Skin layer recovery of free-surface wakes: Relationship to surface renewal and dependence on heat flux and background turbulence

The thermal signatures of free-surface wakes observed in the open ocean show that the recovery of the cool skin layer is related to the degree of surface mixing and to ambient environmental conditions. Wakes produced by two surface-piercing cables of O(10−2 m) in diameter are analyzed using infrared imagery. Under low-wind-speed conditions when the swell and surface current were aligned, the wakes exhibited distinctive patchlike features of O(1 m) in diameter that were generated by the passage of individual waves. The time t* required by the skin layer to recover from these disturbances is compared to the surface-renewal timescale τ used in heat and gas flux models. At low wind speeds, t* is comparable to τ, but at moderate wind speeds the agreement is poor. The spatial and temporal variations in the skin temperature of these wakes are related to a wave Reynolds number used to characterize the strength of the disturbance due to the waves. The recovery process is characterized in terms of the restoring internal energy flux Jr which is proportional to both the initial thickness and the thermal recovery rate of the skin layer and was found to be directly related to the strength of the surface disruption. Comparison of the wake results with laboratory and other field measurements of breaking waves implies that Jr is also a strong function of the net heat flux and background turbulence, which relate directly to the existing environmental conditions such as wind stress and sea state. Our results demonstrate that Jr may vary by several orders of magnitude, depending on the environmental conditions

KRAS and PIK3CA mutation frequencies in patient derived xenograft (PDX) models of pancreatic and colorectal cancer are reflective of patient tumors and stable across passages

One key obstacle to the translation of advances in cancer research into the clinic is a deficiency of adequate preclinical models that recapitulate human disease. The development and application of validated preclinical models that reflect patient histological, cellular, and molecular characteristics is needed. Current preclinical models rely heavily on conventional cell line xenograft models which are established by engrafting human tumor cell lines cultured in the laboratory into mice. This model is widely acknowledged to provide useful, but unreliable predictive capacity for anti-tumor activity in humans (Sharpless and Depinho 2006). One possible explanation for the unreliability of cell line xenograft results translating to the clinic, is that these cells represent clonal tumor populations that have selectively grown on plastic and have adapted to growth outside of the natural tumor microenvironment (Frese and Tuveson 2007; Tentler et al. 2012). Because cell line xenograft models lack stromal cells, which are increasingly recognized as a critical element for tumorigenesis, these models fail to accurately recapitulate tumor biology and tumor response to therapy (Bhowmick et al. 2004; Sharpless and Depinho 2006; Frese and Tuveson 2007)

Obol: Integrating Language and Meaning in Bio-Ontologies

Ontologies are intended to capture and formalize a domain of knowledge. The ontologies comprising the Open Biological Ontologies (OBO) project, which includes the Gene Ontology (GO), are formalizations of various domains of biological knowledge. Ontologies within OBO typically lack computable definitions that serve to differentiate a term from other similar terms. The computer is unable to determine the meaning of a term, which presents problems for tools such as automated reasoners. Reasoners can be of enormous benefit in managing a complex ontology. OBO term names frequently implicitly encode the kind of definitions that can be used by computational tools, such as automated reasoners. The definitions encoded in the names are not easily amenable to computation, because the names are ostensibly natural language phrases designed for human users. These names are highly regular in their grammar, and can thus be treated as valid sentences in some formal or computable language.With a description of the rules underlying this formal language, term names can be parsed to derive computable definitions, which can then be reasoned over. This paper describes the effort to elucidate that language, called Obol, and the attempts to reason over the resulting definitions. The current implementation finds unique non-trivial definitions for around half of the terms in the GO, and has been used to find 223 missing relationships, which have since been added to the ontology. Obol has utility as an ontology maintenance tool, and as a means of generating computable definitions for a whole ontology

Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma

Drug delivery to pancreatic tumors is impaired by a unique desmoplastic response and poor tumor vascularization. A drug delivery device capable of overcoming these barriers could provide substantial benefit for patients with pancreatic cancer. In this study, we show that local iontophoretic delivery of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) resulted in better tumor response and tolerability compared with i.v. FOLFIRINOX. Given the low systemic exposure of FOLFIRINOX using iontophoretic delivery, it may be possible to use in combination with systemic delivery to treat micrometastatic disease. Local iontophoretic delivery of cytotoxic agents should be considered as a neoadjuvant approach to improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer

Pheochromocytomatosis associated with a novel TMEM127 mutation

Pheochromocytomatosis, a very rare form of pheochromocytoma recurrence, refers to new, multiple, and often small pheochromocytomas growing in and around the surgical resection bed of a previous adrenalectomy for a solitary pheochromocytoma. We here report a case of pheochromocytomatosis in a 70-year-old female. At age 64 years, she was diagnosed with a 6-cm right pheochromocytoma. She underwent laparoscopic right adrenalectomy, during which the tumor capsule was ruptured. At age 67 years, CT of abdomen did not detect recurrence. At age 69 years, she began experiencing episodes of headache and diaphoresis. At age 70 years, biochemical markers of pheochromocytoma became elevated with normal calcitonin level. CT revealed multiple nodules of various sizes in the right adrenal fossa, some of which were positive on metaiodobenzylguanidine (MIBG) scan. She underwent open resection of pheochromocytomatosis. Histological examination confirmed numerous pheochromocytomas ranging 0.1–1.2 cm in size. Next-generation sequencing of a panel of genes found a novel heterozygous germline c.570delC mutation in TMEM127, one of the genes that, if mutated, confers susceptibility to syndromic pheochromocytoma. Molecular analysis showed that the c.570delC mutation is likely pathogenic. Our case highlights the typical presentation of pheochromocytomatosis, a rare complication of adrenalectomy for pheochromocytoma. Previous cases and ours collectively demonstrate that tumor capsule rupture during adrenalectomy is a risk factor for pheochromocytomatosis. We also report a novel TMEM127 mutation in this case

Infection with hepatitis B virus carrying novel pre-S/S gene mutations in female siblings vaccinated at birth: two case reports

<p>Abstract</p> <p>Introduction</p> <p>After the initiation of a mass hepatitis B vaccination program in Taiwan, the prevalence of hepatitis B virus infection has declined progressively. However, about 1 percent of the young generation, who received hepatitis B vaccination at birth, remain carriers. Infection with vaccine-escape hepatitis B virus mutants always occurs shortly after birth. Here, we report two female siblings in whom the infection occurred in their adolescence. This report raises the question of whether a booster for hepatitis B vaccination is needed.</p> <p>Case presentation</p> <p>Two 19 and 14-year-old Taiwanese female siblings were born to a mother infected with hepatitis B virus and received a complete course of hepatitis B vaccination at birth. They remained negative for serum hepatitis B surface antigen and positive for serum anti-hepatitis B surface antibody throughout their childhood. However, both were infected with the hepatitis B virus in their adolescence. Hepatitis B virus DNA was extracted from serum samples from the mother and two siblings. Hepatitis B virus pre-S/S sequence was amplified by polymerase chain reaction followed by nucleotide sequencing. When compared with the sequence obtained from the mother, multiple amino acid substitutions located near or in the major hydrophilic region of the surface antigen were identified in the elder sister. Four of these mutations (sL97S, sL98S, sG102R, and sA159P) were novel. A novel in-frame deletion (14 amino acids deleted, pre-S 127-140) was found in the hepatitis B virus pre-S2 region in the younger sister.</p> <p>Conclusions</p> <p>Despite having received hepatitis B vaccination at birth, hepatitis B virus infection can still occur in adolescence with the emergence of novel mutations in the pre-S/S gene. This is a rare event and, to the best of our knowledge, has not been previously reported.</p

Tumor slice culture as a biologic surrogate of human cancer.

Background: The tumor microenvironment (TME) is critical to every aspect of cancer biology. Organotypic tumor slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but the association between clinicopathologic parameters and Methods: One hundred and eight fresh tumor specimens from liver resections at a tertiary academic center were procured and precisely cut with a Vibratome to create 250 μm × 6 mm slices. These fixed-dimension TSCs were grown on polytetrafluoroethylene inserts, and their metabolic activities were determined by a colorimetric assay. Correlation between baseline activities and clinicopathologic parameters was assessed. Tissue CEA mRNA expression was determined by RNAseq. Results: By standardizing the dimensions of a slice, we found that adjacent tumor slices have equivalent metabolic activities, while those derived from different tumors exhibit \u3e30-fold range in baseline MTS absorbances, which correlated significantly with the percentage of tumor necrosis based on histologic assessment. Extending this to individual cancers, we were able to detect intra-tumoral heterogeneity over a span of a few millimeters, which reflects differences in tumor cell density and Ki-67 positivity. For colorectal cancers, tissue CEA expression based on RNAseq of tumor slices was found to correlate with clinical response to chemotherapies. Conclusions: We report a standardized method to assess and compare human cancer growth ex vivo across a wide spectrum of tumor samples. TSC reflects the state of tumor behavior and heterogeneity, thus providing a simple approach to study of human cancers with an intact TME

Circulating Tumor Cells as a Biomarker of Response to Treatment in Patient-Derived Xenograft Mouse Models of Pancreatic Adenocarcinoma

Circulating tumor cells (CTCs) are cells shed from solid tumors into circulation and have been shown to be prognostic in the setting of metastatic disease. These cells are obtained through a routine blood draw and may serve as an easily accessible marker for monitoring treatment effectiveness. Because of the rapid progression of pancreatic ductal adenocarcinoma (PDAC), early insight into treatment effectiveness may allow for necessary and timely changes in treatment regimens. The objective of this study was to evaluate CTC burden as a biomarker of response to treatment with a oral phosphatidylinositol-3-kinase inhibitor, BKM120, in patient-derived xenograft (PDX) mouse models of PDAC. PDX mice were randomized to receive vehicle or BKM120 treatment for 28 days and CTCs were enumerated from whole blood before and after treatment using a microfluidic chip that selected for EpCAM (epithelial cell adhesion molecule) positive cells. This microfluidic device allowed for the release of captured CTCs and enumeration of these cells via their electrical impedance signatures. Median CTC counts significantly decreased in the BKM120 group from pre- to post-treatment (26.61 to 2.21 CTCs/250 µL, p = 0.0207) while no significant change was observed in the vehicle group (23.26 to 11.89 CTCs/250 µL, p = 0.8081). This reduction in CTC burden in the treatment group correlated with tumor growth inhibition indicating CTC burden is a promising biomarker of response to treatment in preclinical models. Mutant enriched sequencing of isolated CTCs confirmed that they harbored KRAS G12V mutations, identical to the matched tumors. In the long-term, PDX mice are a useful preclinical model for furthering our understanding of CTCs. Clinically, mutational analysis of CTCs and serial monitoring of CTC burden may be used as a minimally invasive approach to predict and monitor treatment response to guide therapeutic regimens

Relationships of the Psychological Influence of Food and Barriers to Lifestyle Change to Weight and Utilization of Online Weight Loss Tools

Abstract: Introduction: The psychological influence of food (PFS) and perceived barriers to lifestyle change (PBLC) were considered as predictors of body mass index and website tool utilization (TU) in an online weight loss program. Materials and Methodology: An archival analysis of all (N = 1361) overweight/obese (BMI M = 31.6 + 6.24 kg/m 2), adult (M = 42.0 + 10.72 years) users (82.4 % female) of an evidence-based, multidisciplinary Internet weight loss program was performed. Predictor variables included: PFS and PBLC, age, and longest maintained weight loss in relation to 1) BMI 2

Defining trauma-induced coagulopathy with respect to future implications for patient management : Communication from the SSC of the ISTH

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