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In the domain of scratch card gambling, "pushes" refer to outcomes in which a prize is won that is equal to the cost of a scratch card game. Despite resulting in no net monetary gain, these outcomes are categorized as wins by lottery operators, effectively inflating published scratch card information (e.g., posted odds of winning). Additionally, the experience of obtaining a push shares similarities (e.g., the revealing of matching symbols) with the experience of obtaining a win and thus may be experienced similarly to wins by gamblers. Across four studies (N = 1502), we examined the impact of push outcomes on participants' perceptions of scratch card games. In Studies 1 and 2, participants reported feeling more likely to win, more excitement to play, and a stronger urge to gamble when presented with a scratch card that categorized push outcomes as wins compared to when presented a scratch card that did not categorize these outcomes as wins. In Study 3, participants experiencing a push outcome prior to a loss reported feeling more likely to win compared to those not experiencing a push outcome yet experiencing the same net monetary loss. In Study 4, push outcomes were found to elicit more excitement and a stronger urge to gamble compared to losses but less excitement and a weaker urge to gamble compared to wins. Overall, the present investigation suggests that push outcomes, a prevalent feature of scratch card games, can bias gambling-related judgments and increase the appeal of scratch card games. [ABSTRACT FROM AUTHOR]

Past work has demonstrated that presenting statistical information in a foreground–background icon array can improve risk understanding, reduce decision-making biases, and decrease the salience of low-probability risks. In the present study, we assess whether presenting readily available gambling information within a foreground–background icon array influences individuals' gambling-related judgments (e.g., their perceived likelihood of winning a prize). Across two experiments (N = 1151), we find that using icon arrays to present gambling information reduces the appeal of scratch card games. That is, participants presented with gambling information in a foreground–background icon array, as opposed to a non-graphical numerical format, reported feeling less likely to win a prize, less excitement to play, and less urge to gamble on a scratch card game presented in a hypothetical gambling task. Overall, we conclude that presenting gambling information in an icon array format represents a simple yet promising tool for correcting gamblers' often overly-optimistic perceptions and reducing the appeal of negative expected value scratch card games. [ABSTRACT FROM AUTHOR]

The Keats heuristic suggests that people find esthetically pleasing expressions more accurate than mundane expressions. We test this notion with chiastic statements. Chiasmus is a stylistic phenomenon in which at least two linguistic constituents are repeated in reverse order, conventionally represented by the formula A-B-B-A. Our study focuses on the specific form of chiasmus known as antimetabole, in which the reverse-repeated constituents are words (e.g., All for one and one for all; A = all, B = one). In three out of four experiments (N = 797), we find evidence that people judge antimetabolic statements (e.g., Success is getting what you want. Happiness is wanting what you get.) as more accurate than semantically equivalent nonantimetabolic statements (e.g., Success is getting what you wish. Happiness is wanting what you receive.). Furthermore, we evaluate fluency as a potential mechanism explaining the observed accuracy benefit afforded to antimetabolic statements, finding that the increased speed (i.e., fluency) with which antimetabolic statements were processed predicted judgments of accuracy. Overall, the present work is consistent with the growing literature on stylistic factors biasing assessments of truth, using the distinctive stylistic pattern of antimetabole. We find that information communicated using an antimetabolic structure is judged to be more accurate than nonantimetabolic paraphrases. [ABSTRACT FROM AUTHOR]

Prostate cancer germline testing informs precision therapy, screening, and hereditary cancer risk. Identifying and consenting for germline testing is complex, requiring new practice strategies. We identified multiple knowledge and practice gaps among a spectrum of providers which informed the development of Helix, a digital educational and clinical/family history collection tool. User testing was promising, supporting clinical use of Helix. Background: Prostate cancer (PCA) germline testing (GT) is now standard-of-care for men with advanced PCA. Thousands of men may consider GT due to clinical and family history (FH) features. Identifying and consenting men for GT can be complex. Here we identified barriers and facilitators of GT across a spectrum of providers which informed the development of Helix - an educational and clinical/FH collection tool to facilitate GT in practice. Materials and Methods: A 12-question survey assessing knowledge of genetics PCA risk and FH was administered December 2017 to March 2018 in the Philadelphia area and at the Mid-Atlantic AUA meeting (March 2018). Responses were analyzed using descr iptive statistics. Semi-str uctured interviews were conducted with medical oncologists, radiation oncologists, and urologists across practice settings from March-October 2020 as part of a larger study based on the Tailored Implementation in Chronic Diseases framework. Helix was then developed followed by user testing. Results: Fifty-six providers (50% urologists) responded to the survey. Multiple FH and genetic knowledge gaps were identified: only 66% collected maternal FH and 43% correctly identified BRCA2 and association to aggressive PCA. Genetic counseling gaps included low rates of discussing genetic discrimination laws (45%). Provider interviews (n = 14) identified barriers to FH intake including access to details and time needed. In user testing (n = 10), providers found Helix helpful for FH collection. All providers found Helix easy to use, suggesting expanded clinical use. Conclusion: Helix addressed multiple GT knowledge and practice gaps across a spectrum of providers. This tool will become publicly available soon to facilitate PCA GT in clinical practice. [ABSTRACT FROM AUTHOR]

Case Presentation: A 54-year-old South African man with a medical history of type 2 diabetes mellitus, seizure disorder, OSA, and latent TB presented to the ER with gradually progressive dyspnea over months. He also reported occasional dry cough and fatigue at presentation but denied fever, chills, chest pain, leg swelling, palpitations, or lightheadedness. He was treated with a course of levofloxacin for presumed community-acquired pneumonia as an outpatient without improvement and had tested negative for COVID-19. He denied occupational or environmental exposures or sick contacts, though he had traveled back to South Africa 1 year before presentation. He had complex partial seizures for the past 22 years, which had been well controlled on phenytoin (300 mg daily). His other home medications included dulaglutide, sertraline, and atorvastatin and had no recent changes. He quit smoking 30 years ago after smoking one pack per day for 10 years. [ABSTRACT FROM AUTHOR]

The advent of laparoscopic live-donor nephrectomy for renal transplantation has prompted the need to define the precise anatomical relations of the left renal vein (LRV) and its tributaries. The left kidney is preferred as the greater length of the LRV facilitates implantation in the recipient. While previous studies have described variations in the LRV system, the connections between the left ascending lumbar vein (LALV) and LRV tributaries have been less well-defined. This study aims to further characterise the LALV and proposes a novel classification for its relation to other veins. Dissection of the LRV system, including the left suprarenal vein (LSV), left gonadal vein (LGV) and LALV, was performed in 38 cadavers. Their drainage points into the LRV were recorded, and measurements taken of the distances from these points to the junction of the LRV and inferior vena cava (IVC). The position of the LRV in relation to the aorta was anterior in 35 cases (92%), entirely posterior in 1 case (3%), and circumaortic in 2 cases (5%). Duplication of the LSV and LGV occurred in 6 (16%) and 10 (27%) cases respectively. A direct posterior connection between the LALV and LRV was identified in 32 (86%) cases. The drainage point of the LALV into the LRV lay between the IVC and LGV in 8 (25%) cases. In 20 cases (63%), the drainage points of the LALV and LGV were equidistant from the IVC; and in 5 cases (16%), those of the LALV and posterior branch of the LRV were equidistant from the IVC. In these two groups, the vessels shared a confluent trunk in 10 and 4 cases respectively. In 3 cases, connections were observed between all three vessels (LALV, LGV and posterior branch of LRV). No confluence trunk was shared by the LALV and LSV. These results confirm the high incidence of communicating LALVs, which represent a potentially troublesome source of operative bleeding if unrecognised. Confluent venous trunks may also present difficulties during vessel ligation prior to nephrectomy. It is suggested that a novel classification of the relation of the LALV based on these findings may assist in surgical planning and reduce complications. [ABSTRACT FROM AUTHOR]

The lower Green River episodically narrowed between the mid-1930s and present day through deposition of new floodplains within a wider channel that had been established and/or maintained during the early twentieth century pluvial period. Comparison of air photos spanning a 74-yr period (1940-2014) and covering a 61 km study area shows that the channel narrowed by 12% from 138 ± 3.4 m to 122 ± 2.1 m. Stratigraphic and sedimentologic analysis and tree ring dating of a floodplain trench corroborates the air photo analysis and suggests that the initial phase of floodplain formation began by the mid-1930s, approximately the same time that the flow regime decreased in total annual and peak annual flow. Tamarisk, a nonnative shrub, began to establish in the 1930s as well. Narrowing from the 1940s to the mid-1980s was insignificant, because floodplain formation was approximately matched by bank erosion. Air photo analysis demonstrates that the most significant episode of narrowing was underway by the late 1980s, and analysis of the trench shows that floodplain formation had begun in the mid-1980s during a multi-year period of low peak annual flow. Air photo analysis shows that mean channel width decreased by ~7% between 1993 and 2009. A new phase of narrowing may have begun in 2003, based on evidence in the trench. Comparison of field surveys made in 1998 and 2015 in an 8.5 km reach near Fort Bottom suggests that narrowing continues and demonstrates that new floodplain formation has been a very small proportion of the total annual fine sediment flux of the Green River. Vertical accretion of new floodplains near Fort Bottom averaged 2.4 m between 1998 and 2015 but only accounted for ~1.5% of the estimated fine sediment flux during that period. Flood control by Flaming Gorge Dam after 1962 significantly influenced flow regime, reducing the magnitude of the annual snowmelt flood and increasing the magnitude of base flows. Though narrowing was initiated by changes in flow regime, native and nonnative riparian vegetation promoted floodplain formation and channel narrowing especially through establishment on channel bars and incipient floodplains during years of small annual floods. [ABSTRACT FROM AUTHOR]

Postmarketing safety surveillance studies address two actionable questions: (1) Is the test product riskier than a standard? (2) Is the risk associated with the test product within some tolerable margin by comparison to the standard? Established techniques, not commonly applied to the setting of such complementary one-sided hypotheses, lead to useful conclusions in practice. For two-group studies, a search over possible one-sided binomial test results yields sample sizes that guarantee that the confidence bounds exclude one or the other of the hypotheses. With continuous monitoring, simple curtailment reduces the sample size. Point and interval estimates follow from the binomial distribution of events at the end of the study or from component negative binomials for crossing a bound of simple curtailment with continuous monitoring and earlier stopping. An asymptotic derivation corresponds to the problem of constructing a confidence interval that is smaller than the distance between the parameter values for tolerable excess and the absence of excess risk. Studies with guaranteed rejection of one of the pair of complementary hypotheses are somewhat larger than corresponding studies of a single hypothesis under usual power requirements, but the increase may be tolerable in return for certainty that there will be an actionable conclusion. [ABSTRACT FROM AUTHOR]

Influenza A virus encodes a viral RNA-dependent RNA polymerase (FluPolA), which is responsible for transcribing and replicating the negative-sense viral RNA (vRNA) genome. FluPolA transcribes vRNA using a host capped mRNA primer, and replicates it by synthesising a positive-sense complementary RNA (cRNA) intermediate which is copied back into vRNA. To carry out these functions, FluPolA interacts with vRNA and cRNA using conserved promoter elements at the 5' and 3' termini. Recent structural studies have identified a new surface binding site for the 3' vRNA and cRNA promoters on FluPolA, referred to as the Mode B site. However, the role of this binding site in FluPolA function is unknown. In this study we used a combination of cell-based and biochemical assays to show that the Mode B site is important for both viral genome transcription and replication. Furthermore, we show that the Mode B site is not needed for initiating transcription in vitro but is required to synthesise a full-length product. This is consistent with a model in which the 3' terminus of the vRNA template binds in the Mode B site during elongation. Our data provide the first functional insights into the role of the Mode B site on FluPolA, which advances our understanding of FluPolA function and influenza A virus replication. Importance Influenza viruses are responsible for up to 650000 deaths per year through seasonal epidemics, and pandemics have caused tens of millions of deaths in the past. Most current therapeutics suffer from widespread resistance, creating a need for new drug targets against influenza virus. The virus encodes an RNA-dependent RNA polymerase, which replicates and transcribes the vRNA genome. The polymerase interacts with vRNA and the complementary replicative intermediate cRNA using several specific binding sites, however, the functions associated with these binding sites remain unknown. Here, we functionally characterise a binding site for the 3' vRNA and cRNA promoters. Our data offer insight into the mechanism of viral genome transcription by the influenza virus polymerase, and may be applicable to other related viruses. [ABSTRACT FROM AUTHOR]

Previous work has demonstrated that peoples' gambling-related judgments (e.g., perceived likelihood of winning) are often biased by non-diagnostic unclaimed prize information (i.e., the number of prizes still available to be won) resulting in non-optimal scratch card preferences. Another line of research suggests that people make less biased decisions (e.g., are less affected by the framing of a gamble) when using a foreign language. In the current study, we investigated whether using a foreign language (as opposed to one's native language) reduced the biasing effects of unclaimed prize information and consequently led to more optimal scratch card preferences. Across three experiments (N = 409), we found that people were equally biased by unclaimed prize information regardless of whether they completed our scratch card gambling task in their native (Polish) or foreign (English) language. In conclusion, it appears that using a foreign language does not help people be less biased in utilizing gambling-related information, and consequently does not lead to more optimal scratch card preferences. [ABSTRACT FROM AUTHOR]

For an integer b ⩾ 2 and a set S ⊂ { 0 , ... , b − 1 } , we define the Kempner set K (S , b) to be the set of all nonnegative integers whose base-b digital expansions contain only digits from S. These well-studied sparse sets provide a rich setting for additive number theory, and in this article we study various questions relating to the appearance of arithmetic progressions in these sets. In particular, for all b we determine exactly the maximal length of an arithmetic progression that omits a base-b digit. [ABSTRACT FROM AUTHOR]

Across four studies participants (N = 818) rated the profoundness of abstract art images accompanied with varying categories of titles, including: pseudo-profound bullshit titles (e.g., The Deaf Echo), mundane titles (e.g., Canvas 8), and no titles. Randomly generated pseudo-profound bullshit titles increased the perceived profoundness of computer-generated abstract art, compared to when no titles were present (Study 1). Mundane titles did not enhance the perception of profoundness, indicating that pseudo-profound bullshit titles specifically (as opposed to titles in general) enhance the perceived profoundness of abstract art (Study 2). Furthermore, these effects generalize to artist-created abstract art (Study 3). Finally, we report a large correlation between profoundness ratings for pseudo-profound bullshit and "International Art English" statements (Study 4), a mode and style of communication commonly employed by artists to discuss their work. This correlation suggests that these two independently developed communicative modes share underlying cognitive mechanisms in their interpretations. We discuss the potential for these results to be integrated into a larger, new theoretical framework of bullshit as a low-cost strategy for gaining advantages in prestige awarding domains. [ABSTRACT FROM AUTHOR]

The domain of gambling is rife with both diagnostic and non-diagnostic information. Previous studies examining scratch card gambling have demonstrated that people are often biased by intuitively appealing, yet non-diagnostic information (i.e., unclaimed prize information). The current study investigated how varying the presentation format of a diagnostic piece of information (i.e., payback percentage) could influence participants' use of this information when in conflict with unclaimed prize information. We hypothesized that when payback percentage information was presented in a graphical, as opposed to a numerical format, participants would be better at ignoring unclaimed prize information and correspondingly have their preferences become congruent with the true value of the presented scratch cards. In Experiment 1 (N = 201), with payback percentage presented in a numerical format, participants displayed a non-optimal preference for cards with greater numbers of unclaimed prizes and lower payback percentages. This preference was reversed in Experiment 2 (N = 201) when payback percentage was presented in a graphical format. In conclusion, the results of the current study demonstrate how judgments in a scratch card gambling domain can be improved by simply changing the presentation format of a single piece of information. [ABSTRACT FROM AUTHOR]

The influenza virus RNA-dependent RNA polymerase (RdRP) cleaves the 5′ end of nascent capped host RNAs and uses the capped RNA fragment to prime viral transcription in a mechanism called 'cap snatching'. Cap snatching requires an intimate association between influenza RdRP and cellular RNA polymerase II (Pol II), which is the source of nascent capped host RNAs targeted by influenza virus. Recent structural studies have revealed how influenza RdRP binds to Pol II and how this binding promotes the initiation of viral transcription by influenza RdRP. In this review we focus on these recent insights into the mechanism of cap snatching by influenza virus and the impact of cap snatching on host gene expression during influenza virus infection. Highlights Influenza virus RdRP associates with cellular Pol II. This provides influenza RdRP with a source of nascent capped host RNAs which it targets in a process called 'cap snatching' to generate primers for viral transcription. Influenza RdRP makes direct interactions with the Pol II C terminal domain (CTD). Molecular details of these interactions have recently been determined, and there is evidence that Pol II CTD binding promotes viral transcription by modulating the conformation of influenza RdRP. Influenza RdRP cap snatches small nuclear/nucleolar RNAs most frequently. When cap snatching generates suboptimal capped RNA fragments, influenza RdRP can use a prime-and-realign mechanism to promote transcription initiation. Influenza virus infection reduces Pol II abundance in gene bodies, suggesting that cap snatching contributes to host shut-off. [ABSTRACT FROM AUTHOR]

Previous research has demonstrated a link between illusory pattern perception and various irrational beliefs. On this basis, we hypothesized that participants who displayed greater degrees of illusory pattern perception would also be more likely to rate pseudo-profound bullshit statements as profound. We find support for this prediction across three experiments (N = 627) and four distinct measures of pattern perception. We further demonstrate that this observed relation is restricted to illusory pattern perception, with participants displaying greater endorsement of non-illusory patterns being no more likely to rate pseudo-profound bullshit statements as profound. Additionally, this relation is not a product of a general proclivity to rate all statements as profound and is not accounted for by individual differences in analytic thinking. Overall, we demonstrate that individuals with a tendency to go beyond the available data such that they uncritically endorse patterns where no patterns exist are also more likely to create and endorse false-meaning in meaningless pseudo-profound statements. These findings are discussed in the context of a proposed framework that views individuals' receptivity to pseudo-profound bullshit as, in part, an unfortunate consequence of an otherwise adaptive process: that of pattern perception. [ABSTRACT FROM AUTHOR]

Previous research has revealed that intuitive confidence is an important predictor of how people choose between an intuitive and non-intuitive alternative when faced with information that opposes the intuitive response. In the current study, we investigated the speed of intuition generation as a predictor of intuitive confidence and participant choice in choice conflict situations. Participants predicted the outcomes of several National Basketball Association games, both with and without reference to a point spread. As hypothesized, the faster participants were to predict the outright winner of a game (i.e., generate an intuition) the more likely they were to predict the favourite against the point spread for that game (i.e., endorse the intuitive response). Overall, our findings are consistent with the notion that the speed of intuition generation acts as a determinant of intuitive confidence and a predictor of choice in situations featuring equally valid intuitive and non-intuitive alternatives. [ABSTRACT FROM AUTHOR]

Background and aims: Scratch cards are a popular form of lottery gambling available in many jurisdictions. However, there is a paucity of research that examines associations between individual differences in thinking style, participation in scratch card gambling, and problem gambling severity. Methods: In three studies, we sought to examine the relationships among these variables in large, online samples of participants. Participants completed the Cognitive Reflection Test (CRT), the Problem Gambling Severity Index (PGSI), the Actively Open-Minded Thinking Scale, and self-reported their frequency of scratch card gambling. Results: Throughout all three studies, specific associations were reliably established. Specifically, negative associations were observed between participants' CRT and PGSI scores, as well as between participants' CRT scores and scratch card gambling frequency. In addition, we found a positive association between problem gambling severity and scratch card gambling frequency. Finally, problem gambling severity was shown to correlate positively with participants' willingness to pay for irrelevant information in a scratch card gambling scenario. Discussion and conclusions: Overall, we observed that problem gambling severity is associated with an individuals' thinking style and scratch card gambling behavior. This study adds to the existing literature examining problem gambling, and highlights the role of thinking style in understanding gambling behavior and problematic gambling. [ABSTRACT FROM AUTHOR]

Unclaimed prize information (i.e., the number of prizes still available to be won) is information commonly provided to scratch card gamblers. However, unless the number of tickets remaining to be purchased is also provided, this information is uninformative. Despite its lack of utility in assisting gamblers in choosing the most favourable type of scratch card to play, we hypothesized that unclaimed prize information would bias participants' judgments within a scratch card gambling context. In Experiment 1 (N = 201), we showed that participants are influenced by this information such that they felt more likely to win, were more excited to play, and preferred to hypothetically purchase more of the scratch card with the greatest number of unclaimed prizes. In Experiment 2 (N = 201), we attempted to ameliorate this bias by providing participants with the number of tickets remaining to be purchased and equating the payback percentages of all three games. The bias, although attenuated, still persisted in these conditions. Finally, in Experiment 3 (N = 200), we manipulated the hypothetical scratch cards such that games with the highest number of unclaimed prizes were the least favourable, and vice versa. As in Experiment 2, participants still favoured cards with greater numbers of unclaimed prizes. Possible mechanisms underlying this bias are discussed. In conclusion, across three experiments, we demonstrate that salient unclaimed prize information is capable of exerting a strong effect over judgments related to scratch card games. [ABSTRACT FROM AUTHOR]

Background and aims: Scratch cards are a popular form of lottery gambling available in many jurisdictions. However, there is a paucity of research that examines associations between individual differences in thinking style, participation in scratch card gambling, and problem gambling severity. Methods: In three studies, we sought to examine the relationships among these variables in large, online samples of participants. Participants completed the Cognitive Reflection Test (CRT), the Problem Gambling Severity Index (PGSI), the Actively Open-Minded Thinking Scale, and self-reported their frequency of scratch card gambling. Results: Throughout all three studies, specific associations were reliably established. Specifically, negative associations were observed between participants' CRT and PGSI scores, as well as between participants' CRT scores and scratch card gambling frequency. In addition, we found a positive association between problem gambling severity and scratch card gambling frequency. Finally, problem gambling severity was shown to correlate positively with participants' willingness to pay for irrelevant information in a scratch card gambling scenario. Discussion and conclusions: Overall, we observed that problem gambling severity is associated with an individuals' thinking style and scratch card gambling behavior. This study adds to the existing literature examining problem gambling, and highlights the role of thinking style in understanding gambling behavior and problematic gambling. [ABSTRACT FROM AUTHOR]

In the current study, cross-task interactions between number order and sound intensity judgments were assessed using a dual-task paradigm. Participants first categorized numerical sequences composed of Arabic digits as either ordered (ascending, descending) or non-ordered. Following each number sequence, participants then had to judge the intensity level of a target sound. Experiment 1 emphasized processing the two tasks independently (serialprocessing), while Experiments 2 and 3 emphasized processing the two tasks simultaneously (parallelprocessing). Cross-task interference occurred only when the task required parallel processing and was specific to ascending numerical sequences, which led to a higher proportion ofloudersound intensity judgments. In Experiment 4 we examined whether this unidirectional interaction was the result of participants misattributing enhanced processing fluency experienced on ascending sequences as indicating a louder target sound. The unidirectional finding could not be entirely attributed to misattributed processing fluency, and may also be connected to experientially derived conceptual associations between ascending number sequences and greater magnitude, consistent with conceptual mapping theory. [ABSTRACT FROM PUBLISHER]

Cinnamyl alcohol dehydrogenase (CAD) catalyzes the final step in monolignol biosynthesis, reducing sinapaldehyde, coniferaldehyde, and p-coumaraldehyde to their corresponding alcohols in an NADPH-dependent manner. Because of its terminal location in monolignol biosynthesis, the variation in substrate specificity and activity of CAD can result in significant changes in overall composition and amount of lignin. Our in-depth characterization of two major CAD isoforms, SbCAD2 (Brown midrib 6 [bmr6]) and SbCAD4, in lignifying tissues of sorghum (Sorghum bicolor), a strategic plant for generating renewable chemicals and fuels, indicates their similarity in both structure and activity to Arabidopsis (Arabidopsis thaliana) CAD5 and Populus tremuloides sinapyl alcohol dehydrogenase, respectively. This first crystal structure of a monocot CAD combined with enzyme kinetic data and a catalytic model supported by site-directed mutagenesis allows full comparison with dicot CADs and elucidates the potential signature sequence for their substrate specificity and activity. The L119W/G301F-SbCAD4 double mutant displayed its substrate preference in the order coniferaldehyde > p-coumaraldehyde > sinapaldehyde, with higher catalytic efficiency than that of both wild-type SbCAD4 and SbCAD2. As SbCAD4 is the only major CAD isoform in bmr6 mutants, replacing SbCAD4 with L119W/G301F-SbCAD4 in bmr6 plants could produce a phenotype that is more amenable to biomass processing. [ABSTRACT FROM AUTHOR]

Cinnamoyl-coenzyme A reductase (CCR) catalyzes the reduction of hydroxycinnamoyl-coenzyme A (CoA) esters using NADPH to produce hydroxycinnamyl aldehyde precursors in lignin synthesis. The catalytic mechanism and substrate specificity of cinnamoyl-CoA reductases from sorghum (Sorghum bicolor), a strategic plant for bioenergy production, were deduced from crystal structures, site-directed mutagenesis, and kinetic and thermodynamic analyses. Although SbCCR1 displayed higher affinity for caffeoyl-CoA or p-coumaroyl-CoA than for feruloyl-CoA, the enzyme showed significantly higher activity for the latter substrate. Through molecular docking and comparisons between the crystal structures of the Vitis vinifera dihydroflavonol reductase and SbCCR1, residues threonine-154 and tyrosine-310 were pinpointed as being involved in binding CoA-conjugated phenylpropanoids. Threonine-154 of SbCCR1 and other CCRs likely confers strong substrate specificity for feruloyl-CoA over other cinnamoyl-CoA thioesters, and the T154Y mutation in SbCCR1 led to broader substrate specificity and faster turnover. Through data mining using our structural and biochemical information, four additional putative CCR genes were discovered from sorghum genomic data. One of these, SbCCR2, displayed greater activity toward p-coumaroyl-CoA than did SbCCR1, which could imply a role in the synthesis of defense-related lignin. Taken together, these findings provide knowledge about critical residues and substrate preference among CCRs and provide, to our knowledge, the first three-dimensional structure information for a CCR from a monocot species. [ABSTRACT FROM AUTHOR]

Caffeoyl-coenzyme A 3-O-methyltransferase (CCoAOMT) is an S-adenosyl methionine (SAM)-dependent O-methyltransferase responsible for methylation of the meta-hydroxyl group of caffeoyl-coenzyme A (CoA) on the pathway to monolignols, with their ring methoxylation status characteristic of guaiacyl or syringyl units in lignin. In order to better understand the unique class of type 2 O-methyltransferases from monocots, we have characterized CCoAOMT from sorghum (Sorghum bicolor; SbCCoAOMT), including the SAM binary complex crystal structure and steady-state enzyme kinetics. Key amino acid residues were validated with site-directed mutagenesis. Isothermal titration calorimetry data indicated a sequential binding mechanism for SbCCoAOMT, wherein SAM binds prior to caffeoyl-CoA, and the enzyme showed allosteric behavior with respect to it. 5-Hydroxyferuloyl-CoA was not a substrate for SbCCoAOMT. We propose a catalytic mechanism in which lysine-180 acts as a catalytic base and deprotonates the reactive hydroxyl group of caffeoyl-CoA. This deprotonation is facilitated by the coordination of the reactive hydroxyl group by Ca2+ in the active site, lowering the pKa of the 3'-OH group. Collectively, these data give a new perspective on the catalytic mechanism of CCoAOMTs and provide a basis for the functional diversity exhibited by type 2 plant OMTs that contain a unique insertion loop (residues 208-231) conferring affinity for phenylpropanoid-CoA thioesters. The structural model of SbCCoAOMT can serve as the basis for protein engineering approaches to enhance the nutritional, agronomic, and industrially relevant properties of sorghum. [ABSTRACT FROM AUTHOR]

Purpose: To describe how computer-assisted presentation of case data can lead experts to infer machine-implementable rules for case definition in electronic health records. As an illustration the technique has been applied to obtain a definition of acute liver dysfunction (ALD) in persons with inflammatory bowel disease (IBD).Methods: The technique consists of repeatedly sampling new batches of case candidates from an enriched pool of persons meeting presumed minimal inclusion criteria, classifying the candidates by a machine-implementable candidate rule and by a human expert, and then updating the rule so that it captures new distinctions introduced by the expert. Iteration continues until an update results in an acceptably small number of changes to form a final case definition.Results: The technique was applied to structured data and terms derived by natural language processing from text records in 29,336 adults with IBD. Over three rounds the technique led to rules with increasing predictive value, as the experts identified exceptions, and increasing sensitivity, as the experts identified missing inclusion criteria. In the final rule inclusion and exclusion terms were often keyed to an ALD onset date. When compared against clinical review in an independent test round, the derived final case definition had a sensitivity of 92% and a positive predictive value of 79%.Conclusion: An iterative technique of machine-supported expert review can yield a case definition that accommodates available data, incorporates pre-existing medical knowledge, is transparent and is open to continuous improvement. The expert updates to rules may be informative in themselves. In this limited setting, the final case definition for ALD performed better than previous, published attempts using expert definitions. [ABSTRACT FROM AUTHOR]

In the current study, we examined how the contextual repetition of magnitude information presented in either symbolic (Arabic digits) or nonsymbolic (numerosities) formats impacted on the perceived duration of a later occurring target number. The results of the current study demonstrated a time-magnitude bias in which, on average, large magnitude target numbers were judged to last for longer durations relative to small magnitude target numbers, regardless of notation (symbolic number and numerosity). Furthermore, context effects were found, in which a greater discrepancy in the target’s magnitude from the initial context led to longer perceived duration ratings. However, this was found to be asymmetrical, occurring only for large magnitude targets. Additionally, the type of context effect was shown to be determined by whether the context was presented in the same notation as the target or a different notation. [ABSTRACT FROM AUTHOR]

The cross-modal impact of number magnitude (i.e. Arabic digits) on perceived sound loudness was examined. Participants compared a target sound's intensity level against a previously heard reference sound (which they judged as quieter or louder ). Paired with each target sound was a task irrelevant Arabic digit that varied in magnitude, being either small (1, 2, 3) or large (7, 8, 9). The degree to which the sound and the digit were synchronized was manipulated, with the digit and sound occurring simultaneously in Experiment 1, and the digit preceding the sound in Experiment 2. Firstly, when target sounds and digits occurred simultaneously, sounds paired with large digits were categorized as loud more frequently than sounds paired with small digits. Secondly, when the events were separated, number magnitude ceased to bias sound intensity judgments. In Experiment 3, the events were still separated, however the participants held the number in short-term memory. In this instance the bias returned. [ABSTRACT FROM AUTHOR]

With the increased prevalence of obesity worldwide, the incidence of obstructive sleep apnoea (OSA) has risen substantially. OSA is now also more commonly recognized within the pregnant population. The diagnosis of OSA during pregnancy is logistically difficult for many reasons. The symptoms of an uncomplicated pregnancy are traditionally believed to include sleep disruption and daytime sleepiness, without many specific data differentiating 'normal' from 'pathological', thus complicating the screening process for a true sleep disorder based on symptoms alone. Untreated OSA during pregnancy is associated with a variety of gestational health disorders, along with increased complications during delivery. Although screening protocols and increased healthcare provider awareness have led to earlier diagnosis and treatment of OSA in the general population, their implementation in the pregnant population is lacking. Studies on the use of continuous positive airway pressure in pregnancy have demonstrated its safety, but further research is needed to determine its benefits in this cohort. [ABSTRACT FROM AUTHOR]

Introduction Nonarteritic anterior ischemic optic neuropathy ( NAION), a rare visual disorder, has been reported in men using phosphodiesterase type 5 inhibitors ( PDE5i) for erectile dysfunction. Aim We examined whether intermittent use of PDE5i is associated with acute NAION onset within approximately five half-lives following drug ingestion. Methods One hundred two ophthalmology centers in the United States and Europe identified potential cases of NAION. An expert adjudication committee conducted a blind review of the records of those with recent PDE5i use to classify cases as Definite, Possible, or not NAION. Subjects provided information on PDEi use via telephone interview. Each NAION case's PDE5i exposure immediately prior to onset was compared against his recent patterns of use in an observational case-crossover design. A sample size of 40 cases with intermittent PDE5i exposure in the 30 days prior to NAION onset was needed to detect an odds ratio ( OR) of 3.0 with 80% power. Main Outcome Measures The daily relative risk for acute NAION on days within five half-lives of PDE5i use vs. other days was estimated via an OR obtained from conditional logistic regression. Results Among 43 Definite NAION cases with PDE5i exposure in the prior 30 days, the OR was 2.15 (95% confidence interval [ CI]: 1.06, 4.34). When 21 Possible NAION cases were included (n = 64), the OR was 2.36 (95% CI: 1.33, 4.19). Conclusions We found an approximately twofold increased risk of acute NAION within five half-lives of PDE5i use compared with use in a more prior time period. Bias from inaccurate recall of exposure was unlikely to have substantially affected the results. Based on our results, we estimate that weekly use of PDE5i adds three NAION cases per 100,000 men 50 years and older annually. Campbell UB, Walker AM, Gaffney M, Petronis KR, Creanga D, Quinn S, Klein BEK, Laties AM, Lewis M, Sharlip ID, Kolitsopoulos F, Klee BJ, Mo J, and Reynolds RF. Acute nonarteritic anterior ischemic optic neuropathy and exposure to phosphodiesterase type 5 inhibitors. J Sex Med 2015;12:139-151. [ABSTRACT FROM AUTHOR]

Individuals often assess themselves as being less susceptible to common biases compared to others. This bias blind spot (BBS) is thought to represent a metacognitive error. In this research, we tested three explanations for the effect: The cognitive sophistication hypothesis posits that individualswho display the BBS more strongly are actually less biased than others. The introspection bias hypothesis posits that the BBS occurs because people rely on introspection morewhen assessing themselves compared to others. The conversational processes hypothesis posits that the effect is largely a consequence of the pragmatic aspects of the experimental situation rather than true metacognitive error. In two experiments (N = 1057) examining 18 social/motivational and cognitive biases, therewas strong evidence of theBBS.Among the three hypotheses examined, the conversational processes hypothesis attracted the greatest support, thus raising questions about the extent to which the BBS is a metacognitive effect. [ABSTRACT FROM AUTHOR]

• In-situ multiple sulphur isotopes from the Andromeda prospect of the Fraser Zone. • The material analysed includes brecciated orebody and host rock sulphides. • Significant sulphur sources likely include seawater and host lithologies. • MIF-S signature inherited via fluid flow along a proximal transcrustal shear zone. • Multiple sulphur cycling pathways operating within a Proterozoic mineralised system. Sulphur isotope analysis can be used to fingerprint sulphur sources within mineral systems and trace sulphur cycles through geological time. In this work we present petrographic and in-situ sulphur isotope analyses of sulphide minerals from the Zn–Cu–Au–Ag Andromeda volcanogenic massive sulphide (VMS) prospect, Fraser Zone, Albany-Fraser Orogen, Australia. Sulphide mineral assemblages of pyrrhotite, pyrite, chalcopyrite and sphalerite occur within deformed lenses of sulphide breccia at Andromeda, with the presence of sphalerite contrasting with typical magmatic sulphide mineral assemblages recorded elsewhere within the Fraser Zone. The δ 34S values of Andromeda sulphides range from 4.50‰ to 6.70‰, characteristic of Archaean and Proterozoic VMS-style deposits worldwide. The Δ33S data show evidence of mass-independent fractionation of sulphur (MIF-S), which indicates that sulphur from Archaean sediments was included within Andromeda sulphides, which formed in close proximity to the Fraser Shear Zone (FSZ). This contrasts with the findings of previous studies of sulphur isotopes within magmatic sulphides elsewhere in the Fraser Zone, which are distal to major shear zones, and in which sulphur derived from Archaean sediments is absent. The absence of a MIF-S signature from the magmatic sulphides is interpreted to reflect cycling of surface-derived sulphur through the ocean prior to incorporation into the magmatic sulphides. The presence of Archaean sedimentary sulphur at Andromeda is attributed to transport from a reservoir of sulphur recording MIF-S within the older Biranup Zone, which is in close proximity to the FSZ, a lithosphere-scale structure. Fluid movement through the FSZ is a viable mechanism that might have transferred sulphur recording MIF-S from Archaean sulphur-bearing pyrite in the Biranup Zone to sulphides at Andromeda. These findings support multiple modes of sulphur cycling within a single Proterozoic mineralised setting and imply that similar polymodal sulphur cycling might have occurred on other Proterozoic continental margins worldwide, with implications for mineralisation and global sulphur cycle systematics. [ABSTRACT FROM AUTHOR]

Across six studies (N = 2646), we demonstrate the role that perceptions of predictability play in judgments of moral character, finding that people demonstrate a moral preference for more predictable immoral actors. Participants judged agents performing an immoral action (e.g., assault) for an unintelligible reason as less predictable and less moral than agents performing the same immoral action, along with an additional immoral action (e.g., theft), for a well-understood immoral reason (Studies 1–4). Additionally, agents performing an immoral action for an unintelligible reason were judged as less predictable and less moral compared to agents performing the same immoral act for an unstated reason (Studies 3–5). This moral preference persisted when participants viewed video footage of each agent's immoral action (Study 5). Finally, agents performing immoral actions in an unusual way were judged as less predictable and less moral than those performing the same actions in a more common manner (Study 6). The present research demonstrates how immoral actions performed without a clear motive or in an unpredictable way are perceived to be especially indicative of poor moral character. In revealing peoples' moral preference for predictable immoral actors, we propose that perceptions of predictability play an important, yet overlooked, role in judgments of moral character. Furthermore, we propose that predictability influences judgments of moral character for its ultimate role in reducing social uncertainty and facilitating cooperation with trustworthy individuals and discuss how these findings may be accommodated by person-centered theories of moral judgment and theories of morality-as-cooperation. • We investigate the role perceptions of predictability play in judgments of morality. • Participants judged the morality of predictable and unpredictable immoral actors. • Unpredictable actors were judged as less moral even when performing fewer immoral acts. • Overall, we observed a moral preference for more predictable immoral actors. • Perceptions of predictability play an important role in judgments of moral character. [ABSTRACT FROM AUTHOR]

Across six studies (N = 1988 US residents and 81 traditional people of Papua), participants judged agents acting in sacrificial moral dilemmas. Utilitarian agents, described as opting to sacrifice a single individual for the greater good, were perceived as less predictable and less moral than deontological agents whose inaction resulted in five people being harmed. These effects generalize to a non-Western sample of the Dani people, a traditional indigenous society of Papua, and persist when controlling for homophily and notions of behavioral typicality. Notably, deontological agents are no longer morally preferred when the actions of utilitarian agents are made to seem more predictable. Lastly, we find that peoples' lay theory of predictability is flexible and multi-faceted, but nevertheless understood and used holistically in assessing the moral character of others. On the basis of our findings, we propose that assessments of predictability play an important role when judging the morality of others. [ABSTRACT FROM AUTHOR]

In the developing liver, bipotent epithelial progenitor cells undergo lineage segregation to form hepatocytes, which constitute the bulk of the liver parenchyma, and biliary epithelial cells (cholangiocytes), which comprise the bile duct (a complex tubular network that is critical for normal liver function). Notch and TGFβ signalling promote the formation of a sheet of biliary epithelial cells, the ductal plate, that organises into discontinuous tubular structures. How these structures elongate and connect to form a continuous duct remains undefined. We aimed to define the mechanisms by which the ductal plate transitions from a simple sheet of epithelial cells into a complex and connected bile duct. By combining single-cell RNA sequencing of embryonic mouse livers with genetic tools and organoid models we functionally dissected the role of planar cell polarity in duct patterning. We show that the planar cell polarity protein VANGL2 is expressed late in intrahepatic bile duct development and patterns the formation of cell-cell contacts between biliary cells. The patterning of these cell contacts regulates the normal polarisation of the actin cytoskeleton within biliary cells and loss of Vangl2 function results in the abnormal distribution of cortical actin remodelling, leading to the failure of bile duct formation. Planar cell polarity is a critical step in the post-specification sculpture of the bile duct and is essential for establishing normal tissue architecture. Like other branched tissues, such as the lung and kidney, the bile ducts use planar cell polarity signalling to coordinate cell movements; however, how these biochemical signals are linked to ductular patterning remains unclear. Here we show that the core planar cell polarity protein VANGL2 patterns how cell-cell contacts form in the mammalian bile duct and how ductular cells transmit confluent mechanical changes along the length of a duct. This work sheds light on how biological tubes are patterned across mammalian tissues (including within the liver) and will be important in how we promote ductular growth in patients where the duct is mis-patterned or poorly formed. [Display omitted] • Bile ducts express high levels of planar cell polarity genes when they are undergoing morphogenesis. • VANGL2 physically interacts with desmosome protein DSG1A and patterns cell-cell contacts. • Loss of functional VANGL2 prevents ducts from coordinating their actin cytoskeleton normally. • Ducts with dysregulated cytoskeletal dynamics because of dysfunctional VANGL2 fail to connect and form a continuous biliary tree. [ABSTRACT FROM AUTHOR]

We describe a vision for a national-scale heavy mineral (HM) map generated through automated mineralogical identification and quantification of HMs contained in floodplain sediments from large catchments covering most of Australia. The composition of the sediments reflects the dominant rock types in each catchment, with the generally resistant HMs largely preserving the mineralogical fingerprint of their host protoliths through the weathering-transport-deposition cycle. Heavy mineral presence/absence, absolute and relative abundance, and co-occurrence are metrics useful to map, discover and interpret catchment lithotype(s), geodynamic setting, magmatism, metamorphic grade, alteration and/or mineralization. Underpinning this vision is a pilot project, focusing on a subset from the national sediment sample archive, which is used to demonstrate the feasibility of the larger, national-scale project. We preview a bespoke, cloud-based mineral network analysis (MNA) tool to visualize, explore and discover relationships between HMs as well as between them and geological settings or mineral deposits. We envisage that the Heavy Mineral Map of Australia and MNA tool will contribute significantly to mineral prospectivity analysis and modeling, particularly for technology critical elements and their host minerals, which are central to the global economy transitioning to a more sustainable, lower carbon energy model. [ABSTRACT FROM AUTHOR]

The present work (N = 1906 U.S. residents) investigates the extent to which peoples' evaluations of actions can be biased by the strategic use of euphemistic (agreeable) and dysphemistic (disagreeable) terms. We find that participants' evaluations of actions are made more favorable by replacing a disagreeable term (e.g., torture) with a semantically related agreeable term (e.g., enhanced interrogation) in an act's description. Notably, the influence of agreeable and disagreeable terms was reduced (but not eliminated) when making actions less ambiguous by providing participants with a detailed description of each action. Despite their influence, participants judged both agreeable and disagreeable action descriptions as largely truthful and distinct from lies, and judged agents using such descriptions as more trustworthy and moral than liars. Overall, the results of the current study suggest that a strategic speaker can, through the careful use of language, sway the opinions of others in a preferred direction while avoiding many of the reputational costs associated with less subtle forms of linguistic manipulation (e.g., lying). Like the much-studied phenomenon of "fake news," manipulative language can serve as a tool for misleading the public, doing so not with falsehoods but rather the strategic use of language. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, public health guidance (e.g., regarding the use of non-medical masks) changed over time. Although many revisions were a result of gains in scientific understanding, we nonetheless hypothesized that making changes in guidance salient would negatively affect evaluations of experts and health-protective intentions. In Study 1 (N = 300), we demonstrate that describing COVID-19 guidance in terms of inconsistency (versus consistency) leads people to perceive scientists and public health authorities less favorably (e.g., as less expert). For participants in Canada (n = 190), though not the U.S. (n = 110), making guidance change salient also reduced intentions to download a contact tracing app. In Study 2 (N = 1399), we show that a brief forewarning intervention mitigates detrimental effects of changes in guidance. In the absence of forewarning, emphasizing inconsistency harmed judgments of public health authorities and reduced health-protective intentions, but forewarning eliminated this effect. [ABSTRACT FROM AUTHOR]

Alteration of magmatic sulphides within the regolith, or soil profile, is well documented, but alteration at depth, where meteoric fluids may infiltrate fresh rock adjacent to faults, is less studied and poorly understood. Yet such alteration may affect the mineralogy of the magmatic sulphides, and the characteristics of this alteration provide insights into the distribution and timescales of fluid flow and redox processes within the upper crust. Pentlandite [(Fe,Ni) 9 S 8 ] is a Ni-rich sulphide mineral, found in magmatic sulphide assemblages with chalcopyrite (CuFeS 2) and pyrrhotite (Fe 1−x S). Pentlandite associated with massive sulphides from apparently fresh rock at the Mawson Deposit, Western Australia, shows in-situ partial replacement by violarite (nominally FeNi 2 S 4), whereas pentlandite associated with adjacent disseminated sulphides is unaltered. Petrographic, geochemical, and in-situ sulphur isotope analysis reveals that violarite has variable Fe:Ni ratios. Constant volume and constant sulphur mass balance calculations indicate an overall loss of Ni and other metal cations during violarite formation. In addition, newly formed violarite has a 34S-depleted isotopic composition compared to precursor pentlandite. Altered pentlandite (δ34S = 1.02 ‰) is isotopically fractionated relative to co-existing pyrrhotite (3.44 ‰) and chalcopyrite (3.15 ‰), in contrast to the unfractionated sulphur isotope ratios expected for co-crystallising magmatic sulphides. These features are interpreted as a consequence of electrochemical alteration within electrically connected massive sulphides and addition of isotopically light sulphur derived by bacterial sulphate reduction. Based on previous evidence of deep-seated fluid flow along long-lived regional faults, the alteration is plausibly associated with Cenozoic neotectonic deformation and short-lived pulses of fluid flow with durations of hundreds to thousands of years. Similar petrographic evidence of deep alteration in apparently fresh sulphides from samples across the regional study area indicate this could be an under-reported feature in magmatic sulphides globally. [ABSTRACT FROM AUTHOR]

Navigating social systems efficiently is critical to our species. Humans appear endowed with a cognitive system that has formed to meet the unique challenges that emerge for highly social species. Bullshitting, communication characterised by an intent to be convincing or impressive without concern for truth, is ubiquitous within human societies. Across two studies (N = 1,017), we assess participants' ability to produce satisfying and seemingly accurate bullshit as an honest signal of their intelligence. We find that bullshit ability is associated with an individual's intelligence and individuals capable of producing more satisfying bullshit are judged by second-hand observers to be more intelligent. We interpret these results as adding evidence for intelligence being geared towards the navigation of social systems. The ability to produce satisfying bullshit may serve to assist individuals in negotiating their social world, both as an energetically efficient strategy for impressing others and as an honest signal of intelligence. [ABSTRACT FROM AUTHOR]

Across two experiments (N=799) we demonstrate that people's use of quantitative information (e.g., base-rates) when making a judgment varies as the causal link of qualitative information (e.g., stereotypes) changes. That is, when a clear causal link for stereotypes is provided, people make judgments that are far more in line with them. When the causal link is heavily diminished, people readily incorporate non-causal base-rates into their judgments instead. We suggest that people use and integrate all of the information that is provided to them to make judgements, but heavily prioritize information that is causal in nature. Further, people are sensitive to the underlying causal structures in their environment and adapt their decision making as such. [ABSTRACT FROM AUTHOR]

Lobular neoplasia (LN) involves proliferative changes within the breast lobules. LN is divided into lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LCIS can be further subdivided into three subtypes: classic LCIS, pleomorphic LCIS, and LCIS with necrosis (florid type). Because classic LCIS is now considered as a benign etiology, current guidelines recommend close follow-up with imaging versus surgical excision. The goal of our study was to determine if the diagnosis of classic LN on core needle biopsy (CNB) merits surgical excision. This is a retrospective, observational study conducted at Mount Auburn Hospital, Cambridge, MA, from May 17, 2017, through June 30, 2020. We reviewed the data of breast biopsies conducted at our hospital over this period and included patients who were diagnosed with classic LN (LCIS and/or ALH) and excluded patients having any other atypical lesions on CNB. All known cancer patients were excluded. Of the 2707 CNBs performed during the study period, we identified 68 women who were diagnosed with ALH or LCIS on CNB. CNB was performed for an abnormal mammogram in the majority of patients (60; 88%) while 7(10.3%) had an abnormal breast magnetic resonance imaging study (MRI), and 1 had an abnormal ultrasound (US). A total of 58 patients (85%) underwent excisional biopsy, of which 3 (5.2%) showed malignancy, including 2 cases of DCIS and 1 invasive carcinoma. In addition, there was 1 case (1.7%) with pleomorphic LCIS and 11 cases with ADH (15.5%). The management of LN found on core biopsy is evolving, with some advocating surgical excision and others recommending observation. Our data show a change in diagnosis with excisional biopsy in 13 (22.4%) of patients with 2 cases of DCIS, 1 invasive carcinoma, 1 pleomorphic LCIS, and 9 cases of ADH, diagnosed on excisional biopsy. While ALH and classic LCIS are considered benign, the choice of ongoing surveillance versus excisional biopsy should be made with shared decision making with the patient, with consideration of personal and family history, as well as patient preferences. [ABSTRACT FROM AUTHOR]

Background: Information exists as unstructured medical text in healthcare databases. Such information is not routinely considered in safety surveillance but typically relies solely on structured (coded) data. Natural language processing (NLP) may allow the capture of concepts from unstructured data and thus enhance safety surveillance capability.Objectives: We sought to assess the added contribution of unstructured data extracted from medical text by NLP for detecting acute liver dysfunction (ALD) in patients with inflammatory bowel disease (IBD).Methods: Using a previously developed rule, we evaluated structured and unstructured NLP-extracted terms from a commercially available electronic medical record (EMR) system. The rule was intended to identify ALD diagnosis and timing of onset and was the result of three iterations of rule development using 150 ALD candidate cases. We evaluated the performance of the rule with or without NLP among all candidate cases and among 50 new cases with clinical adjudication.Results: NLP terms were necessary for the diagnosis of 9% of cases and for ruling out 3% of false-positive cases. Inclusion of NLP terms led to an identification of an additional  9% of ALD-onset dates, with consequent earlier recognition in 5%.Conclusions: NLP-derived terms in one large commercially available EMR system modestly improved the sensitivity and specificity in the identification of ALD and identified earlier onset. [ABSTRACT FROM AUTHOR]

We produce nontrivial asymptotic estimates for shifted sums of the form ∑ a (h) b (m) c (2 m − h) , in which a (n) , b (n) , c (n) are un-normalized Fourier coefficients of holomorphic cusp forms. These results are unconditional, but we demonstrate how to strengthen them under the Riemann Hypothesis. As an application, we show that there are infinitely many three term arithmetic progressions n − h , n , n + h such that a (n − h) a (n) a (n + h) ≠ 0. [ABSTRACT FROM AUTHOR]

Predictions of river channel adjustment to changes in streamflow regime based on relations between mean channel characteristics and mean flood magnitude can be useful to evaluate average channel response. However, because these relations assume equilibrium sediment transport, their applicability to cases where streamflow and sediment transport are decoupled may be limited. These general relations also lack the specificity that is required to connect specific characteristics of the streamflow and sediment regime with the dynamics of channel morphological change that create channel complexity, which is often of ecological interest. We integrate historical records of channel change, observations of scour and fill during a snowmelt flood, measurements of sediment transport, and predictions from a two-dimensional streamflow model to describe how annual peak flow magnitude and peak-flow duration interact with the upstream sediment supply to control channel form for a 15-km study reach on the regulated Green River in Canyonlands National Park, Utah. Two major decadal-scale episodes of channel narrowing have occurred within the study area. For each of these episodes, the reduction in average channel width was consistent with the change predicted by hydraulic geometry relations as a function of average flood magnitude. However, channel narrowing occurred during periods of exceptionally low annual floods. The most recent episode of channel narrowing occurred between 1988 and 2009, during low-flow cycles when the 5-yr mean peak flow was less than 60% of the long-term (1959–2016) mean peak flow. These findings, together with findings from previous studies, demonstrate that decreases in peak-flow magnitude caused by streamflow regulation, climate change, or a combination of those factors have driven episodes of channel narrowing on the Green River. Observations of streamflow, sediment-transport, and morphologic change coupled with predictions from a two-dimensional streamflow model indicate that peak flow magnitudes of at least 75% of the long-term mean peak flow are required to transport bed-material sand in suspension in all regions of the multi-thread channel and that the ~2-month duration of the snowmelt flood played an important role in creating conditions necessary to maintain channel conveyance. These results indicate that detailed characterizations of channel response such as these are needed to predict how river channels will respond to changes in streamflow regime that affect annual peak flow magnitude and duration. • Streamflow regulation by dams and drought has contributed to channel narrowing. • Magnitude of channel narrowing was consistent with magnitude of flood reduction. • Channel narrowing initiated by consecutive years of low flood magnitude • Maintenance of channel width depends on both flood magnitude and duration. • Floods ≥75% of the average flood needed to transport bed material in suspension [ABSTRACT FROM AUTHOR]

Background: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up.Methods: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs.Results: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24).Conclusions: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study. [ABSTRACT FROM AUTHOR]

The Portland Metropolitan region, a single economic and ecological region with a bifurcated state and local governance structure, provides an opportunity to compare governance models and state policy environments in a single region. Using stakeholder interviews and secondary sources, we examine the role of state government policy in shaping and supporting different regimes. We find that Portland exhibits a stable, “smart-growth” regime that we characterized as a metropolitan eco-regime whereas Vancouver is in a period of fragmentation without a stable metropolitan regime. This is best explained by the differing state-level regulatory contexts and the different forms of polycentricity influenced by state action. Differences in regime and governance structure result in differently drawn and expanded urban growth boundaries with subsequent differences in land-use outcomes. We conclude with observations about state-level action and subsequent forms of polycentricity to support metropolitan eco-regimes. [ABSTRACT FROM AUTHOR]

We extend the axiomatization for detecting and quantifying sign changes of Meher and Murty [24] to sequences of complex numbers. We further generalize this result when the sequence is comprised of the coefficients of an L -function. As immediate applications, we prove that there are sign changes in intervals within sequences of coefficients of GL ( 2 ) holomorphic cusp forms, GL ( 2 ) Maass forms, and GL ( 3 ) Maass forms. Building on [13,14] , we prove that there are sign changes in intervals within sequences of partial sums of coefficients of GL ( 2 ) holomorphic cusp forms and Maass forms. [ABSTRACT FROM AUTHOR]

Let f and g be weight k holomorphic cusp forms and let S f ( n ) and S g ( n ) denote the sums of their first n Fourier coefficients. Hafner and Ivić [9] proved asymptotics for ∑ n ≤ X | S f ( n ) | 2 and proved that the Classical Conjecture, that S f ( X ) ≪ X k − 1 2 + 1 4 + ϵ , holds on average over long intervals. In this paper, we introduce and obtain meromorphic continuations for the Dirichlet series D ( s , S f × S g ) = ∑ S f ( n ) S g ( n ) ‾ × n − ( s + k − 1 ) and D ( s , S f × S g ‾ ) = ∑ n S f ( n ) S g ( n ) n − ( s + k − 1 ) . We then prove asymptotics for the smoothed second moment sums ∑ S f ( n ) S g ( n ) ‾ e − n / X , giving a smoothed generalization of [9] . We also attain asymptotics for analogous sums of normalized Fourier coefficients. Our methodology extends to a wide variety of weights and levels, and comparison with [4] indicates very general cancellation between the Rankin–Selberg L -function L ( s , f × g ) and convolution sums of the coefficients of f and g . In forthcoming works, the authors apply the results of this paper to prove the Classical Conjecture on | S f ( n ) | 2 is true on short intervals, and to prove sign change results on { S f ( n ) } n ∈ N . [ABSTRACT FROM AUTHOR]