A longitudinal study to examine the influence of farming practices and environmental factors on pathogen prevalence using structural equation modeling

The contamination of fresh produce with foodborne pathogens has been an on-going concern with outbreaks linked to these commodities. Evaluation of farm practices, such as use of manure, irrigation water source, and other factors that could influence pathogen prevalence in the farming environment could lead to improved mitigation strategies to reduce the potential for contamination events. Soil, water, manure, and compost were sampled from farms in Ohio and Georgia to identify the prevalence of Salmonella, Listeria monocytogenes (Lm), Campylobacter, and Shiga-toxin-producing Escherichia coli (STEC), as well as Arcobacter, an emerging human pathogen. This study investigated agricultural practices to determine which influenced pathogen prevalence, i.e., the percent positive samples. These efforts identified a low prevalence of Salmonella, STEC, and Campylobacter in soil and water (< 10%), preventing statistical modeling of these pathogens. However, Lm and Arcobacter were found in soil (13 and 7%, respectively), manure (49 and 32%, respectively), and water samples (18 and 39%, respectively) at a comparatively higher prevalence, suggesting different dynamics are involved in their survival in the farm environment. Lm and Arcobacter prevalence data, soil chemical characteristics, as well as farm practices and weather, were analyzed using structural equation modeling to identify which factors play a role, directly or indirectly, on the prevalence of these pathogens. These analyses identified an association between pathogen prevalence and weather, as well as biological soil amendments of animal origin. Increasing air temperature increased Arcobacter and decreased Lm. Lm prevalence was found to be inversely correlated with the use of surface water for irrigation, despite a high Lm prevalence in surface water suggesting other factors may play a role. Furthermore, Lm prevalence increased when the microbiome’s Simpson’s Diversity Index decreased, which occurred as soil fertility increased, leading to an indirect positive effect for soil fertility on Lm prevalence. These results suggest that pathogen, environment, and farm management practices, in addition to produce commodities, all need to be considered when developing mitigation strategies. The prevalence of Arcobacter and Lm versus the other pathogens suggests that multiple mitigation strategies may need to be employed to control these pathogens

Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis

PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known

Walking on a tightrope: caring for ambivalent woman considering abortions in the first trimester

Aims and objectives To improve the understanding and competence of health personnel when caring for ambivalent pregnant women, the aim of this study is to explore the experiences of encountering women who are unsure whether to complete or terminate pregnancy. Background Feelings of ambivalence are present in a significant number of women preparing for abortions and may challenge the provision of healthcare. Health personnel have reported an ideal to be non-judgmental and supportive. Insufficient attention has been directed to the experiences of health personnel who prepare women for abortions in gynecological units. Design Qualitative design with a hermeneutic-phenomenological approach. Methods Focus group interviews were conducted with health personnel from four gynecological outpatient clinics and wards in Norway (n=20). Results The health personnel felt responsible for contributing to patient well-being. This demanded focused attention towards all women being prepared for abortions and meant a consciousness and balancing act towards revealing, handling and being involved in the woman’s potential unsureness without influencing her decision. When involved, the health personnel risked being confronted with their own vulnerabilities and values. Conclusions The health personnel tried to balance their care and support without influencing the woman’s decision. Although they viewed the women as fully autonomous and responsible, they became personally involved, to varying degrees, in the uncertainty and were faced with their own vulnerabilities and values. They lacked a possibility for immediate debriefing and regular counseling after complicated consultations. Relevance to clinical practice Knowledge of the experiences of health personnel can provide input for professional development at gynecological departments. These findings contribute to discussions about what information should be given and whether the woman's feelings should be discussed in preparation for an abortion. The ability of health personnel to discuss subjects related to ethically challenging encounters with women who are considering abortions should be established, namely, professional education and workshops at the national level and small groups with counseling and case study discussions at hospitals.publishedVersio

Functional and molecular characterization of PD1+ tumor-infiltrating lymphocytes from lung cancer patients.

Antibody-mediated cancer immunotherapy targets inhibitory surface molecules, such as PD1, PD-L1, and CTLA-4, aiming to re-invigorate dysfunctional T cells. We purified and characterized tumor-infiltrating lymphocytes (TILs) and their patient-matched non-tumor counterparts from treatment-naïve NSCLC patient biopsies to evaluate the effect of PD1 expression on the functional and molecular profiles of tumor-resident T cells. We show that PD1+ CD8+ TILs have elevated expression of the transcriptional regulator ID3 and that the cytotoxic potential of CD8 T cells can be improved by knocking down ID3, defining it as a potential regulator of T cell effector function. PD1+ CD4+ memory TILs display transcriptional patterns consistent with both helper and regulator function, but can robustly facilitate B cell activation and expansion. Furthermore, we show that expanding ex vivo-prepared TILs in vitro broadly preserves their functionality with respect to tumor cell killing, B cell help, and TCR repertoire. Although purified PD1+ CD8+ TILs generally maintain an exhausted phenotype upon expansion in vitro, transcriptional analysis reveals a downregulation of markers of T-cell dysfunction, including the co-inhibitory molecules PD1 and CTLA-4 and transcription factors ID3, TOX and TOX2, while genes involved in cell cycle and DNA repair are upregulated. We find reduced expression of WNT signaling components to be a hallmark of PD1+ CD8+ exhausted T cells in vivo and in vitro and demonstrate that restoring WNT signaling, by pharmacological blockade of GSK3β, can improve effector function. These data unveil novel targets for tumor immunotherapy and have promising implications for the development of a personalized TIL-based cell therapy for lung cancer

"Wir bringen die breite Basis mit" – Gemeinsames Plädoyer für eine enge Einbindung der Landesinitiativen für Forschungsdatenmanagement in die Nationale Forschungsdateninfrastruktur

Der Erfolg einer nationalen Forschungsdateninfrastruktur hängt von der Einbindung der gesamten Wissenschaftsgemeinschaft und -infrastruktur ab. In zahlreichen Bundesländern existieren Landesinitiativen für Forschungsdatenmanagement oder ähnliche Einrichtungen, die dazu beitragen können, diese Einbindung zu erreichen. Das gemeinsame Papier von Vertretern aus verschiedenen Bundesländern argumentiert, dass eine enge Verknüpfung der Landesinitiativen mit dem NFDI e.V. erfolgen sollte, um die Potentiale der Zusammenarbeit zu nutzen

"Wir bringen die breite Basis mit" – Gemeinsames Plädoyer für eine enge Einbindung der Landesinitiativen für Forschungsdatenmanagement in die Nationale Forschungsdateninfrastruktur : gemeinsames Papier der Landesinitiativen von Baden-Württemberg (bw2FDM), Brandenburg (FDM-BB), Hessen (HeFDI), Nordrhein-Westfalen (fdm.nrw), Sachsen (SaxFDM), Thüringen (TKFDM) sowie Vertretern aus Bayern, Hamburg, Sachsen-Anhalt und Schleswig-Holstein

Der Erfolg einer nationalen Forschungsdateninfrastruktur hängt von der Einbindung der gesamten Wissenschaftsgemeinschaft und -infrastruktur ab. In zahlreichen Bundesländern existieren Landesinitiativen für Forschungsdatenmanagement oder ähnliche Einrichtungen, die dazu beitragen können, diese Einbindung zu erreichen. Das gemeinsame Papier von Vertretern aus verschiedenen Bundesländern argumentiert, dass eine enge Verknüpfung der Landesinitiativen mit dem NFDI e.V. erfolgen sollte, um die Potentiale der Zusammenarbeit zu nutzen. Der NFDI e. V. wird einen bedeutsamen Beitrag für einen besseren Umgang mit Forschungsdaten leisten, doch der Erfolg der nationalen Forschungsdateninfrastruktur ist letztlich von einer Einbindung der gesamten Wissenschaftsgemeinschaft und -infrastruktur abhängig. Die vielfältigen Forschungseinrichtungen einzubinden, erfordert Koordination auf vielen Ebenen. Speziell Hochschulen haben eine tragende Rolle für sowohl disziplinäre und interdisziplinäre Forschung als auch wissenschaftliche Ausbildung in Deutschland und sind damit zentrale Akteure für die fachübergreifende Forschungsdateninfrastruktur. Durch die Förderung von Kooperationen und Koordination auf Ebene von Ländern oder Länderverbünden lässt sich die Entwicklung der nationalen Forschungsdateninfrastruktur unterstützen. Landesinitiativen für Forschungsdatenmanagement (FDM) oder ähnliche koordinierende Einrichtungen können die digitale Transformation in der Forschung durch Information, den Aufbau von Kooperationen und die Qualifikation von Personal unterstützen. Ihre Einrichtung, dauerhafte Etablierung und Einbeziehung in die Arbeit des NFDI e. V. ist ein wichtiger Beitrag zur Schaffung einer nationalen Forschungsdateninfrastruktur