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Background: Hirschsprung’s disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. Aims: This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. Methods: Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. Results: Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. Conclusion: In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.

Background: The VATER/VACTERL association (VACTERL) is defined as the non-random occurrence of the following congenital anomalies: Vertebral, Anal, Cardiac, Tracheal-Esophageal, Renal, and Limb anomalies. As no unequivocal candidate gene has been identified yet, patients are diagnosed phenotypically. The aims of this study were to identify patients with monogenic disorders using a genetics-first approach, and to study whether variants in candidate genes are involved in the etiology of VACTERL or the individual features of VACTERL: Anorectal malformation (ARM) or esophageal atresia with or without trachea-esophageal fistula (EA/TEF). Methods: Using molecular inversion probes, a candidate gene panel of 56 genes was sequenced in three patient groups: VACTERL (n = 211), ARM (n = 204), and EA/TEF (n = 95). Loss-of-function (LoF) and additional likely pathogenic missense variants, were prioritized and validated using Sanger sequencing. Validated variants were tested for segregation and patients were clinically re-evaluated. Results: In 7 out of the 510 patients (1.4%), pathogenic or likely pathogenic variants were identified in SALL1, SALL4, and MID1, genes that are associated with Townes-Brocks, Duane-radial-ray, and Opitz-G/BBB syndrome. These syndromes always include ARM or EA/TEF, in combination with at least two other VACTERL features. We did not identify LoF variants in the remaining candidate genes. Conclusions: None of the other candidate genes were identified as novel unequivocal disease genes for VACTERL. However, a genetics-first approach allowed refinement of the clinical diagnosis in seven patients, in whom an alternative molecular-based diagnosis was found with important implications for the counseling of the families.

Objectives: Clinicians have increasingly adopted the widespread use of topical agents to manage chronic wound infections, despite limited data on their effectiveness in vivo. This study sought to evaluate the evidence for commonly employed topical agents used in wounds for the purpose of treating chronic infections caused by biofilm. Method: We included in vitro, animal and human in vivo studies where topical agents were tested for their efficacy against biofilms, for use in wound care. For human studies, we only included those which utilised appropriate identification techniques for visualising and confirming the presence of biofilms. Result: A total of 640 articles were identified, with 43 included after meeting eligibility. In vitro testing accounted for 90% (n = 39) of all included studies, five studies using animal models and three human in vivo studies. Sixteen different laboratory models were utilised, with the most frequent being the minimum biofilm eradication concentration (MBEC™) / well plate assay (38%, n = 15 of 39). A total of 44 commercially available topical agents were grouped into twelve categories with the most commonly tested agents being silver, iodine and polyhexamethylene biguanide (PHMB). In vitro results on efficacy demonstrated iodine as having the highest mean log10 reductions of all agents (4.81, ±3.14). Conclusion: There is large disparity in the translation of laboratory studies to researchers undertaking human trials relating to the effectiveness of commercially available topical agents. There is insufficient human in vivo evidence to definitively recommend any commercially available topical agent over another for the treatment of chronic wound biofilms. The heterogeneity identified between study designs (in vitro to in vivo) further limits the generalisability of results.

The ARM-Net (anorectal malformation network) consortium held a consensus meeting in which the classification of ARM and preoperative workup were evaluated with the aim of improving monitoring of treatment and outcome. The Krickenbeck classification of ARM and preoperative workup suggested by Levitt and Peña, used as a template, were discussed, and a collaborative consensus was achieved. The Krickenbeck classification is appropriate in describing ARM for clinical use. The preoperative workup was slightly modified. In males with a visible fistula, no cross-table lateral X-ray is needed and an anoplasty or (mini-) posterior sagittal anorectoplasty can directly be performed. In females with a small vestibular fistula (Hegar size <5 mm), a primary repair or colostomy is recommended; the repair may be delayed if the fistula admits a Hegar size >5 mm, and in the meantime, gentle painless dilatations can be performed. In both male and female perineal fistula and either a low birth weight (<2,000 g) or severe associated congenital anomalies, prolonged preoperative painless dilatations might be indicated to decrease perioperative morbidity caused by general anesthesia. The Krickenbeck classification is appropriate in describing ARM for clinical use. Some minor modifications to the preoperative workup by Levitt and Peña have been introduced in order to refine terminology and establish a comprehensive preoperative workup.

We review recent developments in the study of the multifractal properties of dynamical processes in disordered systems. In particular, we discuss the multifractality of the growth probabilities of DLA clusters and of the probability density for random walks on random fractals. The results for multifractality in DLA are based mainly on numerical studies, while the results for random walks on random fractals are based on analytical results. We find that although a phase transition in the multifractal spectrum occurs for d = 2 DLA, there seems to be no phase transition for d = 3 DLA. This might be explained by the topological differences between d = 2 and d = 3 DLA clusters. For the probability density of random walks on random fractals, it is found that multifractality occurs for a finite range of moments q, qmin < q < qmax. The approach can be applied to other dynamical processes, such as fractons or tracer concentration in stratified media. © 1993.

We calculate the minimum growth probability for diffusion-limited aggregation (DLA) as a function of the cluster mass M, and find a novel singularity of the form -lnpmin(M)(lnM)y with y2. We interpret this result in terms of a simple model for DLA structure, which is characterized by a hierarchy of self-similar voids separated by channels whose diameter increases slower than the cluster diameter. © 1990 The American Physical Society.

We briefly review some recent attempts to achieve some genuine understanding of diffusion-limited aggregation (DLA), the paradigm model for dynamical mechanisms of disorderly growth processes. We shall see that the seminal ideas of Professor Cyril Domb have influenced to a great degree many of the recent theoretical approaches. In particular, the Domb-Hunter constant-gap scaling hypothesis becomes replaced by a continuum of gap exponents. Moreover, while the growth probabilities for the tips of the DLA structure do scale in the conventional fashion, there is evidence that the growth probabilities of the fjords do not scale. Does this competition between one part of DLA that does scale, and another that does not, underlie many of the unusual properties of this model? © 1990.

RFID is used today in many fields of every day life like access control, anti-theft protection or logistics. Within this article a short overview of the basic RFID principles and the EPC protocol flow is given at first. Afterwards new design approaches for RFID systems within the scope of the research project RFID-S are presented.