant populations of mosquitoes and prevent transmission of vector-borne diseases (VBDs). Organismal screens of chemical collections have played an important role in the search for new vector insecticides and the identification of active ingredients (AIs) that cause rapid mortality of mosquitoes. Advances in image-based screening offer an opportunity to identify chemistries that operate via novel biochemical modes and investigate the range of phenotypes exhibited by mosquitoes following exposure to lethal and sub-lethal chemical dose. An automated, high throughput phenotypic screen (HTS) employing high-content imaging of first instar (L1) Aedes aegypti larvae was developed to identify chemistries associated with mortality and atypical morphological phenotypes. A pilot screen of the Library of Pharmacologically Active Compounds (LOPAC1280) identified 92 chemistries that disrupted larval activity and development, including conventional insecticides and chemistries known to modulate G protein-coupled receptors (GPCRs) and other molecular targets in mammalian systems. Secondary assay series were used to evaluate a selection of chemistries for impacts on mosquito activity, survival and development. Ritodrine hydrochloride reduced mobility of larvae but had no observable effect on survival and development of mosquitoes. High doses of metergoline suppressed larval activity and sub-lethal dose resulted in pupal mortality. Assay data support the utility of phenotypic screening and diverse entomological end-points for discovery of novel insecticidal chemical scaffolds. The insecticide discovery process must consider how multi-modal efficacy spectra contribute to vector and VBD control.

Internal Delensing of Cosmic Microwave Background Polarization B-Modes with the POLARBEAR Experiment.

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

The Simons Observatory: Cryogenic half wave plate rotation mechanism for the small aperture telescopes.

We present the requirements, design, and evaluation of the cryogenic continuously rotating half-wave plate (CHWP) for the Simons Observatory (SO). SO is a cosmic microwave background polarization experiment at Parque Astronómico de Atacama in northern Chile that covers a wide range of angular scales using both small (⌀0.42 m) and large (⌀6 m) aperture telescopes. In particular, the small aperture telescopes (SATs) focus on large angular scales for primordial B-mode polarization. To this end, the SATs employ a CHWP to modulate the polarization of the incident light at 8 Hz, suppressing atmospheric 1/f noise and mitigating systematic uncertainties that would otherwise arise due to the differential response of detectors sensitive to orthogonal polarizations. The CHWP consists of a 505 mm diameter achromatic sapphire HWP and a cryogenic rotation mechanism, both of which are cooled down to ∼50 K to reduce detector thermal loading. Under normal operation, the HWP is suspended by a superconducting magnetic bearing and rotates with a constant 2 Hz frequency, controlled by an electromagnetic synchronous motor. We find that the number of superconductors and the number of magnets that make up the superconducting magnetic bearing are important design parameters, especially for the rotation mechanism's vibration performance. The rotation angle is detected through an angular encoder with a noise level of 0.07 µrad s. During a cooldown process, the rotor is held in place by a grip-and-release mechanism that serves as both an alignment device and a thermal path. In this paper, we provide an overview of the SO SAT CHWP: its requirements, hardware design, and laboratory performance.

Extension MRI is clinically useful in cervical myelopathy.

INTRODUCTION: Cervical spine MRI with the neck in extension has been well described over the last 10 years, but its clinical value remains unknown. METHODS: We performed extension imaging in 60 patients in whom the initial neutral study showed borderline cord compression. Images were assessed using a previously validated grading system for cord compression. Multiple linear and area measurements were also obtained. Images were scored blindly and randomly. Inter- and intra-rater variability were determined in a subset of 20 cases. Independent clinical assessment utilised the Ranwat criteria. RESULTS: For most parameters inter/intra-observer variance of kappa/ICC > 0.6 was highly satisfactory. Standard MR was poor at discriminating between patients with and without myelopathy (ROC analysis, area under the curve (AUC), 0.52). This was considerably improved with extension imaging (AUC, 0.60), or by using the change in compression score between neutral and extension studies. Most measurements were not helpful; however, the ratio of cord area/CSF area at the level of maximum compression on extended images was the best discriminator (AUC, 0.71), as well as the presence of T2 change in cord substance (AUC, 0.68). CONCLUSION: This is the first study to demonstrate added clinical value utilising extension MRI. In this cohort of difficult patients, when there was no T2 signal change in the cord, the presence of clinical myelopathy could only be predicted by utilising the data from extension imaging.

Effect of puffing intensity on cigarette smoke yields.

Two US blend style cigarette products, one ventilated, were smoked under 16 smoking regimes. 'Tar', nicotine, carbon monoxide (TNCO) and water smoke yields determined with these regimes, are shown to form part of continuous functions linked with puffing intensity (the product of puff volume and puff frequency) and total puff volume (the product of puff volume and puff number). This allows the prediction of yields for any regime and leads to the conclusion that the characterisation of cigarette products with these analytes is achievable from using a single smoking regime. The rate of increase of TNCO yields decreases as the puffing intensity increases, due to the more rapid burning of the tobacco available for smoking, although (particulate phase) water yield, relative to TNCO, increases considerably with intensity. Total puff volume is linearly related to TNCO machine yields from a range of regimes, to duplicated human yields and to the nicotine and solanesol retained in spent filters. The concentration of these smoke components is essentially independent of the regime used to generate them. This is not the case with water for which the yield in smoke increases exponentially with the total puff volume and its concentration increases rapidly with intensity.

Evaluation of the therapeutic benefit of delayed administration of erythropoietin following early hypoxic-ischemic injury in rodents.

Hypoxia-ischemia (HI) and associated brain injuries are seen in premature as well as term infants with birth complications. The resulting impairments involve deficits in many cognitive domains, including language development. Poor rapid auditory processing is hypothesized to be one possible underlying factor leading to subsequent language delays. Mild hypothermia treatment for HI injuries in term infants is widely used as an intervention but can be costly and time consuming. Data suggest that the effectiveness of hypothermia treatment following HI injury declines beyond 6 h following injury. Consequently, the availability of a therapeutic alternative without these limitations could allow doctors to treat HI-injured infants more effectively and thus reduce deleterious cognitive and language outcomes. Evidence from both human studies and animal models of neonatal HI suggests that erythropoietin (Epo), an endogenous cytokine hormone, may be a therapeutic agent that can ameliorate HI brain injury and preserve subsequent cognitive development and function. The current study sought to investigate the therapeutic effectiveness of Epo when administered immediately after HI injury, or delayed at intervals following the injury, in neonatal rodents. Rat pups received an induced HI injury on postnatal day 7, followed by an intraperitoneal injection of Epo (1,000 U/kg) immediately, 60 min, or 180 min following induction of injury. Subjects were tested on rapid auditory processing tasks in juvenile (P38-42) and adult periods (P80-85). Ventricular and cortical size was also measured from post mortem tissue. Results from the current study show a therapeutic benefit of Epo when given immediately following induction of HI injury, with diminished benefit from a 60-min-delayed injection of Epo and no protection following a 180-min-delayed injection. The current data thus show that the effectiveness of a single dose of Epo in ameliorating auditory processing deficits following HI injury decreases precipitously as treatment is delayed following injury. These data may have important implications for experimental human neonatal intervention with Epo.

Inhibition of X-linked inhibitor of apoptosis with embelin differentially affects male versus female behavioral outcome following neonatal hypoxia-ischemia in rats.

Hypoxia-ischemia (HI; concurrent oxygen/blood deficiency) and associated encephalopathy represent a common cause of neurological injury in premature/low-birth-weight infants and term infants with birth complications. Resulting behavioral impairments include cognitive and/or sensory processing deficits, as well as language disabilities, and clinical evidence shows that male infants with HI exhibit more severe cognitive deficits compared to females with equivalent injury. Evidence also demonstrates activation of sex-dependent apoptotic pathways following HI events, with males preferentially activating a caspase-independent cascade of cell death and females preferentially activating a caspase-dependent cascade following neonatal hypoxic and/or ischemic insults. Based on these combined data, the 'female protection' following HI injury may reflect the endogenous X-linked inhibitor of apoptosis (XIAP), which effectively binds effector caspases and halts downstream cleavage of effector caspases (thus reducing cell death). To test this theory, the current study utilized neonatal injections of vehicle or embelin (a small molecule inhibitor of XIAP) in male and female rats with or without induced HI injury on postnatal day 7 (P7). Subsequent behavioral testing using a clinically relevant task revealed that the inhibition of XIAP exacerbated HI-induced persistent behavioral deficits in females, with no effect on HI males. These results support sex differences in mechanisms of cell death following early HI injuries, and suggest a potential clinical benefit from the development of sex-specific neuroprotectants for the treatment of HI.

The novel carbohydrate tumor antigen C2-O-sLe x is upregulated in canine gastric carcinomas.

Sialyl Lewis x-modified core 2 branched O-glycans (C2-O-sLe(x)) on human leukocytes mediate much higher-affinity adhesion to selectins on activated vascular endothelium than does sialyl Lewis x on other structures. In some canine and human carcinomas, high expression of sLe(x)-decorated carbohydrates has been associated with metastasis and, in humans, a poor prognosis, but detection in canine gastric carcinomas is unreported. The authors hypothesized that these carbohydrates are highly expressed in more malignant types of canine gastric carcinomas, they promote metastasis, and they are associated with a poorer prognosis for dogs. The objectives were to determine the presence and importance of C2-O-sLe(x) expression in canine gastric carcinomas. Routine histological sections of 16 canine gastric carcinomas were categorized on the basis of 3 classification schemes: World Health Organization, Lauren, and Goseki. Serial sections were stained with antibodies directed against C2-O-sLe(x) (CHO-131 monoclonal antibody), cytokeratin (Lu-5 monoclonal antibody), and stains to detect neutral and acid mucins (periodic acid-Schiff and alcian blue). Whereas normal gastric mucosal epithelial cells were negative for C2-O-sLe(x), 56% of the tumors examined were positive for C2-O-sLe(x). Importantly, the majority of more poorly differentiated tumor types had more numerous and larger intensely stained areas of C2-O-sLe(x) expression compared with moderate to well-differentiated tumor types. Signet ring-type carcinomas had markedly higher distribution and intensity of periodic acid-Schiff and alcian blue staining than did tubular carcinomas. These findings suggest that C2-O-sLe(x) is a tumor-associated antigen that may play a role in the invasiveness and metastatic potential of certain types of canine gastric carcinomas.

A cryogenic continuously rotating half-wave plate mechanism for the POLARBEAR-2b cosmic microwave background receiver.

We present the design and laboratory evaluation of a cryogenic continuously rotating half-wave plate (CHWP) for the POLARBEAR-2b (PB-2b) cosmic microwave background receiver, the second installment of the Simons Array. PB-2b will observe at 5200 m elevation in the Atacama Desert of Chile in two frequency bands centered at 90 GHz and 150 GHz. In order to suppress atmospheric 1/f noise and mitigate systematic effects that arise when differencing orthogonal detectors, PB-2b modulates linear sky polarization using a CHWP rotating at 2 Hz. The CHWP has a 440 mm clear aperture diameter and is cooled to ≈50 K in the PB-2b receiver cryostat. It consists of a low-friction superconducting magnetic bearing and a low-torque synchronous electromagnetic motor, which together dissipate <2 W. During cooldown, a grip-and-release mechanism centers the rotor to <0.5 mm, and during continuous rotation, an incremental optical encoder measures the rotor angle with a noise level of 0.1 µrad/Hz. We discuss the experimental requirements for the PB-2b CHWP, the designs of its various subsystems, and the results of its evaluation in the laboratory. The presented CHWP has been deployed to Chile and is expected to see first light on PB-2b in 2020 or 2021.

Huntite flowstone in carlsbad caverns, new Mexico.

Huntite flowstone has recently been discovered in Carlsbad Caverns. This flowstone occurs as a thin, white layer of microcrystals (approximately 1 to 60 micrometers in diameter) which appears buckled and crinkled. The huntite is believed to be precipitating directly from magnesium-rich solutions rather than forming by alteration of preexisting minerals.

Band-like intracranial calcification with simplified gyration and polymicrogyria: a distinct "pseudo-TORCH" phenotype.

The combination of intracranial calcification and polymicrogyria is usually seen in the context of intrauterine infection, most frequently due to cytomegalovirus. Rare familial occurrences have been reported. We describe five patients-two male-female sibling pairs, one pair born to consanguineous parents, and an unrelated female-with a distinct pattern of band-like intracranial calcification associated with simplified gyration and polymicrogyria. Clinical features include severe post-natal microcephaly, seizures and profound developmental arrest. Testing for infectious agents was negative. We consider that these children have the same recognizable "pseudo-TORCH" phenotype inherited as an autosomal recessive trait.

Tick genomics: the Ixodes genome project and beyond.

Ticks and mites (subphylum Chelicerata; subclass Acari) include important pests of animals and plants worldwide. The Ixodes scapularis (black-legged tick) genome sequencing project marks the beginning of the genomics era for the field of acarology. This project is the first to sequence the genome of a blood-feeding tick vector of human disease and a member of the subphylum Chelicerata. Genome projects for other species of Acari are forthcoming and their genome sequences will likely feature significantly in the future of tick research. Parasitologists interested in advancing the field of tick genomics research will be faced with specific challenges. The development of genetic tools and resources, and the size and repetitive nature of tick genomes are important considerations. Innovative approaches may be required to sequence, assemble, annotate and analyse tick genomes. Overcoming these challenges will enable scientists to investigate the genes and genome organisation of this important group of arthropods and may ultimately lead to new solutions for control of ticks and tick-borne diseases.

Morphometric analysis of atrophic changes in human lingual epithelium in iron deficiency anaemia.

A stereological analysis of epithelial structure at the lateral surface of the tongue showed that iron deficiency anaemia was associated with reduced epithelial thickness despite the absence of overt mucosal abnormalities. The epithelial atrophy was entirely due to a reduction in the size and number of cells in the maturation compartment. By contrast, the progenitor cell compartment was increased in thickness due to an increase in the number of cells. This hyperplastic reaction may be a trophic response to the overall loss of epithelium in this condition.

Ultrasound determination of the normal location of the conus medullaris in neonates.

PURPOSE: To establish the normal range of the position of the conus medullaris in neonates and determine whether it differs from that in adults. METHODS: One hundred five healthy neonates born over an 18-day period in a single obstetric unit had ultrasound examinations of their lower spines to relate the conus medullaris to the nearest intervertebral disk or midvertebral level. RESULTS: The mean position of the conus was midway between the L1-2 disk and mid-L-2 body, ranging from T-12/L-1 to L-3, with the modal position being L1-2 (47.6%). A small but significant rise in position from 33 to 42 weeks postconceptual age was identified. Comparison with data previously reported from adults showed a small but highly significant difference in conus position of approximately 0.25 vertebral levels. DISCUSSION: Our data confirm studies suggesting that ascent of the cord after birth is minor.

Affiliation motivation: people who need people ... but in different ways.

The Interpersonal Orientation Scale was developed to focus on four dimensions assumed to underlie affiliation motivation: social comparison, emotional support, positive stimulation, and attention. Factor analyses basically supported the proposed multidimensional construct. Evidence for the validity of the four dimensions was provided by their correlations with measures of constructs conceptually related to affiliation motivation and their lack of correlation with measures conceptually unrelated to affiliation motivation. Moreover, in a laboratory study, each motivational subscale tended to correlate most highly with role-played responses in a situation affording the relevant incentive type. Future research on social motivation and interaction will profit from identifying the particular incentives that are salient in a giving setting.

Does myodil introduced for ventriculography lead to symptomatic lumbar arachnoiditis?

Although there is a substantial body of evidence implicating Myodil or Pantopaque as a cause of lumbar arachnoiditis, assessment of the clinically based evidence is complicated by the additional potentially causative factors present in a high proportion of cases. These include pre-existing spinal pathology, traumatic lumbar puncture and surgery. The aim of this retrospective study was to attempt to ascertain whether Myodil introduced via ventricular catheter was associated with subsequent development of symptomatic lumbar arachnoiditis. In 222 patients in whom clinical records were reviewed there was no excess of back pain following ventriculography compared to the general population. Myodil ventriculography does not appear to be a major cause of symptomatic lumbar arachnoiditis. Several unavoidable problems with the methodology of this study are discussed.

The biochemistry of vitreous humour. A comparative study of the potassium, sodium and urate concentrations in the eyes at identical time intervals after death.

Analysis of the vitreous humour from an individual's eyes collected at the same time since death showed variation between the eyes in the concentration of potassium, sodium and/or urate. This previously unreported finding would limit the use of measuring these electrolytes in determining the time of death.

The biochemical changes in pericardial fluid after death. An investigation of the relationship between the time since death and the rise or fall in electrolyte and enzyme concentrations and their possible usefulness in determining the time of death.

This paper reports the biochemical changes that occur in pericardial fluid after death. Significant changes in relation to the time since death occurred in potassium, sodium, phosphate, protein and several commonly measured enzymes. The variation in individual results at similar times since death would limit the use of pericardial fluid biochemistry in determining the time of death.