Search

Background. Pancreatic islet transplantation (PIT) has proven effective in achieving insulin independence, but to date, the impact of PIT on health-related quality of life (HRQL) has not been studied. Methods. Ten patients who have undergone PIT at our institution were administered three HRQL questionnaires: the Hypoglycemia Fear Survey, the 36-Item Short Form Health Survey (SF-36), and a fatigue questionnaire. HRQL was assessed before PIT, then 3, 6, and 12 months after PIT. Responses were compared by analysis of variance and paired Student’s t tests. Results. Hypoglycemia Fear Survey responses demonstrated that hypoglycemia-related anxiety and hypoglycemia-related behavior modification occurred less frequently after PIT (P=0.003 and 0.0001, respectively). The total scores of the hypoglycemia questionnaire were also significantly improved after PIT, from a median score of 156 points before transplantation to 55 points 3 months after PIT (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after PIT (P=0.04). The median scores of all SF-36 components also improved after PIT. No significant changes were seen in the fatigue symptoms as assessed by the fatigue questionnaire. Conclusion. PIT recipients have less anxiety about the symptoms and consequences of hypoglycemia. PIT recipients also indicate that their behavior requires significantly less modification to prevent or treat hypoglycemia after PIT compared with before PIT. Further investigation is needed to determine whether PIT improves generic measures of HRQL.

It is increasingly important to be able to monitor and maintain the quality of estuaries for overwintering shorebirds. Bird numbers alone are not sufficient to indicate quality nor, as recent research shows, can it be assumed that site quality is being maintained simply because there is enough food to meet the birds’ physiological demands; i.e., the amount of food available per bird in autumn needs to be greater than the amount eaten. But how much greater? We used a simple individuals-based and behaviour-based model to explore the factors that affect the relationship between overwinter mortality and the amount of food available per bird in autumn (the food:bird ratio). The aims were to explore how the natural history characteristics of a shorebird species affected the shape of this relationship, in order to identify characteristics of the system that should be included in any monitoring programme of site quality. In all cases there was a minimum threshold food:bird ratio above which mortality did not vary and below which mortality increased steadily. The amount of food per bird required at the threshold varied from one to six times the amount actually consumed by each bird during winter, depending on the amount of realism included in the model. The minimum threshold ratio was most strongly influenced by the shape of the relationship between intake rate and prey density – the functional response – and, when interference competition occurred, by the distribution of the birds’ main food supply. Simulations with realistic spatial distributions of prey predicted that the minimum required amount of food per bird would be between two and five times the amount actually consumed. The threshold approach could provide a simple method of monitoring estuary quality based on food supply and bird numbers. It also provides a potentially clearly-defined and unambiguous measure of the carrying capacity of a site. If applied to a sufficient number of real estuaries, general guidelines for maintaining estuary quality based on estuary characteristics, food supply and bird species might be established.

A behaviour-based model was used to explore the effect of an extension of the port at Le Havre (Port 2000), and the effect of proposed mitigation measures, on the mortality and body condition of the three main shorebird species that overwinter in the estuary of the river Seine, France. In the model, a 20% reduction in the area of mudflats on the north side of the estuary had little effect on curlew Numenius arquata mortality and body condition but significantly increased mortality and decreased body condition in dunlin Calidris alpina and oystercatchers Haematopus ostralegus. Disturbance of feeding birds both day and night had a significant effect on the mortality and body condition of all three shorebird species, as did disturbance of roosting birds. Disturbance of feeding birds in the daytime only had a significant effect on dunlin mortality and body condition, but not that of curlew and oystercatchers. In the model, the creation of a buffer zone to reduce disturbance of feeding birds restored shorebird mortality and body condition to pre-disturbance levels. A new mudflat area was also effective in mitigating the effect of habitat loss on all three shorebirds and in mitigating the effect of roost disturbance on dunlin and curlew. However, a new mudflat area was not effective in mitigating the effect of roost disturbance on oystercatcher mortality and body condition. The effectiveness of the mitigating mudflat depended as much on its size as its quality. We believe that this is the first time that anyone has been able to forecast the efficacy of proposed mitigation measures.

The evaluation of long-term cellular immunity to EBV in pediatric orthotopic liver transplant (OLT) recipients after treatment with the humanized anti-CD20 monoclonal antibody (Rituximab) has not yet been explored. At our institution, one child with EBV-related mononucleosis-like syndrome and five children with polymorphic-EBV-PTLD occurring 6-88 months after OLT were treated with Rituximab. Treatment was well tolerated. All children achieved complete remission. After Rituximab, B-lymphocytes were undetectable in the peripheral blood and EBV-load, monitored with real-time PCR, decreased to undetectable levels in all children from >4000 copies/microg DNA at diagnosis. Four to eight months after Rituximab, EBV-load increased (>4000 copies/microg DNA) in four children, and PTLD recurred in three. Their frequency of EBV-specific T-cell precursors, measured by Elispot analysis, remained lower than in healthy controls. Rituximab effectively induced regression of PTLD in OLT recipients. However, EBV-specific T-cell immunocompetence, which may be crucial for the long-term control of EBV-mediated proliferation, did not improve.

Background An asymptomatic, self-limited transaminitis uniformly follows pancreatic islet transplantation (PIT) performed through portal vein (PV) infusion. The underlying cause and significance of this transaminitis is unclear. Study design Records of all patients with insulin-dependent diabetes mellitus who had undergone PIT at our institution were reviewed. All PITs were performed in conjunction with a remote pancreatic islet isolation center and done through percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels, serum glucose concentrations, insulin requirements, and color-flow Doppler ultrasonography examinations of the right upper quadrant were assessed before and after PIT. Results Eleven patients have undergone a total of 26 PITs. An elevated ALT level occurred in all 11 patients (100%) after the first PIT, with the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less frequent and less marked after the second PIT. A negative correlation between viability of the pancreatic islets transplanted (r = −0.44, p = 0.03) and a positive correlation between the ratio of maximum to initial PV pressure (r = 0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler ultrasonography examinations showed no occurrences of PV thrombosis or intrahepatic hematoma. Finally, the degree of transaminitis did not correlate with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot be used to measure allograft rejection or function. Conclusions Transaminitis after PIT is common and self-limited. Post-PIT transaminitis does not signal acute rejection or serious procedure-related complications such as PV thrombosis or intrahepatic hematoma.

Recent advances in clinical protocols have improved the outcomes of pancreatic islet transplantation (PIT), yet PIT recipients typically require pancreatic islet grafts derived from multiple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of pancreatic islet tissue undergoes apoptosis within the first several days post-transplantation, strongly suggest the involvement of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1β appears to be among the most important inflammatory mediators, causing pancreatic islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) synthase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the pancreatic islets, and depletion or inhibition of Kupffer cells improves outcomes following experimental PIT. Imediately after transplantation, the pancreatic islets are perfused only by portal vein blood until the process of angiogenesis restores arterial blood flow some 7–10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion molecules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the immediate post-transplant period, hepatocytes may contribute to pancreatic islet injury through the production of NO. This paper reviews literature regarding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the pathophysiology of hepatic ischemia-reperfusion and their relation to the survival and function of intrahepatic pancreatic islet grafts.

The relative inefficiency of the islet purification process may hamper obtaining enough islets for transplantation even with adequate pre-purification counts. In this study, we determined the effect of an additional purification step on total islet yields and pancreas utilization at our center. Twenty-five pancreata were processed using the automated method followed by continuous gradient purification (CGP), and the less pure islet fractions were subjected to additional rescue gradient purification (RGP). CGP and RGP islets were combined and transplanted into patients with type 1 diabetes. CGP and RGP islets showed no significant differences in cell viability, insulin secretion in vitro and function when transplanted into chemically diabetic mice. Mean RGP contribution to the final preparation was 27.9 ± 19.9%. In 12 of 25 preparations, CGP yielded

The conservation importance of estuaries is often measured by bird numbers, but monitoring numbers is not necessarily a reliable way of assessing changes in site quality. We used an individual-based model, comprised of fitness-maximising individuals, to assess the quality of the Humber estuary, UK, for 9 shorebirds; dunlin Calidris alpina, common ringed plover Charadrius hiaticula, red knot Calidris canutus, common redshank Tringa totanus, grey plover Pluvialis squatarola, black-tailed godwit Limosa limosa, bar-tailed godwit L. lapponica, Eurasian oystercatcher Haematopus ostralegus and Eurasian curlew Numenius arquata. We measured site quality as predicted overwinter survival. The model accurately predicted the observed shorebird distribution (if non-starving birds were assumed to feed on any prey or patch on which intake rate equalled or exceeded their requirements), and the diets of most species. Predicted survival rates were highest in dunlin and common ringed plovers, the smallest species, and in Eurasian oystercatchers, which consumed larger prey than the other species. Shorebird survival was most strongly influenced by the biomass densities of annelid worms, and the bivalve molluscs Cerastoderma edule and Macoma balthica. A 2 to 8 % reduction in intertidal area (the magnitude expected through sea level rise and industrial developments) decreased predicted survival rates of all species except the dunlin, common ringed plover, red knot and Eurasian oystercatcher. This paper shows how an individual-based model can assess present-day site quality and predict how site quality may change in the future. The model was developed using existing data from intertidal invertebrate and bird monitoring schemes plus new intertidal invertebrate data collected over 2 winters. We believe that individual-based models are useful tools for assessing estuarine site quality.

Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in the pediatric population. The outcomes of liver transplantation for biliary atresia, however, have not been formally examined on a national scale. The objective of this study was to identify pretransplant variables that predict patient survival after primary liver transplantation for biliary atresia. A cohort of 1,976 pediatric patients undergoing primary liver transplantation for biliary atresia between 1/1988 to 12/2003 was enrolled from the United Network for Organ Sharing database after excluding patients with a history of multiorgan transplant or previous liver transplant. Follow-up data up to 16 years post-OLT was available. The 5- and 10-year actuarial survival rates of patients that underwent liver transplantation for biliary atresia in the United States are 87.2% and 85.8%, respectively, and the 5- and 10-year graft actuarial survival rates are 76.2% and 72.7%, respectively. Early deaths (≤90 days post-OLT) were more often caused by graft failure (P = 0.01), whereas late deaths (>90 days post-OLT) were more often due to malignancy (P < 0.01). An analysis of outcomes over time demonstrated a decrease in post-OLT survival and an increase in the number of OLTs done for biliary atresia at an increasing number of centers. A multivariate analysis revealed that cadaveric partial/reduced liver grafts, a history of life support at the time of OLT, and decreased age were independent predictors of increased post-OLT mortality. In conclusion, OLT is an effective treatment for biliary atresia. Certain pretransplant variables may help predict patient survival following liver transplantation for biliary atresia. (Liver Transpl 2005;11:1193–1200.)

Graft-versus-host disease (GVHD) often occurs after bone marrow transplantation (BMT). GVHD may lead to cirrhosis or complete destruction of the bile ducts, and few effective treatment options exist for such cases. Orthotopic liver transplantation (OLT) has been described as an option, but to date the patient survival, graft survival, and GVHD recurrence rates after OLT have been unknown. Cases of OLT for GVHD were accumulated from several sources: (1) cases of OLT performed at a single institution, (2) the English-language medical literature, and (3) the United Network for Organ Sharing (UNOS) liver transplant registry. Descriptive data were derived from pre- and post-OLT information; survival analysis was performed using the Kaplan-Meier method. One case of OLT for GVHD after BMT was found at our institution, and another 6 cases were previously reported in the literature. Extrahepatic GVHD recurred in 2 cases, but no recurrence of hepatic GVHD was reported. The UNOS registry contained an additional 73 patients who underwent OLT for hepatic GVHD. The 1- and 5-year actuarial patient survival rates were 72.4% and 62.9%, respectively. Although 4 patients required retransplantation, no deaths or retransplants were attributed to the recurrence of hepatic GVHD. OLT is an effective treatment for hepatic GVHD after BMT or non-liver organ transplant. Long-term disease-free survival is obtainable in these cases, and recurrence of hepatic GVHD has not been reported. These findings suggest that OLT should be considered as an effective treatment option for cases of hepatic GVHD recalcitrant to medical treatment.

t t s i c a i r s n s i o a m d m p s uring the past 10 to 15 years, the number of medical tudents applying to general surgery residency programs as decreased considerably. Approximately 7.8% of raduating US medical students matched to general surery in 1987 compared with only 5.8% in 2002. hough a recent increase in applications has been enouraging, concerns over an inadequate general surgeon orkforce have been raised. Many recent discussions ave focused on the lifestyle of general surgery. Although his may be a very important factor considered by medcal students when deciding on a specialty, there are learly other factors involved. With this in mind, we ndertook a review of past literature examining medical tudents’ specialty choice.

In spite of antiviral prophylaxis, the transmission rate of cytomegalovirus (CMV) after solid organ transplantation remains high. In contrast, CMV transmission has never been reported following pancreatic islet transplantation (PIT). Eleven (seven CMV seronegative, four CMV seropositive) recipients underwent a total of 26 PITs. Following PIT recipients were monitored clinically and tested monthly for CMV antigenemia. Valganciclovir was given to all patients for 100 days after each PIT. Follow-up ranged from 6 to 24 months (median 14.5 months). Pancreatic islet grafts were procured from 18 CMV seropositive and 8 seronegative donors (69% and 31% of donors, respectively). In total there were 6 R+D+, 3 R+D-, 12 R-D+, and 5 R-D-PITs. No patient developed CMV antigenemia or symptoms consistent with CMV infection at any time following PIT. Routine posttransplant testing of PIT recipients demonstrated that neither CMV transmission nor CMV infection occurred after PIT.

Urea cycle defects (UCDs) typically present with hyperammonemia, the duration and peak levels of which are directly related to the neurologic outcome. Liver transplantation can cure the underlying defect for some conditions, but the preexisting neurologic status is a major factor in the final outcome. Multicenter data indicate that most of the children who receive transplants remain significantly neurologically impaired. We wanted to determine whether aggressive metabolic management of ammonia levels after early referral/transfer to a metabolism center and early liver transplantation would result in better neurologic outcomes. We report on 5 children with UCDs, ie, 2 male patients with X-linked ornithine transcarbamylase deficiency and 2 male patients with carbamoyl phosphate synthase deficiency, all of whom had neonatal presentations and underwent orthotopic liver transplantation before 1 year of age, and 1 female patient with partial X-linked ornithine transcarbamylase deficiency that was intractable to medical therapy, who underwent transplantation at 35 months of age. Developmental testing with the Griffiths scale was performed on 3 occasions each, 12 months apart, up to 45 months after transplantation. Full-scale indices for 3 children who underwent early transplantation showed average developmental quotients of 67. All 5 children had metabolic cures. There were no deaths (30-month survival rate: 100%). One child is currently listed for repeat transplantation because of bile duct stenosis and cirrhosis. We conclude that early liver transplantation and aggressive metabolic management improve early neurologic outcomes for children with UCDs, but longer follow-up monitoring is needed.

Bottom cultivation of mussels on intertidal flats is practiced throughout the world. This often generates conflicts between commercial interests and competing birds such as oystercatchers. At the Menai Strait, United Kingdom, the overwinter consumption of 242 tonnes (1 metric tonne = 1000 kg) of commercially harvestable mussels (>40 mm) by oystercatchers in 1999–2000 was worth £133 000 ($226 000 U.S. dollars). This represents 19% of the value of the landings. We used a behavior-based simulation model to predict the extent to which such losses can be reduced by novel commercial management practices, and to explore the consequences for the oystercatcher population. Simulations of novel lay management practices indicated that the losses of commercially harvestable mussels to oystercatchers can be considerably reduced by altering the shore level and/or extent of the commercial lays. We propose a novel management strategy for the bottom cultivation of mussels in intertidal areas. Seed mussels (15–20 mm) should...

The type III secretion signal of Yersinia enterocolitica YopN was mapped using a gene fusion approach. yopN codons 1 to 12 were identified as critical for signal function. Several synonymous mutations that abolish secretion of hybrid proteins without altering the codon specificity of yopN mRNA were identified.

Malignant glioma is a fatal human cancer in which surgery, chemo- and radiation therapies are ineffective. Therapeutic gene transfer used in combination with current treatment methods may augment their effectiveness with improved clinical outcome. We have shown that NUREL-C2, a replication-defective multigene HSV-based vector, is effective in treating animal models of glioma. Here, we report safety and biodistribution studies of NUREL-C2 using rhesus macaques as a model host. Increasing total doses (1 x 10(7) to 1 x 10(9) plaque forming units (PFU)) of NUREL-C2 were delivered into the cortex with concomitant delivery of ganciclovir (GCV). The animals were evaluated for changes in behavior, alterations in blood cell counts and chemistry. The results showed that animal behavior was generally unchanged, although the chronic intermediate dose animal became slightly ataxic on day 12 postinjection, a condition resolved by treatment with aspirin. The blood chemistries were unremarkable for all doses. At 4 days following vector injections, magnetic resonance imaging showed inflammatory changes at sites of vector injections concomitant with HSV-TK and TNFalpha expression. The inflammatory response was reduced at 14 days, resolving by 1 month postinjection, a time point when transgene expression also became undetectable. Immunohistochemical staining following animal killing showed the presence of a diffuse low-grade gliosis with infiltrating macrophages localized to the injection site, which also resolved by 1 month postinoculation. Viral antigens were not detected and injected animals did not develop HSV-neutralizing antibodies. Biodistribution studies revealed that vector genomes remained at the site of injection and were not detected in other tissues including contralateral brain. We concluded that intracranial delivery of 1 x 10(9) PFU NUREL-C2, the highest anticipated patient dose, was well tolerated and should be suitable for safety testing in humans.

Background There are five types of choledochal cysts, which are anomalies that involve intrahepatic or extrahepatic bile ducts, or both. These lesions are found most frequently in patients who are Asian, female, infants but are recognized with increasing frequency in adults. Methods We have managed 16 patients with this anomaly. One patient was Asian, and 1 was a child. There were 3 males and 13 females. The mean age was 29 years. There were 9 type I, 1 type II, 1 type III, 4 type IV, and 1 type V cysts. Resection of cysts and hepatico Roux-en-Y jejunostomy were performed in 9 patients for type I cysts. Pancreaticoduodenectomy was performed for a type I and a type IV cyst. The extrahepatic portion of a type IV cyst along with a segment of liver was resected in 1 patient. Operation was terminated on 1 patient with a type IV cyst because of extensive involvement of the intrahepatic ducts. She will undergo liver transplantation. The type II cyst was resected. No surgery was performed on a type III and type V cyst. Four of these patients were previously treated unsuccessfully by internal drainage procedures. Results There was no mortality. Morbidity was limited to a patient who previously underwent incomplete resection of a cyst and a cyst Roux-Y jejununostomy. No cholangiocarcinoma has been encountered in our patients after a mean follow-up of 5.5 years from the time of initial discovery of the choledochal cyst. Conclusions Management of choledochal cysts is successful after their complete removal. Partial cyst resection and internal drainage is less satisfactory because of occasional pancreatitis, cholangitis, and cholangiocarcinoma. Resection of the intrahepatic and intrapancreatic portions of the cysts reduces the risk of cancer even though this risk is low after incomplete cyst excision. Biliary continuity after cyst resection is best established by Roux-Y hepaticojejunostomy.

In a number of extensive coastal areas in northwest Europe, large numbers of long-lived migrant birds eat shellfish that are also commercially harvested. Competition between birds and people for this resource often leads to conflicts between commercial and conservation interests. One policy to prevent shellfishing from harming birds is to ensure that enough food remains after harvesting to meet most or all of their energy demands. Using simulations with behaviour-based models of five areas, we show here that even leaving enough shellfish to meet 100% of the birds' demands may fail to ensure that birds survive in good condition. Up to almost eight times this amount is needed to protect them from being harmed by the shellfishery, even when the birds can consume other kinds of non-harvested prey.

Partial hepatectomy leads to an orchestrated regenerative response, activating a cascade of cell signaling events necessary for cell cycle progression and proliferation of hepatocytes. However, the identity of the humoral factors that trigger the activation of these pathways in the concerted regenerative response in hepatocytes remains elusive. In recent years, extracellular ATP has emerged as a rapidly acting signaling molecule that influences a variety of liver functions, but its role in hepatocyte growth and regeneration is unknown. In this study, we sought to determine if purinergic signaling can lead to the activation of c-jun N-terminal kinase (JNK), a known central player in hepatocyte proliferation and liver regeneration. Hepatocyte treatment with ATPgammaS, a nonhydrolyzable ATP analog, recapitulated early signaling events associated with liver regeneration-that is, rapid and transient activation of JNK signaling, induction of immediate early genes c-fos and c-jun, and activator protein-1 (AP-1) DNA-binding activity. The rank order of agonist preference, UTP>ATP>ATPgammaS, suggests that the effects of extracellular ATP is mediated through the activation of P2Y2 receptors in hepatocytes. ATPgammaS treatment alone and in combination with epidermal growth factor (EGF) substantially increased cyclin D1 and proliferating cell nuclear antigen (PCNA) protein expression and hepatocyte proliferation in vitro. Extracellular ATP as low as 10 nM was sufficient to potentiate EGF-induced cyclin D1 expression. Infusion of ATP by way of the portal vein directly activated hepatic JNK signaling, while infusion of a P2 purinergic receptor antagonist prior to partial hepatectomy inhibited JNK activation. In conclusion, extracellular ATP is a hepatic mitogen that can activate JNK signaling and hepatocyte proliferation in vitro and initiate JNK signaling in regenerating liver in vivo. These findings have implications for enhancing our understanding of novel factors involved in the initiation of regeneration, liver growth, and development.

Summary 1 The debate over the interaction between shellfishing and shorebirds is long-running. Behaviour-based models predict how animal populations are influenced by environmental change from the behavioural responses of individual animals to this change. These models are a potential tool for addressing shellfishery problems, but to be of value they must produce reliable predictions using data that are readily available or can be collected relatively quickly. 2 We parameterized a behaviour-based model for the oystercatcher population of the Wash, UK, for 1990–99 using data from shellfishery (mussels and cockles), shorebird and climate monitoring schemes. During the 1990s the overwinter mortality rates of Wash oystercatchers varied widely. The model correctly identified the years in which the observed overwinter mortality was either low (1–2%) or high (10–26%) from annual variation in the food supply, oystercatcher population size and temperature. 3 Many oystercatchers were observed and predicted to die when only a fraction of the available food was consumed. Within the model at least, this was because interference competition excluded the least dominant birds from part of the food supply and the least efficient foragers died before the food supply was fully depleted. A simplified model, which excluded interference and individual variation, incorrectly predicted that all birds survived in all years. Models that exclude these two components of behaviour will tend to underestimate the effect of mussel and cockle food shortage on oystercatchers. Shellfishery management based on such predictions may cause high oystercatcher mortality rates even though enough food would appear to be reserved for the birds. 4 Synthesis and applications. This study shows how a behaviour-based model can be parameterized and predict annual variation in oystercatcher mortality using data routinely collected from the Wash. The principle on which the model is based, that animals behave in order to maximize their chances of survival and reproduction, applies to any system, and the shellfishery, bird and climate data used to parameterize the model are widely available. The model can be used to advise how to manage shellfisheries, by predicting the proportion of the stock that needs to remain unfished in order to maintain low oystercatcher mortality rates.

In animal pairs, males are often more vigilant than females. This is generally assumed to result from mate guarding (either against predators or other males). However, when males have conspicuous secondary sexual characteristics, they could be constrained to be more vigilant because of a higher predation risk than females. We attempted to distinguish between the ‘‘male constraint hypothesis’’ and two variations of the mate-guarding hypothesis by studying the vigilance behavior of the sexually dimorphic wigeon during early winter, when some males are in breeding plumage and some are not and when not all males are paired. The proportion of time spent vigilant by paired males in breeding plumage was five times higher than any other category of males or females. We found no significant differences between the vigilance levels of unpaired male wigeon in cryptic and in breeding plumage and therefore rejected the male constraint hypothesis. As vigilance levels of paired and unpaired females did not differ either, we rejected the hypothesis that paired males invest in vigilance to reduce their mate’s need to be vigilant to predation risks. Paired females interacted less frequently with other wigeon than unpaired ones, and it is probably to protect their female from other males that paired male wigeon increase their vigilance times. Key words: Anas penelope, Eurasian wigeon, mate guarding, predation risk, sexual differences, vigilance. [Behav Ecol 14:724–729 (2003)]

SUMMARY Recipients of solid-organ transplantation are at risk of severe infections due to their life-long immunosuppression. Despite emerging evidence that vaccinations are safe and effective among immunosuppressed patients, most vaccines are still underutilized in these patients. The efficacy, safety, and protocols of several vaccines in this patient population are poorly understood. Timing of vaccination appears to be critical because response to vaccinations is decreased in patients with end-stage organ disease and in the first 6 months after transplantation. For these reasons, the primary immunizations should be given before transplantation, as early as possible during the course of disease. Vaccination strategy should include vaccination of household contacts and health care workers at transplant centers unless contraindicated. No conclusive data are available on the use of immunoadjuvants and screening for protective titers. Most vaccines appear to be safe in solid-organ transplantation recipients, but live vaccines should be avoided until further studies are available. The risk of rejection appears minimal. Recommended vaccines include pneumovax, hepatitis A and B, influenza, and tetanus-diphtheria. We outline specific protocols and recommendations in this particular patient population. Specific contraindications exist for other vaccines, such as yellow fever, oral polio vaccine, bacillus Calmette-Guerin, and vaccinia. We conclude that solid-organ recipients will benefit from consistent immunization practices. Further studies are recommended to improve established protocols in this patient population.

Very little is known about iron metabolism and the mediators of iron metabolism in liver subjected to cold storage before transplantation. Therefore, in this study, we investigated the effect of cold storage on iron homeostasis in the rat liver. When livers were stored at 4 degrees C in University of Wisconsin solution for up to 6 and 24 hours, significant increases occurred in the labile iron pool, ferritin protein, and heme oxygenase activity. Significant decreases in heme content and iron regulatory protein 1 and 2 binding activities occurred by 24 hours. Liver injury indicated by significant increases in University of Wisconsin solution transaminase activity and liver lipid hydroperoxide levels occurred by 6 and 24 hours. Taken together, these results suggest that during pretransplantation cold storage of the liver, an aberrant iron homeostasis develops that contributes to preservation injury, and predisposes the liver to reperfusion injury by iron-dependent reactive oxygen species/Fenton reaction.

Mussel Mytilus edulis cultivation on intertidal flats affects the invertebrate community, often adversely, and this may have detrimental consequences for shorebirds. Here we present the results of an experimental study to quantify the effects of intertidal mussel cultivation on shorebirds. A study area of 4.32 ha, comprising experimental plots and control plots, was laid out in summer 1999 on the mudflats of the Menai Strait in Wales. Regular counts throughout winter of 1999/2000 estab- lished pre-cultivation patterns of bird usage. Mussels were laid in the experimental plots in April 2000 and bird usage in these plots and the controls was monitored over the 2 subsequent winters. Although no species were lost from the experimental plots, the bird assemblage in them changed. This reflected variation in the distribution of the 5 most abundant species. However, none of these key species declined in abundance following the laying of mussels. Curlew Numenius arquata and redshank Tringa totanus increased in abundance, although, unexpectedly, oystercatchers Haemato- pus ostralegus did not. At this study site, commercial mussel cultivation may have beneficial effects, not just for the birds that eat mussels, but also for other species that can take advantage of the asso- ciated changes to the benthic fauna and habitat complexity. However, features of conservation inter- est at other localities may mean that bottom cultivation of mussels will have detrimental rather than beneficial effects. The environmental effects of proposals to initiate or expand bottom cultivation of mussels need to be assessed on a case-by-case basis.

The Burry inlet, South Wales, supports a licensed cockle Cerastoderma edule fishery and occasional mussel Mytilus edulis fishery. It is also an important overwintering ground for oystercatchers Haematopus ostralegus. In recent years mussels have settled over parts of some cockle beds, preventing cockle fishery there and leading to a request by shellfishers to remove this 'mussel crumble'. Conservation managers, however, were concerned that the mussel crumble might be providing a high-quality food source for the oystercatchers, making its removal detrimental to the birds. A behaviour-based model of oystercatcher feeding on cockles and mussels was parameterised for the inlet and its predictions tested against the distribution of birds across the shellfish beds and the amount of time they spent feeding. The model was then used to explore whether the birds were currently food-limited and what would be the effects on their mortality rate and body condition if the mussel crumble were to be removed, thereby re-exposing underlying cockle beds. The model predicted successfully the proportion of birds feeding on the different types of food and the number of hours birds spent feeding on neap tides. It was predicted that, at current bird population sizes, there would have to be a 50% reduction in shellfish stocks and the areas of shellfish beds from 2000-01 levels to cause noticeable extra emigration or mortality. A given area of mussel bed was predicted to be able to support more birds than the same area of cockle bed, but the greater area of the cockle beds meant that they were more important than mussels in determining the number of birds supported by the inlet. The simulated removal of mussel crumble to expose underlying cockles had no effect on predicted bird mortality and body condition at 2000-01 shellfish stock levels. However, there were circumstances under which the mussel crumble was predicted to increase the inlet's capacity to support birds, particularly when the area of existing cockle and mussel beds was substantially reduced.

The response of foraging animals to human disturbance can be considered as a trade-off between the increased perceived predation risk of tolerating disturbance and the increased starvation risk of not feeding and avoiding disturbance. We show how the response of overwintering oystercatchers Haematopus ostralegus to disturbance is related to their starvation risk of avoiding disturbance. As winter progresses, oystercatcher energy requirements increase and their feeding conditions deteriorate. To survive they spend longer feeding and so have less spare time in which to compensate for disturbance. Later in winter, birds approach a disturbance source more closely and return more quickly after a disturbance. Their behavioural response to disturbance is less when they are having more difficulty surviving and hence their starvation risk of avoiding disturbance is greater. These results have implications for studies which assume that a larger behavioural response means that a species is more vulnerable to disturbance. The opposite may be true. To more fully understand the impact of disturbance, studies should measure both behavioural responses and the ease with which animals are meeting their requirements. Conservation effort should be directed towards species which need to spend a high proportion of their time feeding, but still have a large response to disturbance.

To assess the long-term effects of human disturbance on birds, ways of predicting its impacts on individual fitness and population size must be found. In this paper we use a behaviour-based model to predict the impact of human disturbance on oystercatchers (Haematopus ostralegus) on their intertidal feeding grounds in the Exe estuary in winter. The model predicted that, for the same overall area disturbed, numerous small disturbances would be more damaging than fewer, larger disturbances. When the time and energy costs arising from disturbance were included, disturbance could be more damaging than permanent habitat loss. Preventing disturbance during late winter, when feeding conditions were harder, practically eliminated its predicted population consequences. Although disturbance can cause increased mortality, it was not predicted to do so at the levels currently occurring in the Exe estuary.

Summary 1 Interference between foraging animals can be quantified directly only through intensive studies. A quicker alternative is to predict the strength of interference using behaviour-based models. We describe a field method to parameterize an interference model for shorebirds, Charadrii. 2 Kleptoparasitic attack distance is the main factor affecting the strength of interference but has rarely been measured. Attack distance is related to handling time, a frequently measured parameter, allowing the model to be parameterized for systems in which attack distance has not been measured. 3 The model accurately predicts the strength of interference between oystercatchers Haematopus ostralegus L. feeding on cockles Cerastoderma edule L. and the absence of interference between bar-tailed godwits Limosa lapponica L. feeding on lugworms Arenicola marina L. at low competitor densities. 4 We predict the strength of interference in black-tailed godwit Limosa limosa L. and oystercatcher systems in which it has not been measured previously. The strength of interference is almost entirely determined by attack distance; interference is stronger in systems with longer attacks. Interference is usually weaker in black-tailed godwits because handling time is generally shorter and this limits attack distance. 5 The interference model can be parameterized much more quickly than the alternative of measuring interference directly. Behaviour-based models have the potential to be a valuable tool for predicting the strength of interference.

Background It has been shown that in situ split-liver transplantation (SLT) expands the cadaveric donor pool, decreases recipient waiting time, and decreases pretransplant morbidity. However, the technique as previously described requires a microvascular left hepatic artery anastomosis. In an attempt to decrease the incidence of hepatic artery thrombosis and to increase collaboration among transplant teams, in the current report, we describe a modification of the in situ SLT technique that maintains the celiac trunk with the left-sided liver allograft. Methods Twelve in situ split-liver procurements resulted in 24 segmental liver allografts; 11 right trisegments, 11 left lateral segments, 1 right lobe, and 1 left lobe. The common bile duct and main portal vein were maintained with the right-sided liver allograft in all cases. The right hepatic artery was divided, and the celiac trunk was maintained with the left-sided liver allograft in nine cases. In one case the left hepatic artery was divided and the celiac trunk was maintained with the right-sided allograft. Two of the 12 donors had a completely replaced left hepatic artery originating from the left gastric artery, which was divided at its origin from the celiac trunk. When the celiac trunk was maintained with the left-sided allografts, arterial reconstruction of the right-sided allograft was performed with an external iliac arterial interposition graft. Nineteen of the 24 split-liver allografts were transplanted at our center. The remaining five liver allografts were shared with regional liver transplant centers. Results In this series, 1-year actuarial patient and allograft survival rates are 100% and 96%, respectively. Hepatic artery thrombosis (HAT) did not occur in any patient receiving a left-sided split allograft in which the celiac trunk or left gastric artery was maintained; in addition, HAT did not occur in any of the right-sided allografts. HAT did occur immediately after transplantation in the one patient who was transplanted with a left lateral segment without the celiac trunk. This allograft was salvaged by early thrombectomy and interposition grafting. One patient required retransplantation, owing to portal vein thrombosis. Hepatic venous outflow obstruction did not occur in any of the patients. Two patients required reexploration in the posttransplant period because of arterial anastomotic site bleeding, and one of the left lateral segment allograft recipients had a cut-surface bile leak, which was managed nonoperatively. All of the patients are alive and well, including the five patients who received their transplants at other centers, with a median follow-up of 10 months (range, 1-27 months). Conclusions In summary, our data demonstrate that maintaining the celiac trunk with the left-sided allograft in SLT provides excellent early survival results with low complication rates. This technical modification obviates the need for a left hepatic artery microvascular anastomosis and should lower the incidence of hepatic artery thrombosis in the small-caliber left hepatic artery. We have also shown that this technique allows sharing among liver transplant centers without compromise in patient or allograft survival rates. It is hoped that this modification in SLT will increase the number of livers split, and will promote sharing among transplant centers to truly optimize the number of liver allografts available from the cadaveric pool.

Slc11a1 (solute carrier family 11 member 1) (formerly Nramp1) modulation of iron metabolism in macrophages plays an important role in early phase macrophage activation, and therefore host innate immunity. This review focuses on the role of Nramp1 in intramacrophage iron metabolism, with emphasis on the two prevailing mechanisms of Nramp1 modulation of iron metabolism in macrophages.

Adoptive immunotherapy with EBV-specific CTL (EBV-CTL) effectively prevents and treats EBV-driven lymphoproliferation in immunocompromised hosts. EBV-seronegative solid organ transplant recipients are at high risk of EBV-driven lymphoproliferation because they lack EBV-specific memory T cells. For the same reason, standard techniques for generating EBV-CTL in vitro from EBV-naive individuals are unsuccessful. To overcome this problem, we compared several methods of expanding EBV-CTL from seronegative adults and children. First, the standard protocol, using EBV-transformed lymphoblastoid B cell lines (LCL) as the source of APC, was compared with protocols using EBV-Ag-loaded dendritic cells as APC. Surprisingly, the standard protocol effectively generated CTL from all seronegative adults. The additional finding of EBV-DNA in the peripheral blood of three of these four adults suggested that some individuals may develop cellular, but not humoral, immune responses to EBV. By contrast, LCL failed to reactivate EBV-CTL from any of the six EBV-seronegative children. EBV-Ag-loaded dendritic cells could expand EBV-CTL, but only in a minority of children. However, the selective expansion of CD25-expressing T cells, 9–11 days after activation with LCL alone, proved to be a simple and reliable method for generating EBV-CTL from all seronegative children. The majority of these CTL were CD4+ (71 ± 26%) and demonstrated HLA class II-restricted, EBV-specific killing. Our results suggest that a negative EBV serology does not accurately identify EBV-negative individuals. In addition, our method for selecting EBV-specific CTL from naive individuals by precursor cell enrichment may be applicable to the immunotherapy of cancer patients with a low frequency of tumor- or virus-specific CTL.

Sensenbrenner syndrome, or cranioectodermal dysplasia, is a rare heterogeneic autosomal recessive disorder, affecting ~1 of 1 000 000 live births. The syndrome usually manifests within the first year of life and can present with progressive liver and renal involvement. For all Sensenbrenner patients, renal and liver diseases are the main contributors of morbidity and mortality. In this report, we present the case of a 7-year-old boy with congenital liver disease progressing to liver failure secondary to Sensenbrenner syndrome. For this patient, evidence of liver dysfunction was evident from 2 months of age and progressed to frank cirrhosis and severe portal hypertension with multiple episodes of life-threatening variceal bleeding by age 6. This report illustrates the capability of orthotopic liver transplantation as a viable therapy for those pediatric patients suffering from severe liver failure secondary to a congenital ciliopathy, such as Sensenbrenner syndrome. In fact, early emphasis should be placed on the renal and liver involvement associated with Sensenbrenner syndrome with particular consideration for early referral for transplantation in cases with severe disease. Although the condition is rare, clinicians should be aware of it and its association with fatal liver disease to facilitate appropriate evaluation and referral.

Drowning, a common cause of death in the pediatric population, is a potentially large donor pool for OLT. Anecdotally, transplant centers have deemed these organs high risk over concerns for infection and graft dysfunction. We theorized drowned donor liver allografts do not portend worse outcomes and therefore should not be excluded from the donation pool. We reviewed our single-center experience of pediatric OLTs between 1988 and 2015 and identified 33 drowned donor recipients. These OLTs were matched 1:2 to head trauma donor OLTs from our center. A chart review assessed postoperative peak AST and ALT, incidence of HAT, graft and recipient survival. Recipient survival at one year between patients with drowned donor vs head trauma donor allografts was not statistically significant (94% vs 97%, P=.63). HAT incidence was 6.1% in the drowned donor group vs 7.6% in the control group (P=.78). Mean postoperative peak AST and ALT was 683 U/L and 450 U/L for drowned donors vs 1119 U/L and 828 U/L in the matched cohort. These results suggest drowned donor liver allografts do not portend worse outcomes in comparison with those procured from head trauma donors.

Portosystemic shunts can serve as a bridge to liver transplantation in patients with end-stage liver disease by providing portal decompression to treat life-threatening variceal bleeding and prevent recurrent episodes until an organ becomes available. The conventional TIPS procedure, however, is technically challenging to perform in infants due to the small size of their intrahepatic vasculature. We report two cases of emergent creation of portosystemic shunts as a bridge to liver transplantation in infants with life-threatening variceal bleeding using a conventional TIPS technique in the first case and a percutaneous DIPS technique in the other. Both procedures were successful at reducing the portosystemic pressure gradient and preventing further variceal bleeds until a liver transplant could be performed. The novel percutaneous DIPS procedure is a valuable alternative to the conventional TIPS in infants, as it is better suited for small or challenging intrahepatic vascular anatomy.

Purpose of review Orthotopic liver transplantation in the pediatric population is a technically challenging undertaking, requiring highly specialized surgical techniques unique to this group. This review describes the most current method of transplantation for these patients. Recent findings Pediatric liver transplantation employs multiple modifications of standard transplant technique, including alternative methods of vascular and biliary anastomoses as well as technical variant grafts. We herein describe how these methods are employed in procurement, back-table preparation, hepatectomy, and allograft implantation. Summary This review provides concise direction of surgical technique for pediatric liver transplant recipients.

Biliary atresia (BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches: (1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and (2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.

A prognostic index to predict survival after liver transplantation could address several clinical needs. Here, we devised a scoring system that predicts recipient survival after pediatric liver transplantation. We used univariate and multivariate analysis on 4565 pediatric liver transplant recipients data and identified independent recipient and donor risk factors for posttransplant mortality at 3 months. Multiple imputation was used to account for missing variables. We identified five factors as significant predictors of recipient mortality after pediatric liver transplantation: two previous transplants (OR 5.88, CI 2.88-12.01), one previous transplant (OR 2.54, CI 1.75-3.68), life support (OR 3.68, CI 2.39-5.67), renal insufficiency (OR 2.66, CI 1.84-3.84), recipient weight under 6 kilograms (OR 1.67, CI 1.12-2.36) and cadaveric technical variant allograft (OR 1.38, CI 1.03-1.83). The Survival Outcomes Following Pediatric Liver Transplant score assigns weighted risk points to each of these factors in a scoring system to predict 3-month recipient survival after liver transplantation with a C-statistic of 0.74. Although quite accurate when compared with other posttransplant survival models, we would not advocate individual clinical application of the index.

Initiation of ring constriction and completion of cell division are delayed in blt1Δ cells because contractile rings recruit and retain less Sid2p and Mob1p. This results in slower, reduced accumulation of Clp1p phosphatase and β-glucan synthase Bgs1p at the cleavage furrow, delaying the onset of ring constriction and completion of cell division., Spatial and temporal regulation of cytokinesis is essential for cell division, yet the mechanisms that control the formation and constriction of the contractile ring are incompletely understood. In the fission yeast Schizosaccharomyces pombe proteins that contribute to the cytokinetic contractile ring accumulate during interphase in nodes—precursor structures around the equatorial cortex. During mitosis, additional proteins join these nodes, which condense to form the contractile ring. The cytokinesis protein Blt1p is unique in being present continuously in nodes from early interphase through to the contractile ring until cell separation. Blt1p was shown to stabilize interphase nodes, but its functions later in mitosis were unclear. We use analytical ultracentrifugation to show that purified Blt1p is a tetramer. We find that Blt1p interacts physically with Sid2p and Mob1p, a protein kinase complex of the septation initiation network, and confirm known interactions with F-BAR protein Cdc15p. Contractile rings assemble normally in blt1∆ cells, but the initiation of ring constriction and completion of cell division are delayed. We find three defects that likely contribute to this delay. Without Blt1p, contractile rings recruited and retained less Sid2p/Mob1p and Clp1p phosphatase, and β-glucan synthase Bgs1p accumulated slowly at the cleavage site.

Focal nodular hyperplasia (FNH) is uncommonly diagnosed in pediatric patients and may be difficult to distinguish from a malignancy. We present a review of all children with a tissue diagnosis of FNH at our institution, describe the diagnostic modalities, and provide recommendations for diagnosis and follow-up based on our experience and review of the literature.A retrospective review of children18years of age diagnosed with FNH at a single institution was performed from 2000 to 2013.Twelve patients were identified with a tissue diagnosis of FNH. Two patients required surgical resection of their lesion owing to concern for malignancy. Ten patients were managed expectantly with imaging surveillance after biopsy confirmed a diagnosis of FNH. All patients who underwent MRI had very typical findings including hypointensity on T1 weighted sequences, hyperintensity on T2, and homogenous uptake of contrast on the arterial phase. On follow-up all patients had either a stable lesion or reduction in size.Focal nodular hyperplasia presents typically in children with liver disease, have undergone chemotherapy, and adolescent females. Young children, particularly5years of age, without underlying liver disease or history of chemotherapy can pose a diagnostic dilemma. In this unique subgroup of children with FNH, MRI and/or needle biopsy should be adequate diagnostic modalities for these lesions.

Background. Split-liver transplantation offers a unique opportunity to expand the existing donor pool. However, it has previously been stated that due to inadequate liver volume the advantages of split-liver transplantation would be lost when attempting to split the liver for two adult recipients. In this study, we sought to determine the safety, efficacy, and applicability of split-liver transplantation in select adult liver transplant recipients. Methods. Liver allografts for eight adult recipients were procured by in situ splitting of four adult cadaveric livers. The donor ages were 17, 19, 22, and 25 years and weights were 72, 77, 78, and 87 kg, respectively. In situ splitting resulted in three right trisegmental grafts, one right lobe graft, one left lobe graft, and three left lateral segmental grafts. The median recipient age was 49 years (range 38-61 years), whereas the median recipient weight was 84 kg (range 78-98 kg) for the right-sided grafts and 52 kg (range 51-53 kg) for recipients of the left-sided grafts. The median graft-to-recipient body weight ratio for right trisegmental, right lobe, left lobe, and left lateral segmental grafts was 1.31%, 1.26%, 1.35%, and 0.70%, respectively. Results. Overall patient and graft survival in this series is 100%. All prothrombin times were normalized within 4 days of transplantation. No evidence of ascites or prolonged hyperbilirubinemia was encountered in any right- or left-sided graft recipient. The incidence of hepatic artery, portal vein, and hepatic vein thrombosis is 0%, 0%, and 0%, respectively. Hepatic arterial anastomotic bleeding and a cut surface bile leak each occurred in one patient. Median United Network for Organ Sharing (UNOS) waiting time was 242 days (range 4-454 days) for the patients to which the donor liver was allocated. In contrast, the median waiting time for the four patients receiving the extra split-liver graft was reduced significantly to 37 days (range 21-101 days) (P

Background Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disorders (PTLD) affect 2%-27% of solid organ transplant (SOT) recipients. Adoptive immunotherapy may have therapeutic potential in this setting, but there is little experience in generating autologous EBV-specific cytotoxic T-cell lymphocytes (EBV-CTLs) from SOT recipients, and their efficacy and persistence in an immunosuppressed environment is unknown. Methods EBV-CTLs were generated from eight SOT recipients, using weekly stimulations with autologous lymphoblastoid cell lines (LCLs) and interleukin-2. CTL phenotype and function were evaluated in the presence of therapeutic concentration of cyclosporin A or FK506. Results In all cases, CTLs expanded with normal kinetics. The majority was CD3+CD8+ (mean, 76%), with less than 3% of natural killer cells. All ex vivo-generated CTLs produced significantly higher killing of autologous LCLs than of HLA-mismatched LCLs (mean, 56% vs. 14% at 20:1 ratio). No lysis of autologous or allogeneic PHA blasts was observed. The CTL expansion rate was reduced in a concentration-dependent manner in the presence of immunosuppressive drugs; however, neither lytic activity nor phenotype was affected. Conclusions Using methods that are approved for clinical application, EBV-CTLs can be generated from SOT recipients, even those with frank lymphoma, or who are receiving immunosuppressive drugs. These CTLs retain their function in the presence of immunosuppressive agents. Although in vivo efficacy, safety, and persistence can be assessed only in clinical trials, our results suggest that CTLs can be effective for the treatment of PTLD, even when immunosuppression cannot be reduced because of the high risk of graft rejection.

Background. Initiated in 1995, the Studies of Pediatric Liver Transplantation (SPLIT) registry database is a cooperative research network of pediatric transplantation centers in the United States and Canada. The primary objectives are to characterize and follow trends in transplant indications, transplantation techniques, and outcomes (e.g., patient/graft survival, rejection, growth parameters, and immunosuppressive therapy.) Methods. As of June 15, 2000, 29 centers registered 1144 patients, 640 of whom received their first liver-only transplant while registered in SPLIT. Patients are followed every 6 months for 2 years and yearly thereafter. Data are submitted to a central coordinating center. Results. One/two-year patient survival and graft loss estimates are 0.85/0.82 and 0.77/0.72, respectively. Risk factors for death include: in ICU at transplant (relative risk (RR) = 2.63, P

Parasite loads vary among feeding sites in European oystercatchers, Haematopus ostralegus, hibernating in the Exe Estuary, in Great Britain. This variation might be the result of active or passive selection of non-parasitised mussels (Mytilus edulis) because they are the preferred food of the oystercatcher in the area and are also the intermediate hosts of one of the main parasites of the bird. Parasite loads (Renicola sp. and Psilostomum brevicolle) of the mussels were studied in relation to morphological parameters known to influence the choice of prey by the oystercatcher: length of mussel, meat content, and thickness of shell. Smaller mussels generally carry the lightest parasite loads, but the number of metacercariae of the two parasites potentially consumed in a day varies with feeding site and mussel size. Thus, an oystercatcher will ingest fewer metacercariae of Renicola sp. and P. brevicolle by selecting smaller mussels from bank 1, which is one of the least visited sites in the estuary. However, the birds will have to select mussels of 37 mm or more on banks 30 and 31, which are among the most used sites. We suggest that there is no active selection of non-parasitised mussels, but rather a kind of passive selection as the mussels chosen for their energetic value happen to be also the least parasitised.[Journal translation]

Measurements were made of Oystercatcher corpses to find the most reliable measure of body condition in live birds. Total body weight was as accurate as muscle thickness in assessing the weight of the pectoral muscles, a major store of protein reserves. Total body weight was also a good indicator of fat reserves. Wing-length was the most reliable measure of body size. Body condition in live birds was measured as an individual's residual weight derived from a general linear model of (loge) body weight against age, month, (loge) wing-length and time since capture. On the Exe estuary in autumn, there was no significant difference in body condition between same-age Oystercatchers of different diets and feeding methods. In the winter months, however, body condition differed significantly between mussel feeders using different feeding methods, and between mussel feeders and birds that fed on worms and clams. Differences between diet/feeding methods were not the same for each age group. Birds with the highest mean body condition index in adults were mussel hammerers, in immatures mussel stabbers and in juveniles, worm/clam feeders. No significant difference in body condition was found between the sexes in any age group in autumn. In winter, when birds with the same diet/feeding method were considered, females were significantly heavier than males. However, when birds of all diets and feeding methods were combined, weight differences between the sexes were not apparent. We examine reasons why birds with certain diets and feeding methods may be heavier than others in winter, and why females are sometimes heavier than males. We conclude that, in most cases, it is due to differences between birds in their ability to achieve a common target weight. However, we conclude that adult females try to achieve a higher target weight than males, probably as a premigratory and prebreeding strategy. In the light of this, we consider the consequences for adult females, in terms of reproductive success and survival, of specializing in diets and feeding methods associated with lower body weights in winter.

Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different populations uncovered 30 candidate driver genes and 11 core pathway modules. Furthermore, a collaboration of two large-scale cancer genome projects comparatively analyzed the trans-ancestry substitution signatures in 608 liver cancer cases and identified unique mutational signatures that predominantly contribute to Asian cases. This work elucidates previously unexplored ancestry-associated mutational processes in HCC development. A combination of hotspot TERT promoter mutation, TERT focal amplification and viral genome integration occurs in more than 68% of cases, implicating TERT as a central and ancestry-independent node of hepatocarcinogenesis. Newly identified alterations in genes encoding metabolic enzymes, chromatin remodelers and a high proportion of mTOR pathway activations offer potential therapeutic and diagnostic opportunities.