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Many mental disorders (MD) share common etiology, fuelling debates about the specificity of clinical categories and whether the presence of specific risk factors (RF) can distinguish among them. The study of developmental language disorder (DLD), more specifically, has been further hindered by a lack of consensus regarding its definition. These limitations increase the risk of under-detection and lifelong consequences for affected children. This paper aims (1) to document which individual RF allow differentiating DLD from other MD and (2) to compare the cumulative RF between children with DLD versus other MD. This case-control design study used medical records of a psychiatric sample of 795 preschoolers (mean age 4:11, 75% boys). A logistic regression measured the predictive value of potential RF on DLD. Later first sentences, maternal immigration and family history of language delay were identified as significant in explaining 30% of the variance for DLD diagnosis. An ANCOVA revealed that children with DLD were exposed to a significantly higher number of RF than were children with other MD. Public health policies informed with the knowledge of specific RF associated with DLD, and their cumulative impact, could improve early detection and reduce the cascade of negative consequences associated with DLD.

Synthetic androgenic anabolic steroids (AAS) are banned compounds and considered as major threats by both racing and sports international authorities. Hence, doping control laboratories are continually looking into analytical improvements to increase their detection capabilities, notably by means of emerging technologies. To enhance analytical performances for the detection of synthetic AAS such as stanozolol, specific chromatographic procedures have been developed using recent quaternary liquid chromatography technology originally designed for high-throughput standardized proteomics connected to mass spectrometry. Applying the newly designed elution procedures described in this paper to the analyses of stanozolol and its metabolites in complex matrixes revealed improved sensitivity compared to previously described high-throughput methods. Indeed, we report the consistent and reliable detection of 16β-hydroxy-stanozolol down to 10 pg/mL in equine urine and being detectable up-to 3 months after a microdosing administration. Furthermore, a five months long elimination of stanozolol and its metabolites could be monitored on horse mane sections after a single dose administration. Our work highlights novel solutions to detect AAS with improved sensitivity. The application of such developments constitutes new landmarks for doping control laboratories and could be extended to other targeted compounds in residue analysis, toxicology, and metabolomics. Based on this work, the developed chromatographic method is now freely available within the Evosep Plus program.

Nowadays, numerous websites attempt to commercialize over the internet various products, regardless of the lack of approval by the EMA or the FDA either for human or veterinary use. These products are often produced after aborted drug development due to insufficient or deleterious biological effects, synthesized based on natural products, or only based on scientific literature. However, the administration of such products is dangerous, considering the lack of official control over the production of these substances and the absence of approval by health authorities. In this short communication, we provide an extensive analysis of three misbranded and adulterated products sold over the internet named TB500, TB1000, and SGF1000. We confirm that the content of TB500/TB1000 products is not systematically consistent with it's former descriptions, but also that SGF1000 is mainly composed of sheep extracellular matrix (ECM) and blood proteins, and the signal corresponding to the purported growth promoters is excessively diluted.

According to international sport institutions, the use of peroxisome proliferator activated receptor (PPAR)-δ agonists is forbidden at any time in athlete career due to their capabilities to increase physical and endurance performances. The (PPAR)-δ agonist GW501516 is prohibited for sale but is easily available on internet and can be used by cheaters. In the context of doping control, urine is the preferred matrix because of the non-invasive nature of sampling and providing broader exposure detection times to forbidden molecules but often not detected under its native form due to the organism's metabolism. Even if urinary metabolism of G501516 has been extensively studied in human subjects, knowledge on GW501516 metabolism in horses remains limited. To fight against doping practices in horses' races, GW501516 metabolism has to be studied in horse urine to identify and characterize the most relevant target metabolites to ensure an efficient doping control. In this article, in vitro and in vivo experiments have been conducted using horse S9 liver microsome fractions and horse oral administration route, respectively. These investigations determined that the detection of GW501516 must be performed in urine on its metabolites because the parent molecule was extremely metabolized. To maximize analytical method sensitivity, the extraction conditions have been optimized. In accordance with these results, a qualitative analytical method was validated to detect the abuse of GW501516 based on its most relevant metabolites in urine. This work enabled the Laboratoire des Courses Hippiques (LCH) to highlight two cases of illicit administration of this forbidden molecule in post-race samples.

Recombinant human erythropoietin (rHuEPO) belongs to the therapeutic class of erythropoiesis stimulating agents (ESAs) due to its implication in the creation pathway of red blood cells and thus enhancement of oxygenation. Because of this bioactivity, rHuEPO has been considered as a major doping agent in sports competitions for decades. Over the years, doping control laboratories designed several analytical strategies applied to human and animal samples to highlight any misuse. Even though multiple analytical approaches have been reported, none has yet been dedicated to racing camels. Here, we describe an analytical strategy to test camel plasma samples at screening using an ELISA assay and a targeted nano-liquid chromatography-high-resolution tandem mass spectrometry for confirmatory analysis. The method was validated and has been successfully applied to post-race samples, allowing the detection of a positive case of rHuEPO administration.

With recent advances in analytical chemistry, liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) has become an essential tool for metabolite discovery and detection. Even if most of the common drug transformations have already been extensively described, manual search of drug metabolites in LC-HRMS/MS datasets is still a common practice in toxicology laboratories, complicating metabolite discovery. Furthermore, the availability of free open-source software for metabolite discovery is still limited. In this article, we present MetIDfyR, an open-source and cross-platform R package for in silico drug phase I/II biotransformation prediction and mass-spectrometric data mining. MetIDfyR has proven its efficacy for advanced metabolite identification in semi-complex and complex mixtures in in vitro or in vivo drug studies and is freely available at github.com/agnesblch/MetIDfyR.

After administration to humans or animals, small-molecule drugs most frequently undergo several biochemical transformations by the endogenous enzymatic machinery, called phase I and phase II metabolism. These molecular processes allow organisms to eliminate xenobiotics through modification of their chemical properties and generate metabolites. With recent advances in analytical chemistry, LC-HRMS/MS has become an essential tool for metabolite discovery and detection. Even if most common drug transformations have already been extensively described, manual search of drug metabolites in LC-HRMS/MS datasets is still a common practice in toxicology laboratories, disabling efficient metabolite discovery. Furthermore, the availability of free open-source software for metabolite discovery is still limited. In this article, we present MetIDfyR, an open-source and cross-platform R package for in-silico drug phase I/II biotransformations prediction and mass-spectrometric data mining. MetIDfyR has proven efficacy for advanced metabolite identification in semi-complex and complex mixtures in in-vitro or in-vivo drug studies and is freely available at https://github.com/agnesblch/MetIDfyR.

Recent court rulings effectively barred Argentina from international capital markets until she honored previous sovereign debt contracts. These rulings have been criticized by some in the legal community for possibly harming New York’s standing as a preeminent capital market and hindering developing countries’ ability to borrow. This article asks whether such criticism is warranted and notes that a similar enforcement mechanism was employed by the London Stock Exchange before World War I to deny sovereign borrowers in breach of their contracts access to international capital markets.The pre-World War I era provides us with clues into how the sovereign debt market could evolve in the wake of the Argentina rulings. In contrast to the dire warnings, capital markets have historically worked well when sovereign borrowers face sanctions. The existence of sanctions gave sovereign borrowers the means to credibly signal their intent to repay. By including contract clauses that made default costly, historical sovereign borrowers of less than pristine reputation were able to signal their good intentions and enjoy the benefits of cheap access to world capital markets.

Governments often attempt to increase the confidence of financial market participants by making implicit or explicit guarantees of uncertain credibility. Confidence in these guarantees presumably alters the size of the financial sector, but observing the long-run consequences of failed guarantees is difficult in the modern era. We look to America’s free-banking era and compare the consequences of a broken guarantee during the Indiana-centered Panic of 1854 to the Panic of 1857 in which guarantees were honored. Our estimates of a model of endogenous market structure indicate substantial negative long-run consequences to financial depth when panics cast doubt upon a government’s ability to honor its guarantees.

Contracts among sophisticated players, students in a basic contract law class are taught, are carefully vetted by the parties and their lawyers and the terms and conditions are understood clearly by everyone. Under such conditions, theory tells us, courts should err on the side of doing what the parties, through the explicit terms of their contracts, say what their deal is. After all, these are sophisticated parties who know what deal is best for them. What one does not expect to see in the world of sophisticated high finance are contract terms that parties across an entire industry use and have been using for over a hundred years yet neither party seems to understand. One would think, after all, that after repeated use for over a century, contract terms would become better and better understood. That then brings us to the story of the pari passu clause in sovereign debt instruments. This little clause, generally no more than a couple of lines long and sporting a bit of latin finery, has become perhaps the most controversial and well-known clause in international finance, while at the same time also being the least understood. The clause has been Key points

We argue that evolutionary and ecological models of territorial behavior are useful to archaeologists holding varied theoretical positions. First, we explain how evolutionary and ecological approaches complement, rather than conflict with, social agency and historicist approaches. Second, we review and expand upon models from evolutionary ecology and their application to the ethnographic and archaeological records. This review reveals that territorial behavior spans a continuum from defense of selected resources, to control of “home ranges” or spheres of influence, to complete defense of a proscribed geographic area. Third, we emphasize that archaeologists and modelers should explicitly define the demographic scale of territorial behavior under consideration, given that resource defense by large groups requires solutions to collective action problems. Finally, we suggest that the economic defensibility logic underlying ecological models of territoriality applies to any resource type, not just territory. Furthermore, social and political power often require successfully defending spatial territory. [evolutionary ecology, economic defensibility, territoriality, human behavioral variation, archaeology]

Men's hunting has dominated the discourse on energy capture and flow in the past decade or so. We turn to women's roles as critical to household formation, pair-bonding, and intergenerational bonds. Their pivotal contributions in food processing and distribution likely promoted kinship, both genetic and affinal, and appear to be the foundation from which households evolved. With conscious recognition of household social units, variable cultural constructions of human kinship systems that were sensitive to environmental and technological conditions could emerge. Kinship dramatically altered the organization of resource access for our species, creating what we term "kinship ecologies." We present simple mathematical models to show how hunting leads to dependence on women's contributions, bonds men to women, and bonds generations together. Kinship, as it organized transfers of food and labor energy centered on women, also became integrated with the biological evolution of human reproduction and life history.

A commonly cited benefit of the classical gold standard is that it reduced borrowing costs by signaling a country's commitment to financial probity. Using a new dataset, this paper tests whether gold-standard adherence was negatively correlated with the cost of capital. Conditional on UK risk factors, there is no evidence that the bonds issued by countries off gold earned systematically higher excess returns than the bonds issued by countries on gold. This conclusion is robust to allowing betas to differ across exchange-rate regimes; to including other determinants of the country risk premium; and to controlling for the British Empire effect.

Why did Victorian Britain send so much capital abroad? We collect over 500,000 monthly British and foreign security returns between 1866 and 1907 and investigate the effect of international diversification on Victorian investors’ portfolios. This is the first study to use nineteenth-century data that is both broad enough and sampled at a high enough frequency to examine if foreign assets expanded the mean-variance efficient frontier of British investors and how valuable this expansion was in terms of utility. We find that foreign assets significantly expanded the mean-variance frontier and resulted in utility gains equivalent to large increases in wealth.

We combine self-collected historical data from 1867 to 1907 with CRSP data from 1926 to 2012, to examine the risk and return over the past 140 years of one of the most popular mechanical trading strategies — momentum. We find that momentum has earned abnormally high risk-adjusted returns — a three factor alpha of 1 percent per month between 1927 and 2012 and 0.5 percent per month between 1867 and 1907 — both statistically significantly different from zero. However, the momentum strategy also exposed investors to large losses (crashes) during both periods. Momentum crashes were predictable — more likely when momentum recently performed well (both eras), interest rates were relatively low (1867–1907), or momentum had recently outperformed the stock market (CRSP era) — times when borrowing or attracting return chasing “blind capital” would have been easier. Based on a stylized model and simulated outcomes from a richer model, we argue that a money manager has an incentive to remain invested in momentum even when the crash risk is known to be high when (1) he competes for funds from return-chasing investors and (2) he is compensated via fees that are convex in the amount of money managed and the return on that money.

communication par affiche; International audience

On July 18, 2013, Detroit became the largest municipality to seek protection under Chapter 9 of the U.S. Bankruptcy Code. This article describes several ways in which Detroit’s bankruptcy filing has the potential to alter some of the key assumptions of municipal bond (muni) finance, and examines the market reaction to date.

Late 19th century investors demanded compensation to invest in countries with poor institutional protection of property rights. Using the monthly stock returns of 1,808 firms located in 43 countries but traded in London between 1866 and 1907, we estimate the country-specific cost of capital. We find a negative relationship between institutions that protect property rights and capital costs. Firms located in countries with weak institutions were charged a premium compared to similarly risky firms located in countries with strong institutions, and this penalty appeared to be costly in terms of future growth. Countries that paid a premium for borrowing in London during this period grew more slowly after 1913 and are poorer today. We thus identify the capital market as a channel through which strong institutions promote growth.

How costly were the banking panics of the National Banking Era (1861-1913)? I combine two hand-collected data sets - the weekly statements of the New York Clearing House banks and the monthly holding period return of every stock listed on the NYSE - to estimate the cost of banking panics in an era before “too big to fail.” The bank statements allow me to construct a hypothetical insurance contract which would have allowed investors to insure against sudden deposit withdrawals and the cross-section of stock returns allow us to draw inferences about the marginal utility during panic states. Panics were costly. The cross-section of gilded-age stock returns imply investors would have willingly paid a 14% annual premium above actuarial fair value to insure $100 against unexpected deposit withdrawals The implied consumption of stock investors suggests that the consumption loss associated with National Banking Era bank runs was far more costly than the consumption loss from stock market crashes.

A commonly cited benefit of the pre‐World War One gold standard is that it reduced the cost of international borrowing by signaling a country’s commitment to financial probity. Using a newly constructed data set that consists of more than 55,000 monthly sovereign bond returns, we test if gold‐standard adherence was negatively correlated with the cost of capital. Conditional on UK risk factors, we find no evidence that the bonds issued by countries off gold earned systematically higher excess returns than the bonds issued by countries on gold. Our results are robust to allowing betas to differ across bonds issued by countries off‐ and on‐gold; to including proxies that capture the effect of fiscal, monetary, and trade shocks on the commitment to gold; and to controlling for the effect of membership in the British Empire.

We evaluate the importance of “Limits to Arbitrage” to explain profitability of momentum strategies. Specifically, when the availability of arbitrage capital is in short supply, momentum cycles last longer, and breaks in momentum cycles are shorter. We demonstrate the robustness of our findings with a unique database of stock returns from 1866-1907 London and the CRSP database. Momentum cycle durations are similar in both databases and all other momentum facts documented in the literature using the CRSP database hold for the Victorian period as well, except for the January reversal due to the absence of capital gains taxation.

We evaluate the importance of "Limits to Arbitrage" to explain profitability of momentum strategies. Specifically, when the availability of arbitrage capital is in short supply, momentum cycles last longer, and breaks in momentum cycles are shorter. We demonstrate the robustness of our findings with a unique database of stock returns from1866-1907 London and the CRSP database. Momentum cycle durations are similar in both databases and all other momentum facts documented in the literature using the CRSP database hold for the Victorian period as well, except for the January reversal due to the absence of capital gains taxation.

Why did Victorian Britain invest so much capital abroad? We collect over 500,000 monthly returns of British and foreign securities trading in London and the United States between 1866 and 1907. These heretofore-unknown data allow us to better quantify the historical benefits of international diversification and revisit the question of whether British Victorian investor bias starved new domestic industries of capital. We find no evidence of bias. A British investor who increased his investment in new British industry at the expense of foreign diversification would have been worse off. The addition of foreign assets significantly expanded the mean-variance frontier and resulted in utility gains equivalent to a meaningful increase in lifetime consumption.

We find that price momentum in stocks was a pervasive phenomenon during the Victorian age (1866-1907) as well. Momentum strategy profits have little systematic risk even at business cycle frequencies; disappear periodically only to reappear later; exhibit long run reversal; and are higher following up markets, suggesting limited availability of arbitrage capital relative to opportunities during those times. Since there were no capital gains taxes during the Victorian age, the long run reversal of momentum profits must have a fundamental component, that is unrelated to tax based trading, identified by Grinblatt and Moskowitz (2004) using CRSP era data.

We find that price momentum in stocks was a pervasive phenomenon during the Victorian age (1866-1907) as well. Momentum strategy profits have little systematic risk even at business cycle frequencies; disappear periodically only to reappear later; exhibit long run reversal; and are higher following up markets, suggesting limited availability of arbitrage capital relative to opportunities during those times. Since there were no capital gains taxes during the Victorian age, the long run reversal of momentum profits must have a fundamental component, that is unrelated to tax based trading, identified by Grinblatt and Moskowitz (2004) using CRSP era data.

In this enjoyable work, Kenneth Lipartito and Carol Peters share with us the story of John Elliot Tappan, a Minneapolis lawyer who brought financial innovation to the American heartland. In an era before mutual funds, money market accounts, and in many locations safe diversified savings banks, Tappan saw the need for a safe, small denomination, financial instrument for middle-class savers. The result was Investors Syndicate and its “face-value” certificate, a combination of zero-coupon bond and term life insurance that savers of modest means could purchase in small installments. By providing the small investor with a safe means of saving a small amount each month, Investors Syndicate (latter IDS and American Express Financial Advisors) would grow into one of the nations financial behemoths. Along the way, Tappan and his company would overcome financial panic, depression, war, epidemic, and corrupt postal inspectors (the federal regulators of the day).