Fast Monte Carlo simulations and singularities in the probability distributions of non-equilibrium systems

A numerical technique is introduced that reduces exponentially the time required for Monte Carlo simulations of non-equilibrium systems. Results for the quasi-stationary probability distribution in two model systems are compared with the asymptotically exact theory in the limit of extremely small noise intensity. Singularities of the non-equilibrium distributions are revealed by the simulations.Comment: 4 pages, 4 figure

Tidal resource and interactions between multiple channels in the Goto Islands, Japan

The Goto Islands in Nagasaki Prefecture, Japan, contain three parallel channels that are suitable for tidal energy development and are the planned location for a tidal energy test centre. Energy extraction is added to a 3D numerical hydrodynamic model of the region, using a sub-grid momentum sink approach, to predict the effects of tidal development. The available resource with first-generation turbines is estimated at 50-107MW peak output. Spreading turbine thrust across the whole cross-section to prevent bypass flow results in a 64% increase in peak power in one channel, highlighting the importance of 3D over 2D modelling. The energy available for extraction in each strait appears to be independent of the level of extraction in other straits. This contrasts with theoretical and numerical studies of other multi-channel systems. The weak interactions found in this study can be traced to the hydraulic effects of energy extraction not extending to neighbouring channels due to their geometry

Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy

Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.Grant support from: R01 CA175382/CA/NCI NIH HHS/United States, R21 CA191970/CA/NCI NIH HHS/United States, and R21 CA193958/CA/NCI NIH HHS/United State

“Not walled facts, their essence”: Derek Walcott’s Tiepolo’s Hound and Camille Pissarro

Life-writing — a genre which goes beyond traditional biography, includes both fact and fiction, and is concerned with either entire lives or days-in-the-lives of individuals, communities, objects, or institutions — has always played an important role in Derek Walcott’s work, from Another Life (1973),Walcott’s autobiography in verse, to his last play O Starry Starry Night (2014), where he re-imagines Paul Gauguin and Vincent Van Gogh’s (often tempestuous) cohabitation in the so-called “Yellow House” in 1888 Arles. In Tiepolo’s Hound (2000), Walcott’s life rhymes with that of the Impressionist painter Jacob Camille Pissarro, who was born in the Caribbean island of St Thomas in 1830. In this work, biographical and autobiographical impulses, fact and fiction, are productively combined, as “creation” (what “might have happened”) shapes Walcott’s life-writing as much as “recreation” (what “actually” happened). Walcott’s Pissarro is an individual immersed in a set of historical networks but also a figure at the centre of a web of imagined relations which illuminate the predicament of present and past artists in the Caribbean region and the ways in which they articulate their vision vis-à-vis the metropolitan centre, their relationship with their social and natural environment, and their individual and collective identity. Tiepolo’s Hound is enriched by the inclusion of twenty-six of Walcott’s own paintings which engage in conversation with the poet’s words and add complexity to his meditation on the nature and purpose of (re)writing and (re)creating lives. Extending the catholicity of life-writing to animals, in this case dogs and, in particular, mongrels, Tiepolo’s Hound also entails a careful, if counterintuitive, evaluation of anonymity

Breaking down the barriers: fMRI applications in pain, analgesia and analgesics

This review summarizes functional magnetic resonance imaging (fMRI) findings that have informed our current understanding of pain, analgesia and related phenomena, and discusses the potential role of fMRI in improved therapeutic approaches to pain. It is divided into 3 main sections: (1) fMRI studies of acute and chronic pain. Physiological studies of pain have found numerous regions of the brain to be involved in the interpretation of the 'pain experience'; studies in chronic pain conditions have identified a significant CNS component; and fMRI studies of surrogate models of chronic pain are also being used to further this understanding. (2) fMRI studies of endogenous pain processing including placebo, empathy, attention or cognitive modulation of pain. (3) The use of fMRI to evaluate the effects of analgesics on brain function in acute and chronic pain. fMRI has already provided novel insights into the neurobiology of pain. These insights should significantly advance therapeutic approaches to chronic pain

Future policy implications of tidal energy array interactions

Tidal stream energy technology has progressed to a point where commercial exploitation of this sustainable resource is practical, but tidal physics dictates interactions between tidal farms that raise political, legal and managerial challenges that are yet to be met. Fully optimising the design of a turbine array requires its developer to know about other farms that will be built nearby in the future. Consequently future developments, even those in adjacent channels, have the potential to impact on project efficiency. Here we review the relevant physics, consider the implications for marine policy, and discuss potential solutions. Possible management paths range from minimal regulation to prioritise a free market, to strongly interventionist approaches that prioritise efficient resource use. An attractive exemplar of the latter is unitization, an approach to resource allocation widely used in the oil and gas industry. We argue that an interventionist approach is necessary if the greatest possible energy yield is to be produced for a given level of environmental impact

Massachusetts Bar Discipline: History, Practice, and Procedure

While there have been several publications describing the bar discipline process for violations of the Massachusetts Rules of Professional Conduct, no work has described that process in great detail while also analyzing the related sanctions. The treatise seeks to fill this gap and make the practice more accessible to participants and observers by referencing, in a single volume, materials that had not previously been collected and analyzed. We begin with an overview of the history of bar discipline in the Commonwealth, followed by a discussion of the participants in, and structure of, the disciplinary process. Part II takes the reader through the steps of a typical bar discipline case from the initial complaint through the hearing. Part III discusses in detail some typical misconduct, including that related to competence, confidentiality, safekeeping of trust property, and advertising—and the sanctions typically imposed for it. This is followed by a discussion in Part IV of conduct that may aggravate or mitigate the presumptive sanction. Lastly, Part V discusses the post-hearing process as well as reciprocal discipline, resignations, duties after suspension or disbarment, reinstatement, and registration. While this volume is not a dissertation on legal ethics per se, it addresses the Rules of Professional Conduct as they arise in bar discipline

The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study

BACKGROUND Since 2007 junior doctors in the UK have had to make major career decisions at a point when previously many had not yet chosen a specialty. This study examined when doctors in this new system make specialty choices, which factors influence choices, and whether doctors who choose a specialty they were interested in at medical school are more confident in their choice than those doctors whose interests change post-graduation. METHODS Two cohorts of students in their penultimate year at one medical school (n = 227/239) were asked which specialty interested them as a career. Two years later, 210/227 were sent a questionnaire measuring actual specialty chosen, confidence, influence of perceptions of the specialty and experiences on choice, satisfaction with medicine, personality, self-efficacy, and demographics. Medical school and post-graduation choices in the same category were deemed 'stable'. Predictors of stability, and of not having chosen a specialty, were calculated using bootstrapped logistic regression. Differences between specialties on questionnaire factors were analysed. RESULTS 50% responded (n = 105/277; 44% of the 239 Year 4 students). 65% specialty choices were 'stable'. Factors univariately associated with stability were specialty chosen, having enjoyed the specialty at medical school or since starting work, having first considered the specialty earlier. A regression found doctors who chose psychiatry were more likely to have changed choice than those who chose general practice. Confidence in the choice was not associated with stability. Those who chose general practice valued lifestyle factors. A psychiatry choice was associated with needing a job and using one's intellect to help others. The decision to choose surgical training tended to be made early. Not having applied for specialty training was associated with being lower on agreeableness and conscientiousness. CONCLUSION Medical school experiences are important in specialty choice but experiences post-graduation remain significant, particularly in some specialties (psychiatry in our sample). Career guidance is important at medical school and should be continued post-graduation, with senior clinicians supported in advising juniors. Careers advice in the first year post-graduation may be particularly important, especially for specialties which have difficulty recruiting or are poorly represented at medical school

Femoral Neck Shaft Angle in Men with Fragility Fractures

Introduction. Femoral neck shaft angle (NSA) has been reported to be an independent predictor of hip fracture risk in men. We aimed to assess the role of NSA in UK men. Methods. The NSA was measured manually from the DXA scan printout in men with hip (62, 31 femoral neck and 31 trochanteric), symptomatic vertebral (91), and distal forearm (67) fractures and 389 age-matched control subjects. Age, height, weight, and BMD (g/cm2: lumbar spine, femoral neck, and total femur) measurements were performed. Results. There was no significant difference in mean NSA between men with femoral neck and trochanteric hip fractures, so all further analyses of hip fractures utilised the combined data. There was no difference in NSA between those with hip fractures and those without (either using the combined data or analysing trochanteric and femoral neck shaft fractures separately), nor between fracture subjects as a whole and controls. Mean NSA was smaller in those with vertebral fractures (129.2° versus 131°: P = 0.001), but larger in those with distal forearm fractures (129.8° versus 128.5°: P = 0.01). Conclusions. The conflicting results suggest that femoral NSA is not an important determinant of hip fracture risk in UK men