104 research outputs found

    Erotic Devotional Poetry: Resisting Neoplatonism in Protestant Christianity

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    A genre best known for its appearance in Eastern religions, erotic devotional poetry uses sensual imagery to access an experience of the divine. Historically, many Christian traditions, excluding the mystical ones, have pushed back against such literature, seeing it as an impure model that degrades divinity by association with the physical, especially in the specific physical ritual of sex. This stance is a hallmark of Protestant Christianity. The idea of a dichotomy and hierarchy between soul and body, though, comes not from theology but from the introduction theologians made between Western philosophy, particularly Platonic Dualism, and Christianity, which was then solidified by Enlightenment ideals. My project identifies the theological and philosophical basis for erotic devotional poems and looks to the way that they, particularly in the writing of Rainer Maria Rilke, have resisted the intrusion of neoplatonism upon spiritual practice

    Optimising integrated stroke care in regional networks:A nationwide self-assessment study in 2012, 2015 and 2019

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    Background: To help enhance the quality of integrated stroke care delivery, regional stroke services networks in the Netherlands participated in a self-assessment study in 2012, 2015 and 2019. Methods: Coordinators of the regional stroke services networks filled out an online self-assessment questionnaire in 2012, 2015 and 2019. The questionnaire, which was based on the Development Model for Integrated Care, consisted of 97 questions in nine clusters (themes). Cluster scores were calculated as proportions of the activities implemented. Associations between clusters and features of stroke services were assessed by regression analysis. Results: The response rate varied from 93.1% (2012) to 85.5% (2019). Over the years, the regional stroke services networks increased in ‘size’: the median number of organisations involved and the volume of patients per network increased (7 and 499 in 2019, compared to 5 and 364 in 2012). At the same time, fewer coordinators were appointed for more than 1 day a week in 2019 (35.1%) compared to 2012 (45.9%). Between 2012 and 2019, there were statistically significantly more elements implemented in four out of nine clusters: ‘Transparent entrepreneurship’ (MD = 18.0% F(1) = 10.693, p = 0.001), ‘Roles and tasks’ (MD = 14.0% F(1) = 9.255, p = 0.003), ‘Patient-centeredness’ (MD = 12.9% F(1) = 9.255, p = 0.003), and ‘Commitment’ (MD = 11.2%, F(1) = 4.982, p = 0.028). A statistically significant positive correlation was found for all clusters between implementation of activities and age of the network. In addition, the number of involved organisations is associated with better execution of implemented activities for ‘Transparent entrepreneurship’, ‘Result-focused learning’ and ‘Quality of care’. Conversely, there are small but negative associations between the volume of patients and implementation rates for ‘Interprofessional teamwork’ and ‘Patient-centredness’. Conclusion: This long-term analyses of stroke service development in the Netherlands, showed that between 2012 and 2019, integrated care activities within the regional stroke networks increased. Experience in collaboration between organisations within a network benefits the uptake of integrated care activities

    Inhibition of the succinyl dehydrogenase complex in acute myeloid leukemia leads to a lactate-fuelled respiratory metabolic vulnerability

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    Metabolic programs can differ substantially across genetically distinct subtypes of acute myeloid leukemia (AML). These programs are not static entities but can change swiftly as a consequence of extracellular changes or in response to pathway-inhibiting drugs. Here, we uncover that AML patients with FLT3 internal tandem duplications (FLT3-ITD+) are characterized by a high expression of succinate-CoA ligases and high activity of mitochondrial electron transport chain (ETC) complex II, thereby driving high mitochondrial respiration activity linked to the Krebs cycle. While inhibition of ETC complex II enhances apoptosis in FLT3-ITD+ AML, cells also quickly adapt by importing lactate from the extracellular microenvironment. 13C3-labelled lactate metabolic flux analyses reveal that AML cells use lactate as a fuel for mitochondrial respiration. Inhibition of lactate transport by blocking Monocarboxylic Acid Transporter 1 (MCT1) strongly enhances sensitivity to ETC complex II inhibition in vitro as well as in vivo. Our study highlights a metabolic adaptability of cancer cells that can be exploited therapeutically.</p

    The Glycolytic Gatekeeper PDK1 defines different metabolic states between genetically distinct subtypes of human acute myeloid leukemia

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    Acute myeloid leukemia remains difficult to treat due to strong genetic heterogeneity between and within individual patients. Here, we show that Pyruvate dehydrogenase kinase 1 (PDK1) acts as a targetable determinant of different metabolic states in acute myeloid leukemia (AML). PDK1(low) AMLs are OXPHOS-driven, are enriched for leukemic granulocyte-monocyte progenitor (L-GMP) signatures, and are associated with FLT3-ITD and NPM1cyt mutations. PDK1(high) AMLs however are OXPHOS(low), wild type for FLT3 and NPM1, and are enriched for stemness signatures. Metabolic states can even differ between genetically distinct subclones within individual patients. Loss of PDK1 activity releases glycolytic cells into an OXPHOS state associated with increased ROS levels resulting in enhanced apoptosis in leukemic but not in healthy stem/progenitor cells. This coincides with an enhanced dependency on glutamine uptake and reduced proliferation in vitro and in vivo in humanized xenograft mouse models. We show that human leukemias display distinct metabolic states and adaptation mechanisms that can serve as targets for treatment

    Temperature variations at diffuse and focused flow hydrothermal vent sites along the northern East Pacific Rise

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    Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 7 (2006): Q03002, doi:10.1029/2005GC001094.In the decade following documented volcanic activity on the East Pacific Rise near 9°50′N, we monitored hydrothermal vent fluid temperature variations in conjunction with approximately yearly vent fluid sampling to better understand the processes and physical conditions that govern the evolution of seafloor hydrothermal systems. The temperature of both diffuse flow (low-temperature) and focused flow (high-temperature) vent fluids decreased significantly within several years of eruptions in 1991 and 1992. After mid-1994, focused flow vents generally exhibited periods of relatively stable, slowly varying temperatures, with occasional high- and low-temperature excursions lasting days to weeks. One such positive temperature excursion was associated with a crustal cracking event. Another with both positive and negative excursions demonstrated a subsurface connection between adjacent focused flow and diffuse flow vents. Diffuse flow vents exhibit much greater temperature variability than adjacent higher-temperature vents. On timescales of a week or less, temperatures at a given position within a diffuse flow field often varied by 5°–10°C, synchronous with near-bottom currents dominated by tidal and inertial forcing. On timescales of a week and longer, diffuse flow temperatures varied slowly and incoherently among different vent fields. At diffuse flow vent sites, the conceptual model of a thermal boundary layer immediately above the seafloor explains many of the temporal and spatial temperature variations observed within a single vent field. The thermal boundary layer is a lens of warm water injected from beneath the seafloor that is mixed and distended by lateral near-bottom currents. The volume of the boundary layer is delineated by the position of mature communities of sessile (e.g., tubeworms) and relatively slow-moving organisms (e.g., mussels). Vertical flow rates of hydrothermal fluids exiting the seafloor at diffuse vents are less than lateral flow rates of near-bottom currents (5–10 cm/s). The presence of a subsurface, shallow reservoir of warm hydrothermal fluids can explain differing temperature behaviors of adjacent diffuse flow and focused flow vents at 9°50′N. Different average temperatures and daily temperature ranges are explained by variable amounts of mixing of hydrothermal fluids with ambient seawater through subsurface conduits that have varying lateral permeability.Field and shore-based analyses have been supported by the National Science Foundation (OCE-0096468, OCE-8917311, OCE-9217026, OCE-9302205, OCE-0327261), the Woods Hole Oceanographic Institution's Vetlesen Fund and W. A. Clark Senior Scientist Chair (DJF), and the Devonshire Foundation (TMS)

    Primary care nurses: effects on secondary care referrals for diabetes

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    Background: Primary care nurses play an important role in diabetes care, and were introduced in GP-practice partly to shift care from hospital to primary care. The aim of this study was to assess whether the referral rate for hospital treatment for diabetes type II (T2DM) patients has changed with the introduction of primary care nurses, and whether these changes were related to the number of diabetes-related contacts in a general practice. Methods: Healthcare utilisation was assessed for a period of 365 days for 301 newly diagnosed and 2124 known T2DM patients in 2004 and 450 and 3226 patients in 2006 from general practices that participated in the Netherlands Information Network of General Practice (LINH). Multilevel logistic and linear regression analyses were used to analyse the effect of the introduction of primary care nurses on referrals to internists, ophthalmologists and cardiologists and diabetes-related contact rate. Separate analyses were conducted for newly diagnosed and known T2DM patients. Results: Referrals to internists for newly diagnosed T2DM patients decreased between 2004 and 2006 (OR:0.44; 95%CI:0.22-0.87) in all practices. For known T2DM patients no overall decrease in referrals to internists was found, but practices with a primary care nurse had a lower trend (OR:0.59). The number of diabetes-related contacts did not differ between practices with and without primary care nurses. Cardiologists’ and ophthalmologists’ referral rate did not change. Conclusions: The introduction of primary care nurses seems to have led to a shift of care from internists to primary care for known diabetes patients, while the diabetes-related contact rate seem to have remained unchanged.

    The Sound Generated by Mid-Ocean Ridge Black Smoker Hydrothermal Vents

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    Hydrothermal flow through seafloor black smoker vents is typically turbulent and vigorous, with speeds often exceeding 1 m/s. Although theory predicts that these flows will generate sound, the prevailing view has been that black smokers are essentially silent. Here we present the first unambiguous field recordings showing that these vents radiate significant acoustic energy. The sounds contain a broadband component and narrowband tones which are indicative of resonance. The amplitude of the broadband component shows tidal modulation which is indicative of discharge rate variations related to the mechanics of tidal loading. Vent sounds will provide researchers with new ways to study flow through sulfide structures, and may provide some local organisms with behavioral or navigational cues
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