Systematic Review and Meta-analysis of SurgicalTreatment of Non-Zenker?s Oesophageal Diverticula

Background Oesophageal diverticula are rare outpouchings of the oesophagus which may be classified anatomically as pharyngeal (Zenker’s), mid-oesophageal and epiphrenic. While surgery is indicated for symptomatic patients, no consensus exists regarding the optimum technique for non-Zenker’s oesophageal diverticula. The aim of this study was to determine the outcome of surgery in patients with non-Zenker’s oesophageal diverticula. Methods PubMed, MEDLINE and the Cochrane Library (January 1990 to January 2016) were searched for studies which reported outcomes of surgery in patients with non-Zenker’s oesophageal diverticula. Primary outcome measure was the rate of staple line leakage. Results Twenty-five observational studies involving 511 patients (259 male, median age 62 years) with mid-oesophageal (n = 53) and epiphrenic oesophageal (n = 458) diverticula who had undergone surgery [thoracotomy (n = 252), laparoscopy (n = 204), thoracoscopy (n = 42), laparotomy (n = 5), combined laparoscopy and thoracoscopy (n = 8)] were analysed. Myotomy was performed in 437 patients (85.5%), and anti-reflux procedures were performed in 342 patients (69.5%). Overall pooled staple line leak rates were reported in 13.3% [95% c.i. (11.0–15.7), p < 0.001] and were less common after myotomy (12.4%) compared with no myotomy (26.1%, p = 0.002). Conclusions No consensus exists regarding the surgical treatment of non-Zenker’s oesophageal diverticula, but staple line leakage is common and is reduced significantly by myotomy

InnateDB: facilitating systems-level analyses of the mammalian innate immune response

Although considerable progress has been made in dissecting the signaling pathways involved in the innate immune response, it is now apparent that this response can no longer be productively thought of in terms of simple linear pathways. InnateDB (www.innatedb.ca) has been developed to facilitate systems-level analyses that will provide better insight into the complex networks of pathways and interactions that govern the innate immune response. InnateDB is a publicly available, manually curated, integrative biology database of the human and mouse molecules, experimentally verified interactions and pathways involved in innate immunity, along with centralized annotation on the broader human and mouse interactomes. To date, more than 3500 innate immunity-relevant interactions have been contextually annotated through the review of 1000 plus publications. Integrated into InnateDB are novel bioinformatics resources, including network visualization software, pathway analysis, orthologous interaction network construction and the ability to overlay user-supplied gene expression data in an intuitively displayed molecular interaction network and pathway context, which will enable biologists without a computational background to explore their data in a more systems-oriented manner

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

From differentiating metabolites to biomarkers

The current developments in metabolomics and metabolic profiling technologies have led to the discovery of several new metabolic biomarkers. Finding metabolites present in significantly different levels between sample sets, however, does not necessarily make these metabolites useful biomarkers. The route to valid and applicable biomarkers (biomarker qualification) is long and demands a significant amount of work. In this overview, we critically discuss the current state-of-the-art of metabolic biomarker discovery, with highlights and shortcomings, and suggest a pathway to clinical usefulness

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Temperature and time stability of whole blood lactate: implications for feasibility of pre-hospital measurement.

Background To determine the time and temperature stability of whole blood lactate using experimental conditions applicable to the out-of-hospital environment. Findings We performed a prospective, clinical laboratory-based study at an academic hospital. Whole blood lactate was obtained by venipuncture from five post-prandial, resting subjects. Blood was stored in lithium heparinized vacutainers in three temperature conditions: 1) room temperature (20°C), 2) wrapped in a portable, instant ice pack (0°C), or 3) wet ice (0°C). Lactate concentrations (mmol/L) were measured at 0, 5, 10, 20, and 30 minutes after sampling, and compared using repeated measures analysis of variance. Mean baseline lactate among resting subjects (N = 5) was 1.24 mmol/L (95%CI: 0.49,1.98 mmol/L). After 30 minutes, lactate concentration increased, on average, by 0.08 mmol/L (95%CI: 0.02,0.13 mmol/L), 0.18 mmol/L (95%CI: 0.07,0.28 mmol/L), and 0.36 mmol/L (95%CI: 0.24,0.47 mmol/L) when stored in wet ice, ice pack, and room temperature, respectively. The increase in lactate was similar in samples wrapped in portable ice pack or stored in wet ice at all time points (p > 0.05), and met criteria for equivalence at 30 minutes. However, lactate measurements from whole blood stored at room temperature were significantly greater, on average, than wet ice or portable ice pack within five and ten minutes, respectively (p < 0.05). Conclusions Whole blood lactate measurements using samples stored in a portable ice pack are similar to wet ice for up to 30 minutes. These conditions are applicable to the out-of-hospital environment, and should inform future studies of pre-hospital measurement of lactate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85785/1/Seymour - Temperature and time stability.pd

Monitoring the Morphology of M87* in 2009-2017 with the Event Horizon Telescope

The Event Horizon Telescope (EHT) has recently delivered the first resolved images of M87*, the supermassive black hole in the center of the M87 galaxy. These images were produced using 230 GHz observations performed in 2017 April. Additional observations are required to investigate the persistence of the primary image feature—a ring with azimuthal brightness asymmetry—and to quantify the image variability on event horizon scales. To address this need, we analyze M87* data collected with prototype EHT arrays in 2009, 2011, 2012, and 2013. While these observations do not contain enough information to produce images, they are sufficient to constrain simple geometric models. We develop a modeling approach based on the framework utilized for the 2017 EHT data analysis and validate our procedures using synthetic data. Applying the same approach to the observational data sets, we find the M87* morphology in 2009-2017 to be consistent with a persistent asymmetric ring of ∼40 μas diameter. The position angle of the peak intensity varies in time. In particular, we find a significant difference between the position angle measured in 2013 and 2017. These variations are in broad agreement with predictions of a subset of general relativistic magnetohydrodynamic simulations. We show that quantifying the variability across multiple observational epochs has the potential to constrain the physical properties of the source, such as the accretion state or the black hole spin

Contribution of Transcription Factor Binding Site Motif Variants to Condition-Specific Gene Expression Patterns in Budding Yeast

It is now experimentally well known that variant sequences of a cis transcription factor binding site motif can contribute to differential regulation of genes. We characterize the relationship between motif variants and gene expression by analyzing expression microarray data and binding site predictions. To accomplish this, we statistically detect motif variants with effects that differ among environments. Such environmental specificity may be due to either affinity differences between variants or, more likely, differential interactions of TFs bound to these variants with cofactors, and with differential presence of cofactors across environments. We examine conservation of functional variants across four Saccharomyces species, and find that about a third of transcription factors have target genes that are differentially expressed in a condition-specific manner that is correlated with the nucleotide at variant motif positions. We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1). These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation