A magnetic massive star has experienced a stellar merger.

Massive stars (those ≥8 solar masses at formation) have radiative envelopes that cannot sustain a dynamo, the mechanism that produces magnetic fields in lower-mass stars. Despite this, approximately 7% of massive stars have observed magnetic fields, the origin of which is debated. We used multi-epoch interferometric and spectroscopic observations to characterize HD 148937, a binary system of two massive stars. We found that only one star is magnetic and that it appears younger than its companion. The system properties and a surrounding bipolar nebula can be reproduced with a model in which two stars merged (in a previous triple system) to produce the magnetic massive star. Our results provide observational evidence that magnetic fields form in at least some massive stars through stellar mergers.

Multi-qubit entanglement and algorithms on a neutral-atom quantum computer.

Gate-model quantum computers promise to solve currently intractable computational problems if they can be operated at scale with long coherence times and high-fidelity logic. Neutral-atom hyperfine qubits provide inherent scalability owing to their identical characteristics, long coherence times and ability to be trapped in dense, multidimensional arrays1. Combined with the strong entangling interactions provided by Rydberg states2-4, all the necessary characteristics for quantum computation are available. Here we demonstrate several quantum algorithms on a programmable gate-model neutral-atom quantum computer in an architecture based on individual addressing of single atoms with tightly focused optical beams scanned across a two-dimensional array of qubits. Preparation of entangled Greenberger-Horne-Zeilinger (GHZ) states5 with up to six qubits, quantum phase estimation for a chemistry problem6 and the quantum approximate optimization algorithm (QAOA)7 for the maximum cut (MaxCut) graph problem are demonstrated. These results highlight the emergent capability of neutral-atom qubit arrays for universal, programmable quantum computation, as well as preparation of non-classical states of use for quantum-enhanced sensing.

Ligand-based G Protein Coupled Receptor pharmacophore modeling: Assessing the role of ligand function in model development.

Integral membrane proteins in the G Protein-Coupled Receptor (GPCR) class are attractive drug development targets. However, computational methods applicable to ligand discovery for many GPCR targets are restricted by limited numbers of known ligands. Pharmacophore models can be developed using variously sized training sets and applied in database mining to prioritize candidate ligands for subsequent validation. This in silico study assessed the impact of key pharmacophore modeling decisions that arise when known ligand numbers for a target of interest are low. GPCR included in this study are the adrenergic alpha-1A, 1D and 2A, adrenergic beta 2 and 3, kappa, delta and mu opioid, serotonin 1A and 2A, and the muscarinic 1 and 2 receptors, all of which have rich ligand data sets suitable to assess the performance of protocols intended for application to GPCR with limited ligand data availability. Impact of ligand function, potency and structural diversity in training set selection was assessed to define when pharmacophore modeling targeting GPCR with limited known ligands becomes viable. Pharmacophore elements and pharmacophore model selection criteria were also assessed. Pharmacophore model assessment was based on percent pharmacophore model generation failure, as well as Güner-Henry enrichment and goodness-of-hit scores. Three of seven pharmacophore element schemes evaluated in MOE 2018.0101, Unified, PCHD, and CHD, showed substantially lower failure rates and higher enrichment scores than the others. Enrichment and GH scores were used to compare construction protocol for pharmacophore models of varying purposes- such as function specific versus nonspecific ligand identification. Notably, pharmacophore models constructed from ligands of mixed functions (agonists and antagonists) were capable of enriching hitlists with active compounds, and therefore can be used when available sets of known ligands are limited in number.

Detection of free-living amoebae in domestic cats with and without naturally-acquired keratitis.

Pathogenic free-living amoebae, most notably Acanthamoeba spp., are important pathogens of the human cornea. The importance of infection with free-living amoebae in cats with keratitis is currently unclear. The aim of this study was to determine the frequency of amoeba detection in corneas of cats with naturally-acquired keratitis and in the ocular surface microflora of cats without ocular disease. Clinical ophthalmic and in vivo corneal confocal microscopic examinations were performed on 60 cats with keratitis. Corneal scrapings were analyzed by amoeba culture; cytological evaluation; and Acanthamoeba, Hartmannella, and Vahlkampfia PCR assays. Following ophthalmic examination, conjunctival specimens collected from 60 cats without clinically apparent ocular disease were analyzed similarly. In one cat with ulcerative keratitis, amoeba cysts and trophozoites were detected by in vivo corneal confocal microscopy; an Acanthamoeba sp. was isolated from corneal specimens and detected by Acanthamoeba PCR assay; and suppurative corneal inflammation was present cytologically. An Acanthamoeba sp. was isolated from conjunctival specimens from one cat without clinically apparent ocular disease, but with suppurative inflammation demonstrated cytologically. Both Acanthamoeba isolates belonged to the T4 genotype. Naegleria-like amoebae were isolated in samples from two cats with keratitis and seven cats without clinical ocular disease, but amoebae were not detected by the other assays in these samples. Amoeba detection by culture was significantly (P = 0.01) associated with cytologically diagnosed corneoconjunctival inflammation. This study identified naturally-acquired Acanthamoeba keratitis in cats. Detection of Naegleria-like amoebae in samples from cats with and without keratitis is of uncertain pathological significance.

Role of defects in determining the magnetic ground state of ytterbium titanate.

Pyrochlore systems are ideally suited to the exploration of geometrical frustration in three dimensions, and their rich phenomenology encompasses topological order and fractional excitations. Classical spin ices provide the first context in which it is possible to control emergent magnetic monopoles, and anisotropic exchange leads to even richer behaviour associated with large quantum fluctuations. Whether the magnetic ground state of Yb2Ti2O7 is a quantum spin liquid or a ferromagnetic phase induced by a Higgs transition appears to be sample dependent. Here we have determined the role of structural defects on the magnetic ground state via the diffuse scattering of neutrons. We find that oxygen vacancies stabilise the spin liquid phase and the stuffing of Ti sites by Yb suppresses it. Samples in which the oxygen vacancies have been eliminated by annealing in oxygen exhibit a transition to a ferromagnetic phase, and this is the true magnetic ground state.

Inactivation of the bacterial pathogens Staphylococcus pseudintermedius and Acinetobacter baumannii by butanoic acid.

AIMS: This study was performed to evaluate the efficacy of butanoic acid against bacterial pathogens including Acinetobacter baumannii and Staphylococcus pseudintermedius. METHODS AND RESULTS: Vegetative bacteria were exposed to butanoic acid in vitro and log reduction was quantified using viable count assays. The maximum (8 and 9) log inactivation was determined by qualitatively assaying for growth/no-growth after a 48-h incubation (37°C). Membrane integrity after exposure to butanoic acid was determined by propidium iodide staining, scanning electron microscopy, membrane depolarization and inductively coupled plasma analysis. Cytosolic pH was measured by 5-(6-)carboxyfluorescein succinimidyl ester. CONCLUSIONS: Inhibitory concentrations of butanoic acid ranged between 11 and 21 mmol l-1 for Gram-positive and Gram-negative species tested. The maximum log reduction of A. baumannii was achieved with a 10-s exposure of 0·50 mol l-1 of butanoic acid. Staphylococcus pseudintermedius required 0·40 mol l-1 of butanoic acid to achieve the same level of reduction in the same time period. Inactivation was associated with membrane permeability and acidification of the cytosol. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibiotic resistance among bacterial pathogens necessitates the utilization of novel therapeutics for disinfection and biological control. These results may facilitate the development of butanoic acid as an effective agent against a broad-spectrum of antibiotic-resistant bacterial pathogens.

High-fidelity phase and amplitude control of phase-only computer generated holograms using conjugate gradient minimisation.

We demonstrate simultaneous control of both the phase and amplitude of light using a conjugate gradient minimisation-based hologram calculation technique and a single phase-only spatial light modulator (SLM). A cost function, which incorporates the inner product of the light field with a chosen target field within a defined measure region, is efficiently minimised to create high fidelity patterns in the Fourier plane of the SLM. A fidelity of F = 0.999997 is achieved for a pattern resembling an LG10 mode with a calculated light-usage efficiency of 41.5%. Possible applications of our method in optical trapping and ultracold atoms are presented and we show uncorrected experimental realisation of our patterns with F = 0.97 and 7.8% light efficiency.

Evaluation of capsule endoscopy to detect mucosal lesions associated with gastrointestinal bleeding in dogs.

OBJECTIVE: The objective of this study was to examine the utility of capsule endoscopy to detect mucosal abnormalities in dogs with gastrointestinal haemorrhage. METHODS: Capsules were administered to 2 healthy controls and 8 patients with gastrointestinal haemorrhage. Images were evaluated for quality, gastric emptying time, small intestinal transit time and presence of lesions. RESULTS: There were no adverse effects of capsule endoscopy in dogs weighing from 7·7 to 58 kg. The capsule traversed the entire gastrointestinal tract in 5 of 8 patients, with high quality images obtained in the stomach and small intestine. Gastric emptying time and small intestinal transit time ranged from 1 to 270 and 15 to 180 minutes, respectively. In 3 of 8 patients, the capsule remained in the stomach despite pro-kinetics. Gastric lesions included mild haemorrhage and pinpoint erosion (4 of 8), a mass (1) and thickened bleeding pyloric mucosa (2). Two of 3 dogs with capsule retention had gastric lesions. Intestinal lesions included a healing duodenal ulcer, abnormal villi, ileal ulceration and colonic bleeding. Lesions identified by capsule endoscopy were considered a significant source of haemorrhage in 4 of 7 dogs with active bleeding. The relevance of pinpoint gastric mucosal erosions to blood loss is unclear. CLINICAL SIGNIFICANCE: Capsule endoscopy can enable the non-invasive detection of gastric and small intestinal mucosal lesions in dogs presenting for evaluation of gastrointestinal bleeding.

Subspectacular nematodiasis caused by a novel Serpentirhabdias species in ball pythons (Python regius).

Subspectacular nematodiasis was diagnosed in three captive-bred juvenile ball pythons (Python regius) from two unrelated facilities within a 6-month period. The snakes were presented with similar lesions, including swelling of facial, periocular and oral tissues. Bilaterally, the subspectacular spaces were distended and filled with an opaque fluid, which contained nematodes and eggs. Histopathology showed nematodes throughout the periocular tissue, subspectacular space and subcutaneous tissue of the head. The nematodes from both facilities were morphologically indistinguishable and most closely resembled Serpentirhabdias species. Morphological characterization and genetic sequencing indicate this is a previously undescribed rhabdiasid nematode.

World Association for the Advancement of Veterinary Parasitology (WAAVP): Guideline for the evaluation of drug efficacy against non-coccidial gastrointestinal protozoa in livestock and companion animals.

The current guideline was written to aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against non-coccidial gastrointestinal protozoan parasites, with Giardia spp. as the leading example. The information provided in this guideline deals with aspects of how to conduct controlled studies using experimental infection models (dose determination and dose confirmation) and efficacy studies in commercial facilities (field effectiveness studies). Furthermore, the selection of suitable animals, housing, infection procedure, choice of diagnostic technique and data analysis are discussed. This guideline is intended to assist investigators in conducting specific studies, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new drugs and to facilitate the worldwide adoption of uniform procedures. The primary parameter for drug efficacy is the reduction in either parasite excretion or parasite counts and a minimum efficacy of 90% is required against non-coccidial gastrointestinal protozoa. A supporting efficacy parameter is a significant difference in the proportion of infected animals between treated and non-treated groups. Persistent efficacy is considered as an additional claim to therapeutic efficacy.

Human ocular onchocerciasis caused by Onchocerca lupi (Spirurida, Onchocercidae) in Iran.

Cases of canine onchocerciasis caused by Onchocerca lupi are increasingly reported from Europe and the western United States of America. The zoonotic role of this parasite had already been suspected in Europe as the clinical signs and histopathology seen in two ocular cases from Albania and the Crimean region were very similar to those of canine ocular onchocerciasis. In the most recent reports of human onchocerciasis, O. lupi has been morphologically and molecularly identified as the causative agent of ocular infestation in two patients from Turkey, and one patient from Tunisia. Here, we report an additional case of nodular lesions involving two, and possibly more, immature worms in a patient from Iran. The parasite was found to belong to the genus Onchocerca based on morphological features and the species was confirmed as O. lupi from a partial sequence analysis of 12S ribosomal DNA.

Applications of pathology-assisted image analysis of immunohistochemistry-based biomarkers in oncology.

Immunohistochemistry-based biomarkers are commonly used to understand target inhibition in key cancer pathways in preclinical models and clinical studies. Automated slide-scanning and advanced high-throughput image analysis software technologies have evolved into a routine methodology for quantitative analysis of immunohistochemistry-based biomarkers. Alongside the traditional pathology H-score based on physical slides, the pathology world is welcoming digital pathology and advanced quantitative image analysis, which have enabled tissue- and cellular-level analysis. An automated workflow was implemented that includes automated staining, slide-scanning, and image analysis methodologies to explore biomarkers involved in 2 cancer targets: Aurora A and NEDD8-activating enzyme (NAE). The 2 workflows highlight the evolution of our immunohistochemistry laboratory and the different needs and requirements of each biological assay. Skin biopsies obtained from MLN8237 (Aurora A inhibitor) phase 1 clinical trials were evaluated for mitotic and apoptotic index, while mitotic index and defects in chromosome alignment and spindles were assessed in tumor biopsies to demonstrate Aurora A inhibition. Additionally, in both preclinical xenograft models and an acute myeloid leukemia phase 1 trial of the NAE inhibitor MLN4924, development of a novel image algorithm enabled measurement of downstream pathway modulation upon NAE inhibition. In the highlighted studies, developing a biomarker strategy based on automated image analysis solutions enabled project teams to confirm target and pathway inhibition and understand downstream outcomes of target inhibition with increased throughput and quantitative accuracy. These case studies demonstrate a strategy that combines a pathologist's expertise with automated image analysis to support oncology drug discovery and development programs.

Cryptosporidium parvum: determination of ID50 and the dose-response relationship in experimentally challenged dairy calves.

The objectives were to determine the median infective dose (ID50) of Cryptosporidium parvum and to describe the dose-response relationship including associated clinical illness in experimentally challenged dairy calves. Within the first 24h of life, 27 test calves were experimentally challenged with C. parvum oocysts and 3 control calves were sham dosed. Test calves received 1 of 8 possible doses (25, 50, 100, 500, 1 × 10(3), 1 × 10(4), 1 × 10(5), and 1 × 10(6) oocysts). All 27 test calves developed diarrhea. Fecal oocyst shedding occurred in 25 (92.6%) test calves and in 0 control calves. The 2 non-shedding test calves both received 25 oocysts. There was an inverse relationship between dose and time to onset of fecal oocyst shedding (P=0.005). There was no relationship found between dose and duration (P=0.2) or cessation (P=0.3) of fecal oocyst shedding. In addition, there was not a significant relationship between log-dose and the log-peak oocysts (P=0.2) or log-total oocysts (P=0.5) counted/g of feces across the dose groups. There was a positive dose-response relationship between log-dose and diarrhea (P=0.01). However, when controlling for other factors, such as onset and cessation of fecal oocyst shedding, dose was not a significant predictor of diarrhea (P=0.5). Onset and cessation of fecal oocyst shedding were found to be the best predictors of diarrhea (P=0.0006 and P=0.04, respectively). The ID50 for fecal oocyst shedding was 5.8 oocysts, for diarrhea was 9.7 oocysts, and for fecal oocyst shedding with diarrhea was 16.6 oocysts. Given that the ID50 of C. parvum is far less than would be excreted into the environment by a naturally infected calf, prevention and control of cryptosporidiosis is a formidable challenge.

Giant eucalypts - globally unique fire-adapted rain-forest trees?

Tree species exceeding 70 m in height are rare globally. Giant gymnosperms are concentrated near the Pacific coast of the USA, while the tallest angiosperms are eucalypts (Eucalyptus spp.) in southern and eastern Australia. Giant eucalypts co-occur with rain-forest trees in eastern Australia, creating unique vegetation communities comprising fire-dependent trees above fire-intolerant rain-forest. However, giant eucalypts can also tower over shrubby understoreys (e.g. in Western Australia). The local abundance of giant eucalypts is controlled by interactions between fire activity and landscape setting. Giant eucalypts have features that increase flammability (e.g. oil-rich foliage and open crowns) relative to other rain-forest trees but it is debatable if these features are adaptations. Probable drivers of eucalypt gigantism are intense intra-specific competition following severe fires, and inter-specific competition among adult trees. However, we suggest that this was made possible by a general capacity of eucalypts for 'hyper-emergence'. We argue that, because giant eucalypts occur in rain-forest climates and share traits with rain-forest pioneers, they should be regarded as long-lived rain-forest pioneers, albeit with a particular dependence on fire for regeneration. These unique ecosystems are of high conservation value, following substantial clearing and logging over 150 yr. Contents Summary 1001 I. Introduction 1001 II. Giant eucalypts in a global context 1002 III. Giant eucalypts - taxonomy and distribution 1004 IV. Growth of giant eucalypts 1006 V. Fire and regeneration of giant eucalypts 1008 VI. Are giant eucalypts different from other rain-forest trees? 1009 VII. Conclusions 1010 Acknowledgements 1011 References 1011.

Antibody responses following administration of a Cryptosporidium parvum rCP15/60 vaccine to pregnant cattle.

Cryptosporidium parvum is a zoonotic Apicomplexa-protozoan pathogen that causes gastroenteritis and diarrhea in mammals worldwide. Globally, C. parvum is ubiquitous on dairy operations and is the pathogen most commonly diagnosed in association with calf diarrhea. Here, we describe the antibody response in 20 pregnant cows to a recombinant C. parvum oocyst surface protein (rCP15/60) vaccine compared with 20 controls, and the antibody response in 19 calves fed the rCP15/60-immune colostrum from these vaccinated cows compared with 20 control calves. Cows vaccinated with rCP15/60 produced a significantly greater antibody response compared to controls (p<0.0001) and this response was strongly associated with the subsequent level of colostral antibody (r=0.82, p<0.0001). Calves fed rCP15/60-immune colostrum showed a dose-dependent absorption of antibody, also associated with colostral antibody levels (r=0.83, p<0.0001). Currently, drug therapy against cryptosporidiosis is limited making development of an effective vaccine attractive. This report describes the first stages in development of a C. parvum rCP15/60 vaccine designed to confer passive protection to calves against cryptosporidiosis.

The prevalence of Cryptosporidium, and identification of the Cryptosporidium horse genotype in foals in New York State.

To date, little is known about the prevalence, genotypes and zoonotic potential of Cryptosporidium spp. affecting horses, especially in North America. A cross-sectional study was conducted in New York, USA between February 25th and May 1st 2009. Fecal samples were collected from three hundred and forty nine 1-10-week-old foals and their dams on 14 different broodmare farms. All fecal samples were screened for Cryptosporidium spp. using a direct immunofluorescence assay (DFA). DNA extraction and PCR-RFLP analysis of the small-subunit (SSU) rRNA gene were performed on all the foal samples. PCR-positive samples were subtyped by DNA sequencing of the 60-kDa glycoprotein (gp60) gene. On DFA, 13/175 (7.4%) foal samples and 3/174 (1.7%) mare samples were designated positive for Cryptosporidium spp., whereas on SSU rRNA-based PCR, 9/175 (5.1%) foal samples were positive. Cryptosporidium PCR-positive foals were significantly older (13-40 days, median age of 28 days) compared with negative foals (4-67 days, median 18 days, p=0.02). The number of foals with diarrhea or soft feces was not significantly different between positive and negative foals (p=0.09). PCR-RFLP analysis of the SSU rRNA gene and DNA sequencing of the gp60 gene identified the parasite as subtype VIaA14G2 of the horse genotype. This is the first report of a group of foals affected with the Cryptosporidium horse genotype, which has recently been detected in humans. As other contemporary molecular studies have identified C. parvum in foals, it seems that equine cryptosporidiosis should be considered a zoonosis.

Comparison of 4 Giardia diagnostic tests in diagnosis of naturally acquired canine chronic subclinical giardiasis.

BACKGROUND: The performance of Giardia diagnostic tests that detect either cysts or fecal antigens has not been thoroughly examined. HYPOTHESIS/OBJECTIVES: We examined the concordance and agreement among 4 Giardia diagnostic tests (2 cyst and 2 coproantigen detection methods) in a colony of dogs chronically and subclinically infected with Giardia. ANIMALS: Twenty dogs with chronic, subclinical Giardia infection. METHODS: Giardia diagnostic tests were performed repeatedly on each dog over 120 days. Fecal cyst detection methods (ZnSO4 flotation and fluorescent antibody [FAB] coproscopy) were performed 3 times per week. Coproantigen methods (Giardia SNAP test and quantitative ELISA) were performed weekly. Results were analyzed and compared among methods. RESULTS: When compared with FAB coproscopy, all of the in-house diagnostic tests had excellent positive predictive values (PPVs, 95-99%) at the study prevalence (89%). At lower prevalence rates, ZnSO4, SNAP, and ELISA tests all had good negative predictive values (NPVs), but poor PPVs. There was poor to good agreement among tests by kappa analysis. CONCLUSION AND CLINICAL RELEVANCE: Our findings show that most commonly used in-house Giardia diagnostic tests have poor agreement with the gold standard method (FAB coproscopy). The in-house tests have good NPVs, but poor PPVs, at prevalence rates common in most clinical settings.

Consultation activities of clinical ethics committees in the United Kingdom: an empirical study and wake-up call.

OBJECTIVE: To identify the consultation activities of clinical ethics committees (CECs) in the UK and the views of CEC chairpersons regarding such activities. METHODS: An anonymous, password-protected online questionnaire was sent by e-mail to 70 CEC chairpersons. The questionnaire contained 14 items. RESULTS: Of the 70 CECs contacted, 30 responded (a response rate of 43%). There has been an almost fourfold increase in the number of CECs in the past 7 years. Over half of the CECs that responded had considered three or fewer active cases and three or fewer retrospective cases in the preceding year. Eighty percent of chairpersons felt that the number of active cases considered by their committee was too low. Seventy percent of CECs had rapid response teams. Aside from low consultation caseloads, chairpersons identified a number of concerns, including education and training of members, composition of CECs, low profile and lack of funding and support. Although most respondents believed there is a need for clinical ethics support in the NHS, many noted the limited use of the services, even after efforts to increase the visibility of their CEC. CONCLUSION: Despite a sharp increase in the absolute numbers of CECs across the UK, the number of cases considered by the majority of CECs is low. The findings presented here suggest we must reflect on the reasons for such low caseloads and pause to consider whether the committee model is most appropriate for the UK context.