Gastric Outlet Obstruction Palliation: A Novel Stent-Based Solution

Gastric outlet obstruction (GOO) after esophagectomy is a morbid outcome and significantly hinders quality of life for end-stage esophageal cancer patients. In the pre-stent era, palliation consisted of chemotherapy, radiation, tumor ablation, or stricture dilation. In the current era, palliative stenting has emerged as an additional tool; however, migration and tumor ingrowth are ongoing challenges. To mitigate these challenges, we developed a novel, hybrid, stent-based approach for the palliative management of GOO. We present a patient with esophageal cancer diagnosed with recurrent, metastatic disease 1 year after esophagectomy. She developed dehydration and intractable emesis, which significantly interfered with her quality of life. For palliation, we dilated the stenosis and proceeded with our stent-based solution. Using a combined endoscopic and fluoroscopic approach, we placed a 12-mm silicone salivary bypass tube across the pylorus, where it kinked slightly because of local tumor biology. To bridge this defect and ensure luminal patency, we placed a nitinol tracheobronchial stent through the silicone stent. Clinically, the patient had immediate relief from her pre-operative symptoms and was discharged home on a liquid diet. In conclusion, GOO and malignant dysphagia after esophagectomy are significant challenges for patients with end-stage disease. Palliative stenting is a viable option, but migration and tumor ingrowth are common complications. The hybrid approach presented here provides a unique solution to these potential pitfalls. The flared silicone tube minimized the chance of migration and impaired tumor ingrowth. The nitinol stent aided with patency and overcame the challenges of the soft tube. This novel strategy achieved palliation, describing another endoscopic option in the treatment of malignant GOO

MTHFD1 controls DNA methylation in Arabidopsis.

DNA methylation is an epigenetic mechanism that has important functions in transcriptional silencing and is associated with repressive histone methylation (H3K9me). To further investigate silencing mechanisms, we screened a mutagenized Arabidopsis thaliana population for expression of SDCpro-GFP, redundantly controlled by DNA methyltransferases DRM2 and CMT3. Here, we identify the hypomorphic mutant mthfd1-1, carrying a mutation (R175Q) in the cytoplasmic bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (MTHFD1). Decreased levels of oxidized tetrahydrofolates in mthfd1-1 and lethality of loss-of-function demonstrate the essential enzymatic role of MTHFD1 in Arabidopsis. Accumulation of homocysteine and S-adenosylhomocysteine, genome-wide DNA hypomethylation, loss of H3K9me and transposon derepression indicate that S-adenosylmethionine-dependent transmethylation is inhibited in mthfd1-1. Comparative analysis of DNA methylation revealed that the CMT3 and CMT2 pathways involving positive feedback with H3K9me are mostly affected. Our work highlights the sensitivity of epigenetic networks to one-carbon metabolism due to their common S-adenosylmethionine-dependent transmethylation and has implications for human MTHFD1-associated diseases

The First Provenance Challenge

The first Provenance Challenge was set up in order to provide a forum for the community to help understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a Functional Magnetic Resonance Imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the challenge, and submitted their inputs. In this paper, we present the challenge workflow and queries, and summarise the participants contributions

Hubble Space Telescope WFPC2 Imaging of M16: Photoevaporation and Emerging Young Stellar Objects

We present Hubble Space Telescope WFPC2 images of elephant trunks in the H II region M16. There are three principle results of this study. First, the morphology and stratified ionization structure of the interface between the dense molecular material and the interior of the H II region is well understood in terms of photoionization of a photoevaporative flow. Photoionization models of an empirical density profile capture the essential features of the observations, including the extremely localized region of [S II] emission at the interface and the observed offset between emission peaks in lower and higher ionization lines. The details of this structure are found to be a sensitive function both of the density profile of the interface and of the shape of the ionizing continuum. Interpretation of the interaction of the photoevaporative flow with gas in the interior of the nebula supports the view that much of the emission from H II regions may arise in such flows. Photoionization of photoevaporative flows may provide a useful paradigm for interpreting a wide range of observations of H II regions. Second, we report the discovery of a population of small cometary globules that are being uncovered as the main bodies of the elephant trunks are dispersed. Several lines of evidence connect these globules to ongoing star formation, including the association of a number of globules with stellar objects seen in IR images of M16 or in the continuum HST images themselves. We refer to these structures as evaporating gaseous globules, or "EGGs." These appear to be the same type of object as the nebular condensations seen previously in M42. The primary difference between the two cases is that in M16 we are seeing the objects from the side, while in M42 the objects are seen more nearly face-on against the backdrop of the ionized face of the molecular cloud. We find that the "evaporating globule" interpretation naturally accounts for the properties of objects in both nebulae, while avoiding serious difficulties with the competing "evaporating disk" model previously applied to the objects in M42. More generally, we find that disk-like structures are relatively rare in either nebula. Third, the data indicate that photoevaporation may have uncovered many EGGs while the stellar objects in them were still accreting mass, thereby freezing the mass distribution of the protostars at an early stage in their evolution. We conclude that the masses of stars in the cluster environment in M16 are generally determined not by the onset of stellar winds, as in more isolated regions of star formation, but rather by disruption of the star forming environment by the nearby O stars

The Open Provenance Model (v1.01)

In this paper, we introduce the Open Provenance Model, a model for provenance that is designed to meet the following requirements: (1) To allow provenance information to be exchanged between systems, by means of a compatibility layer based on a shared provenance model. (2) To allow developers to build and share tools that operate on such a provenance model. (3) To define the model in a precise, technology-agnostic manner. (4) To support a digital representation of provenance for any "thing", whether produced by computer systems or not. (5) To define a core set of rules that identify the valid inferences that can be made on provenance graphs

Pharyngostomy tubes for gastric conduit decompression

ObjectiveThis article illustrates our operative technique for pharyngostomy tube placement and describes our clinical experience with pharyngostomy use for gastric conduit decompression after esophagectomy.MethodsWe retrospectively reviewed patients undergoing pharyngostomy tube placement for gastric conduit decompression after esophagectomy from January 2008 to August 2009. Patients were included if they had a pharyngostomy tube placed at esophagectomy (prophylactic placement) or as a means of decompression after postesophagectomy anastomotic leak (therapeutic placement). We collected operative and clinical data and performed a descriptive statistical analysis.ResultsWe placed 25 pharyngostomy tubes for gastric conduit decompression after esophagectomy. Eleven were placed prophylactically (44%); the remaining 14 were placed therapeutically (56%) after anastomotic leak. Prophylactic pharyngostomy tubes remained in place a median of 8 days (range 4–17 days), whereas therapeutic pharyngostomy tubes were left in place a median of 15 days (range 7–125 days). There were 4 infectious complications (16%) unrelated to length of pharyngostomy use: 2 cases of cellulitis (resolved with antibiotics, tube remaining in place) and 2 superficial abscesses after tube removal requiring bedside débridement. Seventy-two percent of patients underwent swallow evaluation; 22% of these patients had radiographic evidence of aspiration.ConclusionsPharyngostomy tube placement for gastric conduit decompression after esophagectomy is simple, and tubes can stay in place for prolonged periods. Our experience suggests that pharyngostomy tubes are a safe alternative to nasogastric drainage