Results on the Colombeau products of the distribution x_+^−r−1/2 with the distributions x_-^−k−1/2 and x_-^k−1/2

Results on the products of the distribution x_+^−r−1/2 with the distributions x_-^−k−1/2 and x_-^k−1/2 are obtained in the differential algebra G(R) of Colombeau generalized functions, which contains the space D'(R) of Schwartz distributions as a subspace; in this algebra the notion of association is defined, which is a faithful generalization of weak equality in G(R). This enables treating the results in terms of distributions again

Pan-cancer landscape of homologous recombination deficiency

Homologous recombination deficiency (HRD) results in impaired double strand break repair and is a frequent driver of tumorigenesis. Here, we develop a genome-wide mutational scarbased pan-cancer Classifier of HOmologous Recombination Deficiency (CHORD) that can discriminate BRCA1- and BRCA2-subtypes. Analysis of a metastatic (n = 3,504) and primary (n = 1,854) pan-cancer cohort reveals that HRD is most frequent in ovarian and breast cancer, followed by pancreatic and prostate cancer. We identify biallelic inactivation of BRCA1, BRCA2, RAD51C or PALB2 as the most common genetic cause of HRD, with RAD51C and PALB2 inactivation resulting in BRCA2-type HRD. We find that while the specific genetic cause of HRD is cancer type specific, biallelic inactivation is predominantly associated with loss-of-heterozygosity (LOH), with increased contribution of deep deletions in prostate cancer. Our results demonstrate the value of pan-cancer genomics-based HRD testing and its

Distinct Genomic Profiles Are Associated with Treatment Response and Survival in Ovarian Cancer

SIMPLE SUMMARY: In most patients with ovarian cancer, their disease eventually becomes resistant to chemotherapy. The timing and type of treatment given are therefore highly important. Currently, treatment choice is mainly based on the subtype of cancer (from a histological point of view), prior response to chemotherapy, and the time it takes for the disease to recur. In this study, we combined complete genome data of the tumor with clinical data to better understand treatment responses. In total, 132 tumor samples were included, all from patients with disease that had spread beyond the primary location. By clustering the samples based on genetic characteristics, we have identified subgroups with distinct response rates and survival outcomes. We suggest that in the future, this data can be used to make more informed treatment choices for individuals with ovarian cancer. ABSTRACT: The majority of patients with ovarian cancer ultimately develop recurrent chemotherapy-resistant disease. Treatment stratification is mainly based on histological subtype and stage, prior response to platinum-based chemotherapy, and time to recurrent disease. Here, we integrated clinical treatment, treatment response, and survival data with whole-genome sequencing profiles of 132 solid tumor biopsies of metastatic epithelial ovarian cancer to explore genome-informed stratification opportunities. Samples from primary and recurrent disease harbored comparable numbers of single nucleotide variants and structural variants. Mutational signatures represented platinum exposure, homologous recombination deficiency, and aging. Unsupervised hierarchical clustering based on genomic input data identified specific ovarian cancer subgroups, characterized by homologous recombination deficiency, genome stability, and duplications. The clusters exhibited distinct response rates and survival probabilities which could thus potentially be used for genome-informed therapy stratification for more personalized ovarian cancer treatment

Detailed Chemical Evolution of Carina and Sagittarius Dwarf Spheroidal Galaxies

In order to verify the effects of the most recent data on the evolution of Carina and Sagittarius Dwarf Spheroidal Galaxies (dSph) and to set tight constraints on the main parameters of chemical evolution models, we study in detail the chemical evolution of these galaxies through comparisons between the new data and the predictions of a model, already tested to reproduce the main observational constraints in dSphs. Several abundance ratios, such as [$\alpha$/Fe], [Ba/Fe] and [Eu/Fe], and the metallicity distribution of stars are compared to the predictions of our models adopting the observationally derived star formation histories in these galaxies. These new comparisons confirm our previously suggested scenario for the evolution of these galaxies, and allow us to better fix the star formation and wind parameters. In particular, for Carina the comparisons indicate that the best efficiency of star formation is $\nu = 0.15 Gyr^{-1}$, that the best wind efficiency parameter is $w_i$ = 5 (the wind rate is five times stronger than the star formation rate), and that the star formation history, which produces the best fit to the observed metallicity distribution of stars is characterized by several episodes of activity. In the case of Sagittarius our results suggest that $\nu=3 Gyr^{-1}$ and $w_i=9$, again in agreement with our previous work. Finally, we show new predictions for [N/Fe] and [C/Fe] ratios for the two galaxies suggesting a scenario for Sagittarius very similar to the one of the solar vicinity in the Milky Way, except for a slight decrease of [N/Fe] ratio at high metallicities due to the galactic wind. For Carina we predict a larger [N/Fe] ratio at low metallicities, reflecting the lower star formation efficiency of this galaxy relative to Sagittarius and the Milky Way.Comment: 11 pages, 7 figures, accepted for publication in Asttronomy & Astrophysic

Chemical Evolution of Dwarf Spheroidal and Blue Compact Galaxies

We studied the chemical evolution of Dwarf Spheroidal (dSph) and Blue Compact Galaxies (BCGs) by means of comparison between the predictions of chemical evolution models and several observed abundance ratios. Detailed models with up to date nucleosynthesis taking into account the role played by supernovae of different types (II, Ia) were developed for both types of galaxies allowing us to follow the evolution of several chemical elements. The models are specified by the prescriptions of the star formation (SF) and galactic wind efficiencies chosen to reproduce the main features of these galaxies. We also investigated a possible connection in the evolution of dSph and BCGs and compared the predictions of the models to the abundance ratios observed in Damped Lyman alpha Systems (DLAs). The main conclusions are: i) the observed distribution of [alpha/Fe] vs. [Fe/H] in dSph is mainly a result of the SF rate coupled with the wind efficiency; ii) a low SF efficiency and a high wind efficiency are required to reproduce the observational data for dSph; iii) the low gas content of these galaxies is the result of the combined action of gas consumption by SF and gas removal by galactic winds; iv) the BCGs abundance ratios are reproduced by models with 2 to 7 bursts of SF with low efficiencies ; v) the low values of N/O observed in BCGs are the natural result of a bursting SF; vi) a connection between dSph and BCGs in an unified evolutionary scenario is unlikely; vii) the models for the dSph and BCGs imply different formation scenarios for the DLAs; viii) a suitable amount of primary N produced in massive stars can be perhaps an explanation for the low plateau in the [N/$\alpha$] distribution observed in DLAs, if real.Comment: 16 pages, 17 figures, accepted for publication in MNRA

Homologous recombination deficiency scar: mutations and beyond—implications for precision oncology

Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and targeted anticancer therapies. However, current clinical assessment of HRD mainly relies on determining germline BRCA1/2 mutational status and is insufficient for adequate patient stratification as mechanisms of HRD occurrence extend beyond functional BRCA1/2 loss. HRD, regardless of BRCA1/2 status, is associated with specific forms of genomic and mutational signatures termed HRD scar. Detection of this HRD scar might therefore be a more reliable biomarker for HRD. This review discusses and compares different methods of assessing HRD and HRD scar, their advances into the clinic, and their potential implications for precision oncology

Workplace experience of radiographers: impact of structural and interpersonal interventions

PURPOSE: Within the framework of organisational development, an assessment of the workplace experience of radiographers (RGs) was conducted. The aims of this study were to develop structural and interpersonal interventions and to prove their effectiveness and feasibility. METHODS: A questionnaire consisting of work-related factors, e.g. time management and communication, and two validated instruments (Workplace Analysis Questionnaire, Effort-Reward Imbalance Scale) was distributed to all RGs (n = 33) at baseline (T1). Interventions were implemented and a follow-up survey (T2) was performed 18 months after the initial assessment. RESULTS: At T1, areas with highest dissatisfaction were communication and time management for ambulant patients (bad/very bad, 57% each). The interventions addressed adaptation of work plans, coaching in developing interpersonal and team leadership skills, and regular team meetings. The follow-up survey (T2) showed significantly improved communication and cooperation within the team and improved qualification opportunities, whereas no significant changes could be identified in time management and in the workplace-related scales 'effort' expended at work and 'reward' received in return for the effort. CONCLUSION: Motivating workplace experience is important for high-level service quality and for attracting well-qualified radiographers to work at a place and to stay in the team for a longer period

The evolution of the photometric properties of Local Group dwarf spheroidal galaxies

We investigate the present-day photometric properties of the dwarf spheroidal galaxies in the Local Group. From the analysis of their integrated colours, we consider a possible link between dwarf spheroidals and giant ellipticals. From the analysis of the V vs (B-V) plot, we search for a possible evolutionary link between dwarf spheroidal galaxies (dSphs) and dwarf irregular galaxies (dIrrs). By means of chemical evolution models combined with a spectro-photometric model, we study the evolution of six Local Group dwarf spheroidal galaxies (Carina, Draco, Sagittarius, Sculptor, Sextans and Ursa Minor). The chemical evolution models, which adopt up-to-date nucleosynthesis from low and intermediate mass stars as well as nucleosynthesis and energetic feedback from supernovae type Ia and II, reproduce several observational constraints of these galaxies, such as abundance ratios versus metallicity and the metallicity distributions. The proposed scenario for the evolution of these galaxies is characterised by low star formation rates and high galactic wind efficiencies. Such a scenario allows us to predict integrated colours and magnitudes which agree with observations. Our results strongly suggest that the first few Gyrs of evolution, when the star formation is most active, are crucial to define the luminosities, colours, and other photometric properties as observed today. After the star formation epoch, the galactic wind sweeps away a large fraction of the gas of each galaxy, which then evolves passively. Our results indicate that it is likely that at a certain stage of their evolution, dSphs and dIrrs presented similar photometric properties. However, after that phase, they evolved along different paths, leading them to their currently disparate properties.Comment: 13 pages, Astronomy & Astrophysics, accepte

110 Years of Avipoxvirus in the Galapagos Islands

The role of disease in regulating populations is controversial, partly owing to the absence of good disease records in historic wildlife populations. We examined birds collected in the Galapagos Islands between 1891 and 1906 that are currently held at the California Academy of Sciences and the Zoologisches Staatssammlung Muenchen, including 3973 specimens representing species from two well-studied families of endemic passerine birds: finches and mockingbirds. Beginning with samples collected in 1899, we observed cutaneous lesions consistent with Avipoxvirus on 226 (6.3%) specimens. Histopathology and viral genotyping of 59 candidate tissue samples from six islands showed that 21 (35.6%) were positive for Avipoxvirus, while alternative diagnoses for some of those testing negative by both methods were feather follicle cysts, non-specific dermatitis, or post mortem fungal colonization. Positive specimens were significantly nonrandomly distributed among islands both for mockingbirds (San Cristobal vs. Espanola, Santa Fe and Santa Cruz) and for finches (San Cristobal and Isabela vs. Santa Cruz and Floreana), and overall highly significantly distributed toward islands that were inhabited by humans (San Cristobal, Isabela, Floreana) vs. uninhabited at the time of collection (Santa Cruz, Santa Fe, Espanola), with only one positive individual on an uninhabited island. Eleven of the positive specimens sequenced successfully were identical at four diagnostic sites to the two canarypox variants previously described in contemporary Galapagos passerines. We conclude that this virus was introduced late in 1890′s and was dispersed among islands by a variety of mechanisms, including regular human movements among colonized islands. At present, this disease represents an ongoing threat to the birds on the Galapagos Islands