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From AD 567-568, at the onset of the Avar period, populations from the Eurasian Steppe settled in the Carpathian Basin for approximately 250 years 1 . Extensive sampling for archaeogenomics (424 individuals) and isotopes, combined with archaeological, anthropological and historical contextualization of four Avar-period cemeteries, allowed for a detailed description of the genomic structure of these communities and their kinship and social practices. We present a set of large pedigrees, reconstructed using ancient DNA, spanning nine generations and comprising around 300 individuals. We uncover a strict patrilineal kinship system, in which patrilocality and female exogamy were the norm and multiple reproductive partnering and levirate unions were common. The absence of consanguinity indicates that this society maintained a detailed memory of ancestry over generations. These kinship practices correspond with previous evidence from historical sources and anthropological research on Eurasian Steppe societies 2 . Network analyses of identity-by-descent DNA connections suggest that social cohesion between communities was maintained via female exogamy. Finally, despite the absence of major ancestry shifts, the level of resolution of our analyses allowed us to detect genetic discontinuity caused by the replacement of a community at one of the sites. This was paralleled with changes in the archaeological record and was probably a result of local political realignment., (© 2024. The Author(s).)

Background: The "Leo&Giulia standing for public health" project is an innovative digital health education model targeting primary school children. The project, developed during the COVID-19 pandemic, aims to educate primary school-aged children about public health issues through an animated cartoon series. It highlights the importance of early-life health promotion and the potential role of educational settings in shaping health behaviours., Study Design: A 2-year school-based cluster-randomized controlled community trial will be conducted among 8-10-year-old pupils in the province of Pavia, Northern Italy., Methods: The intervention group will receive an educational programme via a new episode of "Leo&Giulia" animated series, focusing on smoking prevention. The study will assess changes in knowledge, attitudes towards smoking, and communication about smoking risks among peers and parents. The trial involves baseline and follow-up assessments through questionnaires targeting both children and parents., Results (expected): We assume that children in the intervention group will demonstrate increased knowledge and awareness of smoking-related health risks and develop negative attitudes towards tobacco use compared to the control group. Enhanced communication about tobacco harms among peers and between children and parents, as well as increased parental involvement in anti-smoking socialization practices, are expected secondary outcomes., Discussion and Conclusions: "Leo&Giulia" integrates health education into the school curriculum, leveraging the appeal of animated content to engage children in public health topics. The project is expected to contribute to the field of health education by demonstrating the effectiveness of digital health interventions in childhood, foreseeing potential long-term impacts on health behaviors and in shaping future public health strategies.

Molecular diagnostic methods to detect and quantify viral RNA in clinical samples rely on the purification of the genetic material prior to reverse transcription polymerase chain reaction (qRT-PCR). Due to the large number of samples processed in clinical laboratories, automation has become a necessity in order to increase method processivity and maximize throughput per unit of time. An attractive option for isolating viral RNA is based on the magnetic solid phase separation procedure (MSPS) using magnetic microparticles. This method offers the advantage over other alternative methods of making it possible to automate the process. In this study, we report the results of the MSPS method based on magnetic microparticles obtained by a simple synthesis process, to purify RNA from oro- and nasopharyngeal swab samples of patients suspected of COVID-19 provided by three diagnostic laboratories located in the Buenos Aires Province, Argentina. Magnetite nanoparticles of Fe 3 O 4 (MNPs) were synthesized by the coprecipitation method and then coated with silica (SiO 2 ) produced by hydrolysis of tetraethyl orthosilicate (TEOS). After preliminary tests on samples from the A549 human lung cell line and swabs, an extraction protocol was developed. The quantity and purity of the RNA obtained were determined by gel electrophoresis, spectrophotometry, and qRT-PCR. Tests on samples from naso- and oropharyngeal swabs were performed in order to validate the method for RNA purification in high-throughput SARS-CoV-2 diagnosis by qRT-PCR. The method was compared to the spin columns method and the automated method using commercial magnetic particles. The results show that the method developed is efficient for RNA extraction from nasal and oropharyngeal swab samples, and also comparable to other extraction methods in terms of sensitivity for SARS-CoV-2 detection. Of note, this procedure and reagents developed locally were intended to overcome the shortage of imported diagnostic supplies as the sudden spread of COVID-19 required unexpected quantities of nucleic acid isolation and diagnostic kits worldwide., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Executive Functions (EFs) are high-order cognitive processes relevant to learning and adaptation and frequently impaired in children with specific learning disorders (SLDs). This study aimed to investigate EFs in children with SLD and explore the role of specific EF-related subprocesses, such as stimuli processing and processing speed. Fifty-seven SLD and 114 typically developing (TD) children, matched for gender and age, completed four tasks measuring response inhibition, interference control, shifting, and updating on a web-based teleassessment platform. The results show that SLD children performed lower in all EF tasks than TD children, regardless of stimulus type and condition. Mediation analyses suggested that differences between the SLD and TD groups are mediated by EF-related subprocesses, offering an interpretative model of EF deficits in children with SLD., Competing Interests: Declaration of interest statement MIUR Project RiDi Fisr2020 – TD MEPA 1760961 and Regione Toscana PROTENEUCO project CUP: C89C20000290002., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The study investigates whether Italian verbal inflectional morphology is associated with inhibitory control skills after controlling for receptive vocabulary and verbal working memory. A sample of Italian preschoolers aged 4;0 to 6;0 was assessed using a standardized inhibitory control task tapping two different inhibitory skills (response inhibition and interference suppression), and a morphological task requiring simple and complex inflections of verbs. The hierarchical multiple regression analyses showed that working memory and the interference suppression scores were significantly associated with complex inflections but not with simple inflections of the verbs.

Background: Triatoma infestans is the main vector of Chagas disease in the Americas, currently transmitting it in Argentina, Paraguay, and Bolivia. Many T. infestans populations present insecticide resistance, reducing the efficiency of control campaigns. Alternative vector control methods are needed, and molecular targets mediating fundamental physiological processes can be a promising option to manipulate kissing bug behavior. Therefore, it is necessary to characterize the main sensory targets, as well as to determine whether they are modulated by physiological factors. In order to identify gene candidates potentially mediating host cue detection, the antennal transcripts of T. infestans fifth instar larvae were sequenced and assembled. Besides, we evaluated whether a blood meal had an effect on transcriptional profiles, as responsiveness to host-emitted sensory cues depends on bug starvation., Results: The sensory-related gene families of T. infestans were annotated (127 odorant receptors, 38 ionotropic receptors, 11 gustatory receptors, 41 odorant binding proteins, and 25 chemosensory proteins, among others) and compared to those of several other hemipterans, including four triatomine species. Several triatomine-specific lineages representing sensory adaptations developed through the evolution of these blood-feeding heteropterans were identified. As well, we report here various conserved sensory gene orthogroups shared by heteropterans. The absence of the thermosensor pyrexia, of pickpocket receptor subfamilies IV and VII, together with clearly expanded takeout repertoires, are revealed features of the molecular bases of heteropteran antennal physiology. Finally, out of 2,122 genes whose antennal expression was significantly altered by the ingestion of a blood meal, a set of 41 T. infestans sensory-related genes (9 up-regulated; 32 down-regulated) was detected., Conclusions: We propose that the set of genes presenting nutritionally-triggered modulation on their expression represent candidates to mediate triatomine host-seeking behavior. Besides, the triatomine-specific gene lineages found represent molecular adaptations to their risky natural history that involves stealing blood from an enormously diverse set of vertebrates. Heteropteran gene orthogroups identified may represent unknown features of the sensory specificities of this largest group of hemipteroids. Our work is the first molecular characterization of the peripheral modulation of sensory processes in a non-dipteran vector of human disease., (© 2022. The Author(s).)

Background: Hemiptera is one of the most speciose orders of insects, and the most speciose considering Hemimetabola. Through their evolutive history, hemipterans with different feeding habits have adapted to deal with different chemical challenges. Three major gene families are involved in xenobiotic detoxification in insects: the cytochromes P450 (CYPs), carboxyl/cholinesterases (CCEs), and glutathione transferases (GSTs). Here we perform a comparative analysis on the complement of these gene superfamilies across five hemipteran species; four heteropterans (the pentatomid plant feeders Nezara viridula and Halyomorpha halys; the hematophagous Cimex lectularius, Cimicidae, and Rhodnius prolixus, Reduviidae), and one Auchenorrhyncha plant feeder (Nilaparvata lugens)., Results: Our results point to an expansion of several enzyme families associated with xenobiotic detoxification in heteropterans with respect to other species and the existence of a dynamic evolution pattern including CYP3 clan, hormone and pheromone processing class in the CCE superfamily, and sigma class in GST superfamily. Other detoxification-related families are reduced in the hemipteran species analyzed here: reduction or even absence of epsilon class and reduced delta class in GST superfamily; absence of mitochondrial CYP12 family; absence of CYP9 family in CYP3 clan; and reduction or even absence of some dietary/detoxification groups of CCEs. Interestingly, the most polyphagous species analyzed here (H. halys) is also the one that presents the largest repertoire of detoxification enzymes. Gene cluster analysis suggests that this could be due to gene duplication events., Conclusions: The evolutionary analysis performed here reveals characteristics that are both common and particular for heteropterans. The composition and organization of detoxification-related gene families could shed light on evolutionary forces that shaped their divergence. These families are important for both the detoxification of diet products and for conferring tolerance or resistance to synthetic insecticides. Furthermore, we present the first comprehensive analysis of detoxification gene superfamilies in N. viridula, an understudied species in spite of its economic relevance as a crop pest. The information obtained is of interest for basic insect science as well as for the control of harmful species and the management of insecticide resistance., (© 2022. The Author(s).)

Background: Triatoma infestans is the main vector of Chagas disease in the Southern Cone. The resistance to pyrethroid insecticides developed by populations of this species impairs the effectiveness of vector control campaigns in wide regions of Argentina. The study of the global transcriptomic response to pyrethroid insecticides is important to deepen the knowledge about detoxification in triatomines., Methodology and Findings: We used RNA-Seq to explore the early transcriptomic response after intoxication with deltamethrin in a population of T. infestans which presents low resistance to pyrethroids. We were able to assemble a complete transcriptome of this vector and found evidence of differentially expressed genes belonging to diverse families such as chemosensory and odorant-binding proteins, ABC transporters and heat-shock proteins. Moreover, genes related to transcription and translation, energetic metabolism and cuticle rearrangements were also modulated. Finally, we characterized the repertoire of previously uncharacterized detoxification-related gene families in T. infestans and Rhodnius prolixus., Conclusions and Significance: Our work contributes to the understanding of the detoxification response in vectors of Chagas disease. Given the absence of an annotated genome from T. infestans, the analysis presented here constitutes a resource for molecular and physiological studies in this species. The results increase the knowledge on detoxification processes in vectors of Chagas disease, and provide relevant information to explore undescribed potential insecticide resistance mechanisms in populations of these insects., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: J.M.L.E, G.F, P.L, G.M.C and S.O are investigators from Consejo Nacional de Ciencia y Tecnologıa (CONICET; https://www.conicet.gov.ar/). L.T. is recipient of a research fellowship from CONICET.

The Impulsivity/Reflexivity issue in inhibitory control ability has seldom been investigated in terms of individual differences in typically developing populations. Although there is evidence of changes in executive functioning (EF), including inhibition, in adolescence, very little is known about the role of individual differences. Using the data from 240 14-to-19-year-old high school students who completed a battery of EF tasks (Flanker, Go No-Go, Antisaccade, and Stop signal task), measures of emotion regulation strategies and behavioral difficulties, we performed a latent profile analysis to identify qualitatively distinct score profiles. The results showed the existence in adolescence of two inhibition profiles, Impulsive vs Reflexive, differing in performances at the inhibition tasks. The two profiles were not associated with socio-demographic characteristics, or to psychological variables, such as behavioral characteristics and emotional regulation strategies., (© 2021. The Author(s).)

Uniparental genetic systems are unique sex indicators and complement the study of autosomal diversity by providing landmarks of human migrations that repeatedly shaped the structure of extant populations. Our knowledge of the variation of the male-specific region of the Y chromosome in Native Americans is still rather scarce and scattered, but by merging sequence information from modern and ancient individuals, we here provide a comprehensive and updated phylogeny of the distinctive Native American branches of haplogroups C and Q. Our analyses confirm C-MPB373, C-P39, Q-Z780, Q-M848, and Q-Y4276 as the main founding haplogroups and identify traces of unsuccessful (pre-Q-F1096) or extinct (C-L1373*, Q-YP4010*) Y-chromosome lineages, indicating that haplogroup diversity of the founder populations that first entered the Americas was greater than that observed in the Indigenous component of modern populations. In addition, through a diachronic and phylogeographic dissection of newly identified Q-M848 branches, we provide the first Y-chromosome insights into the early peopling of the South American hinterland (Q-BY104773 and Q-BY15730) and on overlying inland migrations (Q-BY139813).

This study aims at investigating the relationship between working memory updating and working memory capacity in preschool children. A sample of 176 preschoolers (36-74 months) was administered a working memory updating task (Magic House) along with three working memory capacity tests that specifically measure their core attentional component (M capacity, as defined in the theory of constructive operators): Backward Word Span, Mr. Cucumber, and Direction Following Task. Correlational analyses and cross-classification prediction analyses were performed. Updating and capacity were significantly correlated, although the correlations were not high when age was partialled out. Capacity increased with age, and mediated the relation between age and updating. More importantly, cross-classification prediction analysis revealed that high updating scores with low M capacity, and low updating scores with relatively high M capacity, are possible events; the only combination ruled out was a low updating score with precocious development of M capacity. These facts demonstrate that updating skills in preschoolers depends on M capacity but does not coincide with it. Therefore, in cognitive developmental theories, the constructs of working memory updating and capacity should be distinguished, and on practical grounds, different tests should be used to measure them.

Background: Aedes aegypti (L.) is an urban mosquito, vector of several arboviruses that cause severe diseases in hundreds of million people each year. The resistance to synthetic insecticides developed by Ae. aegypti populations worldwide has contributed to failures in vector control campaigns, increasing the impact of arbovirus diseases. In this context, plant-derived essential oils with larvicidal activity could be an attractive alternative for vector control. However, the mode of action and the detoxificant response of mosquitoes to plant derived compounds have not been established, impairing the optimization of their use., Methods and Findings: Here we compare gene expression in Ae. aegypti larvae after 14 hrs of exposure to Eucalyptus camaldulensis essential oil with a control group exposed to vehicle (acetone) for the same lapse, by using RNA-Seq. We found differentially expressed genes encoding for cuticle proteins, fatty-acid synthesis, membrane transporters and detoxificant related gene families (i.e. heat shock proteins, cytochromes P450, glutathione transferases, UDP-glycosyltransferases and ABC transporters). Finally, our RNA-Seq and molecular docking results provide evidence pointing to a central involvement of chemosensory proteins in the detoxificant response in mosquitoes., Conclusions and Significance: Our work contributes to the understanding of the physiological response of Ae. aegypti larvae to an intoxication with a natural toxic distilled from Eucalyptus leafs. The results suggest an involvement of most of the gene families associated to detoxification of xenobiotics in insects. Noteworthy, this work provides important information regarding the implication of chemosensory proteins in the detoxification of a natural larvicide. Understanding the mode of detoxification of Eucalyptus distilled compounds could contribute to their implementation as a tool in mosquito control., Competing Interests: The authors have declared that no competing interests exist.

The southern green stink bug, Nezara viridula is one of the primary soybean pests and causes significant economic losses around the world. In spite of the high proteases inhibitor (PI) levels, N. viridula can feed on developing seeds of field-grown soybean and reduce crop yields. Although the PI-induced responses have been extensively investigated in many pest insects, there is lack of knowledge about the mechanisms that stink bugs employ to withstand cysteine PIs of soybean seeds. This study demonstrated that feeding on developing seeds of field-grown soybean inhibited total proteases activity of N. viridula, as result of inhibition of cathepsin B-like activity in the gut. In addition, from the 30 digestive cathepsins recognized in this study, 6 were identified as cathepsin B-like. Stink bugs that fed on growing seeds of field-grown soybean had similar gut pH to those reared in the laboratory, and both cathepsin B- and L-like had an optima pH of 6.5. Therefore, using specific proteases inhibitors we found that the main proteolytic activity in the gut is from cysteine proteases when N. viridula feeds on soybean crops. Since cathepsin L-like activity was not inhibited by soybean PIs, our results suggested that N. viridula relays on cathepsin L-like to feed on soybean. To our knowledge no study before has shown the impact of seed PIs of field-grown soybean on digestive proteases (cathepsin B- and L-like) of N. viridula. This study suggests that the activity of PI-insensitive cathepsins L-like in the gut would be part of an adaptive strategy to feed on developing soybean seeds. In agreement, the expansions of cathepsin L-like complement observed in pentatomids could confer to the insects a higher versatility to counteract the effects of different PIs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The purpose of this study was to analyze the contribution of specific executive function (EF) components to different number knowledge skills. A sample of 143 children attending the last year of preschool educational services (M age  = 65.01 months, SD = 3.57) were tested on five number knowledge tasks from the Numerical Intelligence Battery and four EF tasks assessing working memory (WM) and inhibition. First, we examined the interrelationship between different number skills; the results suggested that the relationship between basic informal skills (set comparison and number sequence) and formal skills (seriation of Arabic numerals and number comparison) was mediated by the ability to link sets to numerals. Next, we explored the contribution of WM and inhibition to different number knowledge skills. The structural equation model showed that WM and inhibition were differentially related to specific number knowledge skills. Specifically, WM predicted most components of number knowledge, including the two basic informal skills and the number comparison, whereas inhibition contributed to the seriation of Arabic numerals. The ability to link sets to numerals was predicted only by number sequence, not by EF components., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Radiation greatly exceeding blackbody between two objects separated by microscale distances has attracted great interest. However, challenges in reaching such a small separation between two plates have so far prevented studies below a separation distance of about 25 nm. Here, we report a study of radiation enhancement in the near-field regime of less than 10 nm between two parallel plates. We make use of bulk, rigid plates to approach small separation distances without the adverse snap-in effect, develop embedded temperature sensors to allow near-zero separation, and employ advanced sensing method to level the plates and approach and maintain small separations. Our findings agree with theoretical predictions between parallel surfaces with separations down to 7 nm where an 18000 times enhancement in radiation between two quartz plates is observed. Our method can also be used to explore heat transfer between other materials and can possibly be extended to smaller separation gaps.

The Indian meal moth Plodia interpunctella is a pest of stored products worldwide. Plant-derived essential oils with insecticidal activity could be safe products to control this species. The scarce information about the mode of action of most plant-derived products limits their use for the control of insect pests. Here, we demonstrate that an essential oil distilled from Lippia turbinata ("poleo") has insecticidal activity on P. interpunctella larvae. Furthermore, we performed a comprehensive characterization of P. interpunctella neuroendocrine system, in comparison with other lepidopteran species., (© 2020 Wiley Periodicals, Inc.)

In this study we examine the effectiveness and far transfer effects of a training that was found to be effective in promoting Executive Function (EF) in a sample of 5-year-old children (Traverso et al., 2015). By contrast with Traverso et al. (2015), the intervention was administered by regular teachers to verify its ecological validity. Far transfer was assessed by evaluating the training effects on pre-academic skills. 126 children attending the last year of Italian preschool educational services took part in the study (mainly 5-year-old children). Pre- and post-test assessments were conducted using a large EF and pre-academic skill task battery. The results indicate that the experimental group outperformed the control group in an interference suppression composite score. Moreover, significant far transfer effects to pre-academic skills in literacy domain were found. In addition, we found that the improvement in the pre academic skills (in both literacy and math domains) was mediated by the improvement in the interference suppression score. The results suggest the possibility that this intervention, which may be easily implemented in the context of educational services, can promote EF during the preschool period before entry to primary school.

Background: The Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building upon recent sequencing of hemipteran pests such as phloem-feeding aphids and blood-feeding bed bugs, we present the genome sequence and comparative analyses centered on the milkweed bug Oncopeltus fasciatus, a seed feeder of the family Lygaeidae., Results: The 926-Mb Oncopeltus genome is well represented by the current assembly and official gene set. We use our genomic and RNA-seq data not only to characterize the protein-coding gene repertoire and perform isoform-specific RNAi, but also to elucidate patterns of molecular evolution and physiology. We find ongoing, lineage-specific expansion and diversification of repressive C2H2 zinc finger proteins. The discovery of intron gain and turnover specific to the Hemiptera also prompted the evaluation of lineage and genome size as predictors of gene structure evolution. Furthermore, we identify enzymatic gains and losses that correlate with feeding biology, particularly for reductions associated with derived, fluid nutrition feeding., Conclusions: With the milkweed bug, we now have a critical mass of sequenced species for a hemimetabolous insect order and close outgroup to the Holometabola, substantially improving the diversity of insect genomics. We thereby define commonalities among the Hemiptera and delve into how hemipteran genomes reflect distinct feeding ecologies. Given Oncopeltus's strength as an experimental model, these new sequence resources bolster the foundation for molecular research and highlight technical considerations for the analysis of medium-sized invertebrate genomes.

Objectives: Pancreatic duct disruption (PDD) after acute pancreatitis can cause pancreatic collections in the early phase and biliary stenosis (BS) or gastric outlet obstruction (GOO) in the late phase. We aimed to document those late complications after moderate or severe acute pancreatitis., Methods: Between September 2010 and August 2014, 141 patients showed pancreatic collections on computed tomography. Percutaneous drainage was primarily performed for patients with signs or symptoms of uncontrolled pancreatic juice leakage. Pancreatic duct disruption was defined as persistent amylase-rich drain fluid or a pancreatic duct cut-off on imaging. Clinical course of the patients who developed BS or GOO was investigated., Results: Among the 141 patients with collections, 33 patients showed PDD in the pancreatic head/neck area. Among them, 9 patients (27%) developed BS 65 days after onset and required stenting for 150 days, and 5 patients (15%) developed GOO 92 days after onset and required gastric decompression and jejunal tube feeding for 147 days (days shown in median). All 33 patients recovered successfully without requiring surgical intervention., Conclusions: Anatomic proximity of the bile duct or duodenum to the site of PDD and severe inflammation seemed to contribute to the late onset of BS or GOO. Conservative management successfully reversed these complications.

The present study aims to investigate inhibition in individuals with Down Syndrome compared to typically developing children with different inhibitory tasks tapping response inhibition and interference suppression. Previous studies that aimed to investigate inhibition in individuals with Down Syndrome reported contradictory results that are difficult to compare given the different types of inhibitory tasks used and the lack of reference to a theoretical model of inhibition that was tested in children (see Bunge et al., 2002; Gandolfi et al., 2014). Three groups took part in the study: 32 individuals with Down Syndrome (DS) with a mean age of 14 years and 4 months, 35 typically developing children 5 years of age (5TD), and 30 typically developing children 6 years of age (6TD). No difference emerged among the groups in fluid intelligence. Based on a confirmatory factor analysis, two different inhibition factors were identified (response inhibition and interference suppression), and two composite scores were calculated. An ANOVA was then executed with the composite inhibitory scores as dependent variables and group membership as the between-subject variable to explore the group differences in inhibition components. The 6TD group outperformed the 5TD group in both response inhibition and interference suppression component scores. No differences were found in both inhibition components between the DS group and 5TD. In contrast, the 6TD group outperformed the DS group in both response inhibition and in the interference suppression component's scores. Summarizing, our findings show that both response inhibition and interference suppression significantly increased during school transition and that individuals with DS showed a delay in both response inhibition and interference suppression components compared to typically developing 6-year-olds, but their performance was similar to typically developing 5-year-olds.

This article provides a selective review of the literature on executive function development and related topics, focusing on the conceptual and terminological confusions that might hinder communication among researchers in the field. The distinctions between working memory and updating, and between shifting and flexibility, are discussed. Methodological problems, which have implications regarding whether a certain task can be considered a measure of a psychological construct, are also discussed. Research on preschoolers is examined with particular attention because it is a rapidly growing but controversial field that seems in particular need of greater conceptual clarity. As a specific touchstone case, we discuss whether the Multidimensional Card Selection Task (MCST) created by Podjarny, Kamawar, and Andrews (2017) should better be considered a measure of concurrent cognitive flexibility or working memory capacity. It is argued that connecting tasks to theoretical constructs is not warranted unless based on rigorous empirical testing of well-formulated models., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Successful surgical resection combined with effective perioperative therapy is essential for maximizing long-term survival for pancreatic adenocarcinoma., Patients and Methods: All patients with pancreatic adenocarcinoma who underwent curative resection at our institution from January 2003 to May 2010 were reviewed. Demographic and clinical details were retrospectively collected from medical records and cancer registry data., Results: Overall, 176 patients were included in the analysis (148 with de novo resectable disease and 28 with borderline resectable disease at presentation). Among 106 patients who received all perioperative therapy at our institution, 94% received neoadjuvant and/or adjuvant treatment in addition to resection. Actual all-cause 5-year overall survival (OS) for all 176 patients was 30.7%, with a median OS of 33.9 months [95% confidence interval (CI) 28.1-39.6 months]. For patients who received all perioperative therapy at our institution, actual all-cause 5-year disease-free survival (DFS) was 32.1%, with a median DFS of 28.8 months (95% CI 20.1-43.6 months). Of these patients, 67/106 (63%) recurred: 8 (8%) locoregional only; 52 (49%) systemic only; and 7 (7%) combined recurrence. No difference in survival rates or recurrence patterns was seen between resectable and borderline resectable patients. In multivariate analysis, tumor differentiation (poor vs. non-poor) and lymph node ratio >20% produced a useful clinical model., Conclusion: The actual OS rates for resected pancreatic cancer shown in this study are reflective of those currently achievable at a tertiary medical center dedicated to this patient population. In considering these results, both frequency and type of adjuvant/neoadjuvant therapy administered in the context of the clinical experience/management techniques of providers administering these treatments will be discussed.

Background: Triatomine insects are vectors of Trypanosoma cruzi, a protozoan parasite that is the causative agent of Chagas' disease. This is a neglected disease affecting approximately 8 million people in Latin America. The existence of diverse pyrethroid resistant populations of at least two species demonstrates the potential of triatomines to develop high levels of insecticide resistance. Therefore, the incorporation of strategies for resistance management is a main concern for vector control programs. Three enzymatic superfamilies are thought to mediate xenobiotic detoxification and resistance: Glutathione Transferases (GSTs), Cytochromes P450 (CYPs) and Carboxyl/Cholinesterases (CCEs). Improving our knowledge of key triatomine detoxification enzymes will strengthen our understanding of insecticide resistance processes in vectors of Chagas' disease., Methods and Findings: The discovery and description of detoxification gene superfamilies in normalized transcriptomes of three triatomine species: Triatoma dimidiata, Triatoma infestans and Triatoma pallidipennis is presented. Furthermore, a comparative analysis of these superfamilies among the triatomine transcriptomes and the genome of Rhodnius prolixus, also a triatomine vector of Chagas' disease, and other well-studied insect genomes was performed. The expression pattern of detoxification genes in R. prolixus transcriptomes from key organs was analyzed. The comparisons reveal gene expansions in Sigma class GSTs, CYP3 in CYP superfamily and clade E in CCE superfamily. Moreover, several CYP families identified in these triatomines have not yet been described in other insects. Conversely, several groups of insecticide resistance related enzymes within each enzyme superfamily are reduced or lacking in triatomines. Furthermore, our qRT-PCR results showed an increase in the expression of a CYP4 gene in a T. infestans population resistant to pyrethroids. These results could point to an involvement of metabolic detoxification mechanisms on the high levels of pyrethroid resistance detected in triatomines from the Gran Chaco ecoregion., Conclusions and Significance: Our results help to elucidate the potential insecticide resistance mechanisms in vectors of Chagas' disease and provide new relevant information for this field. This study shows that metabolic resistance might be a contributing cause of the high pyrethroid resistance observed in wild T. infestans populations from the Gran Chaco ecoregion, area in which although subjected to intense pyrethroid treatments, vector control has failed. This study opens new avenues for further functional studies on triatomine detoxification mechanisms.

We report a new type of plasmonic nanoscale ridge aperture and its fabrication process which is based on layer-by-layer planar lithography. This new fabrication method allows us to create desired nanoscale features of a plasmonic ridge waveguide nanoscale aperture, which helps to confine a near-field spot to sub-wavelength dimensions. Numerical simulations using Finite Element Method (FEM) are performed to calculate the near-field distribution around the exit of the aperture. Measurements using scattering near-field scanning optical microscopy (s-NSOM) confirm the design and demonstrate that the aperture is capable of producing focused spots in the ridge gap at the exit of the aperture. The planar lithography process is a step toward mass production of such plasmonic structures for applications including heat-assisted magnetic recording (HAMR).

Chagas' disease, affecting up to 6-7 million people worldwide, is transmitted to humans through the feces of triatomine kissing bugs. From these, Rhodnius prolixus, Triatoma dimidiata, Triatoma infestans and Triatoma pallidipennis are important vectors distributed throughout the Latin American subcontinent. Resistance to pyrethroids has been developed by some triatomine populations, especially T. infestans, obstructing their control. Given their role in the regulation of physiological processes, neuroendocrine-derived factors have been proposed as a source of molecular targets for new-generation insecticides. However, the involvement of neuropeptides in insecticide metabolism and resistance in insects has been poorly studied. In the present work, the sequences of 20 neuropeptide precursor genes in T. infestans, 16 in T. dimidiata, and 13 in T. pallidipennis detected in transcriptomic databases are reported, and a comparative analysis in triatomines is presented. A total of 59 neuropeptides were validated by liquid chromatography-tandem mass spectrometry in brain and nervous ganglia from T. infestans, revealing the existence of differential post-translational modifications, extended and truncated forms. The results suggest a high sequence conservation in some neuropeptide systems in triatomines, whereas remarkable differences occur in several others within the core domains. Comparisons of the basal expression levels for several neuropeptide precursor genes between pyrethroid sensitive and resistant population of T. infestans are also presented here, in order to introduce a proof of concept to test the involvement of neuropeptides in insecticide resistance. From the precursors tested, NVP and ITG peptides are significantly higher expressed in the resistant population. To our knowledge, this is the first report to associate differential neuropeptide expression with insecticide resistance. The information provided here contributes to creating conditions to widely extend functional and genetic studies involving neuropeptides in triatomines., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To compare outcomes after percutaneous catheter drainage (PCD) for acute necrotizing pancreatitis versus those in a randomized controlled trial as a reference standard., Materials and Methods: Between September 2010 and August 2014, CT-guided PCD was the primary treatment for 39 consecutive patients with pancreatic necrosis. The indication for PCD was the clinical finding of uncontrolled pancreatic juice leakage rather than infected necrosis. Subsequent to PCD, the drains were proactively studied with fluoroscopic contrast medium every 3 days to ensure patency and position. Drains were ultimately maneuvered to the site of leakage. These 39 patients were compared with 43 patients from the Pancreatitis, Necrosectomy versus Step-up Approach (PANTER) trial., Results: The CT severity index was similar between studies (median of 8 in each). Time from onset of acute pancreatitis to PCD was shorter in the present series (median, 23 d vs 30 d). The total number of procedures (PCD and subsequent fluoroscopic drain studies) per patient was greater in the present series (mean, 14 vs 2). More patients in the PANTER trial had organ failure (62% vs 84%), required open or endoscopic necrosectomy (0% vs 60%), and experienced in-hospital mortality (0% vs 19%; P < .05 for all)., Conclusions: Even though patients in the present series had a similar CT severity index as those in the PANTER trial, the former group showed lower incidences of organ failure, need for necrosectomy, and in-hospital mortality. The use of a proactive PCD protocol early, before the development of severe sepsis, appeared to be effective., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Epidural anesthesia is an accepted measure of pain control after major abdominal surgery. However, if the epidural anesthesia is unsuccessful, a variety of adverse effects can occur - excessive stress response, poor patient mobilization, increased opioid use, and hypotension due to vasodilation. The aim of this study was to evaluate the influence of epidural dysfunction on outcomes after pan-createctomy., Methods: Between August 2010 and October 2014, 72 patients underwent open pancreatectomy with epidural anesthesia. Epidural dysfunction was defined as either hypo-function due to inadequate pain control (requirement of epidural replacement, conversion to intravenous continuous opioid infusion, or intravenous bolus opioid use) or hyper-function (hypotension or oliguria). We then analyzed for an association between epidural dysfunction and surgical outcomes., Results: Epidural dysfunction occurred in 49% after pancreatectomy - hypo-function in 35% and hyper-function in 14%. Epidural dysfunction was independently associated with the development of overall (P < 0.001), pancreas-related (P = 0.041), and non-pancreas-related complications (P = 0.001). Hypo-function alone was independently associated with both pancreas-related (P = 0.015) and non-pancreas-related complications (P = 0.004). Hyper-function was independently associated with non-pancreas-related complications (P = 0.002)., Conclusions: Outcomes after pancreatic resection can be improved by increasing the success rate of epidural anesthesia., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objective: To report the long-term impact of adjuvant interferon-based chemoradiation therapy (IFN-CRT) after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC)., Background: In 2003, we reported an actuarial 5-year overall survival (OS) of 55% (22 months median follow-up) using adjuvant IFN-CRT after PD. As the original cohort is now 10 years distant from PD, we sought to examine their actual survival, describe patterns of recurrence, and determine prognostic factors., Methods: From 1995 to 2002, 43 patients underwent PD for PDAC and received adjuvant IFN-CRT consisting of external-beam irradiation, continuous 5-fluorouracil infusion, weekly intravenous bolus cisplatin, and subcutaneous interferon-α. Survival was calculated by the method of Kaplan and Meier, and prognostic factors were compared using a log-rank test and a Cox proportional hazards model., Results: With all patients at least 10 years from PD, the 5-year actual survival was 42% and 10-year actual survival was 28% with median OS of 42 months (95% confidence interval: 22-110 months). Nine patients survived beyond 10 years with 7 currently alive without evidence of disease. Initial recurrence included 4 local, 17 distant, and 4 combined sites at a median of 25 months. IFN-CRT was interrupted in 70% of patients because of grade 3 or 4 toxicity, whereas 42% of patients required hospitalization. Adverse prognostic factors included lymph node ratio of 50% or more, Eastern Cooperative Oncology Group performance status of 1 or higher, and IFN-CRT treatment interruption., Conclusions: Adjuvant IFN-CRT after PD can provide long-term survival in resected PDAC. Further studies should focus on patient and tumor factors to maximize benefit and minimize toxicity.

This longitudinal study analyzes whether selected components of executive function (EF) measured during the preschool period predict several indices of math achievement in primary school. Six EF measures were assessed in a sample of 5-year-old children (N = 175). The math achievement of the same children was then tested in Grades 1 and 3 using both a composite math score and three single indices of written calculation, arithmetical facts, and problem solving. Using previous results obtained from the same sample of children, a confirmatory factor analysis examining the latent EF structure in kindergarten indicated that a two-factor model provided the best fit for the data. In this model, inhibition and working memory (WM)-flexibility were separate dimensions. A full structural equation model was then used to test the hypothesis that math achievement (the composite math score and single math scores) in Grades 1 and 3 could be explained by the two EF components comprising the kindergarten model. The results indicate that the WM-flexibility component measured during the preschool period substantially predicts mathematical achievement, especially in Grade 3. The math composite scores were predicted by the WM-flexibility factor at both grade levels. In Grade 3, both problem solving and arithmetical facts were predicted by the WM-flexibility component. The results empirically support interventions that target EF as an important component of early childhood mathematics education., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Optical lithography, the enabling process for defining features, has been widely used in semiconductor industry and many other nanotechnology applications. Advances of nanotechnology require developments of high-throughput optical lithography capabilities to overcome the optical diffraction limit and meet the ever-decreasing device dimensions. We report our recent experimental advancements to scale up diffraction unlimited optical lithography in a massive scale using the near field nanolithography capabilities of bowtie apertures. A record number of near-field optical elements, an array of 1,024 bowtie antenna apertures, are simultaneously employed to generate a large number of patterns by carefully controlling their working distances over the entire array using an optical gap metrology system. Our experimental results reiterated the ability of using massively-parallel near-field devices to achieve high-throughput optical nanolithography, which can be promising for many important nanotechnology applications such as computation, data storage, communication, and energy.

Background: According to the revised Atlanta classification, severe and moderately severe acute pancreatitis (AP) includes patients with pancreatic and peripancreatic collections with or without organ failure. These collections suggest the presence of pancreatic juice leakage. The aim of this study was to evaluate the efficacy of a percutaneous catheter drainage (PCD) protocol designed to control leakage and decrease disease severity., Methods: Among 663 patients with clinical AP, 122 were classified as moderately severe or severe AP (all had collections). The computed tomography severity index (CTSI) score was calculated. The indication for PCD was based on progressive clinical signs and symptoms. Drain patency, position, and need for additional drainage sites were assessed using CT scans and drain studies initially every 3 days using a proactive protocol. Drain fluid was examined for amylase concentration and microbiological culture. Clinicopathological variables for patients with and without PCD were compared. Since there was no mortality, we used prolonged drainage time to measure the success of PCD. Within the group treated with PCD, variables that resulted in prolonged drainage time were analyzed., Results: PCD was used in 47/122 (39 %) patients of which 33/47 (70 %) had necrosis. PCD cases had a median CTSI of 8 and were classified as moderately severe AP (57 %) and severe AP (43 %). Inhospital mortality was zero. Surgical necrosectomy was not required for patients with necrosis. Independent risk factors for prolonged drainage time were persistent organ failure >48 h (P = 0.001), CTSI 8-10 (P = 0.038), prolonged duration of amylase-rich fluid in drains (P < 0.001), and polymicrobial culture fluid in drains (P = 0.015)., Conclusions: A proactive PCD protocol persistently maintaining drain patency advanced to the site of leak controlled the prolonged amylase in drainage fluid resulting in a mortality rate of zero.

Neither extended surgery nor extended indication for surgery has improved survival in patients with pancreatic cancer. According to autopsy studies, presumably 90% are metastatic. The only cure is complete removal of the tumor at an early stage before it becomes a systemic disease or becomes invasive. Early detection and screening of individuals at risk is currently under way. This article reviews the evidence and methods for screening, either familial or sporadic. Indication for early-stage surgery and precursors are discussed. Surgeons should be familiar with screening because it may provide patients with a chance for cure by surgical resection., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Executive function (EF) refers to a set of higher order cognitive processes that control and modulate cognition under continuously changing and multiple task demands. EF plays a central role in early childhood, is associated and predictive of important cognitive achievements and has been recognized as a significant aspect of school readiness. This study examines the efficacy of a group based intervention for 5-year-old children that focuses on basic components of EF (working memory, inhibitory control, cognitive flexibility). The intervention included 12 sessions, lasted 1 month and used low-cost materials. Seventy-five children took part in the study. The results indicate that the children who attended the intervention outperformed controls in simple and more complex EF tasks. Specifically, these children exhibited increased abilities to delay gratification, to control on-going responses, to process and update information, and to manage high cognitive conflict. These results suggest the possibility that this intervention, which may be easily implemented in educational services, can promote EF during preschool period before the entrance in primary school.

Background: Pancreatoduodenectomy (PD) provides the best chance for cure in the treatment of patients with localized pancreatic head cancer. In patients with a suspected, clinically resectable pancreatic head malignancy, the need for histologic confirmation before proceeding with PD has not historically been required, but remains controversial., Methods: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature and worked together to establish a consensus on when to perform a PD in the absence of positive histology., Results: The incidence of benign disease after PD for a presumed malignancy is 5-13%. Diagnosis by endoscopic cholangiopancreatography brushings and percutaneous fine-needle aspiration are highly specific, but poorly sensitive. Aspiration biopsy guided by endoscopic ultrasonography (EUS) has greater sensitivity, but it is highly operator dependent and increases expense. The incidence of autoimmune pancreatitis (AIP) in the benign resected specimens is 30-43%. EUS-guided Trucut biopsy, serum levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to therapy) are used for diagnosis. If AIP is suspected but not confirmed, the response to a short course of steroids is helpful for diagnosis., Conclusion: In the presence of a solid mass suspicious for malignancy, consensus was reached that biopsy proof is not required before proceeding with resection. Confirmation of malignancy, however, is mandatory for patients with borderline resectable disease to be treated with neoadjuvant therapy before exploration for resection. When a diagnosis of AIP is highly suspected, a biopsy is recommended, and a short course of steroid treatment should be considered if the biopsy does not reveal features suspicious for malignancy., (Copyright © 2014 Mosby, Inc. All rights reserved.)

The aim of this study was to investigate the nature of inhibitory processes in early childhood. A confirmatory factor analysis was used to examine the latent structure of inhibitory processes in day-care center children aged 24-32 months and in preschool children aged 36-48 months. The best fit to the data for the younger sample was a single undifferentiated inhibition factor model; in older children, a two-factor model was differently identified in which response inhibition and interference suppression were distinguished.

Pancreatic cancer is still a highly lethal disease with a 5-year survival rate of approximately 5 %. Early detection offers one of the best hopes for improving survival. Previous cohort studies and case-control studies showed that 4-10 % of pancreatic cancers have a hereditary basis, and individuals with a family history have an increased risk of developing pancreatic and extra-pancreatic malignancies. Since individuals with a family history of pancreatic cancer and those with a known genetic syndrome that predisposes to pancreatic cancer will be the first to benefit from early detection tests as they become available, familial pancreatic cancer (FPC) registries have been established in the US and Europe, but not yet in Japan. Such registries form the basis for epidemiological studies, clinical trials, and basic research on familial pancreatic cancer. There is a need for FPC registries in Japan as cancer risk varies among different populations and discoveries made in Western populations may not translate to the Japanese population. These registries in Japan will align with ongoing international efforts and add to a better understanding of the natural history, risk factors, screening strategies, and responsible genes, for improving survival of this dismal disease., (© 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The ability to assess and compare the impact of postoperative complications in major cancer surgery is currently limited. The Accordion Severity Grading System provides the opportunity to categorize complications according to treatment responses and resource use., Study Design: A retrospective review of patient demographics, perioperative outcomes, and costs was performed using a prospective IRB-approved database of patients undergoing esophagectomy from 2000 to 2008., Results: This study included 285 consecutive patients, 83% were male, and mean age was 63.7 years. Histology was predominantly adenocarcinoma (80%). For patients with invasive cancer, overall survival at 5 years was 50%. Mean overall cost and length of stay were $23,419 and 10.4 days, respectively. Neoadjuvant therapy was used in 156 patients (54.7%) and operative mortality rate was 0.7%. Complications were documented in 144 patients (50.5%), with Accordion grades assigned as 1 (29%), 2 (59%), 3 (3%), 4 (6%), 5 (2%), and 6 (0.7%). Accordion grade was significantly related to costs and length of stay in univariate (p < 0.005) and multivariate analyses (p < 0.005). There was a statistically significant difference in survival between those patients who did and did not experience complications; however, no significant differences were noted among individual Accordion grades. Cox regression multivariate analysis demonstrated a significant relationship between overall survival and occurrence of postoperative complications., Conclusions: The Accordion Severity Grading System provides a meaningful approach to classifying complications according to resource use, which also directly correlates with treatment costs and length of stay. Survival is affected by overall occurrence of complications, but was not related to individual Accordion grades in this study. The Accordion Severity Grading System should be a component of prospective data collections and can be used in major cancer surgery to study areas appropriate for quality improvement and cost containment., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Hypothesis: The method to lower postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) involves controlling risk factors for leakage from the pancreatic stump., Goal: The aim of this study was to identify controllable risk factors for POPF., Methods: In order to promote homogeneity, we used a single surgeon case series and then calculated POPF with a public web-based tool based on the severity classification system of the International Study Group of Pancreatic Surgery (ISGPS). A total of 223 consecutive cases of DPs were reviewed. DP involved the same hand-sewn fish-mouth closure of the pancreatic stump. All received postoperative epidural anesthesia. Logistic regression analysis identified risk factors for clinically relevant POPF (grade B/C)., Results: Mortality was zero. ISGPS gradings were: no POPF 53%, grade A = 32%, B = 13.9%, and C = 0.9%. The clinical-relevant POPF (B/C) rate was 14.8% of which 24% represented surgical drain failure due to lack of patency and/or misplaced from their original location. Preoperative endoscopic ablation and/or stenting of Wirsung's duct was a significant risk factor to lower grade B/C leak (3%). Multivariate analysis identified two controllable risk factors-intraoperative blood loss >1,000 ml and those who did not undergo preoperative endoscopic interventions of Wirsung's duct. In the group with presumed intact pancreatic sphincters (no endoscopic intervention, n = 177), the use of postoperative intravenous opioids (with epidural failure) was a risk factor for B/C leak (34%). These findings suggest that increased back pressure in the pancreatic duct has a role in promoting pancreatic stump leakage., Conclusions: Using the ISGPS definition and its web-based tool, the incidence of clinically relevant leakage was 14.8% in 223 cases of DP. Opportunities to lower this rate are improving our surgical drain technology, limiting intraoperative blood loss, and avoiding postoperative intravenous narcotics with epidural analgesia.

The process of Intraductal papillary mucinous neoplasms (IPMN) follows the adenoma-to-carcinoma sequence. If it progresses to malignancy about 5 years is required. Even though the process is slow IPMN provides the clinician with the opportunity to avoid malignancy if the patient is at risk. The natural history as observed through Kaplan Meier event curves for occurrence of malignancy show the process to malignancy is much faster (50% within 2 years) if pancreatitis-like symptoms are present or if the main pancreatic duct (MPD) is involved. Almost all decisions to resect (95% in our experience) are based on the presence of symptoms or the MPD location. Cyst size is used infrequently. Every patient with an IPMN should always have a planned follow-up and the frequency depends on the perceived risk of malignancy-immediate imaging if becomes symptomatic to every 2 to 3 years if asymptomatic side branch lesions. The natural history provides modern guidelines for making decisions in patients with a newly discovered IPMN.

Background: Symptomatic walled-off pancreatic necrosis (WOPN) treated with dual modality endoscopic and percutaneous drainage (DMD) has been shown to decrease length of hospitalization (LOH) and use of radiological resources in comparison to standard percutaneous drainage (SPD)., Aim: The aim of this study is to demonstrate that as the cohort of DMD and SPD patients expand, the original conclusions are durable., Methods: The database of patients receiving treatment for WOPN between January 2006 and April 2011 was analyzed retrospectively., Patients: One hundred two patients with symptomatic WOPN who had no previous drainage procedures were evaluated: 49 with DMD and 46 with SPD; 7 were excluded due to a salvage procedure., Results: Patient characteristics including age, sex, etiology of pancreatitis, and severity of disease based on computed tomographic severity index were indistinguishable between the two cohorts. The DMD cohort had shorter LOH, time until removal of percutaneous drains, fewer CT scans, drain studies, and endoscopic retrograde cholangiopancreatography (ERCPs; p < 0.05 for all). There were 12 identifiable complications during DMD, which were successfully treated without the need for surgery. The 30-day mortality in DMD was 4% (one multi-system organ failure and one out of the hospital with congestive heart failure). Three patients receiving SPD had surgery, and three (7%) died in the hospital., Conclusion: DMD for symptomatic WOPN reduces LOH, radiological procedures, and number of ERCPs compared to SPD.

Background: There are limited data on the incidence of afferent limb syndrome and other delayed GI problems in pancreatic cancer (PaC) patients, especially among long-term survivors (>2 years)., Objective: To evaluate the incidence of afferent limb syndrome (chronic afferent limb obstruction resulting in pancreatobiliary obstruction) and delayed GI problems in PaC patients after pancreaticoduodenectomy (PD)., Design: Retrospective case series., Setting: Tertiary referral center., Patients: PaC patients treated with PD (N = 186) over a 14-year period (January 1995-October 2009)., Interventions: Endoscopic balloon dilation and stent placement, percutaneous biliary drainage., Main Outcome Measurements: Incidence of afferent limb syndrome and delayed GI complications (marginal ulcers, radiation enteropathy, anastomotic strictures)., Results: Mean age was 63 ± 10 years; 55% of patients were male. Afferent limb syndrome was noted in 24 patients (13%). Median time to diagnosis was 1.2 years (range 0.03-12.3 years); obstruction was primarily caused by recurrent PaC (8 patients, 33%) and radiation enteropathy (9 patients, 38%). Afferent limb syndrome was more likely to develop in patients with 2 years or longer of follow-up (n = 71, [38%]) compared with patients with 2 years or less of follow-up, after controlling for age, sex, surgery type, and adjuvant treatment (adjusted odds ratio, 4.5; 95% CI, 1.8-11.7). Other delayed GI problems included radiation enteropathy (6%), marginal ulcers (5%), anastomotic strictures (4%), cholangitis/liver abscesses (5%), and GI bleeding (6%)., Limitations: Retrospective, single-center study., Conclusions: GI problems, including afferent limb syndrome, are relatively common in PaC patients after surgery and adjuvant therapy. Clinicians should recognize and effectively treat these delayed GI problems, especially in long-term survivors., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Introduction: Using Kaplan-Meier curves, a 2006 study illustrated a shorter time interval between development of symptoms and detection of malignant IPMN in the main pancreatic duct versus a side-branch duct location. Of 93 cases, only 62 were confirmed histologically. To support these interesting findings, we examined a larger cohort of cases where the diagnosis was confirmed histologically and asked if symptoms by themselves, as well as main duct location, were associated with malignant detection., Methods: Between 1989 and 2009, 210 IPMN cases meeting international criteria were resected and histologically examined. Actuarial rates of malignant detection over time were calculated from the first clinical symptom to malignant detection (resection). These rates of malignant detection over time were compared for main vs. side-branch duct location and symptomatic vs. asymptomatic cases., Results: The most common indications for resection were symptoms (88%) and main pancreatic duct location (65%). The actuarial malignant detection rates were significantly shorter for main duct location and also for symptomatic cases, regardless of duct location., Conclusions: Presence of symptoms followed by main pancreatic duct location had a significantly shorter elapsed time to malignant detection. The visual depiction of these actuarial rates highlights the importance of the clinical history. To determine malignant risk, the primary determinants for resection were either symptoms or main duct location (but not cyst size), confirming the 2006 study with a larger cohort of histologically confirmed cases.

Background: Standardization of surgical and pathologic techniques is crucial to the interpretation of studies evaluating adjuvant therapies for pancreatic cancer (PC)., Methods: To assess the degree to which treatment administered prior to enrollment of patients in trials of adjuvant therapy is quality controlled, the operative and pathology reports of patients in American College of Surgeons Oncology Group (ACOSOG) Z5031-a national trial of chemoradiation following pancreaticoduodenectomy (PD)-were rigorously evaluated. We analyzed variables with the potential to influence staging or outcome., Results: 80 patients reported to have undergone R0 (75%) or R1 (25%) pylorus-preserving (38%) or standard (62%) PD were evaluated. A search for metastases was documented in 96% of cases. The proximity of the tumor to the superior mesenteric vein was reported in 69%; vein resection was required in 9% and lateral venorrhaphy in 14%. The method of dissection along the superior mesenteric artery (SMA) was described in 68%, being ultrasonic dissection (17%), stapler (24%), and clamp and cut (59%). SMA skeletonization was described in 25%, and absence of disease following resection was documented in 24%. The surgeon reported marking the critical SMA margin in 25%; inking was documented in 65% of cases and evaluation of the SMA margin was reported in 47%. A range of 1-49 lymph nodes was evaluated. Only 34% of pathology reports met College of American Pathologists criteria., Conclusions: Trials of adjuvant therapy following PD suffer from a lack of standardization and quality control prior to patient enrollment. These data suggest areas for improvement in the design of multidisciplinary treatment protocols.

Background: We have observed that leakage from pancreaticojejunostomy is reduced when a surgical microscope is used to construct the pancreaticojejunostomy during pancreaticoduodenectomy. To validate our hypothesis that better vision improves the technical performance of pancreaticojejunostomy, we limited inclusion criteria to those patients at high risk for leak, performed more cases, and used the grading system of the International Study Group of Pancreatic Surgery., Study Design: From 1988 through 2008, 507 consecutive pancreaticoduodenectomies were performed with pancreaticojejunostomy. A subset of 283 patients at risk for leak had a main pancreatic duct (MPD) ≤3 mm at the surgical margin. Pancreaticojejunostomy was completed with surgical loupes (n = 135) or surgical microscope (n = 148). Incidence of pancreaticojejunostomy leak and delayed gastric emptying was determined using a Web-based calculator for the severity grading scale of the International Study Group of Pancreatic Surgery., Results: Within the 507 pancreaticoduodenectomies, the clinically relevant pancreaticojejunostomy leak for those with an MPD >3 mm (n = 224) was 4%, and with an MPD ≤3 mm (n = 283) it was 16% (p < 0.0001). For these 283 high-risk patients, outcomes were worse in the loupes versus microscope group, ie, clinically relevant pancreaticojejunostomy leak (21% versus 11%; p = 0.021), pancreas-related complications (31% versus 19%; p = 0.018), clinically relevant delayed gastric emptying (19% versus 9%; p = 0.016), and hospital length of stay (12.9 versus 9.5 days; p < 0.0001)., Conclusions: In a subset of pancreaticoduodenectomy patients at high risk for pancreaticojejunostomy leak, the increased visual acuity of the surgical microscope reduced clinically relevant pancreatic anastomotic failure, delayed gastric emptying, and hospital length of stay., (Copyright © 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Our objective was to measure human stool elastase-1 to determine the effect of distal pancreatectomy on exocrine function., Methods: During a 72-month period, 115 patients underwent resection. Stool elastase values were measured preoperatively in 83 patients and repeated at 3, 12, and 24 months. The amount of pancreas resected was divided into two categories-limited to the left of the portal vein and those resections over or extended to the right of the vein., Results: Elastase values were normal in 84% (n = 70) of cases prior to resection (33% if chronic pancreatitis, 70% if pancreatic adenocarcinoma). In the 70 patients with normal preoperative values, exocrine function was maintained in those with resection that was limited to the left of the portal vein at 3, 12, and, 24 months. If the resection was over or extended to right of the portal vein, then 88% maintained normal exocrine function at 3 months, 92% at 12 months, and 100% were normal at 24 months., Conclusion: Of patients undergoing distal pancreatectomy, one sixth will have preoperative pancreatic insufficiency, most commonly those with pancreatic adenocarcinoma or chronic pancreatitis. Postoperative pancreatic insufficiency was seen transiently in those with resection that extended to the portal vein or beyond.

Background: Peritoneal lavage cytology in the staging of pancreatic cancer is not widely used given improvements in computed tomography (CT). The aim of this study was to determine the utility of peritoneal lavage cytology in predicting survival in locally advanced pancreatic cancer., Methods: Between 2000 and 2008, 202 patients with biopsy-proven pancreatic cancer who were determined by pancreas protocol CT to be locally advanced and not currently resectable underwent diagnostic laparoscopy and peritoneal lavage for cytology (DL-PLC)., Results: DL-PLC upstaged 58 of 202 patients (29%) to stage IV, who had a significantly worse median survival of 11 months versus 16 months (P = .03). Positive cytology was an independent predictor of worse survival (P = .02)., Discussion: Positive peritoneal cytology (stage IV disease) in locally advanced pancreatic cancer is common and predicts worse survival. This survival difference suggests that peritoneal cytology status might be useful in deciding treatment regimens in patients with locally advanced disease based on CT., (Copyright 2010. Published by Elsevier Inc.)

Background: Many definitions are used in the literature for pancreatic anastomotic failure (PAF) and delayed gastric emptying (DGE) after pancreatoduodenectomy (PD). To promote homogeneity, published reports after 2005 have used the International Study Group on Pancreatic Surgery (ISGPS) consensus definition for PAF and DGE; however, subsequent authors have had to interpret or modify the ISGPS classification to make it useable. The solution might be to create a web-based calculator, test it for ambiguity and reliability with a large number of cases, and then make it available to the public., Methods: Using 507 consecutive patients undergoing PD and 14 questions, we created a web-based calculator based on the ISPGS classification to assess the incidence and grade of clinical impact (none, moderate, or major deviation) for PAF and DGE. As the calculator's formulas were tested, ambiguous terms were identified and resolved., Results: The incidence for cases with clinical impact from PAF was 10% and from DGE it was 12%. Multivariate analysis identified 4 factors predictive for PAF: male sex, body mass index (BMI) >30 kg/m2, soft gland texture, and main pancreatic duct size < or =3 mm. Predictive factors for DGE included 2 factors: not using a surgical microscope, and simultaneous PAF., Conclusion: A web-based calculator was developed to promote homogeneity of method for grading of PAF and DGE after PD. Anyone with access to the web can now compare their results to the current study., (Copyright 2010. Published by Mosby, Inc.)