The relationship between reductions in knee loading and immediate pain response whilst wearing lateral wedged insoles in knee osteoarthritis

Studies of lateral wedge insoles (LWIs) in medial knee osteoarthritis (OA) have shown reductions in the average external knee adduction moment (EKAM) but no lessening of knee pain. Some treated patients actually experience increases in the EKAM which could explain the overall absence of pain response. We examined whether, in patients with painful medial OA, reductions in the EKAM were associated with lessening of knee pain. Each patient underwent gait analysis whilst walking in a control shoe and two LWI's. We evaluated the relationship between change in EKAM and change in knee pain using Spearman Rank Correlation coefficients and tested whether dichotomizing patients into biomechanical responders (decreased EKAM) and non-responders (increased EKAM) would identify those with reductions in knee pain. In 70 patients studied, the EKAM was reduced in both LWIs versus control shoe (−5.21% and −6.29% for typical and supported wedges, respectively). The change in EKAM using LWIs was not significantly associated with the direction of knee pain change. Further, 54% were biomechanical responders, but these persons did not have more knee pain reduction than non-responders. Whilst LWIs reduce EKAM, there is no clearcut relationship between change in medial load when wearing LWIs and corresponding change in knee pain

A Theoretical Model of Ultrasonic Examination of Smooth Flat Cracks

As the Introductory Paper to this Conference explains,1 the CEGB and other high technology organisations are very interested in quantitative NDE for the guidance it gives in the design of inspections and for the support it offers in Safety Submissions to the Regulatory Authorities. An important part of this work is the theoretical modelling and prediction of defect detectability and signal behaviour. This present paper complements the Introductory Paper by describing the technical content of a model we have developed at the CEGB NDT Applications Centre

Numerical Modeling of Fluid Flow in Solid Tumors

A mathematical model of interstitial fluid flow is developed, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for a predefined tumor geometry. The interstitial fluid pressure and velocity are calculated using a numerical method, element based finite volume. Simulations of interstitial fluid transport in a homogeneous solid tumor demonstrate that, in a uniformly perfused tumor, i.e., one with no necrotic region, because of the interstitial pressure distribution, the distribution of drug particles is non-uniform. Pressure distribution for different values of necrotic radii is examined and two new parameters, the critical tumor radius and critical necrotic radius, are defined. Simulation results show that: 1) tumor radii have a critical size. Below this size, the maximum interstitial fluid pressure is less than what is generally considered to be effective pressure (a parameter determined by vascular pressure, plasma osmotic pressure, and interstitial osmotic pressure). Above this size, the maximum interstitial fluid pressure is equal to effective pressure. As a consequence, drugs transport to the center of smaller tumors is much easier than transport to the center of a tumor whose radius is greater than the critical tumor radius; 2) there is a critical necrotic radius, below which the interstitial fluid pressure at the tumor center is at its maximum value. If the tumor radius is greater than the critical tumor radius, this maximum pressure is equal to effective pressure. Above this critical necrotic radius, the interstitial fluid pressure at the tumor center is below effective pressure. In specific ranges of these critical sizes, drug amount and therefore therapeutic effects are higher because the opposing force, interstitial fluid pressure, is low in these ranges

Adrenal suppression in patients taking inhaled glucocorticoids is highly prevalent and management can be guided by morning cortisol

Context Up to 3% of US and UK populations are prescribed glucocorticoids (GC). Suppression of the hypothalamo–pituitary–adrenal axis with the potential risk of adrenal crisis is a recognized complication of therapy. The 250 μg short Synacthen stimulation test (SST) is the most commonly used dynamic assessment to diagnose adrenal insufficiency. There are challenges to the use of the SST in routine clinical practice, including both the staff and time constraints and a significant recent increase in Synacthen cost. Methods We performed a retrospective analysis to determine the prevalence of adrenal suppression due to prescribed GCs and the utility of a morning serum cortisol for rapid assessment of adrenal reserve in the routine clinical setting. Results In total, 2773 patients underwent 3603 SSTs in a large secondary/tertiary centre between 2008 and 2013 and 17.9% (n=496) failed the SST. Of 404 patients taking oral, topical, intranasal or inhaled GC therapy for non-endocrine conditions, 33.2% (n=134) had a subnormal SST response. In patients taking inhaled GCs without additional GC therapy, 20.5% (34/166) failed an SST and suppression of adrenal function increased in a dose-dependent fashion. Using receiver operating characteristic curve analysis in patients currently taking inhaled GCs, a basal cortisol ≥348 nmol/l provided 100% specificity for passing the SST; a cortisol value <34 nmol/l had 100% sensitivity for SST failure. Using these cut-offs, 50% (n=83) of SSTs performed on patients prescribed inhaled GCs were unnecessary. Conclusion Adrenal suppression due to GC treatment, particularly inhaled GCs, is common. A basal serum cortisol concentration has utility in helping determine which patients should undergo dynamic assessment of adrenal function

Stellar winds from Massive Stars

We review the various techniques through which wind properties of massive stars - O stars, AB supergiants, Luminous Blue Variables (LBVs), Wolf-Rayet (WR) stars and cool supergiants - are derived. The wind momentum-luminosity relation (e.g. Kudritzki et al. 1999) provides a method of predicting mass-loss rates of O stars and blue supergiants which is superior to previous parameterizations. Assuming the theoretical sqrt(Z) metallicity dependence, Magellanic Cloud O star mass-loss rates are typically matched to within a factor of two for various calibrations. Stellar winds from LBVs are typically denser and slower than equivalent B supergiants, with exceptional mass-loss rates during giant eruptions Mdot=10^-3 .. 10^-1 Mo/yr (Drissen et al. 2001). Recent mass-loss rates for Galactic WR stars indicate a downward revision of 2-4 relative to previous calibrations due to clumping (e.g. Schmutz 1997), although evidence for a metallicity dependence remains inconclusive (Crowther 2000). Mass-loss properties of luminous (> 10^5 Lo) yellow and red supergiants from alternative techniques remain highly contradictory. Recent Galactic and LMC results for RSG reveal a large scatter such that typical mass-loss rates lie in the range 10^-6 .. 10^-4 Mo/yr, with a few cases exhibiting 10^-3 Mo/yr.Comment: 16 pages, 2 figures, Review paper to appear in Proc `The influence of binaries on stellar population studies', Brussels, Aug 2000 (D. Vanbeveren ed.), Kluwe

‘Carbon-Monoxide-Releasing Molecule-2 (CORM-2)’ Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects

Carbon monoxide (CO)-releasing molecules (CORMs) are used to deliver CO, a biological ‘gasotransmitter’, in biological chemistry and biomedicine. CORMs kill bacteria in culture and in animal models, but are reportedly benign towards mammalian cells. CORM-2 (tricarbonyldichlororuthenium(II) dimer, Ru2Cl4(CO)6), the first widely used and commercially available CORM, displays numerous pharmacological, biochemical and microbiological activities, generally attributed to CO release. Here, we investigate the basis of its potent antibacterial activity against Escherichia coli and demonstrate, using three globin CO sensors, that CORM-2 releases negligible CO (<0.1 mol CO per mol CORM-2). A strong negative correlation between viability and cellular ruthenium accumulation implies that ruthenium toxicity underlies biocidal activity. Exogenous amino acids and thiols (especially cysteine, glutathione and N-acetyl cysteine) protected bacteria against inhibition of growth by CORM-2. Bacteria treated with 30 μM CORM-2, with added cysteine and histidine, exhibited no significant loss of viability, but were killed in the absence of these amino acids. Their prevention of toxicity correlates with their CORM-2-binding affinities (Cys, Kd 3 μM; His, Kd 130 μM) as determined by 1H-NMR. Glutathione is proposed to be an important intracellular target of CORM-2, with CORM-2 having a much higher affinity for reduced glutathione (GSH) than oxidised glutathione (GSSG) (GSH, Kd 2 μM; GSSG, Kd 25,000 μM). The toxicity of low, but potent, levels (15 μM) of CORM-2 was accompanied by cell lysis, as judged by the release of cytoplasmic ATP pools. The biological effects of CORM-2 and related CORMs, and the design of biological experiments, must be re-examined in the light of these data

Noiseonomics: The relationship between ambient noise levels in the sea and global economic trends

In recent years, the topic of noise in the sea and its effects on marine mammals has attracted considerable attention from both the scientific community and the general public. Since marine mammals rely heavily on acoustics as a primary means of communicating, navigating, and foraging in the ocean, any change in their acoustic environment may have an impact on their behavior. Specifically, a growing body of literature suggests that low-frequency, ambient noise levels in the open ocean increased approximately 3.3 dB per decade during the period 1950–2007. Here we show that this increase can be attributed primarily to commercial shipping activity, which in turn, can be linked to global economic growth. As a corollary, we conclude that ambient noise levels can be directly related to global economic conditions. We provide experimental evidence supporting this theory and discuss its implications for predicting future noise levels based on global economic trends

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Automated Detection of Radiology Reports that Document Non-routine Communication of Critical or Significant Results

The purpose of this investigation is to develop an automated method to accurately detect radiology reports that indicate non-routine communication of critical or significant results. Such a classification system would be valuable for performance monitoring and accreditation. Using a database of 2.3 million free-text radiology reports, a rule-based query algorithm was developed after analyzing hundreds of radiology reports that indicated communication of critical or significant results to a healthcare provider. This algorithm consisted of words and phrases used by radiologists to indicate such communications combined with specific handcrafted rules. This algorithm was iteratively refined and retested on hundreds of reports until the precision and recall did not significantly change between iterations. The algorithm was then validated on the entire database of 2.3 million reports, excluding those reports used during the testing and refinement process. Human review was used as the reference standard. The accuracy of this algorithm was determined using precision, recall, and F measure. Confidence intervals were calculated using the adjusted Wald method. The developed algorithm for detecting critical result communication has a precision of 97.0% (95% CI, 93.5–98.8%), recall 98.2% (95% CI, 93.4–100%), and F measure of 97.6% (ß = 1). Our query algorithm is accurate for identifying radiology reports that contain non-routine communication of critical or significant results. This algorithm can be applied to a radiology reports database for quality control purposes and help satisfy accreditation requirements