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A 45-year-old female was admitted to our hospital due to severe aortic stenosis. Transthoracic and transesophageal echocardiography indicated the aortic valve was bicuspid, but we confirmed that the aortic valve was unicuspid by intraoperative finding. There was 1 open commissure between the left coronary cusp and the noncoronary cusp position. Aortic valve replacement was performed with a mechanical valve, and the postoperative course was uneventful. We report a very rare case of unicuspid aortic valve replacement.

In this paper, we present for the first time a “Gate-Cut-Last” integration scheme completed within the Replacement Metal Gate (RMG) module. This novel gate cut (CT) technique allows the scaling of gate extension length past the end fin which reduces parasitic capacitance, leakage and performance variation. In addition, we demonstrate that CT-in-RMG is a promising alternative integration process that can enable scaling for future logic technology nodes. Device, circuit and reliability results are shown to compare this novel CT-in-RMG process to the conventional gate cut method.

Duodenal and rectal obstructions due to urological malignancies are relatively uncommon. We report an autopsy case of an 83-year-old man with a history of renal pelvic cancer who presented these obstructions. Autopsy revealed that urothelial cancer infiltrated the bladder wall, duodenal wall, rectal wall, and prostate and widely spread in the retroperitoneal lymphatic vessel. We concluded that renal pelvic cancer recurred in the bladder wall and then infiltrated into each organ because of lymphatic dissemination. The gastrointestinal obstructions due to urinary tract cancer were lethal. Further knowledge and clinical experience regarding these types of obstructions are crucial. Keywords: Duodenal obstruction, Lymphatic dissemination, Rectal obstruction, Urothelial carcinoma

Cerebral infarction in patients with cancer is often called Trousseau's syndrome, which is a cancer-associated hypercoagulative state that causes thrombosis; however, the syndrome is rarely caused by bladder cancer. We report a case of Trousseau's syndrome manifesting as multiple cerebral infarctions caused by advanced bladder cancer in a 46-year-old male patient. The patient died due to the infarctions in the hospital. The prognosis of patients with Trousseau's syndrome caused by advanced cancer is poor. According to changing urological clinical settings, considering the risk of Trousseau's syndrome has become crucial for urologists treating patients with advanced cancer. Keywords: Bladder cancer, Cerebral infarction, Trousseau's syndrome, Urothelial cancer

Specialized hardware for deep learning using analog memory devices has the potential to outperform conventional GPUs by a large margin. At the core of such hardware are arrays of non-volatile-memory (NVM) devices that can perform the simple matrix operations needed for deep learning in parallel and in constant time. Several implementations can be found in the literature that use different materials as memory elements, including phase-change-memory (PCM), resistive-random-access-memory (RRAM), electrochemical-random-access-memory (ECRAM), and ferroelectric devices. While the current focus is to demonstrate functionality, there is an increasing concern about the reliability margins of this emerging technology. In this paper we will briefly describe operation and device requirements, and then focus on possible reliability exposure in terms of variability, stability and drift, retention and durability.

Neuromorphic computing represents a potential paradigm shift from conventional von Neumann computing architecture and shows promise for achieving massive parallelism and power efficiency for such data-centric tasks as image recognition and language processing. Based on the concept of synaptic plasticity, human-like machine learning can be potentially realized by use of arrays of electronic synapses that function in an analogous manner to biological neurons. One of the key features of this type of computing is the ability to control synaptic weights in an analog-like fashion for use in both inference and training applications. A number of existing device technologies in non-volatile memory systems exhibit attractive characteristics for such synaptic devices.[1,2] In particular, resistive switching devices (resistive random-access memory or ReRAM) can change and store their conductance value (G) in response to electrical stimuli making them potentially enabling for deep learning applications involving synaptic weights. For ReRAM devices, HfO2-based thin films can be utilized for filamentary oxide ReRAM and are an attractive option due to their fab-friendly processing and current implementation in high-volume manufacturing. In this study, we evaluated atomic layer deposition (ALD) for the growth of HfO2 for integration in both front-end-of-line (FEOL) and back-end-of-line (BEOL) compatible test structures on 300 mm wafers in order to optimize electrical performance for use as synaptic device elements in neuromorphic architectures. The effect of oxidant in the ALD process was evaluated and it was shown that H2O outperformed O3 in terms of better uniformity and lower forming voltage. By utilizing a hydrogen-based plasma either after the deposition or inserted as an intermediate step during deposition we were able to further decrease forming voltage for a fixed dielectric thickness. Reducing deposition temperature to 200°C in conjunction with the hydrogen-based plasma treatment offered an additional tuning knob to further reduce forming voltage. Stable high-resistance switching (> 100 kΩ) with analog behavior in scaled BEOL devices was also obtained using this optimized HfO2-based ReRAM. Additionally, a tight distribution of forming voltage was obtained ensuring that 99.9999% devices in a 14 nm ReRAM module can be formed below the targeted voltage. References Kuzum et al., Nanotechnology, 24, 382001 (2013) W. Burr et al., Advanced in Physics:X, 2, 89 (2016)

To study discoid meniscus in children who underwent arthroscopic surgery at our center.Thirty-four patients (39 knees) younger than 15 years with discoid lateral meniscus (mean age, 12.9 years; 13 males, 21 females) who underwent arthroscopic surgeries since 2007 were studied. The surgical procedure consisted of, in principle, saucerization with additional suture repair in the case of meniscal instability at the peripheral rim of the residual meniscus. The mechanisms of symptom onset, symptoms, complications and postoperative outcome in these cases were examined. In addition, Lysholm scores were obtained before surgery and at the last postoperative follow-up in all patients.Symptom onset was associated with sports in 18 knees, fall in 3 knees, and no definitive trigger in the remaining knees. The presenting symptoms were pain in 32 knees, catching in 11 knees, and locking in 6 knees. According to Watanabe classification, 26 knees were complete type and 13 knees were incomplete type. The modes of tear included horizontal tear in 10 knees and longitudinal tear in 10 knees, while no definitive tear was present on the knee joint surface. The surgical procedures included saucerization only in 22 knees, partial meniscectomy in 10 knees, and saucerization with suture repair in 5 knees. The mean Lysholm score was 63.9 before surgery, and improved significantly to 92.3 at the last follow-up. Only two knees developed osteochondritis dissecans after surgery. Two knees required reoperation; one knee underwent subtotal meniscectomy and one knee had partial meniscectomy with suturing.Although the short-term outcome after saucerization with or without suture repair for discoid meniscus is favorable, degenerative change or change of lower limb alignment may occur in the long term. Further long-term study is required.

Little is known regarding the epidemiology of idiopathic nephrotic syndrome (INS) in East Asia. Previous studies have suggested higher incidence of INS in Asian children, though decreasing trend of its incidence has also been shown. We conducted a nationwide study of Japanese children aged 6 months to 15 years with INS. Children who were newly diagnosed with INS between 1 January 2010 and 31 December 2012 were eligible. Children with congenital nephrotic syndrome or nephrotic syndrome secondary to nephritis were excluded. A total of 2099 children were initially diagnosed with INS and were followed for up to 4 years. The estimated incidence of INS was 6.49 cases/100,000 children per year, without clear correlation with geographical region. The male:female ratio was 1.9 and approximately 50 % of children were

IL-1β is one of the inflammatory cytokines and is cleaved from pro-IL-1β proteolytically by activated Caspase 1. For the activation of Caspase 1, inflammasome was formed by two signals, what is called, priming and triggering signals. In this study, it was found that mouse macrophage J774.1 cells, when treated by single large amount of lipopolysaccharide (LPS), produced a significant amount of IL-1β. On the other hand, IL-1β production was not detected when treated by a single, small amount of LPS. Then, focusing on endoplasmic reticulum (ER) stress response among stress responses induced by a large amount of LPS, when GSK2656157, a PERK inhibitor, was used for inhibition of ER stress, GSK2656157 reduced IL-1β production dose-dependently. Next, when Thapsigargin, an ER stress reagent, was added with LPS, IL-1β production increased more than by LPS alone. Thus, these results suggested that ER stress was involved in LPS-induced IL-1β production. When the activation of Caspase 1 was examined by fluorescence activated cell sorter analysis, it was found that GSK2656157 inhibited LPS-induced Caspase 1 activation. Further, it was confirmed that GSK2656157 did not affect LPS-induced TNF-α production and activation of NF-κB and specifically inhibited the PERK/eIF-2α pathway. Therefore, it was found that GSK2656157 specifically inhibited ER stress induced by large amount of LPS and reduced LPS-induced IL-1β production through inhibition of Caspase 1 activation.

A 37-year-old man was hospitalized for an evaluation of acute bilateral multiple subcortical infarcts. There were no specific signal abnormalities in the temporal pole or external capsule. An abdominal skin biopsy showed granular, electron-dense, osmiophilic material (GOM) in the smooth muscle cells on electron microscopy. A direct sequencing analysis of NOTCH3 revealed a heterozygous c.986G>A substitution in exon 6, resulting in a Cys329Tyr amino acid replacement. According to these findings, the patient was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencehalopathy (CADASIL). Thus, early phases of CADASIL can present as acute bilateral multiple subcortical infarcts without a characteristic temporal pole or any external capsule lesions.

To identify proteins related to the pathophysiology of aortic valve stenosis (AS), we investigated the protein profiles of AS aortic valves. Specifically, proteins were extracted from a thickened and calcified area (AS-C) and an apparently non-thickened and non-calcified area (AS-N) in an identical aortic valve leaflet in each of 6 AS patients. The proteins were then separated by 2-dimensional gel electrophoresis (2DE). Protein spots detected by 2DE were compared between the AS-C and AS-N samples. Protein spots of interest were subjected to protein identification by mass spectrometry.In total, 670 protein spots were detected by 2DE, 28 of which showed more than 1.5-fold different intensity (P < 0.05) between the AS-C and AS-N samples. Proteins were identified in 17 out of the 28 spots. Fibrinogen and lumican were identified in 9 and 3 spots, respectively. Intensity of these 12 spots was lower in the AS-C samples than in the AS-N samples. In the 1D-Western blot analysis, 4 lumican bands (80 kDa, 75 kDa, 65 kDa, and 53 kDa) were detected, of which 2 bands with 80 kDa and 75 kDa showed lower intensity in the AS-C samples than in the AS-N samples. When de-glycosylated protein samples were used in the 1D-Western blot, only a single lumican band with ~40 kDa was detected, indicating that lumican was variously glycosylated and that highly glycosylated lumican molecules were decreased in AS-C.Collectively, insufficient glycosylation of lumican in the thickened and calcified areas of AS aortic valves may be involved in the pathophysiology of AS.

We developed an Al2O3/HfO2 bi-layer gate dielectric with an in-situ O3 treatment for interface state density (Dit) and gate leakage current density (Jg) reductions on SiGe channels. We observed Ge-content dependent equivalent oxide thickness (EOT) scaling and EOT 0.44 nm was achieved with an MOS capacitor with a Si0.05Ge0.95 substrate. The O3 treatment enabled application to non-planar device structures and we demonstrated five orders of magnitude lower off currents (IOFF), a sub-threshold slope of 68 mV/decade, and a very high hole mobility of 457 cm $^{2}\text{V}^{\mathrm {-1}}\text{s}^{\mathrm {-1}}$ at an inversion carrier density (Ninv) of $1\times 10^{13}$ cm $^{\mathrm {-2}}$ for asymmetrically strained SiGe PMOSFETs with Ge% of 65%–70%.

We demonstrate a MIM capacitor structure using ZrO2 for the dielectric layer which exhibits a 25% capacitance increase (from ~43fF/mm2 to >55fF/mm2 for a ~55 Å film) with minimal leakage current increase compared to Hf based dielectrics, extending the usefulness of MIM on-chip decoupling capacitors. The MIM structure, suitable for BEOL processing is TiN/ZrO2/TiN combined with an anneal which is shown to improve the capacitance vs. leakage performance compared to doped and undoped HfO2 based control structures. GI-XRD measurements demonstrate that the capacitance increase corresponds with a phase transformation of the ZrO2 from amorphous to cubic phase, which is shown to have a dielectric constant (k) up to 35. Reliability models based on hard-breakdown (HBD) show that this structure exceeds the end-of-life targets. Servers and high-performance chips have historically relied on on-chip decoupling capacitors (decap) to reduce power supply noise in order to achieve 3 – 5.4 GHz operating frequency. Although packaging decap can be very effective at mitigating low and mid-frequency noise, on-chip decap, such as MIMCAP, is critical for mitigating mid and high-frequency noise. As Fig. 1 shows, an increase in on-chip decap can result in a significant performance benefit, due to their fast response time slowing the fastest droops, giving time for slower response elements to contribute. One method of achieving this increased decap is to increase the k of the material being used as the insulator in the MIMCAP. Following high-k gate dielectric technology, HfO2 and other Hf based dielectric stacks have been used for this layer successfully [1]. But there is a significant difference in the thermal budget that the dielectric is exposed to following the deposition between gate dielectric and MIMCAP applications. The gate dielectric, deposited prior to any metallization, will typically be exposed to a relatively high thermal budget compared to the insulator layer of a decoupling MIMCAP, which is usually placed between wiring levels in the back end of the line (BEOL) [2]. Since the thermal budget after deposition will affect the crystal structure of a material, and different crystal phases of the same material can have dramatically different dielectric constants [3], the actual dielectric constant of a particular high-k material may vary significantly depending on whether it is used as the gate dielectric or as the MIM insulator. In this work, we explore the use of a ZrO2 as the high- k layer for MIMCAP applications and show that its low crystallization temperature enables it to achieve a significantly higher k value compared to HfO2 when processed under BEOL compatible thermal conditions. Fig. 2 shows the development of the high-k phase of a 55 Å ZrO2 film as the anneal temperature is increased. The peaks at 35°, 42° and 52° are the signature of the bottom TiN electrode and do not change with anneals; but the peaks at 30.2° and 50.3° , which are seen to develop as the anneal temperature increases, match with the 111 and 220 planes of the cubic phase of ZrO2. MIMCAPs built using similarly annealed ZrO2 layers as dielectrics exhibit an increase in capacitance as shown in Fig. 3a: there is a slight increase after anneal A, significantly more increase after anneal B, and additional moderate increases after C and D. No such capacitance increase is seen when Hf based dielectrics are used (Fig. 3b). The maximum capacitance is found to be ~56fF/um2 after anneal D compared to ~43fF/um2 for the unannealed device, an increase of more than 25%, while the leakage current remains virtually unchanged at 1V, and increases by k phase at temperatures relatively lower than is typical for HfO2. Thus, we can achieve high capacitance with a relatively thick high-k layer, keeping the leakage current low, all while maintaining compatibility with BEOL processing. [1] T. Ando et al., “CMOS Compatible MIM Decoupling Capacitor with Reliable Sub-nm EOT High-k Stacks for the 7nm Node and Beyond,” Tech. Dig. IEDM 2016, pp. 9.4.1 - 9.4.4. [2] K. Fischer et al., “Low-k Interconnect Stack with multi-layer Air Gap and Tri-Metal-Insulator-Metal Capacitors for 14-nm High Volume Manufacturing,” IEEE Interconnect Tech. Conf. 2015, 10.1109/IITC-MAM.2015.7325600. [3] X. Zhao and D. Vanderbilt, “First-principles Study of Electronic and Dielectric Properties of ZrO2 and HfO2” MRS Proceedings, 747. doi:10.1557/PROC-747-T5.2/N7.2. Figure 1

In this paper, a thorough review of minimum- and maximum-value statistical distributions is provided. Using the Weibull model (statistics of minima) and the Gumbel model (statistics of maxima) along with the respective scaling properties of their scale-factor and distribution-percentile with device area (size), the application of these two types of extreme-value distributions to dielectric breakdown (BD) and memory operations is discussed. In the case of dielectric breakdown, the minimum-value distribution (the Weibull model) provides an indispensable tool to establish a valid voltage/field acceleration model from experimental perspectives. On the other hand, recent advances in the introduction of maximum-value distribution (the Gumbel model) overcomes the shortcomings of the conventional practice of adopting the normal distribution to characterize memory functional operations and provides much needed mathematical rigor and physical insight particularly for the rapid growing field of resistive random-access memory devices.

In this work, we report an extensive experimental investigation of the important statistical properties of resistive random access memory (RRAM) switching conductance. We demonstrate the Gumbel statistics, a maximum extreme-value distribution for switching-filament conductance, as opposed to the minimum extreme-value distribution such as Weibull model. We apply a Poisson random statistical distribution for the spatial generation of percolation filaments to link the RRAM conductance measurements with device areas. As a result, we can derive two important relations: area scaling properties of percentiles and scale-factors. We show the validity of this maximum extreme-value distribution model by rigorously examining the vertical percentile-scaling characteristics of experimental data. The independently extracted shape-factor from the area-dependence of scale-factors captures the merged conductance distributions in good agreement with the experimental conductance data. It is revealed that larger variability associated with RRAM conductance measurements is directly linked to the maximum-valued statistical characteristics of this model. We also demonstrate that RRAM conductance, rather than resistance, is a fundamental statistical variable.

Spallation reaction for the long-lived fission product 107Pd has been studied for the purpose of nuclear waste transmutation. The isotopic-distribution cross sections on both proton and deuteron were obtained at 118 MeV/nucleon in inverse kinematics at the RIKEN Radioactive Isotope Beam Factory. A large cross-section difference was found between the proton and deuteron results for the light-mass products. The data were compared with the SPACS semi-empirical parameterization and the PHITS calculations including both the intranuclear cascade and evaporation processes. In addition, the potential of spallation reaction for transmutation of 107Pd is discussed.

BackgroundInformation on the epidemiology of idiopathic nephrotic syndrome (INS) in children, complications of INS and the side effects of steroid therapy is scarce.MethodsThe Japanese Pediatric Survey Holding Information of Nephrotic Syndrome, a nationwide cohort study, was conducted by the Japanese Study Group of Renal Disease in Children and enrolled 2099 children with newly diagnosed INS between 1 January 2010 and 31 December 2012. We conducted a follow-up study of the complications during the first onset and the patients’ prognosis in this cohort.ResultsWe obtained follow-up data on 999 children (672 males) with a median age at onset of 4.5 years [interquartile range (IQR) 2.8–9.4] and a median follow-up period of 4.1 years (IQR 2.5–5.1). At the first onset, 24% of patients experienced severe acute kidney injury (AKI), defined as a serum creatinine increase to a level two or more times the baseline. On logistic regression analysis, age, hematuria, severe hypoalbuminemia (serum albumin ConclusionBased on the results of a multicenter questionnaire survey, the overall survival and renal survival rates were found to be excellent. However, proper management of complications, particularly in AKI and ocular hypertension, is mandatory.

Background The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. Patients and methods Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. Results One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39–0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61–1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17–0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. Conclusions The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.

Background In Japan, several large healthcare databases have become available for research since the early 2000’s. However, validation studies to examine the accuracy of these databases remain scarce. We conducted a validation study in order to estimate the positive predictive value (PPV) of local or ICD-10 codes for acute myocardial infarction (AMI) in Japanese claims. In particular, we examined whether the PPV differs between claims in the Diagnosis Procedure Combination case mix scheme (DPC claims) and in non-DPC claims. Methods We selected a random sample of 200 patients from all patients hospitalized at a large tertiary-care university hospital between January 1, 2009 and December 31, 2011 who had an inpatient claim assigned a local or ICD-10 code for AMI. We used a standardized data abstraction form to collect the relevant information from an electronic medical records system. Abstracted information was then categorized by a single cardiologist as being either definite or not having AMI. Results In a random sample of 200 patients, the average age was 67.7 years and the proportion of males was 78.0%. The PPV of the local or ICD-10 code for AMI was 82.5% in this sample of 200 patients. Further, of 178 patients who had an ICD-10 code for AMI based on any of the 7 types of condition codes in the DPC claims, the PPV was 89.3%, whereas of the 161 patients who had an ICD-10 code for AMI based on any of 3 major types of condition codes in the DPC claims, the PPV was 93.8%. Conclusion The PPV of the local or ICD-10 code for AMI was high for inpatient claims in Japan. The PPV was even higher for the ICD-10 code for AMI for those patients who received AMI care through the DPC case mix scheme. The current study was conducted in a single center, suggesting that a multi-center study involving different types of hospitals is needed in the future. The accuracy of condition codes for DPC claims in Japan may also be worth examining for conditions other than AMI such as stroke.

Recently, advanced technique and device of thoracic endovascular aortic repair (TEVAR) enabled surgical intervention for type B acute aortic dissection (BAD). However, BAD have often serious complications;cerebral infarction, spinal cord infarction, multi-organ ischemia or necrosis, and retrograde type A acute aortic dissection. TEVAR is performed for complicated BAD for the aim of life saving in such a failure case of conservative treatment. Here we reported our surgical experience of total arch replacement using frozen elephant trunk (FET) by median sternotomy, for BAD with failed conservative treatment. There are 3 advantages;brain protection using selective cerebral perfusion, main entry closure using FET, and prevention of retrograde type A acute aortic dissection following prosthetic graft replacement. We examined how to select a FET product size and described operative procedures.

Context Cyclic Cushing syndrome is a rare variant of Cushing syndrome that demonstrates periodic cortisol excess. It has been thought that inhibition of a glucocorticoid positive-feedback loop is associated with remission of hypercortisolism in ACTH-dependent cyclic Cushing syndrome. However, the underlying mechanism that triggers the development of the hypercortisolism is still unknown. We observed a case of ACTH-dependent cyclic Cushing syndrome that was developed by exogenous glucocorticoids, possibly through a glucocorticoid positive-feedback loop. Case Description A 75-year-old woman had experienced cyclic ACTH and cortisol elevations six times in the previous 4 years. Her diagnosis was cyclic Cushing syndrome. During the hypercortisolemic phase, neither low-dose nor high-dose dexamethasone suppressed her plasma ACTH and cortisol levels. Daily metyrapone therapy decreased her plasma cortisol and ACTH levels during every hypercortisolemic phase. After the sixth remission of a hypercortisolemic phase, she took 25 mg of hydrocortisone for 4 weeks and developed ACTH-dependent hypercortisolemia. Treatment with 1 mg of dexamethasone gradually increased both plasma ACTH and cortisol levels over 2 weeks, resulting in the eighth hypercortisolemic phase. Treatment using a combination of dexamethasone and metyrapone did not increase plasma ACTH or cortisol level and successfully prevented development of ACTH-dependent hypercortisolism. Conclusion We present an interesting case of cyclic Cushing syndrome in which ACTH-dependent hypercortisolemic phases relapsed during exogenous glucocorticoid treatment. A glucocorticoid positive-feedback loop and endogenous glucocorticoid synthesis may play key roles in the periodicity of hypercortisolism in cyclic Cushing syndrome.

Background Clostridium ramosum is a generally non-pathogenic enteric anaerobe, and Fournier’s gangrene is a rare necrotizing soft tissue infection with male predisposition affecting the perineum and the genital area. We report, to our knowledge, the first case of Fournier’s gangrene caused by C. ramosum in a female patient with multiple underlying conditions. Case presentation A 44-year-old woman with a 6-year history of insulin-dependent diabetes mellitus after total pancreatectomy and an 11-year history of central diabetes insipidus developed a pain in the genital area after a month of urinary catheter use. The lower abdominal pain worsened gradually over 2 weeks, and the pain, general fatigue, and loss of appetite prompted the patient’s hospital admission. As she had severe edema in her pelvic and bilateral femoral areas, ceftriaxone was started empirically after collecting two sets of blood cultures. On hospital day 2, CT examination revealed the presence of necrotizing faciitis in the genital and pelvic areas, and the antibiotics were changed to a combination of meropenem, vancomycin, and clindamycin. Gram-positive cocci and gram-positive rods were isolated from blood cultures, which were finally identified as Streptococcus constellatus and C. ramosum using superoxide dismutase and 16S rDNA sequencing. An emergent surgery was performed on hospital day 2 to remove the affected tissue. Despite undergoing debridement and receiving combined antimicrobial chemotherapies, the patient’s clinical improvement remained limited. The patient’s condition continued to deteriorate, and she eventually died on hospital day 8. In the present case, the underlying diabetes mellitus, urinary incontinence due to central diabetes insipidus, undernutrition, and edema served as the predisposing conditions. Conclusions C. ramosum is a potentially opportunistic pathogen among immunosuppressed persons and a rare cause of necrotizing fasciitis.

Structural changes in nucleus pulposus cells induce intervertebral disc (IVD) degeneration as a consequence of cytokine generation, biochemical products, and changes in the local environment. We have previously shown that inflammatory cytokines induce murine IVD (mIVD) angiogenesis and macrophage migration. Although the physiological roles of thrombin, a known proinflammatory factor, are documented, its relationship to IVD degeneration remains largely unexplored. Thrombin mediates cellular responses via the activation of protease-activated receptors such as PAR1 which has been studied in numerous cell types, but not extensively in IVD cells. This study was designed to investigate the endogenous expression of thrombin, tissue factor, and PAR1 in cultured coccygeal mIVDs. Thrombin exclusively induced MCP-1 via the MAPK-ERK and PI3K-AKT pathways. MCP-1 produced by mIVDs induced macrophage migration and thrombin treatment increased MMP-3 production to induce mIVD degeneration. These effects of thrombin on mIVDs were abrogated by a PAR1 inhibitor and suggest that thrombin may be a novel factor capable of stimulating cytokine activity implicated in the regulation several aspects of mIVDs. Mechanisms governing mIVDs, which are regulated by thrombin/PAR1 signaling, require elucidation if our understanding of IVD degenerative mechanisms is to advance.

We describe a case of Carney complex (CNC), a rare hereditary condition, that resulted in the development of cardiac myxomas. We would like to emphasize that we detected the first myxomas in both ventricles, followed by the second myxoma in the right atrium, although cardiac myxomas often originate in the left atrium. We highlight the heightened risk of recurrence and emphasize the importance of performing regular ultrasonic cardiac echography to preclude such outcomes.

A power packet dispatching system for the robot arm operation is discussed. Recent wide-band-gap power semiconductor technology realizes high speed and low switching loss devices such as SiC and GaN. The power packet dispatching system is the power distribution system in which DC voltage is delivered with the information tag in the same power line. To include the information into the packet, switching speed of the switching device is desired over MHz range. SiC or GaN device is attracting solution to realize the power packet system. Six arm robot operation with the power packet dispatching system is designed and evaluated. Design concept is described to interface the power and the information in simultaneously. Realization of the proposed method was evaluated.

Using devices with well passivated interfaces and reduced electron trapping, it is demonstrated that significant interface-state generation occurs during PBTI stress in InGaAs MOS capacitors with Al 2 O 3 /HfO 2 /TiN gate stacks. These observations on capacitors imply that the impact of interface-state generation on mobility and subthreshold-degradation need to be monitored in III-V nFET in addition to electron trapping in the gate stack.

Carney complex(CNC) is a rare genetic syndrome, characterized by spotty pigmentation of the skin, cardiac myxomas and multiple endocrine tumors. We present a case of asymptomatic cardiac myxoma associated with CNC. She was 49 year-old healthy woman whose son was known to have CNC. She was also diagnosed as CNC due to her family history, typical cutaneous findings and screening endocrine test. Screening ultrasound echocardiography resulted in discovering her asymptomatic left atrial myxoma of 30 mm size. Tumor was successfully resected via median sternotomy and no signs of recurrence were observed at 1 year follow up. Periodical follow up is mandatory because of its high recurrence rate.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cold plasma-stimulated medium (PSM) have been shown to exhibit tumor-selective cytotoxicity and have emerged as promising new tools for cancer treatment. However, to date, at least to the best of our knowledge, no data are available as to which substance is more potent in killing cancer cells. Thus, in this study, we systematically compared their abilities to kill human malignant cells from different origins. We found that PSM dose-dependently killed TRAIL-resistant melanoma, osteosarcoma and neuroblastoma cells. Moreover, PSM had little cytotoxicity toward osteoblasts. PSM was more potent than TRAIL in inducing caspase-3/7 activation, mitochondrial network aberration and caspase-independent cell death. We also found that PSM was more potent in inducing plasma membrane depolarization (PMD) and disrupting endoplasmic-mitochondrial Ca2+ homeostasis. Moreover, persistent PMD was caused by different membrane-depolarizing agents; the use of the anti-type II diabetes drug, glibenclamide, alone caused mitochondrial fragmentation and enhanced TRAIL-induced Ca2+ modulation, mitochondrial network abnormalities and caspase-independent cell killing. These results demonstrate that PSM has a therapeutic advantage over TRAIL owing to its greater capacity to evoke caspase-independent cell death via mitochondrial network aberration by disrupting membrane potential and Ca2+ homeostasis. These findings may provide a strong rationale for developing PSM as a novel approach for the treatment of TRAIL-resistant malignant cells.

This chapter discusses limits of gate dielectric scaling for advanced metal oxide semiconductor field effect transistor (MOSFET). We will review details of hafnium oxide (HfO2) gate oxide and how HfO2 can be modified to hafnium oxynitrides (HfON) and hafnium lanthanum oxynitrides (HfLaON) to increase dielectric constant for continuous equivalent oxide thickness (EOT) scaling. Bilayer hafnium oxide/titanium oxide (HfO2/TiO2) as a higher ‘k’ dielectric option for FinFET gate length (Lg) scaling is discussed. Interfacial layer (IL) scaling technologies for overall EOT scaling are also covered in this chapter. Ab-initio modeling results to evaluate ternary and quaternary gate oxide for higher ‘k’ dielectrics options, and effective metal work functions calculations to optimize and develop new metal gates are discussed. New gate dielectric reliability failure mechanisms due to three dimensional natures of FinFET devices are reviewed. Thermal oxide equivalent quality deposited silicon dioxide (SiO2) using atomic layer deposition (ALD) with post-treatments (e.g., plasma nitridation and anneals) as a high voltage input/output (I/O) gate oxide with silicon-germanium channel (SiGe) results are shown. Finally, we give a brief overview of silicon germanium pFET channel material as a gate dielectric scaling knob, and how it can enable continued EOT scaling without reliability degradation.

Whether early surgery for hip fractures is effective remains controversial. The current Japanese medical system poses some constraints on conducting early surgery. We examined the usefulness of early surgery and factors that delay surgery in patients with hip fractures treated at our hospital.Among 314 patients aged ≥60 years treated for hip fractures since January 2006, 270 patients (55 men, 215 women; mean age 84.1 years; femoral neck fracture in 111, trochanteric fracture in 159) who underwent surgery were studied. They were divided into an early surgery group (surgery up to 1 day after admission) and a delayed surgery group (later than 1 day). Clinical parameters analyzed included age, gender, pre-injury residence, pre-injury ambulatory ability, admission during public holiday, fracture site, fracture type, blood tests and urinalysis at admission, chest radiography, electrocardiography, number of systemic chronic diseases, dementia, surgical modality, blood transfusion, length of hospital stay, ambulatory ability at discharge, and hospital death. After performing univariate analysis between two groups, the parameters that were identified as significant were further tested by multivariate analysis.Among 270 patients treated for hip fracture, 112 patients (41.5%) received early surgery. Multivariate analysis identified admission during public holiday, electrocardiographic abnormalities, femoral head replacement, and length of hospital stay as significant independent factors.The causes of surgical delay were admission during public holiday, electrocardiographic abnormalities, and femoral head replacement. Although length of hospital stay was shorter in patients with early surgery, there was no difference in outcome.

To investigate the frequency of meniscal tear and the location of tear associated with anterior cruciate ligament (ACL) injury.We studied 549 patients (552 knees) who were diagnosed with ACL injury by arthroscopy at our center between January 2006 and March 2014 (8 years and 3 months). The subjects comprised 289 males and 263 females ranging in age from 13 to 66 (mean 26.1) years. The cause of injury was sports-related in 89.1 %, and the mean interval from injury to initial arthroscopy was 23 months. The patients were divided into two groups: arthroscopy performed within 8 weeks after injury (acute group; 256 knees) and more than 8 weeks after injury (chronic group; 296 knees). Frequency of meniscal tear and location of tear were compared between two groups.The incidence of meniscal tear diagnosed by arthroscopic examination was 79.2 % (437 of 552 knees) in all subjects; 72.7 % (186 of 256 knees) in acute group and 84.8 % (251 of 296 knees) in chronic group, and was significantly higher in chronic group. Regarding the locations of meniscal tears, in acute group (186 knees), medial meniscal tear only was found in 20 knees (10.8 %), lateral meniscal tear only in 129 knees (69.4 %), and bilateral (including medial and lateral) meniscal tears in 37 knees (19.9 %). In chronic group (251 knees), medial meniscal tear only was found in 62 knees (24.7 %), lateral meniscal tear only in 85 knees (33.9 %), and bilateral meniscal tears in 104 knees (41.4 %). Lateral meniscal tear was commonly associated with acute ACL injury, while medial meniscal tear with chronic ACL injury. Bucket handle tear was observed in 25 knees (medial: 17 knees, lateral: 8 knees) in acute group, and 81 knees (medial: 69 knees, lateral: 12 knees) in chronic group, and was more common in the chronic group.The incidence of meniscal tear associated with ACL injury is higher in chronic cases; the number of medial meniscal tears is particularly high, many of which require meniscectomy. Early ACL reconstruction is recommended also for the prevention of secondary meniscal tear.

The long-term outcome of pediatric IgA nephropathy (IgAN) is unclear. Objective IgAN remission criteria were proposed by the Japanese Society of Nephrology in 2013. Children with newly developed IgAN followed for >5 years were analyzed. They were divided into two groups based on histological findings at initial kidney biopsy: the focal mesangial proliferation group (Focal group) and diffuse mesangial proliferation group (Diffuse group). The primary outcome was the remission rate according to the newly proposed IgAN remission criteria. The patients comprised 53 children (31 boys; mean age at IgAN onset, 10.0 years). The Focal and Diffuse groups comprised 21 and 32 patients, respectively. No significant differences in patient characteristics were found between the groups except for steroid administration. The median follow-up period from onset was 9.9 years. Sixteen patients in the Diffuse group and 10 in the Focal group had not achieved remission at the last observation. Patient conditions 2 years after the initial treatment were almost identical to those at the last observation. Multivariate analysis revealed that proteinuria, particularly

Background This study aimed to evaluate risk factors for resistance to proton-pump inhibitor (PPI) therapy among patients with reflux esophagitis (RE) and nonerosive reflux disease (NERD) in gastroesophageal reflux disease (GERD) using a standardized questionnaire in Japan: the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG).

Objectives: The correlations of the ratio of long-/short-chain DNA fragments in blood with the existence of cancer and the clinicopathological features of colorectal cancer (CRC) were examined. The potential use of this ratio for diagnostic screening was evaluated. Methods: DNA concentrations were amplified using Alu247 for long-chain DNA fragments and Alu115 for long- and short-chain DNA fragments. The Alu247/115 ratio was calculated for 60 patients with CRC and 24 healthy volunteers. The correlation of the Alu247/115 ratio with clinicopathological variables and the efficacy of this ratio as a tumor marker were examined. The Alu247/115 ratio cut-off value was set using a receiver operating characteristic (ROC) curve. Results: The Alu247/115 ratio was significantly higher in patients with CRC than in healthy volunteers (P

Strained-SiGe, with high-Ge-content, has recently drawn significant attention as an alternate p-channel option for advance FinFETs. Among various technological challenges, gate stack is so critical to enable high-performance FETs. In this paper, key process details of the optimized gate stacks in high-Ge SiGe, such as IL formation and passivation, are disclosed and feasibility of Vth tuning by an ultra-thin replacement metal-gate scheme down to 15nm LG is demonstrated, for the first time. Moreover, near ideal SS, excellent reliability and mobility at scaled EOTs are achieved, which has led to high transconductance devices with proper junction engineering. In addition, we demonstrate the most aggressively-scaled SiGe fins reported to date formed by 3D-Ge-condensation, exhibiting excellent short-channel characteristics.

In this paper, we report multi-threshold-voltage (multi-Vt) options for stacked Nanosheet gate-all-around (GAA) transistors. V t can be modulated through workfunction metal (WFM) thickness as well as the inter-nanosheet spacing (T sus ), the combination of which may be leveraged to increase the number of undoped V t offerings within a CMOS device menu relative to a FinFET CMOS device menu, which fundamentally does not have T sus as a V t tuning option. Hence we propose our multi-V t scheme by taking advantage of the unique structure of stacked GAA transistor.

Dense crossbar arrays of non-volatile memory (NVM) can potentially enable massively parallel and highly energy-efficient neuromorphic computing systems. The key requirements for the NVM elements are continuous (analog-like) conductance tuning capability and switching symmetry with acceptable noise levels. However, most NVM devices show non-linear and asymmetric switching behaviors. Such non-linear behaviors render separation of signal and noise extremely difficult with conventional characterization techniques. In this study, we establish a practical methodology based on Gaussian process regression to address this issue. The methodology is agnostic to switching mechanisms and applicable to various NVM devices. We show tradeoff between switching symmetry and signal-to-noise ratio for HfO2-based resistive random access memory. Then, we characterize 1000 phase-change memory devices based on Ge2Sb2Te5 and separate total variability into device-to-device variability and inherent randomness from individual devices. These results highlight the usefulness of our methodology to realize ideal NVM devices for neuromorphic computing., The application of resistive and phase-change memories in neuromorphic computation will require efficient methods to quantify device-to-device and switching variability. Here, the authors assess the impact of a broad range of device switching mechanisms using machine learning regression techniques.