Management of the patient with acute pancreatitis

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A Glasgow tipple-transjugular intrahepatic portosystemic shunt insertion prior to Whipple resection

Abdominal surgery performed in patients with significant liver disease and portal hypertension is associated with high mortality rates, with even poorer outcomes associated with complex pancreaticobiliary operations. We report on a patient requiring portal decompression via transjugular intrahepatic portosystemic shunt (TIPS) prior to a pancreaticoduodenectomy. The 49-year-old patient presented with pain, jaundice and weight loss. At ERCP an edematous ampulla was biopsied, revealing high-grade dysplasia within a distal bile duct adenoma. Liver biopsy was performed to investigate portal hypertension, confirming congenital hepatic fibrosis (CHF). A TIPS was performed to enable a pancreaticoduodenectomy. Prophylactic TIPS can be performed for preoperative portal decompression for patients requiring pancreatic resection. A potentially curative resection was performed when abdominal surgery was initially thought impossible. Notably, CHF has been associated with the development of cholangiocarcinoma in only four previous instances, with this case being only the second reported distal bile duct cholangiocarcinoma

Nitrate stable isotopes and major ions in snow and ice samples from four Svalbard sites

Increasing reactive nitrogen (N-r) deposition in the Arctic may adversely impact N-limited ecosystems. To investigate atmospheric transport of N-r to Svalbard, Norwegian Arctic, snow and firn samples were collected from glaciers and analysed to define spatial and temporal variations (1 10 years) in major ion concentrations and the stable isotope composition (delta N-15 and delta O-18) of nitrate (NO3-) across the archipelago. The delta N-15(NO3-) and delta O-18(NO3-) averaged -4 parts per thousand and 67 parts per thousand in seasonal snow (2010-11) and -9 parts per thousand and 74 parts per thousand in firn accumulated over the decade 2001-2011. East-west zonal gradients were observed across the archipelago for some major ions (non-sea salt sulphate and magnesium) and also for delta N-15(NO3-) and delta O-18(NO3-) in snow, which suggests a different origin for air masses arriving in different sectors of Svalbard. We propose that snowfall associated with long-distance air mass transport over the Arctic Ocean inherits relatively low delta N-15(NO3-) due to in-transport N isotope fractionation. In contrast, faster air mass transport from the north-west Atlantic or northern Europe results in snowfall with higher delta N-15(NO3-) because in-transport fractionation of N is then time-limited

Scaling ozone responses of forest trees to the ecosystem level in a changing climate

Many uncertainties remain regarding how climate change will alter the structure and function of forest ecosystems. At the Aspen FACE experiment in northern Wisconsin, we are attempting to understand how an aspen/birch/maple forest ecosystem responds to long-term exposure to elevated carbon dioxide (CO 2 ) and ozone (O 3 ), alone and in combination, from establishment onward. We examine how O 3 affects the flow of carbon through the ecosystem from the leaf level through to the roots and into the soil micro-organisms in present and future atmospheric CO 2 conditions. We provide evidence of adverse effects of O 3 , with or without co-occurring elevated CO 2 , that cascade through the entire ecosystem impacting complex trophic interactions and food webs on all three species in the study: trembling aspen ( Populus tremuloides Michx . ), paper birch ( Betula papyrifera Marsh), and sugar maple ( Acer saccharum Marsh). Interestingly, the negative effect of O 3 on the growth of sugar maple did not become evident until 3 years into the study. The negative effect of O 3 effect was most noticeable on paper birch trees growing under elevated CO 2 . Our results demonstrate the importance of long-term studies to detect subtle effects of atmospheric change and of the need for studies of interacting stresses whose responses could not be predicted by studies of single factors. In biologically complex forest ecosystems, effects at one scale can be very different from those at another scale. For scaling purposes, then, linking process with canopy level models is essential if O 3 impacts are to be accurately predicted. Finally, we describe how outputs from our long-term multispecies Aspen FACE experiment are being used to develop simple, coupled models to estimate productivity gain/loss from changing O 3 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72464/1/j.1365-3040.2005.01362.x.pd

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries