30-day morbidity and mortality after transoral robotic surgery for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma: A retrospective analysis of two prospective adjuvant de-escalation trials (MC1273 & MC1675).

OBJECTIVE: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials. MATERIALS AND METHODS: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement. RESULTS: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage. CONCLUSION AND RELEVANCE: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.

Non-opioid analgesics and post-operative pain following transoral robotic surgery for oropharyngeal cancer.

OBJECTIVE: To investigate associations between multimodal analgesia and post-operative pain among patients undergoing transoral robotic surgery for oropharyngeal squamous cell carcinoma. METHODS: Records of patients who underwent surgery from 5 September 2012 to 30 November 2016 were abstracted. Associations were assessed using multivariable analysis. RESULTS: A total of 216 patients (mean age of 59.1 years, 89.4 per cent male) underwent transoral robotic surgery (92.6 per cent were human papilloma virus positive, 87.5 per cent had stage T1-T2 tumours, and 82.9 per cent had stage N0-N1 nodes). Gabapentin (n = 86) was not associated with a reduction in severe pain. Ibuprofen (n = 72) was administered less often in patients with severe pain. Gabapentin was not associated with increased post-operative sedation (p = 0.624) and ibuprofen was not associated with increased bleeding (p = 0.221). Post-operative opioid usage was not associated with surgical duration, pharyngotomy, bilateral neck dissections, tumour stage, tumour size, subsite or gabapentin. CONCLUSION: Scheduled low-dose gabapentin was not associated with improved pain control or increased respiratory depression. Ibuprofen was not associated with an increased risk of bleeding and may be under-utilised.

Baseline characteristics of the patient population in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus (SAVOR)-TIMI 53 trial.

BACKGROUND AND AIMS: SAVOR-TIMI 53 was designed to study the effects of the DPP-4 inhibitor saxagliptin on cardiovascular outcomes in high risk type 2 diabetes patients with diverse levels of diabetes control and background anti-diabetic drugs. The goal of this article is to describe the baseline characteristics of this hypothesis driven study. MATERIALS AND METHODS: A total of 16 496 diabetic patients from North America (31.9%), Western Europe (26.0%), Eastern Europe (17.3%), Latin America (16.4%) and Asia (8.3%), with either established cardiovascular disease (78.3%) or with ≥two additional cardiovascular risk factors (21.7%) were randomised to saxagliptin or placebo. Biomarkers of inflammation and insulin resistance were taken at baseline and 2 years later in order to correlate saxagliptin effect on cardiovascular outcome to its effect on inflammation and insulin resistance. RESULTS: Mean [+/-standard deviation (SD)] age was 65.0 (+/-8.6) years, 66.9% were male, body mass index was 31.2 kg/m² (+/-5.6), mean diabetes duration was 11.9 years (+/-8.9) and the mean HbA1c 8.0% (+/-1.4%). HbA1c < 7% was most prevalent among North Americans (30.8%) and least among Asians (15.1%), whereas HbA1c > 9% was 30.7% in Latin America 27.0% in Asia and 15.1% in North America. Diabetic retinopathy was reported in 12.3% of patients, nephropathy in 17.7% and amputation in 2.5%. Diabetic treatments categories were as follows: no medication (5.4%), 1 oral anti-diabetic drug (OAD) (25.0%), ≥2 OAD (27.7%) and/or insulin (40.9%). The prevalence of micro-albuminuria was twice as high among insulin users compared with users of ≥2 OAD. Baseline statin use (78.3% overall) varied by region. CONCLUSION: The SAVOR-TIMI 53 patient population, with differing background diabetes control and anti-diabetic treatment, provides global representation of diabetic patients with established cardiovascular disease or at high risk for cardiovascular disease and is well-positioned to determine the effect of saxagliptin on cardiovascular events.

Multiscale imaging characterization of dopamine transporter knockout mice reveals regional alterations in spine density of medium spiny neurons.

The dopamine transporter knockout (DAT KO) mouse is a model of chronic hyperdopaminergia used to study a wide range of neuropsychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), drug abuse, depression, and Parkinson's disease (PD). Early studies characterizing this mouse model revealed a subtle, but significant, decrease in the anterior striatal volume of DAT KO mice accompanied by a decrease in neuronal cell body numbers (Cyr et al., 2005). The present studies were conducted to examine medium spiny neuron (MSN) morphology by extending these earlier reports to include multiscale imaging studies using correlated light microscopy (LM) and electron microscopy (EM) techniques. Specifically, we set out to determine if chronic hyperdopaminergia results in quantifiable or qualitative changes in DAT KO mouse MSNs relative to wild-type (WT) littermates. Using Neurolucida Explorer's morphometric analysis, we measured spine density, dendritic length and synapse number at ages that correspond with the previously reported changes in striatal volume and progressive cell loss. Light microscopic analysis using Neurolucida tracings of photoconverted striatal MSNs revealed a highly localized loss of dendritic spines on the proximal portion of the dendrite (30 µm from the soma) in the DAT KO group. Next, thick sections containing MSN dendritic segments located at a distance of 20-60 µm from the cell soma, a region of the dendrite where spine density is reported to be the highest, were analyzed using electron microscope tomography (EMT). Because of the resolution limits of LM, the EM analysis was an extra measure taken to assure that our analysis included nearly all spines. Spine density measurements collected from the EMT data revealed only a modest decrease in the DAT KO group (n=3 mice) compared to age-matched WT controls (n=3 mice), a trend that supports the LM findings. Finally, a synaptic quantification using unbiased stereology did not detect a difference between DAT KO mice (n=6 mice) and WT controls (n=7 mice) at the EM level, supporting the focal nature of the early synaptic loss. These findings suggest that DAT KO mice have MSNs with highly localized spine loss and not an overall morphologically distinct cell shape. The characterization of morphological changes in DAT KO mice may provide information about the neural substrates underlying altered behaviors in these mice, with relevance for human neurological disorders thought to involve altered dopaminergic homeostasis. Results from this study also indicate the difficulty in correlating structural changes across scales, as the results on fine structure revealed thus far are subtle and non-uniform across striatal MSNs. The complexities associated with multiscale studies are driving the development of shared online informatics resources by gaining access to data where it is being analyzed.

Hierarchical classification of switchgrass genotypes using SSR and chloroplast sequences: ecotypes, ploidies, gene pools, and cultivars.

Switchgrass (Panicum virgatum L.) is an important crop for bioenergy feedstock development. Switchgrass has two main ecotypes: the lowland ecotype being exclusively tetraploid (2n = 4x = 36) and the upland ecotype being mainly tetraploid and octaploid (2n = 8x = 72). Because there is a significant difference in ploidy, morphology, growth pattern, and zone of adaptation between and within the upland and lowland ecotypes, it is important to discriminate switchgrass plants belonging to different genetic pools. We used 55 simple sequence repeats (SSR) loci and six chloroplast sequences to identify patterns of variation between and within 18 switchgrass cultivars representing seven lowland and 11 upland cultivars from different geographic regions and of varying ploidy levels. We report consistent discrimination of switchgrass cultivars into ecotype membership and demonstrate unambiguous molecular differentiation among switchgrass ploidy levels using genetic markers. Also, SSR and chloroplast markers identified genetic pools related to the geographic origin of the 18 cultivars with respect to ecotype, ploidy, and geographical, and cultivar sources. SSR loci were highly informative for cultivar fingerprinting and to classify plants of unknown origin. This classification system is the first step toward developing switchgrass complementary gene pools that can be expected to provide a significant heterotic increase in biomass yield.

Tracking the effects of rigidity percolation down to the liquid state: relaxational dynamics of binary chalcogen melts.

The stochastic dynamics of binary liquids with formula AxB1-x, x=0-0.4 is investigated by neutron spin-echo spectroscopy. These compositions comprise samples of varying chemical connectivity, ranging from twofold-coordinated liquid Se to higher average coordinated As2S3. The parameters giving the temperature dependence of the relaxation patterns show a quasilinear dependence on the average coordination number. The results thus extend the validity of the rigidity concept into the normal liquid state and emphasize the role played by the fine details of atomic bonding on the dynamics at 10 ps-1 ns scales.

Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice.

beta-Site APP-cleaving enzyme 1 (BACE1) is required for the penultimate cleavage of the amyloid-beta precursor protein (APP) leading to the generation of amyloid-beta peptides that is central to the pathogenesis of Alzheimer's disease. In addition to its role in endoproteolysis of APP, BACE1 participates in the proteolytic processing of neuregulin 1 (NRG1) and influences the myelination of central and peripheral axons. Although NRG1 has been genetically linked to schizophrenia and NRG1(+/-) mice exhibit a number of schizophrenia-like behavioral traits, it is not known whether altered BACE1-dependent NRG1 signaling can cause similar behavioral abnormalities. To test this hypothesis, we analyze the behaviors considered to be rodent analogs of clinical features of schizophrenia in BACE1(-/-) mice with impaired processing of NRG1. We demonstrate that BACE1(-/-) mice exhibit deficits in prepulse inhibition, novelty-induced hyperactivity, hypersensitivity to a glutamatergic psychostimulant (MK-801), cognitive impairments, and deficits in social recognition. Importantly, some of these manifestations were responsive to treatment with clozapine, an atypical antipsychotic drug. Moreover, although the total amount of ErbB4, a receptor for NRG1 was not changed, binding of ErbB4 with postsynaptic density protein 95 (PSD95) was significantly reduced in the brains of BACE1(-/-) mice. Consistent with the role of ErbB4 in spine morphology and synaptic function, BACE1(-/-) mice displayed reduced spine density in hippocampal pyramidal neurons. Collectively, our findings suggest that alterations in BACE1-dependent NRG1/ErbB4 signaling may participate in the pathogenesis of schizophrenia and related psychiatric disorders.

Development of structural order during supercooling of a fragile oxide melt.

The authors have studied the structural evolution of the fragile glass-forming liquid CaAl2O4 during supercooling from the stable liquid phase to the cold glass below Tg. The evolution is characterized by a sharpening of the first diffraction peak and a shortening of the average nearest-neighbor bond length around 1.25Tg, indicating an increase in the degree of both intermediate-range and short-range orders occurring close to the dynamical crossover temperature. The cooling curve developed a kink at this temperature, indicating a simultaneous change in thermodynamic properties.

Longitudinal excitations in Mg-Al-O refractory oxide melts studied by inelastic x-ray scattering.

The dynamic structure factor S(Q,omega) of the refractory oxide melts MgAl2O4 and MgAl4O7 is studied by inelastic x-ray scattering with aerodynamic levitation and laser heating. This technique allows the authors to measure simultaneously the elastic response and transport properties of melts under extreme temperatures. Over the wave vector Q range of 1-8 nm-1 the data can be fitted with a generalized hydrodynamic model that incorporates a slow component described by a single relaxation time and an effectively instantaneous fast component. Their study provides estimates of high-frequency sound velocities and viscosities of the Mg-Al-O melts. In contrast to liquid metals, the dispersion of the high-frequency sound mode is found to be linear, and the generalized viscosity to be Q independent. Both experiment and simulation show a weak viscosity maximum around the MgAl4O7 composition.

Structure of molten yttrium aluminates: a neutron diffraction study.

We used the aerodynamic levitation technique combined with CO2 laser heating to study the structure of liquid yttrium aluminates above their melting point with neutron diffraction. For various yttria contents, we determined the structure factors and corresponding pair correlation functions describing the short-range order in the liquids. In particular, we derived Al-O and Y-O bond distances and coordination numbers. Experimental data are compared with ab initio molecular dynamics, carried out using the VASP code where the interatomic forces are obtained from density functional theory. In particular, partial pair correlation functions have been calculated and are in relatively good agreement with the experimental observations.

Magnetic critical scattering in solid Co80Pd20.

Using small-angle neutron scattering combined with a containerless aerodynamic levitation technique for high temperatures, we have measured the temperature dependence of the correlation length ξ of near-critical magnetic fluctuations in the solid phase of the completely miscible fcc alloy Co80Pd20. A fit to our data yields a critical exponent ν = 0.76 ± 0.05 for the divergence of ξ(T) above the ferromagnetic transition temperature Tc. This value of ν is consistent with the prediction of the three-dimensional Heisenberg model for magnetic critical scattering.

Quantum and classical relaxation in the proton glass.

The hydrogen-bond network formed from a crystalline solution of ferroelectric RbH2PO4 and antiferroelectric NH4H2PO4 demonstrates glassy behavior, with proton tunneling the dominant mechanism for relaxation at low temperature. We characterize the dielectric response over seven decades of frequency and quantitatively fit the long-time relaxation by directly measuring the local potential energy landscape via neutron Compton scattering. The collective motion of protons rearranges the hydrogen bonds in the network. By analogy with vortex tunneling in superconductors, we relate the logarithmic decay of the polarization to the quantum-mechanical action.

Automated microscopy system for mosaic acquisition and processing.

An automatic mosaic acquisition and processing system for a multiphoton microscope is described for imaging large expanses of biological specimens at or near the resolution limit of light microscopy. In a mosaic, a larger image is created from a series of smaller images individually acquired systematically across a specimen. Mosaics allow wide-field views of biological specimens to be acquired without sacrificing resolution, providing detailed views of biological specimens within context. The system is composed of a fast-scanning, multiphoton, confocal microscope fitted with a motorized, high-precision stage and custom-developed software programs for automatic image acquisition, image normalization, image alignment and stitching. Our current capabilities allow us to acquire data sets comprised of thousands to tens of thousands of individual images per mosaic. The large number of individual images involved in creating a single mosaic necessitated software development to automate both the mosaic acquisition and processing steps. In this report, we describe the methods and challenges involved in the routine creation of very large scale mosaics from brain tissue labelled with multiple fluorescent probes.

Structural properties of molten dilute aluminium-transition metal alloys.

The short-range order in liquid binary Al-rich alloys (Al-Fe, Al-Ti) was studied by x-ray diffraction. The measurements were performed using a novel containerless technique which combines aerodynamic levitation with inductive heating. The average structure factors, S(Q), have been determined for various temperatures and compositions in the stable liquid state. From S(Q), the pair correlation functions, g(r), have been calculated. The first interatomic distance is nearly temperature-independent, whereas the first-shell coordination number decreases with increasing temperature for all the alloys investigated. For the Al-Fe alloys, room-temperature scanning electron microscropy (SEM) studies show the formation of a microstructure, namely the existence of Al(13)Fe(4) inclusions in the Al matrix.

A review of the current use of magnetic resonance imaging in pregnancy and safety implications for the fetus.

This paper presents an overview of the application of and risks of exposure to Magnetic Resonance Imaging (MRI) in pregnancy. It reviews the risks to the fetus by considering the hazards in terms of the three main components of an MRI system. These are the static magnetic field, the time-varying magnetic gradient fields and the pulsed radio frequency fields. The hazards discussed are biological effects, miscarriage, heating effects and acoustic noise exposure. This paper also presents a survey of MRI sites within the United Kingdom to ascertain the extent of MRI usage in pregnancy. To validate the situation of MRI in pregnancy a survey was sent to 352 MR units throughout the United Kingdom. The questions were grouped to assess (a) maternal MRI diagnosis (b) fetal MRI and (c) work practices for pregnant MRI staff. The results showed that 91% of sites were imaging pregnant women in need of diagnosis in the second and third trimester. This paper highlights that MRI can add information for fetal central nervous system abnormalities identified by ultrasound screening, however within the UK direct fetal imaging was only performed in 8% of sites. This paper indicates the need for research to be undertaken for specific MRI clinical conditions. It also advises that risk assessment for pregnant staff working in MRI is performed, and that there is a clear need for further research into the effects of MRI in pregnancy as there is a need for clear authoritive advice.

Unconventional density dependence of the stochastic dynamics in an organic liquid.

The density dependence of the diffusive rotational and center-of-mass dynamics of 2-methyl-pyridine is investigated by means of the concurrent use of quasielastic neutron scattering and molecular dynamics simulations. The dependence of both translation and rotational diffusion coefficients shows a distinctive change of slope with increasing density taking place about rho=0.975 g/cm3. Such a change in the dynamics can be related to observations made in other liquids composed of oblate-spheroidal particles.

Intermediate-range order in permanently densified GeO2 glass.

Information about the partial structure factors of densified GeO2 glass has been obtained from neutron and x-ray diffraction measurements. Densification causes a reduction in the length scale of the intermediate range order (IRO). The difference structure factors obtained by combining the x-ray and neutron data so as to eliminate one partial structure factor at a time shows the greatest effects when the Ge-Ge correlations are eliminated and least when O-O correlations are eliminated. This implies that the reduced length scale results from a decrease in the next-nearest neighbor Ge-O and O-O distance caused by a rotation about the Ge-O-Ge bonds and a distortion of the GeO4 tetrahedra.

Microscopic dynamics of liquid aluminum oxide.

Collective excitations have been observed in liquid aluminum oxide at high temperatures by combining a containerless sample environment with inelastic x-ray scattering. The excitation spectra show a well-defined triplet peak structure at lower wave vectors Q (1 to 6 nanometers-1) and a single quasi-elastic peak at higher Q. The high-Q spectra are well described by kinetic theory. The low-Q spectra require a frequency-dependent viscosity and provide previously unknown experimental constraints on the behavior of liquids at the interface between atomistic and continuum theory.

Observations of Breinlia booliati in a new host, Rattus rattus jalorensis, from Kuantan, state of Pahang, Malaysia.

Breinlia booliati Singh and Ho, 1973 is described from the Malaysian wood rat, Rattus rattus jalorensis Bonhote. The parasites presented here were originally discovered in 1955 in Kuantan, Malaysia, but were not classified until now. On the basis of morphological observations of anatomical structures and comparisons with other species of Breinlia, it was determined that the parasites were B. booliati. The parasites discussed here show slight deviation from B. booliati, but they do not warrant a new species classification. There is some variation in anatomical measurements, the number of male caudal papillae, and the morphology of the microfilariae. Breinlia booliati from a new host is described in this article, with a brief discussion on Rattus species that are hosts of B. booliati and vectors that transmit the parasite. The occurrence of B. booliati in R. r. jalorensis represents the first report of the parasite in this host.

Effects of anti-odor automobile air-conditioning system products on adherence of Serratia marcescens to aluminum.

Sixteen commercial products for use in automobile air-conditioning systems (ACS), most designated for abatement of malodors presumably of microbial origin, were examined for their potential to inhibit attachment and to detach cells of the Gram-negative bacterium Serratia marcescens on aluminum sections. Numbers of attached cells were appreciably reduced (>60%) following immersion in three alcohol-type and two acrylic-coating-type products. Several products had essentially no effect on the attached cells. Most of the products indicated for alleviation of associated microbial odors from ACS provided only short-term effects. When products were coated onto aluminum prior to exposure to the cells, water-insoluble coatings appeared to provide more consistent inhibition of primary adherence of S. marcescens. The differences in degrees of primary adherence of a selected strain of S. marcescens to variously treated aluminum provided a rapid and reproducible assessment of potential antimicrobial efficacy of ACS products.