Tick Haller\u27s Organ, a New Paradigm for Arthropod Olfaction: How Ticks Differ from Insects

Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller\u27s organ, not found in any other animals, presumed to function like the insect antennae in chemosensation but morphologically very different. The mechanism of tick chemoreception is unknown. Utilizing next-generation sequencing and comparative transcriptomics between the 1st and 4th legs (the latter without the Haller\u27s organ), we characterized 1st leg specific and putative Haller\u27s organ specific transcripts from adult American dog ticks, Dermacentor variabilis. The analysis suggested that the Haller\u27s organ is involved in olfaction, not gustation. No known odorant binding proteins like those found in insects, chemosensory lipocalins or typical insect olfactory mechanisms were identified; with the transcriptomic data only supporting a possible olfactory G-protein coupled receptor (GPCR) signal cascade unique to the Haller\u27s organ. Each component of the olfactory GPCR signal cascade was identified and characterized. The expression of GPCR, Gαo and β-arrestin transcripts identified exclusively in the 1st leg transcriptome, and putatively Haller\u27s organ specific, were examined in unfed and blood-fed adult female and male D. variabilis. Blood feeding to repletion in adult females down-regulated the expression of all three chemosensory transcripts in females but not in males; consistent with differences in post-feeding tick behavior between sexes and an expected reduced chemosensory function in females as they leave the host. Data are presented for the first time of the potential hormonal regulation of tick chemosensation; behavioral assays confirmed the role of the Haller\u27s organ in N,N-diethyl-meta-toluamide (DEET) repellency but showed no role for the Haller\u27s organ in host attachment. Further research is needed to understand the potential role of the GPCR cascade in olfaction

Electrophysiological Properties of Adult Zebrafish Oligodendrocyte Progenitor Cells

Low remyelination efficiency after spinal cord injury (SCI) is a major restraint to successful axonal and functional regeneration in mammals. In contrast, adult zebrafish can: (i) regenerate oligodendrocytes and myelin sheaths within 2 weeks post lesion; (ii) re-grow axonal projections across the lesion site and (iii) recover locomotor function within 6 weeks after spinal cord transection. However, little is known about the intrinsic properties of oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the central nervous system (CNS). Here, we demonstrate that purified OPCs from the adult zebrafish spinal cord are electrically active. They functionally express voltage-gated K+ and Na+ channels, glutamate receptors and exhibit depolarizing, tetrodotoxin (TTX)-sensitive spikes, as previously seen in rodent and human OPCs. Furthermore, we show that the percentage of zebrafish OPCs exhibiting depolarizing spikes and Nav-mediated currents is lower as compared to rodent white matter OPCs, where these membrane characteristics have been shown to underlie OPC injury susceptibility. These findings imply that adult zebrafish OPCs resemble electrical properties found in mammals and represent a relevant cell type towards understanding the biology of the primary cells targeted in remyelination therapies for non-regenerative species. The in vitro platform introduced in this study could be used in the future to: (i) elucidate how membrane characteristics of zebrafish OPCs change upon injury and (ii) identify potential signaling components underlying OPC injury recognition

Urinary p75(ECD): A prognostic, disease progression, and pharmacodynamic biomarker in ALS.

OBJECTIVE: To evaluate urinary neurotrophin receptor p75 extracellular domain (p75(ECD)) levels as disease progression and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). METHODS: The population in this study comprised 45 healthy controls and 54 people with ALS, 31 of whom were sampled longitudinally. Urinary p75(ECD) was measured using an enzyme-linked immunoassay and validation included intra-assay and inter-assay coefficients of variation, effect of circadian rhythm, and stability over time at room temperature, 4°C, and repeated freeze-thaw cycles. Longitudinal changes in urinary p75(ECD) were examined by mixed model analysis, and the prognostic value of baseline p75(ECD) was explored by survival analysis. RESULTS: Confirming our previous findings, p75(ECD) was higher in patients with ALS (5.6 ± 2.2 ng/mg creatinine) compared to controls (3.6 ± 1.4 ng/mg creatinine, p < 0.0001). Assay reproducibility was high, with p75(ECD) showing stability across repeated freeze-thaw cycles, at room temperature and 4°C for 2 days, and no diurnal variation. Urinary p75(ECD) correlated with the revised ALS Functional Rating Scale at first evaluation (r = -0.44, p = 0.008) and across all study visits (r = -0.36, p < 0.0001). p75(ECD) also increased as disease progressed at an average rate of 0.19 ng/mg creatinine per month (p < 0.0001). In multivariate prognostic analysis, bulbar onset (hazard ratio [HR] 3.0, p = 0.0035), rate of disease progression from onset to baseline (HR 4.4, p < 0.0001), and baseline p75(ECD) (HR 1.3, p = 0.0004) were predictors of survival. CONCLUSIONS: The assay for urinary p75(ECD) is analytically robust and shows promise as an ALS biomarker with prognostic, disease progression, and potential pharmacodynamic application. Baseline urinary p75(ECD) provides prognostic information and is currently the only biological fluid-based biomarker of disease progression

Evidence of dispersion and refraction of a spectrally broad gravity wave packet in the mesopause region observed by the Na lidar and Mesospheric Temperature Mapper above Logan, Utah

Gravity wave packets excited by a source of finite duration and size possess a broad frequency and wave number spectrum and thus span a range of temporal and spatial scales. Observing at a single location relatively close to the source, the wave components with higher frequency and larger vertical wavelength dominate at earlier times and at higher altitudes, while the lower frequency components, with shorter vertical wavelength, dominate during the latter part of the propagation. Utilizing observations from the Na lidar at Utah State University and the nearby Mesospheric Temperature Mapper at Bear Lake Observatory (41.9ÁN, 111.4ÁW), we investigate a unique case of vertical dispersion for a spectrally broad gravity wave packet in the mesopause region over Logan, Utah (41.7ÁN, 111.8ÁW), that occurred on 2 September 2011, to study the waves\u27 evolution as it propagates upward. The lidar-observed temperature perturbation was dominated by close to a 1 h modulation at 100 km during the early hours but gradually evolved into a 1.5 h modulation during the second half of the night. The vertical wavelength also decreased simultaneously, while the vertical group and phase velocities of the packet apparently slowed, as it was approaching a critical level during the second half of the night. A two-dimensional numerical model is used to simulate the observed gravity wave processes, finding that the location of the lidar relative to the source can strongly influence which portion of the spectrum can be observed at a particular location relative to a source. © 2015. American Geophysical Union. All Rights Reserved

Reflector-Guided Localisation of Non-Palpable Breast Lesions: A Prospective Evaluation of the SAVI SCOUT® System.

Wire-guided localisation (WGL) has been the mainstay for localising non-palpable breast lesions before excision. Due to its limitations, various wireless alternatives have been developed. In this prospective study, we evaluate the role of radiation-free wireless localisation using the SAVI SCOUT® system at the London Breast Institute. A total of 72 reflectors were deployed in 67 consecutive patients undergoing breast conserving surgery for non-palpable breast lesions. The mean interval between deployment and surgery for the therapeutic cases was 18.8 days (range: 0-210). The median deployment duration was 5 min (range: 1-15 min). The mean distance from the lesion was 1.1 mm (median distance: 0; range: 0-20 mm). The rate of surgical localisation and retrieval of the reflector was 98.6% and 100%, respectively. The median operating time was 28 min (range: 15-55 min) for the therapeutic excision of malignancy and 17 min (range: 15-24) for diagnostic excision. The incidence of reflector migration was 0%. Radial margin positivity in malignant cases was 7%. The median weight for malignant lesions was 19.6 g (range: 3.5-70 g). Radiologists and surgeons rated the system higher than WGL (93.7% and 98.6%, respectively; 60/64 and 70/71). The patient mean satisfaction score was 9.7/10 (n = 47, median = 10; range: 7-10). One instance of signal failure was reported. In patients who had breast MRI after the deployment of the reflector, the MRI void signal was <5 mm (n = 6). There was no specific technique-related surgical complication. Our study demonstrates that wire-free localisation using SAVI SCOUT® is an effective and time-efficient alternative to WGL with excellent physician and patient acceptance

Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial)

Purpose To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features. Materials and Methods In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29–85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images. Reviewers had no access to results of previous examinations. Overall sensitivities and specificities were calculated for younger women and those with dense breasts. Results Overall sensitivity was 87% for 2D mammography, 89% for 2D mammography plus DBT, and 88% for synthetic 2D mammography plus DBT. The addition of DBT was associated with a 34% increase in the odds of depicting cancer (odds ratio [OR] = 1.34, P = .06); however, this level did not achieve significance. For patients aged 50–59 years old, sensitivity was significantly higher (P = .01) for 2D mammography plus DBT than it was for 2D mammography. For those with breast density of 50% or more, sensitivity was 86% for 2D mammography compared with 93% for 2D mammography plus DBT (P = .03). Specificity was 57% for 2D mammography, 70% for 2D mammography plus DBT, and 72% for synthetic 2D mammography plusmDBT. Specificity was significantly higher than 2D mammography (P < .001in both cases) and was observed for all subgroups (P < .001 for all cases). Conclusion The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups. The use of synthetic 2D DBT demonstrated performance similar to that of standard 2D mammography with DBT. DBT is of potential benefit to screening programs, particularly in younger women with dense breasts. © RSNA, 2015The TOMMY Trial (a comparison of digital breast tomosynthesis with mammography in the UK Breast Screening Programme) was supported by the NIHR Health Technology Assessment Programme.This is the final published version of the article. It was originally published in Radiology (Gilbert et al., Radiology, 2015, doi:10.1148/radiol.2015142566). The final version is available at http://dx.doi.org/10.1148/radiol.201514256

Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial).

PURPOSE: To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features. MATERIALS AND METHODS: In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29-85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images. Reviewers had no access to results of previous examinations. Overall sensitivities and specificities were calculated for younger women and those with dense breasts. RESULTS: Overall sensitivity was 87% for 2D mammography, 89% for 2D mammography plus DBT, and 88% for synthetic 2D mammography plus DBT. The addition of DBT was associated with a 34% increase in the odds of depicting cancer (odds ratio [OR] = 1.34, P = .06); however, this level did not achieve significance. For patients aged 50-59 years old, sensitivity was significantly higher (P = .01) for 2D mammography plus DBT than it was for 2D mammography. For those with breast density of 50% or more, sensitivity was 86% for 2D mammography compared with 93% for 2D mammography plus DBT (P = .03). Specificity was 57% for 2D mammography, 70% for 2D mammography plus DBT, and 72% for synthetic 2D mammography plusmDBT. Specificity was significantly higher than 2D mammography (P < .001in both cases) and was observed for all subgroups (P < .001 for all cases). CONCLUSION: The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups. The use of synthetic 2D DBT demonstrated performance similar to that of standard 2D mammography with DBT. DBT is of potential benefit to screening programs, particularly in younger women with dense breasts. (©) RSNA, 2015.The TOMMY Trial (a comparison of digital breast tomosynthesis with mammography in the UK Breast Screening Programme) was supported by the NIHR Health Technology Assessment Programme.This is the final published version of the article. It was originally published in Radiology (Gilbert et al., Radiology, 2015, doi:10.1148/radiol.2015142566). The final version is available at http://dx.doi.org/10.1148/radiol.201514256

The Poetics of Dissolution: The Representation of Maori Culture in Janet Frame's Fiction

This essay examines Janet Frame's early short story "The Lagoon", and argues that the story alludes to Maori experience, albeit tangentially, in a way which anticipates similar evocations in novels such as A State of Siege and The Carpathians. A close reading shows that cultural imperialism in Frame runs parallel to, or is a side-effect of, interpersonal appropriations. These, in turn, seem to be rooted in human beings' reluctance to accommodate otherness. Recurrently Janet Frame points to a model of cultural and interpersonal interaction which is detached from proprietorial forms of appropriation, but which entails nothing less than the dissolution of the ruling ego. Selfdissolution shall emerge in this reading as the key to a utopian state consisting of the total permeability between the self and the remainder of the world. In this state, transactions become reciprocal since the divisions between self and non-self no longer exist