CHANGING STRUCTURES IN THE BARLEY PRODUCTION AND MALTING INDUSTRIES OF THE UNITED STATES AND CANADA

Substantial changes have taken place recently in the regulation of agricultural trade in North America. The effect of these changes on trade in agricultural commodities is of particular interest to producers and policymakers in the Northern Plains and Rockies region. In this paper, we discuss specifically the malt barley production, malting, and brewing industries in light of these new trade agreements and their ramifications. We evaluate the incentives that free trade provides for mergers between barley malting firms, and then we assess the consequences of these mergers on the realized gains from trade for consumers, barley producers, and malting firms. The globalization of markets has fundamentally changed the world in which economic agents operate. Trade has been liberalized through multilateral world-wide agreements such as the General Agreement on Trade and Tariffs (GATT) and through regional free trade agreements such as those within the European Union, the Canadian/United States Trade Agreement (CUSTA), and the North American Free Trade Agreement (NAFTA). A striking phenomena which has accompanied trade liberalization has been the international merger of firms and the creation of many jointly owned multinational operations. There are two distinct types of malt barley that differ in their yield and in their production areas in North America. Montana and the Canadian provinces grow primarily high-quality two row barley, while North Dakota and Minnesota produce primarily six row malting varieties. Two row barley yields more malt per bushel for maltsters, but it is more prone to disease for barley producers. The opening of the border between the United States and Canada has made large quantities of two row barley available to U.S. malting firms and brewers. The trade policy literature suggests that trade liberalization will have a profound impact on domestic policy choice, making the costs of any government action to increase market prices above the prevailing world price more expensive. Open borders should also provide discipline on how industries price in the domestic market. With import restrictions such as tariffs in place, the non-competitive industry structures that raise prices in the domestic market can exist with limited fear of foreign competition. With freer trade, however, the industry faces more potential competition. When a free trade policy merges formally distinct markets for which stable industry structures exist, this creates additional incentives for mergers within the newly combined industry that reduce these gains from free trade. This analysis was motivated by observing the malting barley industry in Canada and the United States. In 1985, prior to CUSTA, the two domestic markets for barley malt were distinctly separated by import license requirements into Canada and import tariffs in the United States. As such, both countries had large malting industries, but there was little trade flow between the two countries in malting barley, in barley malt, or in beer. Four firms controlled 90 percent of the Canadian malting market, and six firms controlled over 80 percent of the U.S. malting market before CUSTA. As a result of mergers after CUSTA, five firms owned 90 percent of the malting capacity in North America. Economies of scale and elimination of high cost plants often drive industry consolidation. Interestingly enough, despite all of the merger activity among malting firms, there were very few plant closures and very little new capacity built. Even new entrants to either the United States or Canadian industries purchased the assets of existing firms, rather than building new plants. We review relevant literature for firm behavior and report the results of a model for the incentives for plant mergers in the North American malting industry following CUSTA. We evaluate malting firm profits, the changes in malting margins, the price effects, and the overall welfare effects of the creation of the free trade area and subsequent mergers within the industry. We found that free trade, in the absence of mergers, increases output in both countries and reduces malting margins leading to large gains for consumers and producers of malt barley. The agreement, however, also increases incentives for mergers. With the mergers that took place, we show that merging barley malting firms have incentives to decrease output by about 21 percent, while their producers' surplus increased by approximately 34 percent. The net benefits of free trade to consumers and input suppliers are reduced by mergers, while the profits of merging firms are increased by them. Overall, with free trade and mergers, there is still a net social gain relative to pre-CUSTA. Malt production in Canada increases by over 12 percent, while that in the U.S. is slightly lower, leaving North American consumers, firms, and barley producers better off.malting barley, industry concentration, free trade agreement, Industrial Organization, Q1, F1,

APOE and FABP2 Polymorphisms and History of Myocardial Infarction, Stroke, Diabetes, and Gallbladder Disease

Dysfunctional lipid metabolism plays a central role in pathogenesis of major chronic diseases, and genetic factors are important determinants of individual lipid profiles. We analyzed the associations of two well-established functional polymorphisms (FABP2 A54T and APOE isoforms) with past and family histories of 1492 population samples. FABP2-T54 allele was associated with an increased risk of past history of myocardial infarction (odds ratio (OR) = 1.51). Likewise, the subjects with APOE4, compared with E2 and E3, had a significantly increased risk of past history myocardial infarction (OR = 1.89). The OR associated with APOE4 was specifically increased in women for past history of myocardial infarction but decreased for gallstone disease. Interactions between gender and APOE isoforms were also significant or marginally significant for these two conditions. FABP2-T54 allele may be a potential genetic marker for myocardial infarction, and APOE4 may exert sex-dependent effects on myocardial infarction and gallbladder disease

Monitoring cryptic amphibians and reptiles in a Florida state park

We monitored cryptic herpetofauna at Savannas Preserve State Park, Florida, by combining artificial cover counts with a quantitative paradigm for constructing and calculating population indices. Weekly indices were calculated from two consecutive days of data collection each week for 7 months from mid-winter to mid-summer in three habitats. Seventeen species were observed at least once, and time trends using index values were followed for six species. Among these, abundance and seasonal pattern information were obtained for an exotic species (greenhouse frog) and a species identified by the Florida Committee on Rare and Endangered Plants and Animals as threatened (Florida scrub lizard). We identified winter as the optimal time in this area to monitor populations for conducting annual assessments. This combined observation and indexing approach could provide managers or researchers with an economical means to quantitatively index population trends for multiple cryptic herpetofauna species simultaneously. Using artificial cover to sample within a population indexing design can be generalized beyond monitoring herpetofauna. Other forms of artificial cover that can be used as observation stations include aquatic artificial substrates, artificial tree cavities, artificial reefs, and other artificial aquatic structures and artificial sea grass units, among many others, and a wide range of taxa are suitable for population monitoring using artificial cover as observation stations in the approach we present, including insects, soil invertebrates, micro and macro aquatic invertebrates, fish, crustaceans, and small mammals

Cancer Among Arab Americans in the Metropolitan Detroit Area

Detroit is home to one of the largest populations of Arab Americans outside of the Middle East, yet little is known about the cancer distribution in this ethnic group. The authors of this study created an Arab/Chaldean surname list and matched it with the Detroit SEER Registry to identify cancer cases of probable Arabic descent. We then determined proportional incidence ratios (PIR) for specific cancer sites among metropolitan Detroit Arab Americans as compared to non-Arab Whites, and contrasted the results with Middle Eastern data. Arab/Chaldean men had greater proportions of leukemia (29%), multiple myeloma (46%), liver (64%), kidney (33%), and urinary bladder (26%) cancers. Arab/Chaldean women had greater proportions of leukemia (23%), thyroid (57%), and brain (35%) cancers as compared with non-Arab White men and women. The cancers with significantly increased PIRs in the Detroit Arab/Chaldean population also are frequently diagnosed in Middle Eastern countries

Closed-loop optimization of fast-charging protocols for batteries with machine learning.

Simultaneously optimizing many design parameters in time-consuming experiments causes bottlenecks in a broad range of scientific and engineering disciplines1,2. One such example is process and control optimization for lithium-ion batteries during materials selection, cell manufacturing and operation. A typical objective is to maximize battery lifetime; however, conducting even a single experiment to evaluate lifetime can take months to years3-5. Furthermore, both large parameter spaces and high sampling variability3,6,7 necessitate a large number of experiments. Hence, the key challenge is to reduce both the number and the duration of the experiments required. Here we develop and demonstrate a machine learning methodology  to efficiently optimize a parameter space specifying the current and voltage profiles of six-step, ten-minute fast-charging protocols for maximizing battery cycle life, which can alleviate range anxiety for electric-vehicle users8,9. We combine two key elements to reduce the optimization cost: an early-prediction model5, which reduces the time per experiment by predicting the final cycle life using data from the first few cycles, and a Bayesian optimization algorithm10,11, which reduces the number of experiments by balancing exploration and exploitation to efficiently probe the parameter space of charging protocols. Using this methodology, we rapidly identify high-cycle-life charging protocols among 224 candidates in 16 days (compared with over 500 days using exhaustive search without early prediction), and subsequently validate the accuracy and efficiency of our optimization approach. Our closed-loop methodology automatically incorporates feedback from past experiments to inform future decisions and can be generalized to other applications in battery design and, more broadly, other scientific domains that involve time-intensive experiments and multi-dimensional design spaces

Epidemiologic Evaluation of Measurement Data in the Presence of Detection Limits

Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of “fill-in” values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5–10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case–control study of non-Hodgkin lymphoma

Pregnancy outcomes in female childhood and adolescent cancer survivors: a linked cancer-birth registry analysis

Objective: To compare birth outcomes among childhood and adolescent female cancer survivors who subsequently bear children, relative to those of women without cancer history. Design: Retrospective cohort study. Setting: 4 U.S. regions. Participants: Cancer registries identified girls <20 years, diagnosed with cancer 1973-2000. Linked birth records identified first live births after diagnosis (n=1898). Comparison subjects were selected from birth records (n=14278). Cervical/genital tract cancer cases were analyzed separately. Main Exposure: Cancer diagnosis <20 years. Outcome Measures: Infant low birth weight, preterm delivery, sex ratio, malformations, mortality, delivery method; maternal diabetes, anemia, preeclampsia. Results: Childhood cancer survivors’ infants were more likely to be preterm (relative risk [RR] 1.54, 95% CI 1.30-1.83) and weigh <2500 g (RR 1.31, 95% CI 1.10-1.57). For cervical/genital cancer patients’ offspring, estimates were 1.33 (95% CI 1.13, 1.56), and 1.29 (95% CI 1.10-1.53), respectively. There were no increased risks of malformations, infant death, or altered sex ratio, suggesting no increased germ cell mutagenicity. In exploratory analysis, bone cancer survivors had an increased risk of diabetes (RR 4.92, 95% CI 1.60-15.13), and anemia was more common among brain tumor survivors (RR 3.05, 95% CI 1.16-7.98) and childhood cancer survivors with initial treatment of chemotherapy only (RR 2.45, 95% CI 1.16-5.17). Conclusions: Infants of female childhood and adolescent cancer patients were not at increased risk of malformations or death. Increased occurrence of preterm delivery and low birth weight suggest close monitoring is warranted. Increased diabetes and anemia among sub-groups have not been reported, suggesting areas for study

Reproductive outcomes in male childhood cancer survivors: a linked cancer-birth registry analysis

OBJECTIVE: Compare the risk of reproductive and infant outcomes between male childhood cancer survivors and a population-based comparison group. DESIGN: Retrospective cohort study. SETTING: 4 U.S. regions. PARTICIPANTS: Cancer registries identified males <20 years old diagnosed with cancer 1973-2000. Linked birth certificates identified first subsequent live offspring (n=470). Comparison subjects were identified from remaining birth certificates, frequency-matched on year and age at fatherhood, and race/ethnicity (n=4150). MAIN EXPOSURE: Cancer diagnosis prior to age 20. OUTCOME MEASURES: Pregnancy and infant outcomes identified from birth certificates. RESULTS: Compared with infants born to unaffected males, offspring of cancer survivors had a borderline risk of birth weight <2500 g (RR 1.43, 95% CI 0.99-2.05), with risk associated most strongly with younger age of cancer diagnosis and exposure to any chemotherapy (RR 1.96, 95% CI 1.22-3.17) or radiotherapy (RR 1.95, 95% CI 1.14-3.35). However, they were not at risk of being born prematurely, small for gestational age, having malformations or an altered male:female sex ratio. Overall, female partners of male survivors were not more likely to have maternal complications recorded on birth records versus the comparison group. However, preeclampsia was associated with some cancers, especially central nervous system tumors (RR 3.36, 95% CI 1.63-6.90). CONCLUSIONS: Most pregnancies resulting in live births among partners of male childhood cancer survivors were not at significantly greater risk of complications versus comparison subjects. The possibility of a paternal component affected by prior cancer history influencing predisposition towards some adverse perinatal outcomes merits further investigation

RAF inhibitors activate the integrated stress response by direct activation of GCN2

Paradoxical RAF activation by chemical RAF inhibitors (RAFi) is a well-understood on-target biological and clinical response. In this study, we show that a range of RAFi drive ERK1/2-independent activation of the Unfolded Protein Response (UPR), including expression of ATF4 and CHOP, that required the translation initiation factor eIF2-alpha. RAFi-induced ATF4 and CHOP expression was not reversed by inhibition of PERK, a known upstream activator of the eIF2-alpha-dependent Integrated Stress Response (ISR). Rather, we found that RAFi exposure activated GCN2, an alternate eIF2-alpha kinase, leading to eIF2-alpha-dependent (and ERK1/2-independent) ATF4 and CHOP expression. The GCN2 kinase inhibitor A-92, GCN2 RNAi, GCN2 knock-out or ISRIB (an eIF2-alpha antagonist) all reversed RAFi-induced expression of ATF4 and CHOP indicating that RAFi require GCN2 to activate the ISR. RAFi also activated full-length recombinant GCN2 in vitro and in cells, generating a characteristic bell-shaped concentration-response curve, reminiscent of RAFi-driven paradoxical activation of WT RAF dimers. Activation of the ISR by RAFi was abolished by GCN2 kinase dead mutations and M802A or M802G gatekeeper mutations, suggesting that RAFi bind directly to the GCN2 kinase domain; this was supported by mechanistic structural models of RAFi interaction with GCN2. Since the ISR is a critical pathway for determining cell survival or death, our observations may be relevant to the clinical use of RAFi, where paradoxical GCN2 activation may be a previously unappreciated off-target effect that may modulate tumour cell responses