Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence?

Standard laboratory coagulation tests (SLTs) such as prothrombin time/international normalized ratio or partial thromboplastin time are frequently used to assess coagulopathy and to guide haemostatic interventions. However, this has been challenged by numerous reports, including the current European guidelines for perioperative bleeding management, which question the utility and reliability of SLTs in this setting. Furthermore, the arbitrary definition of coagulopathy (i.e. SLTs are prolonged by more than 1.5-fold) has been questioned. The present study aims to review the evidence for the usefulness of SLTs to assess coagulopathy and to guide bleeding management in the perioperative and massive bleeding setting. Medline was searched for investigations using results of SLTs as a means to determine coagulopathy or to guide bleeding management, and the outcomes (i.e. blood loss, transfusion requirements, mortality) were reported. A total of 11 guidelines for management of massive bleeding or perioperative bleeding and 64 studies investigating the usefulness of SLTs in this setting were identified and were included for final data synthesis. Referenced evidence for the usefulness of SLTs was found in only three prospective trials, investigating a total of 108 patients (whereby microvascular bleeding was a rare finding). Furthermore, no data from randomized controlled trials support the use of SLTs. In contrast, numerous investigations have challenged the reliability of SLTs to assess coagulopathy or guide bleeding management. There is actually no sound evidence from well-designed studies that confirm the usefulness of SLTs for diagnosis of coagulopathy or to guide haemostatic therap

The Increasing Role of Percutaneous Transluminal Angioplasty in the Primary Management of Critical Limb Ischaemia

AbstractObjective: to review the current role and results of angioplasty in the management of critical limb ischaemia (CLI) in a single institution.Methods: data on 526 patients with 608 ischaemic limbs, treated between January 1994 and December 1999 was collected prospectively and analysed retrospectively. Patients were divided into 3 groups according to the date of presentation: group 1 (1994–95), group 2 (1996–97) and group 3 (1998–99). The groups were comparable in terms of demographics, mode of presentation and level of disease.Results: Revascularisation was attempted in 87%, 81% and 91% for groups 1, 2 and 3 respectively (NS). Primary percutaneous transluminal angioplasty (PTA) rates increased from 44% (1994–95) to 69% (1998–99) (p < 0.001), and surgical revascularisation rates decreased correspondingly (p<0.01). Overall cumulative patient survival and limb salvage rates were 82% and 89% for 1 year and 45% and 87% for 5 years, respectively. No statistically significant difference existed between the three groups regarding patient survival, limb salvage rates and mean hospital stay (19, 12 and 12 days, respectively).Conclusion: PTA is increasingly replacing bypass surgery in the treatment of CLI, without compromising patient survival or limb salvage rates

Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement

Suppression of Implanted MDA-MB 231 Human Breast Cancer Growth in Nude Mice by Dietary Walnut

Walnuts contain components that may slow cancer growth including omega 3 fatty acids, phytosterols, polyphenols, carotenoids, and melatonin. A pilot study was performed to determine whether consumption of walnuts could affect growth of MDA-MB 231 human breast cancers implanted into nude mice. Tumor cells were injected into nude mice that were consuming an AIN-76A diet slightly modified to contain 10% corn oil. After the tumors reached 3 to 5 mm diameter, the diet of one group of mice was changed to include ground walnuts, equivalent to 56 g (2 oz) per day in humans. The tumor growth rate from Day 10, when tumor sizes began to diverge, until the end of the study of the group that consumed walnuts (2.9 ± 1.1 mm3/day; mean ± standard error of the mean) was significantly less (P \u3e 0.05, t-test of the growth rates) than that of the group that did not consume walnuts (14.6 ± 1.3 mm 3 /day). The eicosapentaenoic and docosahexaenoic acid fractions of the livers of the group that consumed walnuts were significantly higher than that of the group that did not consume walnuts. Tumor cell proliferation was decreased, but apoptosis was not altered due to walnut consumption. Further work is merited to investigate applications to cancer in humans

Quantum tunneling dynamics of an interacting Bose-Einstein condensate through a Gaussian barrier

The transmission of an interacting Bose-Einstein condensate incident on a repulsive Gaussian barrier is investigated through numerical simulation. The dynamics associated with interatomic interactions are studied across a broad parameter range not previously explored. Effective 1D Gross-Pitaevskii equation (GPE) simulations are compared to classical Boltzmann-Vlasov equation (BVE) simulations in order to isolate purely coherent matterwave effects. Quantum tunneling is then defined as the portion of the GPE transmission not described by the classical BVE. An exponential dependence of transmission on barrier height is observed in the purely classical simulation, suggesting that observing such exponential dependence is not a sufficient condition for quantum tunneling. Furthermore, the transmission is found to be predominately described by classical effects, although interatomic interactions are shown to modify the magnitude of the quantum tunneling. Interactions are also seen to affect the amount of classical transmission, producing transmission in regions where the non-interacting equivalent has none. This theoretical investigation clarifies the contribution quantum tunneling makes to overall transmission in many-particle interacting systems, potentially informing future tunneling experiments with ultracold atoms.Comment: Close to the published versio

Optically guided linear Mach Zehnder atom interferometer

We demonstrate a horizontal, linearly guided Mach Zehnder atom interferometer in an optical waveguide. Intended as a proof-of-principle experiment, the interferometer utilises a Bose-Einstein condensate in the magnetically insensitive |F=1,mF=0> state of Rubidium-87 as an acceleration sensitive test mass. We achieve a modest sensitivity to acceleration of da = 7x10^-4 m/s^2. Our fringe visibility is as high as 38% in this optically guided atom interferometer. We observe a time-of-flight in the waveguide of over half a second, demonstrating the utility of our optical guide for future sensors.Comment: 6 pages, 3 figures. Submitted to Phys. Rev.

Playing by white rules of racial equality:student athlete experiences of racism in British university sport

Inequalities related to racial identity are consistently reported across social institutions, not least education, and sport. These inequalities consistently challenge ‘post-race’ narratives that rationalise racism down to individual prejudices and poor decision-making. This paper presents part of the findings from a wider a twelve-month research project commissioned by British University and Colleges Sport (BUCS) to explore race equality. This wider research privileged the voices of non-White students and staff in an exploration of race and equality in British UK university sport. ‘Non-white’ was chosen as a race identifier to focus on Whiteness, the normalised, raceless power that reproduces itself both knowingly and unknowingly, to ensure racial ‘others’ remain subordinate. This paper presents the findings of the student voices. In this study a research team of academic and student researchers explored the experiences of 38 students across five universities. Generating case studies from each university, the data was analysed from an Intersectional and Critical Race Theory perspective. Two core themes relating to negotiating Whiteness were developed from the data analysis which reflected experiences of university sport as predominantly White spaces; ‘Play by the Rules’ and ‘Keep You Guessing’. Racial abuse was subtle, camouflaged in comments and actions that happened momentarily and hence were implausible to capture and evidence. For incidents to be addressed, evidence had to meet a ‘beyond doubt’ standard. Students were required to consciously negotiate racial bias and abuse to ensure they did not provide a justification for abuse. Navigating racialisation and stereotypes, plus White denial, was additional emotional labour for students. This mechanism of silencing the victim served to normalise racism for both the abused and perpetrator. The conclusion explores potential ways of disrupting these mechanisms of Whiteness in placing students’ welfare at the heart of university sport