Covariation of the amplitude and latency of motor evoked potentials elicited by transcranial magnetic stimulation in a resting hand muscle.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique used to study human neurophysiology. A single TMS pulse delivered to the primary motor cortex can elicit a motor evoked potential (MEP) in a target muscle. MEP amplitude is a measure of corticospinal excitability and MEP latency is a measure of the time taken for intracortical processing, corticofugal conduction, spinal processing, and neuromuscular transmission. Although MEP amplitude is known to vary across trials with constant stimulus intensity, little is known about MEP latency variation. To investigate MEP amplitude and latency variation at the individual level, we scored single-pulse MEP amplitude and latency in a resting hand muscle from two datasets. MEP latency varied from trial to trial in individual participants with a median range of 3.9 ms. Shorter MEP latencies were associated with larger MEP amplitudes for most individuals (median r = - 0.47), showing that latency and amplitude are jointly determined by the excitability of the corticospinal system when TMS is delivered. TMS delivered during heightened excitability could discharge a greater number of cortico-cortical and corticospinal cells, increasing the amplitude and, by recurrent activation of corticospinal cells, the number of descending indirect waves. An increase in the amplitude and number of indirect waves would progressively recruit larger spinal motor neurons with large-diameter fast-conducting fibers, which would shorten MEP onset latency and increase MEP amplitude. In addition to MEP amplitude variability, understanding MEP latency variability is important given that these parameters are used to help characterize pathophysiology of movement disorders.

Long-interval intracortical inhibition is asymmetric in young but not older adults.

Aging is typically accompanied by a decline in manual dexterity and handedness; the dominant hand executes tasks of manual dexterity more quickly and accurately than the nondominant hand in younger adults, but this advantage typically declines with age. Age-related changes in intracortical inhibitory processes might play a role in the age-related decline in manual dexterity. Long-interval intracortical inhibition (LICI) is asymmetric in young adults, with more sensitive and more powerful LICI circuits in the dominant hemisphere than in the nondominant hemisphere. Here we investigated whether the hemispheric asymmetry in LICI in younger adults persists in healthy older adults. Paired-pulse transcranial magnetic stimulation was used to measure LICI in the dominant and nondominant hemispheres of younger and older adults; LICI stimulus-response curves were obtained by varying conditioning stimulus intensity at two different interstimulus intervals [100 ms (LICI100) and 150 ms]. We have replicated the finding that LICI100 circuits are more sensitive and more powerful in the dominant than the nondominant hemisphere of young adults and extend this finding to show that the hemispheric asymmetry in LICI100 is lost with age. In the context of behavioral observations showing that dominant hand movements in younger adults are more fluent than nondominant hand movements in younger adults and dominant hand movements in older adults, we speculate a role of LICI100 in the age-related decline in manual dexterity.NEW & NOTEWORTHY In younger adults, more sensitive and more powerful long-interval intracortical inhibitory circuits are evident in the hemisphere controlling the more dexterous hand; this is not the case in older adults, for whom long-interval intracortical inhibitory circuits are symmetric and more variable than in younger adults. We speculate that the highly sensitive and powerful long-interval intracortical inhibition circuits in the dominant hemisphere play a role in manual dexterity.

First reported case of multidrug-resistant Candida auris in Canada.

Candida auris is a fungal pathogen that has recently emerged as a global threat to public health. It was first described in Japan in 2009 and has since been reported in 17 countries on five continents. This case report describes the first reported case of multidrug-resistant C. auris in Canada. In May 2017, a 64-year-old individual was evaluated for chronic otitis externa. Past medical history included a recent hospitalization in India for elective oral surgery that was complicated by an odontogenic brain abscess. Upon return to Canada, the individual was admitted to a hospital for neurosurgical drainage of the brain abscess and parenteral antibiotics. Early during hospitalization, the patient was identified as a carrier of carbapenem-resistant Enterobacteriaceae and was placed on contact precautions. Also early during this hospitalization, a chronic otitis media was managed with placement of a typanostomy tube with drainage of clear fluid from the ear, which continued through the admission and after discharge to a post-neurosurgical rehabilitation facility. During outpatient follow-up, swabs of the ear discharge cultured C. auris that was resistant to fluconazole and amphotericin B. There was no clinical response to ototopical antifungal therapy. Surgical evaluation for management of the otomastoiditis is pending. There is a potential for C. auris to cause infection in health care settings. It can persist in hospital environments, has the potential for transmission and can cause invasive disease. It is difficult to identify and is often resistant to antifungal medications. The application of infection prevention and control recommendations can help prevent nosocomial transmission. It is now prudent to consider the risk of C. auris, in addition to the known risk of other antimicrobial resistant organisms, in any traveller who has been hospitalized while outside the country. When identified, contacting local public health can assist in the tracking and management of this emerging disease.

Integrating Nanostructured Artificial Receptors with Whispering Gallery Mode Optical Microresonators via Inorganic Molecular Imprinting Techniques.

The creation of label-free biosensors capable of accurately detecting trace contaminants, particularly small organic molecules, is of significant interest for applications in environmental monitoring. This is achieved by pairing a high-sensitivity signal transducer with a biorecognition element that imparts selectivity towards the compound of interest. However, many environmental pollutants do not have corresponding biorecognition elements. Fortunately, biomimetic chemistries, such as molecular imprinting, allow for the design of artificial receptors with very high selectivity for the target. Here, we perform a proof-of-concept study to show how artificial receptors may be created from inorganic silanes using the molecular imprinting technique and paired with high-sensitivity transducers without loss of device performance. Silica microsphere Whispering Gallery Mode optical microresonators are coated with a silica thin film templated by a small fluorescent dye, fluorescein isothiocyanate, which serves as our model target. Oxygen plasma degradation and solvent extraction of the template are compared. Extracted optical devices are interacted with the template molecule to confirm successful sorption of the template. Surface characterization is accomplished via fluorescence and optical microscopy, ellipsometry, optical profilometry, and contact angle measurements. The quality factors of the devices are measured to evaluate the impact of the coating on device sensitivity. The resulting devices show uniform surface coating with no microstructural damage with Q factors above 106. This is the first report demonstrating the integration of these devices with molecular imprinting techniques, and could lead to new routes to biosensor creation for environmental monitoring.

Measurement of the Earth tides with a MEMS gravimeter.

The ability to measure tiny variations in the local gravitational acceleration allows, besides other applications, the detection of hidden hydrocarbon reserves, magma build-up before volcanic eruptions, and subterranean tunnels. Several technologies are available that achieve the sensitivities required for such applications (tens of microgal per hertz(1/2)): free-fall gravimeters, spring-based gravimeters, superconducting gravimeters, and atom interferometers. All of these devices can observe the Earth tides: the elastic deformation of the Earth's crust as a result of tidal forces. This is a universally predictable gravitational signal that requires both high sensitivity and high stability over timescales of several days to measure. All present gravimeters, however, have limitations of high cost (more than 100,000 US dollars) and high mass (more than 8 kilograms). Here we present a microelectromechanical system (MEMS) device with a sensitivity of 40 microgal per hertz(1/2) only a few cubic centimetres in size. We use it to measure the Earth tides, revealing the long-term stability of our instrument compared to any other MEMS device. MEMS accelerometers--found in most smart phones--can be mass-produced remarkably cheaply, but none are stable enough to be called a gravimeter. Our device has thus made the transition from accelerometer to gravimeter. The small size and low cost of this MEMS gravimeter suggests many applications in gravity mapping. For example, it could be mounted on a drone instead of low-flying aircraft for distributed land surveying and exploration, deployed to monitor volcanoes, or built into multi-pixel density-contrast imaging arrays.

Computed tomography and magnetic resonance diagnosis of variations in the anatomical location of the major salivary glands in 1680 dogs and 187 cats.

During assessment of routine clinical magnetic resonance imaging (MRI) of the heads of dogs, variations in the location of mandibular and zygomatic salivary glands (SGs) were observed incidentally. The aims of this retrospective study were to describe anatomical variations of the major SGs found on MRI and computed tomography (CT) studies of the head in dogs and cats and to investigate possible clinical relevancy. No anatomical variation of the SGs was seen in cats, but in dogs, although variation of the parotid SG was not identified, that of the mandibular SG was found in 33/1680 animals (2%), either unilaterally (6/33 right-sided, 13/33 left-sided) or bilaterally (14/33). The Border terrier breed (19/33, 58%) was over-represented. Each atypically located mandibular SG was positioned medial to the digastric muscle and rostral to the retropharyngeal lymph node. The sublingual glands were difficult to delineate from the mandibular glands. Anatomical variation of one zygomatic gland (3/4 left-sided) was identified in four small-breed dogs (0.2%). Each atypically located zygomatic gland was tilted at the ventrorostral aspect of the masseter muscle underneath the skin surface. MRI and CT characteristics were not different between typically and atypically located SGs. None of the dogs had clinical signs related with SG disease. It was concluded that, with suspected breed predispositions, incidental unilateral or bilateral anatomical variations of mandibular and zygomatic SGs can be encountered in dogs and an awareness of these possible variations may be important in pre-surgical planning.

ViPAR: a software platform for the Virtual Pooling and Analysis of Research Data.

BACKGROUND: Research studies exploring the determinants of disease require sufficient statistical power to detect meaningful effects. Sample size is often increased through centralized pooling of disparately located datasets, though ethical, privacy and data ownership issues can often hamper this process. Methods that facilitate the sharing of research data that are sympathetic with these issues and which allow flexible and detailed statistical analyses are therefore in critical need. We have created a software platform for the Virtual Pooling and Analysis of Research data (ViPAR), which employs free and open source methods to provide researchers with a web-based platform to analyse datasets housed in disparate locations. METHODS: Database federation permits controlled access to remotely located datasets from a central location. The Secure Shell protocol allows data to be securely exchanged between devices over an insecure network. ViPAR combines these free technologies into a solution that facilitates 'virtual pooling' where data can be temporarily pooled into computer memory and made available for analysis without the need for permanent central storage. RESULTS: Within the ViPAR infrastructure, remote sites manage their own harmonized research dataset in a database hosted at their site, while a central server hosts the data federation component and a secure analysis portal. When an analysis is initiated, requested data are retrieved from each remote site and virtually pooled at the central site. The data are then analysed by statistical software and, on completion, results of the analysis are returned to the user and the virtually pooled data are removed from memory. CONCLUSIONS: ViPAR is a secure, flexible and powerful analysis platform built on open source technology that is currently in use by large international consortia, and is made publicly available at [http://bioinformatics.childhealthresearch.org.au/software/vipar/].

Evaluation of the ventro 20° rostral-dorsocaudal oblique radiographic projection for the investigation of canine nasal disease.

OBJECTIVE: To assess the ventro 20° rostral-dorsocaudal oblique projection for canine nasal disease as an alternative to the dorsoventral intra-oral view. MATERIALS AND METHODS: Thirty-one dogs with nasal disease underwent radiography and computed tomography with a final diagnosis of underlying cause achieved through rhinoscopy, biopsy or cytology. Three independent observers, blinded to diagnosis, reviewed the nasal radiographs on two separate occasions. Intra- and inter-observer agreement and level of confidence on radiographic diagnosis were evaluated and radiographic diagnosis was compared with computed tomography and definitive diagnosis. RESULTS: The ventro 20° rostral-dorsocaudal oblique projection of canine nasal cavities was feasible in anaesthetised dogs and gave diagnostic quality images in most dogs. Assessment of this view showed moderate to substantial agreement with computed tomography diagnosis but gave lower confidence in diagnosis. Interpretation of this radiographic projection had substantial to almost perfect repeatability but moderate reproducibility. CLINICAL SIGNIFICANCE: The ventro 20° rostral-dorsocaudal oblique projection may be used as a valuable initial screening tool for canine nasal pathology in practices without access to advanced imaging, although computed tomography is still likely to provide greater diagnostic information.

Diagnostic Exercise: Circling and Behavioral Changes in a Cat.

A 4-year old spayed male domestic shorthair cat was presented with a history of circling and behavioral changes. Neurologic examination showed mild proprioceptive deficits. The lesion was localized in the forebrain, and magnetic resonance imaging revealed the presence of a large midline intracranial mass extending from the frontal lobe to the tentorial region of the brain. Euthanasia was elected due to poor prognosis. Histopathologic evaluation confirmed the presence of a mass composed by sheets and aggregates of large round/polygonal cells and multinucleate cells associated with deposits of cholesterol clefts, scattered hemorrhages and hemosiderin-laden macrophages. Immunohistochemistry showed that the round/polygonal cells and multinucleate cells were strongly positive for major histocompatibility complex class II antigen, variably positive for CD18, and occasionally positive for S100. Subsets of spindle cells showing variable expression of vimentin, S100, and neuron-specific enolase were also present. The final diagnosis was cholesterol granuloma. Differential diagnosis with meningioma is discussed.

Evaluating the performance of parallel subsurface simulators: An illustrative example with PFLOTRAN.

[1] To better inform the subsurface scientist on the expected performance of parallel simulators, this work investigates performance of the reactive multiphase flow and multicomponent biogeochemical transport code PFLOTRAN as it is applied to several realistic modeling scenarios run on the Jaguar supercomputer. After a brief introduction to the code's parallel layout and code design, PFLOTRAN's parallel performance (measured through strong and weak scalability analyses) is evaluated in the context of conceptual model layout, software and algorithmic design, and known hardware limitations. PFLOTRAN scales well (with regard to strong scaling) for three realistic problem scenarios: (1) in situ leaching of copper from a mineral ore deposit within a 5-spot flow regime, (2) transient flow and solute transport within a regional doublet, and (3) a real-world problem involving uranium surface complexation within a heterogeneous and extremely dynamic variably saturated flow field. Weak scalability is discussed in detail for the regional doublet problem, and several difficulties with its interpretation are noted.

Repeatability and intra- and inter-observer agreement of cervical vertebral sagittal diameter ratios in horses with neurological disease.

BACKGROUND: Sagittal ratio values (SRVs) of cervical vertebrae are used for ante-mortem diagnosis of cervical vertebral stenotic myelopathy, but intraobserver and interobserver variability in measurement may influence radiographic interpretation of vertebral stenosis in horses with neurological disease. OBJECTIVES: To determine intraobserver repeatability in SRVs, intra- and interobserver agreement in SRVs and whether or not agreement was influenced by animal age. ANIMALS: Forty-two horses (>1 year old) with neurological disease from which laterolateral computed radiographic images of C2-C7 were obtained. METHODS: Four observers made measurements from C2 to C7 for each horse and interobserver agreement for intra- and intervertebral SRVs was determined using Bland-Altman analysis (acceptable agreement: limits of agreement [LOA] ≤ 0.05) on all horses and those ≤3 (n = 25) and >3 (n = 17) years old. Each observer also made repeated measurements for 10 horses and intraobserver repeatability and agreement were determined. RESULTS: Adequate intraobserver repeatability was achieved for 6 sites. Within observers, paired measurements had a median difference ≤5.7%, but a large range in differences often occurred, most frequently at intervertebral sites. For C5, C6, C7, and C3-4, LOA ≤ 0.05 were achieved by at least 1 observer. With the exception of C5 for 1 pair, LOA were >0.05 for interobserver agreement, regardless of animal age. LOA were largest at intervertebral sites. CONCLUSIONS AND CLINICAL IMPORTANCE: Within and between observers, measurement error may limit the diagnostic accuracy of SRVs and result in discrepancies of diagnosis and treatment and warrants consideration when used clinically in horses with neurological disease.

The association of middle ear effusion with trigeminal nerve mass lesions in dogs.

The trigeminal nerve is involved in the opening of the pharyngeal orifice of the Eustachian tube by operating the tensor veli palatini muscle. The hypothesis was investigated that middle ear effusion occurs in a more severe disease phenotype of canine trigeminal nerve mass lesions compared with dogs without middle ear effusion. Three observers reviewed canine MRIs with an MRI-diagnosis of trigeminal nerve mass lesion from three institutions. Various parameters describing the musculature innervated by the trigeminal nerve were scored and compared between dogs with and without middle ear effusion. Nineteen dogs met the inclusion criteria. Ipsilateral middle ear effusion was observed in 63 per cent (95% CI 48.4 per cent to 77.6 per cent) of the dogs. The size of the trigeminal nerve mass lesions was positively correlated with the severity of masticatory muscle mass loss (Spearman r=0.5, P=0.03). Dogs with middle ear effusion had a significantly increased generalised masticatory muscle mass loss (P=0.02) or tensor veli palatini muscle loss score (P=0.03) compared with those without. Larger trigeminal nerve mass lesions were associated with a greater degree of masticatory muscle mass loss. Masticatory muscle mass and, importantly, tensor veli palatini muscle mass was more severely affected in dogs with middle ear effusion suggesting an associated Eustachian tube dysfunction.

Computed tomographic features of basihyoid ectopic thyroid carcinoma in dogs.

Eight dogs with a firm, nonpainful swelling in the ventral laryngeal region and with a final diagnosis of ectopic thyroid carcinoma were investigated by Computed Tomography (CT) at six different institutions. Computed Tomography findings were reviewed, focusing on lesion volume, shape, margins, relationship with surrounding structures and adjacent vessels, attenuation characteristics, and presence of metastases. Ectopic thyroid carcinomas were seen as oval-to-bilobed masses centered on the basihyoid bone with associated bone lysis, highly vascularized capsules with central poorly contrast enhancing areas. In all cases there was laryngeal wall infiltration, in two dogs invasion of the laryngeal lumen and in one case invasion of the ventral muscular and subcutaneous plane. Metastases were found in retropharyngeal lymph nodes (three cases) and in the lung (two cases). Ectopic thyroid carcinoma should be considered in the differential diagnosis when a mass in the basihyoid region is present. Described CT features may be typical for ectopic thyroid neoplasia and could be used to help decide the therapeutic plan.

Changes in risk factors for preterm birth in Western Australia 1984-2006.

OBJECTIVE: To characterise changing risk factors of preterm birth in Western Australia between 1984 and 2006. DESIGN: Population-based study. SETTING: Western Australia. POPULATION: All non-Aboriginal women giving birth to live singleton infants between 1984 and 2006. METHODS: Multinomial, multivariable regression models were used to assess antecedent profiles by preterm status and labour onset types (spontaneous, medically indicated, prelabour rupture of membranes [PROM]). Population attributable fraction (PAF) estimates characterized the contribution of individual antecedents as well as the overall contribution of two antecedent groups: pre-existing medical conditions (including previous obstetric history) and pregnancy complications. MAIN OUTCOME MEASURE: Antecedent relationships with preterm birth, stratified by labour onset type. RESULTS: Marked increases in maternal age and primiparous births were observed. A four-fold increase in the rates of pre-existing medical complications over time was observed. Rates of pregnancy complications remained stable. Multinomial regression showed differences in antecedent profiles across labour onset types. PAF estimates indicated that 50% of medically indicated preterm deliveries could be eliminated after removing six antecedents from the population; estimates for PROM and spontaneous preterm reduction were between 10 and 20%. Variables pertaining to previous and current obstetric complications (previous preterm birth, previous caesarean section, pre-eclampsia and antepartum haemorrhage) were the most influential predictors of preterm birth and adverse labour onset (PROM and medically indicated). CONCLUSIONS: Preterm antecedent profiles have changed markedly over the 23 years studied. Some changes may be attributable to true change, others to advances in surveillance and detection. Still others may signify change in clinical practice.

Duplicated ectopic ureter in a nine-year-old Labrador.

A nine-year-old male neutered Labrador retriever presented with a history of chronic urinary tract infections and occasional dribbling of urine. Abdominal ultrasound showed changes suggestive of a left ectopic ureter. A pneumocystogram revealed an air-filled distended tubular and tortuous structure extending from the region of the prostatic urethra to the left kidney, consistent with an ectopic ureter. Intravenous urography depicted the presence of an additional left ureter with only slightly larger diameter than the right and with normal insertion in the bladder neck. A duplicated ectopic left ureter was suspected and confirmed during surgery. To the authors' knowledge, this is the first description of a duplicated ectopic ureter in the canine species. The combination of ultrasound and contrast radiography was important to reach the diagnosis.

Gold-catalyzed annulations of 2-alkynyl benzaldehydes with vinyl ethers: synthesis of dihydronaphthalene, isochromene, and bicyclo[2.2.2]octane derivatives.

With the suitable selection of a gold catalyst as well as the appropriate control of the reaction conditions, various new gold-catalyzed cyclizations of 2-alkynyl benzaldehyde with acyclic or cyclic vinyl ethers have been developed. Acetal-tethered dihydronaphthalene and isochromenes were obtained from the reactions of 2-alkynyl benzaldehydes with acyclic vinyl ethers under mild conditions. And, more interestingly, the gold-catalyzed reactions of 2-alkynyl benzaldehyde with a cyclic vinyl ether afforded the bicyclo[2.2.2]octane derivative involving two molecules of cyclic vinyl ethers. These products contain interesting substructures that have been found in many biologically active molecules and natural products. In addition, a gold-catalyzed homo-dimerization of 2-phenylethynyl benzaldehyde 1a was observed when the reaction was carried out in the absence of vinyl ether, affording a set of separable diastereomeric products. Plausible mechanisms for these transformations are discussed; a gold-containing benzopyrylium was regarded as the crucial intermediate by which a number of these new transformations took place.

Two different corticosteroid-binding globulin variants that lack cortisol-binding activity in a greek woman.

BACKGROUND: Corticosteroid-binding globulin (CBG), encoded by SERPINA6, is the principal plasma binding protein for cortisol. Most nonsynonymous single-nucleotide polymorphisms that alter the production or function of CBG occur rarely, and their clinical significance remains obscure. METHODS: Serum and DNA were obtained from a Greek woman with low morning cortisol levels and from family members. SERPINA6 exons were sequenced, and serum CBG was measured by ELISA and cortisol-binding capacity assay. Recombinant CBG variants were produced for detailed functional studies. RESULTS: A novel heterozygous c.1282G>C transversion in exon 5 of SERPINA6, resulting in a p.Trp393Ser (W371S) substitution, was identified in the proband, who was also heterozygous for single-nucleotide polymorphisms encoding the CBG Lyon (D367N) and CBG A224S variants. The proband had no measurable plasma cortisol-binding activity despite a CBG level of 273 nm by ELISA. She inherited CBG W371S from her mother whose plasma cortisol-binding capacity was approximately 50% lower than the CBG measurements by ELISA (314 nm). The proband's father and four children were heterozygous for CBG D367N; their CBG levels by ELISA were normal, but corresponding cortisol-binding capacity measurements were 50% lower. Pedigree analysis revealed that W371S segregates with A224 and that D367N and W371S segregate separately. Recombinant CBG D367N and CBG W371S had no measureable cortisol-binding activity. CONCLUSION: A new CBG Athens (W371S) variant that lacks cortisol-binding activity has been identified in a carrier of the cortisol-binding deficient CBG Lyon (D367N) variant. Analyses of CBG levels in this pedigree illustrate how immunoassays fail to accurately reflect cortisol-binding activity.