Proceedings of the Joint Ontology Workshops co-located with the Bolzano Summer of Knowledge (BOSK 2020)

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Real-world Trends, Rural-urban Differences, and Socioeconomic Disparities in Utilization of Narrow versus Broad Next-generation Sequencing Panels

UNLABELLED: Advances in genetic technology have led to the increasing use of genomic panels in precision oncology practice, with panels ranging from a couple to hundreds of genes. However, the clinical utilization and utility of oncology genomic panels, especially among vulnerable populations, is unclear. We examined the association of panel size with socioeconomic status and clinical trial matching. We retrospectively identified 9,886 eligible adult subjects in the Mayo Clinic Health System who underwent genomic testing between January 1, 2016 and June 30, 2020. Patient data were retrieved from structured and unstructured data sources of institutional collections, including cancer registries, clinical data warehouses, and clinical notes. Socioeconomic surrogates were approximated using the Area Deprivation Index (ADI) corresponding to primary residence addresses. Logistic regression was performed to analyze relationships between ADI or rural/urban status and (i) use of genomic test by panel size; (ii) clinical trial matching status. Compared with patients from the most affluent areas, patients had a lower odds of receiving a panel test (vs. a single-gene test) if from areas of higher socioeconomic deprivation [OR (95% confidence interval (CI): 0.71 (0.61-0.83), P \u3c 0.01] or a rural area [OR (95% CI): 0.85 (0.76-0.96), P \u3c 0.01]. Patients in areas of higher socioeconomic deprivation were less likely to be matched to clinical trials if receiving medium panel tests [(OR) (95% CI): 0.69 (0.49-0.97), P = 0.03]; however, there was no difference among patients receiving large panel tests (P \u3e 0.05) and rural patients were almost 2x greater odds of being matched if receiving a large panel test [(OR) (95% CI): 1.76 (1.21-2.55), P \u3c 0.01]. SIGNIFICANCE: We identified socioeconomic and rurality disparities in the use of genomic tests and trial matching by panel size, which may have implications for equal access to targeted therapies. The lack of association between large panel tests and clinical trial matching by socioeconomic status, suggests a potential health equity impact, while removing barriers in access to large panels for rural patients may improve access to trials. However, further research is needed

On the absence of bound-state stabilization through short ultra-intense fields

We address the question of whether atomic bound states begin to stabilize in the short ultra-intense field limit. We provide a general theory of ionization probability and investigate its gauge invariance. For a wide range of potentials we find an upper and lower bound by non-perturbative methods, which clearly exclude the possibility that the ultra intense field might have a stabilizing effect on the atom. For short pulses we find almost complete ionization as the field strength increases.Comment: 34 pages Late

On the Influence of Pulse Shapes on Ionization Probability

We investigate analytical expressions for the upper and lower bounds for the ionization probability through ultra-intense shortly pulsed laser radiation. We take several different pulse shapes into account, including in particular those with a smooth adiabatic turn-on and turn-off. For all situations for which our bounds are applicable we do not find any evidence for bound-state stabilization.Comment: 21 pages LateX, 10 figure

Ionization Probabilities through ultra-intense Fields in the extreme Limit

We continue our investigation concerning the question of whether atomic bound states begin to stabilize in the ultra-intense field limit. The pulses considered are essentially arbitrary, but we distinguish between three situations. First the total classical momentum transfer is non-vanishing, second not both the total classical momentum transfer and the total classical displacement are vanishing together with the requirement that the potential has a finite number of bound states and third both the total classical momentum transfer and the total classical displacement are vanishing. For the first two cases we rigorously prove, that the ionization probability tends to one when the amplitude of the pulse tends to infinity and the pulse shape remains fixed. In the third case the limit is strictly smaller than one. This case is also related to the high frequency limit considered by Gavrila et al.Comment: 16 pages LateX, 2 figure

Multiphoton detachment of electrons from negative ions

A simple analytical solution for the problem of multiphoton detachment from negative ions by a linearly polarized laser field is found. It is valid in the wide range of intensities and frequencies of the field, from the perturbation theory to the tunneling regime, and is applicable to the excess-photon as well as near-threshold detachment. Practically, the formulae are valid when the number of photons is greater than two. They produce the total detachment rates, relative intensities of the excess-photon peaks, and photoelectron angular distributions for the hydrogen and halogen negative ions, in agreement with those obtained in other, more numerically involved calculations in both perturbative and non-perturbative regimes. Our approach explains the extreme sensitivity of the multiphoton detachment probability to the asymptotic behaviour of the bound-state wave function. Rapid oscillations in the angular dependence of the $n$-photon detachment probability are shown to arise due to interference of the two classical trajectories which lead to the same final state after the electron emerges at the opposite sides of the atom when the field is close to maximal.Comment: 27 pages, Latex, and PostScript figures fig1.ps, fig2.ps, fig3.ps, accepted for publication in Phys. Rev.

Investigating the cross-talk between microglia and oligodendrocyte progenitors in brain ischemia

Oligodendrocytes, the myelin-forming cells in the brain, are severely affected by ischemia (Arai et al. 2009, Biol Pharm Bull), contributing to stroke-associated deficits. The possibility to implement spontaneous post-injury repair mechanisms still represents an unexplored field. Recent data obtained by fate-mapping analysis using the conditional GPR17-iCreERT2xCAG-eGFP transgenic mice, showed that the subpopulation of adult Oligodendrocyte Progenitor Cells (OPCs) expressing the GPR17 receptor (GFP+-cells) represent \u201ca reserve pool\u201d that is maintained for repair purposes after brain damage (Vigano\u300 et al. 2016, Glia). Accordingly, our data demonstrated that, after brain ischemia, GFP+-cells actively respond to injury increasing their proliferation rate and migratory capacity. However, at later stages, only a few percentage of these cells undergo maturation. This limited post-stroke repair is likely due to local unfavourable inflammatory milieu mediated by macrophages and resident microglia, which participate to post-ischemic inflammation assuming both detrimental and beneficial phenotypes. Here, we aimed at: (i) characterizing the spatio-temporal distribution of GFP+-cells in relation to microglia and macrophage polarization after brain ischemia in the middle cerebral artery occlusion MCAo, rodent model; (ii) exploring the cross-talk between microglia and OPCs, by assessing how vesicles released extracellularly (EVs) by microglia, polarized toward the pro- and anti- inflammatory states, influence OPC behaviour. In vivo studies showed that GFP+-cells accumulate at the border of the ischemic lesion starting from 72h after ischemia, when immune cells show both pro- and anti-inflammatory features. One week after stroke, the absolute number of pro-inflammatory cells increases, whereas immune cells with anti-inflammatory phenotype were found to be decreased. In vitro studies pointed out that EVs produced by pro-inflammatory microglia limit OPC proliferation. On the contrary, 48h exposure to EVs from either pro- or anti-inflammatory microglia (but not resting cells) promote OPC maturation and myelination. Interestingly, EVs from pro-rigenerative cells also increased OPC migration. These data suggest that EVs contain signals able to influence OPC proliferation, migration and maturation. Shedding light on the mechanisms by which microglia activation interferes with the regeneration potential of OPCs is important for developing therapeutic interventions to implement functional recovery after stroke

Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk:a Mendelian randomization analysis

Endometrial cancer is the most common gynaecological cancer in high-income countries. Elevated body mass index (BMI) is an established modifiable risk factor for this condition and is estimated to confer a larger effect on endometrial cancer risk than any other cancer site. However, the molecular mechanisms underpinning this association remain unclear. We used Mendelian randomization (MR) to evaluate the causal role of 14 molecular risk factors (hormonal, metabolic and inflammatory markers) in endometrial cancer risk. We then evaluated and quantified the potential mediating role of these molecular traits in the relationship between BMI and endometrial cancer using multivariable MR. Methods Genetic instruments to proxy 14 molecular risk factors and BMI were constructed by identifying single-nucleotide polymorphisms (SNPs) reliably associated (P < 5.0 × 10−8) with each respective risk factor in previous genome-wide association studies (GWAS). Summary statistics for the association of these SNPs with overall and subtype-specific endometrial cancer risk (12,906 cases and 108,979 controls) were obtained from a GWAS meta-analysis of the Endometrial Cancer Association Consortium (ECAC), Epidemiology of Endometrial Cancer Consortium (E2C2) and UK Biobank. SNPs were combined into multi-allelic models and odds ratios (ORs) and 95% confidence intervals (95% CIs) were generated using inverse-variance weighted random-effects models. The mediating roles of the molecular risk factors in the relationship between BMI and endometrial cancer were then estimated using multivariable MR