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Allosteric function is a critical component of many of the parts used to construct gene networks throughout synthetic biology. In this review, we discuss an emerging field of research and education, biomolecular systems engineering, that expands on the synthetic biology edifice—integrating workflows and strategies from protein engineering, chemical engineering, electrical engineering, and computer science principles. We focus on the role of engineered allosteric communication as it relates to transcriptional gene regulators—i.e., transcription factors and corresponding unit operations. In this review, we ( a) explore allosteric communication in the lactose repressor LacI topology, ( b) demonstrate how to leverage this understanding of allostery in the LacI system to engineer non-natural BUFFER and NOT logical operations, ( c) illustrate how engineering workflows can be used to confer alternate allosteric functions in disparate systems that share the LacI topology, and ( d) demonstrate how fundamental unit operations can be directed to form combinational logical operations.

We read with interest the study by S Kumar et al that noted that patients with new gastrointestinal (GI) bleeding during admission to the intensive care unit (ICU) were more likely to die during hospitalisation.1 GI bleeding cannot always be controlled or identified at gastroscopy; therefore, guidelines recommend radiological intervention.2 3 Radiological intervention may be of value in uncontrolled GI bleeding where a lesion has already been identified at endoscopy or if no lesion has been detected endoscopically but the patient continues to be haemodynamically unstable. Fluoroscopic angiography (FA) is time consuming, requires significant expertise and has significant ionising radiation exposure. However, the recent advent of CT angiography (CTA) potentially offers a sensitive, rapid and accurate diagnosis of the source of persisting GI bleeding and has a lesser risk of vessel dissection or damage than catheter angiography. For these …

There have been few case reports describing cystic duct stent insertion in the management of acute cholecystitis secondary to benign disease with no case series published to date. We present our series demonstrating the role of cystic duct stents in managing benign gallbladder disease in those patients unfit for surgery. Thirty three patients unfit for surgery in our institution underwent cystic duct stent insertion for the management of acute cholecystitis in the period June 2008 to June 2013. Patients underwent a mixture of transperitoneal and transhepatic gallbladder puncture. The cystic duct was cannulated with a hydrophilic guidewire which was subsequently passed through the common bile duct and into the duodenum. An 8Fr 12-cm double-pigtail stent was placed with the distal end lying within the duodenum and the proximal end within the gallbladder. Ten patients presented with gallbladder perforation, 21 patients with acute cholecystitis, 1 with acute cholangitis and 1 with necrotising pancreatitis. The technical success rate was 91 %. We experienced a 13 % complication rate with 3 % mortality rate at 30 days. Cystic duct stent insertion can be successfully used to manage acute cholecystitis, gallbladder empyema or gallbladder perforations in those unfit for surgery and should be considered alongside external gallbladder drainage as a definitive mid-term treatment option.

PTC and stenting procedures are associated with significant risks including life-threatening haemorrhage, sepsis, renal failure and high mortality rates. PTC tract closure methods are utilised to reduce haemorrhagic complications despite little evidence to support their use. The current study assesses the incidence of haemorrhagic complications following PTC and stenting procedures, both prior to and following the introduction of a dedicated expanding gelatin foam-targeted embolisation liver tract closure technique. Haemorrhagic complications were retrospectively identified in patients undergoing PTC procedures both prior to (subgroup 1) and following (subgroup 2) the introduction of a dedicated targeted liver tract closure method between 9/11/2010 and 10/08/2012 in a single tertiary referral centre. Mean blood Hb decrease following PTC was established in subgroups 1 and 2. Kaplan–Meier life-table analysis was performed to compare survival outcomes between subgroups using the log-rank test. Haemorrhagic complications were significantly reduced following the introduction of the targeted PTC tract closure method [(12 vs. 3 % of subgroups 1 (n = 101) and 2 (n = 92), respectively (p = 0.027)]. Mean blood Hb decrease following PTC was 1.40 versus 0.68 g/dL in subgroups 1 and 2, respectively (p = 0.069). 30-day mortality was 14 and 12 % in subgroups 1 and 2, respectively. 50 % of the entire cohort had died by 174 days post-PTC. Introduction of liver tract embolisation significantly reduced haemorrhagic complications in our patient cohort. Utilisation of this method has the potential to reduce the morbidity and mortality burden associated with post-PTC haemorrhage by preventing bleeding from the liver access tract.

Pumping a tail stage of resin coat proppant (RCP) is well documented method to control proppant flowback in a wide variety of oil and gas wells. The performance of RCP can be impacted by reservoir temperature and closure stress, as well as fluid and fracture placement parameters. RCP systems were originally designed for higher temperature applications although the use of lower temperature curable resins in shallow lower stress reservoirs has been discussed since at least mid-2005. 1,2,3 Strong oil prices and relatively weak gas prices have recently (2012) been driving the development of relatively shallow tight oil reservoirs within the Western Canadian Sedimentary Basin (WCSB) including the Slave Point, Cardium, Bakken, Viking and others. These reservoirs typically have relatively low reservoir temperatures and closure stresses which highlight the importance of looking beyond the reservoir temperature with a holistic evaluation of the fracture fluid interactions and fracture placement efficiency that can significantly impact RCP placement and performance; existing SPE publications also provide good background to the impact of these contributing factors.4,5 Most RCP literature focuses on clastic applications. In conjunction with our proppant supplier and pumping service partner, Lone Pine Resources Canada Ltd (LPR) has recently conducted laboratory testing designed to optimize the use of RCP within the Slave Point carbonate reservoir that LPR is successfully developing with multi-fractured horizontal wells (MFHZ). The Slave Point reservoir presents a challenge to RCP performance with a combination of a cool reservoir temperature of 40°C (100°F) and low closure pressures of roughly 20 MPa (2,900 psi). During Q1/Q2 2012 LPR identified a proppant flowback that was inhibiting production and increasing workover expenditures. Study of the problem identified proppant mixing and a lack of RCP bonding as root cause issues. A holistic review of the LPR Slave Point fracture program resulted in significant changes to the fracture treatment design and execution including the RCP type, resin activation parameters and base fluid changes. LPR has been able to minimize proppant flowback to the point that bottomhole pump failures as a result of proppant production have been significantly reduced, if not eliminated, and no incremental proppant clean-out operations have been required since the implementation of an optimized fracturing program that includes higher viscosity fracturing fluid and an optimized RCP-LT and activator program. In addition, no measurable proppant flowback volumes have been recovered during initial CT clean-out from the last four July 2012 fractured wells. These are very positive indicators that the RCP-LT and activator changes, improved fracture fluid viscosity and proppant placement has solved the proppant inflow problem.

Introduction Gastrointestinal (GI) bleeding cannot always be controlled or identified at endoscopy (OGD), therefore guidelines recommend radiological intervention in an unstable patient. The options are fluoroscopic angiogram (FA) which is time consuming, requires significant expertise, and has significant radiation exposure. Alternatively a CT angiogram (CTA) may offer a sensitive, rapid diagnosis of the source of GI bleeding to allow definitive treatment. Data on the role and diagnostic yield of CTA are lacking. We present the largest international study to assess the impact of CTA in upper GI bleeding. Method A retrospective analysis of endoscopy and radiology databases was used to identify patients who underwent radiological intervention for GI bleeding at Sheffield Teaching Hospitals between 2003 and 2013. A control group of 757 patients (who did not undergo FA or CTA) from the South Yorkshire GI bleed audit 2011 was used for comparison. Pre-endoscopy Rockall scores, routine haematology and biochemistry results taken prior to endoscopy and inpatient mortality rates were compared. Results 59 patients (35 male, mean age 69.3) underwent imaging for upper GI bleeding during the study period. In 49/59 (mean age=68.3, mean Rockall = 3.8, mean Hb = 84.7) a source was initially identified at OGD but with continued bleeding. CTA was performed in 31 with the other 18 having immediate FA. For patients having a CTA first a source was identified in 15 (48%) requiring embolization in 10. 4 patients who did not have an abnormality seen on CTA subsequently required FA and embolization and 2 of these patients died. For the other 10/59 (16.9%) (mean age 74.3 mean Rockall=4, mean Hb=84.2) no source was identified at OGD and they underwent CTA identifying 8 bleeds which proceeded to FA and then embolization in 6. Inpatient mortality in this group was 50% which was significantly higher than 14.3% for those patients with an identified source for upper GI bleed (p = 0.02). Patients who underwent CTA were older (p = 0.039) and presented with higher median pre-endoscopy Rockall scores (p = 0.003) than controls. Both CTA and ‘direct to FA patients’ presented with lower Hb (p Inpatient mortality rates were higher in those who underwent CTA prior to FA (22%) compared to those who went directly to FA (11%) but this was not significant (p = 0.5). Conclusion Radiological imaging resulted in embolization in 55.9% of patients referred. Patients requiring radiological intervention for GI bleeds have more significant bleeding with lower haemoglobin and higher Rockall scores. Patients with no source of bleeding on OGD have higher inpatient mortality despite radiological intervention. Disclosure of interest None Declared.

Purpose There have been very few case reports describing cystic duct stent insertion in the management of acute cholecystitis secondary to benign disease with no case series published to date. Both Gatenby et al and Comin et al describe only a single case. We present our series demonstrating the role of cystic duct stents in managing gallbladder disease in those patients unfit for surgery. Materials and Methods 14 patients in our institution underwent cystic duct stent insertion for the management of acute cholecystitis in the period June 2008 to June 2012. Patients underwent a mixture of direct and transhepatic gallbladder puncture. The cystic duct was cannulated with a hydrophilic guidewire which was subsequently passed through the common bile duct and into the duodenum. An 8Fr double pigtail stent was placed with the distal end lying within the duodenum and the proximal end within the gallbladder. Results 6 patients presented with gallbladder perforation, 7 patients presented with gallbladder empyema/severe cholecystitis and 1 with necrotsing pancreatitis. We experienced a 93% technical success rate. Clinical follow up revealed all technical successes did well post procedure with symptom resolution. 1 patient developed acute pancreatitis post procedure. None have experienced any subsequent episodes of acute cholecystitis (follow-up 14 days - 48 months). Conclusion Cystic duct stent insertion can be successfully used to manage acute cholecystitis/gallbladder empyema or gallbladder perforation in those unfit for surgery and should be considered alongside external gallbladder drainage. We hope to further refine this technique for use in patients fit for surgery as a bridge to laparoscopic cholecystectomy.