Exergetic analysis of direct contact membrane distillation (DCMD) using PVDF hollow fiber membranes for the desalination brine treatment.

The brines from desalination plants need to be disposed of due to their strong impact on the environment. Membrane operations, like direct contact membrane distillation (DCMD), provide a possible solution to reduce the amount of brine while producing further desalinated water. In this study, an exergy analysis of a laboratory membrane distillation unit working with brines from reverse osmosis (RO) is analyzed. Exergy analysis enables us to assess the energy lost in entropy generation; therefore, it commits us to identify the less efficient configuration of the DCMD module. Unlike other exergy analyses for distillation, in this study, only module inputs and outputs were incorporated. The exergy is calculated at different infeed temperatures, for both in-out and out-in feed configurations of hollow fiber membrane modules. Also, exergy difference, flux, and exergetic efficiency for both configurations are calculated. At high feed temperatures, there is an increase in both flux and exergy change, which increases water recovery and feed side exergetic efficiency. The highest flux that is obtained in the out-in configuration is 13.3 kg/h.m2 while it is only 6.23 kg/h.m2 for the in-out system of the module. Also, these exergy changes and feed efficiencies are higher in the out-in module configuration than in the in-out module configuration. Conversely, the exergetic efficiency of the permeate is higher at lower feed temperatures, due to the lower accumulation of concentration polarization along the membrane wall.

siRNA Library Screening Identifies a Druggable Immune-Signature Driving Esophageal Adenocarcinoma Cell Growth.

BACKGROUND & AIMS: Effective therapeutic approaches are urgently required to tackle the alarmingly poor survival outcomes in esophageal adenocarcinoma (EAC) patients. EAC originates from within the intestinal-type metaplasia, Barrett's esophagus, a condition arising on a background of gastroesophageal reflux disease and associated inflammation. METHODS: This study used a druggable genome small interfering RNA (siRNA) screening library of 6022 siRNAs in conjunction with bioinformatics platforms, genomic studies of EAC tissues, somatic variation data of EAC from The Cancer Genome Atlas data of EAC, and pathologic and functional studies to define novel EAC-associated, and targetable, immune factors. RESULTS: By using a druggable genome library we defined genes that sustain EAC cell growth, which included an unexpected immunologic signature. Integrating Cancer Genome Atlas data with druggable siRNA targets showed a striking concordance and an EAC-specific gene amplification event associated with 7 druggable targets co-encoded at Chr6p21.1. Over-representation of immune pathway-associated genes supporting EAC cell growth included leukemia inhibitory factor, complement component 1, q subcomponent A chain (C1QA), and triggering receptor expressed on myeloid cells 2 (TREM2), which were validated further as targets sharing downstream signaling pathways through genomic and pathologic studies. Finally, targeting the triggering receptor expressed on myeloid cells 2-, C1q-, and leukemia inhibitory factor-activated signaling pathways (TYROBP-spleen tyrosine kinase and JAK-STAT3) with spleen tyrosine kinase and Janus-activated kinase inhibitor fostamatinib R788 triggered EAC cell death, growth arrest, and reduced tumor burden in NOD scid gamma mice. CONCLUSIONS: These data highlight a subset of genes co-identified through siRNA targeting and genomic studies of expression and somatic variation, specifically highlighting the contribution that immune-related factors play in support of EAC development and suggesting their suitability as targets in the treatment of EAC.

The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival.

Barrett's oesophagus (BO), an intestinal-type metaplasia (IM), typically arising in conjunction with gastro-oesophageal reflux disease, is a prominent risk factor for the development of oesophageal adenocarcinoma (OAC). The molecular similarities between IM and normal intestinal tissues are ill-defined. Consequently, the contribution of intestine-enriched factors expressed within BO to oncogenesis is unclear. Herein, using transcriptomics we define the intestine-enriched genes expressed in meta-profiles of BO and OAC. Interestingly, 77% of the genes differentially expressed in a meta-profile of BO were similarly expressed in intestinal tissues. Furthermore, 85% of this intestine-like signature was maintained upon transition to OAC. Gene networking analysis of transcription factors within this signature revealed a network centred upon NR5A2, GATA6 and FOXA2, whose over-expression was determined in a cohort of BO and OAC patients. Simulated acid reflux was observed to induce the expression of both NR5A2 and GATA6. Using siRNA-mediated silencing and an NR5A2 antagonist we demonstrate that NR5A2-mediated cancer cell survival is facilitated through augmentation of GATA6 and anti-apoptotic factor BCL-XL levels. Abrogation of NR5A2-GATA6 expression in conjunction with BCL-XL co-silencing resulted in synergistically increased sensitivity to chemotherapeutics and photo-dynamic therapeutics. These findings characterize the intestine-like signature associated with IM which may have important consequences to adenocarcinogenesis.

The diagnostic accuracy of endoscopic ultrasound in suspected biliary obstruction and its impact on endoscopic retrograde cholangiopancreatography burden in real clinical practice: a consecutive analysis.

BACKGROUND AND AIMS: Performing endoscopic ultrasound (EUS) before endoscopic retrograde cholangiopancreatography (ERCP) has been described to be useful in cases of suspected biliary obstruction where EUS can triage patients for ERCP. We aimed to determine the diagnostic accuracy of EUS and its impact on ERCP burden in real clinical practice. We also evaluated the safety and efficacy of EUS+ERCP in a single endoscopic session. PATIENTS AND METHODS: Four hundred and eighteen consecutive patients with suspected but unexplained biliary obstruction referred for EUS before possible ERCP were evaluated. The diagnostic accuracy of EUS and its value in predicting the need for ERCP were determined. EUS established whether pancreaticobiliary disorder (PBD) was present and whether therapeutic ERCP was required. These decisions were matched with ERCP findings, histology, clinical course, and follow-up. Where ERCP was indicated, it was performed in the same endoscopic session. RESULTS: EUS was performed in 412/418 patients (feasibility 98.5%), and ERCP was considered necessary in 64% (ERCP avoided in 36%). The single-session EUS and ERCP was safe and effective (264 patients). The diagnostic accuracy of EUS was as follows: choledocholithiasis 99%, malignant strictures 90%, and benign strictures 92%. EUS showed pathology in 42% of patients who had a nondilated biliary system at initial investigations. When EUS indicated a normal common bile duct (n=119), this had a 100% positive predictive value for non-necessity for ERCP. The median overall follow-up period was 12 months (range 6-34 months). CONCLUSION: EUS demonstrated high diagnostic accuracy in this mixed group of PBD. This accurately guided ERCP need and avoided unnecessary ERCP in 36%. EUS and ERCP in the same endoscopic session for the evaluation and management of PBD is technically feasible, with safety and efficacy profiles equivalent to that of each procedure performed independently in different sessions.