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Purpose: Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8+ T-cell activity and improves clinical activity of immune checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors.Methods:We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients versus BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05. ResultsOf 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; [1.54-5.03]; p=0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; [0.09, 0.62]; P=0.0031). Conclusions:Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy.

The COVID-19 pandemic first became evident at the end of 2019, and because of the many unknown aspects of this emerging infectious disease, the internet quickly became a source of information for consumers. It is important for any vital information to be written unambiguously, and at a level that can be understood by all people regardless of education levels. The purpose of this study was to assess the readability of 50 sources of COVID19 testing information online. Only 6 websites out of 50 received an appropriate readability score on more than one assessment. One-sample, one-tailed t-tests (α = 0.05, df = 49) were used to see if the websites with information on COVID-19 testing are being written at appropriate reading levels. The resulting p-values indicate that each p-value recorded is substantially below 0.05, it is very unlikely that websites on this topic are being written at the recommended levels. Even the optimal messages on COVID-19 reflect a confusing and rapidly changing public health crisis, however if messages are kept simple and clear, individuals will have the best possible chance of optimizing behavioral mitigation strategies. These are compelling reasons for informational hosts to take necessary steps to ensure that messages are written in as simple terms as possible. To this end, it is suggested that internet sites dispersing COVID-19 testing information build in text analysis methods for all published messages, particularly those meant to inform best health practices in the time of a pandemic.

Objectives Immune checkpoint inhibitors (ICIs) are being increasingly used across cancer types. Emergency room (ER) and inpatient (IP) care, common in patients with cancer, remain poorly defined in this specific population, and risk factors for such care are unknown. Methods We retrospectively reviewed charts for patients with solid tumors who received >1 ICI dose at 1 of 2 sites from January 1, 2011 to April 28, 2017. Demographics, medical history, cancer diagnosis/therapy/toxicity details, and outcomes were recorded. Descriptive data detailing ER/IP care at the 2 associated hospitals during ICI therapy (from first dose to 3 mo after last dose) were collected. The Fisher exact test and multivariate regression analysis was used to study differences between patients with versus without ER/IP care during ICI treatment. Results Among 345 patients studied, 50% had at least 1 ER visit during ICI treatment and 43% had at least 1 IP admission. Six percent of ER/IP visits eventually required intensive care. A total of 12% of ER/IP visits were associated with suspected or confirmed immune-related adverse events. Predictors of ER care were African-American race (odds ratio [OR]: 3.83, P=0.001), Hispanic ethnicity (OR: 3.12, P=0.007), and coronary artery disease (OR: 2.43, P=0.006). Predictors of IP care were African-American race (OR: 2.38, P=0.024), Hispanic ethnicity (OR: 2.29, P=0.045), chronic kidney disease (OR: 3.89, P=0.006), angiotensin converting enzyme inhibitor/angiotensin receptor blocker medication use (OR: 0.44, P=0.009), and liver metastasis (OR: 2.32, P=0.003). Conclusions Understanding demographic and clinical risk factors for ER/IP care among patients on ICIs can help highlight disparities, prospectively identify high-risk patients, and inform preventive programs aimed at reducing such care.

The Commodity Futures Trading Commission (CFTC) recently identified large intra‐day price changes or “flash events” in continuously traded commodity futures markets. These flash events fueled discussion on whether futures markets are becoming less effective as human intervention is diminishing in favor of automated trading. Using intra‐day data, we examine liquidity resilience during “flash events” in corn and lean hog futures markets from 2014 to 2019. Overall, we find little evidence that the liquidity provision in these two markets relative to normal days becomes fragile when large price movements occur. Our analysis suggests that flash events are heavily influenced by unanticipated changes in fundamentals that may lead to a new equilibrium price. Liquidity dynamics during these events supports the view that active market making helps absorb the increased volume and stabilize markets.

The article sheds light on price jump risk in corn futures prices in the era of electronic trading and after the shift to real‐time announcement of USDA reports. Using intraday prices from 2008 to 2015, we employ a nonparametric test to detect jumps and variance analysis to assess the relative importance of jump risk. Real‐time trading of major USDA reports has substantially increased the frequency and clustering of price jumps, and results in higher market liquidity costs. In contrast, although the presence of jumps on non‐announcement days has doubled recently, their magnitude has declined as have transactions costs during their occurrence. The largest jump risk or execution risk is experienced by high frequency traders due to heightened microstructure noise during price jumps. However, traders holding long‐term market positions are only minimally affected by increased jump risk.

Objective:The purpose of this study was to assess the readability of information on the Internet posted about coronavirus disease 2019 (COVID-19) to determine how closely these materials are written to the recommended reading levels.Methods:Using the search term “coronavirus,” information posted on the first 100 English language websites was identified. Using an online readability calculator, multiple readability tests were conducted to ensure a comprehensive representation would result.Results:The mean readability scores ranged between grade levels 6.2 and 17.8 (graduate school level). Four of the 5 measures (GFI, CLI, SMOG, FRE) found that readability exceeded the 10th grade reading level indicating that the text of these websites would be difficult for the average American to read. The mean reading level for nearly all noncommercial and commercial websites was at or above the 10th grade reading level.Conclusions:Messages about COVID-19 must be readable at an “easy” level, and must contain clear guidelines for behavior. The degree to which individuals seek information in response to risk messages is positively related to the expectation that the information will resolve uncertainty. However, if the information is too complex to interpret and it fails to lead to disambiguation, this can contribute to feelings of panic.

Background: Web-based patient education literature has been shown to be written at reading levels far above what is recommended. Little is known about the overall readability of current internet-based bariatric surgery information. The purpose of this study was to assess the readability of current bariatric material on the internet. Methods: The term "weight loss surgery" was searched using the Chrome browser on the first 15pages of URLs that appeared with content written in English. Using five readability measures, scores were generated using Readable.io for written content on a sample of 96 websites. Scores were sorted into the readability categories of "easy," "average," and "difficult." Results: Almost 93% of websites, both .com and .org, sampled received an unacceptable readability score on each assessment. Conclusion: Accurate and appropriate information about bariatric procedures is critical for patient comprehension and adherence to recommended protocols.

Using quantile regression, we evaluate the forecasting performance of futures prices in the soybean complex. The procedure provides a more complete picture of the distribution of forecasts than mainstream methods that only focus on central tendency measures. Forecast performance differs by location in the futures price distribution. Futures forecast perform well in the centre of the distribution. However, futures prices tend to over-forecast when futures prices are high and under-forecast when futures prices are low, suggesting that futures prices tend to under-estimate price reversion towards the centre of the distribution. Forecast errors are larger when futures prices are high. The findings are related to theories in the literature used to explain pricing bias, and their implications for market participants are discussed.

Clinical trials are critically important for the development of new cancer treatments. According to recent estimates, however, clinical trial enrollment is only about 8%. Lack of patient understanding or awareness of clinical trials is one reason for the low rate of participation. The purpose of this observational study was to evaluate the readability of cancer clinical trial websites designed to educate the general public and patients about clinical trials. Nearly 90% of Americans use Google to search for health-related information. We conducted a Google Chrome Incognito search in 2018 using the keywords “cancer clinical trial” and “cancer clinical trials.” Content of the 100 cancer clinical trial websites was analyzed using an online readability panel consisting of Flesch-Kincaid Grade Level, Flesch Reading Ease, Gunning-Fog Index, Coleman-Liau Index, and Simple Measure of Gobbledygook scales. Reading level difficulty was assessed and compared between commercial versus non-commercial URL extensions. Content readability was found to be “difficult” (10.7 grade level). No significant difference in readability, overall, and between commercial and non-commercial URL extensions was found using 4/5 measures of readability; 90.9% of commercial versus 49.4% of non-commercial websites were written at a >10th grade ( P = .013) using Gunning-Fog Index. Written cancer clinical trials content on the Internet is written at a reading level beyond the literacy capabilities of the average American reader. Improving readability to accommodate readers with basic literacy skills will provide an opportunity for greater comprehension that could potentially result in higher rates of clinical trial enrollment.

Background Caring for young children is a known risk factor for cytomegalovirus (CMV) infection mainly through exposure to their saliva and urine. In a previous study, 36 CMV-seropositive children 2 mo. to 4 years old were categorized as CMV shedders (n = 23) or non-shedders (n = 13) based on detection of CMV DNA in their saliva and urine. The current study evaluated the presence of CMV on surfaces in homes of the children. Methods Study staff made 4 visits to homes of the 36 enrolled children over 100 days. Saliva was collected by swabbing the mouth and urine was collected on filter paper inserted into diapers. In addition, five surface specimens were collected: three in contact with children’s saliva (spoon, child’s cheek, washcloth) and two in contact with children’s urine (diaper changing table, mother’s hand). Samples were tested by PCR and viral culture to quantify the presence of CMV DNA and viable virus. Results A total of 654 surface samples from 36 homes were tested; 136 were CMV DNA positive, 122 of which (90%) were in homes of the children shedding CMV (p

Recently, U.S. live cattle futures prices have experienced high levels of intraday price variance, which have raised concerns about the possible impact of microstructure noise from high frequency trading on market instability. This article identifies both the magnitude and the duration of the bias caused by market microstructure noise in measuring efficient price variance in the live cattle futures market from 2011 to 2016, with emphasis on price variance behavior in recent years. Market microstructure noise increases observed price variance, but its effects are not large and do not last more than three to four minutes in response to changing information. Intraday price variance has increased in recent years, but the findings provide little evidence that high frequency traders were responsible for economically meaningful market noise. Informatively, steps taken by the CME and cattle producers to mitigate noise have not been fruitful to date, and signal that the magnitude of noise will likely vary with the magnitude of changes in demand and cyclical supply.

This paper examines whether USDA announcements and commodity index fund rolling activity have an impact on liquidity costs, measured by the Bid-Ask Spread. Using Huang and Stoll's (1997) model of liquidity costs, we estimate whether changes to liquidity costs are driven by its adverse selection, inventory, or order processing components. Commodity index fund roll activity reduces the asymmetric information cost component of liquidity cost due to an increased proportion of non-information based trading, but the inventory cost component increases as (mostly long only) commodity index funds sell their nearby positions and buy the first deferred contract – raising liquidity providers’ risk of building a position. The sum of these two effects is that liquidity costs remain low during index fund roll periods, averaging very near one ‘tick’ (0.25 cents). On USDA report release days, we find that informed traders raise the asymmetric information component of liquidity costs in the first hour after release, but the inventory cost component is reduced due to the increase in volume associated with trading after the report release. Similar to index fund roll activity, liquidity costs on USDA report release days remain low, averaging very near one ‘tick’ (0.25 cents). Our findings that liquidity costs are very minimally changed during USDA report releases and commodity index fund roll periods is consistent with other recent research on liquidity costs, but we show that what drives liquidity costs differs substantially depending on the circumstances surrounding daily trading. This article is protected by copyright. All rights reserved

This paper examines the usefulness of commodities in an investor's portfolio. Using data on three generations of commodity indices and 15 individual commodity futures for 1991–2015, we find that incorporating most commodity products does little to improve the portfolio's Sharpe ratio especially in an out-of-sample context. The only exception is the third-generation commodity index that is based on a momentum strategy and can substantially enhance portfolio performance. When estimation errors are reduced using a shrinkage estimator, the resulting optimal portfolios are more diversified and stable over time, and importantly, commodities play a much smaller role in terms of risk reduction in portfolios.

This article investigates market reactions to major United States Department of Agriculture announcements during non-trading and trading hours in the soybean futures market using microstructure dat...

We apply an encompassing framework to assess the viability of hedging spot biodiesel price risk for four U.S. markets with a conventionally used heating oil futures contract and a soybean oil futures contract based on the logic that supply shifts (i.e., price of soybean oil as an input) drive biodiesel prices when binding blending mandates are in place. Results indicate that soybean oil futures should in fact be part of a composite hedge, and that in some instances greater hedging weight should be placed on the soybean oil futures contract than the conventionally used heating oil futures contract.

We develop and evaluate quarterly out-of-sample individual and composite density forecasts for U.S. hog prices. Individual density forecasts are generated using time series models and the implied distributions of USDA and Iowa State University outlook forecasts. Composite density forecasts are constructed using linear and logarithmic combinations of the individual forecasts and several weighting schemes. Density forecasts are evaluated on predictive accuracy (sharpness), goodness of fit (calibration), and their economic value in a hedging simulation. Logarithmic combinations using equal and mean square error weights outperform all individual density forecasts and are modestly better than linear composites. Comparison of the outlook forecasts to the best composite demonstrates the usefulness of the composite procedure, and identifies the economic value that more accurate expected price probability distributions can provide to producers.

Futures market contracts with varying maturities are traded concurrently and the speed at which they process information is of value in understanding the pricing discovery process. Using price discovery measures, including Putnins (2013) information leadership share and intraday data, we quantify the proportional contribution of price discovery between nearby and deferred contracts in the corn and live cattle futures markets. Price discovery is more systematic in the corn than in the live cattle market. On average, nearby contracts lead all deferred contracts in price discovery in the corn market, but have a relatively less dominant role in the live cattle market. In both markets, the nearby contract loses dominance when its relative volume share dips below 50%, which occurs about 2-3 weeks before expiration in corn and 5-6 weeks before expiration in live cattle. Regression results indicate that the share of price discovery is most closely linked to trading volume but is also affected, to far less degree, by time to expiration, backwardation, USDA announcements and market crashes. The effects of these other factors vary between the markets which likely reflect the difference in storability as well as other market-related characteristics.

In a well-functioning futures market, the futures price at expiration equals the price of the underlying asset. This condition failed to hold in grain markets for most of 2005-2010, calling into question the ability of these markets to perform their price discovery and risk management functions. During this period, futures contracts expired up to 35% above the cash grain price. We develop a dynamic rational expectations model of commodity storage that explains how these recent convergence failures were generated by the institutional structure of the delivery system. When delivery occurs on a grain futures contract, the firm on the short side of the market provides a delivery instrument (a warehouse receipt or shipping certificate) to the firm on the long side of the market. The firm taking delivery may hold the delivery instrument indefinitely, providing it pays a daily storage rate. The futures exchange sets the maximum allowable storage rate at a fixed value. We show that non-convergence arises in equilibrium when the market price of physical grain storage exceeds the maximum storage rate on delivery instruments. We call the difference between the price of carrying physical grain and the maximum storage rate the wedge , and demonstrate theoretically and empirically that the magnitude of the non-convergence equals the expected present discounted value of a function of future wedges.

The purpose of this study was to describe the content of the most popular YouTube videos related to Clostridium difficile. Across all sources, the kinds of content most likely to be included in the videos was general information, overuse of antibiotics, and symptomatic diarrhea. Health professionals can contribute to existing social media messages related to C. difficile with comprehensive messages that include means for prevention. Keywords: Clostridium difficile, YouTube, Social media

We examine the actual price impact of genetically modified grain contamination events. This paper contributes to the literature by examining the price effects of multiple genetically modified contamination events in the U.S. corn market. Using the relative price of substitute method and time-varying cointegration, we identify two primary structural breaks most relevant to the corn contamination events, StarLink and MIR162 events. Our results support the StarLink event’s large effect on corn prices found in the literature, but the price effect attributed to MIR162 is less clear. The break in prices near the MIR162 event, which was attributed to China’s rejection of the contaminated corn, emerged three months prior to the import ban. The magnitude of the price change was influenced by changes in U.S. corn and sorghum supply, and the EPA’s proposed reduction of the ethanol mandate. Expansion of sorghum exports and subsequent increased corn production also likely kept the pressure on corn prices. While China’s import ban on MIR162 and DDGSs may have resulted in delayed and cumulative changes in prices, the evidence suggests that the subsequent downturn in the U.S. corn market was more likely influenced by other domestic supply and demand changes.

A recently developed testing procedure is used to detect and date-stamp explosive episodes ("bubbles" in corn, soybean, and wheat futures markets during 2004-2013. We find that the markets experienced price explosiveness only approximately two percent of the time and, when bubbles do occur, they are generally short-lived and small in magnitude. The correspondence between observed price spikes and bubbles is rather low, with a large portion of the price explosiveness occurring during downward price movements. Commodity index trader positions do not significantly affect the probability of a positive bubble occurring in grain futures markets, which directly contradicts the argument (the "Masters Hypothesis" that waves of index investment distorted underlying supply-and-demand relationships and led to a series of massive bubbles in agricultural futures markets. In addition, commodity index trader positions tend to reduce negative bubble occurrence, while general speculative activity as measured by Working's T reduces the probability of a positive bubble. There is some evidence that the positions of noncommercial traders have a direct effect on positive bubble occurrence, but the effect declines when accounting for the composition of other traders in the market. Overall, speculation has little effect or negative effects on price explosiveness. Finally, positive bubbles are more likely to occur in the presence of low inventories, strong exports, a weak U.S. dollar, and booming economic growth, whereas negative bubbles are more likely to occur with large inventories, weak exports, and stagnant economic growth.

We use daily prices from individual futures contracts to test whether speculative bubbles exist in 12 agricultural markets and to identify whether patterns of bubble behavior exist over time. The samples begin as far back as 1970 and run through 2011. The findings demonstrate that all 12 agricultural markets experienced multiple periods of price explosiveness. However, bubble episodes represent a very small portion—between 1.5 and 2%—of price behavior during the 42-year period. In addition, most bubbles are short-lived with 80–90% lasting fewer than 10 days. Though receiving far less attention, negative bubbles contribute significantly to price behavior, accounting for more than one-third of explosive episodes. Markets over-react during both positive and negative explosive episodes, leading to a correction as they return to a random walk. This adjustment back to fundamental values is most pronounced with positive bubbles particularly in the earlier part of the sample. While the magnitudes of the corrections are generally small, there were a few instances of significant increases in prices and large over-reactions, most notably in the softs (e.g., cocoa 1973, coffee 1994, cotton 2010). We also find that explosive periods did not become more common or last longer in the second half of the sample period and that the most recent bubble episodes may not have been as severe as in mid-1970s.

This article investigates the announcement effects of major USDA reports using intraday Chicago Board of Trade corn futures prices and trading volume from the electronic trading platform for July 2009 to May 2012. Focusing on intraday market reactions, we analyze the extent to which new information impacts and is rapidly reflected in prices. Results show that USDA reports contain substantial information for market participants. Strongest price reactions to the releases are found immediately after the market opens, and market reactions persist for approximately ten minutes. The electronic corn futures market quickly incorporates this new public information, and little evidence exists to support systematic under- or overreactions in prices. Other more subtle reactions occur in the last trading session before USDA announcements as traders adjust their market exposure in anticipation of the release.

This is the first paper to analyze liquidity costs in agricultural futures markets based on the observed bid‐ask spread (BAS) faced by market participants. The results reveal a highly liquid corn market that mostly offers order execution at minimum cost. The BAS responds negatively to volume and positively to price volatility, but also affects volume traded and price volatility. While statistically significant, these responses on a cents/bushel or a percentage basis are generally small. Liquidity costs are also virtually impervious to short‐term changes in demand for spreading and trend‐following trader activity, as well as differences from day‐of‐the‐week changes in market activity. Much larger cents/bushel and percentage changes in BAS occur during commodity index trader roll periods and on USDA report release days. The roll period findings indicate a sunshine trading effect, while announcement effects identify the importance of unexpected information and adverse selection on order execution costs. Overall, our research demonstrates that the transition to electronic trading in the corn futures market has led to low and stable liquidity costs, despite the market turbulence in 2008–2009.

Using individual trader data from the Commodity Futures Trading Commission's (CFTC) Large Trader Reporting System (LTRS) for the period January 2000 to September 2009, this article investigates whether noncommercial traders in the corn, live cattle and coffee futures markets persist in making profits. Two out-of-sample measures of skill – a winner and a loser ranking test and a top and a bottom decile test – are used to analyse the ability of traders to consistently perform well at monthly, quarterly and annual time horizons. The findings identify significant persistence in rankings – traders in the top half of the profit distribution in a time period tend to stay in the top half in the next period. Differences in magnitude of profitability between the top and bottom deciles also provide support that persistent skill exists among the top 10% of traders. Detailed examination of annual rankings for those traders who were most continuously in the markets further reveals persistence in profits for a smaller s...

Numerous crop marketing and risk management tools are available. Research relating producers’ risk attitudes to their use of these tools has produced mixed results, and most studies focus on individual tools, neglecting potential complementarities in information they provide. Little is known about the proportion in which individual tools are used, e.g., the percentage of the crop that is forward sold as opposed to hedged. This study identifies factors, including risk attitude, that impact the proportion of corn and soybean producers’ sales through spot markets, futures, and options, as well as forward and production contracts, and investigates contract complementarity and substitutability using survey and accounting data, and causal modeling.

How instructive cues present on the cell surface have their precise effects on the actin cytoskeleton is poorly understood. Semaphorins are one of the largest families of these instructive cues and are widely studied for their effects on cell movement, navigation, angiogenesis, immunology and cancer1. Semaphorins/collapsins were characterized in part on the basis of their ability to drastically alter actin cytoskeletal dynamics in neuronal processes2, but despite considerable progress in the identification of semaphorin receptors and their signalling pathways3, the molecules linking them to the precise control of cytoskeletal elements remain unknown. Recently, highly unusual proteins of the Mical family of enzymes have been found to associate with the cytoplasmic portion of plexins, which are large cell-surface semaphorin receptors, and to mediate axon guidance, synaptogenesis, dendritic pruning and other cell morphological changes4, 5, 6, 7. Mical enzymes perform reduction–oxidation (redox) enzymatic reactions4, 5, 8, 9, 10 and also contain domains found in proteins that regulate cell morphology4, 11. However, nothing is known of the role of Mical or its redox activity in mediating morphological changes. Here we report that Mical directly links semaphorins and their plexin receptors to the precise control of actin filament (F-actin) dynamics. We found that Mical is both necessary and sufficient for semaphorin–plexin-mediated F-actin reorganization in vivo. Likewise, we purified Mical protein and found that it directly binds F-actin and disassembles both individual and bundled actin filaments. We also found that Mical utilizes its redox activity to alter F-actin dynamics in vivo and in vitro, indicating a previously unknown role for specific redox signalling events in actin cytoskeletal regulation. Mical therefore is a novel F-actin-disassembly factor that provides a molecular conduit through which actin reorganization—a hallmark of cell morphological changes including axon navigation—can be precisely achieved spatiotemporally in response to semaphorins

This paper evaluates the role that index funds have played in recent convergence problems of Chicago Board of Trade corn, soybean, and wheat futures contracts. These new market participants are widely considered to have inflated futures prices and/or expanded spreads between futures prices. Large spreads in futures markets contribute to a lack of convergence by uncoupling cash and futures markets. Statistical tests provide no evidence that rolling of positions by index funds or the initiation of large index positions in a “crowded market space” have contributed to an expansion of the spreads. Copyright 2011, Oxford University Press.