Access Loop Research Articles

Retrospective analysis of surgical management options of hepatolithiasis in a tertiary care centre in Bangladesh

Background: Hepatolithiasis (HL) is the presence of stones in the bile ducts proximal to the confluence of the hepatic ducts. It is endemic in the Asia-Pacific region. The etiology of hepatolithiasis is not fully understood but genetic, dietary and environmental factors are thought to be contributory. Malnutrition and low socioeconomic conditions are associated with a high incidence of intrahepatic stones. This study aimed to analyze the demographic and clinicopathological factors, appraise the role of surgical management and analyse the postoperative outcomes of HL in a tertiary care centre in Bangladesh. Methods: This study was conducted in the Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplant (HBPS & LT), BIRDEM General Hospital, Dhaka, Bangladesh. Retrospective data of all patients operated for HL from January 2011 to December 2022 were analyzed with regard to clinical parameters, biochemical parameters and different types of surgical management. Results: A total of 52 patients underwent surgical treatment for HL. Of the patients, 65.4% were female and 34.6% were male. Of the patients, 94.2% had abdominal pain, 57.7% had fever and 28.8% presented with jaundice. A total of 30.8% of patients had a history of previous biliary surgery. Liver atrophy was present in 38.5% of cases. Hepaticojejunostomy (HJ) alone was done in 36 (69.2%) patients, hepatic resection with bilioenteric anastomosis was done in 10 (19.2%) patients and hepatic resection with T-tube placement in common bile duct (CBD) done in 6 (11.5%) patients. Endoluminal access loop was done in 2 (3.8%) patients. On followup visits, 60% of patients were asymptomatic. There was no postoperative mortality. Conclusion: Results from present study revealed encouraging results with minimal post operative complications and no mortality. BIRDEM Med J 2024; 14(3): 137-142

How I do it: Pedal access and pedal loop revascularization for patients with chronic limb-threatening ischemia.

An increasing proportion of patients with chronic limb-threatening ischemia are older and have multiple comorbidities, including diabetes and renal failure. For those who are not candidates for a surgical bypass, this set of patients presents a challenge to vascular surgeons and interventionalists owing to the complex below-the-knee and increasingly below-the-ankle disease pattern that can fail traditional approaches for endovascular intervention. Two techniques, the retrograde pedal access and the pedal-plantar loop technique, can be useful in these settings and in skilled hands can be used safely, with a high technical success rate. In patients with chronic limb-threatening ischemia who are not candidates for a single-segment saphenous vein bypass, the retrograde pedal access technique can be used not only in the setting of failed antegrade treatment, but also primarily when faced with a difficult groin or as an adjunct during a planned antegrade-retrograde intervention. The pedal plantar loop technique allows for retrograde access to tibial vessels without retrograde vessel puncture and additionally offers the ability to treat the pedal-plantar arch, which may have added benefit in wound healing. We describe the tips and tricks for these two techniques used in our limb salvage practice.

Hepaticojejunostomy with gastric access loop versus conventional hepaticojejunostomy: a randomized trial

Roux-en-Y hepaticojejunostomy (RYHJ) with the provision of “gastric access loop” was developed to shorten the distance traveled by the endoscope to reach hepaticojejunostomy (HJ) anastomotic site. The aim of our study was to assess modified RYHJ with gastric access loop (RYHJ-GA) and compare it with conventional RYHJ (RYHJ-C) regarding short- and long-term outcomes and, moreover, to evaluate the feasibility and results of future endoscopic access of the modified bilio-enteric anastomosis. Patients eligible for RYHJ between September 2017 and December 2019 were allocated randomly to receive either RYHJ-C or RYHJ-GA. Fifty-two patients were randomly assigned to RYHJ-C (n = 26) or RYHJ-GA (n = 26). Three cases in RYHJ-C and 4 cases in RYHJ- GA developed HJ anastomotic stricture (HJAS) (P=0.68). 3 cases of RYHJ-GA had successful endoscopic dilation and balloon sweeping of biliary mud (one case) or stones (2 cases). Revisional surgery was needed in 2 cases of RYHJ-C and 1 case in RYHJ-GA (P=0.68). Modified RYHJ with gastric access loop is comparable to the classic hepaticojejunostomy regarding complications. However, gastric access enables easy endoscopic access for the management of future HJAS. This modification should be considered in patients with a high risk of HJAS during long-term follow-up.The trial registration number (TRN) and date of registration:ClinicalTrials.gov (NCT03252379), August 17, 2017.

ERCP through the gastric access loop in Billroth II or Roux-en-Y anatomy

ERCP through the gastric access loop in Billroth II or Roux-en-Y anatomy

Therapeutic Role of Subcutaneous Access Loop Created Adjunct to Hepaticojejunostomy for Management of Bile Duct Injury.

Roux-en-Y hepaticojejunostomy (RYHJ) is usually required for major bile duct injury (BDI) as a definitive treatment. Hepaticojejunostomy anastomotic stricture (HJAS) is the most feared long-term complication following RYHJ. The ideal management of HJAS remains undefined. The provision of permanent endoscopic access to the bilio-enteric anastomotic site can make endoscopic management of HJAS feasible and attractive option. In this cohort study, we aimed to evaluate short- and long-term outcomes of subcutaneous access loop created adjunct to RYHJ (RYHJ-SA) for management of BDI and its usefulness for endoscopic management of anastomotic stricture if occurred. This is a prospective study including patients who were diagnosed with iatrogenic BDI and underwent hepaticojejunostomy with subcutaneous access loop between September 2017 and September 2019. This study included a total number of 21 patients whom ages ranged between 18 and 68years. During follow-up, three cases had HJAS. One patient had the access loop in subcutaneous position. Endoscopy was done but failed to dilate the stricture. The other 2 patients had the access loop in subfascial position. Endoscopy of them failed to enter the access loop due to failure of fluoroscopy to identify the access loop. The three cases underwent redo-hepaticojejunostomy. Parajejunal (parastomal) hernia occurs in 2 patients in whom the access loop was fixed subcutaneous position. In conclusion, modified RYHJ with subcutaneous access loop (RYHJ-SA) is associated with reduced quality of life and patient satisfaction. Moreover, its role in endoscopic management of HJAS after biliary reconstruction for major BDI is limited.

Per-oral cholangioscopy via a gastric access loop for the management of recurrent hepatolithiasis

Per-oral cholangioscopy via a gastric access loop for the management of recurrent hepatolithiasis

Hepatolithiasis: A Retrospective Analysis of Surgical Management Options in a Tertiary Care Centre in Southern India.

Introduction: Hepatolithiasis (HL) is the presence of stones in the bile ducts proximal to the confluence of the hepatic ducts. This study aims to analyse the case presentations of HL in a tertiary care centre in South India and define the role of hepatic resection in these cases and their outcomes.Methods: Retrospective data of all patients operated on for HL from 2012 to 2021 were analysed with regard to clinical parameters, biochemical parameters, and different types of surgical management. Descriptive data analyses were done.Results: A total of 42 patients underwent surgical treatment for HL between 2012 and 2021 in our institution. Of the patients, 64% were females. A total of 50% of patients were affected by bilateral HL. Of the patients, 95% had abdominal pain, 57% had a fever, and 29% presented with jaundice. A total of 38% of patients had a history of previous biliary surgery. Atrophy was present in 38% of cases. Choledochoduodenostomy was performed in 26%, and hepatic resection with bilio-enteric anastomosis was done in 36% of patients. Endoluminal access loop was done in 21%. Hepaticojejunostomy alone was done in 14%. On follow-up visits (mean: 61.5 months), 60% of patients were asymptomatic with no recurrence. There was nil 30-day postoperative mortality.Conclusion: The treatment options for HL were based on the extent of liver involvement. The bilio-enteric anastomosis was done after the clearance of stones for uncomplicated HL. Complicated HL may need liver resection with hepaticojejunostomy, with an endoluminal access loop for a good outcome.

Detection of Isopeptide Bonds in Monoclonal Antibody Aggregates

PurposeA major difficulty in monoclonal antibody (mAb) therapeutic development is product aggregation. In this study, intermolecular isopeptide bonds in mAb aggregates were characterized for the first time. We aim to propose a mechanism of covalent aggregation in a model antibody using stressed studies at raised temperatures to aid in the understanding of mAb aggregation pathways.MethodsAggregate fractions were generated using raised temperature and were purified using size-exclusion chromatography (SEC). The fractions were tryptically digested and characterized using liquid chromatography hyphenated to tandem mass-spectrometry (LC–MS/MS).ResultsAn increased amount of clipping between aspartic acid and proline in a solvent accessible loop in the constant heavy 2 (CH2) domain of the mAb was observed under these conditions. Detailed peptide mapping revealed 14 isopeptide bonds between aspartic acid at that cleavage site and lysine residues on adjacent antibodies. Two additional isopeptide bonds were identified between the mAb HC N-terminal glutamic acid or a separate aspartic acid to lysine residues on adjacent antibodies.ConclusionsInter-protein isopeptide bonds between the side chains of acidic amino acids (aspartate and glutamate) and lysine were characterized for the first time in mAb aggregates. A chemical mechanism was presented whereby spontaneous isopeptide bond formation could be facilitated via either the aspartic acid side chain or C-terminus.

A Multi-bit Error Upset Immune 12T SRAM Cell for 5G Satellite Communications

Satellite communication plays a vital role in extending 5G cellular networks to hard-to-reach areas, including airplanes, railways, shipments, other transport mechanisms, and especially in rural regions of the country that are traditionally beyond the reach of cellular service providers. The devices, specifically those incorporating static memories, being employed for satellite communication, face the challenge of getting prone to cosmic radiations or alpha particle strikes. These strikes cause multi-bit errors in static-memory cells that lead to loss of total output yield. This work proposes a low power twelve transistor (12T) SRAM cell that confirms a reduction in multi-bit errors for the Internet of things based devices supporting fifth-generation (5G) communication system. The proposed SRAM ensures improved read and write ability by utilizing a read decoupled access path and loop cutting mechanism, respectively. The proposed design improves read/write stability by 2.02 $$\times$$ /1.05 $$\,\times$$ in comparison to conventional 6T cell with 2.52 $$\times$$ silicon space overhead. The area overhead is neutralized by 3.17 $$\times$$ improvement in $$I_{on}$$ / $$I_{off}$$ ratio that improves cell density of SRAM cell. The improved critical charge of the proposed 12T SRAM cell is compared with four other considered cells to ensure the reduction in multi-bit soft errors, and thereby confirming its suitability for devices supporting satellite communications. The proposed design successfully eliminates the half-select issue that enables the implementation of the bit-interleaved architecture. The leakage power of the proposed 12T cell is improved by 2.65 $$\times$$ in comparison to conventional 6T attributed to series-connected devices used as loop cutting pair. This reduction of leakage power remains sustained till 110 $$^{\circ }$$ temperature. The simulation of this work has been conducted with cadence virtuoso tool using GPDK 45 nm technology file.

Distinct sequence and structural feature of trypanosoma malate dehydrogenase

Glycosomal malate dehydrogenase from Trypanosoma cruzi (tcgMDH) catalyzes the oxidation/reduction of malate/oxaloacetate, a crucial step of the glycolytic process occurring in the glycosome of the human parasite. Inhibition of tcgMDH is considered a druggable trait for the development of trypanocidal drugs. Sequence comparison of MDHs from different organisms revealed a distinct insertion of a prolin rich 9-mer (62-KLPPVPRDP-70) in tcgMDH as compared to other eukaryotic MDHs. Crystal structure of tcgMDH is solved here at 2.6 Å resolution with Rwork/Rfree values of 0.206/0.216. The tcgMDH forms homo-dimer with the solvation free energy (ΔGo) gain of −9.77 kcal/mol. The dimeric form is also confirmed in solution by biochemical assays, chemical-crosslinking and dynamic light scattering. The inserted 9-mer adopts a structure of a solvent accessible loop in the vicinity of NAD+ binding site. The distinct sequence and structural feature of tcgMDH, revealed in the present report, provides an anchor point for the development of inhibitors specific for tcgMDH, possible trypanocidal agents of the future.

A rare case of recurrent pyogenic cholangiohepatitis: Case report

A 47-year-old female presented with Easy fatigability, abdominal pain for 4 days. Past history of open cholecystectomy with Common bile duct exploration and Choledocho Duodenostomy done 13 years before. She later had multiple episodes of abdomen pain with fever on and off. ERCP revealed stone in common bile duct but not retrieved and patient lost follow-up. During this hospitalisation patient had fever, Jaundice and Sepsis with Acute Kidney Injury. Ultrasound Abdomen showed Hypoechoic lesion in seg IV left lobe liver. Mild pneumobilia. CECT Abdomen showed Pneumobilia, ill-defined hypodense lesions in segment IVA, II, III causing left lobe Intrahepatic biliary radicle dilation. MRCP showed Multiple tiny T2 hyperintense lesions with surrounding edema in SEGMENT IVB? Cholangitic abscess. Patient was taken up for surgery. Intraoperatively Left lateral segment II, III fibrotic, left hepatic duct & branches grossly dilated, stones retrieved from LHD; Left lateral sectionectomy, hepaticojejunostomy, jejunojejunostomy with access loop done. This was a rare case of recurrent pyogenic cholangiohepatitis managed surgically.

Benefits of Hepatic Resection in Recurrent Pyogenic Cholangitis among Bangladeshi Residents

Introduction: Surgery is the corner stone treatment strategy for Recurrent pyogenic cholangitis (RPC) with stones and stricture. Sepsis is often a grave complication. Identification of source of sepsis to delineate the extent of disease and resection of unhealthy segment is the key to successful management. Method: This prospective study includes 523 cases of RPC surgically treated in a cohort of Bangladeshi patients, during January 2007 to January 2020. The study intended to analyze outcome of hepatic resection in RPC. Distortion of hepatic parenchymal architecture, stones, strictures and crowding of ducts were indications of hepatic resections with hepatolithotomy followed by T-tube or bilioenteric drainage with or without an access loop were treatment strategies. Result: Patients presented were between 20-77 yrs, 301 male (57.55%) and 222 were female (42.44%). 374 patients (71.51%) from south eastern part of Bangladesh. 29.06 % patients presented with Recurrent abdominal pain, Jaundice and fever. Isolated left duct stone found in 329 patients (62.09%), right duct stone in 33 patients (6.03%,) bilateral stones in 87 patients (14.91%) and both Intra-extrahepatic litihiasis in 74 patients (14.14%). Left Lateral Segmentectomy was the most common procedure in 387 cases. 184 patients required T-tube drainage, hepaticojejunostomy in 339 patients, Access loop in 34 patients (8.22%). Post-operative complications occured in 15% cases. Conclusion: Treatment strategy of RPC is tailored, depends on extent of disease and future remnant liver. Left ductal approach following left lateral segmentectomy ensure better approach to right ductal system for better ductal clearance to prevents recurrence.

Hepaticojejunostomy With or Without Permanent Duodenal Access Loop in Treatment of Iatrogenic Bile Ducts Injuries, a Comparative Study

Hepaticojejunostomy With or Without Permanent Duodenal Access Loop in Treatment of Iatrogenic Bile Ducts Injuries, a Comparative Study

Jejunoduodenal anastomosis as permanent biliary access loop post-hepaticojejunostomy: our experience

Background: Post-hepaticojejunostomy stricture is a common problem may result in liver cirrhosis and portal hypertension and death if not treated. Different modalities to repair it are available including endoscopic management that needs access loop (including jejuno-duodenal access loop) to reach the site of stricture.Methods: This prospective study was done in general surgery department, faculty of medicine, Zagazig University hospitals during the period from January 2016 to December 2018. The study included 23 patients (18 females and 5 males) all needed hepaticojejunostomy to treat biliary injuries during cholecystectomy, biliary stricture post-cholecystectomy or post-hepaticojejunostomy anastomotic stricture. Their ages ranged between 26 to 57 ys with mean age 37.3±5.1. The postoperative course of patients and the feasibility of postoperative endoscopic access to the hepaticojejunostomy and intrahepatic ductal system were assessed.Results: This study included 23 patients (18 females and 5 males) where 19 (82.6%) patients were presented post-cholecystectomy and 4 (17.4%) patients post-hepaticojejunostomy, with different modes of presentation postoperative complications included; 2 patients complicated with chest infection, 3 (13%) patients with wound seroma and infection, 2 (about 8.7%) patients complicated with biliary gastritis and 1 (about 4.4%) patient with mild attack of cholangitis. There was no anastomotic leakage or mortality in the studied group. The trial of access to the hepaticojejunostomy using gastroduodenoscopy was successful in all cases with ease including trial of balloon dilatation. The average hospital stay ranged between 5-7 days.Conclusions: Side-to-side jejunoduodenal anastomosis is a very useful technique as it provides good endoscopic access to hepaticojejunostomy and the intrahepatic ducts and needs more application and further evaluation.

Closing the loop: short term impacts on physical activity of the completion of a loop trail in Sydney, Australia

BackgroundIn Australia, an estimated 57% of the population do not meet physical activity recommendations for health. The built environment is important for active living, and recreational trails provide safe and pleasant settings for this purpose. However, evidence for positive impacts on physical activity from real world natural experiments is sparse. We describe the impact of transforming a recreational trail into a loop on usage by cyclists and pedestrians and users’ physical activity levels.MethodWe conducted time series analyses of pre and post-completion (November 2013–July 2015) counts taken from infrared electronic counters of pedestrians and cyclists on two established sections of the trail adjusted for underlying trend, trend change, weather, holidays and trail closures. Chi-square analyses of pre and post-completion visual counts examined change in the distribution of pedestrian/cyclist, adult/child, and male/female users. Descriptive and bivariate analyses of post-completion intercept survey data of 249 trail users were conducted to examine user characteristics and impact on physical activity.ResultsPedestrian and cyclist counts on established trail sections increased by between 200 and 340% from pre to post-completion. Visual count data showed a significant 7% increase in children (vs adults) using the trail at one site pre to post (p = 0.008). Of previous users, 48% reported doing more physical activity at the trail and this was additional to (not replacing) physical activity done elsewhere. Those users not meeting physical activity recommendations were more likely to report increased total physical activity since the loop was created (55.5% vs 39.2%, p = 0.031). The connected loop nature of the trail and its length was perceived to encourage more and different forms of physical activity.ConclusionCreating an accessible loop trail away from motorised traffic can lead to increased trail use and potentially total physical activity. The modification to the trail encouraged proportionate and real increases in usage among vulnerable populations such as children and perhaps greater total physical activity especially for people not meeting physical activity recommendations. The findings suggest that the benefits of environmental changes such as these can accrue to those most in need of support for being physically active.

Point Mutation of Aquaporin 4 Impairs its Binding in Neuromyelitis Optica

Aquaporin 4 (AQP4) is the principal aquaporin expressed in astrocytes throughout the central nervous system. An autoantibody, IgG, that binds to AQP4 leads to a rare disease called neuromyelitis optica (NMO), which is characterized by paralysis and loss of vision. Current treatments for NMO are few and involve non‐specific immunosuppression. The Summit Country Day School MSOE Center for BioMolecular Modeling MAPS Team used 3D modeling and printing technology to examine structure‐function relationships of the AQP4 epitope for NMO‐IgG. Understanding the molecular structure of the AQP4 epitope is an important step in explaining its binding to NMO‐IgG. NMO‐IgG primarily interacts with the accessible AQP4 extracellular loops A, C, and E. These loops change their conformation when AQP4 arrange into orthogonal arrays of particles, thus enabling attachment of NMO‐IgG and facilitating complement binding. Studies on the point mutation of aspartate in position 69 (D69) revealed conformational changes such as 1) reorientation of threonine in position 62, 2) weakened hydrogen bond interaction between leucine in position 53 and threonine in position 56, 3) increased mobility of loop A, and 4) disruption of epitope reorganization of AQP4. Overall, D69 substitution and the subsequent conformational changes in loop A leads to impairment of binding between AQP4 and the NMO‐IgG. Determining the role of extracellular loop A between and within AQP4 monomers will aid in understanding how it contributes to antigen recognition. Prevention of the binding of AQP4 by NMO‐IgG is an important strategy for developing targeted therapy in NMO.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hepatico-jejuno-duodenal access loop – a modified biliary reconstruction technique for facilitated endoscopic access to biliary tree following surgery for hepatolithiasis

Aims: Management of hepatolithiasis is complicated by residual and recurrent disease, and endoscopic access to biliary tree in such patients enables therapeutic interventions thereby avoiding the morbidity associated with relaparotomy. In this study we assess a modified biliary reconstruction in the form of hepaticojejuno- duodenal access loop (HJDA) with regard to the feasibility of endoscopic access to intrahepatic ducts with follow-up. Methods: From August 2011 till December 2016, all patients treated for hepatolithiasis with bilateral disease, nondilated extrahepatic biliary system or extensive intrahepatic strictures underwent HJDA. After completion of hepaticojejunostomy (HJ), the free end of the Roux loop was anastomosed to the first part of duodenum in a side to side fashion. In the fourth week postoperatively, endoscopy with conventional forward viewing endoscope was performed to explore the possibility of accessing the biliary system. Results: Endoscopic access to the intrahepatic bile ducts through the HJDA was possible in all the patients and mean time taken to access the HJ was 3.5 minutes (2-7 minutes). There were no complications pertinent to construction of the HJDA. One patient had bile leak from HJ, which settled with conservative management and surgical site infection was seen in four. We did not have any mortality in our series. During the follow up, three of our patients (30%) subsequently presented with cholangitis at a mean period of 22 months and were successfully managed with endoscopic procedures alone. One patient required balloon dilatation of the HJ stricture, while the other two were managed by endoscopic removal of calculi. Overall, five endoscopic procedures were required in three patients with recurrent cholangitis in the follow up period with rate of 1.67 procedures per patient. Conclusion: HJDA is a modified biliary reconstruction technique which facilitates endoscopic access to the biliary system for removal of recurrent/residual intrahepatic stones. It is therefore recommended in patients with complicated hepatolithiasis like bilateral disease, recurrence, multiple intrahepatic strictures and for those in whom future endoscopic access to biliary tree is deemed necessary.

Management of hepatolithiasis in a tertiary care centre in South-India

Aim: This study is to analyse the clinicopathologic features, diagnosis and treatment for hepatolithiasis in a tertiary centre. Methods: This is a retrospective study of prospectively maintained database between June 2012 to October 2017. The demography, clinical presentation, surgical management were analyzed. Results: The age range was between 24 to 70 years. The study includes 20 patients (M - 4, F - 16). Hepatectomy was done in 12 patients. Left lateral segmentectomy (8), left hepatectomy(1), Segmental resections done in 3 patients. All these patient had access to the bile duct through Choledochoduodenostomy in 16 patients and Hepaticojejunostomy with Jejunoduodenostomy as access loop to the first part of duodenum (4 cases). Cholecystectomy was done in all patients without prior cholecystectomy. Conclusion: Hepatolithiasis is rare in South India. Surgical management depends on liver parenchymal status, cholangitis, diameter of CBD, biliary stricture and distribution of stones. The access to the biliary system was made either by choledocoduodenostomy or access loop to the first part of duodenum.

Matrix Metalloproteinase-9-Generated COOH-, but Not NH2-Terminal Fragments of Serum Amyloid A1 Retain Potentiating Activity in Neutrophil Migration to CXCL8, With Loss of Direct Chemotactic and Cytokine-Inducing Capacity.

Serum amyloid A1 (SAA1) is a prototypic acute phase protein, induced to extremely high levels by physical insults, including inflammation and infection. Human SAA and its NH2-terminal part have been studied extensively in the context of amyloidosis. By contrast, little is known about COOH-terminal fragments of SAA. Intact SAA1 chemoattracts leukocytes via the G protein-coupled receptor formyl peptide receptor like 1/formyl peptide receptor 2 (FPR2). In addition to direct leukocyte activation, SAA1 induces chemokine production by signaling through toll-like receptor 2. We recently discovered that these induced chemokines synergize with intact SAA1 to chemoattract leukocytes in vitro and in vivo. Gelatinase B or matrix metalloproteinase-9 (MMP-9) is also induced by SAA1 during infection and inflammation and processes many substrates in the immune system. We demonstrate here that MMP-9 rapidly cleaves SAA1 at a known consensus sequence that is also present in gelatins. Processing of SAA1 by MMP-9 at an accessible loop between two alpha helices yielded predominantly three COOH-terminal fragments: SAA1(52–104), SAA1(57–104), and SAA1(58–104), with a relative molecular mass of 5,884.4, 5,327.3, and 5,256.3, respectively. To investigate the effect of proteolytic processing on the biological activity of SAA1, we chemically synthesized the COOH-terminal SAA fragments SAA1(52–104) and SAA1(58–104) and the complementary NH2-terminal peptide SAA1(1–51). In contrast to intact SAA1, the synthesized SAA1 peptides did not induce interleukin-8/CXCL8 in monocytes or fibroblasts. Moreover, these fragments possessed no direct chemotactic activity for neutrophils, as observed for intact SAA1. However, comparable to intact SAA1, SAA1(58–104) cooperated with CXCL8 in neutrophil activation and migration, whereas SAA1(1–51) lacked this potentiating activity. This cooperative interaction between the COOH-terminal SAA1 fragment and CXCL8 in neutrophil chemotaxis was mediated by FPR2. Hence, proteolytic cleavage of SAA1 by MMP-9 fine tunes the inflammatory capacity of this acute phase protein in that only the synergistic interactions with chemokines remain to prolong the duration of inflammation.

A fast stochastic solution method for the Blade Element Momentum equations for long‐term load assessment

AbstractUnsteady power output and long‐term loads (extreme and fatigue) drive wind turbine design. However, these loads are difficult to include in optimization loops and are typically only assessed in a post‐optimization load analysis or via reduced‐order methods. Both alternatives yield suboptimal results. The reason for this difficulty lays in the deterministic approaches to long‐term loads assessment. To model the statistics of lifetime loads they require the analysis of many unsteady load cases, generated from many different random seeds—a computationally expensive procedure. In this paper, we present an alternative: a stochastic solution for the unsteady aerodynamic loads based on a projection of the unsteady Blade Element Momentum (BEM) equations onto a stochastic space spanned by chaos exponentials. This approach is similar to the increasingly popular polynomial chaos expansion, but with 2 major differences. First, the BEM equations constitute a random process, varying in time, while previous polynomial chaos expansion methods were concerned with random parameters (ie, random but constant in time or initial values). Second, a new, more efficient basis (the exponential chaos) is used. This new stochastic method enables us to obtain unsteady long‐term loads much faster, enabling unsteady loads to become accessible inside wind turbine optimization loops. In this paper we derive the stochastic BEM solution and present the most relevant results showing the accuracy of the new method.