A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of ...large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase.
We present the results of a search for gravitational-wave bursts associated with 137 gamma-ray bursts (GRBs) that were detected by satellite-based gamma-ray experiments during the fifth LIGO science ...run and first Virgo science run. The data used in this analysis were collected from 2005 November 4 to 2007 October 1, and most of the GRB triggers were from the Swift satellite. The search uses a coherent network analysis method that takes into account the different locations and orientations of the interferometers at the three LIGO-Virgo sites. We find no evidence for gravitational-wave burst signals associated with this sample of GRBs. Using simulated short-duration (<1 s) waveforms, we set upper limits on the amplitude of gravitational waves associated with each GRB. We also place lower bounds on the distance to each GRB under the assumption of a fixed energy emission in gravitational waves, with typical limits of D ~ 15 Mpc (E_GW^iso / 0.01 M_o c^2)^1/2 for emission at frequencies around 150 Hz, where the LIGO-Virgo detector network has best sensitivity. We present astrophysical interpretations and implications of these results, and prospects for corresponding searches during future LIGO-Virgo runs.
To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array ...genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in
and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in
associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of
.
Surveillance is a key component of any control strategy for healthcare-associated infections (HAIs) and antimicrobial resistance (AMR), and public availability of methodologic aspects is crucial for ...the interpretation of the data. We sought to systematically review publicly available information for HAIs and/or AMR surveillance systems organized by public institutions or scientific societies in European countries.
A systematic review of scientific and grey literature following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed. Information on HAIs and/or AMR surveillance systems published until 31 October 2016 were included.
A total of 112 surveillance systems were detected; 56 from 20 countries were finally included. Most exclusions were due to lack of publicly available information. Regarding AMR, the most frequent indicator was the proportion of resistant isolates (27 of 34 providing information, 79.42%); only 18 (52.9%) included incidence rates; the data were only laboratory based in 33 (78.5%) of the 42 providing this information. Regarding HAIs in intensive care units, all 22 of the systems providing data included central line–associated bloodstream infections, and 19 (86.3%) included ventilator-associated pneumonia and catheter-associated urinary tract infections; incidence density was the most frequent indicator. Regarding surgical site infections, the most frequent procedures included were hip prosthesis, colon surgery and caesarean section (21/22, 95.5%).
Publicly available information about the methods and indicators of the surveillance system is frequently lacking. Despite the efforts of European Centre for Disease Control and Prevention (ECDC) and other organizations, wide heterogeneity in procedures and indicators still exists.
Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ...ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules. Additionally, we evaluate the contribution of this tertiary amine to the elimination of proliferating melanoma cells in culture. We also demonstrate that the presence of the tertiary amine is sufficient to lead to death of tumour cells arrested in G1 phase following vemurafenib treatment. We conclude that blockage of autophagic flux by tenovins is necessary to eliminate melanoma cells that survive B-Raf inhibition and achieve total tumour cell kill and that autophagy blockage can be achieved at a lower concentration than by chloroquine. This observation is of great relevance as relapse and resistance are frequently observed in cancer patients treated with B-Raf inhibitors.
We study the production of the exotic charged charmonium-like state $Z_c^{\pm}(3900)$ in $p \bar p$ collisions through the sequential process $\psi(4260) \rightarrow Z_c^{\pm}(3900) \pi^{\mp}$, ...$Z_c^{\pm}(3900) \rightarrow J/\psi \pi^{\pm}$. Using the subsample of candidates originating from semi-inclusive weak decays of $b$-flavored hadrons, we measure the invariant mass and natural width to be $M=3902.6^{+5.2}_{-5.0}{\rm \thinspace (stat)}^{+3.3}_{-1.4}{\rm \thinspace (syst)}$ MeV and $\Gamma=32 ^{+28}_{-21}{\rm \thinspace (stat)} ^{+26}_{-7}{\rm \thinspace (syst)}$ MeV, respectively. We search for prompt production of the $Z_c^{\pm}(3900)$ through the same sequential process. No significant signal is observed, and we set an upper limit of 0.66 at the 95\% credibility level on the ratio of prompt production to the production via $b$-hadron decays. The study is based on $10.4~\rm{fb^{-1}}$ of $p \overline p $ collision data collected by the D0 experiment at the Fermilab Tevatron collider.
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