Retrospective comparative analysis of choledochoscopic bile duct exploration versus ERCP for bile duct stones.

Debate still exists for the management of choledocholithiasis. The purpose of this study is to quantify the rate of recurrent choledocholithiasis post choledochoscopic bile duct exploration (CBDE) in comparison to ERCP and sphincterotomy, and to demonstrate the feasibility of this approach in a busy metropolitan hospital. Data of patients undergoing CBDE from 2009-2014 at the Northern Hospital, Victoria, Australia, was collected retrospectively. Primary outcomes were bile duct clearance rate and rate of recurrent stones post-clearance. Secondary outcomes measured were post-operative complications, laparoscopic to open conversion rate and operative time. Data of patients undergoing ERCP at the same institution was collected and compared. In total, there were 4,091 cholecystectomy cases performed from 2009-2014, of which 260 (6.3%) of patients had an intraoperative cholangiography (IOC) indicating a common bile duct (CBD) stone. Two hundred and forty-eight patients (95.3%) had a CBDE. The remaining 12 patients (4.6%) had radiological clearance, which were excluded from the study. The overall clearance rate for patients undergoing CBDE was 84% (209/248). The risk of recurrent stones up to 8 years post clearance was 2% (4/209). In the same institution, and between 1998-2012, a total of 1,148 patients underwent ERCP, of which 571 had endoscopic sphincterotomy (ES). Forty-three patients required a repeat ERCP for recurrent CBD stones with a complication rate of 7.5%. Time to recurrence ranged from 6 months to 10 years with a mean of 4.5 years. The rate of recurrence was lower in the CBDE group compared to the patients who had an ERCP (8.9% vs. 2%). CBDE is a feasible and effective method for clearance of CBD stones at the time of laparoscopic cholecystectomy. This approach, although not widely used, reduces the need for ERCP, which has inherent complications. In the longer term, this series showed a significant reduction in the rate of CBD stone recurrence.

Is climate change a threat for water uses in the Mediterranean region? Results from a survey at local scale.

Water scarcity and water security are linked, not only through the direct effects of water shortages on each water users' access to water, but also because of water conflicts generated. Climate change is predicted to raise temperatures in the Mediterranean region and reduce rainfall, leading to a reduction in water yield and possibly worsening the situation of water resource shortages that Mediterranean regions are already experiencing. In its dissemination strategy, the EU FP7 CLIMB project addressed water security threats through an analysis of water uses and water use rivalries within a few target catchments distributed over the Mediterranean region. The present work explores whether climate change is locally perceived by stakeholders (water users and managers) as a key issue for their water uses and water security. Individual interviews, meetings, and compilation of questionnaires were conducted at five sites located in the Mediterranean region. The methodology permitted an analysis of water use and its evolution in the water management context, an identification of the state of awareness of local stakeholders and of the pressures on water use and water use rivalries, and a prioritization of water uses. Currently, the main response to increasing water demand in the Mediterranean region, while not yet considering climate change as a driving force, is a progressive externalization of water resources, with limits represented by national borders and technological possibilities. Overall, 'climate change' was not mentioned by stakeholders during both interviews and in answers to the questionnaires. Even the prospect of decreasing precipitation was not considered a relevant or threatening issue in the coming 20years. This confirms the need to continue all efforts to disseminate the state of knowledge on climate change impacts in the Mediterranean region, such as water scarcity, especially to local water managers, as initiated by various research programs of the European Commission.

A cost-effectiveness analysis of a telephone-linked care intervention for individuals with Type 2 diabetes.

AIM: To assess the cost-effectiveness of an automated telephone-linked care intervention, Australian TLC Diabetes, delivered over 6 months to patients with established Type 2 diabetes mellitus and high glycated haemoglobin level, compared to usual care. METHODS: A Markov model was designed to synthesize data from a randomized controlled trial of TLC Diabetes (n=120) and other published evidence. The 5-year model consisted of three health states related to glycaemic control: 'sub-optimal' HbA1c ≥58mmol/mol (7.5%); 'average' ≥48-57mmol/mol (6.5-7.4%) and 'optimal' <48mmol/mol (6.5%) and a fourth state 'all-cause death'. Key outcomes of the model include discounted health system costs and quality-adjusted life years (QALYS) using SF-6D utility weights. Univariate and probabilistic sensitivity analyses were undertaken. RESULTS: Annual medication costs for the intervention group were lower than usual care [ INTERVENTION: £1076 (95%CI: £947, £1206) versus usual care £1271 (95%CI: £1115, £1428) p=0.052]. The estimated mean cost for intervention group participants over five years, including the intervention cost, was £17,152 versus £17,835 for the usual care group. The corresponding mean QALYs were 3.381 (SD 0.40) for the intervention group and 3.377 (SD 0.41) for the usual care group. Results were sensitive to the model duration, utility values and medication costs. CONCLUSION: The Australian TLC Diabetes intervention was a low-cost investment for individuals with established diabetes and may result in medication cost-savings to the health system. Although QALYs were similar between groups, other benefits arising from the intervention should also be considered when determining the overall value of this strategy.

Strongyloides stercoralis transmission by kidney transplantation in two recipients from a common donor.

Strongyloides stercoralis hyperinfection in an immunocompromised host has a high mortality rate but may initially present with nonspecific pulmonary and gastrointestinal symptoms. Donor-derived S. stercoralis by kidney transplantation is an uncommon diagnosis and difficult to prove. We report two renal allograft recipients on different immunosuppressive maintenance regimens that developed strongyloidiasis after transplantation from the same donor. Recipient 1 presented with a small bowel obstruction. Larvae were demonstrated on a duodenal biopsy and isolated from gastric, pulmonary, and stool samples. Serologic testing for S. stercoralis was negative at a referral laboratory but positive at the Centers for Disease Control. The patient's hospital course was complicated by a hyperinfection syndrome requiring subcutaneous ivermectin due to malabsorption. Recipient 1 survived but the allograft failed. Recipient 2 had larvae detected in stool samples after complaints of diarrhea and was treated. On retrospective testing for S. stercoralis, pretransplant serum collected from the donor and Recipient 1 was positive and negative, respectively. Donor-derived strongyloidiasis by renal transplantation is a preventable disease that may be affected by the immunosuppressive maintenance regimen. Subcutaneous ivermectin is an option in the setting of malabsorption. Finally, routine screening for S. stercoralis infection in donors from endemic areas may prevent future complications.

Species compositions and ecology of the riverine ichthyofaunas in two Sulawesian islands in the biodiversity hotspot of Wallacea.

This account of the riverine ichthyofaunas from the islands of Buton and Kabaena, off south-eastern mainland Sulawesi, represents the first detailed quantitative checklist and ecological study of the riverine fish faunas in the biological hotspot of Wallacea. The results are based on analysis of samples collected by electrofishing at a wide range of sites from July to September in both 2001 and 2002. While the fauna was diverse, with the 2179 fishes caught comprising 64 species representing 43 genera and 22 families, the catches were dominated by the Gobiidae (26 species and 25% by numbers), Eleotridae (seven species and 27% by numbers), Zenarchopteridae (three species and 22% by numbers) and Anguillidae (two species and 12% by numbers). The most abundant species were the eleotrids Eleotris aff. fusca-melanosoma and Ophieleotris aff. aporos, the anguillid Anguilla celebesensis, the zenarchopterids Nomorhamphus sp. and Nomorhamphus ebrardtii and the gobiids Sicyopterus sp. and Glossogobius aff. celebius-kokius. The introduced catfish Clarias batrachus was moderately abundant at a few sites. Cluster analysis, allied with the similarity profiles routine SIMPROF, identified seven discrete groups, which represented samples from sites entirely or predominantly in either Buton (five clusters) or Kabaena (two clusters). Species composition was related to geographical location, distance from river mouth, per cent contribution of sand and silt, altitude and water temperature. The samples from the two islands contained only one species definitively endemic to Sulawesi, i.e. N. ebrardtii and another presumably so, i.e. Nomorhamphus sp., contrasting starkly with the 57 species that are endemic to Sulawesi and, most notably, its large central and deep lake systems on the mainland. This accounts for the ichthyofaunas of these two islands, as well as those of rivers in northern mainland Sulawesi and Flores, being more similar to each other than to those of the central mainland lake systems. This implies that the major adaptive radiation of freshwater fishes in Sulawesi occurred in those lacustrine environments rather than in rivers.

Lysyl oxidase enzymatic function increases stiffness to drive colorectal cancer progression through FAK.

The extracellular, matrix-modifying enzyme lysyl oxidase (LOX) has recently been linked to colorectal cancer (CRC) progression, in particular to the stages of invasion and metastasis. In this report, we use cell lines expressing a catalytically inactive mutant form of LOX to show that catalytic activity is required for LOX-mediated effects on proliferation and invasion in both in vitro and in vivo models of CRC. Furthermore, we use rheology to measure the relative stiffness of modified collagen matrices and subcutaneous tumors, and show that LOX-induced collagen cross-linking results in stiffening of the matrix both in vitro and in vivo. We observe a strong association between matrix stiffness and activation of the FAK (focal adhesion kinase)/SRC-signaling pathway, with a stiffer environment resulting in increased FAK/SRC phosphorylation and a more proliferative and invasive phenotype. We are the first to show a direct relationship between LOX enzymatic activity and tissue stiffness, and to demonstrate a role for stiffness in driving CRC progression. Our findings provide significant evidence to suggest that therapeutic inhibition of LOX activity may provide a novel effective treatment option for patients with metastatic CRC.

Use of in vivo phycocyanin fluorescence to monitor potential microcystin-producing cyanobacterial biovolume in a drinking water source.

The source water of a drinking water treatment plant prone to blooms, dominated by potential microcystin-producing cyanobacteria, was monitored for two seasons in 2007-2008. In the 2008 season, the median value for potential microcystin-producing cyanobacterial biovolume was 87% of the total phytoplankton biovolume in the untreated water of the plant. Depth profiles taken above the plant's intake identified three sampling days at high risk for the contamination of the plant's raw water with potentially toxic cyanobacteria. Chlorophyceae and Bacillariophyceae caused false positive values to be generated by the phycocyanin probe when cyanobacteria represented a small fraction of the total phytoplanktonic biovolume present. However, there was little interference with the phycocyanin probe readings by other algal species when potential microcystin-producing cyanobacteria dominated the phytoplankton of the plant's untreated water. A two-tiered method for source water monitoring, using in vivo phycocyanin fluorescence, is proposed based on (1) a significant relationship between in vivo phycocyanin fluorescence and cyanobacterial biovolume and (2) the calculated maximum potential microcystin concentration produced by dominant Microcystis sp. biovolume. This method monitors locally-generated threshold values for cyanobacterial biovolume and microcystin concentrations using in vivo phycocyanin fluorescence.

Fish and macro-crustacean communities and their dynamics in the Severn Estuary.

The species of fish and macro-crustacean living within the Severn Estuary are reviewed. The fish community is notably species rich and exceeds 100 species in total for the estuary. Standardised long-term sampling at Hinkley Point in Bridgwater Bay gives a total complement of 83 for a single locality and this number is increasing by about one new species every two years. Most of these new species are moving in from centres of population lying to the south of the estuary. Almost all species of fish and macro-crustacean living within the estuary undertake regular migrations so that they tend to move seasonally in waves up and down the estuary. For fish, both species richness and the total abundance reach a maximum in late summer and autumn. The timing of this peak varies between the upper and lower estuary. This seasonal maximum is primarily caused by the arrival of the new recruits which use the estuary as a nursery. In contrast, crustaceans tend to be at their most diverse and abundant in early to mid summer. Using a 30-year time series of fish and crustacean abundance collected at Hinkley Point it is shown that major changes in the structure of the community are now underway and there are considerable recent changes in the abundance. However, some abundant species, including sand goby, Pomatoschistus spp., whiting, Merlangius merlangus and sprat, Sprattus sprattus, the three most abundant species in the estuary, have shown no long-term trend. At present, approximately 20% of the fish and macro-crustaceans observed in Bridgwater Bay are undergoing rapid, typically exponential, change in abundance. For a numerically abundant, diverse, fauna composed of approximately 90 species such levels of change are unexpected and suggest that the system is presently far from equilibrium. In some cases, the observed changes can be related to recent warming and the North Atlantic Oscillation. The overall increase in fish abundance observed may reflect a general improvement in water quality and a reduction in other anthropogenic impacts such as mortality in cooling-water intakes. The potential impacts of tidal power generation in the Severn Estuary are reviewed. There is considerable potential for any major installation to impact the fish and crustacean populations as they migrate and also alter the nature of the habitat resulting in changes in community composition. A particular difficulty in predicting the future impact of harnessing tidal energy is that the present community is already changing rapidly. The ability of fish and crustaceans to pass through the turbines unharmed will be a key issue in an assessment of the impact of tidal power generation.

The "fire stick farming" hypothesis: Australian Aboriginal foraging strategies, biodiversity, and anthropogenic fire mosaics.

Aboriginal burning in Australia has long been assumed to be a "resource management" strategy, but no quantitative tests of this hypothesis have ever been conducted. We combine ethnographic observations of contemporary Aboriginal hunting and burning with satellite image analysis of anthropogenic and natural landscape structure to demonstrate the processes through which Aboriginal burning shapes arid-zone vegetational diversity. Anthropogenic landscapes contain a greater diversity of successional stages than landscapes under a lightning fire regime, and differences are of scale, not of kind. Landscape scale is directly linked to foraging for small, burrowed prey (monitor lizards), which is a specialty of Aboriginal women. The maintenance of small-scale habitat mosaics increases small-animal hunting productivity. These results have implications for understanding the unique biodiversity of the Australian continent, through time and space. In particular, anthropogenic influences on the habitat structure of paleolandscapes are likely to be spatially localized and linked to less mobile, "broad-spectrum" foraging economies.

Functions, regulation and cellular localization of plant cyclin-dependent kinase inhibitors.

The cell cycle is regulated by the cyclin-dependent kinase (CDK), and CDK inhibitors can bind to CDKs and inhibit their activities. This review examines plant CDK inhibitors, with particular emphasis on their molecular and cellular functions, regulation and cellular localization. In plants, a family of ICK/KRP CDK inhibitors represented by ICK1 is known and another type of CDK inhibitor represented by the SIMESE (SIM) has recently been reported. Considerable understanding has been gained with the ICK/KRP CDK inhibitors. These plant CDK inhibitors share only limited sequence similarity in the C-terminal region with the KIP/CIP family of mammalian CDK inhibitors. The ICK/KRP CDK inhibitors thus provide good tools to understand the basic machinery as well as the unique aspects of the plant cell cycle. The ICK/KRP CDK inhibitors interact with D-type cyclins or A-type CDKs or both. Several functional regions and motifs have been identified in ICK1 for CDK inhibition, nuclear localization and protein instability. Clear evidence shows that ICK/KRP proteins are important for the cell cycle and endoreduplication. Preliminary evidence suggests that they may also be involved in cell differentiation and cell death. Results so far show that plant CDK inhibitors are exclusively localized in the nucleus. The molecular sequences regulating the localization and functional significance will be discussed.

Navigating transdermal diffusion with multiphoton fluorescence lifetime imaging.

We demonstrate the potential of fluorescence lifetime imaging by time-correlated single-photon counting as a method for monitoring the transdermal diffusion pathway and diffusion rate of pharmaceuticals in human skin. The current application relies on observing subtle changes in the fluorescence lifetime of the intrinsic fluorophores present in the intracellular region between corneocytes of the stratum corneum. We have comprehensively characterized the measured fluorescence lifetimes from intracorneocyte junctions in three skin section types (dermatomed skin, epidermal membranes and stratum corneum) revealing statistically significant differences of the short lifetime component between each of the types, which we attribute to the sample preparation and imaging method. We show using epidermal membrane sections that application of a drug/solvent formulation consisting of ethinyl estradiol and spectroscopic grade ethanol to the surface gives rise to a slight but statistically significant shortening of the fluorescence lifetime of the long-lived emitting species present in the sample, from approximately 2.8 ns to 2.5 ns. The method may be useful for future studies where the kinetics and pathways of a variety of applied formulations could be investigated.

To what extent are hepatic concentrations of heavy metals in Anguilla anguilla at a site in a contaminated estuary related to body size and age and reflected in the metallothionein concentrations?

We explored how hepatic [metal]s in Anguilla anguilla at a contaminated estuarine site are influenced by body size, age and season, and the extent that [Cu], [Cd] and [Zn]s are reflected in [metallothionein (MT)]s. Although each [metal] and [MT] increased significantly with length, weight and age, those biotic variables explained <10% of the variation in each [metal] and only 11-16% for [MT]. Seasonal changes in [Cu] and [Cd] were paralleled by [MT]. The variation in [MT] explained by Cu (42%) was greater than by Zn (16%) and Cd (13%), and seasonally lay between 43 and 69% for those metals collectively. Thus, hepatic [MT] in eels is closely correlated with hepatic [heavy metal]s. However, the great variability among [MT]s for eels of similar sizes and ages, which reflects marked variability in hepatic [heavy metal]s, means that this variable reflects imprecisely the contamination level at a particular site.

Spectrum of electronic excitations due to the adsorption of atoms on metal surfaces.

The time-dependent, mean-field Newns-Anderson model for a spin-polarized adsorbate approaching a metallic surface is solved in the wide-band limit. Equations for the time evolution of the electronic structure of the adsorbate-metal system are derived and the spectrum of electronic excitations is found. The behavior of the model is demonstrated for a set of physically reasonable parameters.

Optimized temporal response in multichannel two-photon fluorescence lifetime microscopy using a photonic crystal fibre.

The integration of fibre optics into an imaging system for the convenient delivery and collection of light has resulted in many hybrid forms of novel biomedical optical instrumentation. Although it is extremely robust and cost effective, fibre integration requires special consideration in a time-domain fluorescence lifetime imaging schema where multipath propagation in the fibre causes significant spread in photon transit times. In this study, we investigated the effect of the length of a multimode collection fibre on the temporal performance of a multichannel fluorescence lifetime microscope and demonstrated the effectiveness of a photonic crystal fibre as a means of optimizing the collection and delivery of emitted fluorescence in terms of temporal resolution. The findings are pertinent to all studies that employ a multimode optical fibre to collect and deliver an emitted fluorescence signal from a sample to a remote detector for measurement of the characteristic fluorescence lifetime.

Experimental demonstration of the frequency shift of bandgaps in photonic crystal fibers due to refractive index scaling.

Experimental demonstration of the frequency shift of photonic bandgaps due to refractive index scaling using D2O-filled hollow-core photonic crystal fibers is presented. The results confirm a simple scaling law for bandgaps in fibers in which the low-index medium is varied.

Bend loss in all-solid bandgap fibres.

Experimental measurements of all-solid photonic bandgap fibres with an array of high-index rods in a low-index background revealed an unexpected variation of bend loss across different bandgaps. This behaviour was confirmed by calculations of photonic band structure, and explained with reference to the differing field distributions of the modes of the cladding rods. Our understanding was confirmed by further experiments, leading to proposals for the improvement of these fibres.