Direct numerical simulations of long-range infrasound propagation: Implications for source spectra estimation.

The evolution of observed dominant frequencies from a high-intensity infrasonic pulse with receiver range and stratospheric temperature is investigated using direct numerical simulations of the two-dimensional unsteady compressible Navier-Stokes equations. There is a high level of uncertainty in estimating source dominant frequencies based on received signals at sparse points on the ground. Nonlinear propagation effects in the ground-level thermospheric arrivals are found to significantly alter dominant frequency measurements compared to stratospheric arrivals with smaller amplitude sources. With a larger amplitude source, variations in observations are minimized as a result of nonlinear effects being ubiquitous across all atmospheric components of received signals but have a greater offset to the source dominant frequency. An approach to determine the source dominant frequency and minimize atmospheric variability is presented by calculating a source-to-receiver spectral transfer function averaged across the atmospheric states. This method reduces atmospheric variability in source frequency estimates within the pseudo-linear propagation regime and the average error to the known source frequency with a large amplitude source. The reduction of errors in source frequency estimates demonstrates the feasibility of using remote infrasound measurements as an indicator of source frequency and, in turn, the explosive yield of clandestine nuclear weapon test explosions.

Record High-Proximity-Induced Anomalous Hall Effect in (BixSb1-x)2Te3 Thin Film Grown on CrGeTe3 Substrate.

Quantum anomalous Hall effect (QAHE) can only be realized at extremely low temperatures in magnetically doped topological insulators (TIs) due to limitations inherent with the doping process. In an effort to boost the quantization temperature of QAHE, the magnetic proximity effect in magnetic insulator/TI heterostructures has been extensively investigated. However, the observed anomalous Hall resistance has never been more than several ohms, presumably owing to the interfacial disorders caused by the structural and chemical mismatch. Here, we show that, by growing (BixSb1-x)2Te3 (BST) thin films on structurally and chemically well-matched, ferromagnetic-insulating CrGeTe3 (CGT) substrates, the proximity-induced anomalous Hall resistance can be enhanced by more than an order of magnitude. This sheds light on the importance of structural and chemical matches for magnetic insulator/TI proximity systems.

Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition.

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.

High-Temperature Terahertz Optical Diode Effect without Magnetic Order in Polar FeZnMo_{3}O_{8}.

We present a terahertz spectroscopic study of polar ferrimagnet FeZnMo_{3}O_{8}. Our main finding is a giant high-temperature optical diode effect, or nonreciprocal directional dichroism, where the transmitted light intensity in one direction is over 100 times lower than intensity transmitted in the opposite direction. The effect takes place in the paramagnetic phase with no long-range magnetic order in the crystal, which contrasts sharply with all existing reports of the terahertz optical diode effect in other magnetoelectric materials, where the long-range magnetic ordering is a necessary prerequisite. In FeZnMo_{3}O_{8}, the effect occurs resonantly with a strong magnetic dipole active transition centered at 1.27 THz and assigned as electron spin resonance between the eigenstates of the single-ion anisotropy Hamiltonian. We propose that the optical diode effect in paramagnetic FeZnMo_{3}O_{8} is driven by single-ion terms in magnetoelectric free energy.

Successive Magnetic-Field-Induced Transitions and Colossal Magnetoelectric Effect in Ni_{3}TeO_{6}.

We report the discovery of a metamagnetic phase transition in a polar antiferromagnet Ni_{3}TeO_{6} that occurs at 52 T. The new phase transition accompanies a colossal magnetoelectric effect, with a magnetic-field-induced polarization change of 0.3 µC/cm^{2}, a value that is 4 times larger than for the spin-flop transition at 9 T in the same material, and also comparable to the largest magnetically induced polarization changes observed to date. Via density-functional calculations we construct a full microscopic model that describes the data. We model the spin structures in all fields and clarify the physics behind the 52 T transition. The high-field transition involves a competition between multiple different exchange interactions which drives the polarization change through the exchange-striction mechanism. The resultant spin structure is rather counterintuitive and complex, thus providing new insights on design principles for materials with strong magnetoelectric coupling.

Common Pesticides Used in Suicide Attempts Following the 2012 Paraquat Ban in Korea.

To determine the change in pesticides used during suicide attempts after the 2012 paraquat (PQ) ban, we evaluated the annual number of suicide attempts by pesticide ingestion between 2011 and 2014. We extracted demographic, clinical outcome, and pesticide class data from the medical records of 1,331 patients that attempted suicide by pesticide ingestion. Pesticides were sorted into 5 groups: herbicides, insecticides, fungicides, other pesticides, and combined pesticides. Each group was subdivided into various classes based on publications by the respective Resistance Action Committees. The chi-square test for trends was used to compare the annual incidence of categorical variables. The total number of suicide attempts decreased each year, from 399 in 2011 to 245 in 2014. Simultaneously, PQ ingestion decreased from 253 patients in 2011 to 60 in 2014. The proportion of PQ to pesticides also decreased from 63.4% in 2011 to 24.5% in 2014. Furthermore, the rate of decrease in the proportion of PQ to all herbicide categories increased by calendar year. In conclusion, there is a significant trend in increased annual number of suicides and proportion of suicides using glyphosates and glufosinates versus total herbicides. However, the number of suicide attempts using glyphosate and glufosinate is lower than that using PQ. The ratio of persons completing suicide to those attempting suicide after pesticide ingestion has decreased every year after the PQ ban.

Treatment efficacy of electromyography versus fiberscopy-guided botulinum toxin injection in adductor spasmodic dysphonia patients: a prospective comparative study.

INTRODUCTION: This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). METHODS: Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. RESULTS: The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. CONCLUSION: Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

Second primary mucosal malignant melanoma in hypopharynx.

Primary mucosal melanomas of the head and neck are rare. In addition, second primary mucosal melanoma following primary cutaneous malignant melanomas is very rare. We report a second primary mucosal melanoma. A 76-year-old woman, who had a previously cutaneous malignant melanoma of the left foot, visited with a complaint of a foreign body sensation of the throat. Endoscopy revealed a black mass at the left piriform sinus of the hypopharynx. After wide surgical excision of the lesion and reconstruction with a radial forearm free flap, the histopathology was confirmed to be a second primary mucosal malignant melanoma of the hypopharynx. Five months postoperatively, masses were palpated in the neck, and metastasis was diagnosed. The patient was treated with adjuvant chemotherapy and radiotherapy. Eight months postoperatively, computed tomography scans showed other metastatic masses in the liver, spleen, both adrenal glands, soft tissues of the abdominal wall, and both lungs. After that, the patient died 9 months postoperatively. We report a rare case of second primary mucosal malignant melanoma of the hypopharynx. Although rare, this case shows that a detailed examination of the hypopharynx and the head and neck should be a part of the follow-up examination in all cutaneous malignant melanoma patients.

Generation of Fel d 1 chain 2 genome-edited cats by CRISPR-Cas9 system.

Allergens from domestic cats (Felis catus) cause allergy-related health problems worldwide. Fel d 1 is a major allergen that causes severe allergic reactions in humans, including rhinitis, conjunctivitis, and life-threatening asthma. Therefore, patients with cat allergies anticipate hypoallergenic cats. We successfully generated Fel d 1 chain 2 (CH2) genome-edited cats using the CRISPR-Cas9 system in this study. T7 endonuclease 1 assay and Sanger sequencing were used to confirm the mutation in CH2 genome-edited cats. Fel d 1 level in CH2 genome-edited cats were assessed by enzyme-linked immunosorbent assay (ELISA). Remarkably, ELISA showed that the level of Fel d 1 in the CH2 homozygous genome-edited cat (Name: Alsik) was extremely low compared with that in wild type domestic cats and could be hypoallergenic cats. Additionally, we successfully cloned the CH2 homozygous genome-edited cat using cytoplasm injection clone technology. The cloned CH2 homozygous genome-edited cat was verified using microsatellite analysis. Creating hypoallergenic cats using the CRISPR-Cas9 system is a significant step forward because these cats can safely approach allergic patients.

Comparison of carboplatin- and cisplatin-based concurrent chemoradiotherapy in locally advanced cervical cancer patients with morbidity risks.

BACKGROUND: The aim of this study was to assess the activity and toxicity of primary carboplatin-based chemoradiotherapy (CarboRT) and to compare CarboRT with cisplatin-based chemoradiotherapy (CisRT) in patients with locally advanced cervical cancer and poor general condition. PATIENTS AND METHODS: Fifty-one locally advanced cervical cancer patients with morbidity risks were prospectively enrolled between January 2007 and April 2010. Eligible patients received weekly intravenous CarboRT with carboplatin 100 mg/m2, and a comparison was made with a historical patient group that received weekly CisRT with cisplatin 40 mg/m2. RESULTS: Median follow-up was 36 months (range: 4-66 months) in the CarboRT group and 53 months (range: 4-121 months) in the CisRT group. Compared with the historical CisRT group, the CarboRT group showed no statistically significant differences in recurrence (hazard ratio [HR], 1.21; 95% confidence interval [CI], 0.52-2.81) and survival (HR, 1.80; 95% CI, 0.49-6.54). The mean numbers of received cycles of CarboRT and CisRT were 7.5 ± 1.4 and 6.0 ± 1.8, respectively (p < .001). The rates of grade 3-4 toxicity were similar in the two groups. CONCLUSIONS: CarboRT was better tolerated than CisRT without compromising tumor response and survival in patients with locally advanced cervical cancer and poor general condition.

Magnetic resonance imaging and intraoperative frozen sectioning for the evaluation of risk factors associated with lymph node metastasis in endometrial cancer.

INTRODUCTION: To analyze the accuracy of magnetic resonance imaging (MRI) and intraoperative frozen sectioning (IFS) for predicting the low- and high-risk patients and risk factors associated with lymph node (LN) metastasis in patients with surgically staged endometrial cancer. METHODS: The medical records of 175 patients with endometrial cancer who underwent comprehensive surgical staging including pelvic and para-aortic LN dissection between January 2008 and July 2011 were retrospectively analyzed. Results of MRI and IFS of the uterus for the evaluation of risk factors were correlated with final pathology. RESULTS: Our results showed a high specificity and negative predictive value of MRI and IFS for the evaluation of myometrial invasion and cervical stromal invasion. Of the 41 patients identified as low risk by both MRI and IFS, none had pelvic or para-aortic LN metastases in the final pathology. CONCLUSIONS: The results indicate that MRI and IFS may be useful for the evaluation of risk factors associated with LN metastasis in patients with endometrial cancer. Magnetic resonance imaging and IFS can be used to accurately identify low-risk patients who do not need comprehensive surgical staging and may prevent unnecessary lymphadenectomy.

Lymphovascular space invasion is highly associated with lymph node metastasis and recurrence in endometrial cancer.

BACKGROUND: Lymphovascular space invasion (LVSI) has been evaluated as a predictor for nodal metastasis or poor survival in endometrial adenocarcinoma. AIMS: To evaluate whether LVSI is a prognostic factor for lymph node metastasis and relapse of disease in endometrial adenocarcinoma. MATERIALS & METHODS: We retrospectively analysed the medical records of 438 women with endometrial adenocarcinoma treated by surgical staging, including pelvic and paraaortic lymph node dissection, between January 1996 and July 2011. RESULTS: One hundred sixty-three women (37.2%) were LVSI-positive and 275 (62.8%) were negative. LVSI-positive women were significantly older and showed more advanced stage, poorer differentiation, and a higher frequency of non-endometrioid histology type, myometrial invasion, and positive peritoneal cytology than LVSI-negative women. Surgeries by laparotomy rather than laparoscopy and more adjuvant therapies were conducted in LVSI-positive women. The median number of pelvic and paraaortic lymph nodes removed were not different, but LVSI-positive patients showed more lymph node metastases. The LVSI-positive group also showed a higher recurrence of disease and lower survival rates than the LVSI-negative group. Negative predictive values of LVSI for lymph node metastasis and recurrence of disease were 96.4 and 97.1%, respectively. In multivariate analysis, LVSI did not influence overall or disease-free survival after adjusting for several confounding factors. CONCLUSIONS: In the cases that the nodal status has not been assessed in endometrial adenocarcinoma, the presence of LVSI may be a reasonable surrogate in addition to other risk factors, in determining the need for adjuvant therapy.

A new prognostic index model using meta-analysis in early-stage epithelial ovarian cancer.

OBJECTIVES: To construct a novel prognostic index (PI) model of early-stage epithelial ovarian cancer (EOC). METHODS: The PI model was constructed through meta-analyses. The methodological quality of the studies was assessed using the modified Jadad scale for randomized controlled trials (RCTs) and the Newcastle-Ottawa scale for non-RCTs. The prognosis factors of the PI model that had a significant impact on the recurrence-free survival (RFS) of patients with early-stage ovarian cancer were chosen. A total of 177 patients with early-stage ovarian cancer who were treated at Severance Hospital were analyzed using the new PI model to test its utility. RESULTS: The equation PI=2 × age+86 (if grade 2) or 105 (if grade 3)+53 (if stage Ib or Ic) or 130 (if stage II)+53 (if no lymphadenectomy)-43 (for adjuvant chemotherapy of 3 times or more)+10 (calibrating constant) was derived. Based on PI values, the high-risk group showed a significant 5 year-RFS difference compared to the low-risk group (P-value<0.01 by log-rank test) and a borderline significance in comparison to the intermediate-risk group (P-value=0.08). When the cutoff level of PI values was set at 211, the low- and high-risk groups of recurrence within 5 years were also identified by Cox regression analysis (HR=7.25, 95% CI: 2.98-17.65). CONCLUSIONS: Our PI model was predictive in this study and may be effective in clinical practice. Further prospective studies should be conducted to confirm the predictive ability of the new PI model for early-stage EOC recurrence.

Observation of a multiferroic critical end point.

The study of abrupt increases in magnetization with magnetic field known as metamagnetic transitions has opened a rich vein of new physics in itinerant electron systems, including the discovery of quantum critical end points with a marked propensity to develop new kinds of order. However, the electric analogue of the metamagnetic critical end point, a "metaelectric" critical end point, has been rarely studied. Multiferroic materials wherein magnetism and ferroelectricity are cross-coupled are ideal candidates for the exploration of this novel possibility using magnetic-field (H) as a tuning parameter. Herein, we report the discovery of a magnetic-field-induced metaelectric transition in multiferroic BiMn(2)O(5), in which the electric polarization (P) switches polarity along with a concomitant Mn spin-flop transition at a critical magnetic field H(c). The simultaneous metaelectric and spin-flop transitions become sharper upon cooling but remain a continuous cross-over even down to 0.5 K. Near the P = 0 line realized at mu(0)H(c) approximately 18 T below 20 K, the dielectric constant (epsilon) increases significantly over wide field and temperature (T) ranges. Furthermore, a characteristic power-law behavior is found in the P(H) and epsilon(H) curves at T = 0.66 K. These findings indicate that a magnetic-field-induced metaelectric critical end point is realized in BiMn(2)O(5) near zero temperature.

Comparisons of surgical outcomes, complications, and costs between laparotomy and laparoscopy in early-stage ovarian cancer.

OBJECTIVES: The purpose of this study was to compare the surgical outcomes, complications, and costs between laparoscopic staging and laparotomic staging for early-stage ovarian cancer. METHODS: We evaluated 113 patients who underwent laparoscopy (n = 26) or laparotomy (n = 87) for staging. We retrospectively analyzed patients' demographics and operative variables, including operative time, estimated blood loss, lymph node count, hospital stay, complications, postoperative pain, and return to normal activity. In addition, costs for laparoscopy and laparotomy groups were also compared. RESULTS: The mean operation time was longer in laparoscopy group compared to laparotomy group (227.6 minutes vs 184.6 minutes, P = 0.016). The laparoscopy group had less intraoperative blood loss, less transfusion requirement, shorter postoperative hospital stay, earlier general diet intake, shorter time to adjuvant chemotherapy, and lower postoperative pain score after 6, 24, and 48 hours compared with the laparotomy group. The mean number of lymph node retrievals was comparable between the groups. The incidence of operative complications was lower in the laparoscopy group (7.7%) relative to the laparotomy group (23.0%). The total average cost for staging completed via laparotomy was $1237 and that via laparoscopy was $1998, with significant difference. CONCLUSIONS: Complete surgical staging by laparoscopy was achieved in all cases with comparable operative time and less operative complications compared with laparotomy for selected patients with early-stage ovarian cancer. However, the operation costs for laparoscopy were significantly higher than the operation costs for laparotomic staging surgery.

Ethanol Extract of the Flower Chrysanthemum morifolium Augments Pentobarbital-Induced Sleep Behaviors: Involvement of Cl Channel Activation.

Dried Chrysanthemum morifolium flowers have traditionally been used in Korea for the treatment of insomnia. This study was performed to investigate whether the ethanol extract of Chrysanthemum morifolium flowers (EFC) enhances pentobarbital-induced sleep behaviors. EFC prolonged sleep time induced by pentobarbital similar to muscimol, a GABA(A) receptors agonist. EFC also increased sleep rate and sleep time when administrated with pentobarbital at a subhypnotic dosage. Both EFC and pentobarbital increased chloride (Cl(-)) influx in primary cultured cerebellar granule cells. EFC increased glutamic acid decarboxylase (GAD) expression levels, but had no effect on the expression of α1-, ß2-, and γ2-subunits of the GABA(A) receptor in the hippocampus of a mouse brain. This is in contrast to treatment with pentobarbital, which showed decreased α1-subunit expression and no change in GAD expression. In conclusion, EFC augments pentobarbital-induced sleep behaviors; these effects may result from Cl(-) channel activation.

Design of mid-infrared filter array based on plasmonic metal nanodiscs array and its application to on-chip spectrometer.

Mid-infrared wavelengths are called the molecular fingerprint region because it contains the fundamental vibrational modes inherent to the substances of interest. Since the mid-infrared spectrum can provide non-destructive identification and quantitative analysis of unknown substances, miniaturized mid-infrared spectrometers for on-site diagnosis have attained great concern. Filter-array based on-chip spectrometer has been regarded as a promising alternative. In this study, we explore a way of applying a pillar-type plasmonic nanodiscs array, which is advantageous not only for excellent tunability of resonance wavelength but also for 2-dimensional integration through a single layer process, to the multispectral filter array for the on-chip spectrometer. We theoretically and experimentally investigated the optical properties of multi-periodic triangular lattices of metal nanodiscs array that act as stopband filters in the mid-infrared region. Soft-mold reverse nanoimprint lithography with a subsequent lift-off process was employed to fabricate the multispectral filter array and its filter function was successfully extracted using a Fourier transform infrared microscope. With the measured filter function, we tested the feasibility of target spectrum reconstruction using a Tikhonov regularization method for an ill-posed linear problem and evaluated its applicability to the infrared spectroscopic sensor that monitors an oil condition. These results not only verify that the multispectral filter array composed of stopband filters based on the metal nanodiscs array when combined with the spectrum reconstruction technique, has great potential for use to a miniaturized mid-infrared on-chip spectrometer, but also provide effective guidance for the filter design.

Diagnosis and staging of primary ovarian cancer: correlation between PET/CT, Doppler US, and CT or MRI.

PURPOSE: To compare the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT), pelvic Doppler ultrasonography (US), abdomino-pelvic computed tomography (CT), and pelvic magnetic resonance imaging (MRI) for detection of ovarian cancer and to assess the role of PET/CT in evaluating the dissemination of ovarian cancer. PATIENTS AND METHODS: One hundred thirty-three women suspected to have ovarian cancer were enrolled in a prospective study before surgery between March 2005 and August 2007. The accuracy of each modality in detection of malignancy was estimated by computing the relevant areas under a receiver operating characteristics curve. Histopathologic results served as the reference standard. RESULTS: Histopathology showed benign tumors in 25 patients, borderline tumors in 13 patients, and malignant tumors in 95 patients. In distinguishing malignant/borderline from benign ovarian tumors, the accuracy of PET/CT (0.921) was higher than that of pelvis US (0.830) and abdomino-pelvic CT or pelvis MRI (0.749; P=0.013). Radiologic staging by PET/CT was concordant with surgical staging in 78% of patient and PET/CT revealed 15 (15.8%) unpredicted extra-abdominal lymph node metastasis in 95 patients with ovarian cancer. In addition, PET/CT detected new, unexpected co-existing malignant tumors in five (3.8%) cases including two thyroid tumors, two breast tumors, and one pancreatic neuroendocrine cancer. CONCLUSION: PET/CT is superior to pelvis US, abdomino-pelvic CT, and pelvic MRI for diagnosis of malignant ovarian tumors and is useful in revealing metastatic ovarian cancer and co-existing malignant tumors. Therefore, we suggest that PET/CT could be used during pre-operative evaluation of patients suspected to have ovarian cancer.

Robot-assisted staging using three robotic arms for endometrial cancer: comparison to laparoscopy and laparotomy at a single institution.

PURPOSE: To demonstrate the feasibility of robot-assisted staging surgery using three arms in patients with endometrial cancer. METHODS: One hundred nine patients with clinical stage I endometrial cancer who underwent staging surgery at Yonsei University Health System were enrolled from May 2006 to January 2009. Patient demographics and operative outcomes were prospectively collected. RESULTS: Robotic surgery using three arms was performed in 28 patients, laparoscopy in 25, and laparotomy in 56. There were no differences among the three groups in terms of patient demographics. The number of harvested pelvic lymph nodes was lower in the laparoscopy group than in the laparotomy group (18.36 +/- 7.25 vs. 24.39 +/- 10.08, respectively, P = 0.025), but there was no difference between the robot and laparotomy groups. The number of resected para-aortic lymph nodes and operative time did not differ among the three groups. The average hospital stay was longer for the laparotomy group than the robot and laparoscopy groups (10.78 days vs. 7.92 days vs. 7.67 days, respectively, P < 0.001). Operative complications and transfusions developed more frequently in the laparotomy group than in the robot and laparoscopy groups (25.0% vs. 7.1% vs. 8.0%, respectively, P = 0.049; 42.9% vs. 14.3% vs. 16.0%, respectively, P = 0.006). CONCLUSION: Robot-assisted surgery using three arms is a feasible method for surgical staging in patients with clinical stage I endometrial cancer.