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The increasing demand for liver transplantation has led to considerable changes in characteristics of donors and recipients. This study evaluated the short- and long-term mortality of recipients with and without hepatocellular carcinoma (HCC) in the UK between 1997 and 2016.First-time elective adult liver transplant recipients in the UK were identified and four successive eras of transplantation were compared. Hazard ratios (HRs) comparing the impact of era on short-term (first 90 days) and longer-term (from 90 days to 5 years) mortality were estimated, with adjustment for recipient and donor characteristics.Some 1879 recipients with and 7661 without HCC were included. There was an increase in use of organs donated after circulatory death (DCD), from 0 per cent in era 1 to 35·2 per cent in era 4 for recipients with HCC, and from 0·2 to 24·1 per cent for non-HCC recipients. The 3-year mortality rate decreased from 28·3 per cent in era 1 to 16·9 per cent in era 4 (adjusted HR 0·47, 95 per cent c.i. 0·35 to 0·63) for recipients with HCC, and from 20·4 to 9·3 per cent (adjusted HR 0·44, 0·36 to 0·53) for those without HCC. Comparing era 4 with era 1, improvements were more marked in short-term than in long-term mortality, both for recipients with HCC (0-90 days: adjusted HR 0·20, 0·10 to 0·39; 90 days to 5 years: adjusted HR 0·52, 0·35 to 0·75; P = 0·043) and for non-HCC recipients (0-90 days: adjusted HR 0·32, 0·24 to 0·42; 90 days to 5 years: adjusted HR 0·52, 0·40 to 0·67; P = 0·024).In the past 20 years, the mortality rate after liver transplantation has more than halved, despite increasing use of DCD donors. Improvements in overall survival can be explained by decreases in short-term and longer-term mortality.La creciente demanda de trasplante hepático ha determinado cambios considerables en las características de los donantes y receptores. En este estudio, se evaluó la mortalidad a corto y a largo plazo de los receptores de trasplante hepático por carcinoma hepatocelular (hepatocelular carcinoma, HCC) y no-HCC en el Reino Unido entre 1997 y 2016. MÉTODOS: Se identificaron los receptores adultos de un primer trasplante hepático electivo en el Reino Unido y se compararon cuatro eras sucesivas de trasplante. Se estimaron los cocientes de riesgos instantáneos ajustados (adjusted hazard ratio, aHR) que comparaban el impacto de la era en la mortalidad a corto plazo (primeros 90 días) y a largo plazo (de 90 días a 5 años) ajustando por las características del receptor y del donante.Se incluyeron 1.879 receptores HCC y 7.661 receptores no-HCC. Hubo un aumento en el uso de donantes después de parada cardíaca (donors following circulatory death, DCD) del 0% en la era 1 al 35,2% en la era 4 para los receptores HCC y del 0,2% al 24,1% para los receptores no-HCC. La mortalidad a los 3 años disminuyó de 28,3% en la era 1 a 16,9% en la era 4 (aHR 0,47, i.c. del 95% 0,35-0,63) para receptores HCC y de 20,4% a 9,3% (aHR 0,44, 0,36-0,53) para receptores no-HCC. Comparando la era 1 y la era 4, las mejoras en la mortalidad a corto plazo fueron más marcadas que en la mortalidad a largo plazo, tanto para receptores HCC (aHR 0-90 días 0,20, 0,10-0,39; 90 días-5 años 0,52, 0,35-0,75; P =舁0,04) como para receptores no-HCC (aHR 0-90 días 0,32, 0,24-0,42; 90 días-5 años 0,52, 0,40-0,67; P =舁0,02). CONCLUSIÓN: En los últimos 20 años, la mortalidad después del trasplante de hígado se ha reducido a más de la mitad, a pesar del uso cada vez mayor de donantes DCD. Las mejoras en la supervivencia global pueden explicarse por la disminución de la mortalidad a corto y largo plazo.

Multiple intrahepatic arterio-portal fistulas are rare. The majority are isolated and occur secondary to liver trauma including iatrogenic interventions such as liver biopsy. Post–liver transplantation 18 cases have been reported, all secondary to an interventional radiological procedure. We report multiple bi-lobar arterio-portal fistulas in a liver transplant recipient recognized 1 year after transplantation. The donor died due to intracerebral bleeding following blunt head and abdominal trauma. In the present case, the etiology is not very clear. The patient was managed conservatively and to date has not required intervention.

INTRODUCTION: A bronchobiliary fistula (BBF) following liver directed therapy (resection/ablation) is a rare complication in which an abnormal communication between the biliary tract and bronchial tree is formed. This case report describes the successful management of a persistent BBF following multiple liver wedge resections and microwave ablation in a patient with a metastatic neuroendocrine tumour of the terminal ileum. CASE HISTORY: A 69-year-old man presented with unexplained weight loss and was subsequently diagnosed with a neuroendocrine tumour of the terminal ileum and liver metastasis. Following elective right hemicolectomy and multiple bilobar liver wedge resections combined with liver microwave ablation, he developed an early bile leak. A month later, a right subphrenic collection was identified and four months following surgery, biloptysis was noted. Numerous attempts with endoscopic retrograde biliary drainage (ERBD) failed to achieve sufficient drainage. The patient was treated successfully with endoscopic injection of a mixture of Histoacryl(®) glue (B Braun, Sheffield, UK) and Lipiodol(®) (Guerbet, Solihull, UK). There was no evidence of the BBF one year following intervention. CONCLUSIONS: This novel approach for persistent BBF management using endoscopic Histoacryl(®) glue embolisation of the fistula tract should be considered either as an adjunct to ERBD or when biliary tract decompression by drainage and/or sphincterotomy fails, prior to proceeding with surgical interventions.

3559Background: The New EPOC study demonstrated a shorter overall survival (OS) with the addition of cetuximab to chemotherapy for operable colorectal liver metastasis. The combination of a liver r...

Liver transplantation remains the treatment of choice for patients with end-stage liver disease. However, allograft availability continues to be a problem, and extending the criteria for organ acceptance is key. Deceased donors after electrical accidents, as well as electricity-traumatized allografts, are not common but should be considered suitable. This study describes 2 cases of heart-beating organ donors with electrical injury to the liver. In 1 case, the electric shock was the cause of death; in the second case, the injury was caused by defibrillation at organ procurement. Both allografts had sustained sizeable electrical injury, and both resulted in excellent early posttransplant outcomes. These cases demonstrate that electrocution is not a contraindication to donation and that electricity-traumatized allografts may remain transplantable after careful assessment. Education of all staff in the management of such donors can optimize utility of such allografts.

Completion techniques in the Middle Bakken formation have evolved over the years, with cemented Plug & Perf becoming the most common technique in recent years. It relies on stimulation of multiple clusters of perforations, normally 3-5, at one time. As previously demonstrated by multiple papers (SPE 173363, 144326, 167726, 174943) up to 40% of the perforation clusters remain un-stimulated. A novel engineered diversion workflow was implemented in 687 intervals of 20 Williston Basin wells. The purpose of this workflow is to increase cluster efficiency by stimulating the previously un-stimulated clusters. Results from each step down test and engineered workflow evaluation indicate increased cluster efficiency by up to 80%. Moreover, the success criteria for diversion pressure (1000 psi) was achieved on 81% of the intervals. Due to the success of these wells, this workflow has now become the standard diversion technique for one major operator in the Williston Basin.

In treating hepatitis C infection, identification of reliable markers predicting virological non-response appear central to improving outcome and to prompting changes in dynamic treatment approaches. The interrelationship of ribavirin (RBV) concentrations and laboratory variables with clinical outcomes was evaluated in HCV patients treated with ribavirin, and with or without early direct acting antivirals (DAA). Correlations between RBV concentration, laboratory variables (haemoglobin, absolute lymphocyte, platelet and neutrophil counts, serum creatinine and hepatitis C viral load) and patients’ characteristics associated with sustained virological response (SVR) were investigated using multivariate analysis. The 76 patients studied all received interferon (INF) and RBV, with 37 additionally given Boceprevir or Telaprevir. Significant correlations were noted between week 1 RBV concentration and subsequent total exposure at weeks 2, 4 and 12 (P 30 g/L (week 8) experienced higher SVR rates (P 30 g/L. Six factors were predictive of SVR in univariate analysis, and three in multivariate analysis. There is an association between SVR and absolute lymphocyte count, IL-28B CC genotype, and HCV-RNA load fall at week 1 (>80 %) or week 2 (>90 %) in HCV patients treated with INF/RBV and early DAA.

Small-for-size syndrome (SFSS) is a clinical syndrome described following liver transplantation (LT) and extended hepatectomy. New evidence has emerged documenting the importance of preoperative evaluation of functional liver mass, liver quality, influence of portal hypertension, and variations in surgical technique to improve outcome.SFSS is characterized by postoperative coagulopathy and liver dysfunction due to insufficient functional liver mass. Recent radiologic advances allow accurate preoperative estimation of total, graft, and remnant liver volume (RLV). In adult-to-adult living donor liver transplantation (LDLT), a graft-to-recipient body weight ratioor = 0.8% or graft weight ratioor = 30% are important to avoid SFSS. Minimal functional RLV following extended hepatectomy isor = 25% in a normal liver, andor = 40% with preoperative liver dysfunction. Preoperative portal vein or hepatic artery embolization to increase RLV and function after extended hepatectomy, and the increasing use of parenchymal-sparing segmental resections have improved outcome. In LT, the evolving use of split livers, LDLT and marginal grafts has resulted in increased recognition of SFSS. This has led to a renewed interest in defining the pathophysiology, and the development of new surgical techniques to reduce its incidence.Current radiologic imaging techniques can be used to evaluate liver volume and the risk of SFSS following LT and extended hepatectomy. Intraoperative techniques to predict postoperative dysfunction are emerging, and may be helpful in directing the use of pre-emptive surgical interventions. The future lies in the development of perioperative liver protection and support in predicted SFSS, and enhancement of healthy liver regeneration.

Cox17 is an essential protein in the assembly of cytochrome c oxidase within the mitochondrion. Cox17 is implicated in providing copper ions for formation of CuA and CuB sites in the oxidase complex. To address whether Cox17 is functional in shuttling copper ions to the mitochondrion, Cox17 was tethered to the mitochondrial inner membrane by a fusion to the transmembrane domain of the inner membrane protein, Sco2. The copper-binding domain of Sco2 that projects into the inter-mitochondrial membrane space was replaced with Cox17. The Sco2/Cox17 fusion protein containing the mitochondrial import sequence and transmembrane segment of Sco2 is exclusively localized within the mitochondrion. The Sco2/Cox17 protein restores respiratory growth and normal cytochrome oxidase activity in cox17Delta cells. These studies suggest that the function of Cox17 is confined to the mitochondrial intermembrane space. Domain mapping of yeast Cox17 reveals that the carboxyl-terminal segment of the protein has a function within the intermembrane space that is independent of copper ion binding. The essential C-terminal function of Cox17 maps to a candidate amphipathic helix that is important for mitochondrial uptake and retention of the Cox17 protein. This motif can be spatially separated from the N-terminal copper-binding functional motif. Possible roles of the C-terminal motif are discussed.

Hormone replacement therapy (HRT) has been used to prevent osteoporosis in postmenopausal women. However, HRT may increase the incidence of some cancers and has other side effects. There is considerable interest in dietary alternatives that include the consumption of soy and isoflavones derived from soy. The purpose of this study was to determine the effects of dietary soy protein on bone density, formation and resorption in cortical and cancellous bone in aged, ovariectomized rats. Specific emphasis was placed on indices of bone formation. Rats were assigned to the following groups: baseline; sham surgery + casein diet; sham + soy protein diet; ovariectomy (Ovx) + casein diet; Ovx + soy protein diet. The diets were fed for 3 mo. The Ovx Soy group had a greater bone mineral density (BMD) than the Ovx Casein group. There was a trend (P < 0.10) for greater periosteal bone formation rates in the Sham Soy compared with the Sham Casein group. In the Ovx Soy group, indices of endocortical bone formation were greater than those of the Ovx Casein group. There were no significant differences in resorption indices or endochondral growth (bone elongation) rates with soy in either the Sham or Ovx groups. In cancellous bone, the double-labeled surface and bone formation rates were greater in the Ovx Soy group than in the Ovx Casein group. These results show that dietary soy had a beneficial effect on the preservation of BMD associated with estrogen deficiency bone loss in aged rats. These data also show that at the tissue level, soy functions in a manner different from estrogen by increasing or sustaining elevated bone formation rates after ovariectomy.

Lithiation of 4,5-bis(methylsulfanyl)-TTF 9, 4,5-(ethylenedisulfanyl)-TTF 10, 4,5-dimethyl-TTF 11 and 4,5,5′-trimethyl-TTF 12 (TTF=tetrathiafulvalene) followed by reaction with methyl isothiocyanate affords the corresponding (N-methylthio-carbamoyl)-TTF derivatives 14–17, respectively, in 54–70% yields. These new TTF derivatives display a broad intramolecular charge-transfer band in their UV–VIS spectra arising from conjugation between the donor TTF ring and the acceptor N-methylthiocarbamoyl moiety. Steric hindrance between the adjacent N-methylthiocarbamoyl and methyl substituents in 17 causes a marked hyposchromic shift in this band (λmax 395 nm) compared to compounds 14–16 (lambda;max 435–467 nm). Consistent with the electron-withdrawing properties of the N-methylthiocarbamoyl substituent, its attachment to the TTF ring raises slightly the oxidation potential of the system. Charge transfer complexes of these donors and (N-methylthiocarbamoyl)-TTF 2 with 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) and salts with bromide anions are reported, some of which have high room temperature conductivity values. The X-ray crystal structures are presented for 16, 17 and the salts 2·Br, 14·TCNQ and (17)2·20. The structure of 16 comprises orthogonal dimers (kappa packing) while in the structure of 17 individual molecules are orthogonal to each other. There is weak intermolecular hydrogen bonding in both 16 and 17. In the structure of 2·Br, the radical cations 2+· are almost planar and they form an infinite stair-like stack of dimers, with bromide anions situated between the stacks, and linked with the cation by a strong N–H‥Br bond. The structure of 14·TCNQ comprises mixed ‥DDAADD‥ stacks; the N-methylthiocarbamoyl group engages in an interstack N–H‥N bond with a TCNQ anion. Analysis of the bond lengths in the structure suggests that there is partial charge transfer from 14 to TCNQ. In the structure of (17)2·20 molecules form mixed ‥DDADDA‥ stacks and analysis of bond lengths suggests that there is only a small degree of charge transfer from donor to acceptor. The geometries of compounds 2, 14, 16, 17 were optimised using the PM3 semi-empirical method and the results compare favourably with the X-ray structural data.

The rhodium (triphenylphosphine)(ethene) complex [Rh(η5-C5H5)(PPh3)(C2H4)], was synthesized by reaction of [{Rh(C2H4)2Cl}2] with triphenylphosphine and thallium cyclopentadienide. Like in [Rh(η5-C5H5)(PMe3)(C2H4)], the co-ordinated ethene ligand may be displaced photochemically. Photoreaction of [Rh(η5-C5H5)(PPh3)(C2H4)] with SiR3H (R = Pri or Et) and hexafluorobenzene yielded [Rh(η5-C5H5)(PPh3)(SiR3)H] and [Rh(η5-C5H5)(PPh3)(η2-C6F6)], respectively. Oxidative addition of the C–H bonds of partially fluorinated arenes, C6F5H and 1,3-C6F2H4, was demonstrated by NMR spectroscopy to result in formation of [Rh(η5-C5H5)(PPh3)(R)H] (R = C6F5 or 2,6-C6F2H3). Oxidative addition of benzene may be detected following photolysis in benzene–thf mixtures at 233 K, but the product decomposes on warming. The molecular structure of [Rh(η5-C5H5)(PPh3)(SiPri3)H] has been determined crystallographically. The disorder of the isopropyl groups was modelled with two orientations of the SiPri3 with equal occupancies. The Rh–Si bond length is 2.386(2) A, the first example of measurement of such a distance at cyclopentadienyl rhodium(III).

We report the use of fluconazole to control primary immunosuppressive management with tacrolimus in a 9-year-old liver transplant recipient. Progressive increases in the doses of both cyclosporin (up to 20 mg/kg/day) and, subsequently, tacrolimus (up to 60 mg/day) failed to maintain immunosuppressive levels of both agents. After excluding poor compliance, drug interactions and analytical problems and identifying poor bioavailability ( < 2.6 %) and rapid clearance (4.2 l/h), fluconazole (100 mg/day) was initiated to inhibit tacrolimus metabolism and consistent therapeutic blood levels of tacrolimus were achieved. However, graft function had deteriorated irrevocably and retransplantation was performed. Simultaneous use of tacrolimus (5 mg/day) and fluconazole (100 mg/day) maintained immunosuppression after transplantation. Three weeks later, obstruction of the Roux loop caused deteriorating liver function and tacrolimus blood levels fell. After correction at laparotomy, stabilisation was achieved and discharge was possible on 5 mg tacrolimus b. i. d. plus fluconazole (100 mg).

The synthesis and photochemistry of a series of new rhodium complexes of 1,3-divinyl-1,1,3,3-tetramethyldisiloxane, (CH2CHSiMe2)2O, and its disilazane analogue (CH2CHSiMe2)2NH are reported. The divinyldisiloxane or divinyldisilazane ligands in (η5-C5R5)Rh[η4-(CH2CHSiMe2)2X] (R = H, Me; X = O, NH; type 1 complexes) are coordinated through the vinyl groups as for a diene. The structure of (η5-C5Me5)Rh[η4-(CH2CHSiMe2)2O] was established crystallographically. The two coordinated double bonds are arranged with their Si substitutents in a cis orientation with respect to the metal. The strain in the structure is suggested by the scissor geometry of the vinyl CC bonds relative to the C5 plane of the ring, combined with unequal Rh-C and CC bond lengths. Photolysis of (η5-C5R5)Rh(C2H4)2 (R = H, Me) in the presence of (CH2CHSiMe2)2X (X = O, NH) results in the formation of the complexes of type 1, together with an isomer in which the substituents on the coordinated CC bonds are oriented trans at rhodium (2) and speci...

The complications and outcome associated with late CMV infection and disease on the graft are poorly characterized in PLT recipients. We studied the overall incidence, risk factors, and outcome of late CMV infection and disease (infection 6 months after transplant) in 180 PLT recipients admitted between 2008 and 2011 at the King's College Hospital. Antiviral prophylaxis of intravenous ganciclovir was given only to the D+R- group starting at day 7 post-transplant. The remaining groups (D-R+, D+R+, and D-R-) received pre-emptive therapy when they have CMV viremia above cut-off value and treatment for symptomatic CMV infection. The overall incidence of late CMV infection and disease was 9.4% (19/180) and 14.5% (19/130) in D+R-, D-R+, D+R- groups. The D-R+ group had the highest incidence of hepatitis (37.5%) and significantly increased incidence of CMV disease, and single and multiple acute rejection episodes when compared to the D+R- group, which received prophylaxis. The late CMV infection and disease in pediatric LT recipients was comparable to adult LT recipients despite variable duration of antiviral prophylaxis. Our results show that D-R+ group had highest rate of hepatitis and rejection episodes, associated with high morbidity, and should be considered for antiviral prophylaxis.

Mink are known to be very sensitive to the toxic effects of planar polychlorinated biphenyls (pPCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs), collectiv...

The synthesis of the new mono- and di-functionalized tetrathiafulvalene (TTF) derivatives 4, 5 and 12–15 is reported. Compounds 4 and 5 have been studied in detail: their single crystal X-ray structures are reported and theoretical calculations at both semiempirical and ab initio levels have been performed. The TTF moiety in the crystal of 4 is folded, whereas in the crystal of 5 it is essentially planar. In the crystal structure of 4 the molecules related via an inversion centre form close dimers which pack in a severely distorted kappa-arrangement. Molecules of 5 assemble into uniform stacks with TTF moieties overlapping the side chains of adjacent molecules. Calculated geometries are in good agreement with the X-ray data, and the distortion from planarity in the crystal of 4 can be explained by nonbonding interactions between the amide substituent and the TTF rings of adjacent molecules. Evidence for intramolecular charge-transfer from the TTF ring to the electron-withdrawing amide and ester substituents of 4 and 5, respectively, is provided by UV-VIS spectroscopy in solution, analysis of the bond lengths in the crystal structure, and by theoretical calculations.

The increasing role of MQ-1 Predator aircraft in support of intelligence, surveillance, reconnaissance and weapons deployment operations has resulted in the need to increase the number of fully trained pilots. To date, there are no published studies assessing the cognitive functioning of MQ-1 Predator pilots despite the important role these operators have in current unmanned U.S. Air Force (USAF) aviation. To partially fill the gap in the literature, this study obtained comprehensive computer-based intelligence testing (Multidimensional Aptitude Battery-II) and neuropsychological screening (MicroCog) on USAF MQ-1 Predator nonrated pilot training candidates who passed the initial remotely piloted aircraft (RPA) flying screening course (n=108), nonrated training candidates who failed training (n=52), as well as USAF rated pilot training candidates who cross-trained to the MQ-1 Predator from manned airframes (n=157). The results of the study revealed nonrated pilot training candidates performed in the high average to superior range on a measure of intelligence. Nonrated pilot training candidates who passed training scored higher on measures of spatial analyses/reasoning, memory for novel spatial arrangements, general visual reasoning, visual construction, general executive reasoning, and general information processing accuracy when compared with nonrated pilot training candidates who failed training. Furthermore, nonrated pilot training candidates who passed training performed substantially higher on measures of spatial analyses/ reasoning, memory for novel spatial arrangements, visual reasoning, general information processing accuracy, and cognitive proficiency (a combination and accuracy of speed of information processing) in comparison to rated pilots who cross-trained from a manned airframe. The results of the study provide helpful normative data on cognitive and neuropsychological aptitudes that distinguish nonrated pilots who pass the initial RPA flying screening

The majority of transplant centers around the world face an ethical debate whether to retransplant a young non-adherent patient. Non-adherence to lifelong immunosuppressants presents a significant risk for graft loss, yet rates remain consistently high. Despite a number of these patients presenting for retransplantation, there is little evidence to guide professionals in their decision-making. This paper aims to provide such guidance, by systematically reviewing the existing outcome data for retransplantation in patients who are known to be non-adherent to their immunosuppressants. This review searched for original papers that addressed retransplantation of a solid organ and included quantitative data on adherence or graft function. Only one original research paper was found to meet the inclusion criteria. This paper is reviewed, and details of the protocol to determine eligibility for retransplantation are summarized. The findings are discussed within the ethical context that transplant professionals work within, and the arguments for and against retransplantation are considered. The need for effective integration of adherence management into routine practice is highlighted, with an emphasis on reliable measurement of adherence throughout the patient's life. Examples of good practice are discussed, favoring prevention over cure.

A range of alkylthionitroso and arylthionitroso compounds have been generated by thermal fragmentation of N-trimethylsilyl-N-chlorothioalkyl(aryl)amine precursors, and intercepted by reaction with dimethylbutadiene to afford Diels-Alder and ene adducts.

Molecular dynamics of a main chain thermotropic liquid crystal polymer in the smectic A phase has been investigated using multipulse dynamic nuclear magnetic resonance (NMR) techniques. Transverse deuteron spin relaxation times T2ECP from quadrupole echo pulse trains (modified Carr–Purcell–Meiboom–Gill sequence) measured for deuterons in the aromatic rings of the mesogenic units are obtained as a function of pulse spacing τ sample orientation θN, and temperature. Just below the nematic–smectic A phase transition, the relaxation times exhibit a linear dispersion regime T2ECP ∼ τ−1 consistent with smectic director fluctuations. At lower temperatures, the dispersion step gradually disappears, indicating that faster molecular motions are the dominant transverse relaxation process. The observed anisotropy in T2ECP, measured at short pulse spacings, approximately follows the (sin4θN)−1 dependence expected for axial diffusion in a highly ordered medium. Analysis of the experiments is achieved employing a density...

A series of new N-(arylaminosulfanyl)- and N-(heteroarylaminosulfanyl)-phthalimide derivatives 3i–m and 3o–r, has been prepared by reaction of chlorosulfanylphthalimide with the trimethylsilyl derivative of the appropriate arylamine or heteroarylamine. On treatment with triethylamine at room temperature, most of these compounds 3 fragment to yield transient thionitroso species, Ar-NS and Het–NS, 4, which have been intercepted, generally in good yield, with conjugated dienes (2,3dimethylbuta-1,3-diene, isoprene, chloroprene and penta-1,3-diene) to yield cyclic 1,2-thiazine Diels–Alder adducts, and with alkenes (1-methylcyclohexene, α-pinene and β-pinene) to yield acyclic ene adducts. Competitive Diels–Alder and ene addition is observed with dimethylbutadiene and isoprene. The regiochemistry of addition of unsymmetrical dienes to thionitroso species has been elucidated. Sulfilimine 24 rearranges quantitatively to the dihydrothiophene derivative 27, thereby excluding compounds 24 as intermediates in the formation of 1,2-thiazine adducts 5.

Introduction Local haemostatic agents are used for the control of surgical haemorrhage when standard techniques are inadequate, but there are few studies of these products in children. Patients and methods This was a prospective, open-label study in which children (aged 4 weeks to 6 years) undergoing liver resection with or without segmental liver transplantation were treated with TachoSil, a collagen patch coated with a dry layer of human fibrinogen and human thrombin, if minor (i. e., oozing) or moderate bleeding was present after primary haemostatic treatment. Time to haemostasis after TachoSil application was the primary endpoint. Safety was assessed by adverse events (AEs), including post-operative infections, symptoms of graft rejection and re-operations. Results Enrolment was stopped early after 16 children had entered the study. 13 children underwent whole liver resection and transplantation and 3 patients underwent segmental resection. Satisfactory haemostasis was achieved in 13 children (81.3%; 95% CI: 61.8-100%) at 3 min and in 1 child at 8 min. Occurrence of AEs was as expected, with most being known complications of the underlying disease, surgical procedure, or use of immunosuppressive medication. No AEs were considered to be related to the use of TachoSil. Conclusions The use of TachoSil for haemostasis after primary haemostatic treatment appears to be safe and effective in children undergoing liver resection.

Transient thionitrosoarenes, ArN=S, (2) that bear a substituent (CN, Br or Me) ortho to the reactive N=S group have been generated by two entirely different routes and intercepted with dimethylbutadiene to afford mixtures of Diels-Alder and ene adducts, (3) and (4), respectively; the ene adduct predominates for each system.

A range of alkylthionitroso and arylthionitroso compounds have been generated by thermal fragmentation of N-trimethylsilyl-N-chlorothioalkyl(aryl)amine precursors, and intercepted by reaction with dimethylbutadiene to afford Diels-Alder and ene adducts.

Hepatic arterial infusion (HAI) chemotherapy is based on the idea that liver metastases are perfused almost exclusively by the hepatic artery. This approach has been extensively investigated in 1970s and 1980s. Currently, there is a worldwide growing interest in intraarterial therapeutic approaches for hepatic metastases. The principal aim of this review was to define current role of HAI in the management of metastatic colorectal cancer.Data for this review were identified by searches of MEDLINE using the search terms "hepatic arterial infusion", "colorectal cancer" and "chemotherapy". Abstracts and reports from meetings were included only when they related directly to previously published work. Only papers published in English between 1966 and 2005 were included.There are 10 published randomised clinical trials comparing fluoropyrimidine-based HAI with systemic route. Two meta-analyses of the earlier 7 trials confirmed a statistically significant response rate and improved disease-free survival with HAI. However, the cost and complication rates were of primary concern. The last decade witnessed the introducztion of new chemotherapeutic regimens including biologically targeted agents for the management of metastatic colorectal cancer patients and advancement in radiological and surgical techniques. These led to reconsideration of HAI-based therapeutic modalities with many running trials addressing its value in this new era. The results of these trials may help to clarify the role of HAI in the near future.

Transient thionitrosoarenes, ArN=S, (2) that bear a substituent (CN, Br or Me) ortho to the reactive N=S group have been generated by two entirely different routes and intercepted with dimethylbutadiene to afford mixtures of Diels-Alder and ene adducts, (3) and (4), respectively; the ene adduct predominates for each system.

Introduction Trans-arterial chemoembolisation (TACE) is a well established treatment modality for hepatocellular carcinoma (HCC). Recently our standard of care has changed from conventional doxyrubicin TACE (cTACE) to TACE using doxyrubicin eluting beads (TACE-DEB). Evidence has shown equivalent efficacy with reduced side effects. We analysed TACE procedures during this transition to determine impact on clinical outcomes. Method We reviewed the records of 152 TACE procedures performed between April 2013 and January 2014 from our electronic patient record. Demographic, treatment, length of stay and mortality data were collated and analysed for length of stay and subsequent mortality. Multivariate analysis was performed using a Cox model. Results We analysed data from 152 TACE procedures (92 cTACE, 60 TACE-DEB) performed on 109 patients between April 2013 and January 2014. The groups were matched in terms of age, sex, aetiology of underlying liver disease and baseline biochemistry. Length of stay was significantly less with TACE-DEB (mean 2.33 days, SD 1.03) compared to cTACE (mean 2.56 days, SD 1.04); p = 0.045. There was no difference in mortality (p = 0.75). Increased mortality was associated with baseline Child-Pugh score (p = 0.019), MELD (p = 0.008), albumin (p = 0.008), ALP (p = 0.046) and neutrophil count (p = 0.029). Mortality was significantly higher if baseline bilirubin > 30 (p = 0.007), creatinine > 100 (p = 0.0297) or albumin Conclusion TACE-DEB significantly reduced length of stay compared to cTACE in our cohort. Low albumin was the best independent predictor of mortality and is independent of TACE modality. These data help inform relative contraindications for this procedure. Disclosure of interest None Declared.

The surgical advances made in the area of organ transplantation along with the use of more efficacious immunosuppression have meant an increase in patient survival. This longer-living transplant population has started to exhibit cutaneous problems, some of which lead to an increased mortality while others lead to a decline in the quality of life.The primary objective was to determine the different types of cutaneous lesions encountered in the adult liver transplant population. Secondary objectives were to determine the impact, if any, of the duration of transplant, the type of immunosuppression involved and the degree of sun exposure and skin phototype, on the skin cancers encountered in this transplanted population.Two dermatologists examined 100 consecutive liver transplant recipients (LTRs) attending the transplant outpatient department. Skin examination included the face and whole body and lesions found were categorized into the following groups: cutaneous malignancies, squamoproliferative lesions, cutaneous infections and others that did not fall into any of these categories.The reasons for organ transplantation were numerous. The mean age at transplantation was 42.5 years. The average time since transplantation was 5.5 (range 0.75-16 years). Four patients developed skin cancers; among them there were a total of seven skin cancers (one squamous cell carcinoma, six basal cell carcinomas). Fungal infections accounted for 19% of all cutaneous infections seen, viral infections 2% and bacterial infections 5%. Triple-drug immunosuppressive therapy (ciclosporin A, azathioprine and prednisolone) was used in 35% of LTR patients, while dual therapy (tacrolimus and prednisolone) was used in 48% and monotherapy (tacrolimus) was used in 17% of LTRs.Immunosuppressive therapy is believed to be one of the most important risk factors in the development of skin cancer in solid organ transplant recipients. The relatively low prevalence of skin cancer in our liver transplant population may in part be explained by the relatively high percentage of recipients on dual and monotherapy (48% and 17% respectively), and the shorter duration of therapy. Our study suggests that although LTRs are at higher risk of developing nonmelanoma skin cancer than the general population, the risk is comparable with other solid organ transplant recipients.

This paper discusses design and implementation of a new-generation nuclear magnetic resonance (NMR) wireline logging tool. The tool is a multifrequency, eccentered gradient-field design with multiple depths of investigation (DOI) spanning a range of several inches. The broad range of DOIs enables radial profiling of saturation distribution and formation damage. Because of the eccentered mode of operation and sensor design, the DOIs are maintained regardless of hole size and temperature. The DOIs range from 1 to 4 in. The tool features multiple sensors, including a large antenna for fluid characterization and complementary small-aperture antennae for high-resolution acquisition modes. The sensors can be operated either separately or simultaneously at logging speeds of up to 3,000 ft/hr. Comparison of the responses is used to provide high-resolution identification of long T1 fluids such as light hydrocarbons. New NMR acquisition sequences such as Diffusion Editing (DE*) are readily implemented on the new tool, which has a highly flexible pulse programmer. Combining the new acquisition methods with the multifrequency capability of the tool and Magnetic Resonance Fluid (MRF*) characterization processing provides robust fluid saturation and oil viscosity answers.

Neonatal livers have been associated with a higher incidence of vascular complications but are nevertheless used because of donor shortage.We report a complication of hepatic venous outflow obstruction because we retained the neonatal retrohepatic cava from the first transplant for retransplantation using a left lateral segment.Technical and post-operative complications associated with a small "native" inferior cava and transplantation are described.Successful treatment with balloon angioplasty resulted in re-establishing the flow in the hepatic venous outflow tract. The child is well 3 years on with stable graft function.Percutaneous transluminal angioplasty is an effective non-surgical therapy for post liver transplant hepatic venous outflow obstruction. Replacement of the inferior venacava rather than retaining neonatal venacava may be a better option during retransplantation.

The crystal structure of the title compound, 4-(N-methylthiocarbamoyl)-2,2'-bi(1,3-dithiolylidene), C 8 H 7 NS 5 , has been re-determined at 150 K and is compared with that determined by an ambient-temperature study, showing essentially the same motif (κ packing of dimers) and strongly anisotropic thermal expansion

Introduction More than 40% of pancreatic neuroendocrine tumour (PNET) patients have liver metastases (LM) at diagnosis. Whilst it is agreed that, where possible, curative surgery offers the best outcomes, the role of debulking surgery in the context of irresectable LM remains unclear. There is also no clear evidence to support resection of the pancreatic primary in the context of irresectable liver metastases. The aim of this study is to investigate the survival benefits of different surgical treatments of LM. Methods The notes of 111 PNET patients who had visited King’s since 2004 were reviewed. 53 had LM at diagnosis and were divided into 3 cohorts: No Resection (NR) n = 27, Pancreatic Resection (PR) n = 6 and Pancreatic and Liver Resection (PLR) n = 11. Median follow-up was 40.2 months. Results Median survival for all patients with liver metastases was 61.1 months. Survival was significantly worse for patients with no resection; NR (23 months) vs. PR (98 months) p = 0.047, NR (23 months) vs. PLR (n/a) p = 0.008, but there was no significant difference between PR and PLR. Of the 11 PLR patients, 6 received debulking rather than curative resection. Univariate analysis showed no significant survival difference between dubulking and curative liver resection; however, multivariate analysis showed that resectability of liver metastases was not a significant prognostic variable. Conclusion Resection of the primary significantly improves survival in the presence of irrespectable liver metastases. There may be a role for debulking surgery in patients with irresectable liver metastases, however, the data so far does not appear to suggest a survival benefit over primary resection alone; larger studies are needed. Disclosure of Interest None Declared.

Cox17 is the candidate copper metallochaperone for delivery of copper ions to the mitochondrion for assembly of cytochrome c oxidase. Cox17 purified as a recombinant molecule lacking any purification tag binds three Cu(I) ions per monomer in a polycopper cluster as shown by X-ray absorption spectroscopy. The CuCox17 complex exists in a dimer/tetramer equilibrium with a 20 microM k(d). The spectroscopic data do not discern whether the dimeric complex forms a single hexanuclear Cu(I) cluster or two separate trinuclear Cu(I) clusters. The Cu(I) cluster(s) exhibit(s) predominantly trigonal Cu(I) coordination. The cluster(s) in Cox17 resemble(s) the polycopper clusters in Ace1 and the Cup1 metallothionein in being pH-stable and luminescent. The physical properties of the CuCox17 complex purified as an untagged molecule differ from those reported previously for a GST-Cox17 fusion protein. The CuCox17 cluster is distinct from the polycopper cluster in Cup1 in being labile to ligand exchange. CuCox17 localized within the intermitochondrial membrane space appears to be predominantly tetrameric, whereas the cytosolic CuCox17 is primarily a dimeric species. Cys--Ser substitutions at Cys23, Cys24, or Cys26 abolish the Cox17 function and prevent tetramerization, although Cu(I) binding is largely unaffected. Thus, the oligomeric state of Cox17 may be important to its physiological function.