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Some large earthquakes may have been triggered by large slow slip events (SSEs). This paper studies the time it takes from the most recent SSE to seismic failure in a situation where earthquakes are influenced by periodic SSEs, unlike in earlier studies that investigated the impact of a single SSE imposed at an arbitrary timing during a seismic cycle. A single-degree-of-freedom (SDOF) spring-slider model obeying a rate- and state-dependent friction (RSF) law is used to study the time to failure. The results are compared with those in Ohtani et al. which simulates megathrust earthquakes triggered by large, spontaneous SSEs along the deeper extension of a seismogenic zone in a 2-D elastic medium. Suppose a model fault under steady-rate tectonic loading is also impacted by stress steps induced by periodic SSEs. In the absence of SSEs, there is only a unique value of the characteristic slip distance L of RSF for a given seismic return period T. In the presence of SSEs, by contrast, synchronization occurs, and there exists a finite range of L values that corresponds to the same T. The timing (phase difference) of earthquakes relative to the SSEs varies continuously with L within that range. This study focuses on the case where T is triple the SSE return period, T SSE, (T = 3 T SSE) to allow comparison with Ohtani et al. For each value of L in that range, disturbance tests that assign random values to T 0, the timing of the third SSE within the seismic cycle, are conducted to obtain a probability distribution for tf , the time from that SSE to seismic failure. The distribution is converted into P (t; L), the cumulative probability that seismic failure occurs within time t of the SSE. The P (t; L) is averaged over the different L values to produce |$\bar{P}$| (t), which takes account of variability in the strength excess on the seismic fault at the time of the SSE, a parameter that is generally unknown. These numerical disturbance tests are conducted for three different values of an SSE size parameter. It is found that the larger the SSEs, the more intensely seismic failure is concentrated within short time intervals following an SSE. For the largest SSE, whereby a single SSE accounts for 3/10 of the total stress accumulated during a seismic cycle, there is a 50 per cent probability that seismic failure occurs within 132 d. These results contrast with those of Ohtani et al. in which tf was found to be concentrated more intensely within even shorter time intervals following an SSE (80 per cent probability that seismic failure occurs within 2.78 d of the SSE). It is suggested the timing of SSE-triggered seismic failure is concentrated more strongly on a fault embedded in a continuum because of a factor that cannot be taken into account by an SDOF model—a spatial structure of stress concentration that is already there on the fault even before the triggering event, the SSE. [ABSTRACT FROM AUTHOR]

The 1944 Tonankai and 1946 Nankai megathrust earthquakes are likely to have been immediately preceded by a huge slow slip event (SSE) in the deeper brittle‐to‐ductile transition zone, which accumulates slip of a meter or more within several days. The present study investigates the interaction between such huge SSEs and the characteristic earthquakes through earthquake cycle simulations obeying the rate‐ and state‐dependent friction. To simulate huge SSEs, we employ a cutoff velocity (Vcx) above which the friction changes from velocity weakening to velocity strengthening. We assume that Vcx decreases from 10 to 10−9 m/s with depth over the transition zone located between 20‐ and 35‐km depths. Depending on the characteristic slip distance L of rate and state friction, simulation results showed three patterns of earthquake nucleation. If L is small, an SSE in the transition zone directly grows into an earthquake without experiencing a separate nucleation at the brittle zone (brittle nucleation). If L is moderate, an SSE triggers brittle nucleation, which develops into an earthquake. If L is large, an SSE occurs but ceases without triggering an earthquake nor brittle nucleation, then slip deficit accumulates further to finally start brittle nucleation without the direct help of SSE, and an earthquake occurs without a large precursor. In addition, isolated huge SSEs, resembling precursory ones, occur in all cases, at most a few times per cycle. Key Points: We investigate the nucleation of characteristic earthquakes in simulated cycles involving deep huge SSEsThree distinct nucleation patterns were found; two involve a huge SSE; a huge SSE does not necessarily trigger an earthquakeSSEs and earthquake nucleation grow huge because of a unique slip profile characterized by a flatter maximum than an ellipse [ABSTRACT FROM AUTHOR]

A driving stress of the Mw5.8 reverse-faulting Awaji Island earthquake (2013), southwest Japan, was investigated using focal mechanism solutions of earthquakes before and after the mainshock. The seismic records from regional high-sensitivity seismic stations were used. Further, the stress tensor inversion method was applied to infer the stress fields in the source region. The results of the stress tensor inversion and the slip tendency analysis revealed that the stress field within the source region deviates from the surrounding area, in which the stress field locally contains a reverse-faulting component with ENE–WSW compression. This local fluctuation in the stress field is key to producing reverse-faulting earthquakes. The existing knowledge on regional-scale stress (tens to hundreds of km) cannot predict the occurrence of the Awaji Island earthquake, emphasizing the importance of estimating local-scale (< tens of km) stress information. It is possible that the local-scale stress heterogeneity has been formed by local tectonic movement, i.e., the formation of flexures in combination with recurring deep aseismic slips. The coseismic Coulomb stress change, induced by the disastrous 1995 Mw6.9 Kobe earthquake, increased along the fault plane of the Awaji Island earthquake; however, the postseismic stress change was negative. We concluded that the gradual stress build-up, due to the interseismic plate locking along the Nankai trough, overcame the postseismic stress reduction in a few years, pushing the Awaji Island earthquake fault over its failure threshold in 2013. The observation that the earthquake occurred in response to the interseismic plate locking has an important implication in terms of seismotectonics in southwest Japan, facilitating further research on the causal relationship between the inland earthquake activity and the Nankai trough earthquake. Furthermore, this study highlighted that the dataset before the mainshock may not have sufficient information to reflect the stress field in the source region due to the lack of earthquakes in that region. This is because the earthquake fault is generally locked prior to the mainshock. Further research is needed for estimating the stress field in the vicinity of an earthquake fault via seismicity before the mainshock alone. [ABSTRACT FROM AUTHOR]

Recently recognized slow slip events (SSEs) recurring in the deeper extensions of seismogenic zones along plate boundaries are drawing attention to their potential for triggering megathrust earthquakes that rupture the entire seismogenic zone. We describe how earthquakes simulated in a single-degree-of-freedom model are synchronized to the rhythm of imposed periodic SSEs. The time lag tQ from the one most recent SSE to a seismic event varies with system parameters and may take a broad range of eligible values between 0 and TSSE (SSE recurrence period). Earthquakes were found to synchronize with SSEs in various patterns depending on the proportion of SSE-driven loading within an SSE cycle, the recurrence period of the SSEs, and the duration of the SSEs, although synchronization itself remained a prevalent feature. Asynchrony was found only for long SSE durations. [ABSTRACT FROM AUTHOR]

We assessed the seismic potential around the northeastern edge of the Longmenshan fault zone (LFZ) by analyzing the aftershocks of the 2008 Mw 7.9 Wenchuan earthquake, focusing on the right-lateral strike-slip Qingchuan fault (QCF). The data used in the present study were collected from a dense network of broadband seismographs, installed after the Mw 7.9 mainshock by the China Earthquake Administration. We analyzed 440 aftershocks that occurred around the northeastern part of the aftershock area between December 2008 and June 2009, the local magnitudes (ML) of which ranged from 2.0 to 5.2. We determined 127 well-constrained focal mechanism solutions for these aftershocks down to ML 2.5 by using P-wave polarity data in conjunction with body-wave amplitudes. An analysis of the stress tensor inversion revealed that, upon approaching the QCF from the LFZ, the stress field changes from a reverse faulting regime to a mixed regime containing strike-slip components and the orientation of the maximum compressional stress changes from a NW–SE to a WNW–ESE direction. This stress field favors a right-lateral strike-slip movement along the fault. The slip tendency analysis revealed that the QCF is regarded as being favorably oriented to the present-day stress field. The coseismic Coulomb stress changes induced by the mainshock increased along the preferred fault plane in the northeastern half of the QCF, which is further loaded by viscoelastic relaxation. This evidence suggests that the potential for a future earthquake in the QCF is high. [ABSTRACT FROM AUTHOR]

A 72-year-old male had pseudomonal enteritis related to pembrolizumab. Chemotherapy for hypopharyngeal carcinoma with lung metastasis comprised cisplatin, 5-FU, and pembrolizumab. On day 14 of chemotherapy treatment he had a sudden prominent abdominal bulge, decreased consciousness, and drop in blood pressure in septic shock. CT scan showed marked intestinal gas through to intrahepatic bile ducts. Pseudomonas aeruginosa was simultaneously detected in both blood and stool cultures. Intestinal endoscopy revealed ulcerative lesions from the transverse colon to the rectum. Pathological investigations indicated apoptosis of the villus. The patient was diagnosed with pseudomonal enteritis induced by immune-related adverse events from the use of pembrolizumab. Treatment by corticosteroid and meropenem were subsequently switched to cefepime and metronidazole, and this successfully improved his colitis. In this new era of biological-targeted drugs and as clinical experience grows, we recommend a high level of alertness for potential diagnosis of infectious complications. [ABSTRACT FROM AUTHOR]

Biofilm is thought to be involved in the persistent bacterial infections caused by nontypeable Haemophilus influenzae (NTHi). This study aims to evaluate the efficacy of antibiotics against NTHi biofilms. A 96-wells pin replicator assay was applied for evaluation of antimicrobial efficacies against NTHi biofilms. The NTHi IH-202 strain for the standard and 10 clinical strains were evaluated, as well as the viability of NTHi in biofilms after antimicrobial exposures. Biofilms formed by IH-202 strain accumulated during incubation. AMPC if not high concentrations, neither reduce or inhibit biofilm formation, nor eradicate matured NTHi biofilms. The NTHi in matured biofilm were alive after exposure to amoxicillin (AMPC). Even high concentration of AMPC produced live NTHi after suspension of exposure, while tosufloxacin and garenoxacin inhibited biofilm formation of NTHi and eradicated matured biofilms. The respiratory quinolones, but not AMPC, killed NTHi in biofilms even at sub-MIC. NTHi persists in biofilms, even after exposure to AMPC. These findings may eventually lead to a better understanding of effective use of antibiotics to eradicate NTHi growing as biofilms, or even to the development of novel therapeutic agents for treating patients with mucosal NTHi biofilm infections. Meanwhile, respiratory quinolones are attractive agents in reducing NTHi biofilm formation and destroying established biofilm. [ABSTRACT FROM AUTHOR]

Density perturbations accompanying seismic waves are expected to generate prompt gravity perturbations preceding the arrival of P-waves. Vallée et al. (Science 358:1164–1168, 2017, https://doi.org/10.1126/science.aao0746) reported the detection of such pre-P-wave signals in broadband seismograms during the 2011 Tohoku-oki earthquake. Kimura et al. (Earth Planets Space 71:27, 2019, https://doi.org/10.1186/s40623-019-1006-x) considered that their detection involved some uncertain points, including a concern regarding their signal processing procedure. Specifically, to remove the instrumental response, Vallée et al. (2017) applied acausal deconvolution to the seismograms truncated at the P-wave arrivals. Generally, acausal deconvolution produces artifacts at the edge of the time window. However, they did not present quantitative assessment whether the detected signals were artifacts due to the signal processing. To avoid this concern, Kimura et al. (2019) employed another procedure that eliminated acausal processes, resulting in the detection of a pre-P-wave signal with a statistical significance of 7σ in stacked broadband seismograms. Subsequently, Vallée et al. (Earth Planets Space 71:51, 2019, https://doi.org/10.1186/s40623-019-1030-x) commented that the procedure employed by Kimura et al. (2019) for the signal detection was inappropriate because it dismissed the low-frequency components of data. Although we admit the loss of low-frequency components in the data in Kimura et al. (2019), Vallée et al. (2019) have not yet provided a full account of the validity of their own procedure. Here, we assessed the validity of the procedure employed by Vallée et al. (2017) by quantitatively evaluating the magnitude of the acausal artifacts. First, we investigated how the input acceleration waveform, having an ideal signal-like shape, was distorted by their procedure. Their acausal deconvolution indeed generated a large-amplitude terminal artifact; however, it was removed by the causal band-pass filtering performed after the deconvolution and consequently became negligible. Next, we constrained the maximum amplitude of the artifact due to the noise in a seismogram and showed that it was sufficiently small compared to the reported signal amplitudes. These results suggest that the signal waveforms seen after their procedure were not artifacts but were representing the input acceleration with sufficient accuracy. Namely, their procedure well functions as a detection method for pre-P-wave signals. In the context of this validation, we replied to the comments of Vallée et al. (2019). [ABSTRACT FROM AUTHOR]

In 2016, Japanese Society of Chemotherapy and Japan Society for Surgical Infection presented the practical guideline for appropriate usage of antimicrobial agents to prevent postoperative infections. This study aims to exhibit the validity of the guideline as a series of effective strategies for prevention of surgical site infections (SSIs) during reconstructive surgery of the head and neck cancer. We retrospectively evaluated patients who underwent head and neck reconstructive surgery with free or pedicle flaps in a single institute in Japan between July 2010 and July 2020. We evaluated the incidence of SSIs, patient backgrounds, and microbiological characteristics on the basis of antimicrobial prophylaxis recommended by the guideline. Enrolled in this study were 102 patients in our institution who underwent head and neck reconstructive surgery with free or pedicle flaps between July 2010 and July 2020. In the period between January 2018 to July 2020 after the SSI guideline was advocated (SSI guideline period), the ratio of administration of sulbactam/ampicillin (SBT/ABPC) was significantly higher (P < 0.001) and the duration of prophylactic antimicrobial treatment was significantly shorter than in the period between July 2010 to December 2017 before the SSI guideline was advocated (Pre-SSI guideline period) (P < 0.001). Incidence of SSIs were similar, even when antibiotic use was changed to be short-term single-agent administration in accordance with the practical guideline. Adherence to the current Japanese practical guideline on appropriate antimicrobial prophylaxis for SSIs can shorten the duration of usage of antimicrobial treatment without increasing the risk for occurrence of SSIs. [ABSTRACT FROM AUTHOR]

Carcinoma showing thymus-like differentiation (CASTLE) is a rare thyroid cancer. This is the first report of a case of concurrent occurrence of CASTLE with papillary thyroid carcinoma (PTC). A 66-year-old male patient had hoarseness with right vocal cord paralysis. Ultrasonography revealed a hypoechoic nodule in the inferior pole of the right thyroid lobe. Ultrasound-guided fine-needle aspiration cytology suggested differentiated thyroid cancer. The patient underwent total thyroidectomy with neck dissection. Pathological examination revealed two different thyroid cancers: a CASTLE and a follicular variant of PTC. Postoperative radiation therapy was performed. The patient was still alive after 5 year following the initial treatment without evidence of recurrence. The oncological management of patients with concurrent occurrence of different thyroid cancers should consider the biological behavior of both tumors. [ABSTRACT FROM AUTHOR]

Conclusion. The results of this study indicate that transient receptor potential subfamily 1 (TRPV1) may play a functional role in sensory cell physiology and that TRPV4 may be important for fluid homeostasis in the inner ear. Objective. To analyze the expression of TRPV1 and -4 in the normal guinea pig inner ear. Material and methods. Albino guinea pigs were used. The location of TRPV1 and -4 in the inner ear, i.e. cochlea, vestibular end organs and endolymphatic sac, was investigated by means of immunohistochemistry. Results. Immunohistochemistry revealed the presence of TRPV1 in the hair cells and supporting cells of the organ of Corti, in spiral ganglion cells, sensory cells of the vestibular end organs and vestibular ganglion cells. TRPV4 was found in the hair cells and supporting cells of the organ of Corti, in marginal cells of the stria vascularis, spiral ganglion cells, sensory cells, transitional cells, dark cells in the vestibular end organs, vestibular ganglion cells and epithelial cells of the endolymphatic sac. [ABSTRACT FROM AUTHOR]

We investigated changes in prescriptions for antimicrobial agents to treat children with acute otitis media (AOM). A descriptive study using an electronic medical record database. Of 199,896 patients enrolled between 2001 and 2019, a total of 10,797 were aged <16 years and had AOM as their first and primary disease (overall pediatric AOM cohort). In addition, 4786 patients with AOM without other comorbidities (pediatric AOM cohort) were included. In the overall pediatric AOM cohort, the age distribution ranged from 11% to 23% for those younger than 2 years and from 66% to 77% for those younger than 6 years, with no change over time. In the pediatric AOM cohort, the antimicrobial prescription rate was 91% in 2001 but declined to 40% by 2019. Antimicrobial use increased from 0% to 75% for penicillins, whereas use of cephalosporins decreased from 84% to 10%. The prescription rate for acetaminophen alone increased from 33% to 58%. There were no differences in the incidence of adverse reactions among the prescribed antimicrobials. Due to education efforts and promotion of the proper use of antimicrobials through means such as the Clinical practice guidelines for the diagnosis and management of acute otitis media in children (2006) and the Manual of Antimicrobial Stewardship (2016), a change in the use of antimicrobials occurred, leading to a trend to more proper use of these agents. [ABSTRACT FROM AUTHOR]

We previously found a trypsin-like proteinase which momentarily appears immediately before DNA synthesis in the cell cycle of Escherichia coli synchronized by phosphate starvation and which is closely related to the initiation of DNA replication (Kato, M., Irisawa, T., Morimoto, Y. and Muramatu, M., unpublished results). The proteinase was named proteinase In. It was purified approximately 2880-fold with a recovery of 15%. The isolated enzyme appeared homogeneous by gel filtration and electrophoresis. Its molecular mass was estimated by analytical gel filtration and SDS/PAGE as approximately 66 kDa. The isoelectric point of proteinase In is 4.9 and its optimal pH is approximately 9. Although protein In hydrolyzes fluorogenic substrate for trypsin, its hydrolytic activity seems markedly affected by amino-acid sequence lying towards the N-terminal from the P1 (lysine, arginine) residue. The proteinase does not hydrolyze N2-benzoyl-D,L-arginine-4-nitronanilide and fluorogenic substrates for chymotrypsin and elastase. The proteinase activity is inhibited by leupeptin, antipain and 4-nitrophenyl 4-guanidinobenzoate, but the effects of tosyl-L-lysine chloromethane, diisopropylfluorophosphate, benzamidine and pentamidine isethionate on the proteinase activity are weak or not inhibitory. Its activity is strongly affected in the presence of NaCl and KCl, and at a concentration of 1.5 M, these increase the activity 14-fold and 13-fold, respectively, above that without salt. Proteinase In was strongly inhibited by various esters of trans-4-guanidinome-thylcyclohexanecarboxylic acid, and their inhibitory effects were roughly correlated with those on growth of E. coli. Proteinase activity was found in the cytoplasmic fraction. [ABSTRACT FROM AUTHOR]

Density perturbations accompanying seismic waves are expected to generate prompt gravity perturbations preceding the arrival of P-waves. Vallée et al. (Science 358:1164–1168, 2017, https://doi.org/10.1126/science.aao0746) reported the detection of such pre-P-wave signals in broadband seismograms during the 2011 Tohoku-oki earthquake. Kimura et al. (Earth Planets Space 71:27, 2019, https://doi.org/10.1186/s40623-019-1006-x) considered that their detection involved some uncertain points, including a concern regarding their signal processing procedure. Specifically, to remove the instrumental response, Vallée et al. (2017) applied acausal deconvolution to the seismograms truncated at the P-wave arrivals. Generally, acausal deconvolution produces artifacts at the edge of the time window. However, they did not present quantitative assessment whether the detected signals were artifacts due to the signal processing. To avoid this concern, Kimura et al. (2019) employed another procedure that eliminated acausal processes, resulting in the detection of a pre-P-wave signal with a statistical significance of 7σ in stacked broadband seismograms. Subsequently, Vallée et al. (Earth Planets Space 71:51, 2019, https://doi.org/10.1186/s40623-019-1030-x) commented that the procedure employed by Kimura et al. (2019) for the signal detection was inappropriate because it dismissed the low-frequency components of data. Although we admit the loss of low-frequency components in the data in Kimura et al. (2019), Vallée et al. (2019) have not yet provided a full account of the validity of their own procedure. Here, we assessed the validity of the procedure employed by Vallée et al. (2017) by quantitatively evaluating the magnitude of the acausal artifacts. First, we investigated how the input acceleration waveform, having an ideal signal-like shape, was distorted by their procedure. Their acausal deconvolution indeed generated a large-amplitude terminal artifact; however, it was removed by the causal band-pass filtering performed after the deconvolution and consequently became negligible. Next, we constrained the maximum amplitude of the artifact due to the noise in a seismogram and showed that it was sufficiently small compared to the reported signal amplitudes. These results suggest that the signal waveforms seen after their procedure were not artifacts but were representing the input acceleration with sufficient accuracy. Namely, their procedure well functions as a detection method for pre-P-wave signals. In the context of this validation, we replied to the comments of Vallée et al. (2019). [ABSTRACT FROM AUTHOR]

Density perturbations accompanying seismic waves are expected to generate prompt gravity perturbations preceding the arrival of P-waves. Vallée et al. (Science 358:1164–1168, 2017, https://doi.org/10.1126/science.aao0746) reported the detection of such pre-P-wave signals in broadband seismograms during the 2011 Tohoku-oki earthquake. Kimura et al. (Earth Planets Space 71:27, 2019, https://doi.org/10.1186/s40623-019-1006-x) considered that their detection involved some uncertain points, including a concern regarding their signal processing procedure. Specifically, to remove the instrumental response, Vallée et al. (2017) applied acausal deconvolution to the seismograms truncated at the P-wave arrivals. Generally, acausal deconvolution produces artifacts at the edge of the time window. However, they did not present quantitative assessment whether the detected signals were artifacts due to the signal processing. To avoid this concern, Kimura et al. (2019) employed another procedure that eliminated acausal processes, resulting in the detection of a pre-P-wave signal with a statistical significance of 7σ in stacked broadband seismograms. Subsequently, Vallée et al. (Earth Planets Space 71:51, 2019, https://doi.org/10.1186/s40623-019-1030-x) commented that the procedure employed by Kimura et al. (2019) for the signal detection was inappropriate because it dismissed the low-frequency components of data. Although we admit the loss of low-frequency components in the data in Kimura et al. (2019), Vallée et al. (2019) have not yet provided a full account of the validity of their own procedure. Here, we assessed the validity of the procedure employed by Vallée et al. (2017) by quantitatively evaluating the magnitude of the acausal artifacts. First, we investigated how the input acceleration waveform, having an ideal signal-like shape, was distorted by their procedure. Their acausal deconvolution indeed generated a large-amplitude terminal artifact; however, it was removed by the causal band-pass filtering performed after the deconvolution and consequently became negligible. Next, we constrained the maximum amplitude of the artifact due to the noise in a seismogram and showed that it was sufficiently small compared to the reported signal amplitudes. These results suggest that the signal waveforms seen after their procedure were not artifacts but were representing the input acceleration with sufficient accuracy. Namely, their procedure well functions as a detection method for pre-P-wave signals. In the context of this validation, we replied to the comments of Vallée et al. (2019). [ABSTRACT FROM AUTHOR]

Earthquake ruptures cause mass redistribution, which is expected to induce transient gravity perturbations simultaneously at all distances from the source before the arrival of P-waves. A recent research paper reported the detection of such prompt gravity signals from the 2011 Tohoku-Oki earthquake by comparing observed acceleration waveforms and model simulations. The 11 observed waveforms presented in that paper recorded in East Asia shared a similar trend above the background seismic noise and were in good agreement with the simulations. However, the signal detection was less quantitative because the significance of the observed signals was not discussed and the waveforms at other stations in the region were not shown. In this study, similar trends were not observed in most of the data recorded near the stations used in the aforementioned study, suggesting that the reported signals were only local noises. We thus took a different approach to identify the prompt signals. We optimized the multi-channel data recorded by superconducting gravimeters, broadband seismometers, and tiltmeters. Though no signal was identified in the single-trace records, the stacked trace of the broadband seismometer array data in Japan showed a clear signal above the reduced noise level. The signal amplitude was 0.25 nm/s2 for an average distance of 987 km from the event hypocenter. This detection was confirmed with a statistical significance of 7σ, where σ is the standard deviation of the amplitude of the background noise. This result provided the first constraint on the amplitude of the observed prompt signals and may serve as a reference in the detection of prompt signals in future earthquakes. [ABSTRACT FROM AUTHOR]