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Background: Ancestry is often viewed as a more objective and less objectionable population descriptor than race or ethnicity. Perhaps reflecting this, usage of the term “ancestry” is rapidly growing in genetics research, with ancestry groups referenced in many situations. The appropriate usage of population descriptors in genetics research is an ongoing source of debate. Sound normative guidance should rest on an empirical understanding of current usage; in the case of ancestry, questions about how researchers use the concept, and what they mean by it, remain unanswered.Methods: Systematic literature analysis of 205 articles at least tangentially related to human health from diverse disciplines that use the concept of ancestry, and semi-structured interviews with 44 lead authors of some of those articles.Results: Ancestry is relied on to structure research questions and key methodological approaches. Yet researchers struggle to define it, and/or offer diverse definitions. For some ancestry is a genetic concept, but for many—including geneticists—ancestry is only tangentially related to genetics. For some interviewees, ancestry is explicitly equated to ethnicity; for others it is explicitly distanced from it. Ancestry is operationalized using multiple data types (including genetic variation and self-reported identities), though for a large fraction of articles (26%) it is impossible to tell which data types were used. Across the literature and interviews there is no consistent understanding of how ancestry relates to genetic concepts (including genetic ancestry and population structure), nor how these genetic concepts relate to each other. Beyond this conceptual confusion, practices related to summarizing patterns of genetic variation often rest on uninterrogated conventions. Continental labels are by far the most common type of label applied to ancestry groups. We observed many instances of slippage between reference to ancestry groups and racial groups.Conclusion: Ancestry is in practice a highly ambiguous concept, and far from an objective counterpart to race or ethnicity. It is not uniquely a “biological” construct, and it does not represent a “safe haven” for researchers seeking to avoid evoking race or ethnicity in their work. Distinguishing genetic ancestry from ancestry more broadly will be a necessary part of providing conceptual clarity.

Cervical cancer screening is as important in female-to-male transgender (FTMT) patients as it is in cisgender female patients. The aim of this study was to examine the impact of clinical information regarding gender identity and testosterone therapy on the cytological interpretations.A list of FTMT patients and cisgender female patients who had received a cervical Papanicolaou (Pap) test for cancer screening was obtained. The cytological diagnoses, rendered at the time of collection, were recorded. A retrospective slide review with knowledge of the pertinent clinical information, including testosterone therapy status, was performed. The data sets were statistically compared.Of 122 cervical Pap tests in 111 FTMT individuals, 23 (19%) had surgical follow-ups; 73 (60%) had HPV testing, of which 12 (16%) were positive for high-risk strains; and 79 (65%) were known to be receiving testosterone. On the "original" review, 12 (9.8%) tests were diagnosed as unsatisfactory. Seventy-one (58%) Pap tests were initially diagnosed as negative for intraepithelial lesion or malignancy (NILM) without atrophy and 32 (26%) with atrophy. Seven (5.7%) of the tests were initially diagnosed as abnormal. On the "retrospective" review, the rate of unsatisfactory tests remained the same, and atrophy was observed in 76 (62%) tests. The number of abnormal tests was reduced to 4 (3.3%) after the retrospective review. Almost all comparative studies returned a P-value of ≤0.05.Our findings indicate that clinical information regarding whether a subject is transgender and/or is receiving testosterone therapy is crucial to avoiding Pap test overcalls.

We demonstrate that a neural network pre-trained on text and fine-tuned on code solves mathematics course problems, explains solutions, and generates new questions at a human level. We automatically synthesize programs using few-shot learning and OpenAI's Codex transformer and execute them to solve course problems at 81% automatic accuracy. We curate a new dataset of questions from MIT's largest mathematics courses (Single Variable and Multivariable Calculus, Differential Equations, Introduction to Probability and Statistics, Linear Algebra, and Mathematics for Computer Science) and Columbia University's Computational Linear Algebra. We solve questions from a MATH dataset (on Prealgebra, Algebra, Counting and Probability, Intermediate Algebra, Number Theory, and Precalculus), the latest benchmark of advanced mathematics problems designed to assess mathematical reasoning. We randomly sample questions and generate solutions with multiple modalities, including numbers, equations, and plots. The latest GPT-3 language model pre-trained on text automatically solves only 18.8% of these university questions using zero-shot learning and 30.8% using few-shot learning and the most recent chain of thought prompting. In contrast, program synthesis with few-shot learning using Codex fine-tuned on code generates programs that automatically solve 81% of these questions. Our approach improves the previous state-of-the-art automatic solution accuracy on the benchmark topics from 8.8% to 81.1%. We perform a survey to evaluate the quality and difficulty of generated questions. This work is the first to automatically solve university-level mathematics course questions at a human level and the first work to explain and generate university-level mathematics course questions at scale, a milestone for higher education., Comment: 181 pages, 8 figures, 280 tables

It is often believed that for open source software (OSS) projects the faster the release, the better for attracting user interest in the software. Whether this is true, however, is still open to question. There is considerable information asymmetry between OSS projects and potential users as project quality is unobservable to users. We suggest that innovation speed of OSS project can signal the unobservable project quality and attract users’ interest in downloading and using the software. We contextualize innovation speed of OSS projects as initial release speed and update speed and examine their impacts on user interest. Drawing on the signaling theory, we propose a signaling effect through which a higher initial release speed or update speed increases user interest, while the effect diminishes as initial release or update speed increases. Using a large-scale panel data set from 7442 OSS projects on SourceForge between 2007 and 2010, our results corroborate the inverted U-shaped relationships between initial release speed and user downloads and between update speed and user downloads.

Where does lyric significance happen? With recent interdisciplinary studies from the fields of aesthetics and neuroscience offering support to Emmanuel Levinas’s idea of proximity, I propose that proximity is the maternal body of lyrical meaning. In this paper, I will illustrate the case by unpacking the mental processing of the lyrical imageries in Song 2:10–13, and highlight two aspects of proximity along the way. First, the perception of lyrical imagery is more complex than a representational correspondence between the word and the world. It covers the stages from the verbal cues to multisensory imageries, to evoked synaesthetic experiences, to accompanied feelings and provoked actions. Cognitively it is best described as one’s approximation toward the core semantic sense of the verbal cues, which is diversified by the reader’s embodied minds. Second, at the root of the aesthetic experience is one’s sense of self, which is susceptible to the intrigue of alterity. One’s reception of lyrical imageries in Song 2:10–13 can be characterized as an over-abundant synaesthetic experience. It directs one’s attention to an anterior receptivity embedded in subjectivity by way of the excess of the sensing over the semantic, and the sensed over the sensing. This reduction to the baseline level of function, or the sheer sensation of oneself, beckons the lyrical subject to become aware of one’s a prior proximity to alterity. In brief, while the readers’ individualized approximations preclude a verifiable universal reception, they do not warrant the kind of hermeneutic violence that overrides the text with the readers’ contexts. Rather, by being awakened to one’s susceptibility to the otherness of the poem, the lyrical subject realizes that proximity is the ethical precondition in making sense of the poem and oneself.

Pathology is practiced by visual inspection of histochemically stained tissue slides. While the hematoxylin and eosin (H&E) stain is most commonly used, special stains can provide additional contrast to different tissue components. Here, we demonstrate the utility of supervised learning-based computational stain transformation from H&E to special stains (Masson’s Trichrome, periodic acid-Schiff and Jones silver stain) using kidney needle core biopsy tissue sections. Based on the evaluation by three renal pathologists, followed by adjudication by a fourth pathologist, we show that the generation of virtual special stains from existing H&E images improves the diagnosis of several non-neoplastic kidney diseases, sampled from 58 unique subjects (P = 0.0095). A second study found that the quality of the computationally generated special stains was statistically equivalent to those which were histochemically stained. This stain-to-stain transformation framework can improve preliminary diagnoses when additional special stains are needed, also providing significant savings in time and cost., Performing multiple histological stains on a biopsy can be costly and time consuming. Here the authors present a method for the digital transformation of H&E stained tissue into special stains (e.g., PAS, Masson’s Trichrome and Jones silver stain), and demonstrate that it improves diagnoses over the use of H&E only.

The use of legal technology (legal tech) and the lawtech ecosystem of legal start-ups has experienced tremendous growth in recent years. To provide a structured approach of analysing IT innovations in the legal sector, we propose a framework for lawtech applications, classifying them into three groups: internal, B2C and B2B applications. In the context of this framework, we examine technological trends in lawtech and their potential to support and transform processes in specific areas of business or personal law. We acknowledge that within lawtech there is a gap between the areas of interest of legal practitioners, IT professionals and academic researchers, and that some areas have received considerable attention by these groups, while other areas have been left relatively unexplored by one or more of these groups. However, the growing interest by legal practitioners in advanced technology such as artificial intelligence (AI) and natural language processing (NLP) is further closing the gap between academic research, IT professionals and legal practice.

Air pollution is one of the world’s largest environmental health threats. This study aims to use simple remote signals to locate the source of a pollution release, which will significantly enhance our readiness to counter its threat. In urban areas, the flow structures advecting the pollution are extremely complex: boundary layer separation generates vortical structures that increase the spread of pollutants and break the plume into smaller patches by dispersion effect. Furthermore, the blocking and mixing in urban areas make it more obscured to locate the pollution sources. Flow structures were obtained by solving the two-dimensional NavierStokes equations using Computational Fluid Dynamics in a simplified scenario with imaginary urban architectures. We applied the canonical neural network to relate characteristics in the remote pollutant detector signals to the actual location of the pollutant release. The proposed algorithm identifies the source location and its uncertainty through a Monte Carlo analysis. When the number of training samples is small, as limited by the number of trial-releases we can perform in reality, data augmentation is done by introducing noisy measurement as new training samples. While the source localization is reasonable in the cross-flow direction, it is much harder to locate the streamwise location of the source due to signal similarity. The data augmentation technique we applied reduced the uncertainty of the source location by introducing under-fitting phenomena into the model. Furthermore, sensors away from the center line of the flow outperforms the ones near the center line, especially for detecting off-center sources. This indicates a pronounced effect of blocking and mixing right behind the building on the center line, which blurs sensor measurements from different source locations, and thus hinders the ability to trace back to the source.

By using hydrogen quench continuous annealing technology, Stelco Inc. has developed a suite of Advanced High Strength Steel (AHSS) grades with tensile strength greater than 1000MPa to meet standard automotive specifications and for unique customer requirements. These grades were optimized by correlating chemical composition and processing parameters with microstructures and mechanical properties. Dual-Phase 980 (Stelco trademarked STELMAXTM 980DP), Multi-Phase 1180 (STELMAXTM 1180MP), Martensitic Steel 1300 (STELMAXTM 1300M) and 1500 (STELMAXTM 1500M) products met strength and formability requirements with excellent flatness and surface quality. Hydrogen quench continuous annealing technology not only ensures all developed AHSS grades have consistent mechanical properties across the entire strip length (from strip head to tail) and width (from edge to edge), but also produces high product yield compared with other continuous annealing processes.

Register of Chinese Immigrants to Canada, 1886-1949 is a historical dataset openly available to the public. Drawing on the previous studies based on the data and employing computational tools, this study aims to lower the barriers to the data use, as well as to reveal substantive potential of the data that has not been leveraged by scholars.

We use high frequency intra-day data to investigate the influence of unscheduled currency and Bitcoin news on the returns, volume and volatility of the cryptocurrency Bitcoin and traditional currencies over the period from January 2012 to November 2018. Results show that Bitcoin behaves differently to traditional currencies. Traditional currencies typically experience a decrease in returns after negative news arrivals and an increase in returns following positive news whereas Bitcoin reacts positively to both positive and negative news. This suggests investor enthusiasm for Bitcoin irrespective of the sentiment of the news. This phenomenon is exacerbated during bubble periods. Conversely, cryptocurrency cyber-attack news and fraud news dampen this effect, decreasing Bitcoin returns and volatility. Our results contribute to the discussion on the nature of Bitcoin as a currency or an asset. They further inform practitioners about the characteristics of cryptocurrencies as a financial asset and inform regulators about the influence of news on Bitcoin volatility, particularly during bubble periods.

Using NASDAQ trade and Reuters news data, I show that the response of aggressive non‐high‐frequency traders (nHFTs) to news is stronger than that of aggressive high‐frequency traders (HFTs). Classifying news into quantitative (“hard”) and less quantitative (“softer”) news, the trading response of aggressive nHFTs to softer news exceeds HFTs’ response. Positive news elicits greater return and nHFT responses than negative news during the 2008 financial crisis period. As this phenomenon persists even after excluding the 2008 short‐sale ban, the results support the hypothesis of nHFTs exhibiting stronger asymmetric responses during crisis periods.

Stelco has developed a suite of Advanced High-Strength Steels (AHSS) grades with tensile strength greater than 1000 MPa to meet standard automotive specifications and for unique customer requirements. These grades were optimized by correlating chemical composition and processing parameters with microstructures and mechanical properties. Dual-Phase 980 (Stelco trademarked STELMAXTM980DP), Multiphase 1180 (STELMAXTM1180MP), Martensitic 1300 (STELMAXTM1300M) and 1500 (STELMAXTM1500M) products met strength and formability requirements with excellent flatness and consistent mechanical properties across the entire strip length and width by using hydrogen quench continuous annealing technology.

Organisms use various strategies to cope with fluctuating environmental conditions. In diversified bet-hedging, a single genotype exhibits phenotypic heterogeneity with the expectation that some individuals will survive transient selective pressures. To date, empirical evidence for bet-hedging is scarce. Here, we observe that individual Drosophila melanogaster flies exhibit striking variation in light- and temperature-preference behaviors. With a modeling approach that combines real world weather and climate data to simulate temperature preference-dependent survival and reproduction, we find that a bet-hedging strategy may underlie the observed interindividual behavioral diversity. Specifically, bet-hedging outcompetes strategies in which individual thermal preferences are heritable. Animals employing bet-hedging refrain from adapting to the coolness of spring with increased warm-seeking that inevitably becomes counterproductive in the hot summer. This strategy is particularly valuable when mean seasonal temperatures are typical, or when there is considerable fluctuation in temperature within the season. The model predicts, and we experimentally verify, that the behaviors of individual flies are not heritable. Finally, we model the effects of historical weather data, climate change, and geographic seasonal variation on the optimal strategies underlying behavioral variation between individuals, characterizing the regimes in which bet-hedging is advantageous.

Klotho plays an important role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Klotho is highly expressed in the kidney and parathyroid glands, but its presence in the vasculature is debated. Renal Klotho is decreased in CKD, but the effect of uremia on Klotho in other tissues is not defined. The effect of vitamin D receptor activator therapy in CKD on the expression of Klotho in various tissues is also in debate. In uremic rats (surgical 5/6th nephrectomy model), we compared 3 months of treatment with and without paricalcitol on Klotho immunostaining in the kidney, parathyroid glands, and aorta. With uremia, Klotho was unchanged in the parathyroid, significantly decreased in the kidney (66%) and the intimal-medial area of the aorta (69%), and significantly increased in the adventitial area of the aorta (67%) compared with controls. Paricalcitol prevented the decrease of Klotho in the kidney, increased expression in the parathyroid (31%), had no effect in the aortic media, but blunted the increase of Klotho in the aortic adventitia. We propose that fibroblasts are responsible for the expression of Klotho in the adventitia. In hyperplastic human parathyroid tissue from uremic patients, Klotho was higher in oxyphil compared with chief cells. Thus, under our conditions of moderate CKD and mild-to-moderate hyperphosphatemia in rats, the differential expression of Klotho and its regulation by paricalcitol in uremia is tissue-dependent.

I study the role of high-frequency traders (HFTs) and non-high-frequency traders (nHFTs) in transmitting hard price information from the futures market to the stock market using an index arbitrage strategy. Using intraday transaction data with HFT identification, I find that HFTs process hard information faster and trade on it more aggressively than nHFTs. In terms of liquidity supply, HFTs are better at avoiding adverse selection than nHFTs. Consequently, HFTs enhance the linkage between the futures and stock markets, and significantly contribute to information efficiency in the stock market by reducing the delay between the stock and the futures markets.

The role of hyperphosphatemia in the pathogenesis of secondary hyperparathyroidism, cardiovascular disease, and progression of renal failure is widely known. Here we studied effects of dietary phosphate restriction on mortality and vascular calcification in uremic rats. Control and uremic rats were fed a high-phosphate diet and at 3 months a portion of rats of each group were killed. Serum phosphate and the calcium phosphate product increased in uremic rats, as did aortic calcium. Of the rats, 56% had positive aortic staining for calcium (von Kossa), RUNX2, and osteopontin. The remaining uremic rats were continued on diets containing high phosphate without and with sevelamer, or low phosphate, and after 3 more months they were killed. Serum phosphate was highest in uremic rats on high phosphate. Serum PTH and FGF-23 were markedly lower in rats on low phosphate. Mortality on high phosphate was 71.4%, with sevelamer reducing this to 37.5% and phosphate restriction to 5.9%. Positive aortic staining for von Kossa, RUNX2, and osteopontin was increased, but phosphate restriction inhibited this. Kidneys from low-phosphate and sevelamer-treated uremic rats had less interstitial fibrosis, glomerulosclerosis, and inflammation than those of uremic rats on high phosphate. Importantly, kidneys from rats on low phosphate showed improvement over kidneys from high-phosphate rats at 3 months. Left ventricles from rats on low phosphate had less perivascular fibrosis and smaller cardiomyocyte size compared to rats on high phosphate. Thus, intensive phosphate restriction significantly reduces mortality in uremic rats with severe vascular calcification.

Objectives/Hypothesis To examine the sinus-related sequelae of free flap reconstruction for complex orbitofacial defects. Study Design Retrospective chart review. Methods Demographic, clinical, and radiographic data on a series of 55 patients who had undergone free tissue transfer for orbitofacial reconstruction was retrospectively reviewed. Follow-up of ≥ 3 months was available for 49 patients. Outcome measures studied included clinical or radiographic evidence of sinusitis and the need for sinus surgery. Results The most commonly involved sinuses were the ethmoid (n = 40) and maxillary (n = 38) sinuses, and the anterolateral thigh was the most common flap used (n = 41). Clinical and/or radiographic sinusitis was evident in 21 patients (43%), and 10 patients (20%) required sinus surgery at some point during follow-up. Involvement of multiple sinuses in the initial orbitofacial surgery was associated with a significantly increased need for subsequent sinus surgery (P = 0.009). Adjuvant radiotherapy and adjuvant chemoradiotherapy were associated with a significantly increased risk for the development of rhinosinusitis (P = 0.045 and 0.016, respectively). Conclusion Rhinosinusitis and the need for operative management of sinus obstruction are common in patients having undergone complex orbitofacial reconstruction. Careful management of the paranasal sinuses is an important component of the multidisciplinary treatment of such patients. Level of Evidence 4. Laryngoscope, 124:1059–1065, 2014

Background Recurrence of pancreatic adenocarcinoma after pancreaticoduodenectomy (PD) can be increased in patients with pancreatic fistula (PF). The purpose of our study was to determine if a relationship exists between PF and tumor recurrence (both peritoneal and local) in patients after PD for pancreatic ductal adenocarcinoma. Study Design A single-institution, retrospective analysis of 221 patients who underwent PD from January 2001 to December 2009 was conducted. Electronic charts and medical records were queried for tumor characteristics, recurrence, and complications. Presence and grading of PF was determined using the criteria of the International Study Group on Pancreatic Fistula. Data were analyzed using chi-square and Kaplan-Meier survival statistics. Results There were 114 male and 107 female patients. Mean age was 66 years (range 35 to 91 years). The vast majority (84%) of patients had stage II disease; 143 (65%) had positive lymph nodes (median 2 positive nodes; range 1 to 17 positive nodes). Pancreatic fistula developed in 23 patients (grade A, n = 9; grade B, n = 13; grade C, n = 1; 10.2%). Peritoneal recurrence was noted in 20 patients (9%). Of the 23 patients with PF, peritoneal recurrence developed in 3 (13%). Of the 198 patients without PF, peritoneal recurrence developed in 17 (10%). Local recurrence occurred in 47 patients (21%), 5 (2%) in patients with PF and 42 (21%) in those without PF (p = NS). In Kaplan-Meier survival analysis, there was no significant difference in recurrence-free survival (p = 0.4) and overall survival (p = 0.3) for those with PF vs those without PF. Conclusions Patients with PF after PD were not found to have a significant increase in local or peritoneal recurrence. Therefore, in this analysis, postoperative PF does not appear to serve as an adverse prognostic marker.

The results of catalytic treatment of vapors exiting a g/min pyrolysis unit before product condensation to the liquid phase using a Ru/TiO2 catalyst for oak and switchgrass pyrolysis are reported. The pyrolysis is conducted at 500°C and the catalysis at 400°C at atmospheric pressure with a hydrogen partial pressure of 0.58 atm. It is found that the catalytic treatment provides significant conversion of light oxygenates to larger, less oxygenated, molecules and, simultaneously, bio-oil phenolics are also converted to less oxygenated phenolics with methoxy methyl groups transferred to the ring. The activity of the catalyst gradually diminished with increasing biomass fed to the system. Untreated pyrolysis oil forms a single liquid phase with some tarry material, consistent with the literature, whereas the treated liquid product forms separate oil and aqueous phases, the latter of which is about 80% water. The oil from the treated vapors has a lower initial viscosity with only a small increase upon accelerated aging compared to the untreated product oil, which has a dramatic increase in viscosity after aging. This is indicative of poor oil stability for untreated oil that is further confirmed by large increases in molecular weight, while the treated oil has a small increase in molecular weight after accelerated aging. In an effort to understand compatibility with refinery streams, the solubility of the oils in tetralin was examined. The untreated oil was found to have very limited solubility in tetralin, whereas the treated oil phase was completely soluble except for a small aqueous phase that appeared. There are a number of challenges in developing a high yield process for pyrolysis based conversion of biomass to transportation fuels. The Ru/TiO2 catalyst used here shows promise for conducting multiple types of favorable reactions in the presence of the full spectrum of primary pyrolysis products that creates significant product stability under mild conditions. This could lead to higher liquid yields of stable, refinery compatible, product oil. © 2013 American Institute of Chemical Engineers AIChE J, 59: 2275–2285, 2013

Embedded and co-cured composite damping structure is a novel damping processing structure, which possesses excellent damping properties and mechanical performances. In this paper, explicit dynamic analysis software LS-DYNA is employed to simulate low velocity impact on embedded co-cured composite damping structure panels. To illustrate the validity of modeling and calculation method, the simulation results are compared with the experimental data. And the results show that the impact resistance of embedded co-cured composite damping structure is much better than composite panel without damping material.

Transient receptor potential (TRP) channels are nonselective cation channels, several of which are expressed in striated muscle. Because the scaffolding protein Homer 1 has been implicated in TRP channel regulation, we hypothesized that Homer proteins play a significant role in skeletal muscle function. Mice lacking Homer 1 exhibited a myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. Homer 1 knockout myotubes displayed increased basal current density and spontaneous cation influx. This spontaneous cation influx in Homer 1 knockout myotubes was blocked by reexpression of Homer 1b, but not Homer 1a, and by gene silencing of TRPC1. Moreover, diminished Homer 1 expression in mouse models of Duchenne's muscular dystrophy suggests that loss of Homer 1 scaffolding of TRP channels may contribute to the increased stretch-activated channel activity observed in mdx myofibers. These findings provide direct evidence that Homer 1 functions as an important scaffold for TRP channels and regulates mechanotransduction in skeletal muscle.

Organisms use various strategies to cope with fluctuating environmental conditions. In diversified bet-hedging, a single genotype exhibits phenotypic heterogeneity with the expectation that some individuals will survive transient selective pressures. To date, empirical evidence for bet-hedging is scarce. Here, we observe that individual Drosophila melanogaster flies exhibit striking variation in light- and temperature-preference behaviors. With a modeling approach that combines real world weather and climate data to simulate temperature preference-dependent survival and reproduction, we find that a bet-hedging strategy may underlie the observed inter-individual behavioral diversity. Specifically, bet-hedging outcompetes strategies in which individual thermal preferences are heritable. Animals employing bet-hedging refrain from adapting to the coolness of spring with increased warm-seeking that inevitably becomes counterproductive in the hot summer. This strategy is particularly valuable when mean seasonal temperatures are typical, or when there is considerable fluctuation in temperature within the season. The model predicts, and we experimentally verify, that the behaviors of individual flies are not heritable. Finally, we model the effects of historical weather data, climate change, and geographic seasonal variation on the optimal strategies underlying behavioral variation between individuals, characterizing the regimes in which bet-hedging is advantageous.

Treatment halts recurrence of Clostridium difficile bacteria, but a commercial pill is still far off.