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Alternate testing techniques have been progressively adopted as a promising solution due to their effectiveness against classical specification-based test methods. This work presents a built-in test system, which adaptively generates an indirect digital signature characterising the circuit under test, which is later used to diagnose the actual performances relying on a statistical dictionary-based diagnosis method. The system is composed of an integrated digital signature generator and a digital control and acquisition subsystem. The signature generator is based on a converter architecture, in which the analogue range can be adapted to the magnitude of the indirect measure using the well known information of the fault-free circuit. The digital subsystem controls the proposed architecture and stores the digital codes sent by the integrated digital signature generator. The digital signature generator has been designed and fabricated in an industrial 65 nm complementary metal–oxide–semiconductor technology from STMicroelectronics, whereas the digital control and acquisition subsystem have been prototyped in a field-programmable gate array. The fabricated system has been used to test a biquad filter affected by parametric variations. Successful experimental results are reported showing the capabilities of the proposed adaptive test system to diagnose circuit performances with discrepancies as low as 1% of the actual real value.

Background & Aims Liver resection (LR) in patients with hepatocellular carcinoma (HCC) and clinically significant portal hypertension (CSPH) defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg is not encouraged. Here, we reappraised the outcomes of patients with cirrhosis and CSPH who underwent LR for HCC in highly specialised liver centres. Methods This was a retrospective multicentre study from 1999 to 2019. Predictors for postoperative liver decompensation and textbook outcomes were identified. Results In total, 79 patients with a median age of 65 years were included. The Child-Pugh grade was A in 99% of patients, and the median model for end-stage liver disease (MELD) score was 8. The median HVPG was 12 mmHg. Major hepatectomies and laparoscopies were performed in 28% and 34% of patients, respectively. Ninety-day mortality and severe morbidity rates were 6% and 27%, respectively. Postoperative and persistent liver decompensation occurred in 35% and 10% of patients at 3 months. Predictors of liver decompensation included increased preoperative HVPG (p = 0.004), increased serum total bilirubin (p = 0.02), and open approach (p = 0.03). Of the patients, 34% achieved a textbook outcome, of which the laparoscopic approach was the sole predictor (p = 0.004). The 5-year overall survival and recurrence-free survival rates were 55% and 43%, respectively. Conclusions Patients with cirrhosis, HCC and HVPG ≥10 mmHg can undergo LR with acceptable mortality, morbidity, and liver decompensation rates. The laparoscopic approach was the sole predictor of a textbook outcome. Lay summary Patients with cirrhosis, hepatocellular carcinoma, and clinically significant portal hypertension (defined as a hepatic venous pressure gradient ≥10 mmHg) can undergo resection with acceptable mortality, morbidity, liver decompensation rates, and a textbook outcome. These results can be achieved in selected patients with preserved liver function, good general status, and sufficient remnant liver volume., Graphical abstract, Highlights • Patients with HCC and CSPH can undergo resection, with mortality of 6% and severe morbidity of 27%. • Postoperative and persistent liver decompensation occurred in 35% and 10% of patients, respectively. • Textbook outcome was achieved in 34% of patients. • The laparoscopic approach was identified as a predictor of postoperative liver decompensation and textbook outcome.

Les divises van sorgir a finals del segle XIV amb l’objectiu de superar les limitacions del sistema heràldic, subjecte a un codi massa rígid i concebut exclusivament per traslladar conceptes dinàstics i de llinatge. Aquest estudi proposa una dissecció de l’autèntic «alter ego» literari i estètic escollit pel noble Pere de Portugal, efímer rei dels catalans (1464-1466). La cartografia de la seva divisa, present a tota mena d’espais arquitectònics i objectes personals i institucionals, revela que en va fer un ús extraordinàriament intensiu, primer a Portugal i, més tard, a Catalunya. Darrera la majoria d’aquestes manifestacions hi palpiten el desig de legitimació i un fort sentit estètic. Però per damunt de tot la voluntat d’expressar una màxima moral, connectada amb la literatura cavalleresca o especular, inspirada, entre d’altres, en els corrents de la filosofia moral pagana (Sèneca i Boeci) i dels humanistes del tres-cents italià. Només així podem entendre que la divisa Paine pour joie, com altres fórmules emblemàtiques semblants, és fruit de les inquietuds i els anhels intel·lectuals d’un cavaller tardomedieval més que el reflex-sublimació de les seves experiències biogràfiques.

Background The International Study Group for Liver Surgery (ISGLS) definition of post hepatectomy liver failure (PHLF) was developed to be consistent, widely applicable, and to include severity stratification. This international multicentre collaborative study aimed to prospectively validate the ISGLS definition of PHLF. Methods 11 HPB centres from 7 countries developed a standardised reporting form. Prospectively acquired anonymised data on liver resections performed between 01 July 2010 and 30 June 2011 was collected. A multivariate analysis was undertaken of clinically important variables. Results Of the 949 patients included, 86 (9%) met PHLF requirements. On multivariate analyses, age ≥70 years, pre-operative chemotherapy, steatosis, resection of >3 segments, vascular reconstruction and intraoperative blood loss >300 ml significantly increased the risk of PHLF. Receiver operator curve (ROC) analysis of INR and serum bilirubin relationship with PHLF demonstrated post-operative day 3 and 5 INR performed equally in predicting PHLF, and day 5 bilirubin was the strongest predictor of PHLF. Combining ISGLS grades B and C groups resulted in a high sensitivity for predicting mortality compared to the 50-50 rule and Peak bilirubin >7 mg/dl. Conclusions The ISGLS definition performed well in this prospective validation study, and may be the optimal definition for PHLF in future research to allow for comparability of data.

Background The aim of the study was to evaluate the current opinion and clinical decision-making process of international pancreatologists, and to systematically identify key study questions regarding the diagnosis and treatment of chronic pancreatitis (CP) for future research. Methods An online survey, including questions regarding the diagnosis and treatment of CP and several controversial clinical case vignettes, was send by e-mail to members of various international pancreatic associations: IHPBA, APA, EPC, ESGE and DPSG. Results A total of 288 pancreatologists, 56% surgeons and 44% gastroenterologists, from at least 47 countries, participated in the survey. About half (48%) of the specialists used a classification tool for the diagnosis of CP, including the Mayo Clinic (28%), Mannheim (25%), or Buchler (25%) tools. Overall, CT was the preferred imaging modality for evaluation of an enlarged pancreatic head (59%), pseudocyst (55%), calcifications (75%), and peripancreatic fat infiltration (68%). MRI was preferred for assessment of main pancreatic duct (MPD) abnormalities (60%). Total pancreatectomy with auto-islet transplantation was the preferred treatment in patients with parenchymal calcifications without MPD abnormalities and in patients with refractory pain despite maximal medical, endoscopic, and surgical treatment. In patients with an enlarged pancreatic head, 58% preferred initial surgery (PPPD) versus 42% initial endoscopy. In patients with a dilated MPD and intraductal stones 56% preferred initial endoscopic ± ESWL treatment and 29% preferred initial surgical treatment. Conclusion Worldwide, clinical decision-making in CP is largely based on local expertise, beliefs and disbeliefs. Further development of evidence-based guidelines based on well designed (randomized) studies is strongly encouraged.

One of the most challenging aspects in nowadays microelectronics industry is production test and verification of mixed-signal circuits. In order to cope with some of the drawbacks encountered in this scenario, researchers have found alternate test as a promising solution in achieving such endeavor. This work prospects the possibilities of using space tessellations along multiple directions in order to improve the test decision boundary definition in the alternate measure space. The proposed method is able to reduce false positive test outcomes, i.e. test escapes, with acceptable penalty in test yield loss metric. The key idea presented in this work is to use an ensemble of octrees, each of them tessellating the plane along different directions. Such tessellations create a refinement in the non linear test decision boundaries without the need of including extra circuit samples. The tree ensemble, together with a strict test decision criterion, serve as a classifier during the production testing phase. The proposed multi-directional ensemble tessellation strategy has been applied to test a band-pass Biquad filter affected by parametric variations. The proposed method has reported promising simulation results in lowering the test escapes metric as compared to a single octree classifier. The computational overhead of evaluating several octrees is insignificant since 2n-tree data structures are traversed efficiently. The octree ensemble technique has also been compared against a classic specification guard-banding technique reporting better test yield loss metrics for the same test escape target.

Purpose Perioperative chemotherapy confers a 3-year progression free survival advantage following resection of colorectal liver metastases (CRLM), but is associated with significant toxicity. Chemoembolisation using drug eluting PVA microspheres loaded with irinotecan (DEBIRI) allows sustained delivery of drug directly to tumour, maximising response whilst minimising systemic exposure. This phase II single arm study examined the safety and feasibility of DEBIRI before resection of CRLM. Methods Patients with resectable CRLM received lobar DEBIRI 1 month prior to surgery, with a radiological endpoint of near stasis. The trial had a primary end-point of tumour resectability (R0 resection). Secondary end-points included safety, pathologic tumour response and overall survival. Results 40 patients received DEBIRI, with a median dose of 103 mg irinotecan (range 64–175 mg). Morbidity was low (2.5%, CTCAE grade 2) with no evidence of systemic chemotoxicity. All patients proceeded to surgery, with 38 undergoing resection (95%, R0 resection rate 74%). 30-day post-operative mortality was 5% (n = 2), with neither death TACE related. 66 lesions were resected, with histologic major or complete pathologic response seen in 77.3% of targeted lesions. At median follow up of 40.6 months, 12 patients (34.3%) had died of recurrent disease with a median overall survival of 50.9 months. Nominal 1, 3 and 5-year OS was 93, 78 & 49% respectively. Conclusions Resection after neoadjuvant DEBIRI for CRLM is feasible and safe. Single treatment with DEBIRI resulted in tumour pathologic response and median overall survival comparable to that seen after systemic neoadjuvant chemotherapy. Registered at clinicaltrials.gov ( NCT00844233 ).

Introduccion Un alto porcentaje de pacientes que reciben una hepatectomia por metastasis de cancer colorrectal presentaran recidiva hepatica, y en algunas sera posible una nueva reseccion. La utilidad de las hepatectomias repetidas continua siendo discutida. Objetivo Evaluar los resultados obtenidos a corto y largo plazo. Metodo Fueron analizadas 68 rehepatectomias de dos instituciones. Se analizaron datos demograficos y caracteristicas de la enfermedad metastasica y de las resecciones hepaticas. Los tipos de complicaciones y la morbimortalidad tambien fueron analizados, al igual que la supervivencia y el tiempo libre de enfermedad. Se evaluaron algunos de los factores de mal pronostico mencionados en la literatura. Resultados El analisis de los datos de corto plazo no mostro diferencias significativas entre los pacientes de primera hepatectomia y de hepatectomias repetidas, a excepcion del porcentaje de fistulas biliares posoperatorias (p = 0.001). La supervivencia a 1 ano es similar, mientras que a 3 y 5 anos mostro diferencias significativas (p = 0.024 y 0.004, respectivamente). Los factores de mal pronostico referidos en la literatura no fueron representativos en esta serie. Conclusion Los resultados a corto plazo de los pacientes con rehepatectomia son similares a los de aquellos resecados una vez. Los resultados a largo plazo de las rehepatectomias son inferiores a otros publicados. Introduction A high percentage of patients undergoing hepatectomy for metastatic colorectal liver disease will have a recurrence. Of these, some can be subject to a new resection. The usefulness of repeated hepatectomy remains controversial. The aim of this study is to evaluate the results of short and long-term outcomes in repeated hepatectomies. Methods They were re-analyzed 68 repeated hepatectomies from two institutions. Demographics, characteristics of metastatic disease and hepatic resections were analyzed. Types of complications, morbidity and mortality were also analyzed as survival and disease-free time. Some of the factors of poor prognosis mentioned in the literature were evaluated. Results The analysis of short-term data showed no statistically significant differences between patients with first and repeated hepatectomy, except the percentage of postoperative biliary leakage (p = 0.001). The 1-year survival was similar while 3 and 5 years survival showed significant differences (p = 0.024 and 0.004, respectively). The factors of poor prognosis referred in the literature were not representative in this series. Conclusion The short-term results of repeated hepatectomy are similar to those resected once. Long term result are inferior to other published series.

Through-silicon vias (TSVs) are critical elements in 3-D integrated circuits susceptible to defects during fabrication and lifetime. It is desirable to detect defective TSVs in the early steps of the fabrication process to prevent stacking yield loss. Thus, the development of effective prebond testing techniques becomes of great importance. In this direction, recent research effort has been devoted to the development of two main prebond techniques: 1) prebond probing and 2) built-in self-test (BIST) techniques. The prebond probing poses economic and technological challenges, whereas current BIST proposals have disadvantages for certain solutions. Hence, there is still a need for an effective methodology in terms of fault coverage, area overhead, and test time. This paper proposes a BIST technique based on a simple unbalanced circuit comparing the behavior of two TSVs. Electrical simulation results show the viability of the proposal to detect weak defects, i.e., resistive opens and resistive bridges, adding reasonable area overhead in a short-test application time. Furthermore, an experimental design is built on a 65-nm technology, where resistive open defects are intentionally injected. Automated test equipment measurements confirm the simulation results.

Pancreatic cancer (PDAC) lacks reliable diagnostic biomarkers and the search for new biomarkers represents an important challenge. Previous results looking at a small cohort of patients showed an increase in α-1-acid glycoprotein (AGP) fucosylation in advanced PDAC using N-glycan sequencing. Here, we have analysed AGP glycoforms in a larger cohort using several analytical techniques including mass spectrometry (MS), capillary zone electrophoresis (CZE) and enzyme-linked lectin assays (ELLAs) for determining AGP glycoforms which could be PDAC associated. AGP from 31 serum samples, including healthy controls (HC), chronic pancreatitis (ChrP) and PDAC patients, was purified by immunoaffinity chromatography. Stable isotope labelling of AGP released N-glycans and their analysis by zwitterionic hydrophilic interaction capillary liquid chromatography electrospray MS (μZIC-HILIC-ESI-MS) showed an increase in AGP fucosylated glycoforms in PDAC compared to ChrP and HC. By CZE-UV analysis, relative concentrations of some of the AGP isoforms were found significantly different compared to those in PDAC and HC. Finally, ELLAs using Aleuria aurantia lectin displayed a significant increase in AGP fucosylation, before and after AGP neuraminidase treatment, in advanced PDAC compared to ChrP and HC, respectively. Altogether, these results indicate that α1-3 fucosylated glycoforms of AGP are increased in PDAC and could be potentially regarded as a PDAC biomarker. M.B. acknowledges the University of Girona for a pre-doctoral fellowship. This work was supported by the Government of Catalonia (grant 2014 SGR 229), the Spanish Ministry of Science and Innovation (grant BIO 2010-16922, awarded to R. P) and the Spanish Ministry of Economy and Competitiveness (grant CTQ2013-43236, awarded to M.F. and grant CTQ2011-27130, awarded to V. S-N).

Background: Chemotherapy may increase postoperative morbidity and mortality after liver surgery. Especially bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), could have a detrimental effect. To assess the impact of neoadjuvant bevacizumab on clinical outcome after hepatectomy for colorectal liver metastases (CRLMs) this case-matched control study was initiated. Methods: The multicentric data collection was performed in the Swiss HPB Center of the University Hospital Zurich (CH), the Department of Digestive Surgery and Transplantation Strasbourg (F), and the Division of Hepato-biliary-pancreatic surgery of "Josep Tureta” Hospital Girona (E). Consecutive patients operated onbetween July 2005 and December 2007 due to CRLMs who received neoadjuvant chemotherapy were assessed. Patients were divided in two groups: group A had neoadjuvant chemotherapy with bevacicumab, and group B had it without bevacizumab. Results: No differences in overall morbidity (56 vs. 40% in the bevacizumab and control groups, respectively, p=0.23) or mortality could be documented. Similarly, the incidence of severe postoperative complications was not statistically different between the bevacizumab and control groups (31 and 18%, respectively, p=0.31). Wound complications were comparable (11% in the bevacizumab group compared and 9% in the control group, p=1.00). However, bevacizumab was associated with a significantly decreased incidence of postoperative hepatic insufficiency (7 vs. 20%, p=0.03). Conclusions: No impact on the incidence or severity of complications by bevacizumab could be shown. Bevacizumab may even reduce the incidence of liver failure after liver surgery

Background There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19–9 (CA 19–9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. Methods CA 19–9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor- 1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. Results The combination of CA 19–9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19–9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Conclusions Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis

An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team. publisher: Elsevier articletitle: Managing synchronous liver metastases from colorectal cancer: A multidisciplinary international consensus journaltitle: Cancer Treatment Reviews articlelink: http://dx.doi.org/10.1016/j.ctrv.2015.06.006 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd. ispartof: Cancer Treatment Reviews vol:41 issue:9 pages:729-41 ispartof: location:Netherlands status: published

Accurate diagnosis of open defects is key to identifying process problems and achieving fast yield improvement. Current diagnosis methodologies for interconnect full open defects have demonstrated their efficiency, assuming that the defective line voltage is mainly determined by neighboring lines and downstream transistor parasitic capacitances. However, the continuous reduction of oxide thickness with every technology node increases gate leakage current significantly, even for high-k dielectrics. In this context, in nanometer CMOS technologies, the defective line cannot be assumed to be electrically isolated because of the impact of gate leakage currents, which may invalidate diagnosis results provided by present methodologies. In this paper, a new methodology is proposed to diagnose interconnect full open defects under the influence of gate leakage currents in CMOS technologies. To the authors' knowledge, such influence has not been previously considered by any of the existing methodologies. Simulation and experimental results demonstrate the proposal efficiency.

Testing analog and mixed-signal circuits is a costly task due to the required test time targets and high end technical resources. Indirect testing methods partially address these issues providing an efficient solution using easy to measure CUT information that correlates with circuit performances. In this work, a multiple specification band guarding technique is proposed as a method to achieve a test target of misclassified circuits. The acceptance/rejection test regions are encoded using octrees in the measurement space, where the band guarding factors precisely tune the test decision boundary according to the required test yield targets. The generated octree data structure serves to cluster the forthcoming circuits in the production testing phase by solely relying on indirect measurements. The combined use of octree based encoding and multiple specification band guarding makes the testing procedure fast, efficient and highly tunable. The proposed band guarding methodology has been applied to test a band-pass Butterworth filter under parametric variations. Promising simulation results are reported showing remarkable improvements when the multiple specification band guarding criterion is used.

Indirect test strategies have risen as a promising solution to overcome the challenges encountered in analog and mixed-signal circuit testing and the ever increasing device verification costs. This work explores the possibilities of using multidirectional tessellations in the indirect measure space aiming to reduce false positive test outcomes. The key idea of the proposal is to use several rotated 2n-ary trees in order to tessellate and encode the indirect measure space along multiple directions. Such tessellations create a refinement in the highly non linear test decision boundary without the need of including more circuit samples within the training set. The trained trees, together with a strict test decision criterion, serve as a classifier during the production testing phase. The proposed multi-directional tessellation methodology has been applied to test a Biquad filter under the presence of parametric variations. Promising simulation results report considerable improvements in lowering test escape metrics by an average factor of 50 as compared to a single octree tessellation as well as low computational overhead.

There is a close relationship between blood loss during transection and unfavorable outcome. Many different methods have been used in order to cut the parenchyma, while leaving vital structures intact, coagulate small vessels and seal small biliary ducts. The first method described was the finger-fracture technique and, alternatively, the clamp-crushing method using a small forceps. With this technique, the liver is crushed between the ‘jaws’, and the vessels and bile ducts are successively ligated and divided. Technological research using different sources of energy developed the water jet dissectors and the ultrasonic dissectors. The CUSA® has been widely adopted for the fascinating way it could selectively destroy and aspirate parenchyma leaving vascular structures almost intact. Several studies have been addressed to clarify these critical points. However, in the majority of cases they are underpowered to demonstrate clear advantages of one method over the others. In conclusion, the evidence suggested no superiority of other techniques over clamp-crushing. But it must be taken into account that it requires strictly hepatic pedicle clamping. The devices available should be used within the limits of each instrument, as well as the surgical skills of the surgeon. Probably the best option should be a combined approach.

The development of accurate diagnosis methodologies is important to identify process problems and achieve fast yield improvement. As open defects are becoming dominant in some CMOS technologies, their accurate diagnosis is key to improving the quality of new very large-scale integrated circuits. Widely used interconnect full open diagnosis procedures are based on the assumption that neighboring lines determine the voltage of the defective line. However, this assumption decreases the diagnosis efficiency for opens in interconnect lines with fan-out, where the influence of transistor capacitances is significant. This paper presents a diagnosis methodology for interconnect full open defects which considers and models the impact of transistor parasitic capacitances on the defective node accurately. The methodology is able to properly diagnose interconnect opens with fan-out even in the presence of Byzantine behavior. Diagnosis results for real defective devices from different technology nodes are also provided.

An Interconnect full open defect breaks the connection between the driver and the gate terminals of downstream transistors, generating a floating line. The behavior of floating lines is known to depend on several factors, namely parasitic capacitances to neighboring structures, transistor capacitances of downstream gate(s) and trapped charges. For nanometer CMOS technologies, the reduction of oxide thickness leads to a significant increase in gate tunneling leakage. This new phenomenon influences the behavior of circuits with interconnect full open defects. Floating lines can no longer be considered electrically isolated and are subjected to transient evolutions, reaching a steady state determined by the technology, downstream interconnect and gate(s) topology. The occurrence of such defects and the impact of gate tunneling leakage are expected to increase in the future. In this work, interconnect full open defects affecting nanometer CMOS technologies are analyzed and the defective logic response of downstream gates after reaching the steady state is predicted. Experimental evidence of this behavior is presented for circuits belonging to a 180 nm and a 65 nm CMOS technologies. Technology trends show that the impact of gate leakage currents is expected to increase in future technologies.

Decreasing the power supply voltage in dynamic voltage frequency scaling to save power consumption may introduce extra delays in CMOS circuits, which may cause errors. This paper presents the probabilistic delay fault model (PDFM), which describes the probability of an error occurring as a function of the power supply voltage and the clock period in synchronous CMOS circuits. In a wide range of applications (graphic, video, digital filtering, etc.), errors occurring with low probability and not remaining for a long time are acceptable. For combinational circuits which have long critical paths with low probability of excitation, a performance increase is achieved with a certain rate of errors determined by the PDFM compared with the traditional design which considers the worst case. The PDFM applied to array multipliers and ripple carry adders shows the agreement of the predicted probabilities with simulated delay histograms to support the practicality of using the PDFM to select power supply voltage and clock period in dynamic voltage frequency scaling circuits with tolerable error rates.

A technique for extracting the electrical and topological parameters of open defects in process monitor lines is presented. The procedure is based on frequency-domain measurements performed at both end points of the line. The location as well as the resistive value of the open defect are derived from attenuation and phase shift measurements. The characteristic defect-free impedance of the line and its propagation constant are considered to be unknowns, and their values are also derived from the above measurements. In this way, the impact of process parameter variations on the proposed model is diminished. The experimental setup required to perform the characterization measurements and a simple graphical procedure to determine the defect and line parameters are presented. Experimental results show a good agreement between the predicted location of the open and its real location, found by optical beam induced resistance change inspection. Errors smaller than 2% of the total length of the line have been observed in the experiments.

An accurate electrical fault characterization is required for the correct diagnosis and localization of CMOS interconnect defects. It has been traditionally accepted that a resistive open defect located at the beginning of an interconnecting line causes the maximum possible delay. The first-order approximation is sufficient to model the behaviour of high resistive opens. However, in this paper it is shown that low resistive opens do not follow this behaviour. In these cases, a second-order model is required for a more precise prediction of their defective behaviour, since the maximum delay is obtained for an intermediate location, which depends on the relationship between the open resistance, the on-resistance of the transistor network driving the defective net, the parasitic capacitances and the threshold voltage of the transistors driven by the defective net. For that purpose, an experimental circuit has been designed and fabricated where open defects have been intentionally added in a set of interconnect CMOS lines. Both simulation and experimental results on defective interconnect lines show maximum delays for opens located at intermediate positions provided that the resistance of the open is on the order of the on-resistance of the driving transistor network.

The purpose of this study was to evaluate the influence of a steroid-free immunosuppression on hepatitis C virus (HCV) recurrence. A total of 198 liver transplantation (LT) patients were randomized to receive immunosuppression with basiliximab and cyclosporine, either with prednisone (steroid [St] group) or without prednisone (no steroids [NoSt] group). The group of 89 HCV-infected patients was followed up with protocol biopsies for 2 years after LT. This group of HCV patients are the patients evaluated in the present study. The rejection rate was 19% (St: 21% versus NoSt: 17%; P = 0.67). Patients in the St group had a slightly higher rate of bacterial infections (59% versus 38%; P = 0.05). Almost all patients had histological HCV-recurrence (St: 39/40 (97%) versus NoSt: 40/41 (97%); P = 1). The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months, 1 year, and 2 years were, 23%, 49%, and 49% in the NoSt group, compared to 33%, 55%, and 69% in the St group, respectively (P = 0.04 at 2 years). The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months, 1 year, and 2 years were 0%, 8%, and 22% in the NoSt group, compared to 8%, 19%, and 31% in the St group, respectively. Immunosuppression without steroids in HCV patients is safe, reduces bacterial infections and metabolic complications, and improves histological short-term evolution of HCV recurrence.

Throughout this study it is important to highlight the fundamental role that the members of the chapter performed in the geroninian project. For this outstanding group of people, basically coming from the low nobility of Alt Empordà, the new building enterprise resulted in the possibility of satisfaying the desire of promoting ecclesiastic benefits, as well as the objective of having new spaces —the chapels of the choir— conceived as the expression of glory and individual memory as well as the lineage.A lo largo de este estudio se pone de relieve el papel fundamental que desempeñaron los miembros del cabildo en el proyecto y construcción de la cabecera de la catedral gerundense. Para este grupo de personajes, básicamente procedentes de la baja nobleza altoampurdanesa, la nueva empresa edilicia supuso la posibilidad de satisfacer el deseo de promover beneficios eclesiásticos así como el objetivo de disponer de nuevos espacios —las capillas de la girola— concebidos como expresión de la gloria y la memoria individual y del linaje.

Test-pattern generators (TPGs), based on arithmetic operations, are becoming cost-effective built-in self-test solutions for circuits with embedded processors. Similar to pseudorandom TPGs, arithmetic TPGs use reseeding to reach high levels of fault coverage (FC). In this paper, we propose a method of searching for an effective reseeding strategy, guaranteeing a specified FC level. The proposed methodology minimizes the total test time under the constraint of the total memory resource allocated to store the seeds. The minimization is performed by a binary search that speeds up the seed selection. Experiments with benchmark circuits have shown an average reduction of 43.47% in test time compared with the three previous methodologies.

Liver metastases of colorectal cancer are currently treated by multidisciplinary teams using strategies that combine chemotherapy, surgery and ablative techniques. Many patients classically considered non-resectable can now be rescued by neoadjuvant chemotherapy followed by liver resection, with similar results to those obtained in initial resections. While many of those patients will recur, repeat resection is a feasible and safe approach if the recurrence is confined to the liver. Several factors that until recently were considered contraindications are now recognized only as adverse prognostic factors and no longer as contraindications for surgery. The current evaluation process to select patients for surgery is no longer focused on what is to be removed but rather on what will remain. The single most important objective is to achieve a complete (R0) resection within the limits of safety in terms of quantity and quality of the remaining liver. An increasing number of patients with synchronous liver metastases are treated by simultaneous resection of the primary and the liver metastatic tumours. Multilobar disease can also be approached by staged procedures that combine neoadjuvant chemotherapy, limited resections in one lobe, embolization or ligation of the contralateral portal vein and a major resection in a second procedure. Extrahepatic disease is no longer a contraindication for surgery provided that an R0 resection can be achieved. A reverse surgical staged approach (liver metastases first, primary second) is another strategy that has appeared recently. Provided that a careful selection is made, elderly patients can also benefit from surgical treatment of liver metastases.

The CMOS based memories are facing major issues with technology scaling, such as decreased reliability and increased leakage power. A point will be reached when the technology scaling issues will overweight the benefits. For this reason, alternate solutions are being proposed in literature, to possibly replace charge based memories. One of the most promising of these solutions is the spin-transfer-torque magnetic random access memory (STT-MRAM). To evaluate the viability of such solution, one must understand how it behaves under the effect of the various reliability degradation factors. In this paper we propose a methodology which allows for fast reliability evaluation of an STT-MRAM cell under process, voltage, and temperature variations. Our proposed method allows for a sensitivity analysis which will show the designer/test engineer which is the main reliability concern of a certain design. The method is general, and it can be applied to any memory design.

Testing mixed-signal circuits is a challenging task requiring high amounts of human and technical resources. To overcome these drawbacks, indirect testing methods have been adopted as an efficient solution to perform specification based tests using easy to measure CUT information. In this work, the acceptance/rejection regions are encoded using octrees with arbitrary precision regardless of the complexity of the boundary separating these regions. The strategy relies on two phases: (1) A statistical training phase generates the circuit samples to encode the acceptance/rejection regions using octrees. (2) The testing phase corresponds to the actual production testing of the fabricated ICs. The first phase is performed only once and requires sufficient samples of each pass/fail region to generate the octree under realistic CUT variations. The second phase is fast and only requires to evaluate the octree using the measures of the tested IC. In order to illustrate the proposal, the method has been applied to test a band-pass Biquad filter. Successful simulation results are reported showing considerable advantages in terms of test application time.

Pancreatic adenocarcinoma (PDAC) usually shows an enhanced expression of sialyl-Lewis X (sLex) and related epitopes. PDAC may secrete some of the proteins carrying such increased sLex determinant into serum, so they could be used as PDAC markers. Previously, we identified acute-phase proteins with increased sLex in both PDAC and in chronic pancreatitis patients. In this study, depleted sera from the main acute-phase proteins has been analysed for the search of proteins with increased sLex levels in PDAC. Sera from healthy controls, chronic pancreatitis and PDAC patients were depleted, electrophoresed and subjected to sLex immunodetection. Proteins that differentially expressed sLex in PDAC were trypsin digested and identified by LC-ESI-QTOF mass spectrometry. Five protein bands that differentially expressed sLex in PDAC were identified and corresponded to seven different acute-phase proteins. Among them, ceruloplasmin (CP) was selected for further analysis. N-glycan sequencing of CP confirmed the increase of sLex levels in CP in PDAC patients. Healthy controls, chronic pancreatitis and PDAC patients' sera were immunoprecipitated with anti-CP antibodies, and their sLex and CP levels were analysed by western blot. The sLex/CP ratio tended to be higher for the PDAC group, which altogether suggests that the sLex/CP ratio could be a useful biomarker for PDAC This work was supported by the Spanish Ministry of Science and Innovation, grants BIO 2007-61323 and BIO 2010-16922, awarded to R. P., and by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 260600 (“GlycoHIT”), awarded to R. S.

Binning after volume production is a widely accepted technique to classify fabricated integrated circuits (ICs) into different clusters depending on different degrees of specification compliance. This allows the manufacturer to sell nonoptimal devices at lower rates, so adapting to customer’s quality-price requirements. The binning procedure can be carried out by measuring every single circuit performances, but this approach is costly and time-consuming. On the contrary, if alternate measurements are used to characterize the bins, the procedure is considerably enhanced. In such a case, the specification bin boundaries become arbitrary shape regions due to the highly nonlinear mappings between the specifications space and the alternate measurements space. The binning strategy proposed in this paper functions with the same efficiency regardless of these shapes. The digital encoding of the bins in the alternate measurements space using octrees is the key idea of the proposal. The strategy has two phases: 1) the training phase and 2) the binning phase. In the training phase, the specification bins are encoded using octrees. This first phase requires sufficient samples of each class to generate the octree under realistic variations, but it only needs to be performed once. The binning phase corresponds to the actual production binning of the fabricated ICs. This is achieved by evaluating the alternate measurements in the previously generated octree. The binning phase is fast due to the inherent sparsity of the octree data structure. In order to illustrate the proposal, the method has been applied to a band-pass Butterworth filter considering three specification bins as a proof of concept. Successful simulation results are reported showing considerable advantages as compared to a support vector machine (SVM)-based classifier. Similar bin misclassifications are obtained with both methods, 1.68% using octrees and 1.83% using SVM, while binning time is $5\times $ times faster using octrees than using the SVM-based classifier.

In this work we demonstrate the potential of glycan reductive isotope labeling (GRIL) using [12C]- and [13C]-coded aniline and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry (μZIC-HILIC-ESI-MS) for relative quantitation of glycosylation variants in selected glycoproteins present in samples from cancer patients. Human α1-acid-glycoprotein (hAGP) is an acute phase serum glycoprotein whose glycosylation has been described to be altered in cancer and chronic inflammation. However, it is not clear yet whether some particular glycans in hAGP can be used as biomarker for differentiating between these two pathologies. In this work, hAGP was isolated by immunoaffinity chromatography (IAC) from serum samples of healthy individuals and from those suffering chronic pancreatitis and different stages of pancreatic cancer, respectively. After de-N-glycosylation, relative quantitation of the hAGP glycans was carried out using stable isotope labeling and μZIC-HILIC-ESI-MS analysis. First, protein denaturing conditions prior to PNGase F digestion were optimized to achieve quantitative digestion yields, and the reproducibility of the established methodology was evaluated with standard hAGP. Then, the proposed method was applied to the analysis of the clinical samples (control vs. pathological). Pancreatic cancer samples clearly showed an increase in the abundance of fucosylated glycans as the stage of the disease increases and this was unlike to samples from chronic pancreatitis. The results gained here indicate the mentioned glycan in hAGP as a candidate structure worth to be corroborated by an extended study including more clinical cases; especially those with chronic pancreatitis and initial stages of pancreatic cancer. Importantly, the results demonstrate that the presented methodology combining an enrichment of a target protein by IAC with isotope coded relative quantitation of N-glycans can be successfully used for targeted glycomics studies. The methodology is assumed being suitable as well for other such studies aimed at finding novel cancer associated glycoprotein biomarkers Part of this study was supported by the Spanish Ministry of Science and Innovation (CTQ2011-27130 awarded to V. S-N and BIO 2010-16922 awarded to R.P.)

Intragate open defects are responsible for a significant percentage of defects in present technologies. A majority of these defects causes the logic gate to become stuck open, and this is why they are traditionally modeled as stuck-open faults (SOFs). The classical approach to detect the SOFs is based on a two-vector sequence, and has been proved effective for a wide range of technologies. However, factors typically neglected in past technologies have become a major concern in nanometer technologies, i.e., leakage currents and downstream parasitic capacitances. Some recent works have examined the influence of leakage currents. However, to the best of our knowledge, no one has considered the influence of downstream parasitic capacitances. In this paper, the influence of both factors is investigated and experimentally measured with a test chip built on a 65-nm technology. An analysis based on the electrical simulations is performed to quantify the number of test escapes in the presence of SOFs. Test recommendations are derived from the analysis results to maximize the detectability of these faults in present and future technologies.

Steroid-free immunosuppressive regimens reduce corticosteroid-related side effects in liver transplant recipients although their efficacy is very variable. We evaluated the efficacy and safety of a steroid-free regimen in a 6-month, open-label, multicenter, pilot study, which involved 102 liver transplant patients treated with daclizumab (2 mg/kg within 6 h following transplant and 1 mg/kg on day 7), mycophenolate mofetil (MMF, 1 g b.i.d) and tacrolimus (trough levels of 5-15 ng/ml in the first month and 5-10 ng/ml thereafter). One intra-operative dose of methylprednisolone was administered. At 6 months, the acute rejection rate was 9.8%, and patient and graft survival rates were 96% and 95%, respectively. Acute rejection rates were similar for hepatitis C-positive patients (8.6%) and hepatitis C-negative patients (10.4%). Infections occurred in 22% of patients; most cases were considered mild or moderate. Post-transplantation hypertension and diabetes mellitus developed in 37% and 14% of patients, respectively, during the study period, but were markedly less frequent (8% and 6%, respectively) at 6 months. Hypercholesterolemia was observed in only 2% of patients. In conclusion, the steroid-free immunosuppressive regimen of daclizumab, MMF, and tacrolimus effectively prevents acute rejection after liver transplantation without decreasing safety.

We performed a prospective, randomized study of adult patients undergoing orthotopic liver transplantation, comparing hemodynamic and tissular oxygenation during reperfusion of the graft. In 30 patients, revascularization was started through the hepatic artery (i.e., initial arterial revascularization) and 10 minutes later the portal vein was unclamped; in 30 others, revascularization was started through the portal vein (i.e., initial portal revascularization) and 10 minutes later the hepatic artery was unclamped. The primary endpoints of the study were mean systemic arterial pressure and the gastric-end-tidal carbon dioxide partial pressure (PCO(2)) difference. The secondary endpoints were other hemodynamic and metabolic data. The pattern of the hemodynamic parameters and tissue oxygenation values during the dissection and anhepatic stages were similar in both groups At the first unclamping, initial portal revascularization produced higher values of mean pulmonary pressure (25 +/- 7 mm of Hg vs. 17 +/- 4 mm of Hg; P < 0.05) and wedge and central venous pressures. At the second unclamping, initial portal revascularization produced higher values of cardiac output and mean arterial pressure (87 +/- 15 mm of Hg vs. 79 +/- 15 mm of Hg; P < 0.05) and pulmonary blood pressure. Postreperfusion syndrome was present in 13 patients (42.5%) in the arterial group and in 11 patients (36%) in the portal group. During revascularization, the values of gastric and arterial pH decreased in both groups and recovered at the end of the procedure, but were more accentuated in the initial arterial revascularization group. In conclusion, we found that initial arterial revascularization of the graft increases pulmonary pressure less markedly, so it may be indicated for those patients with poor pulmonary and cardiac reserve. Nevertheless, for the remaining patients, initial portal revascularization offers more favorable hemodynamic and metabolic behavior, less inotropic drug use, and earlier normalization of lactate and pH values.

Testing mixed-signal circuits is a difficult task due to defect modeling challenges, observability and controllability restrictions and ATE bandwidth limitations. In this paper, the X-Y Zoning test of a Biquad filter is addressed to select the optimal excitation frequency and the best partition of the X-Y plane. Thus we obtain the best sensitivity of the BIST scheme to parametric shifts of the parameters defining the filter. The study has been particularized to shifts in the natural frequency f0 of the Biquad filter. Analytical results on the best input as well as the best partition of the observed X-Y Lissajous plots are obtained. Extensive MATLAB simulations validate the proposal, which has also been validated experimentally. For these experiments, multiple implementations of the Biquad with nominal and shifted parameters have been performed using a commercial Field Programmable Analog Array (FPAA). The experimental measures show good correlation with the analytical expressions and the simulations performed, and validate the proposed testing methodology.

Test power requirements for complex components are becoming stringent. The purpose of this paper is to reuse a recently proposed RT (Register Transfer) Level test preparation methodology to drive innovative Low-Energy (LE)/Low-Power (LP) BIST solutions for digital SoC (System on a Chip) embedded cores. RTL test generation is carried out through the definition of a reduced set of partially specified input vectors (masks), leading to a high correlation between multiple detection of RTL faults and single detection of likely physical defects. The methodology is referred as masked-based BIST, or m-BIST. BIST quality is evaluated considering three attributes: test effectiveness (TE), test length (TL) and test power (TP). LE BIST sessions are defined as short test sequences leading to high values of RT-level IFMB metrics and low-level Defects Coverage (DC). The energy and power of the BIST sessions, with and without mask forcing, is computed. It is shown that, by forcing vectors with the RTL masks, short BIST sessions, with low energy and with a comparable (or smaller) average power consumption, as compared to pseudo-random test, are derived. The usefulness of the methodology is ascertained using the VeriDOS simulation environment and modules of the CMUDSP and TORCH ITC'99 benchmark circuits.

Analog Switches (AS) play an essential role in a large number of Mixed-Signal circuits. Depending on the use of AS, designers have optimised their topology to meet the needs of each specific switching function. Furthermore, the success of Field Programmable devices in the digital domain (FPGAs) has motivated some manufacturers to explore similar solutions to fast prototype in the Analog and Mixed Signal domains. In this work, we explore the defective behaviours of programmable AS under realistic catastrophic and parametric defects. A classification of the DC defective behaviours for bridging and open defects is presented. This classification shows that the simple fault model with faulty state of permanently transistor “stuck-on” or “stuck-off” is not sufficient to reflect the real behaviour of a defective switch. It has also been found that parametric defects such as threshold voltage variations are not DC testable, and would therefore require additional AC tests.

Analog and mixed-signal circuit testing is a challenging task demanding large amounts of resources. In order to battle against this drawback, alternate testing has been established as an efficient way of testing analog and M-S circuits by using indirect measures instead of the classic specification based testing. In this work we propose the use of Kendall's Tau rank correlation coefficient for rating the suitability of a set of candidate indirect measures to be used in mixed-signal testing. Such criterion is shown to be adequate since it allows to avoid or minimize information redundancy in the measures set. As a proof of concept, a 4th order band-pass Butterworth filter has been simulated under the presence of process variations. The circuit has been tested using a subset of measures selected according to minimum Kendall's Tau coefficient. Analog test efficiency metrics are reported showing test misclassification rate is among the best 15% possible, therefore validating the proposal.

Analog and mixed-signal circuit design demands high amounts of knowledge, expertise and intuition. To that purpose, it is not deniable electrical CAD tools play a crucial role assisting designers in such complex scenario. SPICE-like electrical simulators have been established through the years as the de facto standard for analog and mixed-signal circuit simulation. Such simulation programs work at low level circuit description dealing with explicit component instantiations and electrical connections between them with no possibilities of description at a higher level. In this work, a software tool partially addressing this issue is proposed. The developed tool allows the designer to simulate a signal flow graph (SFG) given its behavioral description. The proposed tool efficiently transforms a behavioral SFG description into a netlist suitable for SPICE. It also generates the required graphical commands for rendering the graph as well as the listing of node equations to be solved algebraically. In order to evaluate the tool, it has been applied to behaviorally describe a transient error and fault tolerant scheme applied to a Biquad filter. The tool has been proven to be efficient in terms of its capabilities for mixing structural and behavioral descriptions in a single netlist, as well as for its simplicity and usefulness when dealing with large linear systems, therefore validating the proposal.

Among several regions in the world hepatic hydatidosis can be considered endemic. Currently there are many available treatments for this disease, been surgery the most effective one. Surgical procedures can be divided in two main groups, radical and non-radical procedures. The goal of this work is to evaluate the morbidity, mortality and percentage of recurrence in patients treated with hepatectomies, comparing them with other publications.This retrospective study was carried out in a series from Spain and Argentina. We analyzed the following data: sex, age, type of resection, associated surgical gestures, presence of liver disease, operative time, blood transfusion, morbidity, mortality, hospital stay, re-hospitalization, recurrence and follow up. Dindo--Clavien classification was used for complications, and International Hepato-Pancreato-Biliary Association (IHPBA) Brisbane classification for hepatectomies. Mortality was considered until 90 days after surgery. To evaluate the recurence we only included patients followed over 6 months.Indications for liver resections were performed in patients with cysts larger than 5 centimeters, multiple cysts, large cysts, with bile duct communicated or suspicion of this communication. Five patients required blood transfusions (10%) with a median for these 5 patients of 740 ml and 74 ml for the complete series. The median operative time was 186 minutes (range 45 to 1,050 minutes). Median hospital stay was 7.7 days. Monitoring more than 6 months was conducted in 38 patients.We believe that hepatic hydatid disease is a multifaceted disease and requires more than one therapeutic approach. Hepatectomy with complete resection of the parasite offers the possibility of doing so in a controlled and safe way by experienced hands, ensuring good results in the treatment of this disease.

Through Silicon Vias (TSVs) are critical elements in three dimensional integrated circuits (3-D ICs) and are susceptible to undergo defects at different stages: during their own fabrication, the bonding stage or during their life time. Typical defects are microvoids, underfilling, misalignement, pinholes in the oxide or misalignments during bonding in such a way that resistive opens become a frequent failure mechanism affecting TSVs. Although there is considerable research effort dedicated to improve TSVs testing, no much attention has been paid to weak defects, especially to weak open defects (resistive opens) causing small delays. In this work, a testing strategy is proposed to detect small delay defects by means of a post-bond oscillation test. Variations in the Duty Cycle of transmitted signals after unbalanced logic gates are shown to detect weak open defects in TSVs. HSPICE simulations including process parameter variations show the effectiveness of the method in the detection of weak open defects above 1 kO.