ASLPrep: a platform for processing of arterial spin labeled MRI and quantification of regional brain perfusion.

Arterial spin labeled (ASL) magnetic resonance imaging (MRI) is the primary method for noninvasively measuring regional brain perfusion in humans. We introduce ASLPrep, a suite of software pipelines that ensure the reproducible and generalizable processing of ASL MRI data.

Associations between neighborhood socioeconomic status, parental education, and executive system activation in youth.

Socioeconomic status (SES) can impact cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may influence cognitive outcomes. Here, we sought to examine how SES at the neighborhood and family level impacts task-related activation of the executive system during adolescence and determine whether this effect mediates the relationship between SES and WM performance. To address these questions, we studied 1,150 youths (age 8-23) that completed a fractal n-back WM task during functional magnetic resonance imaging at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that both higher neighborhood SES and parental education were associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. The association of neighborhood SES remained significant when controlling for task performance, or related factors like exposure to traumatic events. Furthermore, high-dimensional multivariate mediation analysis identified distinct patterns of brain activity within the executive system that significantly mediated the relationship between measures of SES and task performance. These findings underscore the importance of multilevel environmental factors in shaping executive system function and WM in youth.

A Comparison of the Learning Curves of Laparoscopic Liver Surgeons in Differing Stages of the IDEAL Paradigm of Surgical Innovation: Standing on the Shoulders of Pioneers.

OBJECTIVE: To compare the learning curves of the self-taught "pioneers" of laparoscopic liver surgery (LLS) with those of the trained "early adopters" in terms of short- and medium-term patient outcomes to establish if the learning curve can be reduced with specific training. SUMMARY OF BACKGROUND DATA: It is expected that a wider adoption of a laparoscopic approach to liver surgery will be seen in the next few years. Current guidelines stress the need for an incremental, stepwise progression through the learning curve in order to minimize harm to patients. Previous studies have examined the learning curve in Stage 2 of the IDEAL paradigm of surgical innovation; however, LLS is now in stage 3 with specific training being provided to surgeons. METHODS: Using risk-adjusted cumulative sum analysis, the learning curves and short- and medium-term outcomes of 4 "pioneering" surgeons from stage 2 were compared with 4 "early adapting" surgeons from stage 3 who had received specific training for LLS. RESULTS: After 46 procedures, the short- and medium-term outcomes of the "early adopters" were comparable to those achieved by the "pioneers" following 150 procedures in similar cases. CONCLUSIONS: With specific training, "early adapting" laparoscopic liver surgeons are able to overcome the learning curve for minor and major liver resections faster than the "pioneers" who were self-taught in LLS. The findings of this study are applicable to all surgical specialties and highlight the importance of specific training in the safe expansion of novel surgical practice.

Smart Pipe System for a Shipyard 4.0.

As a result of the progressive implantation of the Industry 4.0 paradigm, many industries are experimenting a revolution that shipyards cannot ignore. Therefore, the application of the principles of Industry 4.0 to shipyards are leading to the creation of Shipyards 4.0. Due to this, Navantia, one of the 10 largest shipbuilders in the world, is updating its whole inner workings to keep up with the near-future challenges that a Shipyard 4.0 will have to face. Such challenges can be divided into three groups: the vertical integration of production systems, the horizontal integration of a new generation of value creation networks, and the re-engineering of the entire production chain, making changes that affect the entire life cycle of each piece of a ship. Pipes, which exist in a huge number and varied typology on a ship, are one of the key pieces, and its monitoring constitutes a prospective cyber-physical system. Their improved identification, traceability, and indoor location, from production and through their life, can enhance shipyard productivity and safety. In order to perform such tasks, this article first conducts a thorough analysis of the shipyard environment. From this analysis, the essential hardware and software technical requirements are determined. Next, the concept of smart pipe is presented and defined as an object able to transmit signals periodically that allows for providing enhanced services in a shipyard. In order to build a smart pipe system, different technologies are selected and evaluated, concluding that passive and active RFID (Radio Frequency Identification) are currently the most appropriate technologies to create it. Furthermore, some promising indoor positioning results obtained in a pipe workshop are presented, showing that multi-antenna algorithms and Kalman filtering can help to stabilize Received Signal Strength (RSS) and improve the overall accuracy of the system.

Pulmonary Arterial Tumor Embolism From Recurrent Metastatic Renal Cell Carcinoma on FDG PET/CT.

ABSTRACT: A 55-year-old man with renal cell carcinoma extending into the renal vein/inferior vena cava (status post nephrectomy and inferior vena cava thrombectomy, pT3bN0M0), and perioperative pulmonary bland thromboembolism (resolved with 3-month of anticoagulation), followed by 3.5 years of complete remission, developed new incidental pulmonary arterial filling defects on a surveillance CT examination (asymptomatic, normal d -dimer, no deep vein thrombosis). Despite anticoagulation, the filling defects not only persisted but also demonstrated intense FDG activity on a restaging PET/CT performed 4 months later for new pulmonary oligometastasis. The FDG activity resolved after systemic immunotherapy, which suggested the retrospective diagnosis of pulmonary arterial tumor emboli, a rare finding.

Predictors of early graft survival after pediatric liver transplantation.

The objective of this study was to identify peritransplant predictors of early graft survival and posttransplant parameters that could be used to predict early graft outcomes after pediatric liver transplantation (PLT). The response of children to liver dysfunction after liver transplantation (LT) is poor. No data have been reported for early predictors of poor graft survival, which would potentially be valuable for rescuing children at risk after LT. A retrospective cohort study of 422 PLT procedures performed from 2000 to 2010 at a single center was conducted. Multiple peritransplant variables were analyzed. Univariate and multivariate analyses using receiver operating characteristic curves were performed to identify predictors of early graft loss (ie, at 30, 60, and 90 days). The number needed to treat (NNT) was calculated when the risk factors were identified. Comparisons with the Olthoff criteria for early graft dysfunction in adults were performed. The overall 30-, 60-, and 90-day graft survival rates were 93.6%, 92.6%, and 90.7%, respectively. A recipient age of 0 to 2 or 6 to 16 years, acute liver failure, and a posttransplant day 7 serum bilirubin level > 200 µmol/L were risk factors for graft loss in the 3-strata Cox models. The product of the peak aspartate aminotransferase (AST) level, day 2 international normalized ratio (INR) value, and day 7 bilirubin level [with 30-, 60-, and 90-day areas under the receiver operating characteristic curve (AUROCs) of 0.774, 0.752, and 0.715, respectively] and a day 7 bilirubin level > 200 µmol/L (with 30-, 60-, and 90-day AUROCs of 0.754, 0.661, and 0.635, respectively) provided excellent prediction rates for early graft loss (30-days for Day-7-bilirubin level > 200) in the pediatric population (sensitivity = 72.7%, specificity = 96.6%, positive predictive value = 95.5%, negative predictive value = 78%). The NNT with early retransplantation when the day 7 bilirubin level was >200 µmol/L was 2.17 (unadjusted) or 2.76 (adjusted for graft survival). In conclusion, 2 scores-the product of the peak AST level, day 2 INR value, and day 7 bilirubin level and a posttransplant day 7 bilirubin level > 200 µmol/L-have been identified as clinically valuable tools with high accuracy for predicting early graft loss. A more aggressive attitude to considering early retransplantation in this group may further improve survival after LT.

Auxiliary liver transplantation in children.

PURPOSE OF REVIEW: Auxiliary liver transplantation (ALT) has developed as a technique for treating patients with acute liver failure. The surgical techniques of ALT have been refined and current patient survival appears to be similar to that observed with conventional liver replacement for acute liver failure. RECENT FINDINGS: Our understanding of liver regeneration has improved with experience and it is possible to identify patient and disease groups that are more likely to regenerate and wean off immunosuppression after ALT. Withdrawal of immunosuppression is possible in at least two thirds of survivors up to 4 years post transplant. Young patients have most to gain in the long term from immunosuppression withdrawal. Documentation of liver regeneration should be performed by liver histology, nuclear medicine scanning and CT volumetry. Weaning should be gradual to allow for graft atrophy to avoid complications. ALT has also been utilised for the management of inborn errors of metabolism based in the liver and for other rare problems and these will be briefly addressed in the review. SUMMARY: Auxiliary liver transplantation should be considered for the treatment of children with acute liver failure satisfying current criteria for liver transplantation.

FlywheelTools: Data Curation and Manipulation on the Flywheel Platform.

The recent and growing focus on reproducibility in neuroimaging studies has led many major academic centers to use cloud-based imaging databases for storing, analyzing, and sharing complex imaging data. Flywheel is one such database platform that offers easily accessible, large-scale data management, along with a framework for reproducible analyses through containerized pipelines. The Brain Imaging Data Structure (BIDS) is the de facto standard for neuroimaging data, but curating neuroimaging data into BIDS can be a challenging and time-consuming task. In particular, standard solutions for BIDS curation are limited on Flywheel. To address these challenges, we developed "FlywheelTools," a software toolbox for reproducible data curation and manipulation on Flywheel. FlywheelTools includes two elements: fw-heudiconv, for heuristic-driven curation of data into BIDS, and flaudit, which audits and inventories projects on Flywheel. Together, these tools accelerate reproducible neuroscience research on the widely used Flywheel platform.

Biliary Tract Carcinogenesis Model Based on Bile Metaproteomics.

Purpose: To analyze human and bacteria proteomic profiles in bile, exposed to a tumor vs. non-tumor microenvironment, in order to identify differences between these conditions, which may contribute to a better understanding of pancreatic carcinogenesis. Patients and Methods: Using liquid chromatography and mass spectrometry, human and bacterial proteomic profiles of a total of 20 bile samples (7 from gallstone (GS) patients, and 13 from pancreatic head ductal adenocarcinoma (PDAC) patients) that were collected during surgery and taken directly from the gallbladder, were compared. g:Profiler and KEGG (Kyoto Encyclopedia of Genes and Genomes) Mapper Reconstruct Pathway were used as the main comparative platform focusing on over-represented biological pathways among human proteins and interaction pathways among bacterial proteins. Results: Three bacterial infection pathways were over-represented in the human PDAC group of proteins. IL-8 is the only human protein that coincides in the three pathways and this protein is only present in the PDAC group. Quantitative and qualitative differences in bacterial proteins suggest a dysbiotic microenvironment in the PDAC group, supported by significant participation of antibiotic biosynthesis enzymes. Prokaryotes interaction signaling pathways highlight the presence of zeatin in the GS group and surfactin in the PDAC group, the former in the metabolism of terpenoids and polyketides, and the latter in both metabolisms of terpenoids, polyketides and quorum sensing. Based on our findings, we propose a bacterial-induced carcinogenesis model for the biliary tract. Conclusion: To the best of our knowledge this is the first study with the aim of comparing human and bacterial bile proteins in a tumor vs. non-tumor microenvironment. We proposed a new carcinogenesis model for the biliary tract based on bile metaproteomic findings. Our results suggest that bacteria may be key players in biliary tract carcinogenesis, in a long-lasting dysbiotic and epithelially harmful microenvironment, in which specific bacterial species' biofilm formation is of utmost importance. Our finding should be further explored in future using in vitro and in vivo investigations.

Leveraging multi-shell diffusion for studies of brain development in youth and young adulthood.

Diffusion weighted imaging (DWI) has advanced our understanding of brain microstructure evolution over development. Recently, the use of multi-shell diffusion imaging sequences has coincided with advances in modeling the diffusion signal, such as Neurite Orientation Dispersion and Density Imaging (NODDI) and Laplacian-regularized Mean Apparent Propagator MRI (MAPL). However, the relative utility of recently-developed diffusion models for understanding brain maturation remains sparsely investigated. Additionally, despite evidence that motion artifact is a major confound for studies of development, the vulnerability of metrics derived from contemporary models to in-scanner motion has not been described. Accordingly, in a sample of 120 youth and young adults (ages 12-30) we evaluated metrics derived from diffusion tensor imaging (DTI), NODDI, and MAPL for associations with age and in-scanner head motion at multiple scales. Specifically, we examined mean white matter values, white matter tracts, white matter voxels, and connections in structural brain networks. Our results revealed that multi-shell diffusion imaging data can be leveraged to robustly characterize neurodevelopment, and demonstrate stronger age effects than equivalent single-shell data. Additionally, MAPL-derived metrics were less sensitive to the confounding effects of head motion. Our findings suggest that multi-shell imaging data and contemporary modeling techniques confer important advantages for studies of neurodevelopment.

Accelerated cortical thinning within structural brain networks is associated with irritability in youth.

Irritability is an important dimension of psychopathology that spans multiple clinical diagnostic categories, yet its relationship to patterns of brain development remains sparsely explored. Here, we examined how transdiagnostic symptoms of irritability relate to the development of structural brain networks. All participants (n = 137, 83 females) completed structural brain imaging with 3 Tesla MRI at two timepoints (mean age at follow-up: 21.1 years, mean inter-scan interval: 5.2 years). Irritability at follow-up was assessed using the Affective Reactivity Index, and cortical thickness was quantified using Advanced Normalization Tools software. Structural covariance networks were delineated using non-negative matrix factorization, a multivariate analysis technique. Both cross-sectional and longitudinal associations with irritability at follow-up were evaluated using generalized additive models with penalized splines. The False Discovery Rate (q < 0.05) was used to correct for multiple comparisons. Cross-sectional analysis of follow-up data revealed that 11 of the 24 covariance networks were associated with irritability, with higher levels of irritability being associated with thinner cortex. Longitudinal analyses further revealed that accelerated cortical thinning within nine networks was related to irritability at follow-up. Effects were particularly prominent in brain regions implicated in emotion regulation, including the orbitofrontal, lateral temporal, and medial temporal cortex. Collectively, these findings suggest that irritability is associated with widespread reductions in cortical thickness and accelerated cortical thinning, particularly within the frontal and temporal cortex. Aberrant structural maturation of regions important for emotional regulation may in part underlie symptoms of irritability.

Temporary portocaval shunt in orthotopic liver transplantation: need for a standardized approach?

Maintenance of portal and systemic venous return during the anhepatic phase of liver transplantation (LT) improves hemodynamic stability. With the piggyback technique, caval return is maintained; however, temporary clamping of the portal vein is still necessary. The use of a temporary portocaval shunt (TPCS) has been proposed to minimize the effect of portal venous interruption. The aim of this study was to perform a systematic review of the literature to determine whether there is evidence to support the routine use of a TPCS in LT. An electronic search of the literature from 1963 to 2007 was performed. A total of 4386 articles were identified, of which 8 met all the criteria and were included in the study. Because of the variability in reporting and the small number of studies, statistical comparison was not possible; however, a trend toward a shorter operative time, less blood product transfusion, and maintenance of higher mean arterial pressures during portal vein clamping was seen in patients with a TPCS. In conclusion, the available evidence, albeit scarce, supports the use of a TPCS in patients undergoing LT. A prospective randomized study of patients most likely to benefit from a TPCS is necessary to substantiate these findings.

Vagal dysfunction and the pathogenesis of chronic Chagas disease.

Vagal dysfunction is thought to be an early, primary and specific abnormality of chronic Chagas disease. However, chagasic patients with unequivocal evidence of heart disease, can have normal or abnormal vagal control of heart rate. A common explanation for these apparently discordant and contradictory results is proposed.

Mechanisms of neurohormonal activation in chronic congestive heart failure: pathophysiology and therapeutic implications.

Patients with chronic congestive heart failure have a sequential and incessant activation of those neurohormonal systems, which control body fluids, cardiac output and systemic blood pressure. Neurohormonal activation is initially selective and regional. Generalized activation is a late event in the natural history of congestive heart failure. Although the ultimate stimulus responsible for the activation of these neurohormonal systems is unknown, a decreased cardiac output and diminished effective blood volume have been proposed as the responsible mechanisms. However, extensive clinical and experimental research suggest that cardiac remodeling and loading of low-pressure cardiac receptors with sympathetic afferents could be the triggering events followed by unloading of high-pressure carotid receptors by decreased cardiac output and diminished effective blood volume.

Evaluation of osseous metastasis in bone scintigraphy.

Bone scintigraphy (BS) is an imaging tool commonly used for screening patients with cancer, especially those with high prevalence of osseous metastases including the breast, prostate, lung, thyroid, and kidney, which account for 80% of osseous metastasis. BS has been shown to be of value in the initial and subsequent treatment strategy of various malignancies. The purpose of this article is to evaluate the technical and imaging aspects of BS and to examine the present research into improved detection of osseous metastasis.

Sympathetic nervous system activation, antivenin administration and cardiovascular manifestations of scorpion envenomation.

We performed two-dimensional echocardiograms and determined plasma norepinephrine levels on admission and at 24h after hospitalization, in 16 children with scorpion envenomation. All patients came from areas where scorpions have been identified as Tityus zulianus and received antivenin at the site of the accident or upon admission. Based on the presence or absence of cardiovascular manifestations, patients were divided into two groups. GROUP A: 10 patients had cardiovascular manifestations of pulmonary edema. Four patients had mild pulmonary edema (Left ventricular ejection fraction: 0.43+/-0.19) and six had moderate to severe pulmonary edema (Ejection fraction: 0.31+/-0.09. p=NS, M+/-SD). Plasma norepinephrine was elevated on admission (1279+/-824) and decreased at 24h in seven of eight patients (474+/-140 pg/ml, p<0.03). GROUP B: Six patients had no cardiovascular manifestations. These patients had normal chest X-rays and normal echocardiograms. Plasma norepinephrine was not elevated (188+/-180 pg/ml). Time interval from the accident to antivenin administration was significantly longer in Group A compared to Group B (4.5+/-3.3 vs 1.2+/-0.4h, p<0.03) and correlated directly with the absolute change in plasma norepinephrine (r=0.76, p<001). Consequently, we strongly recommend very early administration of antivenin in the medical management of scorpion envenomation by T. zulianus.

A modified and unifying neurogenic hypothesis can explain the natural history of chronic Chagas heart disease.

The pathogenesis of chronic Chagas disease still is an unresolved and controversial issue. Parasite persistence and autoimmune responses cannot explain the spectrum of chronic Chagas disease. However, a modified neurogenic hypothesis, concerning the timing and mechanisms responsible for the cardiac parasympathetic damage and for the activation of the sympathetic nervous system and of other neurohormonal systems, unifies cardiac remodelling and neurohormonal activation to explain most of the events of the natural history of Chagas disease.

Valsalva maneuver in chagasic patients with documented past medical history of acute chagasic myocarditis.

BACKGROUND: We studied the heart rate responses to the Valsalva maneuver in eight patients with documented past medical history of acute Chagas' disease. METHODS: Four patients were studied 8-21 months after the acute episode and four, 58-68 months thereafter (age 25+/-8.65 years M+/-S.D.). Seventeen healthy subjects of similar age were included as controls (age 27+/-7.5 years, P=NS). RESULTS: Baseline heart rate was higher in chagasic patients (88+/-15 beats/min) compared to controls (69.8+/-9.8, P=0.001). Maximum heart rate at phase II of the maneuver was also higher (114+/-16.3 vs. 101.5+/-9.9, P=0.02). Minimum heart rate at phase IV was, however, not different (57.4+/-10.4 vs. 63.3+/-7.3 P=NS). The magnitude of the absolute negative change at phase IV was larger in the chagasic patients, although, not different (-50.8+/-13.8 vs. -44+/-13.8, P=NS). The Valsalva index was 1.81+/-0.26 in the chagasic patients and 1.82+/-0.42 in the controls (P=NS). Minimum heart rate at phase IV correlated neither with the baseline heart rate (r=-0.28, P=NS) nor with the Valsalva index (r=-0.40, P=NS). The magnitude of the absolute negative change during phase IV correlated with, both, the baseline heart rate (r=-0.80, P<0.01) and the Valsalva index (r=-0.95, P<0.0001). The higher baseline high rate influenced the magnitude of the negative heart rate change, but not the minimum heart rate reached at phase IV. CONCLUSIONS: Chagasic patients with proven past medical history of acute Chagas' disease had unimpaired heart responses to the Valsalva maneuver.

Effects of metoprolol in chagasic patients with severe congestive heart failure.

BACKGROUND: Beta-blockers are the most effective and promising treatment for congestive heart failure secondary to left ventricular dysfunction and sympathetic activation. METHODS: Since chagasic patients with severe congestive heart failure have left ventricular systolic dysfunction and neurohormonal activation, we administered metoprolol to nine chagasic patients who were in severe congestive heart failure. Metoprolol (5 mg p.o. daily) was uptitrated on a weekly basis. RESULTS: Patients were receiving digitalis, diuretics and angiotensin converting enzyme inhibitors and had left ventricular dilatation (6.77+/-0.89 cm), depressed ejection fraction (0.20+/-0.06), low systolic blood pressure (93+/-11 mm Hg), sinus tachycardia (115+/-17 beats/min) and sympathetic activation 400+/-246 pg/ml). One patient was in New York Heart Association Functional class III and eight patients were in functional class IV. At the end of the fifth week of treatment (metoprolol 25 mg), seven patients were in functional class III and two were in functional class II. Heart rate decreased to 85+/-15 beats/min (P<0.05) and the systolic blood pressure increased to 108+/-18 mm Hg (P<0.01). There were no significant changes in left ventricular ejection fraction. By the end of the tenth week of treatment (metoprolol 50 mg), four patients were now in functional class I and five were in functional class II. Left ventricular ejection fraction increased to 0.27+/-0.05 (P<0.01) and the left ventricular systolic diameter decreased from 6.38+/-0.90 at baseline to 5.89+/-0.59 and 5.76+/-0.96 after 25 and 50 mg of metoprolol treatment, respectively (P<0.04). Plasma norepinephrine decreased non-significantly to 288+/-91 pg/ml. CONCLUSION: Beta-blockers improve the clinical status and the left ventricular function of chagasic patients with severe congestive heart failure.