Community Driven Student Leadership: The DOCE Approach

Universities and the communities in which they reside must maintain an interdependence to thrive. The USM LAC Druker Office of Community Engagement (DOCE) follows a unique model of student-faculty collaborative leadership to model how public universities can partner with their communities. Developing long-lasting community-university relationships holds mutual benefits. DOCE connects students, faculty and staff with over 90 community partners. As a synergetic cooperative team, we believe community engagement is essential in the growth and learning of the whole student, faculty and staff of USM. Our recent Community-Based Participatory Research (CPBR) works in integrating the classes and curriculum of the Social and Behavioral Sciences (SBS) with the everyday issues of our surrounding community and the development of creative ways to meet various needs. Keeping the students’ interests and professors’ syllabi in mind, we link students to appropriate partners and help ease the stress of making that new connection

Leibniz, Acosmism, and Incompossibility

Leibniz claims that God acts in the best possible way, and that this includes creating exactly one world. But worlds are aggregates, and aggregates have a low degree of reality or metaphysical perfection, perhaps none at all. This is Leibniz’s tendency toward acosmism, or the view that there this no such thing as creation-as-a-whole. Many interpreters reconcile Leibniz’s acosmist tendency with the high value of worlds by proposing that God sums the value of each substance created, so that the best world is just the world with the most substances. I call this way of determining the value of a world the Additive Theory of Value (ATV), and argue that it leads to the current and insoluble form of the problem of incompossibility. To avoid the problem, I read “possible worlds” in “God chooses the best of all possible worlds” as referring to God’s ideas of worlds. These ideas, though built up from essences, are themselves unities and so well suited to be the value bearers that Leibniz’s theodicy requires. They have their own value, thanks to their unity, and that unity is not preserved when more essences are added

The (un)availability of prognostic information in the last days of life: a prospective observational study.

OBJECTIVES: The aims of this study were (1) to document the clinical condition of patients considered to be in the last 2 weeks of life and (2) to compare patients who did or did not survive for 72 hours. DESIGN: A prospective observational study. SETTING: Two sites in London, UK (a hospice and a hospital palliative care team). PARTICIPANTS: Any inpatient, over 18 years old, English speaking, who was identified by the palliative care team as at risk of dying within the next 2 weeks was eligible. OUTCOME MEASURES: Prognostic signs and symptoms were documented at a one off assessment and patients were followed up 7 days later to determine whether or not they had died. RESULTS: Fifty participants were recruited and 24/50 (48%) died within 72 hours of assessment. The most prevalent prognostic features observed were a decrease in oral food intake (60%) and a rapid decline of the participant's global health status (56%). Participants who died within 72 hours had a lower level of consciousness and had more care needs than those who lived longer. A large portion of data was unavailable, particularly that relating to the psychological and spiritual well-being of the patient, due to the decreased consciousness of the patient. CONCLUSIONS: The prevalence of prognostic signs and symptoms in the final days of life has been documented between those predicted to die and those who did not. How doctors make decisions with missing information is an area for future research, in addition to understanding the best way to use the available information to make more accurate predictions

Modelling the electric field applied to a tokamak

The vector potential for the Ohmic heating coil system of a tokamak is obtained in semi-analytical form. Comparison is made to the potential of a simple, finite solenoid. In the quasi-static limit, the time rate of change of the potential determines the induced electromotive force through the Maxwell-Lodge effect. Discussion of the gauge constraint is included.Comment: 13 pages, 7 figures, final versio

Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce Disease Severity and Immune Responses in Inflammatory Arthritis

Abstract Background Novel biological therapies have revolutionised the management of Rheumatoid Arthritis (RA) but no cure currently exists. Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling via growth factors, cytokines, chemokines and extracellular vesicles (EVs) in the cell secretome; however, MSCs are still not available in the clinic. We evaluated the therapeutic potential of MSCs-derived EVs in an antigen-induced model of arthritis (AIA). Methods EVs isolated from MSCs in normal (21% O 2 , 5% CO 2 ) or hypoxic (2% O 2 , 5% CO 2 ) culture or from MSCs pre-conditioned with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed 3 days post arthritis induction through histopathological analysis of knee joints. Spleens and lymph nodes were collected and assessed for T cell polarisation within the immune response to AIA. Activated naïve CD4+ T cells from spleens of healthy mice were cultured with EVs or MSCs to assess deactivation capabilities. Results All EV treatments significantly reduced knee-joint swelling and histopathological signs of AIA with enhanced responses to normoxic and pro-inflammatory primed EVs. Polarisation of T cells towards CD4+ helper cells expressing IL17a (Th17) was reduced when EV treatments from MSCs cultured in hypoxia or pro-inflammatory priming conditions were applied. Conclusions Hypoxically cultured EVs present a priming methodology that is as effective in reducing swelling, IL-17a expression, Th17 polarisation and T cell proliferation as pro-inflammatory priming. EVs present an effective novel technology for cell-free therapeutic translation in treating inflammatory arthritis and autoimmune disorders such as RA

Direct low field J-edited diffusional proton NMR spectroscopic measurement of COVID-19 inflammatory biomarkers in human serum.

A JEDI NMR pulse experiment incorporating relaxational, diffusional and J-modulation peak editing has been implemented for a low field (80 MHz proton resonance frequency) spectrometer system to measure quantitatively two recently discovered plasma markers of SARS-CoV-2 infection and general inflammation. JEDI spectra capture a unique signature of two biomarker signals from acetylated glycoproteins (Glyc) and the supramolecular phospholipid composite (SPC) signals that are relatively enhanced by the combination of relaxation, diffusion and J-editing properties of the JEDI experiment that strongly attenuate contributions from the other molecular species in plasma. The SPC/Glyc ratio data were essentially identical in the 600 MHz and 80 MHz spectra obtained (R2 = 0.97) and showed significantly different ratios for control (n = 28) versus SARS-CoV-2 positive patients (n = 29) (p = 5.2 × 10-8 and 3.7 × 10-8 respectively). Simplification of the sample preparation allows for data acquisition in a similar time frame to high field machines (∼4 min) and a high-throughput version with 1 min experiment time could be feasible. These data show that these newly discovered inflammatory biomarkers can be measured effectively on low field NMR instruments that do not not require housing in a complex laboratory environment, thus lowering the barrier to clinical translation of this diagnostic technology

Deprotection of centromeric cohesin at meiosis II requires APC/C activity but not kinetochore tension

Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. However, deprotection has been proposed to rely on spindle forces separating the Rec8 protector from cohesin at metaphase II in mammalian oocytes and on APC/C-dependent destruction of the protector at anaphase II in yeast. Here, we have activated APC/C in the absence of sister kinetochore biorientation at meiosis II in yeast and mouse oocytes, and find that bipolar spindle forces are dispensable for sister centromere separation in both systems. Furthermore, we show that at least in yeast, protection of Rec8 by shugoshin and inhibition of separase by securin are both required for the stability of centromeric cohesin at metaphase II. Our data imply that related mechanisms preserve the integrity of dyad chromosomes during the short metaphase II of yeast and the prolonged metaphase II arrest of mammalian oocytes

Direct low field J-edited diffusional proton NMR spectroscopic measurement of COVID-19 inflammatory biomarkers in human serum

A JEDI NMR pulse experiment incorporating relaxational, diffusional and J-modulation peak editing has been implemented for a low field (80 MHz proton resonance frequency) spectrometer system to measure quantitatively two recently discovered plasma markers of SARS-CoV-2 infection and general inflammation. JEDI spectra capture a unique signature of two biomarker signals from acetylated glycoproteins (Glyc) and the supramolecular phospholipid composite (SPC) signals that are relatively enhanced by the combination of relaxation, diffusion and J-editing properties of the JEDI experiment that strongly attenuate contributions from the other molecular species in plasma. The SPC/Glyc ratio data were essentially identical in the 600 MHz and 80 MHz spectra obtained (R2 = 0.97) and showed significantly different ratios for control (n = 28) versus SARS-CoV-2 positive patients (n = 29) (p = 5.2 × 10−8 and 3.7 × 10−8 respectively). Simplification of the sample preparation allows for data acquisition in a similar time frame to high field machines (∼4 min) and a high-throughput version with 1 min experiment time could be feasible. These data show that these newly discovered inflammatory biomarkers can be measured effectively on low field NMR instruments that do not not require housing in a complex laboratory environment, thus lowering the barrier to clinical translation of this diagnostic technology

How do palliative care doctors recognise imminently dying patients? A judgement analysis.

OBJECTIVES: To identify a group of palliative care doctors who perform well on a prognostic test and to understand how they make their survival predictions. DESIGN: Prospective observational study and two cross-sectional online studies. SETTING: Phase I: an online prognostic test, developed from a prospective observational study of patients referred to palliative care. Phase II: an online judgement task consisting of 50 hypothetical vignettes. PARTICIPANTS: All members of the Association of Palliative Medicine (APM) were eligible (n=~1100). 99 doctors completed the prognostic test and were included in the phase I analysis. The top 20% were invited to participate in phase II; 14/19 doctors completed the judgement task and were included in the phase II analysis. MEASURES: Phase I: participants were asked to give a probability of death within 72 hours (0%-100%) for all 20 cases. Accuracy on the prognostic test was measured with the Brier score which was used to identify the 'expert' group (scale range: 0 (expert)-1 (non-expert)). Phase II: participants gave a probability of death within 72 hours (0%-100%). A mixed model regression analysis was completed using the percentage estimate as the outcome and the patient information included in the vignettes as the predictors. RESULTS: The mean Brier score of all participants was 0.237 (95% CI 0.235 to 0.239). The mean Brier score of the 'experts' was 0.184 (95% CI 0.176 to 0.192). Six of the seven prognostic variables included in the hypothetical vignettes were significantly associated with clinician predictions of death. The Palliative Performance Score was identified as being the most influential in the doctors' prognostic decision making (β=0.48, p<0.001). CONCLUSIONS: This study identified six clinical signs and symptoms which influenced the judgement policies of palliative care doctors. These results may be used to teach novice doctors how to improve their prognostic skills

An Information Plane Architecture Supporting Home Network Management

Home networks have evolved to become small-scale versions of enterprise networks. The tools for visualizing and managing such networks are primitive and continue to require networked systems expertise on the part of the home user. As a result, non-expert home users must manually manage non-obvious aspects of the network - e.g., MAC address filtering, network masks, and firewall rules, using these primitive tools. The Homework information plane architecture uses stream database concepts to generate derived events from streams of raw events. This supports a variety of visualization and monitoring techniques, and also enables construction of a closed-loop, policy-based management system. This paper describes the information plane architecture and its associated policy-based management infrastructure. Exemplar visualization and closed-loop management applications enabled by the resulting system (tuned to the skills of non-expert home users) are discussed. © 2011 IEEE.Accepted versio