The synthesis of trifluoromethylated N-nitroaryl-2-amino-1,3-dichloropropane derivatives and their evaluation as potential anti-cancer agents

Six N-nitroaryl-2-amino-1,3-dichloropropane derivatives have been prepared and evaluated against 18 cancer cell lines and two non-cancerous cell lines. Analysis of cell viability data and IC50 values indicated that the presence of a trifluoromethyl group in the nitroaryl moiety is an important structural feature associated with the compounds’ cytotoxicities

Flavoured soft leptogenesis and natural values of the B term

We revisit flavour effects in soft leptogenesis relaxing the assumption of universality for the soft supersymmetry breaking terms. We find that with respect to the case in which the heavy sneutrinos decay with equal rates and equal CP asymmetries for all lepton flavours, hierarchical flavour configurations can enhance the efficiency by more than two orders of magnitude. This translates in more than three order of magnitude with respect to the one-flavour approximation. We verify that lepton flavour equilibration effects related to off-diagonal soft slepton masses are ineffective for damping these large enhancements. We show that soft leptogenesis can be successful for unusual values of the relevant parameters, allowing for $B\sim {\cal O}({\rm TeV})$ and for values of the washout parameter up to $m_{\rm eff}/m_* \sim 5\times 10^{3}$.Comment: 23 pages, 5 figures postscript, Minor changes to match the published version in JHE

On Quantum Effects in Soft Leptogenesis

It has been recently shown that quantum Boltzman equations may be relevant for leptogenesis. Quantum effects, which lead to a time-dependent CP asymmetry, have been shown to be particularly important for resonant leptogenesis when the asymmetry is generated by the decay of two nearly degenerate states. In this work we investigate the impact of the use of quantum Boltzman equations in the framework ``soft leptogenesis'' in which supersymmetry soft-breaking terms give a small mass splitting between the CP-even and CP-odd right-handed sneutrino states of a single generation and provide the CP-violating phase to generate the lepton asymmetry.Comment: 15 pages, 4 figures. Replacement to match published versio

Sleep Loss Produces False Memories

People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a) as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b) as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM) false memory paradigm, subjects learned lists of semantically associated words (e.g., “night”, “dark”, “coal”,…), lacking the strongest common associate or theme word (here: “black”). Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss

American oil palm from Brazil: genetic diversity, population structure, and core collection.

The American oil palm [Elaeis oleifera (Knuth) Cortés] has pronounced importance in oil palm breeding programs. Here, a germplasm bank (GB) of E. oleifera plants collected in the Amazon rainforest in Brazil was submitted to single nucleotide polymorphism (SNP) marker identification, selection, and use, aiming to characterize genetic diversity and population structure and to design a core collection (CC). Five hundred and fifty-three plants from 206 subsamples, collected at 19 localities spread throughout six geographic regions, were submitted to genotyping-by-sequencing analysis. A set of 1,827 high-quality SNP markers was then selected and used to run the genetic diversity and population structure analysis. The genetic diversity found is of moderate degree, and probably only a small portion of the species diversity is represented in the collection. The possible reason for that is the collecting strategy used, which collected subsamples only around the most prominent watercourses in the region. The average degree of genetic differentiation among subsamples is very high, indicating the presence of high interpopulation differentiation. The collection showed a low level of endogamy. The low average gene flow found indicates that genetic isolation caused by drift is occurring, and there is a need to review the conservation strategy. A set of 245 SNPs distributed throughout all 16 chromosomes was used to design CC based on maximizing the strategy of diversity. The optimal adjustment of the validated parameters, maintained while taking fewest subsamples, led to the choice of a model containing 20% of the entire collection as the ideal to form the CC

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake