Duhamel versus transanal endorectal pull through (TERPT) for the surgical treatment of Hirschsprung’s disease

For the surgical treatment of Hirschsprung’s disease, several surgical techniques are used to resect the distal aganglionic colon. Two frequently used techniques are the Duhamel procedure and the transanal endorectal pull-through procedure. During the ‘8th Pediatric Colorectal Course’ in Nijmegen, November 2015, a workshop was organized to share experiences of both techniques by several experts in the field and to discuss (long term) outcomes. Specifically, the objective of the meeting was to discuss the main controversies in relation to the technical execution of both procedures in order to make an initial assessment of the limitations of available evidence for clinical decision-making and to formulate a set of preliminary recommendations for current clinical care and future research

RDF Querying

Reactive Web systems, Web services, and Web-based publish/ subscribe systems communicate events as XML messages, and in many cases require composite event detection: it is not sufficient to react to single event messages, but events have to be considered in relation to other events that are received over time. Emphasizing language design and formal semantics, we describe the rule-based query language XChangeEQ for detecting composite events. XChangeEQ is designed to completely cover and integrate the four complementary querying dimensions: event data, event composition, temporal relationships, and event accumulation. Semantics are provided as model and fixpoint theories; while this is an established approach for rule languages, it has not been applied for event queries before

Surgical Management of Pediatric Inguinal Hernia: A Systematic Review and Guideline from the European Pediatric Surgeons' Association Evidence and Guideline Committee

Introduction: Inguinal hernia repair represents the most common operation in childhood; however, consensus about the optimal management is lacking. Hence, recommendations for clinical practice are needed. This study assesses the available evidence and compiles recommendations on pediatric inguinal hernia. / Materials and Methods: The European Pediatric Surgeons' Association Evidence and Guideline Committee addressed six questions on pediatric inguinal hernia repair with the following topics: (1) open versus laparoscopic repair, (2) extraperitoneal versus transperitoneal repair, (3) contralateral exploration, (4) surgical timing, (5) anesthesia technique in preterm infants, and (6) operation urgency in girls with irreducible ovarian hernia. Systematic literature searches were performed using PubMed, MEDLINE, Embase (Ovid), and The Cochrane Library. Reviews and meta-analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. / Results: Seventy-two out of 5,173 articles were included, 27 in the meta-analyses. Laparoscopic repair shortens bilateral operation time compared with open repair. In preterm infants, hernia repair after neonatal intensive care unit (NICU)/hospital discharge is associated with less respiratory difficulties and recurrences, regional anesthesia is associated with a decrease of postoperative apnea and pain. The review regarding operation urgency for irreducible ovarian hernia gained insufficient evidence of low quality. / Conclusion: Laparoscopic repair may be beneficial for children with bilateral hernia and preterm infants may benefit using regional anesthesia and postponing surgery. However, no definite superiority was found and available evidence was of moderate-to-low quality. Evidence for other topics was less conclusive. For the optimal management of inguinal hernia repair, a tailored approach is recommended taking into account the local facilities, resources, and expertise of the medical team involved

HeLa-cell adherence patterns and actin aggregation of enteropathogenic Escherichia coli (EPEC) and Shiga-toxin-producing E. coli (STEC) strains carrying different eae and tir alleles

A collection of 69 eae-positive strains expressing 29 different intimin types and eight tir alleles was characterized with respect to their adherence patterns to HeLa cells, ability to promote actin accumulation in vitro, the presence of bfpA alleles in positive strains, and bundle-forming pilus (BFP) expression. All of the nine typical enteropathogenic Escherichia coli (tEPEC) studied harbored the enteropathogenic E. coli adherence factor (EAF) plasmid, as shown by PCR and/or EAF probe results. In addition, they were positive for bfpA, as shown by PCR, and BFP expression, as confirmed by immunofluorescence (IFL) and/or immunoblotting (IBL) assays. Localized adherence (LA) was exclusively displayed by those nine tEPEC, while localized-adherence-like (LAL) was the most frequent pattern among atypical EPEC (aEPEC) and Shiga-toxinproducing E. coli (STEC). All LA and LAL strains were able to cause attaching and effacing (AE) lesions, as established by means of the FAS test. There was a significant association between the presence of tir allele α1 and bfpA-positive strains, and consequently, with the LA pattern. However, intimin type or bfpA was not associated with the adherence pattern displayed in HeLa cells. Among the eight bfpA alleles detected, a new type (β10; accession number FN391178) was identified in a strain of serotype O157:H45, and a truncated variant (β3.2-t; accession number FN 391181) in four strains belonging to different pathotypes. [Int Microbiol 2009; 12(4):243-251

Social democracy, embeddedness and decommodification: On the conceptual innovations and intellectual affiliations of Karl Polanyi

Of the several debates that revolve around the work of the economic historian and political economist Karl Polanyi, one that continues to exercise minds concerns his analysis of, and political attitudes toward, post-war capitalism and the welfare state. Simplified a little, it is a debate with two sides. To borrow Iván Szelényi's terms, one side constructs a ‘hard’ Karl Polanyi, the other a ‘soft’ one. The former advocated a socialist mixed economy dominated by redistributive mechanisms. He was a radical socialist for whom the market should never be the dominant mechanism of economic coordination. His ‘soft’ alter ego insisted that the market system remain essentially intact but be complemented by redistributive mechanisms. The ‘double movement’ – the central thesis of his ‘Great Transformation’ – acts, in this reading, as a self-correcting mechanism that moderates the excesses of market fundamentalism; its author was positioned within the social-democratic mainstream for which the only realistic desirable goal is a regulated form of capitalism. In terms of textual evidence there is much to be said for both interpretations. In this article I suggest a different approach, one that focuses upon the meaning of Polanyi's concepts in relation to their socio-political and intellectual environment

The hTERT Promoter Enhances the Antitumor Activity of an Oncolytic Adenovirus under a Hypoxic Microenvironment

Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5). In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen) or a hypoxic (1% oxygen) condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1α and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells

Analysis reveals potential rangeland impacts if Williamson Act eliminated

California budget cuts have resulted in dramatic reductions in state funding for the Williamson Act, a land protection program that reduces property taxes for the owners of 15 million acres of California farms and rangeland. With state reimbursements to counties eliminated, the decision to continue Williamson Act contracts lies with individual counties. We investigated the consequences of eliminating the Williamson Act, using a geospatial analysis and a mail questionnaire asking ranchers for plans under a hypothetical elimination scenario. The geospatial analysis revealed that 72% of rangeland parcels enrolled in Williamson Act contracts contained habitat important for statewide conservation goals. Presented with the elimination scenario, survey respondents reported an intention to sell 20% of their total 496,889 acres. The tendency of survey participants to respond that they would sell land was highest among full-time ranchers with low household incomes and without off-ranch employment. A majority (76%) of the ranchers who reported that they would sell land predicted that the buyers would develop it for nonagricultural uses, suggesting substantial changes to California's landscape in a future without the Williamson Act

A Dynamical Systems Model for Combinatorial Cancer Therapy Enhances Oncolytic Adenovirus Efficacy by MEK-Inhibition

Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced or metastatic cases where treatment options remain limited.National Institutes of Health (U.S.) (Grant R01 CA118545)National Institutes of Health (U.S.) (Grant R01 CA095701)National Institutes of Health (U.S.) (Grant U54 CA11297)National Institutes of Health (U.S.) (Grant U54-CA112967