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Objective: To assess the quality of reporting in diagnostic accuracy studies (DAS) referenced by the Quality Improvement Guidelines for Diagnostic Arteriography and their adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) statement. Materials and Methods: Citations specific to the Society of Interventional Radiology's Quality Improvement Guidelines for Diagnostic Arteriography were collected. Using the 34-item STARD checklist, two authors in a duplicate and blinded fashion documented the number of items reported per diagnostic accuracy study. Authors met, and any discrepancies were resolved in a resolution meeting. Results: Of the 26 diagnostic accuracy studies included, the mean number of STARD items reported was 17.8 (SD ± 3.1). The median adherence was 18 (IQR, 17-19) items. Ten articles were published prior to 2003, the original date of STARD publication, and 16 articles were published after 2003. The mean number of reported items for the articles published prior to STARD 2003, and after STARD 2003 was 17.4 (SD ± 2.4) and 18.1 (SD ± 3.5), respectively. There were 14 STARD items that demonstrated an adherence of < 25%, and 13 an adherence > 75%. Conclusion: The dichotomous distribution of adherence to the STARD statement by DAS investigated demonstrates that areas of deficient reporting may be present and require attention to ensure complete and transparent reporting in the future. [ABSTRACT FROM AUTHOR]

Aim: Assessing reporting quality is important as it allows distinctions to be made between poor methodology and poor reporting practices. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was published in 2017 to improve the thoroughness and reporting quality of clinical practice guidelines (CPGs). CPGs are evidence-based recommendations developed to assist clinician decision-making in the diagnosis and management of patients. The aim of this study is to assess the completeness of reporting in CPGs listed by the American College of Gastroenterology (ACG) and their frequency of reporting items listed in the RIGHT Statement. Methods: Using the 22 criteria (35 items) of the RIGHT Statement checklist, two researchers independently documented the adherence to each item for all eligible guidelines listed by the ACG. This study was conducted from 01/10/18 to 05/12/18. Data were recorded onto a prespecified Google data abstraction form and extracted into MS Excel for statistical analysis. Results: Out of 38 eligible guidelines, nine of the 35 RIGHT (25.7%) checklist items were met with less than 50% adherence. The mean adherence was 26.8 (SD +/- 9.5); median adherence was 30 (interquartile range 21.5-33.5). The publication dates ranged from 2007 to 2017 with seven of the guidelines (18.4%) published between 2007 and 2009, 11 (29%) published between 2010 and 2013, and 20 (52.6%) published between 2014 and 2017. Conclusion: The completeness of reporting in CPGs listed by the ACG remains inadequate in several key areas. Poor adherence to items of the RIGHT Statement checklist demonstrates that there is area for improvement in reporting quality. [ABSTRACT FROM AUTHOR]

We prove an invariance property of intersections of Kudla–Rapoport divisors on a unitary Rapoport–Zink space. [ABSTRACT FROM AUTHOR]

Let F be the field of rational functions on a smooth projective curve over a finite field, and let π be an unramified cuspidal automorphic representation for PGL 2 over F. We prove a variant of the formula of Yun and Zhang relating derivatives of the L -function of π to the self-intersections of Heegner-Drinfeld cycles on moduli spaces of shtukas. In our variant, instead of a self-intersection, we compute the intersection pairing of Heegner-Drinfeld cycles coming from two different quadratic extensions of F , and relate the intersection to the r -th derivative of a product of two toric period integrals. [ABSTRACT FROM AUTHOR]

Patients are faced with many questions surrounding the after effects of the various surgical procedures and their ability to return to preoperative activities. While patients often question whether surgery would provide alleviation of pain, weakness, and instability, they often have additional questions about sexual activity during their convalescence that are not always addressed. Although the literature shows postsurgical improvement in sexual activity in association with improved low back pain, reports vaguely address the variability in sexual activity recommendations based on anatomic location and type of spinal surgery. We conducted a PubMed search of the English language from 1990 to 2018 with the following keywords: sexual activity, postoperative, spinal fusion, spinal decompression, functional outcomes, laminectomy, rehabilitation, biomechanics, lumbar disc surgery, metabolic energy expenditure, coital position, and Oswestry Disability Index. Additional studies are needed that survey both patients and spine surgeons to examine current recommendations and to help formulate future guidelines. [ABSTRACT FROM AUTHOR]

This literature review examines the relative placement of the interbody cage with respect to the unilateral screw construct to address the need for bilateral screw placement versus unilateral screw placement. Transforaminal lumbar interbody fusion (TLIF) has become a widely used technique for correcting lumbar intervertebral pathologies. This review addresses the necessity for further study on the effects of the relative position of intervertebral cage placement on the outcome of lumbar spine surgery after TLIF with unilateral pedicle screw fixation. Previous studies have addressed various factors, including posterior screw fixation, cage size, cage shape, and number of levels fused, that impact the biomechanics of the lumbar spine following TLIF. A simple survey of the literature was conducted. A search of the English literature was conducted using the keywords ‘TLIF,’ ‘transforaminal lumbar interbody fusion,’ ‘graft placement,’ ‘graft position,’ ‘cage position,’ ‘cage placement,’ ‘unilateral pedicle screw,’ ‘unilateral TLIF cage placement,’ ‘lumbar biomechanics,’ ‘lumbar stability,’ ‘lumbar fusion,’ and ‘lumbar intervertebral cage’ with various combinations of the operators ‘AND’ and ‘OR’ and no date restrictions. Seventeen articles in the English literature that were most relevant to this research question were identified. To the best of our knowledge, there are no published data addressing the effects of cage placement relative to the unilateral screw on lumbar stability in TLIF with unilateral pedicle screw fixation. Investigation of the effects of cage placement is, thus, warranted to achieve optimal clinical outcomes in patients undergoing TLIF with unilateral pedicle screw fixation. [ABSTRACT FROM AUTHOR]

Background: Selective outcome reporting is a significant methodological concern. Comparisons between the outcomes reported in clinical trial registrations and those later published allow investigators to understand the extent of selection bias among trialists. We examined the possibility of selective outcome reporting in randomized controlled trials (RCTs) published in neurology journals. Methods: We searched PubMed for randomized controlled trials from Jan 1, 2010 –Dec 31, 2015 published in the top 3 impact factor neurology journals. These articles were screened according to specific inclusion criteria. Each author individually extracted data from trials following a standardized protocol. A second author verified each extracted element and discrepancies were resolved. Consistency between registered and published outcomes was evaluated and correlations between discrepancies and funding, journal, and temporal trends were examined. Results: 180 trials were included for analysis. 10 (6%) primary outcomes were demoted, 38 (21%) primary outcomes were omitted from the publication, and 61 (34%) unregistered primary outcomes were added to the published report. There were 18 (10%) cases of secondary outcomes being upgraded to primary outcomes in the publication, and there were 53 (29%) changes in timing of assessment. Of 82 (46%) major discrepancies with reported p-values, 54 (66.0%) favored publication of statistically significant results. Conclusion: Across trials, we found 180 major discrepancies. 66% of major discrepancies with a reported p-value (n = 82) favored statistically significant results. These results suggest a need within neurology to provide more consistent and timely registration of outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Acute traumatic coagulopathy has been associated with shock and tissue injury, and may be mediated via activation of the protein C pathway. Patients with acute traumatic coagulopathy have prolonged PT and PTT, and decreased activity of factors V and VIII; they are also hypocoagulable by thromboelastometry (ROTEM) and other viscoelastic assays. To test the etiology of this phenomenon, we hypothesized that such coagulopathy could be induced in vitro in healthy human blood with the addition of activated protein C (aPC). Methods: Whole blood was collected from 20 healthy human subjects, and was “spiked” with increasing concentrations of purified human aPC (control, 75, 300, 2000 ng/mL). PT/PTT, factor activity assays, and ROTEM were performed on each sample. Mixed effect regression modeling was performed to assess the association of aPC concentration with PT/PTT, factor activity, and ROTEM parameters. Results: In all subjects, increasing concentrations of aPC produced ROTEM tracings consistent with traumatic coagulopathy. ROTEM EXTEM parameters differed significantly by aPC concentration, with stepwise prolongation of clotting time (CT) and clot formation time (CFT), decreased alpha angle (α), impaired early clot formation (a10 and a20), and reduced maximum clot firmness (MCF). PT and PTT were significantly prolonged at higher aPC concentrations, with corresponding significant decreases in factor V and VIII activity. Conclusion: A phenotype of acute traumatic coagulopathy can be induced in healthy blood by the in vitro addition of aPC alone, as evidenced by viscoelastic measures and confirmed by conventional coagulation assays and factor activity. This may lend further mechanistic insight to the etiology of coagulation abnormalities in trauma, supporting the central role of the protein C pathway. Our findings also represent a model for future investigations in the diagnosis and treatment of acute traumatic coagulopathy. [ABSTRACT FROM AUTHOR]

We study special cycles on integral models of Shimura varieties associated with unitary similitude groups of signature $$(n-1,1)$$ . We construct an arithmetic theta lift from harmonic Maass forms of weight $$2-n$$ to the arithmetic Chow group of the integral model of a unitary Shimura variety, by associating to a harmonic Maass form $$f$$ a linear combination of Kudla-Rapoport divisors, equipped with the Green function given by the regularized theta lift of $$f$$ . Our main result is an equality of two complex numbers: (1) the height pairing of the arithmetic theta lift of $$f$$ against a CM cycle, and (2) the central derivative of the convolution $$L$$ -function of a weight $$n$$ cusp form (depending on $$f$$ ) and the theta function of a positive definite hermitian lattice of rank $$n-1$$ . When specialized to the case $$n=2$$ , this result can be viewed as a variant of the Gross-Zagier formula for Shimura curves associated to unitary groups of signature $$(1,1)$$ . The proof relies on, among other things, a new method for computing improper arithmetic intersections. [ABSTRACT FROM AUTHOR]

This paper is about the arithmetic of Kudla-Rapoport divisors on Shimura varieties of type GU(n - 1,1). In the first part of the paper we construct a toroidal compactification of N. Krämer's integral model of the Shimura variety. This extends work of K.-W. Lan, who constructed a compactification at unramified primes. In the second, and main, part of the paper we use ideas of Kudla to construct Green functions for the Kudla-Rapoport divisors on the open Shimura variety, and analyze the behavior of these functions near the boundary of the compactification. The Green functions turn out to have logarithmic singularities along certain components of the boundary, up to log-log error terms. Thus, by adding a prescribed linear combination of boundary components to a Kudla-Rapoport divisor one obtains a class in the arithmetic Chow group of Burgos-Kramer-Kühn. In the third and final part of the paper we compute the arithmetic intersection of each of these divisors with a cycle of complex multiplication points. The computation is quickly reduced to the calculations of the author's earlier work Complex multiplication cycles and Kudla-Rapoport divisors. The arithmetic intersection multiplicities are shown to appear as Fourier coefficients of the diagonal restriction of the central derivative of a Hilbert modular Eisenstein series. [ABSTRACT FROM AUTHOR]

This paper deals with the geometry of the space [Geometric Invariant Theory (GIT) quotient] M8 of eight points in ℙ1, and the Gale-quotient N′8 of the GIT quotient of eight points in ℙ3.The space M8 comes with a natural embedding in ℙ13, or more precisely, the projectivization of the 8-representation V4, 4. There is a single 8-skew cubic  in ℙ13. The fact that M8 lies on the skew cubic  is a consequence of Thomae's formula for hyperelliptic curves, but more is true: M8 is the singular locus of . These constructions yield the free resolution of M8 and are used in the determination of the ‘single’ equation cutting out the GIT quotient of n points in ℙ1 in general [20].The space N′8 comes with a natural embedding in ℙ13, or more precisely, ℙ V2, 2, 2, 2. There is a single skew quintic  containing N′8 and N′8 is the singular locus of the skew quintic .The skew cubic  and skew quintic  are projectively dual. (In particular, they are surprisingly singular, in the sense of having a dual of remarkably low degree.) The divisor on the skew cubic blown down by the dual map is the secant variety Sec(M8) and the contraction Sec(M8) → N′8 factors through N8 via the space of eight points on a quadric surface. We conjecture (Conjecture 1.1) that the divisor on the skew quintic blown down by the dual map is the quadrisecant variety of N′8 (the closure of the union of quadrisecant lines), and that the quintic  is the trisecant variety. The resulting picture extends the classical duality in the 6-point case between the Segre cubic threefold and the Igusa quartic threefold.We note that there are a number of geometrically natural varieties that are (related to) the singular loci of remarkably singular cubic hypersurfaces (see for example [3, 5]). [ABSTRACT FROM PUBLISHER]

Consider the projective coordinate ring of the Geometric Invariant Theory (GIT) quotient (ℙ1) n //SL(2), with the usual linearization, where n is even. In 1894, Kempe proved that this ring is generated in degree one. In [2] we showed that, over ℚ, the relations between degree one invariants are generated by a class of quadratic relations—the simplest binomial relations—with the exception of n = 6, where there is a single cubic relation. The purpose of this article is to show that these results hold over , and to suggest why they may be true over . [ABSTRACT FROM PUBLISHER]

The ring of projective invariants of n ordered points on the projective line is one of the most basic and earliest studied examples in Geometric Invariant Theory. It is a remarkable fact and the point of this paper that, unlike its close relative the ring of invariants of n unordered points, this ring can be completely and simply described. In 1894 Kempe found generators for this ring, thereby proving the First Main Theorem for it (in the terminology introduced by Weyl). In this paper we compute the relations among Kempe's invariants, thereby proving the SecondMain Theorem (again in the terminology of Weyl), and completing the description of the ring 115 years later. This paper introduces a number of new tools to the problem, and uses the graphical algebra formalismto intermediate between representation-theoretic arguments (for symmetric and Lie groups), and the symmetry-breaking of the Speyer-Sturmfels degeneration. [ABSTRACT FROM AUTHOR]

This is the third of a series of papers relating intersections of special cycles on the integral model of a Shimura surface to Fourier coefficients of Hilbert modular forms. More precisely, we embed the Shimura curve over ℚ associated to a rational quaternion algebra into the Shimura surface associated to the base change of the quaternion algebra to a real quadratic field. After extending the associated moduli problems over ℤ we obtain an arithmetic threefold with a embedded arithmetic surface, which we view as a cycle of codimension one. We then construct a family, indexed by totally positive algebraic integers in the real quadratic field, of codimension two cycles (complex multiplication points) on the arithmetic threefold. The intersection multiplicities of the codimension two cycles with the fixed codimension one cycle are shown to agree with the Fourier coefficients of a (very particular) Hilbert modular form of weight 3/2. The results are higher dimensional variants of results of Kudla-Rapoport-Yang, which relate intersection multiplicities of special cycles on the integral model of a Shimura curve to Fourier coefficients of a modular form in two variables. [ABSTRACT FROM AUTHOR]

Abstract: Let be a Geometric Invariant Theory quotient of a partial flag variety by the action of the maximal torus T in , where P is a parabolic subgroup containing T. The construction of depends upon the choice of a T-linearized line bundle L of F. This note concerns the case is a very ample homogeneous line bundle determined by a dominant weight λ, meaning the associated character extends to P and to no larger parabolic subgroup. If denotes the irreducible representation of with highest weight λ, and is the isotypic component corresponding to a weight μ of the torus, then is equal to . The weight μ is used to twist the canonical T-linearization of , where the canonical T-linearization of is obtained by restricting the unique -linearization of to T. We apply a theorem of Gel''fand, Goresky, MacPherson, and Serganova concerning matroid polytopes to show that if then one gets a well-defined map by taking any basis of . Equivalently, all the semistable partial flags are detected by degree one T-invariants provided is nonzero. We also show that the closure of any T-orbit in F is projectively normal for the projective embedding . [Copyright &y& Elsevier]

Given a weight two modular form f with associated p-adic Galois representation V f , for certain quadratic imaginary fields K one can construct canonical classes in the Galois cohomology of V f by taking the Kummer images of Heegner points on the modular abelian variety attached to f. We show that these classes can be interpolated as f varies in a Hida family and construct an Euler system of big Heegner points for Hida’s universal ordinary deformation of V f . We show that the specialization of this big Euler system to any form in the Hida family is nontrivial, extending results of Cornut and Vatsal from modular forms of weight two and trivial character to all ordinary modular forms, and propose a horizontal nonvanishing conjecture for these cohomology classes. The horizontal nonvanishing conjecture implies, via the theory of Euler systems, a conjecture of Greenberg on the generic ranks of Selmer groups in Hida families. [ABSTRACT FROM AUTHOR]

Abstract: Building on ideas of Vatsal [Uniform distribution of Heegner points, Invent. Math. 148(1) (2002) 1–46], Cornut [Mazur''s conjecture on higher Heegner points, Invent. Math. 148(3) (2002) 495–523] proved a conjecture of Mazur asserting the generic nonvanishing of Heegner points on an elliptic curve as one ascends the anticyclotomic -extension of a quadratic imaginary extension . In the present article, Cornut''s result is extended by replacing the elliptic curve E with the Galois cohomology of Deligne''s two-dimensional -adic representation attached to a modular form of weight , and replacing the family of Heegner points with an analogous family of special cohomology classes. [Copyright &y& Elsevier]

The 1990 Clean Air Act Amendments required the United States Environmental Protection Agency (U.S. EPA) to enact stricter regulations aimed at reducing benzene emissions. In an effort to determine whether these new regulations have been successful in reducing atmospheric benzene concentrations, we have evaluated benzene-to-acetylene ratios from data sets spanning nearly three decades, collected during several field studies and from the U.S. EPA's Photochemical Assessment Monitoring Station (PAMS) network. The field-study data indicate a decrease in benzene relative to acetylene of approximately 40% from 1994 to 2002. This corresponds to a decrease in benzene alone of approximately 56% over the same period. In contrast the PAMS data exhibit high interannual variability with no discernible trend. This discrepancy is attributed to measurement problems in the PAMS data sets. [ABSTRACT FROM AUTHOR]

If E is an elliptic curve defined over a number field and p is a prime of good ordinary reduction for E, a theorem of Rubin relates the p-adic height pairing on the p-power Selmer group of E to the first derivative of a cohomologically defined p-adic L-function attached to E. Bertolini and Darmon have defined a sequence of "derived" p-adic heights. In this paper we give an alternative definition of the p-adic height pairing and prove a generalization of Rubin's result, relating the derived heights to higher derivatives of p-adic L-functions. We also relate degeneracies in the derived heights to the failure of the Selmer group of F over a Zp-extension to be "semi-simple" as an Iwasawa module, generalizing results of Perrin-Riou. [ABSTRACT FROM AUTHOR]

The release of paused RNA polymerase II (RNAPII) from promoter-proximal regions is tightly controlled to ensure proper regulation of gene expression. The elongation factor PTEF-b is known to release paused RNAPII via phosphorylation of the RNAPII C-terminal domain by its cyclin-dependent kinase component, CDK9. However, the signal and stress-specific roles of the various RNAPII-associated macromolecular complexes containing PTEF-b/CDK9 are not yet clear. Here, we identify and characterize the CDK9 complex required for transcriptional response to hypoxia. Contrary to previous reports, our data indicate that a CDK9 complex containing BRD4 but not AFF1/4 is essential for this hypoxic stress response. We demonstrate that BRD4 bromodomains (BET) are dispensable for the release of paused RNAPII at hypoxia-activated genes and that BET inhibition by JQ1 is insufficient to impair hypoxic gene response. Mechanistically, we demonstrate that the C-terminal region of BRD4 is required for Polymerase-Associated Factor-1 Complex (PAF1C) recruitment to establish an elongation-competent RNAPII complex at hypoxia-responsive genes. PAF1C disruption using a small-molecule inhibitor (iPAF1C) impairs hypoxia-induced, BRD4-mediated RNAPII release. Together, our results provide insight into potentially targetable mechanisms that control the hypoxia-responsive transcriptional elongation. [ABSTRACT FROM AUTHOR]

The biological role of the repetitive DNA sequences in the human genome remains an outstanding question. Recent long-read human genome assemblies have allowed us to identify a function for one of these repetitive regions. We have uncovered a tandem array of conserved primate-specific retrogenes encoding the protein Elongin A3 (ELOA3), a homolog of the RNA polymerase II (RNAPII) elongation factor Elongin A (ELOA). Our genomic analysis shows that the ELOA3 gene cluster is conserved among primates and the number of ELOA3 gene repeats is variable in the human population and across primate species. Moreover, the gene cluster has undergone concerted evolution and homogenization within primates. Our biochemical studies show that ELOA3 functions as a promoter-associated RNAPII pause-release elongation factor with distinct biochemical and functional features from its ancestral homolog, ELOA. We propose that the ELOA3 gene cluster has evolved to fulfil a transcriptional regulatory function unique to the primate lineage that can be targeted to regulate cellular hyperproliferation. [ABSTRACT FROM AUTHOR]

The BET family protein BRD4, which forms the CDK9-containing BRD4-PTEFb complex, is considered to be a master regulator of RNA polymerase II (Pol II) pause release. Because its tandem bromodomains interact with acetylated histone lysine residues, it has long been thought that BRD4 requires these bromodomains for its recruitment to chromatin and transcriptional regulatory function. Here, using rapid depletion and genetic complementation with domain deletion mutants, we demonstrate that BRD4 bromodomains are dispensable for Pol II pause release. A minimal, bromodomain-less C-terminal BRD4 fragment containing the PTEFb-interacting C-terminal motif (CTM) is instead both necessary and sufficient to mediate Pol II pause release in the absence of full-length BRD4. Although BRD4-PTEFb can associate with chromatin through acetyl recognition, our results indicate that a distinct, active BRD4-PTEFb population functions to regulate transcription independently of bromodomain-mediated chromatin association. These findings may enable more effective pharmaceutical modulation of BRD4-PTEFb activity. [Display omitted] • Unlike BETi (JQ1), BRD4 degradation causes profound Pol II pausing genome wide • The bromodomains of BRD4 are dispensable for Pol II pause release in living cells • A BET-less C-terminal BRD4 fragment interacts with PTEFb and releases paused Pol II • The C-terminal disordered region of BRD4 secures cyclin T1 in the BRD4-PTEFb complex Zheng et al. demonstrate that while the regulation of Pol II pause release by BRD4 does not require bromodomain-mediated BRD4 binding to acetylated histones, a bromodomain-less, C-terminal fragment of BRD4 is both necessary and sufficient to drive the release of paused Pol II into productive elongation. [ABSTRACT FROM AUTHOR]

Introduction: Recent evidence suggests a lack of standardization of shoulder arthroplasty outcomes. This issue is a limiting factor in systematic reviews. Core outcome set (COS) methodology could address this problem by delineating a minimum set of outcomes for measurement in all shoulder arthroplasty trials. Methods: A ClinicalTrials.gov search yielded 114 results. Eligible trials were coded on the following characteristics: study status, study type, arthroplasty type, sample size, measured outcomes, outcome measurement device, specific metric of measurement, method of aggregation, outcome classification, and adverse events. Results: Sixty-six trials underwent data abstraction and data synthesis. Following abstraction, 383 shoulder arthroplasty outcomes were organized into 11 outcome domains. The most commonly reported outcomes were shoulder outcome score (n = 58), pain (n = 33), and quality of life (n = 15). The most common measurement devices were the Constant-Murley Shoulder Outcome Score (n = 38) and American Shoulder and Elbow Surgeons Shoulder Score (n = 33). Temporal patterns of outcome use was also found. Conclusion: Our study suggests the need for greater standardization of outcomes and instruments. The lack of consistency across trials indicates that developing a core outcome set for shoulder arthroplasty trials would be worthwhile. Such standardization would allow for more effective comparison across studies in systematic reviews, while at the same time consider important outcomes that may be underrepresented otherwise. This review of outcomes provides an evidence-based foundation for the development of a COS for shoulder arthroplasty. [ABSTRACT FROM AUTHOR]