European Defense in A New Age (#EDINA): Geostrategic Changes and European Responses Shaping the Defense Ecosystem

Delve into the transformation of Europe's defense landscape following Russia's Ukraine invasion in 2022 with our comprehensive report. Part of the long-term project on European Defense In a New Age (EDINA), this report provides expert insights on shifts in Europe's military order, defense cooperation, and geopolitical landscape, with a focus on Europe's evolving Defense Technological and Industrial Base (DTIB). Explore key findings on political change, potential divisions, and China's role and discover the seismic shifts reshaping European defense

Patient Attitudes Toward a Physician Led Radiology Review: Improved Understanding of Medical Conditions and a Potential New Quality Metric

Objectives: We were interested in understanding patient perspectives regarding the importance of reviewing their imaging studies with a surgeon. Specific Aims: 1. What value do patients place on viewing their imaging? 2. Do patients have a better understanding of their disease and planned operation after a surgeon led review of imaging studies? 3. Do patients find viewing images an accessible educational tool?https://jdc.jefferson.edu/patientsafetyposters/1022/thumbnail.jp

A Sub-Type of Familial Pancreatic Cancer: Evidence and Implications of Loss-of-Function Polymorphisms in Indoleamine-2,3-Dioxygenase-2.

BACKGROUND: Variation in an individual\u27s genetic status can impact the development of pancreatic ductal adenocarcinoma; however, the majority of familial pancreatic cancers (FPC) cannot yet be attributed to a specific inherited mutation. We present data suggesting a correlation between loss-of-function single nucleotide polymorphisms (SNPs) in an immune regulator gene, indoleamine-2,3-dioxygenase-2 (IDO2), and an increased risk of FPC. STUDY DESIGN: Germline DNA from patients who underwent resection for pancreatic ductal adenocarcinoma (n = 79) was sequenced for the IDO2 SNPs R248W and Y359Stop. Genotypes resulting in inactivation of IDO2 (Y325X homozygous, R248W homozygous) were labeled as homozygous, and the other genotypes were grouped as wild-type or heterozygous. Genotype distributions of each SNP were analyzed for Hardy-Weinberg deviation. A genotype frequency set from the 1000 Genomes Project (n = 99) was used as a genetic control for genotype distribution comparisons. RESULTS: A significant 2-fold increase in the overall prevalence of the Y359Stop homozygous genotype compared with the expected Hardy-Weinberg equilibrium was noted (p \u3c 0.05). Familial pancreatic cancer was noted in 15 cases (19%) and comparison of the FPC cohort set to the genetic control set showed a 3-fold increase in Y359Stop homozygous rates (p = 0.054). Overall in our cohort, the homozygous genotype group was associated with increased risk of FPC (odds ratio 5.4; 95% CI 1.6 to 17.6; p \u3c 0.01). Sex, age at diagnosis, and history of tobacco use were not found to be significantly associated with FPC. CONCLUSIONS: Our preliminary data suggest a strong association between the IDO2 inactivating Y359Stop SNP and an increased risk of FPC when compared with the control group. Future studies will evaluate the value of IDO2 genotyping as a prognostic, early detection marker for pancreatic ductal adenocarcinoma and a predictive marker for novel immune checkpoint therapies

Associations between maternal thyroid function in pregnancy and child neurodevelopmental outcomes at 20 months in the Seychelles Child Development Study, Nutrition Cohort 2 (SCDS NC2)

Maternal thyroid hormones facilitate optimal foetal neurodevelopment; however, the exact role of the thyroid hormones on specific cognitive outcomes is unknown. The present study aimed to investigate associations between maternal thyroid function and neurodevelopmental outcomes in the Seychelles Child Development Study (SCDS) Nutrition 2 cohort (n 1328). Maternal free thyroid hormones (fT3, fT4 and fTSH) were assessed at 28 weeks’ gestation with a range of child cognitive outcomes analysed at 20 months. Dietary iodine intake was analysed for a subset of women through a Food Frequency Questionnaire. Linear regression analysis was used to test associations between serum concentrations of maternal thyroid hormones and child neurodevelopment outcomes. Thyroid hormones were analysed as continuous data and categorised as quintiles. 95% of mothers had optimal thyroid function based on fTSH concentrations. Overall, the present study shows that maternal thyroid function is not associated with neurodevelopmental outcomes in this high fish-eating population. However, a positive association, using quintiles for fT3, was reported for the Mental Developmental Index, between Q3 v. Q4 (β 0⋅073; P 0⋅043) and for Q3 v. Q5 (β value 0⋅086; P 0⋅018). To conclude, mothers in our cohort, who largely have optimal thyroid function and iodine intakes, appear able to regulate thyroid function throughout pregnancy to meet neurodevelopmental needs. However, it is possible that minor imbalances of fT3, as indicated from our secondary analysis, may impact offspring neurodevelopment. Further investigation of the relationship between maternal thyroid function and infant neurodevelopment is warranted, particularly in populations with different dietary patterns and thereby iodine intakes

The Pathway to Low Outlier Status in Venous Thromboembolism Events: An Analysis of Pancreatic Surgery in ACS NSQIP

Introduction: Our institution’s hepatopancreaticobiliary service (HPBS) is a high-volume pancreatic surgery service, which has demonstrated consistently low rates of symptomatic venous thromboembolism (VTE) compared to similar institutions as reported by NSQIP. We sought to determine if the HPBS’s regimented multimodal VTE prophylaxis pathway plays a role in achieving consistently low VTE rates. Methods: We queried the ACS NSQIP Participant User File and our institution’s data from 2011-2016 for major pancreatic operations. We used Chi-squared analysis to compare the HPBS and national patient populations, and created a matched dataset based on preoperative patient factors. Univariate and multivariate analyses were performed on both the aggregate and matched data to determine independent risk factors for symptomatic VTE formation. Results: Among 36,435 NSQIP patients, 850 (2.3%) received surgery by the HPBS. VTE rates were significantly lower for the HPBS (2.0%) compared to the national cohort (3.5%) (p=0.018); this significance was seen in the matched cohort as well (p=0.040). Upon multivariate analysis, having an operation performed by the HPBS independently conferred lower odds of VTE formation in both the aggregate (OR=0.572, p=0.024) and matched (OR=0.530, p=0.041) cohorts. Discussion: The HPBS had statistically lower rates of symptomatic VTE compared to the national cohort as reported by NSQIP. We identified an independent protective effect of the HPBS on VTE formation, which we believe to be due, at least in part, to adherence to a high risk VTE prophylaxis pathway. This pathway could serve as a model for other institutions hoping to improve their VTE rates

Optimizing cancer cure dialog: an analysis of pancreatic cancer patients\u27 views regarding survival and cure.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. Clinicians commonly refer to surgical therapy as resection with curative intent. However, PDA cure rates after resection remain unknown and the definition of cure remains vague. We investigated how patients (the majority undergoing resection), family members, and clinicians understand the concept of cure, to better inform discussions with patients regarding PDA prognosis. METHODS: In a prospective survey, cohorts were asked to indicate the best definition of cure from three choices: 5-year survival endpoint (typically used in the literature), a biological endpoint without biochemical or radiographic signs of disease (similar to the NCI definition), or a practical endpoint where life span approximates similarly aged patients without PDA. Fleiss\u27 kappa statistic was calculated to measure inter-rater agreement. RESULTS: Patients, family members, and health care professionals (N = 200) agreed that renormalization of life expectancy was the preferred definition of cure in the context of pancreatic cancer. Inter-rater agreement was highest for the patient and family member groups (Fleiss\u27 kappa 0.27 and 0.40, respectively, P \u3c 0.001), while variability was observed between health care professionals (Fleiss\u27 kappa 0.11, P \u3c 0.001). CONCLUSIONS: In all groups surveyed, the probability for a normal life expectancy is the preferred long-term metric in patients with early-staged pancreatic cancer. Renormalization of life expectancy appears to be an important therapy goal for PDA patients and it is advisable to address this topic during clinical discussions

NIK-dependent RelB Activation Defines a Unique Signaling Pathway for the Development of Vα14i NKT Cells

A defect in RelB, a member of the Rel/nuclear factor (NF)-κB family of transcription factors, affects antigen presenting cells and the formation of lymphoid organs, but its role in T lymphocyte differentiation is not well characterized. Here, we show that RelB deficiency in mice leads to a selective decrease of NKT cells. RelB must be expressed in an irradiation-resistant host cell that can be CD1d negative, indicating that the RelB expressing cell does not contribute directly to the positive selection of CD1d-dependent NKT cells. Like RelB-deficient mice, aly/aly mice with a mutation for the NF-κB–inducing kinase (NIK), have reduced NKT cell numbers. An analysis of NK1.1 and CD44 expression on NKT cells in the thymus of aly/aly mice reveals a late block in development. In vitro, we show that NIK is necessary for RelB activation upon triggering of surface receptors. This link between NIK and RelB was further demonstrated in vivo by analyzing RelB+/− × aly/+ compound heterozygous mice. After stimulation with α-GalCer, an antigen recognized by NKT cells, these compound heterozygotes had reduced responses compared with either RelB+/− or aly/+ mice. These data illustrate the complex interplay between hemopoietic and nonhemopoietic cell types for the development of NKT cells, and they demonstrate the unique requirement of NKT cells for a signaling pathway mediated by NIK activation of RelB in a thymic stromal cell

Evidence of mTOR Activation by an AKT-Independent Mechanism Provides Support for the Combined Treatment of PTEN-Deficient Prostate Tumors with mTOR and AKT Inhibitors

AbstractActivation of the phosphoinositide 3-kinase pathway is commonly observed in human prostate cancer. Loss of function of phosphatase and tensin homolog (PTEN) is associated with the activation of AKT and mammalian target of rapamycin (mTOR) in many cancer cell lines as well as in other model systems. However, activation of mTOR is also dependent of kinases other than AKT. Here, we show that activation of mTOR is not dependent on AKT in a prostate-specific PTEN-deficient mouse model of prostate cancer. Pathway bifurcation of AKT and mTOR was noted in both mouse and human prostate tumors. We demonstrated for the first time that cotargeting mTOR and AKT with ridaforolimus/MK-8669 and M1K-2206, respectively, delivers additive antitumor effects in vivo when compared to single agents. Our preclinical data suggest that the combination of AKT and mTOR inhibitors might be more effective in treating prostate cancer patients than current treatment regimens or either treatment alone

Stakeholder engagement to ensure the sustainability of biobanks: a survey of potential users of biobank services

Biobanks are important infrastructures facilitating biomedical research. After a decade of rolling out such infrastructures, a shift in attention to the sustainability of biobanks could be observed in recent years. In this regard, an increase in the as yet relatively low utilisation rates of biobanks has been formulated as a goal. Higher utilisation rates can only be achieved if the perspectives of potential users of biobanks-particularly researchers not yet collaborating with biobanks-are adequately considered. To better understand their perspectives, a survey was conducted at ten different research institutions in Germany hosting a centralised biobank. The survey targeted potential users of biobank services, i.e. researchers working with biosamples. It addressed the general demand for biosamples, strategies for biosample acquisition/storage and reasons for/against collaborating with biobanks. In total, 354 researchers filled out the survey. Most interestingly, only a minority of researchers (12%) acquired their biosamples via biobanks. Of the respondents not collaborating with biobanks on sample acquisition, around half were not aware of the (services of the) respective local biobank. Those who actively decided against acquiring biosamples via a biobank provided different reasons. Most commonly, respondents stated that the biosamples required were not available, the costs were too high and information about the available biosamples was not readily accessible. Biobanks can draw many lessons from the results of the survey. Particularly, external communication and outreach should be improved. Additionally, biobanks might have to reassess whether their particular collection strategies are adequately aligned with local researchers' needs

Immersion : Grenzen und Metaphorik des digitalen Subjekts

2. Hrsg. des Heftes: Dawid Kasprowicz Prof. Dr. Jens Schröter, Dr. Pablo Abend und J.-Prof. Dr. Benjamin Beil sind Herausgeber der Reihe. Die Herausgeber der einzelnen Hefte sind renommierte Wissenschaftler und -innen aus dem In- und Ausland.Von der Verschränkung unseres Alltags mit digitalen Medien bis hin zum Erlebniswert technisch-responsiver Räume über das Attunement atmosphärisch gestimmter Arbeitsplätze: All diese Formen der Einbettung oder des Eintauchens in mediatisierte Umwelten finden ihre Bezeichnung als Immersion. Die Immersion ist dabei aber weder für digitale noch für artifizielle Umwelten reserviert. Sie stellt vielmehr eine Medienpraxis für die Konstruktion von Subjektivität und dessen Grenzen dar. Subjektivität ist damit unter Bedingungen der Immersion eben keine Auflösungs- oder Täuschungsfigur. Denn so heterogen das Verfahren der Immersion auch sein mag, so zielt es doch auf die Frage nach neuen Bestimmungen des Selbst, des Körpers sowie der Emotionalität und nicht zuletzt der jeweils neu gesetzten Abgrenzung zur Umwelt ab. Die Beiträge in diesem Heft versammeln solche Verfahren der Immersion anhand von Phänomenen wie dem Affekt, der Musik, der Leiblichkeit, der Animation, dem kollektiven Gedenken oder der kinematographischen Projektion