Intraspecific variation in morphology of spiny pollen grains along an altitudinal gradient in an insect-pollinated shrub.

Intraspecific variations in pollen morphological traits are poorly studied. Interspecific variations are often associated with pollination systems and pollinator types. Altitudinal environmental changes, which can influence local pollinator assemblages, provide opportunities to explore differentiation in pollen traits of a single species over short distances. The aim of this study is to examine intraspecific variations in pollen traits of an insect-pollinated shrub, Weigela hortensis (Caprifoliaceae), along an altitudinal gradient. Pollen spine phenotypes (length, number and density), pollen diameter, lipid mass (pollenkitt) around pollen grains, pollen production per flower and pollinator assemblages were compared at four sites at different altitudes. Spine length and the spine length/diameter ratio of pollen grains were greater at higher altitudes but not correlated with flower or plant size. Spine number and density increased as flower size increased, and pollen lipid mass decreased as plant size increased. Bees were the predominant pollinators at low-altitude sites whereas flies, specifically Oligoneura spp. (Acroceridae), increased in relative abundance with increasing altitude. The results of this study suggest that the increase in spine length with altitude was the result of selection favouring longer spines at higher-altitude sites and/or shorter spines at lower-altitude sites. The altitudinal variation in selection pressure on spine length could reflect changes in local pollinator assemblages with altitude.

Observation of Collective Resonance Modes in a Chiral Spin Soliton Lattice with Tunable Magnon Dispersion.

A chiral spin soliton lattice (CSL), one of the representative systems of a magnetic superstructure, exhibits reconfigurability in periodicity over a macroscopic length scale. Such coherent and tunable characteristics of the CSL lead to an emergence of elementary excitation of the CSL as phononlike modes due to translational symmetry breaking and bring a controllability of the dispersion relation of the CSL phonon. Using a broadband microwave spectroscopy technique, we directly found that higher-order magnetic resonance modes appear in the CSL phase of a chiral helimagnet CrNb_{3}S_{6}, which is ascribed to the CSL phonon response. The resonance frequency of the CSL phonon can be tuned between 16 and 40 GHz in the vicinity of the critical field, where the CSL period alters rapidly. The frequency range of the CSL phonon is expected to extend over 100 GHz as extrapolated on the basis of the theoretical model. The present results indicate that chiral helimagnets could work as materials useful for broadband signal processing in the millimeter-wave band.

Denosumab-related osteonecrosis of the jaw after tooth extraction and the effects of a short drug holiday in cancer patients: a multicenter retrospective study.

Pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer duration of denosumab therapy, and female sex were significantly associated with an increased risk of denosumab-related osteonecrosis of the jaw after tooth extraction in patients with cancer on oncologic doses of denosumab. A short drug holiday did not protect against this complication. INTRODUCTION: This study retrospectively investigated the relationship between various risk factors, including brief discontinuation of denosumab, and development of denosumab-related osteonecrosis of the jaw (DRONJ) after tooth extraction in patients with cancer who were receiving oncologic doses of this agent. METHODS: Data were collected on demographic characteristics, duration of denosumab therapy, whether or not denosumab was discontinued before tooth extraction (drug holiday), duration of discontinuation, presence of pre-existing inflammation, and whether or not additional surgical procedures were performed. Risk factors for DRONJ after tooth extraction were evaluated by univariate and multivariate analyses. RESULTS: A total of 136 dental extractions were performed in 72 patients (31 men, 41 women) with cancer who were receiving oncologic doses of denosumab. Post-extraction DRONJ was diagnosed in 39 teeth (28.7%) in 25 patients. Tooth extraction was significantly associated with development of DRONJ only in patients with pre-existing inflammation (odds ratio [OR] 243.77), those on corticosteroid therapy (OR 73.50), those with periapical periodontitis (OR 14.13), those who had been taking oncologic doses of denosumab for a longer period (OR 4.69), and in women (OR 1.04). There was no significant difference in the occurrence of DRONJ between patients who had a drug holiday before tooth extraction and those who did not. CONCLUSIONS: These findings suggest that inflamed teeth should be extracted immediately in patients with cancer who are receiving oncologic doses of denosumab. Drug holidays have no significant impact on the risk of DRONJ.

Lead-free MCP to improve coincidence time resolution and reduce MCP direct interactions.

Achieving direct imaging of the annihilation position of a positron on an event-by-event basis using an ultrafast detector would have a great impact on the field of nuclear medicine. Cherenkov emission is the most attractive physical phenomenon for realizing such an ultrafast timing performance. Moreover, a microchannel-plate photomultiplier tube (MCP-PMT) is one of the most promising photodetectors for fully exploiting the fast timing properties of Cherenkov emission owing to its excellent single photon time resolution of 25 ps full width at half maximum (FWHM). However, as the MCP structure generally contains a lead compound, the gamma rays frequently and directly interact with the MCP, resulting in the degradation of its timing performance and generation of undesirable side peaks in its coincidence timing histogram. To overcome this problem, we have developed a new MCP-PMT based on an MCP consisting of borosilicate glass, thus drastically reducing the probability of the photoelectric effect occurring in the MCP. To evaluate its insensitivity to gamma rays and its timing performance, a coincidence experiment was performed and showed that the probability of direct interactions was reduced by a factor of 3.4. Moreover, a coincidence time resolution of 35.4 ± 0.4 ps FWHM, which is equivalent to a position resolution of 5.31 mm, was obtained without any pulse height/area cut, improving to 28.7 ± 3.0 ps when selecting on the highest amplitude events by careful optimization of the voltage divider circuit of the new MCP-PMT. The timing performance of this new MCP-PMT presents an important step toward making direct imaging possible.

The use of mechanical restraint in Pacific Rim countries: an international epidemiological study.

AIMS: The use of mechanical restraint is a challenging area for psychiatry. Although mechanical restraint remains accepted as standard practice in some regions, there are ethical, legal and medical reasons to minimise or abolish its use. These concerns have intensified following the Convention on the Rights of Persons with Disabilities. Despite national policies to reduce use, the reporting of mechanical restraint has been poor, hampering a reasonable understanding of the epidemiology of restraint. This paper aims to develop a consistent measure of mechanical restraint and compare the measure within and across countries in the Pacific Rim. METHODS: We used the publicly available data from four Pacific Rim countries (Australia, New Zealand, Japan and the United States) to compare and contrast the reported rates of mechanical restraint. Summary measures were computed so as to enable international comparisons. Variation within each jurisdiction was also analysed. RESULTS: International rates of mechanical restraint in 2017 varied from 0.03 (New Zealand) to 98.9 (Japan) restraint events per million population per day, a variation greater than 3000-fold. Restraint in Australia (0.17 events per million) and the United States (0.37 events per million) fell between these two extremes. Variation as measured by restraint events per 1000 bed-days was less extreme but still substantial. Within all four countries there was also significant variation in restraint across districts. Variation across time did not show a steady reduction in restraint in any country during the period for which data were available (starting from 2003 at the earliest). CONCLUSIONS: Policies to reduce or abolish mechanical restraint do not appear to be effecting change. It is improbable that the variation in restraint within the four examined Pacific Rim countries is accountable for by psychopathology. Greater efforts at reporting, monitoring and carrying out interventions to achieve the stated aim of reducing restraint are urgently needed.

Diagnostic Value of Model-Based Iterative Reconstruction Combined with a Metal Artifact Reduction Algorithm during CT of the Oral Cavity.

BACKGROUND AND PURPOSE: Metal artifacts reduce the quality of CT images and increase the difficulty of interpretation. This study compared the ability of model-based iterative reconstruction and hybrid iterative reconstruction to improve CT image quality in patients with metallic dental artifacts when both techniques were combined with a metal artifact reduction algorithm. MATERIALS AND METHODS: This retrospective clinical study included 40 patients (men, 31; women, 9; mean age, 62.9 ± 12.3 years) with oral and oropharyngeal cancer who had metallic dental fillings or implants and underwent contrast-enhanced ultra-high-resolution CT of the neck. Axial CT images were reconstructed using hybrid iterative reconstruction and model-based iterative reconstruction, and the metal artifact reduction algorithm was applied to all images. Finally, hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithm data were obtained. In the quantitative analysis, SDs were measured in ROIs over the apex of the tongue (metal artifacts) and nuchal muscle (no metal artifacts) and were used to calculate the metal artifact indexes. In a qualitative analysis, 3 radiologists blinded to the patients' conditions assessed the image-quality scores of metal artifact reduction and structural depictions. RESULTS: Hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithms yielded significantly different metal artifact indexes of 82.2 and 73.6, respectively (95% CI, 2.6-14.7; P < .01). The latter algorithms resulted in significant reduction in metal artifacts and significantly improved structural depictions(P < .01). CONCLUSIONS: Model-based iterative reconstruction + metal artifact reduction algorithms significantly reduced the artifacts and improved the image quality of structural depictions on neck CT images.

Visualization of ferroaxial domains in an order-disorder type ferroaxial crystal.

Ferroaxial materials that exhibit spontaneous ordering of a rotational structural distortion with an axial vector symmetry have gained growing interest, motivated by recent extensive studies on ferroic materials. As in conventional ferroics (e.g., ferroelectrics and ferromagnetics), domain states will be present in the ferroaxial materials. However, the observation of ferroaxial domains is non-trivial due to the nature of the order parameter, which is invariant under both time-reversal and space-inversion operations. Here we propose that NiTiO3 is an order-disorder type ferroaxial material, and spatially resolve its ferroaxial domains by using linear electrogyration effect: optical rotation in proportion to an applied electric field. To detect small signals of electrogyration (order of 10-5 deg V-1), we adopt a recently developed difference image-sensing technique. Furthermore, the ferroaxial domains are confirmed on nano-scale spatial resolution with a combined use of scanning transmission electron microscopy and convergent-beam electron diffraction. Our success of the domain visualization will promote the study of ferroaxial materials as a new ferroic state of matter.

Interleukin-4 Restores Insulin Sensitivity in Insulin-Resistant Osteoblasts by Increasing the Expression of Insulin Receptor Substrate 1.

Obesity and latent inflammation can give rise to insulin resistance and type 2 diabetes. Here we established an insulin resistance model of osteoblasts to explore the restoration effect of anti-inflammatory interleukin-4 (IL-4) on insulin sensitivity and its mechanism. We found that IL-4 inhibited cell proliferation in a concentration- and time-dependent manner. Insulation resistance significantly reduced the phosphorylation levels of the insulin receptor substrate 1 (IRS1; Tyr612), Akt (Ser473), and AS160 (Ser318) proteins. The addition of IL-4 to the insulin resistance model led to a dose-dependent stimulation of the phosphorylation of IRS1, Akt, and AS160. IL-4 fully restored the activation of the insulin cascade in insulin-resistant cells at the concentration of 50 ng/ml. Additionally, IL-4 promoted the expression of IRS1 in a time-dependent manner. We conjecture that IL-4 restores insulin sensitivity in osteoblasts by upregulating the expression of IRS1. It was also found that IL-4 promoted the expression of osteoprotegerin depending on the time of exposure. This effect may play an important role in the regulation of the energy metabolism in the whole body.

Precise analysis of the timing performance of Cherenkov-radiator-integrated MCP-PMTs: analytical deconvolution of MCP direct interactions.

In order to achieve the ultimate goal of reducing coincidence time resolution (CTR) to 10 ps, thus enabling reconstruction-less positron emission tomography, a Cherenkov-radiator-integrated microchannel plate photomultiplier tube (CRI) reaching CTR of sub-50 ps full width at half maximum (FWHM) has been developed. However, a histogram of time differences between a pair of the CRIs shows undesirable side peaks, which are caused by gamma rays directly interacting with the micro channel plates (MCPs). Such direct interaction events are detrimental to the timing performance of the CRI. In this paper, we demonstrate an analytical method of deconvolving MCP direct interaction events from the timing histogram. Considering the information of the main and the two side peaks, the timing uncertainty caused by the MCP direct interaction events is deconvolved and the CTR of the CRI is analytically investigated. Consequently, the CTR is improved from 41.7 to 40.5 ps FWHM by the deconvolution. It means that a mixture of the Cherenkov radiator events and the MCP direct interaction events contribute to the CTR by a factor of 10 ps. The timing performance of the MCP direct interaction events are also evaluated. The CTR between the two MCPs is found to be 66.2 ps FWHM. This indicates that a photocathode-free radiation detector with high timing performance is possible. Elimination of the photocathode from the detector would make detector construction easier and more robust.

Postoperative adjuvant therapy for patients with loco-regionally advanced oral squamous cell carcinoma who are at high risk of recurrence.

Extranodal extension (ENE) of lymph node metastasis and the presence of a positive or close margin (PCM) are major risk factors for head and neck squamous cell carcinoma recurrence. This retrospective multicentre cohort study compared the prognostic impact of postoperative radiotherapy (RT) and concurrent chemoradiotherapy (CCRT) in oral squamous cell carcinoma (OSCC) patients at high risk of recurrence. One hundred and eighteen patients with PCM and/or ENE who underwent definitive surgery plus either adjuvant RT or CCRT using cisplatin for OSCC were investigated. The cohort-wide 5-year loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates (the main outcome measures) were 54.3%, 35.8%, and 43.2%, respectively. Multivariate analysis showed that age ≥64 years (hazard ratio (HR) 0.584), cT3-4 stage (HR 1.927), ≥4 metastatic lymph nodes (HR 1.912), and PCM (HR 2.014) were significant independent predictors of OS. Moreover, postoperative CCRT with cisplatin was associated with a significantly improved LRC rate, but not with improved DFS or OS rates, compared to postoperative RT (HR 0.360). Given that CCRT with cisplatin does not significantly improve survival, additional clinical trials will be required to validate new regimens that further improve the outcomes of patients with loco-regionally advanced OSCC going forward.

A Case of Feline T-cell Lymphoma with Tropism for Striated Muscle and Peripheral Nerve.

An 11-year-old female American shorthair cat was presented with a 3-month history of hindlimb ataxia and knuckling of the left forelimb. Clinical abnormalities included weight loss, hyperaesthesia of the neck and back, cardiac murmur and systemic muscle atrophy. The cat died 10 days after the initial presentation and a necropsy examination was performed. Grossly, extensive pale lesions were seen in the wall of the left ventricle and the septum of the heart. There were no detectable masses in the heart, skeletal muscles or peripheral nerves. Histopathological examination revealed diffuse, extensive infiltration of atypical lymphoid cells in the heart; the cardiac muscles were markedly degenerate and atrophic and were replaced by the neoplastic cells. Neoplastic cells with similar morphology were seen in all specimens of the skeletal muscles and peripheral nerves. Clonality analysis of the paraffin wax-embedded heart tissue revealed a monoclonal rearrangement of the gene encoding the T-cell receptor γ chain. Based on these findings, the case was diagnosed as T-cell lymphoma with tropism for striated muscle and peripheral nerve.

Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Characterisation of antibiotic resistance of Salmonella isolated from dog treats in Japan.

Dog treats might be contaminated with Salmonella. In Canada and the USA, outbreaks of human salmonellosis related to exposure to animal-derived dog treats were reported. Consequently, surveillance data on Salmonella contamination of dog treats have been gathered in many countries, but not in Japan. In the current study, we investigated whether dog treats in Japan were contaminated with Salmonella. Overall, 303 dog treats (of which 255 were domestically produced) were randomly collected and the presence of Salmonella investigated. Seven samples were positive for Salmonella enterica subsp. enterica. Among these isolates, three were identified as serovar 4,5,12:i:-; two were serovar Rissen; and two were serovar Thompson. All serovar 4,5,12:i:- and Thompson isolates were resistant to one or more drugs. Two serovar Rissen isolates were fully susceptible to all tested antimicrobial agents. All Salmonella isolates were susceptible to cefotaxime, ciprofloxacin and nalidixic acid. The gene blaTEM was detected in two serovar 4,5,12:i:- isolates. The blaCTX-M and blaCMY genes were not detected in any isolates. This study demonstrated that dog treats in Japan could constitute a potential source of dog and human Salmonella infections, including multidrug-resistant Salmonella isolates.

Coincidence time resolution of 30 ps FWHM using a pair of Cherenkov-radiator-integrated MCP-PMTs.

Radiation detectors dedicated to time-of-flight positron emission tomography (PET) have been developed, and coincidence time resolution (CTR) of sub-100 ps full width at half maximum (FWHM) has been achieved by carefully optimizing scintillators and photodetectors. Achieving a CTR of 30 ps FWHM by using a pair of annihilation γ-rays would allow us to directly localize the annihilation point within an accuracy of 4.5 mm. Such direct localization can potentially eliminate the requirement of image reconstruction processes in clinical PET systems, which would have a huge impact on clinical protocols and molecular imaging. To obtain such a high CTR, researchers have investigated the use of prompt emissions such as Cherenkov radiation and hot-intra band luminescence. Although it is still challenging to achieve a CTR of 30 ps FWHM even with a Cherenkov-based detector, the experimentally measured CTR is approaching the goal. In this work, we developed a Cherenkov-radiator-integrated micro-channel plate photomultiplier tube (CRI-MCP-PMT), where there are no optical boundaries between the radiator and photocathode, and its timing performance was investigated. By removing the optical boundaries, reflections are eliminated and transmission to the photocathode is improved, resulting in high timing capability. As a result, a CTR of 30.1 ± 2.4 ps FWHM, which is equivalent to a position resolution of 4.5 ± 0.3 mm along a line of response (LOR), was obtained by using a pair of CRI-MCP-PMTs.

Medication-related osteonecrosis of the jaw after tooth extraction in cancer patients: a multicenter retrospective study.

Root amputation, immunosuppressive therapy, mandibular tooth extraction, pre-existing inflammation, and longer duration of treatment with bone-modifying agents were significantly associated with an increased risk of medication-related osteonecrosis of the jaw. Hopeless teeth should be extracted without drug holiday before the development of inflammation in cancer patients receiving high-dose bone-modifying agents. INTRODUCTION: No studies have comprehensively analyzed the influence of pre-existing inflammation, surgical procedure-related factors such as primary wound closure, demographic factors, and drug holiday on the incidence of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this study was to retrospectively investigate the relationships between these various factors and the development of MRONJ after tooth extraction in cancer patients receiving high-dose bone-modifying agents (BMAs) such as bisphosphonates or denosumab. METHODS: Risk factors for MRONJ after tooth extraction were evaluated with univariate and multivariate analyses. The following parameters were investigated in all patients: demographics, type and duration of BMA use, whether BMA use was discontinued before tooth extraction (drug holiday), the duration of such discontinuation, the presence of pre-existing inflammation, and whether additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed. RESULTS: We found that root amputation (OR = 22.62), immunosuppressive therapy (OR = 16.61), extraction of mandibular teeth (OR = 12.14), extraction of teeth with pre-existing inflammation, and longer duration (≥ 8 months) of high-dose BMA (OR = 7.85) were all significantly associated with MRONJ. CONCLUSIONS: Tooth extraction should not necessarily be postponed in cancer patients receiving high-dose BMA. The effectiveness of a short-term drug holiday was not confirmed, as drug holidays had no significant impact on MRONJ incidence. Tooth extraction may be acceptable during high-dose BMA therapy until 8 months after initiation.

Moving beyond the conventional stratified analysis to estimate an overall treatment efficacy with the data from a comparative randomized clinical study.

For a two-group comparative study, a stratified inference procedure is routinely used to estimate an overall group contrast to increase the precision of the simple two-sample estimator. Unfortunately, most commonly used methods including the Cochran-Mantel-Haenszel statistic for a binary outcome and the stratified Cox procedure for the event time endpoint do not serve this purpose well. In fact, these procedures may be worse than their two-sample counterparts even when the observed treatment allocations are imbalanced across strata. Various procedures beyond the conventional stratified methods have been proposed to increase the precision of estimation when the naive estimator is consistent. In this paper, we are interested in the case when the treatment allocation proportions vary markedly across strata. We study the stochastic properties of the two-sample naive estimator conditional on the ancillary statistics, the observed treatment allocation proportions and/or the stratum sizes, and present a biased-adjusted estimator. This adjusted estimator is asymptotically equivalent to the augmentation estimators proposed under the unconditional setting. Moreover, this consistent estimation procedure is also equivalent to a rather simple procedure, which estimates the mean response of each treatment group first via a stratum-size weighted average and then constructs the group contrast estimate. This simple procedure is flexible and readily applicable to any target patient population by choosing appropriate stratum weights. All the proposals are illustrated with the data from a cardiovascular clinical trial, whose treatment allocations are imbalanced.