Chandra Observations of Eight Sources Discovered by INTEGRAL

We report on 0.3-10 keV observations with the Chandra X-ray Observatory of eight hard X-ray sources discovered within 8 degrees of the Galactic plane by the INTEGRAL satellite. The short (5 ks) Chandra observations of the IGR source fields have yielded very likely identifications of X-ray counterparts for three of the IGR sources: IGR J14091-6108, IGR J18088-2741, and IGR J18381-0924. The first two have very hard spectra in the Chandra band that can be described by a power-law with photon indices of Gamma = 0.6+/-0.4 and -0.7(+0.4)(-0.3), respectively (90% confidence errors are given), and both have a unique near-IR counterpart consistent with the Chandra position. IGR J14091-6108 also displays a strong iron line and a relatively low X-ray luminosity, and we argue that the most likely source type is a Cataclysmic Variable (CV), although we do not completely rule out the possibility of a High Mass X-ray Binary. IGR J18088-2741 has an optical counterpart with a previously measured 6.84 hr periodicity, which may be the binary orbital period. We also detect five cycles of a possible 800-950 s period in the Chandra light curve, which may be the compact object spin period. We suggest that IGR J18088-2741 is also most likely a CV. For IGR J18381-0924, the spectrum is intrinsically softer with Gamma = 1.5(+0.5)(-0.4), and it is moderately absorbed, nH = (4+/-1)e22 cm-2. There are two near-IR sources consistent with the Chandra position, and they are both classified as galaxies, making it likely that IGR J18381-0924 is an Active Galactic Nucleus (AGN). For the other five IGR sources, we provide lists of nearby Chandra sources, which may be used along with further observations to identify the correct counterparts, and we discuss the implications of the low inferred Chandra count rates for these five sources.Comment: Accepted by ApJ, 14 page

Ontop: answering SPARQL queries over relational databases

We present Ontop, an open-source Ontology-Based Data Access (OBDA) system that allows for querying relational data sources through a conceptual representation of the domain of interest, provided in terms of an ontology, to which the data sources are mapped. Key features of Ontop are its solid theoretical foundations, a virtual approach to OBDA, which avoids materializing triples and is implemented through the query rewriting technique, extensive optimizations exploiting all elements of the OBDA architecture, its compliance to all relevant W3C recommendations (including SPARQL queries, R2RML mappings, and OWL2QL and RDFS ontologies), and its support for all major relational databases

Proteomic profiling of stallion spermatozoa suggests changes in sperm metabolism and compromised redox regulation after cryopreservation

Proteomic technologies allow the detection of thousands of proteins at the same time, being a powerful technique to reveal molecular regulatory mechanisms in spermatozoa and also sperm damage linked to low fertility or specific biotechnologies. Modifications induced by the cryopreservation in the stallion sperm proteome were studied using UHPLC/MS/MS. Ejaculates from fertile stallions were collected and split in two subsamples, one was investigated as fresh (control) samples, and the other aliquot frozen and thawed using standard procedures and investigated as frozen thawed subsamples. UHPLC/MS/MS was used to study the sperm proteome under these two distinct conditions and bioinformatic enrichment analysis conducted. Gene Ontology (GO) and pathway enrichment analysis were performed revealing dramatic changes as consequence of cryopreservation. The terms oxidative phosphorylation, mitochondrial ATP synthesis coupled electron transport and electron transport chain were significantly enriched in fresh samples (P = 5.50 × 10−12, 4.26 × 10−8 and 7.26 × 10–8, respectively), while were not significantly enriched in frozen thawed samples (P = 1). The GO terms oxidation reduction process and oxidoreductase activity were enriched in fresh samples and the enrichment was reduced in frozen thawed samples (1.40 × 10−8, 1.69 × 10−6 versus 1.13 × 10−2 and 2-86 × 10−2 respectively). Reactome pathways (using human orthologs) significantly enriched in fresh sperm were TCA cycle and respiratory electron transport (P = 1.867 × 10−8), Respiratory electron transport ATP synthesis by chemiosmosis coupling (P = 2.124 × 10−5), Citric acid cycle (TCA cycle)(P = 8.395 × 10−4) Pyruvate metabolism and TCA cycle (P = 3.380 × 10−3), Respiratory electron transport (P = 2.764 × 10−2) and Beta oxidation of laurolyl-CoA to decanoyl CoA-CoA (P = 1.854 × 10−2) none of these pathways were enriched in thawed samples (P = 1). We have provided the first detailed study on how the cryopreservation process impacts the stallion sperm proteome. Our findings identify the metabolic proteome and redoxome as the two key groups of proteins affected by the procedure. Significance: In the present manuscript we investigated how the cryopreservation of stallion spermatozoa impacts the proteome of these cells. This procedure is routinely used in horse breeding and has a major impact in the industry, facilitating the trade of genetic material. This is still a suboptimal biotechnology, with numerous unresolved problems. The limited knowledge of the molecular insults occurring during cryopreservation is behind these problems. The application and development of proteomics to the spermatozoa, allow to obtain valuable information of the specific mechanisms affected by the procedure. In this paper, we report that cryopreservation impacts numerous proteins involved in metabolism regulation (mainly mitochondrial proteins involved in the TCA cycle, and oxidative phosphorylation) and also affects proteins with oxidoreductase activity. Moreover, specific proteins involved in the sperm-oocyte interaction are also affected by the procedure. The information gathered in this study, opens interesting questions and offer new lines of research for the improvement of the technology focusing the targets here identified, and the specific steps in the procedure (cooling, toxicity of antioxidants etc.) to be modified to reduce the damage

Experiences with obstetric violence among healthcare professionals and students in Spain: a constructivist grounded theory study

Background Obstetric violence appears to be a worldwide concern and is defined as a type of gender-based violence perpetrated by health professionals. This violence undermines and harms women’s autonomy. In Spain, 38.3 % of women have identified themselves as victims of this type of violence. Aim To explore current information and knowledge about obstetric violence within the Spanish healthcare context, as well as to develop a theoretical model to explain the concept of obstetric violence, based on the experiences of healthcare professionals (midwives, registered nurses, gynaecologists and paediatricians) and nursing students. Methods A constructivist grounded theory study was conducted at Jaume I University in Spain between May and July 2021, including concurrent data collection and interpretation through constant comparison analysis. An inductive analysis was carried out using the ATLAS.ti 9.0 software to organise and analyse the data. Results Twenty in-depth interviews were conducted, which revealed that healthcare professionals and students considered obstetric violence a violation of human rights and a serious public health issue. The interviews allowed them to describe certain characteristics and propose preventive strategies. Three main categories were identified from the data analysis: (i) characteristics of obstetric violence in the daily routine, (ii) defining the problem of obstetric violence and (iii) strategies for addressing obstetric violence. Participants identified obstetric violence as structural gender-based violence and emphasised the importance of understanding its characteristics. Our results indicate how participants’ experiences influence their process of connecting new information to prior knowledge, and they provide a connection to specific micro- and macro-level strategic plans. Discussion Despite the lack of consensus, this study resonates with the established principles of women and childbirth care, but also generates a new theoretical model for healthcare students and professionals to identify and manage obstetric violence based on contextual factors. The term ‘obstetric violence’ offers a distinct contribution to the growing awareness of violence against women, helps to regulate it through national policy and legislation, and involves both structural and interpersonal gender-based abuse, rather than assigning blame only to care providers. Conclusions Obstetric violence is the most accurate term to describe disrespect and mistreatment as forms of interpersonal and structural violence that contribute to gender and social inequality, and the definition of this term contributes to the ongoing awareness of violence against women, which may help to regulate it through national policy and legislation

Lightning Impulse Current Tests on Conductive Fabrics

Submitted to "Journal of Industrial Textiles"The large amount of electric current associated to lightning discharges is hazardous for living beings, equipment, structures and buildings. To protect those targets against lightning are used Lightning Protection Systems (LPS). However, there are some temporary outdoor activities and backcountry places where an adequate LPS cannot be set up mainly due to the large dimensions of its components and its heavy weight. On the search of light weight lightning protection materials that can be used as part of special LPS, we research some types of electroconductive fabrics by applying high lightning impulse currents in laboratory. The fabric samples checked were pieces of 10 cm x 10 cm: two rip-stop type, a plain-weave, a non-woven and a carbon-impregnated polymeric, all of them obtained commercially. Under laboratory conditions, these samples were subject to subsequent lightning impulse currents registering the voltage and current signals. Optical and scanning electron microscope inspections were performed after tests. Despite some changes visualized as marks left on the fabric surface, the results show that investigated conductive textiles can endure ground currents produced by atmospheric lightning since they withstand the several applied laboratory lightning impulse currents. The outcomes suggest that the weave pattern of the conductive fabric influences the lightning current tolerance, enabling some conductive fabrics to be used in heavy-current applications and as part of personal LPS for outdoor, backcountry and mobile shelters, particularly when lightweight and portability are mandatory

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

Acknowledgements The iHARP database was funded by unrestricted grants from Mundipharma International Ltd and Research in Real-Life Ltd; these analyses were funded by an unrestricted grant from Teva Pharmaceuticals. Mundipharma and Teva played no role in study conduct or analysis and did not modify or approve the manuscript. The authors wish to direct a special appreciation to all the participants of the iHARP group who contributed data to this study and to Mundipharma, sponsors of the iHARP group. In addition, we thank Julie von Ziegenweidt for assistance with data extraction and Anna Gilchrist and Valerie L. Ashton, PhD, for editorial assistance. Elizabeth V. Hillyer, DVM, provided editorial and writing support, funded by Research in Real-Life, Ltd.Peer reviewedPublisher PD

Functional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells

Survival for lung cancer patients remains dismal and is largely attributed to treatment resistance. To identify novel target genes the modulation of which could modify platinum resistance, we performed a high-throughput RNAi screen and identified Yes-associated protein (YAP1), a transcription coactivator and a known oncogene, as a potential actionable candidate. YAP1 ablation significantly improved sensitivities not only to cisplatin but also to ionizing radiation, both of which are DNA-damaging interventions, in non-small cell lung cancer (NSCLC) cells. Overall YAP1 was expressed in 75% of NSCLC specimens, whereas nuclear YAP1 which is the active form was present in 45% of 124 resected NSCLC. Interestingly, EGFR-mutated or KRAS-mutated NSCLC were associated with higher nuclear YAP1 staining in comparison to EGFR/KRAS wild-type. Relevantly, YAP1 downregulation improved sensitivity to erlotinib, an EGFR inhibitor. A pharmacological inhibitor of YAP1 signaling, verteporfin also synergized with cisplatin, radiation and erlotinib in NSCLC cells by potentiating cisplatin and radiation-related double-stranded breaks and decreasing expression of YAP1 and EGFR. Taken together, our study is the first to indicate the potential role of YAP1 as a common modulator of resistance mechanisms and a potential novel, actionable target that can improve responses to platinum, radiation and EGFR-targeted therapy in lung cancer

A Metric Framework for quantifying Data Concentration

Poor performance of artificial neural nets when applied to credit-related classification problems is investigated and contrasted with logistic regression classification. We propose that artificial neural nets are less successful because of the inherent structure of credit data rather than any particular aspect of the neural net structure. Three metrics are developed to rationalise the result with such data. The metrics exploit the distributional properties of the data to rationalise neural net results. They are used in conjunction with a variant of an established concentration measure that differentiates between class characteristics. The results are contrasted with those obtained using random data, and are compared with results obtained using logistic regression. We find, in general agreement with previous studies, that logistic regressions out-perform neural nets in the majority of cases. An approximate decision criterion is developed in order to explain adverse results