Purpose of Review
The purpose of this review was to examine the historical roots of endoscopic management of ampullary lesions and explore emerging data on improved techniques, technologies, and ...outcomes. Of specific interest was answering whether there exists a reasonable body of data to support one resection technique or strategy above others.
Recent Findings
Review of recent literature suggests the continued use of endoscopic ampullectomy is a safe and effective means of curative treatment of ampullary adenomas. Complications are relatively infrequent and complete endoscopic resection is possible in a majority of cases, with proper patient and lesion selection.
Summary
Greater than 2 decades of experience with endoscopic ampullectomy have shown this to be a viable, well-tolerated, and highly effective means of treating ampullary adenomas. While few concrete guidelines exist to advise endoscopists on the ideal technique for resection, experience, patient selection, and prior planning can greatly influence the technical and clinical success of endoscopic ampullectomy.
At least two functionally distinct transient outward K+ current (Ito) phenotypes can exist across the free wall of the left ventricle (LV). Based upon their voltage‐dependent kinetics of recovery ...from inactivation, these two phenotypes are designated ‘Ito,fast’ (recovery time constants on the order of tens of milliseconds) and ‘Ito,slow’ (recovery time constants on the order of thousands of milliseconds). Depending upon species, either Ito,fast, Ito,slow or both current phenotypes may be expressed in the LV free wall. The expression gradients of these two Ito phenotypes across the LV free wall are typically heterogeneous and, depending upon species, may consist of functional phenotypic gradients of both Ito,fast and Ito,slow and/or density gradients of either phenotype. We review the present evidence (molecular, biophysical, electrophysiological and pharmacological) for Kv4.2/4.3 α subunits underlying LV Ito,fast and Kv1.4 α subunits underlying LV Ito,slow and speculate upon the potential roles of each of these currents in determining frequency‐dependent action potential characteristics of LV subepicardial versus subendocardial myocytes in different species. We also review the possible functional implications of (i) ancillary subunits that regulate Kv1.4 and Kv4.2/4.3 (Kvβ subunits, DPPs), (ii) KChIP2 isoforms, (iii) spider toxin‐mediated block of Kv4.2/4.3 (Heteropoda toxins, phrixotoxins), and (iv) potential mechanisms of modulation of Ito,fast and Ito,slow by cellular redox state, Ca2+i and kinase‐mediated phosphorylation. Ito phenotypic activation and state‐dependent gating models and molecular structure–function relationships are also discussed.
Beginning in the 1980s, New Zealand experienced rising annual rates of campylobacteriosis that peaked in 2006. We analyzed notification, hospitalization, and other data to explore the 2007-2008 drop ...in campylobacteriosis incidence. Source attribution techniques based on genotyping of Campylobacter jejuni isolates from patients and environmental sources were also used to examine the decline. In 2008, the annual campylobacteriosis notification rate was 161.5/100,000 population, representing a 54% decline compared with the average annual rate of 353.8/100,000 for 2002-2006. A similar decline was seen for hospitalizations. Source attribution findings demonstrated a 74% (95% credible interval 49%-94%) reduction in the number of cases attributed to poultry. These reductions coincided with the introduction of a range of voluntary and regulatory interventions to reduce Campylobacter spp. contamination of poultry. The apparent success of these interventions may inform approaches other countries could consider to help control foodborne campylobacteriosis.
Myc-associated zinc-finger protein (MAZ) is a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression is associated with the progression of ...pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of action of MAZ in PDAC progression is largely unknown. Here, we present evidence that MAZ mRNA expression and protein levels are increased in human PDAC cell lines, tissue samples, a subcutaneous tumor xenograft in a nude mouse model, and spontaneous cancer in the genetically engineered PDAC mouse model. We also found that MAZ is predominantly expressed in pancreatic cancer stem cells. Functional analysis indicated that MAZ depletion in PDAC cells inhibits invasive phenotypes such as the epithelial-to-mesenchymal transition, migration, invasion, and the sphere-forming ability of PDAC cells. Mechanistically, we detected no direct effects of MAZ on the expression of K-Ras mutants, but MAZ increased the activity of CRAF–ERK signaling, a downstream signaling target of K-Ras. The MAZ-induced activation of CRAF–ERK signaling was mediated via p21-activated protein kinase (PAK) and protein kinase B (AKT/PKB) signaling cascades and promoted PDAC cell invasiveness. Moreover, we found that the matricellular oncoprotein cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) regulates MAZ expression via Notch-1–sonic hedgehog signaling in PDAC cells. We propose that Cyr61/CCN1-induced expression of MAZ promotes invasive phenotypes of PDAC cells not through direct K-Ras activation but instead through the activation of CRAF–ERK signaling. Collectively, these results highlight key molecular players in PDAC invasiveness and may help inform therapeutic strategies to improve clinical management and outcomes of PDAC.
The preferential elution of ions from melting snowpacks is a complex problem that has been linked to temporary acidification of water bodies. However, the understanding of these processes in ...snowpacks around the world, including the polar regions that are experiencing unprecedented warming and melting, remains limited despite being instrumental in supporting climate change adaptation.
In this study, data collected from a snowmelt lysimeter and snowpits at meadow and forest-gap sites in a high elevation watershed in Colorado were combined with the PULSE multi-phase snowpack chemistry model to investigate the controls of meltwater chemistry and preferential elution. The snowdepth at the meadow site was 64% of that at the forest-gap site, and the snowmelt rate was greater there (meadow snowpit) due to higher solar irradiance. Cations such as Ca2+ and NH4+ were deposited mostly within the upper layers of both the meadow and forest-gap snowpacks, and acid anions such as NO3− and SO42− were more evenly distributed. The snow ion concentrations were generally greater at the forest-gap snowpit, except for NH4+, which indicates that wind erosion of wet and dry deposited ions from the meadow may have reduced concentrations of residual snow. Furthermore, at the forest-gap site, snow interception and scavenging processes such as sublimation, ventilation, and throughfall led to particular ion enrichment of Ca2+, Mg2+, K+, Cl−, SO42− and NO3−. Model simulations and observations highlight that preferential elution is enhanced by low snowmelt rates, with the model indicating that this is due to lower dilution rates and increased contact time and area between the percolating meltwater and the snow. Results suggest that low snowmelt rates can cause multiple early meltwater ionic pulses for ions subject to lower ion exclusion. Ion exclusion rates at the grain-size level have been estimated for the first time.
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•Ion exclusion rates have been estimated directly from internal snowpack processes for the first time.•Combined low snowmelt and low ion exclusion rates can cause multiple early meltwater ionic pulses.•Snow layer containing much of winter wet and dry deposition can be removed by blowing snow in meadow snowpits.•Wind-unloading of intercepted ion concentration sublimation- and vegetation-enhanced snow can increase concentrations in forest-gap snowpacks.•The model validations presented are a key milestone for improved assessment of climate change impacts on water quality and the cryosphere.
Earth‐based radar observations of the spin state of Mercury at 35 epochs between 2002 and 2012 reveal that its spin axis is tilted by (2.04 ± 0.08) arc min with respect to the orbit normal. The ...direction of the tilt suggests that Mercury is in or near a Cassini state. Observed rotation rate variations clearly exhibit an 88‐day libration pattern which is due to solar gravitational torques acting on the asymmetrically shaped planet. The amplitude of the forced libration, (38.5 ± 1.6) arc sec, corresponds to a longitudinal displacement of ∼450 m at the equator. Combining these measurements of the spin properties with second‐degree gravitational harmonics (Smith et al., 2012) provides an estimate of the polar moment of inertia of MercuryC/MR2 = 0.346 ± 0.014, where M and R are Mercury's mass and radius. The fraction of the moment that corresponds to the outer librating shell, which can be used to estimate the size of the core, is Cm/C = 0.431 ± 0.025.
Key Points
Mercury's obliquity is (2.04 +/‐ 0.08) arcminutes
Mercury exhibits a longitude libration of amplitude (37.8 +/‐ 1.4) arcseconds
Mercury's moment of inertia is 0.346 +/‐ 0.014
Priority setting for food safety management at a national level requires risks to be ranked according to defined criteria. In this study, two approaches (disability-adjusted life years (DALYs) and ...cost of illness (COI)) were used to generate estimates of the burden of disease for certain potentially foodborne diseases (campylobacteriosis, salmonellosis, listeriosis (invasive, perinatal, and nonperinatal), infection with Shiga toxin-producing Escherichia coli (STEC), yersiniosis, and norovirus infection) and their sequelae in New Zealand. A modified Delphi approach was used to estimate the food-attributable proportion for these diseases. The two approaches gave a similar ranking for the selected diseases, with campylobacteriosis and its sequelae accounting for the greatest proportion of the overall burden of disease by far.
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