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Presents a letter to the editor about the association of aseptic subcutaneous abscess with ulcerative colitis, published in the October 1, 2003 issue of the Journal of Gastroenterology and Hepatology.

The viscosity of hexagonal close‐packed (hcp) Fe is a fundamental property controlling the dynamics of the Earth's inner core. We studied the rheology of hcp‐Fe using high‐pressure and ‐temperature deformation experiments with in situ stress and strain measurements. Experiments were conducted using D111‐type and deformation‐DIA apparatuses at pressures of 16.3–22.6 GPa, temperatures of 423–923 K, and uniaxial strain rates of 1.52 × 10−6 to 8.81 × 10−5 s−1 in conjunction with synchrotron radiation. Experimental results showed that power‐law dislocation creep with a stress exponent of n = 4.0 ± 0.3, activation energy of E* = 240 ± 20 kJ/mol, and activation volume of V* = 1.4 ± 0.2 cm3/mol is dominant deformation mechanism at >∼800 K, whereas a mechanism with power‐law breakdown prevails at lower temperatures. An extrapolation of the power‐law dislocation creep flow law based on homologous temperature scaling suggests the viscosity of hcp‐Fe under inner core conditions is ≥∼1019 Pa s. If this power‐law dislocation creep mechanism is assumed to be the dominant mechanism in the Earth's inner core, the equatorial growth or translation mode mechanism may be the dominant geodynamical mechanism causing the observed inner core structure. Plain Language Summary: Although many geodynamic mechanisms have been proposed regarding the origin of the observed complex structure of Earth's inner core, no clear consensus has been reached. This is partly owing to the lack of accurate knowledge of the viscosity in the inner core, which is believed to mostly comprise of hexagonal close‐packed Fe (hcp‐Fe). Here, we studied the viscosity of hcp‐Fe using high‐pressure and high‐temperature deformation experiments. The results showed that the dominant deformation mechanism in hcp‐Fe changes depending on the temperature, with power‐law dislocation creep and low‐temperature creep being most important above and below ∼800 K, respectively. Based on extrapolation of these experimental results we estimate the inner core viscosity to be ≥1019 Pa s. This inner core viscosity suggests the equatorial growth or translation mode model as the dominant geodynamical mechanism in the Earth's inner core. Key Points: We studied rheology of hexagonal close‐packed Fe based on high‐pressure and high‐temperature deformation experimentsDominant deformation mechanism was power‐law dislocation creep at temperatures above ∼800 KWe estimated the viscosity of hexagonal close‐packed Fe under inner core conditions as ≥∼1019 Pa s [ABSTRACT FROM AUTHOR]

An obituary for professor and chemist Robert J. P. Williams at the University of Oxford, Great Britain is presented.

Background: Studies of endoscopic retrograde cholangiopancreatography (ERCP)‐related complications are inconsistent and sometimes have insufficient patient follow‐up. The aim of this study was to investigate risk factors for ERCP‐related events, leading to hospitalization in the case of outpatients and prolonged hospital stay in the case of inpatients, using assiduous follow‐up and contemporaneous recording of data. Methods: Prospectively collected data of 1000 consecutive ERCP procedures performed by a single endoscopist at a tertiary referral centre in Canberra, Australia, were studied and the complications evaluated. Intense short‐term follow‐up with same evening and next day phone calls/consultations was undertaken with contemporaneous recording of indications, results and complications. Results: Of 1000 procedures, 87 patients required unplanned hospitalization or prolongation of hospital stay. Risk factors for prolonged hospital stay included unusual indication (odds ratio (OR): 3.26, confidence interval (CI): 1.36–7.79, P = 0.008), age <50 (OR: 2.05, CI: 1.30–3.23, P = 0.002), procedure time >30 min (OR: 1.85, CI: 1.17–2.94, P = 0.009), being an outpatient (OR: 1.78, CI: 1.13–2.81, P = 0.012), inability to access the bile duct (OR: 1.98, CI: 1.03–3.82, P = 0.038) and placement of a pancreatic stent (OR: 1.93, CI: 1.08–3.45, P = 0.025). Of these, all but procedure time and placement of a pancreatic stent were risk factors if multivariate analysis was used. A total of 26 patients (30% of those with unplanned hospitalization) developed self‐limiting pain without apparent complications. Conclusions: Both patient‐related and procedure‐related factors are important risk factors for determining the likelihood of unplanned post‐ERCP hospitalization. There are a significant number of patients who experience self‐limiting pain following ERCP, without evidence of recognized complications. [ABSTRACT FROM AUTHOR]

Background:Indications for endoscopic retrograde cholangiopancreatography (ERCP) have received little attention, especially in scientific or objective terms. Aim:To review the prevailing ERCP indications in the literature, and to propose and evaluate a new ERCP indication system, which relies on more objective pre-procedure parameters. Methods:An analysis was conducted on 1758 consecutive ERCP procedures, in which contemporaneous use was made of an a-priori indication system. Indications were based on the objective pre-procedure parameters and divided into primary [cholangitis, clinical evidence of biliary leak, acute (biliary) pancreatitis, abnormal intraoperative cholangiogram (IOC), or change/removal of stent for benign/malignant disease] and secondary [combination of two or three of: pain attributable to biliary disease (‘P’), imaging evidence of biliary disease (‘I’), and abnormal liver function tests (LFTs) (‘L’)]. A secondary indication was only used if a primary indication was not present. The relationship between this newly developed classification system and ERCP findings and adverse events was examined. Results:The indications of cholangitis and positive IOC were predictive of choledocholithiasis at ERCP (101/154 and 74/141 procedures, respectively). With respect to secondary indications, only if all three of ‘P’, ‘I’, and ‘L’ were present there was a statistically significant association with choledocholithiasis (χ2(1) = 35.3,p < .001). Adverse events were associated with an unusual indication leading to greater risk of unplanned hospitalization (χ2(1) = 17.0,p < .001). Conclusions:An a-priori-based indication system for ERCP, which relies on pre-ERCP objective parameters, provides a more useful and scientific classification system than is available currently. [ABSTRACT FROM AUTHOR]

Motivation: The rational design of biomolecules is becoming a reality. However, further computational tools are needed to facilitate and accelerate this, and to make it accessible to more users. Results: Here we introduce ISAMBARD, a tool for structural analysis, model building and rational design of biomolecules. ISAMBARD is open-source, modular, computationally scalable and intuitive to use. These features allow non-experts to explore biomolecular design in silico. ISAMBARD addresses a standing issue in protein design, namely, how to introduce backbone variability in a controlled manner. This is achieved through the generalization of tools for parametric modelling, describing the overall shape of proteins geometrically, and without input from experimentally determined structures. This will allow backbone conformations for entire folds and assemblies not observed in nature to be generated de novo, that is, to access the 'dark matter of protein-fold space'. We anticipate that ISAMBARD will find broad applications in biomolecular design, biotechnology and synthetic biology. [ABSTRACT FROM AUTHOR]

ERCP is essential in managing pancreaticobiliary disease, with well-documented complications. Rates of clinically significant complications are about 10%, approximately half of which is related to post-ERCP pancreatitis (PEP). We aimed to quantify the effect of previous sphincterotomy on post-endoiscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Data were collated from a contemporaneously collected database of 2876 consecutive ERCP procedures of a single operator in a tertiary referral centre. Analysis was conducted using R software, and logistic regression models. Of 2876 procedures (mean age 63 years, 56% female), 120 (4.2%) developed PEP and 268 (9.3%) had prolonged/unplanned hospital admission. Univariate analysis showed patients with previous sphincterotomy 28/1054 (2.7%) had decreased risk of PEP compared with those without sphincterotomy 92/1822 (5.0%) (OR 0.52, p =.0021). This difference was not evident when multivariate analysis for age, sex and indication was undertaken due to a particularly low risk of PEP in stent change patients (1.4%), which were disproportionately represented in the previous sphincterotomy group. The rate of prolonged/unplanned hospital admission was recorded for a total of 2876 patients, occurring in 184/1802 (10.1%) in the native ampulla group, versus 84/1045 (8.0%) in the previous sphincterotomy group. The risk of PEP is halved by prior sphincterotomy. The presence of a biliary stent conferred an even lower risk of PEP (1.4%), but those without an in situ stent at the time of ERCP had a similar risk of PEP (4.6%) of prolonged/unplanned hospitalisation to those with a native ampulla. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about bacterial translocation in acute pancreatitis, published in the October 1, 2003 issue of the Journal of Gastroenterology and Hepatology.

In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster-containing homologue of the archetypal O sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O, and also NO, availability. Here we show that FnrP undergoes O-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O concentrations. The rate of the cluster reaction was found to be ~sixfold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers. [ABSTRACT FROM AUTHOR]

An ability to control the assembly of peptide nanotubes (PNTs) would provide biomaterials for applications in nanotechnology and synthetic biology. Recently, we presented a modular design for PNTs using α-helical barrels with tunable internal cavities as building blocks. These first-generation designs thicken beyond single PNTs. Herein we describe strategies for controlling this lateral association, and also for the longitudinal assembly. We show that PNT thickening is pH sensitive, and can be reversed under acidic conditions. Based on this, repulsive charge interactions are engineered into the building blocks leading to the assembly of single PNTs at neutral pH. The building blocks are modified further to produce covalently linked PNTs via native chemical ligation, rendering ca. 100 nm-long nanotubes. Finally, we show that small molecules can be sequestered within the interior lumens of single PNTs. [ABSTRACT FROM AUTHOR]

(PNTs) would provide biomaterials for applications in nanotechnology and synthetic biology. Recently, we presented a modular design for PNTs using α-helical barrels with tunable internal cavities as building blocks. These firstgeneration designs thicken beyond single PNTs. Herein we describe strategies for controlling this lateral association, and also for the longitudinal assembly. We show that PNT thickening is pH sensitive, and can be reversed under acidic conditions. Based on this, repulsive charge interactions are engineered into the building blocks leading to the assembly of single PNTs at neutral pH. The building blocks are modified further to produce covalently linked PNTs via native chemical ligation, rendering ca. 100 nm-long nanotubes. Finally, we show that small molecules can be sequestered within the interior lumens of single PNTs. [ABSTRACT FROM AUTHOR]

Rationale Investigations conducted through Amazon's Mechanical Turk (MTurk) sometimes explicitly note eligibility requirements when recruiting participants; however, the impact of this practice on data integrity is relatively unexplored within the MTurk context. Objective Contextualized in the organ donor registration domain, the current study assessed whether overtly listing eligibility requirements impairs the accuracy of data collected on MTurk. Methods On day 1, the first and third round of data collection did not list eligibility requirements; the second and fourth round overtly listed a qualification requirement: status as a non-registered organ donor. On day 2, the approach was identical, except the order was reversed—the first and third round overtly listed the study qualifications, while the second and fourth did not. These procedures provided eight different waves of data. In addition, all participants were randomly assigned to read an elevating (i.e., morally inspiring) story or a story not intended to elicit any emotion. Regardless of recruitment approach, only participants who were not registered as donors were included in the analysis. Results Results indicated that the recruitment script that explicitly requested non-registered donors resulted in the collection of participants with higher mean intentions scores than the script that did not overtly list the eligibility requirements. Further, even though the elevation induction increased intentions to register as a donor, there was not a significant interaction between recruitment approach and the influence of the elevation manipulation on registration intentions. Conclusion Explicitly listing eligibility requirements can influence the accuracy of estimates derived from data collected through MTurk. [ABSTRACT FROM AUTHOR]

Presents a study using a low-molecular-weight heparin (LMWH) treatment for deep venous thrombosis or pulmonary thromboembolism in pregnancy. The women self-injecting enoxaparin; Suggestion that subcutaneous LMWH has advantages over unfractionated heparin for venous thromboembolism in pregnancy.