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Heart failure represents a major global cause of morbidity and mortality. Ivabradine is a selective funny current (If) inhibitor, which acts on the sinoatrial node, resulting in a reduction in heart rate. Ivabradine is currently licensed for use in patients with symptomatic heart failure with reduced ejection fraction and a heart rate persistently at least 70 beats per minute in spite of otherwise optimal prognostic heart failure pharmacotherapy. In this review article, we examine the mechanism of action of ivabradine, evaluate the clinical trials underpinning its application in heart failure and discuss its current recommended clinical use in this capacity.

Background Navigated total hip arthroplasty (THA) can employ intra-osseous pins through a separate incision to secure reference arrays to the iliac crest. This study is the first to investigate the consequences of pin use in THA in vivo. Methods A prospective, consecutive series of 43 patients presenting for navigated THA were included. Two temporary 125 × 4 mm Schanz screws were inserted into the iliac crest for the attachment of a reference array. Telephone follow-up occurred at 6 and 12 weeks post-operatively. Patients were asked about pain, interference with daily activities, how often the wound was noticed, and duration of discomfort. Patient body mass index was recorded. Results The follow-up rate was 100%. Pin site pain at any time post-operatively was reported by 24 patients (56%). This improved to 30%, 9%, and 2% at 3, 6, and 12 weeks, respectively. On average, pain lasted for 16 days total. The most common complaints after pain were clothing discomfort (23%), pain when wearing a belt (12%), or pain when mobilizing (9%). For the majority (98%) of patients, all symptoms had resolved by 12 weeks. There was no nerve injury, pin site fracture, infection, or screw breakage. Patients with body mass index greater than 30 kg/m2 were up to 3 times more likely to experience pin site pain (P = .05), and had a longer duration of pain (P = .04). Conclusion Surgeons and patients should be aware that using navigational pins for array fixation carries low complication rates but often will cause pain and irritation that resolves in the short term.

Machine learning models used for energy conversion system optimization cannot extrapolate outside the bounds of training data and often produce physically unrealistic results when making predictions in regions of sparse training data. The toy model concept introduced in this work allows machine learning models to extrapolate to some extent and also reduces the possibility of physically unrealistic results. It uses physics to shrink the model input (feature space) of data-based models, so that extrapolations in the data-based feature space tend to become interpolations in the physics-based (toy variable) feature space. The physics-based model can be any model or experiment that can shrink the feature space without affecting interpolation and is termed a ‘toy model’ because it does not need to be accurate or make predictions of interest. The concept has been applied to model experimental data obtained from three complex systems: a. Aerodynamic forces on a spinning and vibrating baseball with inclined axis of rotation (toy model: CFD model), b. Hydraulic turbine efficiency (toy model: PIV images of flow through stationary blades), and c. Combustion generated engine emissions (toy model: system-level 1-D model). All extrapolations were converted into interpolations for the first two systems while a 75% conversion was achieved for the emission predictions. The engine toy model produced 736,281 possible feature spaces from which one unique feature space was chosen for every prediction based on agreement between different machine learning algorithms. It is shown that the ability of the toy variables to reorganize the data is important, while their accuracy is relatively unimportant. The toy model concept was demonstrated to work with neural networks and regression, and can be used to increase model robustness or reduce training data requirements.

Most financial security trading venues prioritize competing liquidity providers with price-time priority; entities displaying the best-priced limit order earliest trade with the next opposite-sided liquidity-demanding order. The New York Stock Exchange (NYSE) rule putting traders “on parity” is a vestige of the traditional floor-based trading model and favors floor-based traders. Parity requires that orders from floor brokers, the designated market maker, and the top of the electronic limit order book trade together. That is, floor trading interests can trade ahead of equally priced, previously arriving orders in the limit order book. The NYSE posits that floor traders provide valuable services to the investing public and one approach to remunerating them for these services is deviating from strict time priority. The cost of the potential benefits of the NYSE’s business model is not transparent. Our research is an initial attempt to quantify this cost.

Introduction Accurate prosthetic cup placement is important in total hip arthroplasty (THA) and can be influenced by patient positioning. This study aims to assess the accuracy of patient positioning prior to THA, describe a new technique of assessment, and evaluate the influence of body mass index (BMI) on positioning error. Methods A consecutive series of 37 patients undergoing unilateral THA were investigated. After patient positioning in lateral decubitus, a lateral fluoroscopic image through the table was taken. The C-arm of the image intensifier was manipulated in 2 planes (coronal, transverse) until a perfect lateral view of the pelvis was obtained, defined as when the native acetabulae were superimposed. Degrees of positioning error in the 2 planes were recorded, along with patient BMI. Results There were 6 patients (16%) positioned within 2° of true lateral in both planes. A further 21 patients (57%) had an error of 5° or more in at least 1 plane. Mean absolute positioning error was 3.0° (SD 2.2°; range 0°-9°) and 3.0° (SD 3.2°; range 0°-13°) in the transverse and coronal planes respectively. Pelvic adduction in the coronal plane was 4.5 fold more likely than abduction (49% vs. 11%). Correlation was shown between patient BMI and the combined error in the 2 planes (R = 0.48, p = 0.001). Discussion Fluoroscopic positioning assessment prior to THA demonstrates that significant malpositioning is common and more likely with increasing BMI. This technique may be particularly useful for patients with a BMI of >30 kg m-2.

Theory suggests that reputations allow nonanonymous markets to attenuate adverse selection in trading. We identify instances in which New York Stock Exchange (NYSE) stocks experience trading floor relocations. Although specialists follow the stocks to their new locations, most brokers do not. We find a discernable increase in liquidity costs around a stock's relocation that is larger for stocks with higher adverse selection and greater broker turnover. We also find that floor brokers relocating with the stock obtain lower trading costs than brokers not moving and brokers beginning trading post-move. Our results suggest that reputation plays an important role in the NYSE's liquidity provision process. KLEIN (1997) DOCUMENTS THAT REPUTATION HAS PLAYED A ROLE in facilitating trade since at least the Middle Ages by reducing information asymmetries between buyers and sellers. Diamond (1991), Boot, Greenbaum, and Thakor (1993), and Wilner (2000) model reputation's role in various financial market settings. Despite its perceived importance, there is little direct empirical evidence as to the economic value of relationships in financial markets. DeJong, Forsythe, and Lundholm (1985) and others find that reputation matters in experimental markets, but it is difficult to generalize these results. Carter and Manaster (1990) find that an underwriter's reputation is associated with returns of initial public equity offerings, but there seems to be no evidence of reputation effects in secondary equity markets.1 Here, we use a natural experiment to evaluate the

In 2001, the Securities and Exchange Commission (SEC) required market centers to publish monthly execution-quality reports in an effort to spur competition for order flow between markets. Using samples of stocks trading on several markets, we investigate whether past execution quality affects order-routing decisions and whether the new disclosure requirements influence this relationship. We find that routing decisions are associated with execution quality; markets reporting low execution costs and fast fills subsequently receive more orders. Moreover, the reports themselves appear to provide information that was unavailable previously. Our results are consistent with active competition for order flow that can be influenced by public disclosure. (JEL G24, G28, K22)

In its response to the 1975 Congressional mandate to implement a national market system for financial securities, the Securities and Exchange Commission (SEC) initially exempted the option market. Recent dramatic changes in the structure of the option market prompted the SEC to revisit this issue. We examine a sample of actively traded, multiply listed equity options to ask whether this market’s characteristics appear consistent with the goals of producing economically efficient transactions and facilitating “best execution.” We find marked changes between June 2000, when quotes are often ignored, and January 2002, when the market more closely resembles a national market. EQUITY OPTION TRADING CHANGED dramatically with the beginning of vigorous competition for order flow in many actively traded options during August 1999; the

The extant execution quality literature generally suggests that brokers routing orders away from the NYSE might not fulfill their fiduciary best execution responsibility. This conclusion is drawn by comparing execution prices across trading venues and presumes that other execution-quality characteristics are equivalent. Using order audit-trail data, we find evidence that retail market orders obtain better trade prices on the NYSE but faster executions, more depth improvement, and order-flow payment at Trimark Securities, a Nasdaq dealer. Thus, non-price dimensions of execution quality are not equivalent across trading venues. Furthermore, considering order flow payments, brokers obtain better net prices with Trimark. If brokers pass enough of these payments through to investors in the form of lower commissions and/or better services, then investors also obtain better net prices with Trimark. Our results suggest that it may be misleading to evaluate execution quality or to base policy decisions on comparisons focusing on only execution prices.

An 81-year-old man presented with sudden-onset slurred speech and right-sided weakness commencing 2 hours previously. Initial National Institute of Health Stroke Scale score was 13. Non-contrast CT brain scan excluded haemorrhage, and he received intravenous thrombolysis. Medical history included tissue aortic valve replacement. On arrival, his temperature was 38°C. Two hours after thrombolysis he had two seizures, and his Glasgow Coma Scale score dropped from 15/15 to 6/15 (breakdown: eyes 1, voice 1, motor 4). Repeat CT demonstrated a left middle cerebral artery territory infarct, and he was transferred to the intensive care unit (figure 1 …

Benveniste et al. J. Financial Econom. 32 (1992) 61–86 argue that repeatedly dealing with the same brokers allows market makers to know when brokers exploit private information. This suggests that broker identity may allow market makers to differentiate between customers when pricing market-making services even when market makers can provide separate quoted prices for each order size. Estimates of a major Nasdaq dealer's gross trading revenue vary substantively among routing brokers after controlling for order size. Furthermore, these differences exhibit a degree of stability over time. This suggests that market makers may effectively enforce clientele pricing schedules in a world where security prices are quoted without a minimum price variation and the limit order book is available to all market participants.

We study the division of market-making revenue among dealer, broker, and trader. When Knight Securities, a major Nasdaq dealer, interacts with market orders in actively traded stocks during the fourth quarter of 1996, we estimate that its revenue is $0.057 per share. Knight pays brokers at least $0.025 per share (44% of revenue) for orders. To examine whether brokers appear to share these payments with traders, we compare net trading costs (trade price net of commissions) for traders using brokers routing Knight orders with estimated net trading costs for traders using the only discount broker we can determine did not directly receive market-making revenue. We find that the net trading cost of the broker refusing order-flow payments does not dominate the net trading cost of all brokers selling order flow to Knight. This finding suggests that order-flow payments do not unambiguously harm traders and challenges the conclusions of extant studies using only trade prices to assess market quality.

Survey evidence suggests that managers choosing to provide earnings guidance do so in order to, among other things, dampen share price volatility. Yet, consultants and influential institutions strongly urge managers to cease guidance — citing a lack of evidence that guidance curbs volatility. Furthermore, recent research links guidance to increased volatility. Hence, some argue that guidance not only fails to promote market tranquility but may actually prompt turbulence. In this paper, we consider the interplay between guidance and volatility, focusing on guidance bundled with quarterly earnings, which now constitutes the vast majority of earnings guidance. Consistent with the notion that volatility concerns factor into managers’ decisions to provide earnings guidance, we find a consistent link between abnormal run-ups in volatility prior to an earnings release and the likelihood that a manager “bundles” a forecast with the firm’s earnings announcement. Our tests also indicate that managers’ efforts do not go unrewarded, as we document abnormally large post-announcement declines in volatility for guidance quarters. Collectively, our evidence supports the view that managers seek to and do mitigate share price volatility with guidance.

On October 19, 2010, the Centers for Disease Control and Prevention (CDC), National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) held its Health Equity Symposium entitled “Establishing a Holistic Framework to Reduce Inequities in Human Immunodeficiency Virus (HIV), Viral Hepatitis, Sexually Transmitted Diseases (STDs), and Tuberculosis (TB) in the United States.” For those of us working on health equity issues at the state level, it was an honor to participate in such an important national event with distinguished colleagues Paula Braveman, MD, and Scott Burris, JD, who offered perspectives on some of the most pressing issues relating to health equity based on specific aspects of the NCHHSTP Strategic Plan.1 Overcoming health inequities in the United States is entirely possible by changing the way we define, think, and address the problem. The preceding statement is meant to challenge public health professionals to champion effective health equity strategies in public health systems. We hope the following thoughts will compel you to seize opportunities to address health inequities using a holistic framework, even when it may be unpopular or uncomfortable to do so.

A technique is presented to assess health risks associated with coating the inside surface of a bulk storage tank. The technique uses a sequential box model to predict the time-varying solvent concentrations at arbitrary points inside the vessel during an ongoing coating process. Input parameters include volumetric flow rates of exhaust and makeup air, solvent threshold limit values and evaporation rates, and a set of exchange coefficients that characterize air circulation inside the vessel. This technique enables engineers to rate quantitatively the anticipated health risks of applying a combination of coatings. The technique also provides engineering managers a predictive tool to organize work schedules so that health and safety can become input parameters to an engineering enterprise.

It is the purpose of this paper to report an outbreak of streptococcic disease that occurred at Keesler Field, Mississippi, a large Army Air Forces training center, during the winter of 1944-45. This outbreak was produced by a sulfadiazine resistant strain of Group A, Type 17 hemolytic streptococcus. It is believed that this is the first example of such an occurrence to be reported. It was possible to study the epidemic in considerable detail. An Army Air Forces Rheumatic Fever Control Program laboratory had been established at the field for a survey of hemolytic streptococci in a supposedly low incidence area. This laboratory had been equipped and staffed to perform streptococcus grouping and typings on a large scale.

Amalgamation of the structure−activity relationship of two series of GlyT1 inhibitors developed at Merck led to the discovery of a clinical candidate, compound 16 (DCCCyB), which demonstrated excellent in vivo occupancy of GlyT1 transporters in rhesus monkey as determined by displacement of a PET tracer ligand.

Chondrosarcoma is the second most common primary malignant bone tumour. Distinguishing between grades is not necessarily straightforward and may alter the disease management. We evaluated the correlation between histological grading of the preoperative image-guided needle biopsy and the resection specimen of 78 consecutive cases of chondrosarcoma of the femur, humerus, and tibia. In 11 instances, there was a discrepancy in histological grade between the biopsy and surgical specimen. Therefore, there was an 85.9% (67/78) accuracy rate for pre-operative histological grading of chondrosarcoma, based on needle biopsy. However, the accuracy of the diagnostic biopsy to distinguish low-grade from high-grade chondrosarcoma was 93.6% (73/78). We conclude that accurate image-guided biopsy is a very useful adjunct in determining histological grade of chondrosarcoma and the subsequent treatment plan. At present, a multidisciplinary approach, comprising experienced orthopaedic surgeons, radiologists, and pathologists, offers the most reliable means of accurately diagnosing and grading of chondrosarcoma of long bones.

In 2001, the SEC required market centers to publish monthly execution-quality reports in an effort to spur competition for order flow between markets. Using samples of stocks trading on several markets, we investigate whether past execution quality affects order-routing decisions and whether the new disclosure requirements influence this relationship. We find that routing decisions are associated with execution quality; markets reporting low execution costs and fast fills subsequently receive more orders. Moreover, the reports themselves appear to provide information that was unavailable previously. Our results are consistent with active competition for order flow that can be influenced by public disclosure.

A 42-year-old woman who had recently emigrated to the UK from Ethiopia presented to her general practitioner with increasing breathlessness and palpitations. Transoesophageal echocardiogram revealed rheumatic heart disease affecting three valves, and severe aortic stenosis. ECG demonstrated atrial fibrillation. She was treated operatively with mitral and aortic valve replacement and tricuspid valve repair and put on lifelong warfarin. Four months later she remains well, with substantially increased exercise tolerance. This case report summarises treatment options for severe rheumatic heart disease and discusses differences in prevention and management between patients presenting in the UK and in the developing world.

We study the division of market-making revenue among dealer, broker, and trader. When Knight Securities, a major Nasdaq dealer, interacts with market orders in actively traded stocks during the fourth quarter of 1996, we estimate that its revenue is $0.057 per share. Knight pays brokers at least $0.025 per share (44% of revenue) for orders. To examine whether brokers appear to share these payments with traders, we compare net trading costs (trade price net of commissions) for traders using brokers routing Knight orders with estimated net trading costs for traders using the only discount broker we can determine did not directly receive market-making revenue. We find that the net trading cost of the broker refusing order-flow payments does not dominate the net trading cost of all brokers selling order flow to Knight. This finding suggests that order-flow payments do not unambiguously harm traders and challenges the conclusions of extant studies using only trade prices to assess market quality.

The design of a grinding booth suitable for large castings and portable hand-held grinders is recommended. Systematically studied were the air velocities within the booth as functions of the geometry of the suction ports, recirculation jets, ventilation flow rate and recirculation flow rate. The rate at which grinding particles are injected into the air from the surface of the grinding wheel was studied and described in terms of a distribution function G(θ) and the metal removal rate.

Fugitive dust generated by industrial haul roads can be reduced by windbreaks placed upwind or downwind of the road. For an elementary wind profile downwind of a windbreak, the fractional efficiency has been predicted as a function of downwind distance, wind speed and windbreak height and porosity. An analytical model and computer algorithm are proposed to enable engineers to predict the fractional efficiency for any source and wind profile of their choosing.