The Role of the Polyunsaturated Aldehydes in the Physiology and Ecology of Diatoms

In the last decade diatoms have been shown to release a wide range of secondary metabolites, such as polyunsaturated aldehydes (PUAs), produced by a wound-activated mechanism. PUAs are highly reactive molecules that in most cases induce a drastic reduction in the reproductive response of predators, such as copepods. The variable toxicity of diatoms observed in nature suggests a modulation of PUA production by environmental factors. My results indicate a strong dependence of PUA production on culture age, nutrient limitation and other stress factors, such as UV exposure and low light conditions, in cultures of Skeletonema marinoi, suggesting a direct link between toxin production and cell physiological state. Since it has been hypothesized that PUAs may be released in seawater also as a result of cell mortality, phytoplankton lysis rates were estimated during four oceanographic cruises conducted during periods of diatom blooms in the Northern Adriatic Sea. High lysis rates were observed and preliminary results indicated substantial amounts of PUAs released in seawater. The effects of dissolved PUAs were therefore investigated on organisms other than predators, such as co-occurring bacteria and phytoplankton in culture. PUAs are toxic for several phytoplankton species at concentrations well within the range potentially produced by diatoms. Diatoms can be immunized by sub-lethal concentrations of PUAs. In this case, PUAs may act as signal molecules for bloom termination. PUAs induce also different effects on bacterial growth; some strains are inhibited while others show remarkable resistance to these compounds, and a few of them were even stimulated. Therefore, PUAs appear to have multiple functions in diatoms, namely as chemical defense against grazers, allelochemicals against phytoplankton and bacteria, and signal molecules within their populations

Effects of pool volume on wet milling efficiency

The volume of slurry in a rotary mill has a bearing on the presence of a pool of slurry and therefore on milling efficiency. Load behaviour was investigated at different volumes of slurry. The insight gained was then used to evaluate the implications of slurry pooling on milling. First, the effects of viscosity on mill charge behaviour were measured using photographic techniques applied to a Perspex mill. A model of the angular location of the free surface of the slurry pool, as affected by slurry filling was proposed. Next, a real ore was used and the load behaviour was measured using non-invasive sensors fitted to a pilot mill. At this point, the angular position of the pool and the net power draw were correlated to the volume of slurry for mill speeds ranging from 65 to 85 % of critical. An additional series of tests was carried out on a mill filled with grinding media only, for speeds spanning from approximately 24 to 110 % of critical. The aim here was to isolate and study the media charge. Lastly, a laboratory mill was used to run batch grinding tests on a Platinum ore for slurry fillings U between 1.0 and 3.0 and at 65 % solids content. Two ball fillings were considered for identical slurry volumes: J = 20 % and 30 %. Results showed that not only did the proposed pool model work well using an artificial slurry in the Perspex mill, but it also worked for the Platinum ore tested in the Wits pilot mill. The behaviour of the media charge was not substantially affected by slurry viscosity and slurry filling. The net power drawn by the ‘dry mill’ compared well with DEM prediction for non-centrifuging speeds. The effect of slurry pooling on net power draw, on the other hand, was best accounted for using a Torque-arm model and an empirical model developed to this end. As for milling kinetics, results suggested that the slurry pool should be avoided because milling efficiency deteriorated as a result. However, the production of fines was not largely altered

Gaze-Aware Cognitive Assistant for Multiscreen Surveillance

Surveillance operators must scan multiple camera feeds to ensure timely detection of incidents; however, variability in scanning behavior can lead to untimely/failed detection of critical information in feeds that were neglected for a long period. Us-ing an eye tracker to monitor screen fixations we can calculate (in real-time) the time elapsed since the last scan of each particular feed, allowing the setting-up of targeted countermeasures contingent on operator oculomotor behavior. One ave-nue is to provide operators with timely alerts to modulate the scan pattern to avoid attentional tunneling and inattentional blindness. We test such an adaptive solution within a major event surveillance simulation and preliminary results show that operator scan behavior can be modulated, although further investigation is re-quired to determine warning frequency and modality to optimize the balance be-tween saliency and workload increase. Future work will focus on adding a real-time vigilance detection and countermeasure capability

Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia

PURPOSE The applicability of FLT3-internal tandem duplications (FLT3-ITD) for assessing measurable residual disease (MRD) in acute myeloid leukemia (AML) in complete remission (CR) has been hampered by patient-specific duplications and potential instability of FLT3-ITD during relapse. Here, we comprehensively investigated the impact of next-generation sequencing (NGS)-based FLT3-ITD MRD detection on treatment outcome in a cohort of patients with newly diagnosed AML in relation to established prognostic factors at diagnosis and other MRD measurements, ie, mutant NPM1 and multiparameter flow cytometry. METHODS In 161 patients with de novo FLT3-ITD AML, NGS was performed at diagnosis and in CR after intensive remission induction treatment. FLT3-ITD MRD status was correlated with the cumulative incidence of relapse and overall survival (OS). RESULTS NGS-based FLT3-ITD MRD was present in 47 of 161 (29%) patients with AML. Presence of FLT3-ITD MRD was associated with increased risk of relapse (4-year cumulative incidence of relapse, 75% FLT3-ITD MRD v 33% no FLT3-ITD MRD; P < .001) and inferior OS (4-year OS, 31% FLT3-ITD MRD v 57% no FLT3-ITD MRD; P < .001). In multivariate analysis, detection of FLT3-ITD MRD in CR confers independent prognostic significance for relapse (hazard ratio, 3.55; P < .001) and OS (hazard ratio 2.51; P = .002). Strikingly, FLT3-ITD MRD exceeds the prognostic value of most generally accepted clinical and molecular prognostic factors, including the FLT3-ITD allelic ratio at diagnosis and MRD assessment by NGS-based mutant NPM1 detection or multiparameter flow cytometry. CONCLUSION NGS-based detection of FLT3-ITD MRD in CR identifies patients with AML with profound risk of relapse and death that outcompetes the significance of most established prognostic factors at diagnosis and during therapy, and furnishes support for FLT3-ITD as a clinically relevant biomarker for dynamic disease risk assessment in AML

Dolutegravir efficacy at 48 weeks in key subgroups of treatment-naive HIV-infected individuals in three randomized trials

Objectives:Dolutegravir (DTG) has been studied in three trials in HIV treatment-naive participants, showing noninferiority compared with raltegravir (RAL), and superiority compared with efavirenz and ritonavir-boosted darunavir. We explored factors that predicted treatment success, the consistency of observed treatment differences across subgroups and the impact of NRTI backbone on treatment outcome.Design:Retrospective exploratory analyses of data from three large, randomized, international comparative trials: SPRING-2, SINGLE, and FLAMINGO.Methods:We examined the efficacy of DTG in HIV-infected participants with respect to relevant demographic and HIV-1-related baseline characteristics using the primary efficacy endpoint from the studies (FDA snapshot) and secondary endpoints that examine specific elements of treatment response. Regression models were used to analyze pooled data from all three studies.Results:Snapshot response was affected by age, hepatitis co-infection, HIV risk factor, baseline CD4+ cell count, and HIV-1 RNA and by third agent. Differences between DTG and other third agents were generally consistent across these subgroups. There was no evidence of a difference in snapshot response between abacavir/lamivudine (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) overall [ABC/3TC 86%, TDF/FTC 85%, difference 1.1%, confidence interval (CI) −1.8, 4.0 percentage points, P = 0.61] or at high viral loads (difference −2.5, 95% CI −8.9, 3.8 percentage points, P = 0.42).Conclusions:DTG is a once-daily, unboosted integrase inhibitor that is effective in combination with either ABC/3TC or TDF/FTC for first-line antiretroviral therapy in HIV-positive individuals with a variety of baseline characteristics

Using an Inbred Horse Breed in a High Density Genome-Wide Scan for Genetic Risk Factors of Insect Bite Hypersensitivity (IBH)

While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions

Copy number variations in Friesian horses and genetic risk factors for insect bite hypersensitivity

Background: Many common and relevant diseases affecting equine welfare have yet to be tested regarding structural variants such as copy number variations (CNVs). CNVs make up a substantial proportion of total genetic variability in populations of many species, resulting in more sequence differences between individuals than SNPs. Associations between CNVs and disease phenotypes have been established in several species, but equine CNV studies have been limited. Aim of this study was to identify CNVs and to perform a genome-wide association (GWA) study in Friesian horses to identify genomic loci associated with insect bite hypersensitivity (IBH), a common seasonal allergic dermatitis observed in many horse breeds worldwide. Results: Genotypes were obtained using the Axiom® Equine Genotyping Array containing 670,796 SNPs. After quality control of genotypes, 15,041 CNVs and 5350 CNV regions (CNVRs) were identified in 222 Friesian horses. Coverage of the total genome by CNVRs was 11.2% with 49.2% of CNVRs containing genes. 58.0% of CNVRs were novel (i.e. so far only identified in Friesian horses). A SNP- and CNV-based GWA analysis was performed, where about half of the horses were affected by IBH. The SNP-based analysis showed a highly significant association between the MHC region on ECA20 and IBH in Friesian horses. Associations between the MHC region on ECA20 and IBH were also detected based on the CNV-based analysis. However, CNVs associated with IBH in Friesian horses were not often in close proximity to SNPs identified to be associated with IBH. Conclusions: CNVs were identified in a large sample of the Friesian horse population, thereby contributing to our knowledge on CNVs in horses and facilitating our understanding of the equine genome and its phenotypic expression. A clear association was identified between the MHC region on ECA20 and IBH in Friesian horses based on both SNP- and CNV-based GWA studies. These results imply that MHC contributes to IBH sensitivity in Friesian horses. Although subsequent analyses are needed for verification, nucleotide differences, as well as more complex structural variations like CNVs, seem to contribute to IBH sensitivity. IBH should be considered as a common disease with a complex genomic architecture