Porcine UL-16 Binding Protein 1 Is Not a Functional Ligand for the Human Natural Killer Cell Activating Receptor NKG2D.

Natural killer (NK) cells play a vital role in xenotransplantation rejection. One approach to induce NK cell immune tolerance is to prevent the NK cell-mediated direct killing of porcine cells by targeting the interaction of the activating receptor NKG2D and its ligands. However, the identity of porcine ligands for the human NKG2D receptor has remained elusive. Previous studies on porcine UL-16 binding protein 1 (pULBP-1) as a ligand for human NKG2D have yielded contradictory results. The goal of the present study was to clarify the role of pULBP-1 in the immune response and its interaction with human NKG2D receptor. To accomplish this, the CRISPR/Cas9 gene editing tool was employed to disrupt the porcine ULBP-1 gene in a 5-gene knockout porcine endothelial cell line (GGTA1, CMAH, ß4galNT2, SLA-I α chain, and ß-2 microglobulin, 5GKO). A colony with two allele mutations in pULBP-1 was established as a 6-gene knockout pig cell line (6GKO). We found that pULBP-1-deficient pig cells exhibited a reduced binding capacity to human NKG2D-Fc, a recombinant chimera protein. However, the removal of ULBP-1 from porcine endothelial cells did not significantly impact human NK cell degranulation or cytotoxicity upon stimulation with the pig cells. These findings conclusively demonstrate that pULBP-1 is not a crucial ligand for initiating xenogeneic human NK cell activation.

Ex vivo biomechanical comparison of four Center of Rotation Angulation Based Leveling Osteotomy fixation methods.

OBJECTIVE: To compare the strength of four constructs used to secure an osteotomy in a Center of Rotation Angulation (CORA)-Based Leveling Osteotomy (CBLO) in an ex vivo model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Thirty-two canine tibiae from 17 skeletally mature cadavers weighing between 18 and 33.2 kg. METHODS: Thirty-two paired tibiae with patella and patellar tendon were collected. Each tibia was randomly allocated to a construct group: plate and pin (Plate), plate with countersink compression screw (HCS), plate with tension band (TB), or plate with HCS and TB (HCSTB). Samples were loaded by distraction until failure. The stiffness, yield load, and ultimate load were compared between each fixation method. RESULTS: No difference in stiffness of the constructs was detected between groups (p = .6937). Yield load for the HCSTB group (1211.06 N) was greater than the TB group (1016.41 N), the HCS group (907.20 N), and the Plate group (787.73 N) (p = .0069). The ultimate load for the HCSTB group (1387.82 N) was greater than the TB group (1076.36 N), HCS group (926.62 N), and the Plate group (774.35 N) (p = .0004). CONCLUSIONS: CBLO fixation augmented with a TB and HCS provided a stronger construct that withstood a greater yield load and ultimate load than either augmentation strategy alone. CLINICAL SIGNIFICANCE: Augmenting a CBLO fixation with a TB and a HCS can provide increased construct strength.

A 3-Decade, Single-Center Experience of Liver Transplantation for Cholangiocarcinoma: Impact of Era, Tumor Size, Location, and Neoadjuvant Therapy.

Liver transplantation (LT) for cholangiocarcinoma (CCA) remains limited to a small number of centers. Although the role of neoadjuvant therapy (NAT) has been explored over time, an in-depth analysis of NAT strategies remains limited. Furthermore, controversy exists regarding acceptable tumor size during patient selection for LT. This study explores the impact of era, tumor size, and NAT strategy on LT outcomes for CCA. We conducted a retrospective review of 53 patients with CCA treated with LT from 1985 to 2019; 19 hilar CCA (hCCA) and 30 intrahepatic CCA (iCCA) were included. The relative contributions of varying NAT (neoadjuvant chemotherapy [NAC], neoadjuvant local therapy [NALT], and combined NAC and NALT [NACLT]) as well as the implication of tumor size and era were analyzed. The primary endpoint was overall survival (OS). Compared with the old era (1985-2007), 5-year OS in patients who underwent LT in the recent era (2008-2019) showed a superior trend. The 5-year OS from initial treatment in patients receiving NACLT for hCCA and iCCA were 88% and 100% versus 9% and 41% in patients without it, respectively (P = 0.01 for hCCA; P = 0.02 for iCCA), whereas NAC or NALT alone did not show significant differences in OS versus no NAT (P > 0.05). Although 33 patients had large-size tumors (hCCA ≥ 30 mm, n = 12, or iCCA ≥ 50 mm, n = 21), tumor size had no impact on survival outcomes. Outcomes of LT for CCA seem to have improved over time. Multimodal NAT is associated with improved survival in LT for both iCCA and hCCA regardless of tumor size.

A rapid assessment framework for food system shocks: Lessons learned from COVID-19 in the Indo-Pacific region.

The frequency and severity of shocks to food systems is accelerating globally, exemplified by the current COVID-19 outbreak. In low- and middle-income countries, the impacts have exacerbated existing food system vulnerabilities and poverty. Governments and donors must respond quickly, but few tools are available that identify interventions to build food system resilience, or emerging opportunities for transformation. In this paper we reflect on the application of a systems-based rapid assessment which we applied across 11 Indo-Pacific countries in May-July 2020. Our approach was shaped by three design parameters: the integration of key informants' perspectives engaged remotely within the countries, applicability to diverse food systems and COVID-19 experiences across the region, and the consideration of food systems as complex systems. For the rapid assessment we adopted an analytical framework proposed by Allen and Prosperi (2016). To include a development lens, we added the analysis of vulnerable groups and their exposure, impacts, recovery potential and resilience, and pro-poor interventions. We concluded that the framework and approach facilitated integration and triangulation of disparate knowledge types and data to identify priority interventions and was sufficiently flexible to be applied across food systems, at both national, sub-national and commodity scales. The step-wise method was simple and enabled structured inquiry and reporting. Although the systems concepts appeared more easily transferrable to key informants in some countries than others, potentially transformational interventions were identified, and also some risks of maladaptation. We present a refined framework that emphasises analysis of political, economic and institutional drivers of exposure and vulnerability, the constraints that they pose for building recovery potential and resilience, and trade-offs amongst winners and losers inherent in proposed interventions.

Functional traits driving species role in the structure of terrestrial vertebrate scavenger networks.

Species assemblages often have a non-random nested organization, which in vertebrate scavenger (carrion-consuming) assemblages is thought to be driven by facilitation in competitive environments. However, not all scavenger species play the same role in maintaining assemblage structure, as some species are obligate scavengers (i.e., vultures) and others are facultative, scavenging opportunistically. We used a database with 177 vertebrate scavenger species from 53 assemblages in 22 countries across five continents to identify which functional traits of scavenger species are key to maintaining the scavenging network structure. We used network analyses to relate ten traits hypothesized to affect assemblage structure with the "role" of each species in the scavenging assemblage in which it appeared. We characterized the role of a species in terms of both the proportion of monitored carcasses on which that species scavenged, or scavenging breadth (i.e., the species "normalized degree"), and the role of that species in the nested structure of the assemblage (i.e., the species "paired nested degree"), therefore identifying possible facilitative interactions among species. We found that species with high olfactory acuity, social foragers, and obligate scavengers had the widest scavenging breadth. We also found that social foragers had a large paired nested degree in scavenger assemblages, probably because their presence is easier to detect by other species to signal carcass occurrence. Our study highlights differences in the functional roles of scavenger species and can be used to identify key species for targeted conservation to maintain the ecological function of scavenger assemblages.

Causal Loop Analysis Can Identify Solutions to Complex Dog Management Problems in Remote Australian Aboriginal Communities.

Companion animal management in Australian remote Aboriginal communities (rAcs) is a complex problem with multiple stakeholders involved, with differing needs, knowledge, power and resources. The Comm4Unity (Cycle of Multiple Methods for Unity-For Community) approach was designed to address such problems. This study represents the second step of the Comm4Unity framework, where a causal loop analysis (CLA) was adapted and tested as a tool to address the issue of dog overpopulation in Wurrumiyanga, and in particular the systemic causes of the problem and necessary transformational management solutions. Ten focus group discussions (FGDs) were held amongst three of the four stakeholder groups identified during the first step in the analysis. The CLA identified 13 positive feedback loops, which drive vicious cycles and perpetuate the dog overpopulation issue. All three groups agreed and developed 22 solutions to address the causes of dog overpopulation. Despite the differences in the framings of the three groups, "training" and "education" were both the top priority solutions for all three groups. The majority of the solutions discussed by the groups were not only transformational but also social, requiring collaboration. This study was successful in so far as transformational actions were co-developed by all FGDs, which may have also built capacity and agency amongst the local community to implement them as a cohesive group.

Frame Analysis: An Inclusive Stakeholder Analysis Tool for Companion Animal Management in Remote Aboriginal Communities.

Companion animal management in Australian remote Aboriginal communities (rAcs) is a complex problem, with multiple stakeholders involved with differing needs, knowledge, power and resources. We present our CoMM4Unity approach, a participatory systemic action research process designed to address such problems. In the first step, frame analysis is used to analyse stakeholders' perspectives, knowledge types and power dynamics to determine their relative roles in animal management. Twenty individuals were interviewed from stakeholder groups involved in animal management in the remote, island rAc of Wurrumiyanga, Tiwi Islands. Frame analysis indicated that stakeholders aligned into four groups with distinct identity frames, knowledge types and power frames: Indigenous Locals, Indigenous Rangers, Non-Indigenous Locals and Animal Managers. All four groups shared overlapping perceptions about companion animals in Wurrumiyanga, and agreed that dog overpopulation was the primary issue. However, the groups differed in their strength of opinions about how dogs should be managed. Therefore, the situation is not one of diametrically opposing frames but more a misalignment of goals and values. Our application showed that frame analysis can reveal subtle variations in stakeholder groups' identities, goals and values, and hence how they prioritise management measures.

Incisional Hernia After Orthotopic Liver Transplantation: A Systematic Review and Meta-analysis.

BACKGROUND: Incisional hernia (IH) is a well-known complication of orthotopic liver transplantation. Despite wide recognition of the impact of this problem, the incidence remains imprecisely known. METHODS: The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to November 2017 for abstracts documenting IH after orthotropic liver transplantation (OLT). The primary endpoint of this study was incidence of IH, secondary endpoints were time to hernia and recurrence. Three reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% CIs. RESULTS: After a review of 77 abstracts, 18 studies were graded as relevant. The methodological quality of studies was assessed with a minimum Oxford Centre for Evidence-Based Medicine level of 2B. These represent a cohort of 981 patients with IH after OLT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidence of 15.1% (CI 12.1%-18.2%). Aggregate recurrence rate reported in the literature is 12.4% (CI 4.3%-20.5%). Overall reported time to IH after OLT was 42.9 months. CONCLUSIONS: Although reported incidences of IH after OLT vary widely across studies, an overall incidence of 15.1% is reported. This is a relatively late complication after transplantation. Recurrence of hernia after initial repair is 12.4% within this patient population.

COVID-19 and food systems in Pacific Island Countries, Papua New Guinea, and Timor-Leste: Opportunities for actions towards the sustainable development goals.

Context: The COVID-19 pandemic has impacted global food systems. This has led to different strategies by communities, governments, and businesses involved in food systems to mitigate and adapt to the unfolding pandemic. Small Island Developing States are particularly exposed to the conflation of risks from COVID-19 disease, economic downturns, underlying climate vulnerabilities and biosecurity risks. Objective: Our study aimed to identify the food systems vulnerabilities, impacts, and opportunities for supporting resilience and sustainable development in selected Pacific Island countries, Papua New Guinea, and Timor-Leste. The study focused on the impacts from the first six months of the pandemic (February-July 2020), with remote data collection and analysis done between May and July 2020. Methods: We conducted 67 interviews, and triangulated information with desktop and news sources emerging at the time. We present results on the effect on smallholder livelihoods, supply chains, governance, communities and employment. Overall, the major impacts of COVID-19 have been on economies, posing risks to future food security and further hampering progress towards key Sustainable Development Goals. Results and conclusions: We found that unemployment and economic contraction have been the most severe effects to date, with long-term consequences for food value chains and smallholder farmers. Disruptions to tourism, labour migration, and remittances have led to varying socio-economic impacts throughout the region. Vulnerable groups, notably women, urban poor, and youth, have been disproportionately affected by unemployment. Timor-Leste has had some social protection measures, whereas in Pacific Countries these have been varied. The lockdowns and State of Emergency initially influenced the distribution and marketing of food, but local food economies are starting to stabilise. The continued functioning of international food supply chains reduced the risk of food insecurity in high import dependent nations, notably import dependent countries like Tuvalu and Kiribati. Significance: The results have significance for three recovery pathways. The first recovery pathway relates to revisiting value chains in light of restricted travel. The second recovery pathway exists through leveraging the adaptive capacities of communities to stimulate innovative agriculture that also integrates climate adaptation and nutrition. The third recovery pathway relates to addressing the structural challenges that perpetuate inequalities and poverty while finding new ways of implementing inclusive policies and research. Our study presents a set of comparative examples of managing a food system shock that can inform future systems-oriented research and policy for sustainable development.

Leukocytosis after distal pancreatectomy and splenectomy as a marker of major complication.

BACKGROUND: The aim of this study was to analyze the associations between the degree of postoperative leukocytosis and major morbidity after elective distal pancreatectomy with splenectomy (DPS). METHODS: Retrospective review of patients undergoing DPS for pancreatic diseases (2013-2016). Receiver operating characteristic curves, Youden's index, and area under the curve were used to identify ideal lab cut-off values and discriminatory ability of postoperative white blood cell count to detect complications. RESULTS: 158 patients underwent DPS. Median age was 57 years (range, 22-90) and 53% of patients were male. POD3 absolute WBC count ≥16 × 109/L or an increase in WBC count ≥9 × 109/L from preoperative baseline was associated with major morbidity after DPS (AUC 0.7 and 0.7, respectively). CONCLUSION: Postoperative day three leukocytosis ≥16 × 109/L or an increase in WBC of ≥9 × 109/L from preoperative baseline should raise clinical awareness for major postoperative complication after DPS.

Specialized care improves outcomes for patients with cirrhosis who require general surgical operations.

BACKGROUND: General surgical operations on patients with cirrhosis have historically been associated with high morbidity and mortality rates. This study examines a contemporary series of patients with cirrhosis undergoing general surgical procedures. METHODS: A retrospective evaluation of 358 cirrhotic patients undergoing general surgical operations at a single institution between 2004-2015 was performed. Thirty- and 90-day mortality along with complications and subsequent transplantation rates were examined. RESULTS: 358 cirrhotic patients were identified. The majority were Child-Turcotte-Pugh class (CTP) A (55.9%) followed by class B (32.4%) and class C (11.7%). Mean MELD score differed significantly between the groups (8.7 vs. 12.1 vs. 20.1; p<0.001). The most common operations were herniorrhaphy (29.9%), cholecystectomy (19.3%), and liver resection (14.5%). The majority of cases were performed semi-electively (68.4%), however, within the CTP C patients most cases were performed emergently (73.8%). Thirty and 90-day mortality for all patients were 5% and 6%, respectively. Mortality rates increased from CTP A to CTP C (30 day: 3.0% vs. 5.2% vs. 14.3%; p = 0.01; 90 day: 4.5% vs. 6.9% vs. 16.7%; p = 0.016). Additionally, 30-day mortality (12.8% vs. 2.3%; p<0.001), 90 day mortality (16.0% vs. 3.4%; p<0.001) were higher for emergent compared to elective cases. A total of 13 (3.6%) patients underwent transplantation ≤ 90 days from surgery. No elective cases resulted in an urgent transplantation. CONCLUSION: Performing general surgical operations on cirrhotic patients carries a significant morbidity and mortality. This contemporary series from a specialized liver center demonstrates improved outcomes compared to historical series. These data strongly support early referral of cirrhotic patients needing general surgical operation to centers with liver expertise to minimize morbidity and mortality.

Ex vivo biomechanical comparison of 2.7 mm string-of-pearl plate versus screw/wire/Polymethylmethacrylate composite fixation and 2.7 mm veterinary acetabular plate for repair of simulated canine acetabular fractures.

BACKGROUND: Acetabular fractures comprise 12-30% of canine pelvic fractures and require accurate anatomic reduction and rigid stability to ensure proper healing and minimize future osteoarthritis. Many techniques have been used to repair these fractures, with common techniques including veterinary acetabular plates or use of screw/wire/polymethylmethacrylate constructs. String-of-Pearl™ plating systems have also been used clinically but there is a lack of research supporting their use for these fractures. The purpose of this study was to compare fracture reduction accuracy, biomechanical characteristics, and mode of failure between String-of-Pearls™, veterinary acetabular plates, screw/wire/polymethylmethacrylate constructs in a simulated, ex-vivo acetabular fracture model. We hypothesized that the String-of-Pearls™ constructs would have equivalent or greater mechanical properties and reduction compared to the other constructs. RESULTS: The mean craniocaudal acetabular diameter before fixation (mean 25.2 mm; range 20 mm - 30.1 mm) was not significantly different from after fixation (mean 23.9 mm; range 20 mm - 28.3 mm) for any fixation method. Comparison of reduction scores between groups revealed no significant differences. No significant differences were noted for cyclical displacement or stiffness. There was significant difference with superior failure load of String-of-Pearls™ compared to screw/wire/polymethylmethacrylate in the 75th percentile of animal weight (P = 0.0021), and superior failure load of String-of-Pearls™ compared to veterinary acetabular plates in the 50th (P = 0.0232) and 75th percentiles (P = 0.0058). Stiffness of the String-of-Pearls™ construct was significantly greater than the veterinary acetabular plate construct (P = 0.0417). For ultimate load, String-of-Pearls™ constructs were significantly greater than screw/wire/polymethylmethacrylate (P = 0.0331) and veterinary acetabular plates (P = 0.0218). CONCLUSION: Although the ease of application for the String-of-Pearls™ implant was subjectively better than other implants, no significant differences were found in fracture reduction scores. The String-of-Pearls™ constructs were stiffer than veterinary acetabular plates and exhibited greater failure and ultimate loads compared to veterinary acetabular plates and screw/wire/polymethylmethacrylate fixations. The String-of-Pearls™ implant appears to be a suitable fixation choice for simple canine acetabular fractures.

Effects of short- and long-term administration of nonsteroidal anti-inflammatory drugs on osteotomy healing in dogs.

OBJECTIVE: To determine the influence of short-term administration of carprofen on bone healing in dogs. STUDY DESIGN: Randomized controlled experimental study. ANIMALS: Eighteen purpose-bred sexually mature hound dogs. METHODS: Tibial osteotomies were performed, and dogs were divided into three groups: no carprofen (n = 6), 2-week administration of carprofen at 2.2 mg/kg twice daily (n = 6), and 8-week administration of carprofen at 2.2 mg/kg twice daily (n = 5). Bone healing was evaluated radiographically at 4 and 8 weeks postoperatively. Postmortem, fracture healing was assessed via biomechanical testing (three-point bending), histological cartilage:callus ratio, and bone mineral density (BMD) with quantitative computed tomography. RESULTS: No biomechanical difference was detected between dogs that received no carprofen and those that received 2 weeks of carprofen or between those that received 2 weeks vs 8 weeks of carprofen. Stiffness (P = .035) and maximum stress (P = .042) were higher in dogs that received no carprofen than in those that received 8 weeks of carprofen. Radiographic healing did not differ between dogs without carprofen and those with 2-week administration of carprofen (P = .9923). However, tibias of dogs without carprofen and those with 2-week administration of carprofen were more healed compared with those in the 8-week-carprofen group at 4 and 8 weeks after surgery (P = .0011). No treatment effect was detected by cartilage:callus ratio or BMD. CONCLUSION: Long-term administration of carprofen had a negative effect on bone healing compared with short-term or no administration of carprofen. CLINICAL SIGNIFICANCE: Nonsteroidal anti-inflammatory drugs should be used cautiously in dogs at risk for delayed bone healing, and administration should be discontinued beyond the perioperative period in dogs with fractures or osteotomies.

Scavenging in the Anthropocene: Human impact drives vertebrate scavenger species richness at a global scale.

Understanding the distribution of biodiversity across the Earth is one of the most challenging questions in biology. Much research has been directed at explaining the species latitudinal pattern showing that communities are richer in tropical areas; however, despite decades of research, a general consensus has not yet emerged. In addition, global biodiversity patterns are being rapidly altered by human activities. Here, we aim to describe large-scale patterns of species richness and diversity in terrestrial vertebrate scavenger (carrion-consuming) assemblages, which provide key ecosystem functions and services. We used a worldwide dataset comprising 43 sites, where vertebrate scavenger assemblages were identified using 2,485 carcasses monitored between 1991 and 2018. First, we evaluated how scavenger richness (number of species) and diversity (Shannon diversity index) varied among seasons (cold vs. warm, wet vs. dry). Then, we studied the potential effects of human impact and a set of macroecological variables related to climatic conditions on the scavenger assemblages. Vertebrate scavenger richness ranged from species-poor to species rich assemblages (4-30 species). Both scavenger richness and diversity also showed some seasonal variation. However, in general, climatic variables did not drive latitudinal patterns, as scavenger richness and diversity were not affected by temperature or rainfall. Rainfall seasonality slightly increased the number of species in the community, but its effect was weak. Instead, the human impact index included in our study was the main predictor of scavenger richness. Scavenger assemblages in highly human-impacted areas sustained the smallest number of scavenger species, suggesting human activity may be overriding other macroecological processes in shaping scavenger communities. Our results highlight the effect of human impact at a global scale. As species-rich assemblages tend to be more functional, we warn about possible reductions in ecosystem functions and the services provided by scavengers in human-dominated landscapes in the Anthropocene.

HLA Class I-sensitized Renal Transplant Patients Have Antibody Binding to SLA Class I Epitopes.

BACKGROUND: Highly sensitized patients are difficult to match with suitable renal allograft donors and may benefit from xenotransplant trials. We evaluate antibody binding from sensitized patients to pig cells and engineered single allele cells to identify anti-human leukocyte antigen (HLA) antibody cross-species reactivity with swine leukocyte antigen (SLA). These novel testing strategies assess HLA/SLA epitopes and antibody-binding patterns and introduce genetic engineering of SLA epitopes. METHODS: Sensitized patient sera were grouped by calculated panel reactive antibody and luminex single antigen reactivity profile and were tested with cloned GGTA1/CMAH/B4GalNT2 glycan knockout porcine cells. Pig reactivity was assessed by direct flow cytometric crossmatch and studied following elution from pig cells. To study the antigenicity of individual class I HLA and SLA alleles in cells, irrelevant sera binding to lymphoblastoid cells were minimized by CRISPR/Cas9 elimination of endogenous class I and class II HLA, B-cell receptor, and Fc receptor genes. Native HLA, SLA, and mutants of these proteins after mutating 144K to Q were assessed for antibody binding. RESULTS: Those with predominately anti-HLA-B&C antibodies, including Bw6 and Bw4 sensitization, frequently have low pig reactivity. Conversely, antibodies eluted from porcine cells are more commonly anti-HLA-A. Single HLA/SLA expressing engineered cells shows variable antigenicity and mutation of 144K to Q reduces antibody binding for some sensitized patients. CONCLUSIONS: Anti-HLA antibodies cross-react with SLA class I in predictable patterns, which can be identified with histocompatibility strategies, and SLA class I is a possible target of genetic engineering.

A cost analysis of producing vaccines in developing countries.

Developing country vaccine manufacturers (DCVMs) supply over half of the vaccines used in developing country immunisation programs. Decisions by developing countries to establish vaccine manufacturing should be based on economic viability, however reliable assessments of vaccine production costs are lacking. This study aimed to quantify the cost of establishing vaccine manufacturing facilities and producing vaccines in developing countries. This study estimates vaccine production costs in developing countries based on twelve vaccines produced by eight DCVMs. The results were based on estimates of the capital and operating costs required to establish vaccine manufacturing facilities under three hypothetical scenarios of production scale and scope. Cost patterns were then compared to vaccine prices paid by countries in both industrialized and developing country markets. The cost of producing vaccines in developing countries was estimated to be on average US$ 2.18 per dose, ranging between US$ 0.98 and US$ 4.85 for different vaccine types and formulations. Vaccine costs-per-dose decrease as production scale and scope increase. Cost-per-dose is mainly driven by fixed costs, but at a scale of production over 20 million doses per year it becomes driven by variable costs. Under the three hypothetical scenarios used, costs-per-dose of vaccines produced by developing countries were around 47% lower than vaccine prices in developing-country markets and 84% lower than prices in industrialized-country markets. This study has found that local production of vaccines in developing countries exhibits both economies of scale and economies of scope. The lower costs relative to prices suggests that a producer surplus and potential profits may be attainable in both developing and developed country markets, supporting sustainable production.

Postoperative renal impairment is associated with increased length of stay for incisional hernia repair after liver transplantation.

BACKGROUND: Incisional hernia repair is the most common procedure after orthotopic liver transplantation. Although enhanced recovery protocols are increasingly employed, the post-orthotopic liver transplantation patient may not benefit from all aspects of these models. The aim of the present study is to assess which perioperative interventions and patient factors affect hospital length of stay in a cohort of post-orthotopic liver transplantation patients undergoing incisional hernia repair. METHODS: We conducted a retrospective review of a series of adult patients undergoing incisional hernia repair after orthotopic liver transplantation. The primary endpoint was length of stay. Results were stratified by demographic, intraoperative, and postoperative variables. RESULTS: Eleven percent (172/1523) of patients who received orthotopic liver transplantation during the study period underwent subsequent incisional hernia repair. Median length of stay was 5 days (range 2-50). The strongest predictor of length of stay was postoperative renal function. Despite liberal intraoperative administration of volume (median 642 mL/h) and brisk intraoperative urine output (median 72 mL/h), postoperative acute kidney injury occurred in 48% of patients. Those that developed acute kidney injury received less intraoperative volume (6 vs 8.5 mL/kg/h; P = .031) and the severity of postoperative renal injury was inversely related to the amount intraoperative volume given. CONCLUSIONS: In patients undergoing incisional hernia repair after orthotopic liver transplantation, postoperative renal function is frequently impaired. Although many aspects of current ERAS protocols may be applied to post-transplant patients, restrictive intraoperative fluid administration strategies should be employed with caution given a high propensity for the development of post-operative acute kidney injury in this complex population.

Outcomes of pancreatoduodenectomy in the cirrhotic patient: risk stratification and meta-analysis.

BACKGROUND: Cirrhosis increases the risk of perioperative mortality in gastrointestinal surgery. Though cirrhosis is sometimes considered a contraindication to pancreatoduodenectomy (PD), few data are available in this patient population. The aim of the present study is to identify predictors of outcome in cirrhotic patients undergoing PD. METHODS: Patients undergoing PD with biopsy-proved cirrhosis were evaluated. Primary endpoints were morbidity and mortality. Child score, MELD score, and radiographic evidence of portal hypertension (pHTN) were assessed for accuracy in preoperative risk stratification. A systematic review of the literature with meta-analysis was also performed to query morbidity and mortality of patients with cirrhosis reported to undergo PD. RESULTS: Between 2005 and 2015, 36 cirrhotic patients underwent PD; three year follow-up was complete. Median Child score was 6 (range 5-10); median MELD score was 9 (range 7-18). Perioperative (90-day) mortality was 6/36. Median survival was 37 months (range 0.2-116). MELD ≥ 10 was associated with increased mortality (4/13 vs. 2/13, p = 0.004). Irrespective of Child or MELD score, those with pHTN had poor outcomes including significantly greater intraoperative blood loss, increased incidence of major complication, and length of stay. Postoperative mortality was significantly higher with pHTN (3/16 vs. 1/13, p = 0.012). CONCLUSION: Pancreatoduodenectomy may be considered in carefully selected cirrhotic patients. MELD ≥ 10 predicts increased risk of postoperative mortality. Specific attention should be afforded to patients with preoperative radiographic evidence of portal hypertension as this group experiences poor outcomes irrespective of MELD or Child score.

Zoonotic Helminth Diseases in Dogs and Dingoes Utilising Shared Resources in an Australian Aboriginal Community.

The impacts of free-roaming canids (domestic and wild) on public health have long been a concern in Australian Indigenous communities. We investigated the prevalence of zoonotic helminth diseases in dogs and sympatric dingoes, and used radio telemetry to measure their spatial overlap, in an Aboriginal community in the Wet Tropics of Australia. Samples collected from dingoes and dogs showed high levels of infection with the zoonotic hookworm, Ancylostoma caninum. Dingoes were also positive for A. ceylanicum infection (11.4%), but dogs were infection free. Whipworm, Trichuris vulpis, infection was far more prevalent in necropsies of domestic dogs (78.6%) than dingoes (3.7%). Dogs were free from Dirofilaria immitis infection, while dingoes recorded 46.2% infection. Eleven dingoes and seven free-roaming domestic dogs were fitted with Global Positioning System collars and tracked over an extended period. Dingo home-ranges almost completely overlapped those of the domestic dogs. However, dingoes and dogs did not utilise the same area at the same time, and dogs may have avoided dingoes. This spatial overlap in resource use presents an opportunity for the indirect spill-over and spill-back of parasites between dogs and dingoes. Tracking and camera traps showed that the community rubbish tip and animal carcasses were areas of concentrated activity for dogs and dingoes.

Corrigendum to "The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation".

[This corrects the article DOI: 10.1155/2017/8415205.].