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The selection criteria for secondary cytoreductive surgery (SCS) for recurrent endometrial cancer (EC) remain to be defined. The present study aimed to identify predictors for favorable survival after SCS for the disease. We retrospectively reviewed the medical records of 112 patients who relapsed by 2016 among 1052 who were diagnosed with primary EC between 1985 and 2014. Characteristics associated with overall survival (OS) after SCS were identified using univariate and multivariate analyses. Twenty-nine of the 112 patients who relapsed underwent SCS. Complete resection was achieved in 18 (62%) patients, whose OS after SCS was significantly better than that of patients receiving incomplete resection (68 vs. 20 months; p = 0.001). Endometrioid histology and performance status (PS) 0 were significant and independent factors for a favorable OS (p = 0.005, and 0.049). The OS of patients with both factors was better than patients with one or no factors (median 75, 19 and 4 months; p = 0.001 and 0.00001). The number of predictors was associated with the rate of complete resection (p = 0.001). Patients with endometrioid histology and PS 0 should be offered SCS for recurrent EC. Prospective trials are warranted to verify this proposal.

We will begin by a quick but thorough look at the effects of faults, errors and failures, caused by terrestrial neutrons originating from cosmic rays, on the terrestrial electronic systems in the variety of industries. Mitigation measures, taken at various levels of design hierarchy from physical to systems level against neutron-induced adverse effects, are then introduced. Challenges for retaining robustness under future technology development are also discussed. Such challenges in mitigation approaches are featured for SRAMs (Static Random Access Memories), FFs (Flip-Flops), FPGAs (Field Programmable Gate Arrays) and computer systems as exemplified in the following articles: (i) Layout aware neutron-induced soft-error simulation and fault tolerant design techniques are introduced for 6T SRAMs. The PNP layout instead of conventional NPN layout is proposed and its robustness is demonstrated by using the MONTE CARLO simulator PHITS. (ii) RHBD (Radiation-Hardened By Design) FFs hardened by using specially designed redundant techniques are extensively evaluated. BCDMR (Bistable Cross-Coupled Dual Modular Redundancy) FFs is proposed in order to avoid MCU (Multi-Cell Upset) impacts on FF reliability. Its robustness is demonstrated thorough a set of neutron irradiation tests. (iii) CGRA (Coarse-Grained Reconfigurable Architecture) is proposed for an FPGA-chip-level tolerance. Prototype CGRA-FPGA chips are manufactured and their robustness is demonstrated under alpha particle/neutron irradiation tests. (iv) Simulation techniques for failures in heterogeneous computer system with memory hierarchy consisting of a register file, an L1 cache, an L2 cache and a main memory are also proposed in conjunction with masking effects of faults/errors.

This chapter introduces the applications of the Flexible Reliability Reconfigurable Array (FRRA) processors, which is presented in Sect. 3.4, in a non-von Neumann architecture, and discusses its advantages when it is used in the Internet of Things (IoT) applications. FRRA is an embodiment of the concept of embedded automaton that we introduce as an essential element for building the IoT. We will start by looking at the role played by embedded system processors and point out that employing non-von Neumann architecture is inevitable (essential) to accomplish the speed/power performance required for embedded system applications. The major target application of embedded microprocessor is the IoT, and space-born sensor applications are quoted in this chapter as examples of the IoT. Space systems are somewhat special but are typical IoT applications which require dependability as an essential feature. Another important aspect of the embedded automaton based on the FRRA architecture is the contribution of behavioral synthesis technology. Practical application implementation on the reconfigurable processor is realized with the maturity of a high-level behavioral synthesis technology called CyberWorkBench (CWB).

Time redundancy is sometimes an only option for enhancing circuit reliability when the circuit area is severely restricted. In this paper, a time-redundant error-correction scheme, which is particularly suitable for coarse-grained reconfigurable arrays (CGRAs), is proposed. It judges the correctness of the executions by comparing the results of two identical runs. Once a mismatch is found, the second run is terminated immediately to start the third run, under the assumption that the errors tend to persist in many applications, for selecting the correct result in the three runs. The circuit area and reliability of the proposed method is compared with a straightforward implementation of time-redundancy and a selective triple modular redundancy (TMR). A case study on a CGRA revealed that the area of the proposed method is 1% larger than that of the implementation for the selective TMR. The study also shows the proposed scheme is up to 2.6x more reliable than the full-TMR when the persistent error is predominant.

ObjectiveElevated plasma D-dimer (DD) is associated with decreased survival among patients with breast, lung, and colon cancers. The present study clarifies the prognostic significance of pretreatment plasma DD levels in patients with epithelial ovarian cancer (EOC).MethodsWe investigated pretreatment DD levels and other variables for overall survival using univariate and multivariate analyses in 134 consecutive patients with EOC stages II to IV who were initially treated between November 2004 and December 2010.ResultsThe median follow-up period was 53 (7–106) months. Univariate analysis significantly associated elevated pretreatment DD (≥2.0 μg/mL) levels to poor 5-year overall survival rates irrespective of previously treated venous thromboembolism (72.2% vs 52.6%,P= 0.039). Cancer antigen 125 levels of 200 U/mL or higher (P= 0.011), distant metastases (P= 0.0004), residual tumors (P< 0.0001), and International Federation of Gynecology and Obstetrics stage III/IV (P= 0.0033) were also poor prognostic factors. Multivariate analysis independently associated DD levels of 2.0 μg/mL or higher (P= 0.041), distant metastases (P= 0.013), and residual tumors (P< 0.0001) with poor overall survival.ConclusionsHigh pretreatment DD levels are associated with poor overall survival in patients with EOC independently of venous thromboembolism and tumor extension and might comprise a promising prognostic biomarker for patients with EOC.

This paper proposes a placement algorithm using analytical placement (AP) and low-temperature simulated annealing (SA) for mixed-grained reconfigurable architecture (MGRA) with dedicated carry chains. The target MGRAs are assumed to have fine-grained blocks with dedicated carry chains to implement high-speed adders/subtracters and coarse-grained blocks to implement complicated arithmetic operations. Although this mixed-grained architecture is expected to enhance the performance of the implemented application circuit, placement becomes problematic because of the inherent placement constraints. For example, some logic blocks have many connections to others and constraints such as these cause simple pair-swap-based SA to converge to a local optimum. The proposed algorithm uses AP to determine an initial placement for SA. The AP explores an appropriate placement of coarse-grained blocks and adders/subtracters consisting of fine-grained blocks and dedicated carry chains. On the other hand, SA is mainly used to determine optimal placement of the remaining fine-grained blocks. The evaluations show that the proposed algorithm reduces the placement cost, critical path delay, and runtime by 18.4%, 6.0%, and 67.6% on average, respectively, over the versatile place and route (VPR) approach. The benchmark includes circuits consisting of only fine-grained logic. Hence, the proposed algorithm is expected to improve the placement quality for a wide range of application circuits.

This paper proposes a mixed-grained reconfigurable architecture consisting of fine-grained and coarse-grained fabrics, each of which can be configured for different levels of reliability depending on the reliability requirement of target applications, e.g. mission-critical applications to consumer products. Thanks to the fine-grained fabrics, the architecture can accommodate a state machine, which is indispensable for exploiting C-based behavioral synthesis to trade latency with resource usage through multi-step processing using dynamic reconfiguration. In implementing the architecture, the strategy of dynamic reconfiguration, the assignment of configuration storage and the number of implementable states are key factors that determine the achievable trade-off between used silicon area and latency. We thus split the configuration bits into two classes; state-wise configuration bits and state-invariant configuration bits for minimizing area overhead of configuration bit storage. Through a case study, we experimentally explore the appropriate number of implementable states. A proof-of-concept VLSI chip was fabricated in 65 nm process. Measurement results show that applications on the chip can be working in a harsh radiation environment. Irradiation tests also show the correlation between the number of sensitive bits and the mean time to failure. Furthermore, the temporal error rate of an example application due to soft errors in the datapath was measured and demonstrated for reliability-aware mapping. key words: reconfigurable architecture, soft error, radiation test, behavioral synthesis, state machine

Background: Radical hysterectomy is recommended for endometrial adenocarcinoma patients with suspected gross cervical involvement. However, the efficacy of operative procedure has not been confirmed. Methods: The patients with endometrial adenocarcinoma who had suspected gross cervical involvement and underwent hysterectomy between 1995 and 2009 at seven institutions were retrospectively analysed (Gynecologic Oncology Trial and Investigation Consortium of North Kanto: GOTIC-005). Primary endpoint was overall survival, and secondary endpoints were progression-free survival and adverse effects. Results: A total of 300 patients who underwent primary surgery were identified: 74 cases with radical hysterectomy (RH), 112 patients with modified radical hysterectomy (mRH), and 114 cases with simple hysterectomy (SH). Median age was 47 years, and median duration of follow-up was 47 months. There were no significant differences of age, performance status, body mass index, stage distribution, and adjuvant therapy among three groups. Multi-regression analysis revealed that age, grade, peritoneal cytology status, and lymph node involvement were identified as prognostic factors for OS; however, type of hysterectomy was not selected as independent prognostic factor for local recurrence-free survival, PFS, and OS. Additionally, patients treated with RH had longer operative time, higher rates of blood transfusion and severe urinary tract dysfunction. Conclusion: Type of hysterectomy was not identified as a prognostic factor in endometrial cancer patients with suspected gross cervical involvement. Perioperative and late adverse events were more frequent in patients treated with RH. The present study could not find any survival benefit from RH for endometrial cancer patients with suspected gross cervical involvement. Surgical treatment in these patients should be further evaluated in prospective clinical studies.

Background: We and others previously reported the prognostic significance of PTEN mutational status on favourable survival in endometrial carcinomas. Here, we demonstrate that loss of PTEN expression in immunohistochemistry is an independent prognostic marker for favourable survival in endometrial carcinomas. Methods: We conducted immunohistochemical analyses of PTEN, PIK3CA, phosphorylated Akt (p-Akt), and p27 in primary endometrial carcinomas from 221 patients. Mutation of PTEN was analysed further. Results: Expression of PTEN was lost in 56 patients (25%), and PIK3CA was overexpressed in 159 patients (72%). Overexpression of PIK3CA was associated with p-Akt overexpression (P

Introduction Silent venous thromboembolism (VTE) often occurs before treatment in ovarian or endometrial cancer and management can decrease VTE after treatment. However, the incidence of VTE before treatment and the impact of management are still unclear in cervical cancer. Materials and Methods We investigated the incidence of VTE before treatment in 272 consecutive patients with cervical cancer, and the impact of management on prevention of VTE during and after treatment. D-dimer levels before treatment were examined in all patients. Venous ultrasonography of the lower extremities was performed in patients with D-dimer ≥ 1.5 μg/ml. Deep vein thrombosis (DVT) in the pelvis or abdomen was diagnosed by enhanced computed tomography. Results Thirteen patients (4.8%; 3 preoperatively, 10 before radiotherapy or concurrent chemoradiotherapy) were diagnosed with DVT, although DVT was symptomatic in only 1 patient. None of the 13 patients showed pulmonary embolism on pulmonary scanning. Although 4 of 128 patients (3.1%) developed VTE after radical hysterectomy, none of the 124 patients who underwent radiotherapy or concurrent chemoradiotherapy developed VTE during or after treatment. Conclusions These data suggest that VTE before treatment occurs less frequently with cervical cancer than with ovarian or endometrial cancer. However, management may decrease VTE during and after treatment, especially radiotherapy.

This paper proposes a novel method to determine a priority for applying selective triple modular redundancy (selective TMR) against single event upset (SEU) to achieve cost-effective reliable implementation of application circuits onto coarse-grained reconfigurable architectures (CGRAs). The priority is determined by an estimation of the vulnerability of each node in the data flow graph (DFG) of the application circuit. The estimation is based on a weighted sum of the node parameters which characterize impact of the SEU in the node on the output data. This method does not require time-consuming placement-and-routing processes, as well as extensive fault simulations for various triplicating patterns, which allows us to identify the set of nodes to be triplicated for minimizing the vulnerability under given area constraint at the early stage of design flow. Therefore, the proposed method enables us efficient design space exploration of reliability-oriented CGRAs and their applications.

A large scale, 50×20 crossbar switch block (CSB) is newly developed for a nonvolatile, highly-dense reconfigurable logic. A compact two-varistors selected complementary atom switch (a.k.a. via-switch) is placed at each cross-point, in which the two control lines connected to the varistors can realize the multiple fan-outs without select transistors. The improved a-Si/SiN/a-Si varistor with a novel triple layered SiN shows superior nonlinearity (NL) of 1.1×105 with J max =1.63MA/cm2 while keeping very low static power of 0.2μW for the CSB. The developed CSB is also applicable for nonvolatile configuration memory for look up tables (LUTs) as well as routing switches used in low power reconfigurable logic.

Infrared sensor system is a major concern for inter-planetary missions that investigate the nature and the formation processes of planets and asteroids. The infrared sensor system requires signal preprocessing functions that compensate for the intensity of infrared image sensors to get high quality data and high compression ratio through the limited capacity of transmission channels towards ground stations. For those implementations, combinations of Field Programmable Gate Arrays (FPGAs) and microprocessors are employed by AKATSUKI, the Venus Climate Orbiter, and HAYABUSA2, the asteroid probe. On the other hand, much smaller size and lower power consumption are demanded for future missions to accommodate more sensors. To fulfill this future demand, we developed a novel processor architecture which consists of reconfigurable cluster cores and programmable-logic cells with complementary atom switches. The complementary atom switches enable hardware programming without configuration memories, and thus soft-error on logic circuit connection is completely eliminated. This is a noteworthy advantage for space applications which cannot be found in conventional re-writable FPGAs. Almost one-tenth of lower power consumption is expected compared to conventional re-writable FPGAs because of the elimination of configuration memories. The proposed processor architecture can be reconfigured by behavioral synthesis with higher level language specification. Consequently, compensation functions are implemented in a single chip without accommodating program memories, which is accompanied with conventional microprocessors, while maintaining the comparable performance. This enables us to embed a processor element on each infrared signal detector output channel.

This paper proposes a highly-dense reconfigurable architecture that introduces via-switch device, which is a kind of resistive RAM and is used in crossbar switches. Since via-switch is implemented in BEOL layers only, the FEOL layer under the crossbar can be fully exploited for highly-dense logic blocks. The proposed architecture uses the FEOL layer for fine-grained look-up tables and coarse-grained arithmetic/memory units for better performance and highly wide applications. In a case study of application mapping, the proposed architecture reduces array area by 76% thanks to mixed grained logic structure and overlay bidirectional interconnection. Thanks to 18F2 footprint and one order of magnitude lower resistivity of via-switch compared to MOS switch, the crossbar density is improved by 26× and the delay and energy in the interconnection are reduced by 90% and 93% at 0.5V operation.

JPEG XR is an emerging image coding standard, based on HD Photo developed by Microsoft Corporation. It supports high compression performance twice as high as the de facto image coding system, namely, JPEG, and also has an advantage over JPEG 2000 in terms of computational cost. JPEG XR is expected to be widespread for many devices including embedded systems in the near future. In this article, we propose a novel architecture for JPEG XR encoding. In previous architectures, entropy coding was the throughput bottleneck because it was implemented as a sequential algorithm to handle data with dependency. We found that there is no dependency in intra-macroblock data, and we could safely pipeline all the encoding processes including the entropy coding. In addition, each module of our architecture, which can be regarded as a pipeline stage, can be parallelized. As a result, our architecture can achieve 12.8 pixel/cycle at its maximum. To demonstrate our architecture, we designed three versions of our architecture with different degrees of parallelism of one, two, and four. Our four-way parallel architecture achieves 579 Mpixel/sec at 181MHz clock frequency for grayscale images.

Aim: Repeated treatment with carboplatin increases the incidence of hypersensitivity reactions. Current managements for carboplatin hypersensitivity reactions involve premedication, desensitization, and replacing agents. However, preventive effects for recurrent reactions by the former two methods are still limited, and substituting non-platinum agent can attenuate efficacy against platinum-sensitive diseases. The aim of this study was to evaluate the safety and efficacy of substituting nedaplatin, another platinum compound, as a strategy to deal with carboplatin hypersensitivity reactions in gynecologic cancers. Material and Methods: Patients who experienced carboplatin hypersensitivity reactions and subsequently switched to nedaplatin between 2001 and 2009 were identified through our database. The incidence and severity of nedaplatin hypersensitivity were examined. Response to nedaplatin therapy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) and serum CA-125 levels. Results: Forty-six of 570 patients (8.1%) experienced carboplatin hypersensitivity reactions, and the increased cycle numbers of carboplatin-based regimens correlated with the high incidence of hypersensitivity (≤6, 0.9% vs ≥7, 19.2%). Of these 46 patients, 38 subsequently switched to nedaplatin-based regimens (ovarian, tubal or peritoneal carcinoma, 30; endometrial carcinoma, 6; cervical carcinoma, 2). Three of the 38 patients (7.9%) eventually developed hypersensitivity against nedaplatin, and all their reactions were grade 2. The response rate to nedaplatin therapy among 32 evaluable patients was 31.3%. Conclusion: Replacing carboplatin with nedaplatin provided a safe and efficacious approach to manage carboplatin hypersensitivity. To the authors' knowledge, this study is the first to indicate the usefulness of nedaplatin after carboplatin hypersensitivity reactions. Further evaluations are warranted to confirm our finding.

We investigate a design strategy for subthreshold circuits focusing on energy-consumption minimization and yield maximization under process variations. The design strategy is based on the following findings related to the operation of low-power CMOS circuits: (1) The minimum operation voltage (VDDmin) of a circuit is dominated by flip-flops (FFs), and VDDmin of an FF can be improved by upsizing a few key transistors, (2) VDDmin of an FF is stochastically modeled by a log-normal distribution, (3) VDDmin of a large circuit can be efficiently estimated by using the above model, which eliminates extensive Monte Carlo simulations, and (4) improving VDDmin may substantially contribute to decreasing energy consumption. The effectiveness of the proposed design strategy has been verified through circuit simulations on various circuits, which clearly show the design tradeoff between voltage scaling and transistor sizing.

The traditional wooden frame structures of Chinese Dong People have passed through the ages. We investigated the details of the construction system of drum towers, bridges, gates, granaries and drama stages in Dong villages, which are constructed with posts and beams. The beams penetrate the columns and are connected and stiffened without using wedges. In addition, nails and steel connectors are not used. The purpose of the investigation is to make clear the construction system of the traditional wooden structures. We deciphered the allotment of timber written on the surface of bamboo, which were very important for marking, processing and construction of the structures.

This paper proposes a reliability evaluation environment for coarse-grained reconfigurable architectures. This environment is designed so that it can be easily extended to different target architectures and applications by automating the generation of the simulation inputs such as HDL codes for fault injection and configuration information. This automation enables us to explore a huge design space in order to efficiently analyze area/reliability trade-offs and find the best solution. This paper also shows demonstrative examples of the design space exploration of coarse-grained reconfigurable architectures using the proposed environment. Through the demonstrations, we discuss relationship between coarse-grained architectures and reliability, which has not yet been addressed in existing literatures and show the feasibility of the proposed environment.

The standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiotherapy (CCRT). Although the activated PI3-kinase/Akt pathway is known to be involved in both cisplatin-resistance and radioresistance, to date, only a few studies have reported significant associations between PIK3CA gene mutational status and outcome by CCRT in the disease. The aim of this study was to clarify the prognostic significance of PIK3CA mutational status in cervical cancers treated by CCRT. We analyzed PIK3CA mutation in 59 patients with stage IIB to IVA cervical carcinomas primarily treated by CCRT with weekly cisplatin using formalin-fixed paraffin-embedded biopsy specimens before treatment. Fifty-seven of 59 patients (97%) had locally advanced cancers with stage IIIA to IVA. Clinicopathologic data and patient survival were retrospectively compared according to PIK3CA mutational status. PIK3CA mutation was found in 7 of 59 patients (12%). No significant differences in clinicopathologic characteristics were observed according to PIK3CA mutational status. Patients with wild-type PIK3CA showed significantly improved cancer-specific survival as compared with mutated patients (P = .044). Subsequent survival analyses revealed that PIK3CA mutation was a significant prognostic factor for poor overall survival [multivariate adjusted hazard ratio (HR), 3.9; 95% confidence interval (95% CI), 1.3–11.8; P = .017] and cancer-specific survival (multivariate adjusted HR, 3.6; 95% CI, 1.2–11.0; P = .024). Together with previous published findings, the current study further supports the clinical significance of PIK3CA mutation in cervical cancer. Our observations suggest that molecular inhibitors targeting the PI3-kinase/Akt pathway may improve the outcome by CCRT in cervical cancers harboring PIK3CA mutation, providing significant implications for novel treatment strategy based on precision medicine in the disease.

Polymorphisms in cytokine genes can influence immune responses to human papillomavirus infection, possibly modifying risks of cervical cancer. Using an amplification refractory mutation system-polymerase chain reaction method, we analyzed a single nucleotide polymorphism (A/G) at position -1082 in interleukin-10 promoter region in 440 Japanese women: 173 women with normal cytology, 163 women with cervical intraepithelial neoplasia and 104 women with invasive cervical cancer. The carrier frequency of interleukin-10 -1082 G alleles associated with higher interleukin-10 production increased with disease severity: 9.8% for normal cytology; 19.6% for cervical intraepithelial neoplasia; 29.8% for invasive cervical cancer (P for trend < 0.001). Among cytologically normal women, human papillomavirus infections were more common in those who were positive for an interleukin-10 -1082 G allele (P = 0.04). In conclusion, our data suggest that interleukin-10 -1082 gene polymorphism may serve as a marker of genetic susceptibility to cervical cancer among Japanese women.

To obtain baseline data for human papillomavirus (HPV) screening and vaccination in Japan, we analyzed HPV DNA data from 2282 Japanese women (1517 normal cytology, 318 cervical intraepithelial neoplasia [CIN] grade 1, 307 CIN2-3, and 140 invasive cervical cancer [ICC]) that visited the University of Tsukuba Hospital or Ibaraki Seinan Medical Center Hospital for screening or treatment of cervical diseases between 1999 and 2007. An L1-based PCR method was used for individual HPV genotyping. The most common HPV types in ICC were, in order of decreasing prevalence, HPV16 (40.5%), HPV18 (24.4%), HPV52 (8.4%), HPV58 (3.1%), and HPV33 (3.1%). Based on the comparison of HPV type distributions between normal cytology and CIN2-3 and ICC, estimated risk of disease progression varied considerably by genotype: HPV16, HPV18, HPV31, HPV33, HPV35, HPV52, and HPV58 (prevalence ratio, 1.92; 95% confidence interval 1.58-2.34); other oncogenic types (0.31, 95% confidence interval 0.19-0.50); and non-oncogenic types (0.09, 95% confidence interval 0.03-0.43). HPV16 and/or HPV18, including coinfections with other types, contributed to 67.1% of ICC and 36.2% of CIN2-3 among Japanese women. More importantly, the overall prevalence of HPV16 and/or HPV18 varied greatly according to the women's age: highest in women aged 20-29 years (ICC, 90.0%; CIN2-3, 53.9%), decreasing with age thereafter, and lowest in women aged 60 years or older (ICC, 56.3%; CIN2-3, 25.0%). In conclusion, type-specific HPV testing may help identify Japanese women at high risk of progression to CIN2-3 and cancer. In Japan, current HPV vaccines are estimated to provide approximately 70% protection against ICC and may be more useful in reducing the incidence of cervical cancer and precancer in young women of reproductive age.

Recently, many researchers tackle accurate object recognition algorithms and many algorithms are proposed. However, these algorithms have some problems caused by variety of real environments such as a direction change of the object or its shading change. The new tracking algorithm, Cascade Particle Filter, is proposed to fill such demands in real environments by constructing the object model while tracking the objects. We have been investigating to implement accurate object recognition on embedded systems in real-time. In order to apply the Cascade Particle Filter to embedded applications such as surveillance, automotives, and robotics, a hardware accelerator is indispensable because of limitations in power consumption. In this paper we propose a hardware implementation of the Discrete AdaBoost algorithm that is the most computationally intensive part of the Cascade Particle Filter. To implement the proposed hardware, we use PICO Express, a high level synthesis tool provided by Synfora, for rapid prototyping. Implementation result shows that the synthesized hardware has 1,132,038 transistors and the die area is 2,195 μm x 1,985 μm under a 0.180 μm library. The simulation result shows that total processing time is about 8.2 milliseconds at 65 MHz operation frequency.

Recently, reconfigurable devices are widely used in the fields of small amount production and trial production. They are also expected to be utilized in such mission-critical fields as space development, because system update and pseudo-repair can be achieved remotely by reconfiguring. However, in the case of conventional reconfigurable devices, configuration memory upsets caused by radiation and alpha particles reconfigure the device unpredictably, resulting in fatal system failures. Therefore, a reconfigurable device with high fault-tolerance against configuration upsets is required. In this paper, we propose an architecture of a fault-tolerant reconfigurable device that autonomously repairs configuration upsets by itself without interrupting system operations. The device consists of a 2D array of “Autonomous-Repair Cells” each of which repairs its upsets autonomously. The architecture has a scalability in fault tolerance; a finer-grained Autonomous-Repair Cell provides higher fault-tolerance. To determine the architecture, we analyze four autonomous repair techniques of the cell experimentally. Then, two autonomous repair techniques, simple multiplexing (S.M.) and memory multiplexing (M.M.), are applied; the former to programmable logics and the latter to cell-to-cell routing resources. Through evaluation, we show that proposed device achieves more than 10 years average lifetime against configuration upsets even in a severe situation such as a satellite orbit.

Venous thromboembolism (VTE) such as deep-vein thrombosis (DVT) and pulmonary thromboembolism (PTE) often occurs after surgery and rarely occurs even before surgery in patients with ovarian cancer. It is well known that levels of plasma D-dimer (DD) before treatment in most ovarian cancer patients are increased. This study therefore examined whether increased levels of DD are associated with presence of VTE before treatment of ovarian cancer. Between November 2004 and March 2007, DD levels prior to initial treatment were measured in 72 consecutive patients with presumed epithelial ovarian cancer (final diagnosis: epithelial ovarian cancer, n=60; and epithelial ovarian borderline malignancy, n=12). Venous ultrasound imaging (VUI) of the lower extremity was conducted for all patients except for two patients in whom DVT was detected by pelvic computed tomography (CT). When DVT was found, pulmonary scintigraphy was subsequently performed to ascertain presence of PTE. D-dimer levels were above the cut-off value (0.5 microg ml(-1)) in 65 of 72 patients (90.2%). Venous ultrasound imaging or CT revealed DVT in 18 of 72 patients (25.0%) and pulmonary scintigraphy found PTE in 8 patients (11.1%). All patients with VTE were asymptomatic when VTE was found. D-dimer levels were associated with incidence of VTE (0-1.4 microg ml(-1); 0 of 26 (0%), 1.5-7.4 microg ml(-1); 9 of 30 (30%) andor =7.5 microg ml(-1); 9 of 16 (56.3%), P for trend=0.0003). However, even if 1.5 microg ml(-1) was used as a cut-off value, this had low specificity and positive predictive value (47.2, 38.3%), though it had high sensitivity and negative predictive value (100, 100%). Therefore, ovarian cancer patients with DD levelor =1.5 microg ml(-1) should be examined using VUI to detect silent DVT. Patients with VTE underwent preventive managements including anticoagulant therapy before initial treatment, chemotherapy or surgery, and after surgery. There was no clinical onset of postoperative VTE in all 72 patients. Measurement of DD levels and subsequent ultrasonography revealed that silent or subclinical VTE frequently occurs before surgery in ovarian cancer. The usefulness of preoperative assessment of VTE needs further confirmation in randomised controlled trials.

Objective The purpose of the study was to demonstrate how the interaction between phenytoin and tacrolimus (FK 506) can be managed clinically and to characterize the change in FK 506 levels after discontinuation of phenytoin in two Japanese heart transplant recipients with different dosing periods ofphenytoin. Methods A drug interaction between phenytoin and FK 506 was investigated in 2 patients. The concentration-dose ratios (CDR: trough blood FK 506 level (ng/ml)/FK 506 dose (mg/day) on the previous day) were calculated as an index of the induction of the CYP3A4 enzyme during and after phenytoin therapy. Results About 2- to 3-fold dosages of FK 506 were required to maintain the required blood level when phenytoin was used concomitantly in the two cases examined. The FK 506 dose was constant within 21 days after discontinuing phenytoin in Patient 1 who had 36 days of phenytoin therapy. In Patient 2 with 21-day phenytoin therapy, the FK 506 doses and CDR varied for 10 days after discontinuing phenytoin, and expected FK 506 C0 levels were achieved within 11 days. Conclusions The persistence of CYP induction after discontinuing phenytoin is dependent on the history of administration and, perhaps, on the dosing period in particular.

Recently, self-reconfigurable devices which can be partially reprogrammed by other part of the same device have been proposed. However, since conventional self-reconfigurable devices are LUT-array-based fine-grained devices, their time efficiency is spoiled by overhead for reconfiguration time to load large amount of configuration data. Therefore, we have to improve architectures. At the architecture design phase, it is difficult to estimate the performance, including reconfiguration overhead, of self-reconfigurable devices by static analysis, since it depends on many architecture parameters and unpredictable run-time behavior. In this paper, we propose a simulation-based platform for design exploration of self-reconfigurable devices. As a demonstration of the proposed platform, we implement an adaptive load distribution model on the devices of various reconfiguration granularities and evaluate performance of the devices.

Neutralizing antibody against human papillomavirus (HPV) minor capsid protein L2 can cross-neutralize different HPV genotypes in vitro. To identify the segments containing the cross-neutralization epitopes of HPV16 L2, we characterized antisera obtained by immunizing two rabbits with each of the ten synthetic peptides of 14 to 20 amino acids (aa) long, which represents a part of the HPV16 L2 sequence from aa 14 to 144. The antisera against the peptides within the region from aa 18 to 144 efficiently bound to HPV16 L1/L2-capsids and neutralized HPV16 pseudovirions, indicating that the region is displayed on the surface of the capsids and contains several neutralization epitopes. Antiserum against the peptide from aa 18 to 38 (anti-P18/38) cross-neutralized HPV18. Anti-P56/75 cross-neutralized HPV18, 31, and 58. Anti-P61/75 and anti-P64/81 cross-neutralized HPV18 and 58. Anti-P96/115 and the antiserum induced by a mutant P96/115 (S and T at aa 101 and 112 were replaced with L and S, respectively) cross-neutralized HPV31 and 58. The mixture of equal volumes of three antisera, anti-P18/38, anti-P56/75, and anti-mutant P96/115, neutralized HPV16, 18, 31, and 58 more efficiently than anti-P56/75 alone, suggesting that there is a synergistic effect of antibodies on the cross-neutralization. The cross-neutralization appears to be correlated with conserved aa sequences among HPV types. The data in this study provide a basis for designing vaccine antigens effective against a broader spectrum of the high-risk HPVs.

The paper describes the concept, architecture, and prototype test results of a packet processor that enables us to implement an application-specific high-speed packet processing system without expert-level programming skills. This processor has a pipelined processing architecture and features coarse-grained instructions that are based on the data formats of the telecommunication packet. Using this processor, target applications can be implemented within a short working period without degrading the processing performance. We implemented a prototype system to evaluate its packet propagation delay and packet forwarding performance. The measured results suggest that the architecture is useful for packet processing on high-speed telecommunication networks.

Background Cyclosporine (CsA), Mycophenolate mofetil (MMF) and prednisolone (PSL) are widely used for the prevention of acute rejection after heart transplantation. Recently, the serum concentration - time curves (AUC) of CsA and MMF have been demonstrated to be precise predictors of acute rejection. Methods and Results Fourteen heart transplant patients were treated concomitantly with CsA, MMF, and PSL between May 1999 and November 2005 at the National Cardiovascular Center and of them 3 had acute rejection episodes [International Society for Heart & Lung Transplantation grade 3a]. Two patients (man in his 30 s; woman in her 40 s) had acute rejection with a mycophenolic acid (MPA) AUC0-12 h

Background The purpose of the study was to characterize the pharmacokinetics of mycophenolic acid (MPA) in Japanese heart transplant recipients and to find the time point that has the best correlation with the MPA area under the plasma concentration curve (AUC). Methods and Results Twenty-two Japanese recipients treated with mycophenolate mofetil were evaluated in the study. Approximately 9 months after transplantation, the area under the MPA serum concentration-time curve from 0 to 12 h (AUC0-12 h) was evaluated. The MPA AUC0-12 h h values in the cyclosporine (CsA) and tacrolimus (FK) groups ranged from 13.11 to 50.98 μg · h/ml and from 39.19 to 93.18 μg · h/ml, respectively. Fourteen models were developed and analyzed for their ability to estimate the MPA AUC0-12 h based on a limited number of samples in the CsA group. Sixteen models were developed in the FK group. The best model for predicting the full MPA AUC0-12 h in the CsA group was a 3-time-point model that included C0 h, C1 h and C2 h (r2, 0.96; mean prediction error, 0.15±7.85%); a 2-time-point model that included C0 h, and C2 h (r2, 0.94; mean prediction error, 0.495±10.35%) was also reliable. In the FK group, a 3-time-point model that included C1 h, C2 h and C4h (r2, 0.73; mean prediction error, 2.73±17.09%) was the best model for predicting the full MPA AUC0-12 h, but it was not reliable in clinical practice. Conclusion A 3-(C0 h, C1 h and C2 h) and a 2-time-point model (C0 h and C2 h) are useful for predicting the full MPA AUC0-12 h in Japanese heart transplant recipients treated with CsA but not with FK. (Circ J 2007; 71: 1022 - 1028)

A nonvolatile and compact switch realizing multiple fan-outs of a crossbar switch for programmable logic devices (PLDs) has been newly developed by using two-varistors selected complementary atom switch (2V-1CAS). The two control lines connected to the varistors realize the accurate programming of each cross-point without select transistors. The novel nitrogen-modulated, TiN/a-Si/SiN/a-Si/TiN varistor shows superior nonlinear (NL) characteristic of ∼105, which are successfully stacked on the top of CAS with dual-hard mask (DHM) process. The developed 2V-1CAS (18F2) gives a promising switch block (SB) used for energy-efficient, nonvolatile PLDs.

In this paper, we design and fabricate a voltage booster circuit, aiming at the realization of a monolithic system LSI that utilize on-chip solar cell to eliminate the need for external voltage supply. Since the voltage that can be obtained from an on-chip solar cell is about −0.5V, we need an efficient voltage booster to obtain voltage around +4.0V if we need to program a non-volatile memory on the same chip. First, it is confirmed by circuit simulation that a 10-stage cross-coupled charge pump circuit using 0.18µm process technology can generate +4.0V from −0.5V input. A ring oscillator using current starved inverters with 2R-1T bias circuit is developed, whose frequency is successfully compensated within ±10% for supply voltage ranging between 0.45V and 0.60V. From measurement of the test chip of proposed circuits using Rohm 0.18µm CMOS process technology, it is confirmed that the voltage booster TEG with 2-stage cross-coupled charge pump circuit generates voltage beyond +0.8V from −0.5V input voltage with about 40% efficiency even at a bright environment of 6.1klux illumination. In addition, it is demonstrated that by implementing an on-chip solar cell, the voltage booster, and a standard-cell-based digital circuit in a single chip, an external piezoelectric diaphragm makes a sound only by the power from on-chip solar cell.

Objective We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). Methods Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. Results The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p

This paper proposes 0-1-A-A LUT, a new programmable logic using atom switches, and a mapping algorithm for it. Atom switch is a non-volatile memory device of very small geometry which is fabricated between metal layers of a VLSI, and it can be used as a switch device that can hold its state. While considerable area reduction of Look Up Tables (LUTs) used in conventional Field Programmable Gate Arrays (FPGAs) has been achieved by simply replacing each SRAM element with a memory element using a pair of atom switches, our 0-1-A-A LUT achieves further area reduction since number of inputs of a multiplexer (MUX) is reduced to a half. This is achieved by applying one of input signals to the switch array. Since the fanout of this input buffer depends on the mapped logic function, it is preferred to choose a logic function with fewer number of fanout in order to reduce delay. To avoid non-preferred functions to be mapped to 0-1-A-A LUTs this paper also proposes a technology mapping algorithm. From our experiments, non-preferred functions are successfully excluded from mapping using our LUT, and the circuit depth using our k-LUT is 25% smaller in the best case compared with using the conventional (k − 1)-LUT which composed of a MUX of the same size as our k-LUT.

The selection criteria for secondary cytoreductive surgery (SCS) in recurrent ovarian cancer are yet to be defined. The aim of this study was to propose the selection criteria through identifying predictive factors for successful SCS. All patients who underwent SCS for recurrent epithelial ovarian, tubal, and peritoneal cancers between 1982 and 2012 at our institution were identified through our database. Potential prognostic factors were evaluated in univariate and multivariate analyses. Survival after SCS was examined by the grouping model based on the number of prognostic factors. We performed SCS in 80 consecutive patients, 48 (60 %) of whom achieved complete resection. Complete/incomplete resection significantly influenced survival (median 65 vs. 26 months; p = 0.0005). Among favorable prognostic factors determined before SCS, treatment-free interval >12 months, absent distant metastasis, solitary disease, and performance status 0 were independently associated with better survival (p = 0.0009, 0.00003, 0.0004, and 0.015, respectively). Patients with 3–4 of those factors had better survival than those with 2 or 0–1 factors (median 79, 26, and 19 months; p

Reconfigurable devices are expected to be utilized in such mission-critical fields as space development and undersea cables, because system updates and pseudo-repair can be achieved remotely by reconfiguring. However, conventional reconfigurable devices suffer from memory-bit upset caused by charged particles in space which results in fatal system problems. In this paper, we propose an architecture of a fault-tolerant reconfigurable device. The proposed device is divided into "autonomous-repair cells" with embedded control circuits. The autonomous-repair cell proposed in this paper is based on error detection and correction (EDAC) and uses hardware and time redundancy. From evaluation, it is shown that the proposed architecture achieves sufficient reliability against configuration memory upset. Trade-offs between performance and cost are also analyzed.

This paper presents an approach of logic mapping into LUT-Array-Based PLD where Boolean functions in the form of the sum of generalized complex terms (SGCTs) can be mapped directly. While previous mapping approach requires predetermined variable ordering, our approach performs mapping and variable reordering simultaneously. For the purpose, we propose a directed acyclic graph based on the multiple valued decision diagram (MDD) and an algorithm to construct the graph. Our algorithm generates candidates of SGCT expressions for each node in a bottom-up manner and selects the variables in the current level by evaluating the sizes of SGCT expressions directly. Experimental results show that our approach reduces the number of terms maximum to 71 percent for the MCNC benchmark circuits.

This paper presents a mixed-grained reconfigurable VLSI array architecture that can cover mission-critical applications to consumer products through C-to-array application mapping. A proof-of-concept VLSI chip was fabricated in a 65nm process. Measurement results show that applications on the chip can be working in a harsh radiation environment.

In cervical cancer screening programs, women with abnormal cytology are referred for colposcopy for histological evaluation. We examined whether a human papillomavirus (HPV) genotyping assay could be used to identify women who do not need immediate colposcopy and biopsy because of low risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+).We prospectively evaluated test performance for 2 carcinogenic HPV genotypes (HPV16/18), for 8 types (HPV16/18/31/33/35/45/52/58), and for 13 types (HPV16/18/31/33/35/45/51/52/56/58/59/68) for prediction of histological CIN3+ results among 427 screen-positive women referred for colposcopy. The study subjects consisted of 214 women with low-grade squamous intraepithelial lesion (LSIL), 184 with high-grade squamous intraepithelial lesion (HSIL), and 29 with atypical squamous cells, cannot exclude HSIL (ASC-H).Among women with LSIL cytology, HPV16/18 positivity was 29.4 % and increased to 58.9 % for 8 types and to 74.8 % for 13 types (P0.001). The risk of CIN3+ biopsy results was still 7.9 % for women testing negative for HPV16/18, but decreased to 0.0 % for those testing negative for at least eight types of HPV (HPV16/18/31/33/35/45/52/58). Although HPV genotyping results enabled additional risk stratification among women with HSIL/ASC-H cytology, the risk of histological CIN3+ diagnosis among women testing negative for eight types or more was still sufficiently high (35 %) to warrant immediate colposcopy referral.Of women with LSIL cytology, those testing negative for at least eight of the highest-risk types of HPV (HPV16/18/31/33/35/45/52/58) may not need immediate colposcopy and biopsy. This would reduce the number of colposcopy referrals by approximately 40 %. However, the HPV genotyping assay is not likely to alter the clinical management of women with HSIL/ASC-H.

Sub- and near-threshold circuits have been attracting growing interests because they are suitable for realizing extremely low power and low energy circuits. The estimation of the minimum operating voltage (VDDmin), under which the circuit does not function correctly, is one of the most important issues in their design. In this paper, the distribution of VDDmin is explored through simulations and measurements. Lognormal model-approximation and a quick VDDmin estimation method are validated by the measurements of 124k FFs. Assuming that the VDDmin of a circuit is limited by that of the FFs, VDDmin distribution for any circuits can be efficiently estimated. The measurements of 192 DCT circuits show that the estimation matches with silicon data very well within 10 mV error.

This paper presents a mixed-grained reconfigurable VLSI array architecture that can cover mission-critical applications to consumer products through C-to-array application mapping. A proof-of-concept VLSI chip was fabricated in 65nm process. Measurement results show that applications on the chip can be working in a harsh radiation environment. Irradiation tests also show the correlation between the number of sensitive bits and the mean time to failure. Furthermore, the temporal error rate of an example application due to soft errors in the datapath were measured and demonstrated for reliability-aware mapping.