The effects of PEG‐based surface modification of PDMS microchannels on long‐term hemocompatibility

The current study demonstrates the first surface modification for poly(dimethylsiloxane) (PDMS) microfluidic networks that displays a long shelf life as well as extended hemocompatibility. Uncoated PDMS microchannel networks rapidly adsorb high levels of fibrinogen in blood contacting applications. Fibrinogen adsorption initiates platelet activation, and causes a rapid increase in pressure across microchannel networks, rendering them useless for long term applications. Here, we describe the modification of sealed PDMS microchannels using an oxygen plasma pretreatment and poly(ethylene glycol) grafting approach. We present results regarding the testing of the coated microchannels after extended periods of aging and blood exposure. Our PEG‐grafted channels showed significantly reduced fibrinogen adsorption and platelet adhesion up to 28 days after application, highlighting the stability and functionality of the coating over time. Our coated microchannel networks also displayed a significant reduction in the coagulation response under whole blood flow. Further, pressure across coated microchannel networks took over 16 times longer to double than the uncoated controls. Collectively, our data implies the potential for a coating platform for microfluidic devices in many blood‐contacting applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4195–4205, 2014.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109295/1/jbma35090.pd

Resilience of Healthcare Providers during COVID-19 Pandemic: A Rapid Assessment using Digital Platform

Introduction: Coronavirus Disease-2019 (COVID-19) pandemic exposed the health workforce to an unprecedented occupational hazard. While taking care of patients they always had to be conscious simultaneously for safeguarding themselves and their family members against the highly infectious virus. In West Bengal, cases were first reported in the last week of March-2020 and reached the peak around October-2020 in the first wave, once the lockdown was lifted. During the initial months, the staggering number of cases, prevailing uncertainty over case management, and untimely demise of colleagues and relatives, took their toll on the physical and mental health of doctors, paramedics, or support staff, both in the government and private sectors. Aim: To measure perceived stress, resilience and psychological well-being of healthcare providers using standard psychometric tools. Materials and Methods: This was a cross-sectional observational study carried out among healthcare workers in hospitals located in West Bengal, India. A self-administered questionnaire was circulated through a digital platform between June-November 2020. The questionnaire was designed using Perceived Stress Scale (PSS-10), Kessler-6 (K6), and Brief Resilient Coping Scale (BRCS) to assess perceived stress, psychiatric morbidity, and resilience of the person. It had three parts, one to capture socio-demographic details of the participants including age, sex, marital status, occupation, family history of psychiatric morbidity, place of stay etc. Second part consisted of psychometric scales and third was designed to capture the views of participants on the coping strategies. Calculated sample size was 189. Results: Based on standard cut-off values, it was found that 65.6% subjects were under moderate or severe stress; 56.6% had compromised mental well-being and 64% were not coping well with the pandemic situation. PSS were significantly poor for females (p-value <0.001), single (p-value <0.001) and those without history of psychiatric morbidity (p-value <0.001) and low resilient copers (p<0.0001). Mental well-being was compromised more among married (p-value=0.01), doctors (p-value=0.008), aged <40 years (p-value=0.003), high resilient copers (p-value=0.02). Popular means of stress reliever were music and yoga/exercise. Correct and updated knowledge on disease transmission, availability of personal protective equipment, pursuing hobbies like music and gardening were few suggested measures to improve coping with stress associated with patient care. Conclusion: The study revealed that majority of the health workers experienced moderate to heavy degree of stress and compromised psychological well-being during the first wave of pandemic. Relationship of stress and psychological well-being with resilience and socio-demographic variables was not always linear

SynthoPlate: A platelet-inspired hemostatic nanotechnology for treatment of bleeding complications

Platelet transfusions are routinely used in the clinic to treat bleeding complications stemming from trauma, surgery, malignancy-related bone marrow dysfunctions, and congenital or drug-related defects platelet defects. These transfusions primarily use allogeneic platelet concentrates (PCs) that pose issues of limited availability and portability, high risk of bacterial contamination, very short shelf life (~3-5 days), need for antigen matching and several biologic side effects. While robust research is being directed at resolving some of these issues, there is in parallel a significant clinical interest in synthetic platelet substitutes that can render efficient hemostasis by leveraging and amplifying endogenous clotting mechanisms while avoiding the above issues. To this end, we have developed a unique platelet-inspired synthetic hemostat technology called the SynthoPlate® (US Patent 9107845). Since platelets promote primary hemostasis via adhesion to vWF and collagen at the injury site and concomitant aggregation via fibrinogen binding to integrin GPIIb-IIIa on active platelets, we have mimicked and integrated these key hemostatic mechanisms on the SynthoPlate® by heteromultivalent surface-engineering of a liposomal platform with vWF-binding peptides (VBP), collagen-binding peptides (CBP) and fibrinogen-mimetic peptides (FMP). These ~150nm diameter SynthoPlate® vesicles are sterilizable and can be stored as lyophilized powder for long periods of time. We demonstrated, in vitro, that this platelet-mimetic integrative design renders hemostatically relevant functions at levels significantly higher than designs that mimic platelet’s adhesion function only or aggregation function only. We further demonstrated in vitro that SynthoPlate®-mediated site-selective amplification of primary hemostatic mechanisms (active platelet recruitment and aggregation) in effect results in site-selective enhancement of secondary hemostatic function (fibrin generation). We also established that SynthoPlate® does not activate and aggregate resting platelets or trigger coagulation mechanisms in plasma, suggesting that this technology will not have systemic pro-thrombotic and coagulatory risks. The hemostatic efficacy of SynthoPlate® was tested in appropriate tail-transection and liver bleeding models in mice, as well as, pilot studies in arterial bleeding model in pigs. In tail-transection bleeding model in normal as well as thrombocytopenic mice, prophylactically administered SynthoPlate® was able to significantly reduce bleeding time by 60-70%. In laparotomy traumatic bleeding model in mice, prophylactically administered SynthoPlate® was able to reduce blood volume loss by ~30%, reduced hypotension effects and increased survival by \u3e80%. In pilot pig models of arterial bleeding, emergency administration of SynthoPlate® has shown substantial reduction in blood volume loss. Immunohistological evaluation of tissues from various treated animals have shown marked co-localization of red fluorescent SynthoPlate® with green fluorescent platelets localized at the clot site. Biodistribution studies in animals indicate that SynthoPlate® is cleared primarily by liver and spleen, similar to clinically known liposomal technologies. We have also demonstrated that the platelet-mimetic heteromultivalent surface-decoration approach can be adapted to other biomedically relevant particle platforms. Altogether, our studies establish the promise of SynthoPlate® nanotechnology as a platelet-mimetic intravenous hemostat for treatment of bleeding complications in prophylactic and emergency scenarios. Ongoing studies are focused on evaluating this technology in clinically motivated large animal bleeding models, with a vision for translation

Military Medicine and Medical Research as a Source of Inspiration and Innovation to Solve National Security and Health Challenges in the 21st Century

The history of military medicine and research is rife with examples of novel treatments and new approaches to heal and cure soldiers and others impacted by war’s devastation. In the 21st century, new threats, like climate change, are combined with traditional threats, like geopolitical conflict, to create novel challenges for our strategic interests. Extreme and inaccessible environments provide heightened risks for warfighter exposure to dangerous bacteria, viruses, and fungi, as well as exposure to toxic substances and extremes of temperature, pressure, or both providing threats to performance and eroding resilience. Back home, caring for our veterans is also a healthcare priority, and the diseases of veterans increasingly overlap with the health needs of an aging society. These trends of climate change, politics, and demographics suggest performance evaluation and resilience planning and response are critical to assuring both warfighter performance and societal health. The Cleveland ecosystem, comprising several hospitals, a leading University, and one of the nation’s larger Veteran’s Health Administration systems, is ideal for incubating and understanding the response to these challenges. In this review, we explore the interconnections of collaborations between Defense agencies, particularly Air Force and Army and academic medical center-based investigators to drive responses to the national health security challenges facing the United States and the world.

Factor XII and Upar Upregulate Neutrophil Functions to Influence Wound Healing

Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to the inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12–/–) had fewer neutrophils recruited than WT mice. We discovered that neutrophils produced a pool of FXII that is functionally distinct from hepatic-derived FXII and contributes to neutrophil trafficking at sites of inflammation. FXII signals in neutrophils through urokinase plasminogen activator receptor–mediated (uPAR-mediated) Akt2 phosphorylation at S474 (pAktS474). Downstream of pAkt2S474, FXII stimulation of neutrophils upregulated surface expression of αMβ2 integrin, increased intracellular calcium, and promoted extracellular DNA release. The sum of these activities contributed to neutrophil cell adhesion, migration, and release of neutrophil extracellular traps in a process called NETosis. Decreased neutrophil signaling in F12–/– mice resulted in less inflammation and faster wound healing. Targeting hepatic F12 with siRNA did not affect neutrophil migration, whereas WT BM transplanted into F12–/– hosts was sufficient to correct the neutrophil migration defect in F12–/– mice and restore wound inflammation. Importantly, these activities were a zymogen FXII function and independent of FXIIa and contact activation, highlighting that FXII has a sophisticated role in vivo that has not been previously appreciated

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio