Polarization Dependent Scattering in Cavity Optomagnonics.

The polarization dependence of magnon-photon scattering in an optical microcavity is reported. Because of the short cavity length, the longitudinal mode-matching conditions found in previously explored, large path-length whispering gallery resonators are absent. Nonetheless, for cross-polarized scattering a strong and broadband suppression of one sideband is observed. This arises due to an interference between the Faraday and second-order Cotton-Mouton effects. To fully account for the suppression of the cross-polarized scattering, it is necessary to consider the squeezing of magnon modes intrinsic to thin-film geometry. A copolarized scattering due to Cotton-Mouton effect is also observed. In addition, the magnon modes involved are identified as Damon-Eshbach surface modes, whose nonreciprocal propagation could be exploited in device applications. This Letter experimentally demonstrates the important role of second-order Cotton-Mouton effect for optomagnonic devices.

Fast Gate-Based Readout of Silicon Quantum Dots Using Josephson Parametric Amplification.

Spins in silicon quantum devices are promising candidates for large-scale quantum computing. Gate-based sensing of spin qubits offers a compact and scalable readout with high fidelity, however, further improvements in sensitivity are required to meet the fidelity thresholds and measurement timescales needed for the implementation of fast feedback in error correction protocols. Here, we combine radio-frequency gate-based sensing at 622 MHz with a Josephson parametric amplifier, that operates in the 500-800 MHz band, to reduce the integration time required to read the state of a silicon double quantum dot formed in a nanowire transistor. Based on our achieved signal-to-noise ratio, we estimate that singlet-triplet single-shot readout with an average fidelity of 99.7% could be performed in 1 µs, well below the requirements for fault-tolerant readout and 30 times faster than without the Josephson parametric amplifier. Additionally, the Josephson parametric amplifier allows operation at a lower radio-frequency power while maintaining identical signal-to-noise ratio. We determine a noise temperature of 200 mK with a contribution from the Josephson parametric amplifier (25%), cryogenic amplifier (25%) and the resonator (50%), showing routes to further increase the readout speed.

A service evaluation of simultaneous near-patient testing for influenza, respiratory syncytial virus, Clostridium difficile and norovirus in a UK district general hospital.

BACKGROUND: The Cepheid® GeneXpert® (GXP) can simultaneously test for norovirus (NV), Clostridium difficile (CD), influenza A/B (IFA/B) and respiratory syncytial virus (RSV). AIM: To compare centralized multiplex polymerase chain reaction (PCR) testing with localized GXP testing at a district general hospital. METHODS: From December 2017 to December 2018, samples received at Whipps Cross University Hospital (WCUH) were first tested at the local laboratory before transport centrally to the Royal London Hospital (RLH). At the RLH, a non-proprietary multiplex reverse transcriptase (RT) PCR assay was performed, which also tested for gastrointestinal or respiratory pathogens not tested for by the GXP. FINDINGS: A total of 1111 stool and respiratory samples were processed at both sites; 591 were respiratory and 520 were stool samples. Compared to centralized testing, the GXP gave sensitivity, specificity, and NPV all in excess of 97%, with the exception of RSV. The RSV assay had a sensitivity of 66.7% (95% confidence interval (CI) 24.1, 94.0) but an NPV of 99.7% (95% CI 98.6, 99.9). At the RLH, 65 (5.9%) additional respiratory or gastrointestinal viruses were detected, predominantly rhinovirus 35 (3.2%) and adenovirus 11 (1.0%). Compared to centralized testing, the median time saved for local respiratory and gastrointestinal sample testing was 19 h and 46 min and 17 h and 6 min, respectively. CONCLUSIONS: Local GXP testing compared to centralized multiplex PCR testing for IF, NV and CD, demonstrated sensitivities, specificities and NPV between 95% and 100%. Turnaround times were faster, enabling quicker infection prevention and control decision making. In our local setting (WCUH), the GXP demonstrated the potential to reduce NV and IFA/B outbreaks.

Triple-Resonant Brillouin Light Scattering in Magneto-Optical Cavities.

An enhancement in Brillouin light scattering of optical photons with magnons is demonstrated in magneto-optical whispering gallery mode resonators tuned to a triple-resonance point. This occurs when both the input and output optical modes are resonant with those of the whispering gallery resonator, with a separation given by the ferromagnetic resonance frequency. The identification and excitation of specific optical modes allows us to gain a clear understanding of the mode-matching conditions. A selection rule due to wave vector matching leads to an intrinsic single-sideband excitation. Strong suppression of one sideband is essential for one-to-one frequency mapping in coherent optical-to-microwave conversion.

The physical demands of Super League rugby: Experiences of a newly promoted franchise.

The physical match demands for a newly promoted European Super League (ESL) squad were analysed over a full season using global positioning systems. Players were classified into four positional groups: outside backs (OB), pivots (PIV), middle unit forwards (MUF) and wide running forwards (WRF). MUF covered less total distance (4318 ± 570 m) than WRF (6408 ± 629 m), PIV (6549 ± 853) and OB (7246 ± 333 m) (P < 0.05) and less sprint distance (185 ± 58 m) than WRF (296 ± 82 m), PIV (306 ± 108) and OB (421 ± 89 m; P < 0.05), likely attributable to less playing time by MUF (47.8 ± 6.6 min) compared with WRF (77.0 ± 9.0 min), PIV (72.8 ± 10.6 min) and OB (86.7 ± 3.4 min; P < 0.05). Metres per minute were greater for MUF (90.8 ± 2.2 m.min(-1)) compared with OB (83.6 ± 2.8 m.min(-1)) and WRF (83.4 ± 2.4 m.min(-1); P = 0.001) although not different from PIV (90.2 ± 3.3 m.min(-1); P > 0.05). WRF (36 ± 5) and MUF (35 ± 6) were involved in more collisions than OB (20 ± 3) and PIV (23 ± 3; P < 0.05). The high-speed running and collision demands observed here were greater than that previously reported in the ESL, which may reflect increased demands placed on the lower ranked teams. The present data may be used to inform coaches if training provides the physical stimulus to adequately prepare their players for competition which may be especially pertinent for newly promoted franchises.

Optical spin-transfer-torque-driven domain-wall motion in a ferromagnetic semiconductor.

We demonstrate optical manipulation of the position of a domain wall in a dilute magnetic semiconductor, GaMnAsP. Two main contributions are identified. First, photocarrier spin exerts a spin-transfer torque on the magnetization via the exchange interaction. The direction of the domain-wall motion can be controlled using the helicity of the laser. Second, the domain wall is attracted to the hot spot generated by the focused laser. Unlike magnetic-field-driven domain-wall depinning, these mechanisms directly drive domain-wall motion, providing an optical tweezerlike ability to position and locally probe domain walls.

From adaptive licensing to adaptive pathways: delivering a flexible life-span approach to bring new drugs to patients.

The concept of adaptive licensing (AL) has met with considerable interest. Yet some remain skeptical about its feasibility. Others argue that the focus and name of AL should be broadened. Against this background of ongoing debate, we examine the environmental changes that will likely make adaptive pathways the preferred approach in the future. The key drivers include: growing patient demand for timely access to promising therapies, emerging science leading to fragmentation of treatment populations, rising payer influence on product accessibility, and pressure on pharma/investors to ensure sustainability of drug development. We also discuss a number of environmental changes that will enable an adaptive paradigm. A life-span approach to bringing innovation to patients is expected to help address the perceived access vs. evidence trade-off, help de-risk drug development, and lead to better outcomes for patients.

Immunohistological Description of Nongestational Ovarian Choriocarcinoma in Two Female Mice With Conditional Loss of Trp53 Driven by the Tie2 Promoter.

Nongestational ovarian choriocarcinoma (NGCO) is a tumor of germ cell origin seldom described in nonhuman species. Few spontaneous cases are reported in macaques and mice, with the B6C3F1 strain overrepresented. This report describes 2 cases of ovarian choriocarcinoma in nulliparous female mice with conditional loss of Trp53 under the Tie2 promoter. The mouse line was maintained on a mixed genetic background including Crl: CD1(ICR) and 129X1/SvJ strains. In both cases, affected ovary was partially replaced by blood-filled lacunae lined by neoplastic trophoblast-like giant cells. Immunohistochemically, neoplastic cells expressed folate-binding protein and prolactin and were invariably negative for p53. To the authors' knowledge, this is the first report characterizing this entity in a genetically engineered mouse (GEM) line. Considering that germ cells (the cell population from which NGCO originates) constitutively express Tie2 receptor, it can be speculated that Tie2-driven deletion of Trp53 may have played a role in the development of these tumors.

Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression.

Deregulation of signaling pathways that control differentiation, expansion and migration of neural crest-derived melanoblasts during normal development contributes also to melanoma progression and metastasis. Although several epithelial-to-mesenchymal (EMT) transcription factors, such as zinc finger E-box binding protein 1 (ZEB1) and ZEB2, have been implicated in neural crest cell biology, little is known about their role in melanocyte homeostasis and melanoma. Here we show that mice lacking Zeb2 in the melanocyte lineage exhibit a melanoblast migration defect and, unexpectedly, a severe melanocyte differentiation defect. Loss of Zeb2 in the melanocyte lineage results in a downregulation of the Microphthalmia-associated transcription factor (Mitf) and melanocyte differentiation markers concomitant with an upregulation of Zeb1. We identify a transcriptional signaling network in which the EMT transcription factor ZEB2 regulates MITF levels to control melanocyte differentiation. Moreover, our data are also relevant for human melanomagenesis as loss of ZEB2 expression is associated with reduced patient survival.

Inverse conoscopy: a method to measure polarization using patterns generated by a single birefringent crystal.

A method to measure the full polarization vector of a laser beam is proposed and demonstrated. Light is focused onto a birefringent crystal cut such that the slow axis is aligned with the optical axis. The polarization vector of each ray experiences a rotation about the radial axis with a retardation phase dependent on the angle of incidence. Illumination over a wide range of angles applies a range of polarization transforms in parallel that generates a distinct pattern detected by a camera. The input polarization is then inferred from the pattern. The setup uses a single birefringent crystal and involves no moving parts.

p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway.

There is growing evidence that the p53 tumour suppressor downregulates vascular endothelial growth factor (VEGF) expression, although the underlying mechanisms remain unclear and controversial. Here we provide insights from in vitro experiments and in vivo xenotransplantation assays that highlight a dual role for p53 in regulating VEGF during hypoxia. Unexpectedly, and for the first time, we demonstrate that p53 rapidly induces VEGF transcription upon hypoxia exposure by binding, in an HIF-1α-dependent manner, to a highly conserved and functional p53-binding site within the VEGF promoter. However, during sustained hypoxia, p53 indirectly downregulates VEGF expression via the retinoblastoma (Rb) pathway in a p21-dependent manner, which is distinct from its role in cell-cycle regulation. Our findings have important implications for cancer therapy, especially for tumours that harbour wild-type TP53 and a dysfunctional Rb pathway.

Rapid identification of bacteria from bioMérieux BacT/ALERT blood culture bottles by MALDI-TOF MS.

Several studies have reported poor results when trying to identify microorganisms directly from the bioMérieux BacT/ALERT blood culture system using matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry. The aim of this study is to evaluate two new methods, Sepsityper and an enrichment method for direct identification of microorganisms from this system. For both methods the samples were processed using the Bruker Microflex LT mass spectrometer (Biotyper) using the Microflex Control software to obtain spectra. The results from direct analysis were compared with those obtained by subculture and subsequent identification. A total of 350 positive blood cultures were processed simultaneously by the two methods. Fifty-three cultures were polymocrobial or failed to grow any organism on subculture, and these results were not included as there was either no subculture result, or for polymicrobial cultures it was known that the Biotyper would not be able to distinguish the constituent organisms correctly. Overall, the results showed that, contrary to previous reports, it is possible to identify bacteria directly from bioMérieux blood culture bottles, as 219/297 (74%) correct identifications were obtained using the Bruker Sepsityper method and 228/297 (77%) were obtained for the enrichment method when there is only one organism was present. Although the enrichment method was simpler, the reagent costs for the Sepsityper method were approximately pound 4.00 per sample compared to pound 0.50. An even simpler and cheaper method, which was less labour-intensive and did not require further reagents, was investigated. Seventy-seven specimens from positive signalled blood cultures were analysed by inoculating prewarmed blood agar plates and analysing any growth after 1-, 2- and 4-h periods of incubation at 37 degrees C, by either direct transfer or alcohol extraction. This method gave the highest number of correct identifications, 66/77 (86%), and was cheaper and less labour-intensive than either of the two above methods.

Tissue-wide overexpression of alpha-T-catenin results in aberrant trophoblast invasion but does not cause embryonic mortality in mice.

Transcriptional activation of CTNNA3, encoding αT-catenin, by the Y153H mutated form of the human STOX1 transcription factor was proposed to be responsible for altered fetal trophoblast invasion into the maternal endometrium during placentation in pre-eclampsia. Here we have generated a mouse model to investigate the in vivo effects of ectopic αT-catenin expression on trophoblast invasion. Histological analysis was used to determine the invasive capacities of trophoblasts from transgenic embryos, as well as proliferation rates of spongiotrophoblasts in the junctional zone. Augmented expression of αT-catenin reduced the number of invading trophoblasts but did not cause embryonic mortality. The, αT-catenin positive cells could still invade into the decidual layer and migrated as deeply as wild-type trophoblasts. Furthermore, the junctional zone is enlarged in placentas of mice overexpressing αT-catenin due to hyperproliferation of the residing spongiotrophoblasts, suggesting a pivotal role of αT-catenin levels in the control of the proliferative versus invasive state of trophoblasts during placentation. Our study provides, for the first time, in vivo data on the effects of increased levels of αT-catenin in the placenta.

The onset of puberty in North American bison (Bison bison) bulls.

Prepubertal testicular development was evaluated in young North American bison (Bison bison) bulls over a 12 months period, by following various parameters of semen quality intended to measure sexual maturity level. The study goals were to characterize bison male reproductive development and to define the age and onset of puberty. Semen was collected by electro-ejaculation from 12 bulls once a month for a period of 12 months, from 13 through 24 months of age. Volume, density, gross motility, individual motility, morphology, live/dead ratio, and concentration were used to judge the quality of the ejaculates. Abnormal sperm were classified into categories according to descriptions used for bovine evaluations and guidelines created by the Western Canadian Association of Bovine Practitioners were used for determining satisfactory semen quality. Minimums of 60% progressive motility and 70% normal sperm cells identified samples as satisfactory. Puberty was defined as the point in testicular development where an ejaculate contains a minimum of 50 x 10(6)sperm cells, showing at least 10% progressive motility. Fecal samples collected from bulls prior to electro-ejaculation for testosterone determination by a commercial testosterone specific antibody radioimmunoassay showed no significant changes in mean fecal testosterone concentrations over time. Changes in mean body weights over the study period were calculated, the average body weight at 13 and 24 months of age were 263+/-18.6 and 475+/-52.2 kg, respectively. Under these experimental conditions, age was determined to be the most significant factor in determining the onset of puberty. On average, bulls reached puberty at 16.5+/-2.5 months. There was a significant increase in the number of normal sperm with increasing bull age as well as significant decreases in proximal cytoplasmic droplets and head defects, but no significant changes in midpiece and principal piece defects. There were significant increases with age in individual progressive motility, gross motility, concentration, density, and volume but not in the percent of live sperm. Bison bulls used for breeding should be capable of passing a breeding soundness evaluation by 24 months of age. The commercial bison industry semen tests, and possibly rejects, many developmentally incomplete bulls between 19 and 21 months of age. We suggest that these may actually be developing normally and should not be hastily discarded; it may be worth testing again at 24 months.

The seasonal fertility of North American bison (Bison bison) bulls.

The objective of this study was to determine the presence and magnitude of seasonal fluctuations in semen quality and other reproductive indices in bison bulls. Testicles from 288 commercially slaughtered bison bulls were collected monthly over a 1-year period. Carcass and testicle weight were determined and measurements of seminiferous tubule lumen, diameter, and epithelial thickness were made. Sperm cell morphology and defects were described and quantified using epididymal semen from each testicle. Twenty-one Plains (Bison bison bison) and Wood bison (Bison bison athabascae) breeding bulls, averaging 6.0 years of age (range 2.5-8.0), from three farms were selected for semen collection and evaluation on the basis of producer co-operation. Semen was collected by electro-ejaculation on four seasonal occasions during a 12-month period. Ejaculate quality was judged on the basis of volume, density, gross and individual motility, morphology, live/dead ratio, and concentration. Sperm cell morphologies were evaluated microscopically and classified according to criteria used for bovine semen. Fecal testosterone was measured at each semen collection using a commercial competitive binding radioimmunoassay. There was an increase in carcass weights over the study period and testis weights were moderately correlated (r=0.44) with carcass weights. However, mean testes weights were heavier (P<0.05) in the summer than in winter, spring, or fall periods. There were no differences in the proportion of normal and abnormal epididymal sperm between seasons but there were seasonal changes in the testicular parenchyma. Seminiferous tubule and lumen diameter, and epithelial thickness were greatest (P<0.05) in summer. Live bulls gained weight between April and November, but lost weight over the winter. Normal sperm cell percentages as well as individual sperm cell motility in electro-ejaculated sperm samples were higher (P<0.05) at the pre-breeding collection relative to other collections, but no change in sperm cell concentrations occurred over the study period. Fecal testosterone concentrations were highest at the pre-breeding period (June) but decreased (P<0.05) in each subsequent collection to reach their lowest levels in the April. While many changes in seen characteristics were not significant, overall results indicate the presence of some reproductive seasonality and increased testicular capacity in the summer breeding season. Bulls showing marginal semen quality in the winter but otherwise carrying desirable genetic traits may warrant another evaluation in late spring prior to being culled from a breeding program.

Fundamentals of pair diffusion in kinematic simulations of turbulence.

We demonstrate that kinematic simulation (KS) of three-dimensional homogeneous turbulence produces fluid element pair statistics in agreement with the predictions of L F. Richardson [Proc. R. Soc. London, Ser. A 110, 709 (1926)] even though KS lacks explicit modeling of turbulent sweeping of small eddies by large ones. This scaling is most clearly evident in the turbulent diffusivity's dependence on rms pair separation and, to a lesser extent, on the pair's travel time statistics. It is also shown that kinematic simulation generates a probability density function of pair separation which is in good agreement with recent theory [S. Goto and J. C. Vassilicos, New J. Phys. 6, 65 (2004)] and with the scaling of the rms pair separation predicted by L. F. Richardson [Proc. R. Soc. London, Ser. A 110, 709 (1926)]. Finally, the statistical persistence hypothesis (SPH) is formulated mathematically and its validity tested in KS. This formulation introduces the concept of stagnation point velocities and relates these to fluid accelerations. The scaling of accelerations found in kinematic simulation supports the SPH, even though KS does not generate a Kolmogorov scaling for the acceleration variance (except for a specific case and a limited range of outer to inner length-scale ratios). An argument is then presented that suggests that the stagnation points in homogeneous isotropic turbulence are on average long-lived.

Acceleration statistics as measures of statistical persistence of streamlines in isotropic turbulence.

We introduce the velocity Vs of stagnation points as a means to characterize and measure statistical persistence of streamlines. Using theoretical arguments, direct numerical simulations (DNS), and kinematic simulations (KS) of three-dimensional isotropic turbulence for different ratios of inner to outer length scales L/eta of the self-similar range, we show that a frame exists where the average Vs = 0 , that the rms values of acceleration, turbulent fluid velocity, and Vs are related by La'/u'2 approximately (V's/u')(L/eta)(2/3+q) , and that V's/u' approximately (L/eta)q with q = -1/3 in Kolmogorov turbulence, q = -1/6 in current DNS, and q = 0 in our KS. The statistical persistence hypothesis is closely related to the Tennekes sweeping hypothesis.

Quantification of corticosteroid-induced skin vasoconstriction: visual ranking, chromameter measurement or digital imaging analysis.

Topical corticosteroid formulations have been evaluated by visual grading protocols for many years. Toward a more objective methodology, several instrumental methods have been evaluated for applicability in quantifying the vasoconstriction side-effect that follows corticosteroid application to the skin. Although the chromameter has been adopted by regulatory bodies throughout the world as the current standard for topical bioequivalence determinations, there is considerable criticism of this instrument from several quarters. A preliminary comparison reported here indicates that digital image analysis provides statistically significant results that are similar to those obtained by visual assessment techniques, and shows considerably greater precision than that obtained by the chromameter. Continued evaluation of objective assessment techniques, such as digital imaging, and continued modernisation of regulatory bioequivalence requirements will assist in protecting patients and optimising clinical results.

Viral, parasitic and prion diseases of farmed deer and bison.

The most important viral disease of farmed deer and bison is malignant catarrhal fever. The other herpesviruses which have been isolated from these species are briefly described. Other viral agents that are recognised in these animals, including adenovirus, parapox, foot and mouth disease, bluetongue, epizootic haemorrhagic disease, bovine virus diarrhoea, rotavirus and coronavirus, are also discussed. Ectoparasites of importance in this group in various parts of the world include a variety of ticks, as well as lice, keds, Oestridae, mange mites and fire ants. Helminth parasites include liver flukes (Fascioloides and Fasciola), gastrointestinal nematodes of the family Trichostrongylidae, pulmonary lungworms of the genus Dictyocaulus and extra-pulmonary lungworms of the family Protostrongylidae. Chronic wasting disease is principally important in North America, where the disease occurs in wild cervids in a limited area and has been reported in farmed deer in a small number of states in the United States of America and one province in Canada. These diseases are summarised in terms of their classification, epidemiology, clinical signs, pathology, diagnosis, treatment and control.