A magnetic analog of the isotope effect in cuprates

We present extensive magnetic measurements of the (Ca_xLa_{1-x})(Ba_{1.75-x}La_{0.25+x})Cu_{3}O_{y} (CLBLCO) system with its four different families (x) having a Tc^max(x) variation of 28% and minimal structural changes. For each family we measured the Neel temperature, the anisotropies of the magnetic interactions, and the spin glass temperature. Our results exhibit a universal relation Tc=c*J*n_s for all families, where c~1, J is the in plane Heisenberg exchange, and n_s is the carrier density. This relates cuprate superconductivity to magnetism in the same sense that phonon mediated superconductivity is related to atomic mass.Comment: With an additional inset in Fig.

The two critical temperatures conundrum in La1.83_{1.83}Sr0.17_{0.17}CuO4_4

The in-plane and out-of-plane superconducting stiffness appear to vanish at different transition temperatures, which contradicts thermodynamical expectation. In addition, we observe a surprisingly strong dependence of the out-of-plane stiffness transition on sample width. With evidence from Monte Carlo simulations, this effect is explained by a crossover from three dimensions into quasi one dimensional behavior of the finite sample. Due to an essential singularity at the thermodynamic transition temperature $T_c$, the out-of-plane stiffness appears to vanish below $T_c$ by an amount which is proportional to the inverse width. A fit of our prediction to the data is used to determine the value of the anisotropy parameter. Analogy to studies of helium superfluids in nanopores is made

SPIKE – a database, visualization and analysis tool of cellular signaling pathways

<p>Abstract</p> <p>Background</p> <p>Biological signaling pathways that govern cellular physiology form an intricate web of tightly regulated interlocking processes. Data on these regulatory networks are accumulating at an unprecedented pace. The assimilation, visualization and interpretation of these data have become a major challenge in biological research, and once met, will greatly boost our ability to understand cell functioning on a systems level.</p> <p>Results</p> <p>To cope with this challenge, we are developing the SPIKE knowledge-base of signaling pathways. SPIKE contains three main software components: 1) A database (DB) of biological signaling pathways. Carefully curated information from the literature and data from large public sources constitute distinct tiers of the DB. 2) A visualization package that allows interactive graphic representations of regulatory interactions stored in the DB and superposition of functional genomic and proteomic data on the maps. 3) An algorithmic inference engine that analyzes the networks for novel functional interplays between network components.</p> <p>SPIKE is designed and implemented as a community tool and therefore provides a user-friendly interface that allows registered users to upload data to SPIKE DB. Our vision is that the DB will be populated by a distributed and highly collaborative effort undertaken by multiple groups in the research community, where each group contributes data in its field of expertise.</p> <p>Conclusion</p> <p>The integrated capabilities of SPIKE make it a powerful platform for the analysis of signaling networks and the integration of knowledge on such networks with <it>omics </it>data. </p

Perianal Pediatric Crohn Disease Is Associated With a Distinct Phenotype and Greater Inflammatory Burden

Objectives: Data on the outcomes of children with perianal Crohn disease (pCD) are limited, although its presence is often used for justifying early use of biologics. We aimed to assess whether pCD in children is associated with more severe outcomes as found in adults. Methods: Data were extracted from the ImageKids database, a prospective, multicenter, longitudinal cohort study. The study enrolled 246 children at disease onset or thereafter. All patients underwent comprehensive clinical, endoscopic, and radiologic evaluation at enrollment;98 children had repeat evaluation at 18 months. Results: Of the 234 included patients (mean age 14.2 +/- 2.4 years;131 [56%] boys), 57 (24%) had perianal findings, whereas only 21 (9%) had fistulizing perianal disease. Children with pCD had reduced weight and height z scores compared with non-pCD patients (-0.9 vs -0.35, P = 0.03 and -0.68 vs -0.23, respectively;P = 0.04), higher weighted pediatric CD activity index (32 [interquartile range 16-50] vs 20 [8-37];P = 0.004), lower serum albumin (3.6 +/- 0.7 vs 4.5 +/- 0.8, P = 0.016), and higher magnetic resonance enterography global inflammatory score (P = 0.04). Children with pCD had more rectal (57% vs 38%, P = 0.04), and jejunal involvement (31% vs 11% P = 0.003) and a higher prevalence of granulomas (64% vs 23%, P = 0.0001). Magnetic resonance enterography-based damage scores did not differ between groups. Patients with skin tags/fissures only, had similar clinical, endoscopic, and radiologic characteristics as patients with no perianal findings. Conclusions: Pediatric patients with pCD with fistulizing disease have distinct phenotypic features and a predisposition to a greater inflammatory burden

Nutrition in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition

Background and Aims:A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients.Methods:A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature.Results:A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment;macronutrients needs;trace elements, minerals, and vitamins;nutrition as a primary therapy of pediatric IBD;probiotics and prebiotics;specific dietary restrictions;and dietary compounds and the risk of IBD.Conclusions:This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD

Antibiotic Cocktail for Pediatric Acute Severe Colitis and the Microbiome : The PRASCO Randomized Controlled Trial

Background: Alterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC). Methods: Hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] >= 65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome. Results: Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 +/- 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 +/- 16.7 vs 40.4 +/- 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm. Conclusion: Patients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes.Peer reviewe

Infliximab in young paediatric IBD patients : it is all about the dosing

Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients = 10 years). Median age was 8.3 years (IQR 6.9-8.9) in YP compared with 14.3 years (IQR 12.8-15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 mu g/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0-12.9) vs. OP; 5.5 mg/kg (IQR 5.0-9.3);p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI - 1.2 to - 1.01);p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP;p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. What is Known

The Medical Management of Paediatric Crohn's Disease : an ECCO-ESPGHAN Guideline Update

Objective: We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn's disease [CD]. Methods: We formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached >= 80% agreement and were retained. Results: We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone. Conclusions: We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.Peer reviewe