We study the Becchi-Rouet-Stora-Tyutin (BRST) renormalization of an alternative formulation of the Yang-Mills theory, where the matrix-propagator of the gluon and the complementary fields is ...diagonal. This procedure involves scalings as well as nonlinear mixings of the fields and sources. We show, in the Landau gauge, that the BRST identities implement a recursive proof of renormalizability to all orders.
We present four new epochs of Ks-band images of the young pre-transitional disk around LkCa 15 and perform extensive forward modeling to derive the physical parameters of the disk. We find ...indications of strongly anisotropic scattering (Henyey-Greenstein g = 0.67-0.11+0.18) and a significantly tapered gap edge (“round wall”) but see no evidence that the inner disk, whose existence is predicted by the spectral energy distribution, shadows the outer regions of the disk visible in our images. We marginally confirm the existence of an offset between the disk center and the star along the line of nodes; however, the magnitude of this offset (x = 27-20+19 mas) is notably lower than that found in our earlier H-band images. Intriguingly, we also find an offset of y=69-25+49 mas perpendicular to the line of nodes at high significance. If confirmed by future observations, this would imply a highly elliptical – or otherwise asymmetric – disk gap with an effective eccentricity of e ≈ 0.3. Such asymmetry would most likely be the result of dynamical sculpting by one or more unseen planets in the system. Finally, we find that the bright arc of scattered light we see in direct imaging observations originates from the near side of the disk and appears brighter than the far side because of strong forward scattering.
Clopidogrel requires transformation into an active metabolite by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. The genes encoding CYP enzymes are polymorphic, with common alleles ...conferring reduced function.
We tested the association between functional genetic variants in CYP genes, plasma concentrations of active drug metabolite, and platelet inhibition in response to clopidogrel in 162 healthy subjects. We then examined the association between these genetic variants and cardiovascular outcomes in a separate cohort of 1477 subjects with acute coronary syndromes who were treated with clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38.
In healthy subjects who were treated with clopidogrel, carriers of at least one CYP2C19 reduced-function allele (approximately 30% of the study population) had a relative reduction of 32.4% in plasma exposure to the active metabolite of clopidogrel, as compared with noncarriers (P<0.001). Carriers also had an absolute reduction in maximal platelet aggregation in response to clopidogrel that was 9 percentage points less than that seen in noncarriers (P<0.001). Among clopidogrel-treated subjects in TRITON-TIMI 38, carriers had a relative increase of 53% in the composite primary efficacy outcome of the risk of death from cardiovascular causes, myocardial infarction, or stroke, as compared with noncarriers (12.1% vs. 8.0%; hazard ratio for carriers, 1.53; 95% confidence interval CI, 1.07 to 2.19; P=0.01) and an increase by a factor of 3 in the risk of stent thrombosis (2.6% vs. 0.8%; hazard ratio, 3.09; 95% CI, 1.19 to 8.00; P=0.02).
Among persons treated with clopidogrel, carriers of a reduced-function CYP2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis, than did noncarriers.
We study the self-consistency of the first-order formulation of quantum gravity, which may be attained by introducing, apart from the graviton field, another auxiliary quantum field. By comparing the ...forms of the generating functional Z before and after integrating out the additional field, we derive a set of structural identities, which must be satisfied by the Green's functions at all orders. These are distinct from the usual Ward identities, being necessary for the self-consistency of the first-order formalism. They relate the Green's functions involving the additional quantum field to those containing a certain composite graviton field, which corresponds to its classical value. Thereby, the structural identities lead to a simple interpretation of the auxiliary field.
Many migratory animals are experiencing rapid population declines, but migration data with the geographic scope and resolution to quantify the complex network of movements between breeding and ...nonbreeding regions are often lacking. Determining the most frequently used migration routes and nonbreeding regions for a species is critical for understanding population dynamics and making effective conservation decisions. We tracked the migration of individual Wood Thrushes (Hylocichla mustelina) (n = 102) from across their range with light‐level geolocators and, for the first time, quantified migration routes and wintering regions for distinct breeding populations. We identified regional and species‐level migratory connectivity networks for this declining songbird by combining our tracking results with range‐wide breeding abundance estimates and forest cover data. More than 50% of the species occupied the eastern wintering range (Honduras to Costa Rica), a region that includes only one‐third of all wintering habitat and that is undergoing intensive deforestation. We estimated that half of all Wood Thrushes in North America migrate south through Florida in fall, whereas in spring approximately 73% funnel northward through a narrow span along the central U.S. Gulf Coast (88–93°W). Identifying migratory networks is a critical step for conservation of songbirds and we demonstrated with Wood Thrushes how it can highlight conservation hotspots for regional populations and species as a whole.
To examine whether risk factor profile, baseline features, and outcome of cervical artery dissection (CEAD) differ according to the dissection site.
We analyzed 982 consecutive patients with CEAD ...included in the Cervical Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with internal carotid artery dissection ICAD, n = 327 with vertebral artery dissection VAD, n = 36 with ICAD and VAD).
Patients with ICAD were older (p < 0.0001), more often men (p = 0.006), more frequently had a recent infection (odds ratio OR = 1.59 95% confidence interval (CI) 1.09-2.31), and tended to report less often a minor neck trauma in the previous month (OR = 0.75 0.56-1.007) compared to patients with VAD. Clinically, patients with ICAD more often presented with headache at admission (OR = 1.36 1.01-1.84) but less frequently complained of cervical pain (OR = 0.36 0.27-0.48) or had cerebral ischemia (OR = 0.32 0.21-0.49) than patients with VAD. Among patients with CEAD who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission was higher in patients with ICAD than patients with VAD (OR = 1.17 1.12-1.22). Aneurysmal dilatation was more common (OR = 1.80 1.13-2.87) and bilateral dissection less frequent (OR = 0.63 0.42-0.95) in patients with ICAD. Multiple concomitant dissections tended to cluster on the same artery type rather than involving both a vertebral and carotid artery. Patients with ICAD had a less favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99 2.32-6.88), but this was no longer significant after adjusting for baseline NIHSS score.
In the largest published series of patients with CEAD, we observed significant differences between VAD and ICAD in terms of risk factors, baseline features, and functional outcome.
Highlights ► We examine magnitude and structure of gait variability in cerebellar ataxia patients. ► Pathological alterations in gait variability are dependent on the walking speed. ► Increased ...levels of gait variability mostly occur at slow and fast walking speeds. ► Preferred walking speed is associated with minimal levels of gait variability.
Aims The metabolic pathways leading to the formation of prasugrel and clopidogrel active metabolites differ. We hypothesized that decreased CYP2C19 activity affects the pharmacokinetic and ...pharmacodynamic response to clopidogrel but not prasugrel. Methods and results Ninety-eight patients with coronary artery disease (CAD) taking either clopidogrel 600 mg loading dose (LD)/75 mg maintenance dose (MD) or prasugrel 60 mg LD/10 mg MD were genotyped for variation in six CYP genes. Based on CYP genotype, patients were segregated into two groups: normal function (extensive) metabolizers (EM) and reduced function metabolizers (RM). Plasma active metabolite concentrations were measured at 30 min, 1, 2, 4, and 6 h post-LD and during the MD period on Day 2, Day 14, and Day 29 at 30 min, 1, 2, and 4 h. Vasodilator-stimulated phosphoprotein (VASP) and VerifyNow™ P2Y12 were measured predose, 2, and 24 ± 4 h post-LD and predose during the MD period on Day 14 ± 3 and Day 29 ± 3. For clopidogrel, active metabolite exposure was significantly lower (P = 0.0015) and VASP platelet reactivity index (PRI, %) and VerifyNow™ P2Y12 reaction unit (PRU) values were significantly higher (P < 0.05) in the CYP2C19 RM compared with the EM group. For prasugrel, there was no statistically significant difference in active metabolite exposure or pharmacodynamic response between CYP2C19 EM and RM. Variation in the other five genes demonstrated no statistically significant differences in pharmacokinetic or pharmacodynamic responses. Conclusion Variation in the gene encoding CYP2C19 in patients with stable CAD contributes to reduced exposure to clopidogrel's active metabolite and a corresponding reduction in P2Y12 inhibition, but has no significant influence on the response to prasugrel.
Data on risk factors for etiologic subtypes of ischemic stroke are still scant. The aim of this study was to characterize stroke subtypes regarding risk factor profile, outcome, and current treatment ...strategies.
We analyzed data from 5017 patients with acute ischemic stroke (42.4% women, aged 65.9+/-14.1 years) who were enrolled in a large multicenter hospital-based stroke data bank. Standardized data assessment and stroke subtype classification were used by all centers.
Sex and age distribution, major risk factors and comorbidities, recurrent stroke, treatment strategies, and outcome were all unevenly distributed among stroke subtypes (P<0.001, respectively). Cardioembolism, the most frequent etiology of stroke (25.6%), was particularly common in the elderly (those aged >70 years) and associated with an adverse outcome, a low rate of early stroke recurrence, and frequent use of thrombolytic therapy and intravenous anticoagulation. Large-artery atherosclerosis (20.9%), the most common cause of stroke in middle-aged patients (those aged 45 to 70 years), showed the highest male preponderance, highest rate of early stroke recurrence, and highest prevalence of previous transient ischemic attack, current smoking, and daily alcohol consumption among all subtypes. The highest prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and obesity was found in small-vessel disease (20.5%), which, in turn, was associated with the lowest stroke severity and mortality.
Our results foster the concept of ischemic stroke as a polyetiologic disease with marked differences between subtypes regarding risk factors and outcome. Therefore, studies involving risk factors of ischemic stroke should differentiate between etiologic stroke subtypes.
Downbeat nystagmus (DBN) is the most common form of acquired involuntary ocular oscillation overriding fixation. According to previous studies, the cause of DBN is unsolved in up to 44% of cases. We ...reviewed 117 patients to establish whether analysis of a large collective and improved diagnostic means would reduce the number of cases with "idiopathic DBN" and thus change the aetiological spectrum.
The medical records of all patients diagnosed with DBN in our Neurological Dizziness Unit between 1992 and 2006 were reviewed. In the final analysis, only those with documented cranial MRI were included. Their workup comprised a detailed history, standardised neurological, neuro-otological and neuro-ophthalmological examination, and further laboratory tests.
In 62% (n = 72) of patients the aetiology was identified ("secondary DBN"), the most frequent causes being cerebellar degeneration (n = 23) and cerebellar ischaemia (n = 10). In 38% (n = 45), no cause was found ("idiopathic DBN"). A major finding was the high comorbidity of both idiopathic and secondary DBN with bilateral vestibulopathy (36%) and the association with polyneuropathy and cerebellar ataxia even without cerebellar pathology on MRI.
Idiopathic DBN remains common despite improved diagnostic techniques. Our findings allow the classification of "idiopathic DBN" into three subgroups: "pure" DBN (n = 17); "cerebellar" DBN (ie, DBN plus further cerebellar signs in the absence of cerebellar pathology on MRI; n = 6); and a "syndromatic" form of DBN associated with at least two of the following: bilateral vestibulopathy, cerebellar signs and peripheral neuropathy (n = 16). The latter may be caused by multisystem neurodegeneration.
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