On modelling fluid/body interactions, impacts and lift-offs

A description is given of recent progress in the understanding of mechanisms in fluid-body interactions where the motion of a body and the motion of the surrounding fluid affect each other substantially. The mathematical modelling of such unsteady interactions is for internal channel and external near-wall flows in two spatial dimensions and time. The emphasis throughout is on analytical developments with accompanying reduced computation. The successive aspects studied here are interactions and impacts in inviscid flows, skimming and sinking, the lift-off, fly-away or bouncing of a body, and viscous effects including especially the interplay between viscous and inviscid contributions. The main findings are concerned with physical and mechanical insights into impact times, lift-off criteria, the borders between impact and fly-away, the principal parameters and their ranges and the influences from body shape and mass

Novel sol–gel preparation of (PO)–(CaO)–(NaO)–(TiO) bioresorbable glasses (X = 0.05, 0.1, and 0.15)

Quaternary phosphate-based glasses in the PO–CaO–NaO–TiO system with a fixed PO and CaO content of 40 and 25 mol% respectively have been successfully synthesised via sol–gel method and bulk, transparent samples were obtained. The structure, elemental proportion, and thermal properties of stabilised sol–gel glasses have been characterised using X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), P nuclear magnetic resonance (P NMR), titanium K-edge X-ray absorption near-edge structure (XANES), fourier transform infrared (FTIR) spectroscopy, and differential thermal analysis (DTA). The XRD results confirmed the amorphous nature for all stabilized sol–gel derived glasses. The EDX result shows the relatively low loss of phosphorus during the sol–gel process and Ti K-edge XANES confirmed titanium in the glass structure is in mainly six-fold coordination environment. The P NMR and FTIR results revealed that the glass structure consist of mainly Q and Q phosphate units and the Ti cation was acting as a cross-linking between phosphate units. In addition DTA results confirmed a decrease in the glass transition and crystallisation temperature with increasing NaO content. Ion release studies also demonstrated a decrease in degradation rates with increasing TiO content therefore supporting the use of these glasses for biomedical applications that require a degree of control over glass degradation. These sol–gel glasses also offer the potential to incorporate proactive molecules for drug delivery application due to the low synthesis temperature employed

The cost-effectiveness of an early interventional strategy in non-ST-elevation acute coronary syndrome based on the RITA 3 trial

The published version of the aritcle can be found at the link below.Background: Evidence suggests that an early interventional strategy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) can improve health outcomes but also increase costs when compared with a conservative strategy.Objective: The aim of this study was to assess the cost-effectiveness of an early interventional strategy in different risk groups from a UK health-service perspective.Design: Decision-analytic model based on randomised clinical trial data.Main outcome measures: Costs in UK Sterling at 2003/2004 prices and quality-adjusted life years (QALYs) combined into an incremental cost-effectiveness ratio.Methods: Data from the third Randomised Intervention Trial of unstable Angina (RITA 3) was employed to estimate rates of cardiovascular death and myocardial infarction, costs and health-related quality of life. Cost-effectiveness was estimated over patients' lifetimes within the decision-analytic model.Results: The mean incremental cost per QALY gained for an early interventional strategy was approximately £55000, £22000 and £12000 for patients at low, intermediate and high risk, respectively. The early interventional strategy is approximately 1%, 35% and 95% likely to be cost-effective for patients at low, intermediate and high risk, respectively, at a threshold of £20000 per QALY. The cost-effectiveness of early intervention in low-risk patients is sensitive to assumptions about the duration of the treatment effect.Conclusion: An early interventional strategy in patients presenting with NSTE-ACS is likely to be considered cost-effective for patients at high and intermediate risk, but this is less likely to be the case for patients at low risk

Greater sleep disturbance and longer sleep onset latency facilitate SCR-specific fear reinstatement in PTSD

Fear reinstatement is one of several paradigms designed to measure fear return following extinction, as a laboratory model for the relapse of Posttraumatic Stress Disorder (PTSD) symptoms. Sleep is a key factor in emotional memory consolidation, and here we examined the relationship between sleep quality and fear reinstatement in PTSD, relative to trauma-exposed and non-exposed controls. The Pittsburgh Sleep Quality Index (PSQI) was used as a subjective measure of sleep quality, and skin conductance responses (SCR) and unconditioned stimulus (US)-expectancy ratings were used to index threat responses during a differential fear conditioning, extinction, and reinstatement paradigm. There were no significant between-group differences in the reinstatement of conditioned responding. Sleep disturbance and sleep onset latency were significant moderators between reinstatement of fear and PTSD symptom severity, such that there was a positive relationship between PTSD symptoms and fear reinstatement for higher levels - but not lower levels - of sleep disturbance and sleep onset latency. To our knowledge, this is the first study to investigate PTSD-specific reinstatement patterns and sleep as a boundary condition of reinstatement. Future research using polysomnographic measures of sleep-wave architecture may further clarify the relationship between fear reinstatement and sleep quality in clinical samples with PTSD relative to controls

Family history of prostate and colorectal cancer and risk of colorectal cancer in the Women's health initiative.

BackgroundEvidence suggests that risk of colorectal and prostate cancer is increased among those with a family history of the same disease, particularly among first-degree relatives. However, the aggregation of colorectal and prostate cancer within families has not been well investigated.MethodsAnalyses were conducted among participants of the Women's Health Initiative (WHI) observational cohort, free of cancer at the baseline examination. Subjects were followed for colorectal cancer through August 31st, 2009. A Cox-proportional hazards regression modeling approach was used to estimate risk of colorectal cancer associated with a family history of prostate cancer, colorectal cancer and both cancers among first-degree relatives of all participants and stratified by race (African American vs. White).ResultsOf 75,999 eligible participants, there were 1122 colorectal cancer cases diagnosed over the study period. A family history of prostate cancer alone was not associated with an increase in colorectal cancer risk after adjustment for confounders (aHR =0.94; 95% CI =0.76, 1.15). Separate analysis examining the joint impact, a family history of both colorectal and prostate cancer was associated with an almost 50% increase in colorectal cancer risk (aHR = 1.48; 95% CI = 1.04, 2.10), but similar to those with a family history of colorectal cancer only (95% CI = 1.31; 95% CI = 1.11, 1.54).ConclusionsOur findings suggest risk of colorectal cancer is increased similarly among women with colorectal cancer only and among those with both colorectal and prostate cancer diagnosed among first-degree family members. Future studies are needed to determine the relative contribution of genes and shared environment to the risk of both cancers

Integrating timescales with time-transfer functions: A practical approach for an INTIMATE database

© 2014 Elsevier Ltd.The purpose of the INTIMATE project is to integrate palaeo-climate information from terrestrial, ice and marine records so that the timing of environmental response to climate forcing can be compared in both space and time. One of the key difficulties in doing this is the range of different methods of dating that can be used across different disciplines. For this reason, one of the main outputs of INTIMATE has been to use an event-stratigraphic approach which enables researchers to co-register synchronous events (such as the deposition of tephra from major volcanic eruptions) in different archives (Blockley etal., 2012). However, this only partly solves the problem, because it gives information only at particular short intervals where such information is present. Between these points the ability to compare different records is necessarily less precise chronologically. What is needed therefore is a way to quantify the uncertainties in the correlations between different records, even if they are dated by different methods, and make maximum use of the information available that links different records. This paper outlines the design of a database that is intended to provide integration of timescales and associated environmental proxy information. The database allows for the fact that all timescales have their own limitations, which should be quantified in terms of the uncertainties quoted. It also makes use of the fact that each timescale has strengths in terms of describing the data directly associated with it. For this reason the approach taken allows users to look at data on any timescale that can in some way be related to the data of interest, rather than specifying a specific timescale or timescales which should always be used. The information going into the database is primarily: proxy information (principally from sediments and ice cores) against depth, age depth models against reference chronologies (typically IntCal or ice core), and time-transfer functions that relate different timescales to each other, through the use of event stratigraphies or global phenomena such as cosmogenic isotope production rate variations

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Rate Effects on Timing, Key Velocity, and Finger Kinematics in Piano Performance

We examined the effect of rate on finger kinematics in goal-directed actions of pianists. In addition, we evaluated whether movement kinematics can be treated as an indicator of personal identity. Pianists' finger movements were recorded with a motion capture system while they performed melodies from memory at different rates. Pianists' peak finger heights above the keys preceding keystrokes increased as tempo increased, and were attained about one tone before keypress. These rate effects were not simply due to a strategy to increase key velocity (associated with tone intensity) of the corresponding keystroke. Greater finger heights may compensate via greater tactile feedback for a speed-accuracy tradeoff that underlies the tendency toward larger temporal variability at faster tempi. This would allow pianists to maintain high temporal accuracy when playing at fast rates. In addition, finger velocity and accelerations as pianists' fingers approached keys were sufficiently unique to allow pianists' identification with a neural-network classifier. Classification success was higher in pianists with more extensive musical training. Pianists' movement “signatures” may reflect unique goal-directed movement kinematic patterns, leading to individualistic sound

Pathomechanisms of ulnar ligament lesions of the wrist in a cadaveric distal radius fracture model

Background and purpose: Mechanisms of injury to ulnar sided ligaments, stabilizing the distal radioulnar joint and the ulna to the carpus, associated with dorsally displaced distal radius fractures are poorly described. We investigated the injury patterns in a human cadaver fracture model. Methods: Fresh frozen human cadaver arms were used. A dorsal open wedge osteotomy was made in the distal radius. In 8 specimens pressure was applied to the palm with the wrist in dorsiflexion and ulnar sided stabilizing structures subsequently severed. Dorsal angulation was measured on digitized radiographs. In 8 more specimens the triangular fibrocartilage complex was forced into rupture by axially loading the forearm with the wrist in dorsiflexion. The ulnar side was dissected and injuries were recorded. Results: Intact ulnar soft tissues limited the dorsal angulation of the distal radius fragment to a median of 32o (16-34o). A combination of bending and shearing of the distal radius fragment was needed to create TFCC injuries. Both palmar and dorsal injuries were observed simultaneously in 6/8 specimens. Interpretation: A TFCC injury can be expected when dorsal angulation of a distal radius fracture exceeds 32o. The extensor carpi ulnaris subsheath may be a functionally integral part of the TFCC. Both dorsal and palmar structures can tear simultaneously. These findings may have implications for reconstruction of ulnar sided soft tissue injuries

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs