Surface Confined Hydrogenation of Graphene Nanoribbons.

On-surface synthesis with designer precursor molecules is considered an effective method for preparing graphene nanoribbons (GNRs) of well-defined widths and with tunable electronic properties. Recent reports have shown that the band gap of ribbons doped with heteroatoms (such as boron, nitrogen, and sulfur) remains unchanged in magnitude in most cases. Nevertheless, theory predicts that a tunable band gap may be engineered by hydrogenation, but experimental evidence for this is so far lacking. Herein, surface-confined hydrogenation studies of 7-armchair graphene nanoribbons (7-AGNRs) grown on Au(111) surfaces, in an ultrahigh vacuum environment, are reported. GNRs are first prepared, then hydrogenated by exposure to activated hydrogen atoms. High resolution electron energy loss spectroscopy (HREELS) and scanning tunneling microscopy (STM) images reveal a self-limited hydrogenation process. By means of a combination of bond-resolved scanning tunneling microscopy (BRSTM) imaging and tip-induced site-specific dehydrogenation, the hydrogenation mechanism is studied in detail, and density-functional theory (DFT) calculation methods are used to complement the experimental findings. In all cases, the results demonstrate the successful modification of the electronic properties of the GNR/Au(111) system by edge and basal-plane hydrogenation, and a mechanism for the hydrogenation process is proposed.

Cold Pulsatile Machine Perfusion Versus Static Cold Storage for Kidneys Donated After Circulatory Death: A Multicenter Randomized Controlled Trial.

BACKGROUND: The benefits of cold pulsatile machine perfusion (MP) for the storage and transportation of kidneys donated after circulatory death are disputed. We conducted a UK-based multicenter, randomized controlled trial to compare outcomes of kidneys stored with MP versus static cold storage (CS). METHODS: Fifty-one pairs of kidneys donated after circulatory death were randomly allocated to receive static CS or cold pulsatile MP. The primary endpoint, delayed graft function, was analyzed by "intention-to-treat" evaluation. RESULTS: There was no difference in the incidence of delayed graft function between CS and MP (32/51 (62.8%) and 30/51 (58.8%) P = 0.69, respectively), although the trial stopped early due to difficulty with recruitment. There was no difference in the incidence of acute rejection, or in graft or patient survival between the CS and MP groups. Median estimated glomerular filtration rate at 3 months following transplantation was significantly lower in the CS group compared with MP (CS 34 mL/min IQR 26-44 vs MP 45 mL/min IQR 36-60, P = 0.006), although there was no significant difference in estimated glomerular filtration rate between CS and MP at 12 months posttransplant. CONCLUSIONS: This study is underpowered, which limits definitive conclusions about the use of MP, as an alternative to static CS. It did not demonstrate that the use of MP reduces the incidence of delayed graft function in donation after circulatory death kidney transplantation.

On-surface condensation of low-dimensional benzotriazole-copper assemblies.

The reactivity of benzotriazole with copper on a gold surface has been studied by a combination of surface sensitive methods with support from DFT (density functional theory) calculations. For some time benzotriazole has been known to enhance the corrosion resistance of copper at the monolayer level, although the exact mechanism is still a matter of discussion and disagreement in the literature. A single crystal Au(111) surface allows evaluation of the interaction of weakly physisorbed, intact benzotriazole molecules with copper atoms dosed to sub-monolayer amounts. These interactions have been characterised, in the temperature range ca. 300-650 K, by scanning tunnelling microscopy, high resolution electron energy loss spectroscopy and synchrotron-based X-ray photoemission spectroscopy and near-edge X-ray absorption fine structure studies. Supporting DFT calculations considered the stability of isolated, gas-phase, benzotriazole/Cu species and their corresponding spectroscopic signature at the N K absorption edge. In agreement with previous investigations, benzotriazole physisorbs on a clean Au(111) surface at room temperature forming a hydrogen-bonded network of flat-lying BTAH molecules, relatively weakly bonded to the underlying gold surface. However, in the presence of co-adsorbed copper atoms, proton removal from the molecules leads to species better described as BTA- interacting directly with Cu atoms. In these situations the molecules adopt a more upright orientation and Cu(BTA)2 and -[Cu(BTA)]n- species are formed, depending on temperature and coverage of the adsorbed species. These species are stable to relatively high temperatures, 550-600 K.

Development of a Prognostic Model That Predicts Survival After Pancreaticoduodenectomy for Ampullary Cancer.

OBJECTIVES: The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS: Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS: The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS: Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: Insights into the physiological role of endogenous heparin.

The properties of commercially prepared heparin as an anticoagulant and antithrombotic agent in medicine are better understood than is the physiological role of heparin in its native form, where it is uniquely found in the secretory granules of mast cells. In the present study we have isolated and characterised the glycosaminoglycans (GAGs) released from degranulating rat peritoneal mast cells. Analysis of the GAGs by NMR spectroscopy showed the presence of both heparin and the galactosaminoglycan dermatan sulphate; heparinase digestion profiles and measurements of anticoagulant activity were consistent with this finding. The rat peritoneal mast cell GAGs significantly inhibited accumulation of leukocytes in the rat peritoneal cavity in response to IL-1ß (p < 0.05, n = 6/group), and inhibited adhesion and diapedesis of leukocytes in the inflamed rat cremasteric microcirculation in response to LPS (p < 0.001, n = 4/group). FTIR spectra of human umbilical vein endothelial cells (HUVECs) were altered by treatment of the cells with heparin degrading enzymes, and restored by the addition of exogenous heparin. In conclusion, we have shown that rat peritoneal mast cells contain a mixture of GAGs that possess anticoagulant and anti-inflammatory properties.

Urgent Multivisceral Transplantation for Widespread Splanchnic Ischemia.

BACKGROUND: Multivisceral transplantation (transplantation of the stomach, intestine, liver, and pancreas) is usually undertaken as a semi-elective procedure after thorough assessment in patients who have intestinal failure with cirrhosis, cirrhosis with portomesenteric venous thrombosis, or tumors such as desmoids involving the liver and mesentery. STUDY DESIGN: Data were collected prospectively from the time of referral and held in a central database. We used it to report the first cases of urgent multivisceral transplantation (MVT) in patients with widespread splanchnic ischemia (occlusion of the celiac axis and superior mesenteric artery) resulting in small bowel infarction and hepatic failure. RESULTS: Three women (ages 33, 48, and 50 years) were referred to our center with superior mesenteric artery and celiac axis occlusion. All other modes of treatment had been considered and/or attempted. After transfer to our institution, all patients were assessed, urgently listed, and underwent transplantation in 10, 7, and 5 days. Two patients are still alive after 2 years and 1 died at 8 months from multiorgan failure due to infections and graft vs host disease. CONCLUSIONS: Treatment options for patients presenting with widespread splanchnic ischemia with hepatic and intestinal failure/infarction were previously limited to salvage surgery and attempted revascularization. In situations in which these failed, the only previous option would have been palliation. In selected cases, we propose that urgent multivisceral transplantation should be considered as a life-saving treatment. This represents a previously unreported indication for MVT.

Salvage pancreaticoduodenectomy after complete response to chemoradiotherapy for a previously unresectable pancreatic adenosquamous carcinoma: a case report.

Pancreatic cancer is known for its typically late presentation and poor survival rates, with overall 5-year survival of less than 5%. The role of chemotherapy alone or with radiotherapy in the management of locally advanced tumors continues to be an area of debate.We report a case of locally advanced, pancreatic adenosquamous carcinoma that was initially deemed unresectable intraoperatively. Nonetheless, the tumor was resected after radiological response to gemcitabine-capecitabine chemoradiotherapy regimen similar to the Selective Chemoradiation in Advanced LOcalised Pancreatic cancer trial. Histological examination revealed complete pathological response with extensive fibrosis (ypT0 N0). On 12-month follow-up CT, a single liver lesion in the left lateral segment was identified and confirmed to be a metastasis with cytological diagnosis via EUS and FNA. The disease remained stable and confined to the solitary hepatic metastasis after further gemcitabine chemotherapy. Therefore, a further successful resection was performed.The 2 main strategies for the management of locally advanced unresectable pancreatic cancer are chemotherapy induction followed by consolidation chemoradiotherapy or chemotherapy alone, with conflicting published evidence. Evidence for the optimal management of the rare histological type of adenosquamous carcinoma is scant. We present a case of such tumor with a complete pathological response to chemoradiotherapy. The results of future studies in the area are eagerly awaited.

Negative predictive value of drain amylase concentration for development of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the major source of morbidity following pancreaticoduodenectomy. A predictive indicator would be highly advantageous. One potential marker is drain amylase concentration (DAC). However, its predictive value has not been fully established. METHODS: 405 patients undergoing pancreaticoduodenectomy at our centre over a 10 year period were reviewed to determine the value of DAC as a predictive indicator for the development of POPF. RESULTS: POPF developed in 58 patients (14%). These patients suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR: 5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal-adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post-operatively were significantly higher in those developing POPF, but with significant overlap. ROC curves revealed optimal threshold values for differentiating POPF and non-POPF patients. A DAC°<°1400 U/ml on day 1 and <768 U/ml on day 2, although having a poor positive predictive value (32-44%), had a very strong negative predictive value (97-99%). CONCLUSION: Our data suggest that post-operative DAC below the determined optimal threshold values on day 1 and 2 following pancreaticoduodenectomy carries high negative predictive value for POPF development and identifies patients in whom early drain removal, and enhanced recovery may be considered, with simultaneous assessment of operative and clinical factors.

Outcomes following liver trauma in equestrian accidents.

BACKGROUND: Equestrian sports are common outdoor activities that may carry a risk of liver injury. Due to the relative infrequency of equestrian accidents the injury patterns and outcomes associated with liver trauma in these patients have not been well characterized. METHODS: We examined our experience of the management of equestrian liver trauma in our regional hepatopancreaticobiliary unit at a tertiary referral center. The medical records of patients who sustained liver trauma secondary to equestrian activities were analysed for parameters such as demographic data, liver function tests, patterns of injury, radiological findings, the need for intervention and outcomes. RESULTS: 20 patients sustained liver trauma after falling from or being kicked by a horse. The majority of patients were haemodynamically stable on admission. Alanine transaminase (ALT) levels were elevated in all patients and right-sided rib fractures were a frequently associated finding. CT demonstrated laceration of the liver in 12 patients, contusion in 3 and subcapsular haematoma in 2. The right lobe of the liver was most commonly affected. Only two patients required laparotomy and liver resection; the remaining 18 were successfully managed conservatively. CONCLUSIONS: The risk of liver injury following a horse kick or falling off a horse should not be overlooked. Early CT imaging is advised in these patients, particularly in the presence of high ALT levels and concomitant chest injuries such as rib fractures. Despite significant liver trauma, conservative management in the form of close observation, ideally in a high-dependency setting, is often sufficient. Laparotomy is only rarely warranted and associated with a significantly higher risk of post-operative bile leaks.

Adsorption of a dihydro-TTF derivative on Au(111) via a thiolate complex bonding to gold adatoms.

A dihydro-TTF derivative with four acetyl-protected thiol ligands was synthesised and adsorbed on Au(111) under UHV conditions. Scanning Tunnelling Microscopy (STM) and Infrared (IR) spectroscopy show that self-organised structures are formed following annealing to 333 K, with each pair of bidentate thiolate ligands bonding to a single gold adatom in a S-Auad-S complex. Due to the lack of a direct orbital overlap between the dihydro-TTF moieties and the surface, relatively little charge transfer between TAT-TTF and the gold surface occurs.

Improved long-term survival after resection of colorectal liver metastases following staging with FDG positron emission tomography.

BACKGROUND AND OBJECTIVES: Actual long-term survival of patients with colorectal liver metastases staged by PET CT has not been reported. Objectives were to investigate whether PET CT staging results in actual improved long-term survival, to examine outcome in patients with 'equivocal' PET CT scans, and those excluded from hepatectomy by PET CT. METHODS: A retrospective analysis of patients undergoing hepatectomy for colorectal liver metastases between March 1998 and September 2008. RESULTS: Overall 5- and 10-year survival was 44.8% and 23.9%. PET CT staging resulted in management changes in 23% of patients. PET CT staged patients showed significantly better survival than those staged by CT alone at 3 years (79.8% vs. 54.1%) and at 5 years (54.1% vs. 37.3%) with median survivals of 6.4 years versus 3.9 years (log rank P = 0.018). Patients with equivocal PET CT scans showed worse median survival than those with favourable PET CT (log rank P = 0.002), but may include a subpopulation whose prognosis trends towards a more favourable outcome than those excluded from liver resection by PET CT, whose median survival remains limited to 21 months. CONCLUSIONS: Staging of patients with colorectal liver metastases by PET CT is associated with significantly improved actual long-term survival, and provides valuable prognostic information which guides surgical and oncological treatments.

Initial stages of benzotriazole adsorption on the Cu(111) surface.

Benzotriazole (BTAH) has been used as a copper corrosion inhibitor since the 1950s; however, the molecular level detail of how inhibition occurs remains a matter of debate. The onset of BTAH adsorption on a Cu(111) single crystal was investigated via scanning tunnelling microscopy (STM), vibrational spectroscopy (RAIRS) and supporting DFT modelling. BTAH adsorbs as anionic (BTA(-)), CuBTA is a minority species, while Cu(BTA)2, the majority of the adsorbed species, form chains, whose sections appear to diffuse in a concerted manner. The copper surface appears to reconstruct in a (2 × 1) fashion.

Preoperative comorbidity correlates inversely with survival after intestinal and multivisceral transplantation in adults.

We investigated the relationship between preoperative comorbidity and postoperative survival after intestinal transplantation. Each patient received a score for preoperative comorbidity. Each comorbidity was given a score based on the degree it impaired function (score range 0-3). A total score was derived from the summation of individual comorbidity scores. Patients (72 adults (M : F, 33 : 39)) received an isolated intestinal graft (27) or a cluster graft (45). Mean (standard deviation) survival was 1501 (1444) days. The Kaplan-Meier analysis revealed a significant inverse association between survival and comorbidity score (logrank test for trend, P < 0.0001). Patients grouped into comorbidity scores of 0 and 1, 2 and 3, 4 and 5, 6, and above had hazard ratios (95% confidence intervals) for death (compared to group 0 + 1), which increased with comorbidity scores: 1.945 (0.7622-5.816), 5.075 (3.314-36.17), and 13.77 (463.3-120100), respectively, (P < 0.0001). Receiver-operator curves at 1, 3, 5, and 10 years postoperative had "C" statistics of 0.88, 0.85, 0.88, and 0.92, respectively. When evaluating patients for transplantation, the degree of comorbidity should be considered as a major factor influencing postoperative survival.

Laparoscopic adrenalectomy: auditing the 10 year experience of a single centre.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard for benign adrenal resection, and has been performed at our centre since 2000. We present a retrospective audit of our ten-year experience, and discuss the learning curve. METHODS: Creating a retrospective database, clinical and outcome data were collected for all resections performed over a ten-year period (2000-2010). Patients were chronologically divided into an 'early' (first 40 cases) and 'late' (subsequent cases) group to provide an insight into the learning curve. RESULTS: Over this period, 134 laparoscopic resections were performed, predominantly for benign adenomas (80.3%), with 48% of patients having primary hyperaldosteronism. There was almost equal sex distribution and mean age was 50.2 years, with a median BMI of 28.2. The mean operating time for left and right procedures were 127 and 124 min respectively, with 56.7% of resections being left sided. Our rate of conversion to open was 3.9%. Median length of stay was 4 days post-operatively. There was no mortality and 8.7% patients experienced a surgical complication. Analysis of the grouped data demonstrated a statistically significant reduction in open conversion rate (p = 0.017) and operative time (p = 0.011) in the 'late' group. Among the two groups there was no statistically significant difference in the length of stay and surgical complication rate. All results were comparable to published series in the literature. CONCLUSION: LA has proven to be a safe procedure with a low complication rate at our centre. Our data provide evidence that operative time and conversion rate improves with experience.

An ordered organic radical adsorbed on a Cu-doped Au(111) surface.

The tri-para-carboxylic polychlorotriphenylmethyl radical adsorption on a Cu/Au(111) surface has been investigated in ultra-high vacuum environment. The presence of copper favours the formation of metal-organic assemblies, which are analysed using scanning tunnelling microscopy (STM) and high resolution electron energy loss spectroscopy (HREELS). DFT methods indicate that the unpaired electron survives after adsorption, thus creating systems which could be regarded as potential candidates for spintronics applications.

Primary hyperoxaluria Type 1: indications for screening and guidance for diagnosis and treatment.

Primary hyperoxaluria Type 1 is a rare autosomal recessive inborn error of glyoxylate metabolism, caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase. The disorder results in overproduction and excessive urinary excretion of oxalate, causing recurrent urolithiasis and nephrocalcinosis. As glomerular filtration rate declines due to progressive renal involvement, oxalate accumulates leading to systemic oxalosis. The diagnosis is based on clinical and sonographic findings, urine oxalate assessment, enzymology and/or DNA analysis. Early initiation of conservative treatment (high fluid intake, pyridoxine, inhibitors of calcium oxalate crystallization) aims at maintaining renal function. In chronic kidney disease Stages 4 and 5, the best outcomes to date were achieved with combined liver-kidney transplantation.

Direct histological processing of EUS biopsies enables rapid molecular biomarker analysis for interventional pancreatic cancer trials.

OBJECTIVE: Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen. METHODS: 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing. RESULTS: We found that direct formalin fixation significantly shortened the time required for diagnosis from 3.6 days to 2.9 days (p<0.05) by reducing the average time (140 vs 33 min/case) and number of slides (9.65 vs 4.67 slides/case) for histopathological processing. Specificity and sensitivity yielded comparable results between the two approaches (82.3% vs 77% and 90.9% vs 100%). Importantly, EUS-FNA histology preserved the tumour tissue architecture with neoplastic glands embedded in stroma in 67.89% of diagnostic cases compared to 27.55% with the standard cytological approach (p < 0.001). Furthermore, micro-core samples were suitable for molecular studies including the immunohistochemical detection of intranuclear Hes1 in malignant cells, and the laser-capture microdissection-mediated measurement of Gli-1 mRNA in tumour stromal myofibroblasts. CONCLUSIONS: Direct formalin fixation of pancreatic EUS-FNA micro-cores demonstrates superiority regarding diagnostic delay, costs, and specimen suitability for molecular studies. We advocate this approach for future investigational trials in pancreatic cancer patients.

Chiral Conformation at a Molecular Level of a Propeller-Like Open-Shell Molecule on Au(111).

A key stage in engineering molecular functional organizations is represented by controlling the supramolecular assembly of single molecular building blocks, tectons, into ordered networks. Here, we show how an open-shell, propeller-like molecule has been deposited under UHV conditions on Au(111) and its supramolecular organization characterized by scanning tunneling microscopy (STM). Racemic islands were observed at room temperature, and their chirality was imaged at the molecular level at low temperature. Modeling further suggests that the observed chirally alternating ordering dominated by intermolecular interactions is energetically favored. Electron paramagnetic resonance and ultraviolet photoemission spectroscopy evidences suggest that the supramolecular networks may preserve the open-shell character of the tecton. These results represent a fundamental step forward toward the engineering of purely organic spintronic devices.

Clinical impact of right accessory hepatic artery injury in deceased donor livers.

BACKGROUND: Right accessory hepatic artery (RAHA) injury at retrieval is a rare complication of deceased liver procurement. Arterial reconstruction is often required under these circumstances which could potentially increase the risk of hepatic artery thrombosis (HAT). The aim of this study is to investigate whether RAHA injury affects the incidence of HAT, early biliary complications, or 3-month graft and patient survival rates. METHODS: All adult liver transplants performed between 1994 and February 2007 at Addenbrooke's Hospital, Cambridge, UK were considered for inclusion in the study. Grafts were divided into three groups depending on the presence of RAHA and injury (Group 1: normal anatomy and single hepatic artery anastomosis; Group 2: RAHA requiring reconstruction; Group 3: RAHA injury requiring reconstruction). RESULTS: Eight hundred and forty-four liver transplants were included in the study (Group 1: 654 grafts; Group 2: 63 grafts; Group 3: 14 grafts). The incidence of HAT (Group 1, 2.9%; Group 2, 6.4%; Group 3, 14.3%) was significantly different between the three groups (P = 0.01); biliary complications at 3 months (Group 1, 7.1%; Group 2, 11.1%; Group 3, 7.1%) were not significantly different. Graft and patient survival at 3 months were significantly worse in Group 3 when compared with Group 2 (61.5 vs. 88.3%, P = 0.01; 81.8 vs. 98.2%, P = 0.02). CONCLUSION: This is the first study analysing the clinical impact of RAHA injury during liver procurement. We conclude that the use of liver grafts with RAHA injury does result in a higher HAT rate and is also associated with lower graft and patient survival rates at 3 months.