Ariel - Volume 9 Number 3

Executive Editor Emily Wofford Business Manager Fredric Jay Matlin University News John Patrick Welch World News George Robert Coar Editorials Editor Steve Levine Features Mark Rubin Brad Feldstein Photo Rick Spaide Circulation Victor Onufreiczuk Lee Wugofski Graphics and Art Steve Hulkower Commons Editor Brenda Peterso

Ultrasound-guided large-core needle biopsies of breast lesions: analysis of 962 cases to determine the number of samples for reliable tumour classification

The objective of this one-institutional study was to determine the number of large-core needle biopsies (LCNB), under three-dimensional ultrasound (3D-US) validation, that are sufficient to obtain a reliable histological diagnosis of a sonographically detectable breast lesion. Over an 28-month period, 962 sonographically guided LCNB were performed under 3D-US validation to assess 962 breast lesions. All biopsies were carried out with an automated core biopsy device fitted with 14-gauge (22 mm excursion) needles. Data of 962 biopsied breast lesions were gathered. Surgical follow-up was available for 659 lesions. Breast malignancies were diagnosed by ultrasound-guided LCNB with a sensitivity of 98.2% by performing three cores per lesion. In few cases, the open surgical specimen revealed the presence of invasive carcinomas in contrast to initial LNCB-based classification as ductal carcinomas in situ (DCIS, 11 lesions), lobular carcinoma in situ (one lesion), and atypical ductal hyperpasia (one lesion). Owing to disagreement between classification based on breast-imaging and histological findings, eight of these tumours were subsequently excised. Of the lesions that were removed at the patients' requests despite benign LCNB diagnosis, two were infiltrating carcinoma and one a DCIS. We demonstrate that three 3D-US-guided percutaneous core specimens are sufficient to achieve tissue for a reliable histological assessment of sonographically detectable breast lesions and allow the detection of malignancies with high sensitivity and low rate of false-negative diagnoses

Inorganic speciation of dissolved elements in seawater: the influence of pH on concentration ratios

Assessments of inorganic elemental speciation in seawater span the past four decades. Experimentation, compilation and critical review of equilibrium data over the past forty years have, in particular, considerably improved our understanding of cation hydrolysis and the complexation of cations by carbonate ions in solution. Through experimental investigations and critical evaluation it is now known that more than forty elements have seawater speciation schemes that are strongly influenced by pH. In the present work, the speciation of the elements in seawater is summarized in a manner that highlights the significance of pH variations. For elements that have pH-dependent species concentration ratios, this work summarizes equilibrium data (S = 35, t = 25°C) that can be used to assess regions of dominance and relative species concentrations. Concentration ratios of complex species are expressed in the form log[A]/[B] = pH - C where brackets denote species concentrations in solution, A and B are species important at higher (A) and lower (B) solution pH, and C is a constant dependent on salinity, temperature and pressure. In the case of equilibria involving complex oxy-anions (MO(x)(OH)(y)) or hydroxy complexes (M(OH)(n)), C is written as pK(n )= -log K(n )or pK(n)* = -log K(n)* respectively, where K(n )and K(n)* are equilibrium constants. For equilibria involving carbonate complexation, the constant C is written as pQ = -log(K(2)(l)K(n )[HCO(3)(-)]) where K(2)(l )is the HCO(3 )(- )dissociation constant, K(n )is a cation complexation constant and [HCO(3)(-)] is approximated as 1.9 × 10(-3 )molar. Equilibrium data expressed in this manner clearly show dominant species transitions, ranges of dominance, and relative concentrations at any pH

The osteology of ‘Periptychus carinidens’: a robust, ungulate-like placental mammal (Mammalia: Periptychidae) from the Paleocene of North America

Periptychus is the archetypal genus of Periptychidae, a clade of prolific Paleocene 'condylarth' mammals from North America that were among the first placental mammals to radiate after the end-Cretaceous extinction, remarkable for their distinctive dental anatomy. A comprehensive understanding of the anatomy of Periptychus has been hindered by a lack of cranial and postcranial material and only cursory description of existing material. We comprehensively describe the cranial, dental and postcranial anatomy of Periptychus carinidens based on new fossil material from the early Paleocene (Torrejonian) of New Mexico, USA. The cranial anatomy of Periptychus is broadly concurrent with the inferred plesiomorphic eutherian condition, albeit more robust in overall construction. The rostrum is moderately elongate with no constriction, the facial region is broad, and the braincase is small with a well-exposed mastoid on the posterolateral corner and tall sagittal and nuchal crests. The dentition of Periptychus is characterized by strongly crenulated enamel, enlarged upper and lower premolars with a tall centralised paracone/protoconid. The postcranial skeleton of Periptychus is that of a robust, medium-sized (~20 Kg) stout-limbed animal that was incipiently mediportal and adopted a plantigrade stance. The structure of the fore- and hindlimb of Periptychus corresponds to that of a typically terrestrial mammal, while morphological features of the forelimb such as the low tubercles of the humerus, long and prominent deltopectoral crest, pronounced medial epicondyle, and hemispherical capitulum indicate some scansorial and/or fossorial ability. Most striking is the strongly dorsoplantarly compressed astragalus of Periptychus, which in combination with the distal crus and calcaneal morphology indicates a moderately mobile cruropedal joint. The anatomy of Periptychus is unique and lacks any extant analogue; it combines a basic early placental body plan with numerous unique specializations in its dental, cranial and postcranial anatomy that exemplify the ability of mammals to adapt and evolve following catastrophic environmental upheaval

Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol

© 2017 The Author(s). Toll-like receptors (TLRs) are major players of the innate immune system. Once activated, they trigger a signalling cascade that leads to NF-ΰ B translocation from the cytoplasm to the nucleus. Single cell analysis shows that NF-ΰ B signalling dynamics are a critical determinant of transcriptional regulation. Moreover, the outcome of innate immune response is also affected by the cross-talk between TLRs and estrogen signalling. Here, we characterized the dynamics of TLR5 signalling, responsible for the recognition of flagellated bacteria, and those changes induced by estradiol in its signalling at the single cell level. TLR5 activation in MCF7 cells induced a single and sustained NF-k B translocation into the nucleus that resulted in high NF-k B transcription activity. The overall magnitude of NF-k B transcription activity was not influenced by the duration of the stimulus. No significant changes are observed in the dynamics of NF-k B translocation to the nucleus when MCF7 cells are incubated with estradiol. However, estradiol significantly decreased NF-k B transcriptional activity while increasing TLR5-mediated AP-1 transcription. The effect of estradiol on transcriptional activity was dependent on the estrogen receptor activated. This fine tuning seems to occur mainly in the nucleus at the transcription level rather than affecting the translocation of the NF-k B transcription factor

ccTSA: A Coverage-Centric Threaded Sequence Assembler

De novo sequencing, a process to find the whole genome or the regions of a species without references, requires much higher computational power compared to mapped sequencing with references. The advent and continuous evolution of next-generation sequencing technologies further stress the demands of high-throughput processing of myriads of short DNA fragments. Recently announced sequence assemblers, such as Velvet, SOAPdenovo, and ABySS, all exploit parallelism to meet these computational demands since contemporary computer systems primarily rely on scaling the number of computing cores to improve performance. However, most of them are not tailored to exploit the full potential of these systems, leading to suboptimal performance. In this paper, we present ccTSA, a parallel sequence assembler that utilizes coverage to prune k-mers, find preferred edges, and resolve conflicts in preferred edges between k-mers. We minimize computation dependencies between threads to effectively parallelize k-mer processing. We also judiciously allocate and reuse memory space in order to lower memory usage and further improve sequencing speed. The results of ccTSA are compelling such that it runs several times faster than other assemblers while providing comparable quality values such as N50

Does the early frog catch the worm? Disentangling potential drivers of a parasite age–intensity relationship in tadpoles

The manner in which parasite intensity and aggregation varies with host age can provide insights into parasite dynamics and help identify potential means of controlling infections in humans and wildlife. A significant challenge is to distinguish among competing mechanistic hypotheses for the relationship between age and parasite intensity or aggregation. Because different mechanisms can generate similar relationships, testing among competing hypotheses can be difficult, particularly in wildlife hosts, and often requires a combination of experimental and model fitting approaches. We used field data, experiments, and model fitting to distinguish among ten plausible drivers of a curvilinear age–intensity relationship and increasing aggregation with host age for echinostome trematode infections of green frogs. We found little support for most of these proposed drivers but did find that the parsimonious explanation for the observed age–intensity relationship was seasonal exposure to echinostomes. The parsimonious explanation for the aggregated distribution of parasites in this host population was heterogeneity in exposure. A predictive model incorporating seasonal exposure indicated that tadpoles hatching early or late in the breeding season should have lower trematode burdens at metamorphosis, particularly with simulated warmer climates. Application of this multi-pronged approach (field surveys, lab experiments, and modeling) to additional parasite–host systems could lead to discovery of general patterns in the drivers of parasite age–intensity and age–distribution relationships

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter