Emerging and Novel Viruses in Passerine Birds.

There is growing interest in emerging viruses that can cause serious or lethal disease in humans and animals. The proliferation of cloacal virome studies, mainly focused on poultry and other domestic birds, reveals a wide variety of viruses, although their pathogenic significance is currently uncertain. Analysis of viruses detected in wild birds is complex and often biased towards waterfowl because of the obvious interest in avian influenza or other zoonotic viruses. Less is known about the viruses present in the order Passeriformes, which comprises approximately 60% of extant bird species. This review aims to compile the most significant contributions on the DNA/RNA viruses affecting passerines, from traditional and metagenomic studies. It highlights that most passerine species have never been sampled. Especially the RNA viruses from Flaviviridae, Orthomyxoviridae and Togaviridae are considered emerging because of increased incidence or avian mortality/morbidity, spread to new geographical areas or hosts and their zoonotic risk. Arguably poxvirus, and perhaps other virus groups, could also be considered "emerging viruses". However, many of these viruses have only recently been described in passerines using metagenomics and their role in the ecosystem is unknown. Finally, it is noteworthy that only one third of the viruses affecting passerines have been officially recognized.

Preclinical safety study of a fully implantable, sub-scalp ring electrode array for long-term EEG recordings.

OBJECTIVE: Long-term electroencephalogram (EEG) recordings can aid diagnosis and management of various neurological conditions such as epilepsy. In this study we characterize the safety and stability of a clinical grade ring electrode arrays by analyzing EEG recordings, fluoroscopy, and computed tomography (CT) imaging with long-term implantation and histopathological tissue response. APPROACH: Seven animals were chronically implanted with EEG recording array consisting of four electrode contacts. Recordings were made bilaterally using a bipolar longitudinal montage. The array was connected to a fully implantable micro-processor controlled electronic device with two low-noise differential amplifiers and a transmitter-receiver coil. An external wearable was used to power, communicate with the implant via an inductive coil, and store the data. The sub-scalp electrode arrays were made using medical grade silicone and platinum. The electrode arrays were tunneled in the subgaleal cleavage plane between the periosteum and the overlying dermis. These were implanted for 3-7 months before euthanasia and histopathological assessment. EEG and impedance were recorded throughout the study. MAIN RESULTS: Impedance measurements remained low throughout the study for 11 of 12 channels over the recording period ranged from 3 to 5 months. There was also a steady amplitude of slow-wave EEG and chewing artifact (noise). The post-mortem CT and histopathology showed the electrodes remained in the subgaleal plane in 6 of 7 sheep. There was minimal inflammation with a thin fibrotic capsule that ranged from 4 to 101µm. There was a variable fibrosis in the subgaleal plane extending from 210 to 3617µm (S3-S7) due to surgical cleavage. One sheep had an inflammatory reaction due to electrode extrusion. The passive electrode array extraction force was around 1N. SIGNIFICANCE: Results show sub-scalp electrode placement was safe and stable for long term implantation. This is advantageous for diagnosis and management of neurological conditions where long-term, EEG monitoring is required.

Critical role of chemical potential to assure effective encapsulation.

HYPOTHESIS: In emulsification-polymerisation avoiding monomer escape from emulsion droplets is the key to successful encapsulation. So far, it is believed that (1) a hydrophobe needs to be included and (2) free-micelles of surfactant need to be depleted. However, these criteria do not always work. The paper explores the critical role of the chemical potential difference between the inside and outside of the emulsion droplet for successful encapsulation. EXPERIMENTS: Crossflow membrane emulsification was used to produce uniform droplets of 1-2 µm of solutions of 3-iodoprop-2-yn-1-yl butylcarbamate (a biocide), castor oil (hydrophobe) in methyl 2-methylprop-2-enoate (monomer) into aqueous solutions with a large amount of free-micelles of surfactant. The encapsulation was followed by polymerisation. The size distribution of microcapsule from different formula were examined. FINDINGS: The biocide encapsulation depends on castor oil content: >12% (full); 6-12% (either full or partial); <6% (minor). Results show a critical molar fraction ratio of the monomer in the droplet to water in the aqueous phase that provides a definitive criterion to assure size retention and full encapsulation. This critical value corresponds to an energy barrier of 116 J/mol to prevent the monomer escaping. This finding is proposed to be used as an advanced rule to guide precision formulation for desired microencapsulation.

Not all low grade dysplasia in Barrett's oesophagus is the same: using specific histological criteria in predicting progression to neoplasia.

Barrett's oesophagus with low grade dysplasia (LGD) is a risk factor for progression to high grade dysplasia (HGD) and oesophageal adenocarcinoma (OAC); however, only a subgroup of LGD will progress. We used a combination of specific histological criteria to identify patients with LGD who are more likely to progress to HGD or OAC. LGD slides from 38 patients within the progressor group (PG) and 17 patients from the non-progressor group (NPG) were obtained and reviewed by two expert GI pathologists, to be stratified by the same four specific histological variables identified by Ten Kate et al.: loss of surface maturation, mucin depletion, nuclear enlargement, and increase of mitosis. After review of LGD slides by two expert GI pathologists, 27 suitable patients were identified. Of these 27 patients there was a higher proportion of patients from the PG with all four specific criteria reported, compared to the NPG: 14 (78%) vs 3 (33%) p=0.0394. Patients with all four specific criteria were more likely to progress compared to those who had one or less specific criteria reported (OR 7, 95% CI 1.1848-41.3585, p=0.032). A combination of ≥2 or ≥3 specific histological criteria was not prognostic. Patients with a combination of all four specific histological criteria (loss of surface maturation, mucin depletion, nuclear enlargement, and increase of mitosis) were associated with greater progression from LGD to HGD or OAC in Barrett's oesophagus.

Classifying Retinal Degeneration in Histological Sections Using Deep Learning.

Purpose: Artificial intelligence (AI) techniques are increasingly being used to classify retinal diseases. In this study we investigated the ability of a convolutional neural network (CNN) in categorizing histological images into different classes of retinal degeneration. Methods: Images were obtained from a chemically induced feline model of monocular retinal dystrophy and split into training and testing sets. The training set was graded for the level of retinal degeneration and used to train various CNN architectures. The testing set was evaluated through the best architecture and graded by six observers. Comparisons between model and observer classifications, and interobserver variability were measured. Finally, the effects of using less training images or images containing half the presentable context were investigated. Results: The best model gave weighted-F1 scores in the range 85% to 90%. Cohen kappa scores reached up to 0.86, indicating high agreement between the model and observers. Interobserver variability was consistent with the model-observer variability in the model's ability to match predictions with the observers. Image context restriction resulted in model performance reduction by up to 6% and at least one training set size resulted in a model performance reduction of 10% compared to the original size. Conclusions: Detecting the presence and severity of up to three classes of retinal degeneration in histological data can be reliably achieved with a deep learning classifier. Translational Relevance: This work lays the foundations for future AI models which could aid in the evaluation of more intricate changes occurring in retinal degeneration, particularly in other types of clinically derived image data.

Opportunities and Challenges for the Introduction of New Food Proteins.

New forms of protein are being developed at a rapid rate as older forms of protein, particularly meat and poultry, are coming under attack for nutritional, environmental, food safety, and animal welfare issues. To date, the FDA and USDA have split oversight of the new technologies that include genetic engineering and precision fermentation. Because these new products address the problems associated with traditional proteins, consumer demand appears to be overcoming fundamental fears associated with innovative foods. Currently, agencies are struggling with naming issues for the new proteins and, in some cases, possibly being forced to use costly and lengthy premarket approvals. Because of the complexity of new production methods, the speed of development, and the potential benefits, a new system of regulation may be necessary. It would consist of one of the existing agencies becoming a super regulator overseeing private companies that specialize and compete with each other and are regulated quickly and competently.

User experiences using FLAME: A Case study modelling conflict in large enterprise system implementations.

The complexity of systems now under consideration (be they biological, physical, chemical, social, etc), together with the technicalities of experimentation in the real-world and the non-linear nature of system dynamics, means that computational modelling is indispensible in the pursuit of furthering our understanding of complex systems. Agent-based modelling and simulation is rapidly increasing in its popularity, in part due to the increased appreciation of the paradigm by the non-computer science community, but also due to the increase in the usability, sophistication and number of modelling frameworks that use the approach. The Flexible Large-scale Agent-based Modelling Environment (FLAME) is a relatively recent addition to the list. FLAME was designed and developed from the outset to deal with massive simulations, and to ensure that the simulation code is portable across different scales of computing and across different operating systems. In this study, we report our experiences when using FLAME to model the development and propagation of conflict within large multi-partner enterprise system implementations, which acts as an example of a complex dynamical social system. We believe FLAME is an excellent choice for experienced modellers, who will be able to fully harness the capabilities that it has to offer, and also be competent in diagnosing and solving any limitations that are encountered. Conversely, because FLAME requires considerable development of instrumentation tools, along with development of statistical analysis scripts, we believe that it is not suitable for the novice modeller, who may be better suited to using a graphical user interface driven framework until their experience with modelling and competence in programming increases.

In vivo feasibility of epiretinal stimulation using ultrananocrystalline diamond electrodes.

OBJECTIVE: Due to their increased proximity to retinal ganglion cells (RGCs), epiretinal visual prostheses present the opportunity for eliciting phosphenes with low thresholds through direct RGC activation. This study characterised the in vivo performance of a novel prototype monolithic epiretinal prosthesis, containing Nitrogen incorporated ultrananocrystalline (N-UNCD) diamond electrodes. APPROACH: A prototype implant containing up to twenty-five 120 × 120 µm N-UNCD electrodes was implanted into 16 anaesthetised cats and attached to the retina either using a single tack or via magnetic coupling with a suprachoroidally placed magnet. Multiunit responses to retinal stimulation using charge-balanced biphasic current pulses were recorded acutely in the visual cortex using a multichannel planar array. Several stimulus parameters were varied including; the stimulating electrode, stimulus polarity, phase duration, return configuration and the number of electrodes stimulated simultaneously. MAIN RESULTS: The rigid nature of the device and its form factor necessitated complex surgical procedures. Surgeries were considered successful in 10/16 animals and cortical responses to single electrode stimulation obtained in eight animals. Clinical imaging and histological outcomes showed severe retinal trauma caused by the device in situ in many instances. Cortical measures were found to significantly depend on the surgical outcomes of individual experiments, phase duration, return configuration and the number of electrodes stimulated simultaneously, but not stimulus polarity. Cortical thresholds were also found to increase over time within an experiment. SIGNIFICANCE: The study successfully demonstrated that an epiretinal prosthesis containing diamond electrodes could produce cortical activity with high precision, albeit only in a small number of cases. Both surgical approaches were highly challenging in terms of reliable and consistent attachment to and stabilisation against the retina, and often resulted in severe retinal trauma. There are key challenges (device form factor and attachment technique) to be resolved for such a device to progress towards clinical application, as current surgical techniques are unable to address these issues.

Sutural loading in bone- versus dental-borne rapid palatal expansion: An ex vivo study.

OBJECTIVES: To measure and compare the success rate and strains generated during bone- (BRPE) and dental-borne rapid palatal expansion (DRPE) at the alveolar bone, zygomaticomaxillary (ZMS) and internasal (INS) sutures. Additionally, the magnitude and the pattern of midpalatal suture (MPS) separation in the 2 groups was assessed. SETTING AND SAMPLE POPULATION: The study was performed ex vivo using 28 pig heads. MATERIALS AND METHODS: Heads were dissected, and the MPS, ZMS, INS and the alveolar bone were exposed. A differential-variable-reluctance-transducer (DVRT) was installed across the MPS, and single-element strain gauges were installed at the remaining sites. Expanders were placed and activated at one turn per minute for 30 turns. Strains at the alveolar bone and the sutures and the separation of the MPS were measured. RESULTS: Successful expansion of the MPS was achieved in 69% of the BRPE subjects compared to 27% in the DRPE group. The average separation of the MPS was higher (230 ± 109 µm per turn vs. 79 ± 61 µm) and the MPS opening happened at an earlier stage of expansion in the BRPE. Higher strains at the ZMS were seen in the BRPE group, while higher strain at the alveolar bone was found in the DRPE group. CONCLUSIONS: The BRPE group demonstrated more successful and effective expansion of the MPS. Higher strain was found at the alveolar bone in the DRPE. A tendency for higher strain at the ZMS was noticed in the BRPE.

Lymphocytic thrombophilic arteritis and cutaneous polyarteritis nodosa: Clinicopathologic comparison with blinded histologic assessment.

BACKGROUND: Lymphocytic thrombophilic arteritis (LTA), or macular lymphocytic arteritis, is defined by a primary lymphocytic vasculitis. However, the nosology of LTA has been controversial, with speculation that it may represent an indolent non-nodule-forming variant of cutaneous polyarteritis nodosa (cPAN). OBJECTIVE: This study compares the clinicopathologic features of patients with LTA or cPAN to assess if these conditions should be considered distinct entities. METHODS: This is a cross-sectional study of all LTA and cPAN cases at a single tertiary center using prospectively collected clinical data and blinded histologic assessment. RESULTS: The study included 17 patients with LTA and 13 patients with cPAN. Clinically, cases of LTA were distinguished by a more widespread pattern of livedo racemosa, which was noninfiltrated and asymptomatic. In contrast, cPAN was associated with localized starburst livedo, purpura, and episodic features including nodules, pain, and large inflammatory ulcers. When patients were separated according to the presence (>5%) or paucity (≤5%) of neutrophils on blinded histology review, they had distinct clinical features and differences in disease course. LIMITATIONS: This was a single-center study. CONCLUSION: Our data support the classification of LTA and cPAN as separate entities rather than a spectrum of the same disorder and highlight the importance of clinicopathologic correlation in distinguishing these conditions.

A Retrospective Mixed Longitudinal Study of Tooth Formation in Children With Clefts.

OBJECTIVE: To test for systematic age changes in cleft children based on dental age. DESIGN: Retrospective case-control longitudinal study. SETTING: One orthodontic solo practice. PATIENTS: Nonsyndromic, complete cleft lip and palateCLP cases, either unilateral or bilateral (102 children; 370 radiographs), between 4 and 16 years of age. INTERVENTIONS: Children were treated with a team approach, but only orthodontic radiographs were studied. MAIN OUTCOME MEASURE: The principal outcome measure was dental age of the cleft cases compared to a sex-specific sample of phenotypically normal children (1107 children), from the same geographical region. Multiple panoramic radiographs taken during the course of orthodontic treatment were examined to track patterns of dental age as children matured. Analysis used linear mixed models primarily testing for sex, cleft type (unilateral, bilateral), and hypodontia differences. Initial expectation was that cleft children would exhibit delayed dental ages from postnatal stressors and would become more deviant with maturity. RESULTS: In childhood (4-6 years), both sexes were significantly delayed (P < .001), but dental age normalized around 8 to 10 years. Boys experienced faster maturation thereafter than girls (P < .001). Only trivial differences occurred between unilateral CLP and bilateral CLP samples.Hypodontia further depressed maturation rates (P < .001). Dental age improved in a decidedly curvilinear fashion (P < .001), with greater change at earlier ages. CONCLUSIONS: This report agrees with other contemporary studies, showing childhood catch-up. Older studies observed that clefting caused significant delays that worsened with growth. This potential "seachange" suggests better recovery and quicker normalization of children with clefts, perhaps due to improved management.

Deformation of the zygomaticomaxillary and nasofrontal sutures during bone-anchored maxillary protraction and reverse-pull headgear treatments: An ex-vivo study.

INTRODUCTION: Bone-anchored maxillary protraction (BAMP) is an emerging treatment that involves applying a protraction load to the maxillary bone. Although it is believed that such an approach results in better sutural separation, this has not been investigated. This study aimed to assess and compare the deformation of 1 circumaxillary suture (zygomaticomaxillary suture [ZMS]) and 1 facial suture (nasofrontal suture [NFS]) during BAMP and reverse-pull headgear (RPHG) treatment. METHODS: The study was performed ex vivo on 15 pig heads. Miniplates were placed in the maxillary bone and the body of the mandible. A molar tube was bonded to the maxillary first molars. Six single-element strain gauges and 3 differential variable reluctance transducers were installed across the ZMS and NFS bilaterally. Each head underwent BAMP and RPHG unilaterally and bilaterally. RESULTS: In unilateral experiments, both BAMP and RPHG resulted in tension on the ipsilateral ZMS and NFS and compression on the contralateral side, with higher magnitude in the BAMP group. In bilateral experiments, both modalities resulted in tension at the ZMS, with higher magnitude in the BAMP group. Deformation of the NFS was different between the 2 groups: tension in majority of the BAMP and compression in most of the RPHG heads. CONCLUSIONS: Our study shows a higher magnitude of sutural separation in BAMP than in RPHG. The pattern of sutural deformation is consistent with a forward displacement of the midface in BAMP compared with an upward and backward rotation in the RPHG. Rotation of the maxilla was also present in some of the subjects who underwent BAMP.

Reclaiming Phosphate from Waste Solutions with Fe(III)-Polysaccharide Hydrogel Beads for Photo-Controlled-Release Fertilizer.

Photoresponsive hydrogels from polysaccharides and Fe(III) were used as a new system to capture and release PO43- from waste solutions. Uptake of 0.6-1.5 mg of phosphate per gram of hydrogels was determined from 800 ppm phosphate solutions (pH 4.8-9.0). These beads also captured 1.2 mg g-1 of phosphate from animal waste (raw manure, 727 ppm phosphate, pH 7.6), which accounted for above 80% phosphate uptake. Irradiation of phosphate-loaded hydrogels degraded the gels due to the photochemistry of the Fe(III)-carboxylates, giving controlled phosphate release (∼81% after 7 days). No release (<2% after 7 days) was seen in the dark. Kale plant trials showed complete degradation of the hydrogels in ∼2 weeks under greenhouse conditions. Biomass analysis of kale treated with phosphate-loaded beads compared to controls indicated no signs of toxicity. These results show that Fe(III)-polysaccharide hydrogels were able to reclaim phosphates from waste solutions and can be used as a controlled-release fertilizer.

Class II correction: Extraction or nonextraction?

The patient with a Class II malocclusion, proclination, or moderate crowding of the mandibular anterior teeth, and a moderate-to-low mandibular plane angle is a treatment-planning challenge. The records of 3 patients are presented. For 2 of them, extraction treatment was used to resolve the Class II malocclusion problem. Each of these patients was treated with the removal of maxillary first premolars and mandibular second premolars. The third patient was treated with Class II elastics without extractions. The clinician must weigh the pros and cons of each approach and decide which approach will give the patient the best long-term benefit.

Spatio-temporal dynamics and aetiology of proliferative leg skin lesions in wild British finches.

Proliferative leg skin lesions have been described in wild finches in Europe although there have been no large-scale studies of their aetiology or epizootiology to date. Firstly, disease surveillance, utilising public reporting of observations of live wild finches was conducted in Great Britain (GB) and showed proliferative leg skin lesions in chaffinches (Fringilla coelebs) to be widespread. Seasonal variation was observed, with a peak during the winter months. Secondly, pathological investigations were performed on a sample of 39 chaffinches, four bullfinches (Pyrrhula pyrrhula), one greenfinch (Chloris chloris) and one goldfinch (Carduelis carduelis) with proliferative leg skin lesions and detected Cnemidocoptes sp. mites in 91% (41/45) of affected finches and from all species examined. Fringilla coelebs papillomavirus (FcPV1) PCR was positive in 74% (23/31) of birds tested: a 394 base pair sequence was derived from 20 of these birds, from all examined species, with 100% identity to reference genomes. Both mites and FcPV1 DNA were detected in 71% (20/28) of birds tested for both pathogens. Histopathological examination of lesions did not discriminate the relative importance of mite or FcPV1 infection as their cause. Development of techniques to localise FcPV1 within lesions is required to elucidate the pathological significance of FcPV1 DNA detection.

Rethinking gamete donor care: A satisfaction survey of egg and sperm donors in the UK.

OBJECTIVE: Despite poor clinic communication and staff treatment being reported by donors, high rates of overall satisfaction are still reported in surveys. This study will evaluate the importance of communication and interaction between donors and fertility clinic staff in gamete donor care. METHODS: We report on 120 egg and sperm donors' responses to a UK-wide online satisfaction survey. The survey focused on donors' interactions with fertility clinic staff pre-, during, and post- donation. Basic cross-tabulation was performed on the data using online survey software. Textual data was read and extracts identified, which illustrated and expanded on the findings from the numerical data. Diagrammatic modeling was also utilised to analyse the textual data, with particular focus to relationships between the donors and clinic staff, the main activities within the gamete donation process, and how these activities may affect donor satisfaction with the gamete donation process. RESULTS: Donors expressed concern for the infertile couple and the resulting child; conveyed frustration at not receiving information on the expenses they could claim; felt lost in the system regarding the ease of making clinic appointments, and once made they were routinely not seen on time for these appointments. Donors also negatively commented on aftercare, the location and condition of the donation room, and information on contraception. In addition, Ovarian Hyperstimulation Syndrome was frequently reported, with these egg donors believing that clinic staff were not concerned with their physical or emotional well-being, but were instead disproportionately focused on extracting the eggs. CONCLUSIONS: The multifaceted notion of donors highlights the complexity inherent to the gamete donation process, which comprises various aspects of uncertainty in the donation system, and ambiguity in the donation process. Categorising donors as Altruist, Customer, and Patient, conveys the particular importance of staff communication and treatment in donor care. These categories are not mutually exclusive however, in that an individual donor may experience more than one of these perspectives during the course of their gamete donation journey. Finally, there were a number of exemplar cases, where donors reported high satisfaction throughout, and these correlated with them being given a single point of contact at the clinic. Subject to resource constraints, we suggest that this practice should be implemented throughout clinics in the UK, so that donors have access to dedicated clinic staff who not only support them emotionally and physically throughout the gamete donation process, but also ensure that communication is open, clear, timely, and consistent.

Molecular identification of papillomavirus in ducks.

Papillomaviruses infect many vertebrates, including birds. Persistent infections by some strains can cause malignant proliferation of cells (i.e. cancer), though more typically infections cause benign tumours, or may be completely subclinical. Sometimes extensive, persistent tumours are recorded-notably in chaffinches and humans. In 2016, a novel papillomavirus genotype was characterized from a duck faecal microbiome, in Bhopal, India; the sixth papillomavirus genotype from birds. Prompted by this finding, we screened 160 cloacal swabs and 968 faecal samples collected from 299 ducks sampled at Ottenby Bird Observatory, Sweden in 2015, using a newly designed real-time PCR. Twenty one samples (1.9%) from six individuals (2%) were positive. Eighteen sequences were identical to the published genotype, duck papillomavirus 1. One additional novel genotype was recovered from three samples. Both genotypes were recovered from a wild strain domestic mallard that was infected for more than 60 days with each genotype. All positive individuals were adult (P = 0.004). Significantly more positive samples were detected from swabs than faecal samples (P < 0.0001). Sample type data suggests transmission may be via direct contact, and only infrequently, via the oral-faecal route. Infection in only adult birds supports the hypothesis that this virus is sexually transmitted, though more work is required to verify this.

Natural history of avian papillomaviruses.

Papillomaviruses (Family: Papillomaviridae) are small non-enveloped viruses that cause skin and mucosa infections in diverse vertebrates. The vast majority have been detected in mammals. However, the number of papillomaviruses described in birds is growing, especially because of metagenomic studies. Seven complete genomes and one partial sequence have been described, corresponding to five papillomavirus genera. These have been detected from various sample types, including skin, internal epithelium, and faecal material, from seven highly diverse wild and captive avian species. This review summarizes the molecular epidemiology of avian papillomaviruses, their genomic organization, evolutionary history and diagnostic techniques used for detection. The most commonly detected avian papillomavirus lesions are cauliflower-shaped papillomas, or warts, found on the tarsus and digits of common chaffinch (Fringilla coelebs) and occasionally brambling (Fringilla montifringilla). Similar warty growths have been detected in African grey parrot (Psittacus erithacus) and northern fulmar (Fulmarus glacialis), on the head and the foot, respectively. Papillomavirus has also been detected in avian tissue with no apparent lesions, similar to findings in humans and other mammals. Papillomavirus involvement was initially suspected to cause other types of lesions, such as internal papillomatosis of parrots (IPP) and proliferative pododermatitis in waterfowl. However, determined efforts failed to demonstrate papillomavirus presence. We briefly describe avian papillomavirus genomic organization and viral gene diversity. Furthermore, we performed a detailed analysis of avian papillomavirus non-coding regions and a preliminary computational analysis of their E9 proteins.

Lymphocytic thrombophilic arteritis complicated by systemic involvement.

Lymphocytic thrombophilic arteritis (LTA) is a recently described entity defined by primary lymphocytic vasculitis; it typically has a chronic indolent course. We describe a patient who presented with clinical and histological findings consistent with LTA and later developed bilateral focal testicular infarcts as well as an acute median nerve neuropathy.