Search

Background: Heavy charged particles after nuclear muon capture are an important nuclear physics background to the muon-to-electron conversion experiments Mu2e and COMET, which will search for charged lepton flavor violation at an unprecedented level of sensitivity. Purpose: The AlCap experiment aimed to measure the yield and energy spectra of protons, deuterons, tritons, and α particles emitted after the nuclear capture of muons stopped in Al, Si, and Ti in the low-energy range relevant for the muon-to-electron conversion experiments. Methods: Individual charged particle types were identified in layered silicon detector packages and their initial energy distributions were unfolded from the observed energy spectra. Results: The proton yields per muon capture were determined as Y p ( Al ) = 26.64 ( 28 stat. ) ( 77 syst. ) × 10 − 3 and Y p ( Ti ) = 26.48 ( 35 ) ( 80 ) × 10 − 3 in the energy range 3.5–20.0 MeV, and as Y p ( Si ) = 52.5 ( 6 ) ( 18 ) × 10 − 3 in the energy range 4.0–20.0 MeV. Detailed information on yields and energy spectra for all observed nuclei are presented in the paper. Conclusions: The yields in the candidate muon stopping targets, Al and Ti, are approximately half of that in Si, which was used in the past to estimate this background. The reduced background allows for less shielding and a better energy resolution in these experiments. It is anticipated that the comprehensive information presented in this paper will stimulate modern theoretical calculations of the rare process of muon capture with charged particle emission and inform the design of future muon-to-electron conversion experiments.

ObjectiveAntipsychotic drugs are well established to alter circulating prolactin levels by blocking dopamine D-2 receptors in the pituitary. Prolactin activates many genes important in the development of breast cancer. The aim of this study was to evaluate the risk of breast cancer in women exposed to antipsychotic drugs, stratified by prolactin elevating potential (high, mid, and low), compared to women taking anticonvulsants and/or lithium.MethodsThe IBM MarketScan Commercial and Medicaid Databases were used to establish a large, observational cohort of women taking antipsychotics drugs compared to control drugs. Invasive breast cancer was identified using diagnostic codes. Bivariable and multivariable Cox proportional hazards models were used to evaluate the risk of breast cancer by antipsychotic drug exposure, both as pooled antipsychotics and by prolactin specific categories.ResultsA total of 2,708 (0.2%) cases of invasive breast cancer were identified among 1,562,839 women. Exposure to antipsychotics with high prolactin elevating potential was associated with a 23% increased risk of breast cancer (aHR 1.23; 95% CI, 1.11-1.35), whereas mid and low prolactin categories of antipsychotics were not significant.ConclusionIn the largest study of antipsychotics taken by women, a modest risk between antipsychotic drug use and the risk for breast cancer was observed, with a differential higher association with high prolactin elevating drugs. Residual confounding factors included incomplete information on parity, race and socioeconomic status, and differential outpatient visits. Clinicians should consider monitoring serum prolactin levels and adopting vigilant mammography screening practices, especially in older women taking category one antipsychotics.

The Muon g - 2 Experiment at Fermi National Accelerator Laboratory (FNAL) has measured the muon anomalous precession frequency omega(m)(a) to an uncertainty of 434 parts per billion (ppb), statistical, and 56 ppb, systematic, with data collected in four storage ring configurations during its first physics run in 2018. When combined with a precision measurement of the magnetic field of the experiment's muon storage ring, the precession frequency measurement determines a muon magnetic anomaly of a(mu) (FNAL) = 116 592 040(54) x 10(-11) (0.46 ppm). This article describes the multiple techniques employed in the reconstruction, analysis, and fitting of the data to measure the precession frequency. It also presents the averaging of the results from the 11 separate determinations of omega(m)(a), and the systematic uncertainties on the result.

The peanosphere (or "mating of trees") construction of Duplantier, Miller, and Sheffield encodes certain types of $\gamma$-Liouville quantum gravity (LQG) surfaces ($\gamma \in (0,2)$) decorated with an independent SLE$_{\kappa}$ ($\kappa = 16/\gamma^2 > 4$) in terms of a correlated two-dimensional Brownian motion and provides a framework for showing that random planar maps decorated with statistical physics models converge to LQG decorated with an SLE. Previously, the correlation for the Brownian motion was only explicitly identified as $-\cos(4\pi/\kappa)$ for $\kappa \in (4,8]$ and unknown for $\kappa > 8$. The main result of this work is that this formula holds for all $\kappa > 4$. This supplies the missing ingredient for proving convergence results of the aforementioned type for $\kappa > 8$. Our proof is based on the calculation of a certain tail exponent for SLE$_{\kappa}$ on a quantum wedge and then matching it with an exponent which is well-known for Brownian motion.

Conformal loop ensembles (CLEs) are random collections of loops in a simply connected domain, whose laws are characterized by a natural conformal invariance property. The set of points not surrounded by any loop is a canonical random connected fractal set — a random and conformally invariant analog of the Sierpinski carpet or gasket. In the present paper, we derive a direct relationship between the CLEs with simple loops (CLEκ for κ ∈ (8/3, 4), whose loops are Schramm’s SLEκ -type curves) and the corresponding CLEs with nonsimple loops (CLEκ 0 with κ 0 := 16/κ ∈ (4, 6), whose loops are SLEκ 0-type curves). This correspondence is the continuum analog of the Edwards–Sokal coupling between the q-state Potts model and the associated FK random cluster model, and its generalization to noninteger q. Like its discrete analog, our continuum correspondence has two directions. First, we show that for each κ ∈ (8/3, 4), one can construct a variant of CLEκ as follows: start with an instance of CLEκ 0 , then use a biased coin to independently color each CLEκ 0 loop in one of two colors, and then consider the outer boundaries of the clusters of loops of a given color. Second, we show how to interpret CLEκ 0 loops as interfaces of a continuum analog of critical Bernoulli percolation within CLEκ carpets — this is the first construction of continuum percolation on a fractal planar domain. It extends and generalizes the continuum percolation on open domains defined by SLE6 and CLE6. These constructions allow us to prove several conjectures made by the second author and provide new and perhaps surprising interpretations of the relationship between CLEs and the Gaussian free field. Along the way, we obtain new results about generalized SLEκ (ρ) curves for ρ < −2, such as their decomposition into collections of SLEκ -type ‘loops’ hanging off of SLEκ 0-type ‘trunks’, and vice versa (exchanging κ and κ 0 ). We also define a continuous family of natural CLE variants called boundary conformal loop ensembles (BCLEs) that share some (but not all) of the conformal symmetries that characterize CLEs, and that should be scaling limits of critical models with special boundary conditions. We extend the CLEκ /CLEκ 0 correspondence to a BCLEκ /BCLEκ 0 correspondence that makes sense for the wider range κ ∈ (2, 4] and κ 0 ∈ [4, 8).

We prove that the uniform infinite half-plane quadrangulation (UIHPQ), with either general or simple boundary, equipped with its graph distance, its natural area measure, and the curve which traces its boundary, converges in the scaling limit to the Brownian half-plane. The topology of convergence is given by the so-called Gromov-Hausdorff-Prokhorov-uniform (GHPU) metric on curve-decorated metric measure spaces, which is a generalization of the Gromov-Hausdorff metric whereby two such spaces $(X_1, d_1 , \mu_1,\eta_1)$ and $(X_2, d_2 , \mu_2,\eta_2)$ are close if they can be isometrically embedded into a common metric space in such a way that the spaces $X_1$ and $X_2$ are close in the Hausdorff distance, the measures $\mu_1$ and $\mu_2$ are close in the Prokhorov distance, and the curves $\eta_1$ and $\eta_2$ are close in the uniform distance., Comment: 41 pages and 4 figures. Revised

The peanosphere (or "mating of trees") construction of Duplantier, Miller, and Sheffield encodes certain types of $\gamma$-Liouville quantum gravity (LQG) surfaces ($\gamma \in (0,2)$) decorated with an independent SLE$_{\kappa}$ ($\kappa = 16/\gamma^2 > 4$) in terms of a correlated two-dimensional Brownian motion and provides a framework for showing that random planar maps decorated with statistical physics models converge to LQG decorated with an SLE. Previously, the correlation for the Brownian motion was only explicitly identified as $-\cos(4\pi/\kappa)$ for $\kappa \in (4,8]$ and unknown for $\kappa > 8$. The main result of this work is that this formula holds for all $\kappa > 4$. This supplies the missing ingredient for proving convergence results of the aforementioned type for $\kappa > 8$. Our proof is based on the calculation of a certain tail exponent for SLE$_{\kappa}$ on a quantum wedge and then matching it with an exponent which is well-known for Brownian motion.

Primary open-angle glaucoma (POAG) is among the leading causes of blindness in the United States and worldwide. While numerous prospective clinical trials have convincingly shown that elevated intraocular pressure (IOP) is a leading risk factor for the development of POAG, an increasingly debated issue in recent years is the effect of IOP fluctuation on the risk of developing POAG. In many applications, this question is addressed via a "naïve" two-step approach where some sample-based estimates (e.g., standard deviation) are first obtained as surrogates for the "true" within-subject variability and then included in Cox regression models as covariates. However, estimates from two-step approach are more likely to suffer from the measurement error inherent in sample-based summary statistics. In this paper we propose a joint model to assess the question whether individuals with different levels of IOP variability have different susceptibility to POAG. In our joint model, the trajectory of IOP is described by a linear mixed model that incorporates patient-specific variance, the time to POAG is fit using a semi-parametric or parametric distribution, and the two models are linked via patient-specific random effects. Parameters in the joint model are estimated under Bayesian framework using Markov chain Monte Carlo (MCMC) methods with Gibbs sampling. The method is applied to data from the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS), two large-scale multi-center randomized trials on the prevention of POAG.

This article provides a unified methodology of meta-analysis that synthesizes medical evidence by using both available individual patient data (IPD) and published summary statistics within the framework of likelihood principle. Most up-to-date scientific evidence on medicine is crucial information not only to consumers but also to decision makers, and can only be obtained when existing evidence from the literature and the most recent individual patient data are optimally synthesized. We propose a general linear mixed effects model to conduct meta-analyses when individual patient data are only available for some of the studies and summary statistics have to be used for the rest of the studies. Our approach includes both the traditional meta-analyses in which only summary statistics are available for all studies and the other extreme case in which individual patient data are available for all studies as special examples. We implement the proposed model with statistical procedures from standard computing packages. We provide measures of heterogeneity based on the proposed model. Finally, we demonstrate the proposed methodology through a real life example studying the cerebrospinal fluid biomarkers to identify individuals with high risk of developing Alzheimer’s disease when they are still cognitively normal.

Subjects with clinically diagnosed senile dementia of the Alzheimer type (n = 37) and healthy controls (n = 5) were assessed clinically until death. Postmortem examination of the brain was performed at age 80 years or older. The brains of all of the group with dementia (except one that was found to have a non-Alzheimer dementia) had substantial densities of neocortical senile plaques regardless of dementia severity; the control brains had very few senile plaques. In those subjects with Alzheimer's disease, moderate correlations were found between dementia duration and severity (cognitive portion of the Blessed Dementia Scale and the Sum of Boxes from the Clinical Dementia Rating) and certain neuropathological lesions, both gross and microscopic. Densities of neocortical neurofibrillary tangles were related to degree of dementia; densities of neocortical senile plaques were unrelated. We conclude that (1) neocortical senile plaque densities differentiate very old subjects with Alzheimer's disease from nondemented controls, but there is a need for more postmortem studies of older persons who are free of dementia; and (2) among the microscopic lesions studied, densities of neocortical neurofibrillary tangles were most closely related to the degree and duration of dementia.

Three investigators have applied different histopathologic methods (modified Bielschowsky silver methods, Congo red-gallocyanin) to differentiate Alzheimer's disease (AD) (n = 7 subjects; four with very mild dementia and three with moderate to advanced dementia) neuropathology from brain changes associated with aging in three nondemented individuals who had been evaluated using a validated dementia severity staging instrument [Washington University Clinical Dementia Rating (CDR)] generally within a year of death. The presence of elevated numbers of neocortical (frontal and temporal) diffuse, mature, and total senile plaques (SP) was strongly correlated with the presence of clinical AD but did not equate with CDR dementia severity. Neocortical neurofibrillary tangle (NFT) density as well as hippocampal NFT and SP density in this small series did not differentiate statistically between AD and controls. NFT density appeared to correlate with CDR better than SP density. Quantitative histopathologic assessment of AD markers in only a few brain regions can accurately predict the presence of clinical AD, including the very mild form of the disease. This is especially true for SP in the neocortex.

The objective of this study was to determine whether there are measurable differences in neuropsychometric performances between HIV-positive asymptomatic subjects and high-risk HIV-negative individuals. We carried out concurrent neuropsychological testing of HIV-positive subjects screened for drug treatment protocols at a clinical research center and HIV-negative subjects seeking confidential testing. Fifty HIV-negative and 33 HIV-positive subjects who did not admit to use of central nervous system (CNS)-active drugs, more than one drink of alcohol per day, or drug use comprised the final group for analysis. A neuropsychological test battery designed to evaluate verbal memory, motor function, orientation and attention was administered to all subjects. In addition, affective state was assessed with the Beck depression inventory. Multivariate analysis of variance indicated no difference in the performance of the two groups. Only one subtest, the Wechsler Adult Intelligence Scale digit span (forward) reached a level of significant difference (P less than 0.05) by univariate analysis. We conclude that neuropsychometric performance of asymptomatic HIV-positive subjects cannot be distinguished from that of high-risk HIV-negative subjects by a battery of traditional neuropsychological tests.

Background: The WW domain is found in a large number of eukaryotic proteins implicated in a variety of cellular processes. WW domains bind proline-rich protein and peptide ligands, but the protein interaction partners of many WW domain-containing proteins in Saccharomyces cerevisiae are largely unknown. Results: We used protein microarray technology to generate a protein interaction map for 12 of the 13 WW domains present in proteins of the yeast S. cerevisiae. We observed 587 interactions between these 12 domains and 207 proteins, most of which have not previously been described. We analyzed the representation of functional annotations within the network, identifying enrichments for proteins with peroxisomal localization, as well as for proteins involved in protein turnover and cofactor biosynthesis. We compared orthologs of the interacting proteins to identify conserved motifs known to mediate WW domain interactions, and found substantial evidence for the structural conservation of such binding motifs throughout the yeast lineages. The comparative approach also revealed that several of the WW domain-containing proteins themselves have evolutionarily conserved WW domain binding sites, suggesting a functional role for inter- or intramolecular association between proteins that harbor WW domains. On the basis of these results, we propose a model for the tuning of interactions between WW domains and their protein interaction partners. Conclusion: Protein microarrays provide an appealing alternative to existing techniques for the construction of protein interaction networks. Here we built a network composed of WW domain-protein interactions that illuminates novel features of WW domain-containing proteins and their protein interaction partners. © 2006 Hesselberth et al.; licensee BioMed Central Ltd.

The muon anomalous magnetic moment has been measured in a new experiment at Brookhaven. Polarized muons were stored in a superferric ring, and the angular frequency difference, omega(a), between the spin precession and orbital frequencies was determined by measuring the time distribution of high-energy decay positrons. The ratio R of omega(a) to the Larmor precession frequency of free protons, omega(p), in the storage-ring magnetic field was measured. We find R = 3.707 220(48) X 10(-3). With mu(mu)/mu(p) = 3.183 345 47(47) this gives a(mu+) = 1 165 925(15) X 10(-9) (+/-13 ppm), in good agreement with the previous CERN measurements for mu(+) and mu(-) and of approximately the same precision.

Clinical management of heterozygous familial hypercholesterolaemia is largely based on evidence from a small number of observational studies and extrapolation from the results of clinical trials of lipid-lowering in patients with polygenic hypercholesterolaemia The objectives of this study were (i) to determine the absolute and relative mortality of patients with treated heterozygous familial hypercholesterolaemia, (ii) to estimate the effect of changes in treatment efficacy on mortality trends over time, and (iii) to examine the implications of these findings for patient management. A cohort of 605 men and 580 women aged 20-79 years with heterozyous familial hypercholesterolaemia were recruited from 21 out-patient lipid clinics in the UK. Patients were followed prospectively from 1980 to 1995 for 8770 person-years. Absolute mortality was calculated, and relative risk was expressed as the ratio of the number of observed deaths to the number expected in the general population of England and Wales. Forty six of the 73 deaths were due to coronary heart disease. In women aged 20-39, despite treatment, the relative risk of a fatal coronary event was increased 125-fold (95% confidence intervals 15-451) and the annual coronary mortality was 0.17%. In men aged 20-39 the relative risk was increased 48-fold (17-105) and the annual coronary mortality was 0.46%. The relative risk decreased with age but the absolute risk increased. For men and women aged 60-79, the annual coronary mortality was 1.1% representing a significant excess mortality for women (relative risk 2.6, 1.3-4.5) but not for men (RR 1.1, 0.5-2.3). Non-coronary mortality was not increased at any age (RR for all ages 0.68, 0.45-0.99). There was a decline in the relative risk for coronary mortality in patients aged 20-59 from an eight-fold (4.8-7.2) increased risk before 1992 to 3.7 (1.6-7.2.) thereafter (P=0.08). The results suggest that the prognosis for patients with heterozygous familial hypercholesterolaemia has improved with the introduction of more effective treatment, and that lipid-lowering therapy is not associated with increased non-coronary mortality. These findings and the excess coronary mortality observed suggest that all affected adult men and post-menopausal women should be treated with HMG-CoA reductase inhibitors.

• Objective. —The influence of age on performance on clinical and psychometric assessments is examined in groups of nondemented persons and individuals with either very mild or mild dementia of the Alzheimer type (DAT). Design. —Initial clinical and psychometric assessments of persons enrolled in longitudinal studies of DAT and nondemented control subjects. Setting. —Alzheimer's Disease Research Center at Washington University, St Louis, Mo. Participants. —Volunteer samples of 108 people (44 men, 64 women) with mild DAT, 61 people (30 men, 31 women) with very mild DAT, and 122 healthy nondemented people (45 men, 77 women) were recruited between 1979 and 1991. Age ranged from 54 to 87 years. Persons with confounding medical, neurologic, or psychiatric disorders were excluded. Dementia severity was staged using the Clinical Dementia Rating scale. Main Outcome Measures. —Five brief quantitative clinical tests included in the 90-minute clinician administered protocol, as well as 14 tests included in a 2-hour psychometric test battery. Results. —Dementia severity affected performance on all measurements. Age did not influence performance on clinical assessments. There was a significant interaction between age and dementia severity on 10 of 14 psychometric measures. In general, older nondemented individuals performed less well than younger nondemented individuals while older mildly demented persons performed about the same as, or slightly better than, their younger counterparts. Conclusions. —Age does not affect performance on brief clinical assessment instruments. However, age affects psychometric performance differently in cognitively intact persons when compared with persons with DAT. As a result, psychometric differentiation between cognitively normal and demented individuals is more difficult in older populations.

{We report the first determination of CP violation parameters from particle-antiparticle asymmetry in the decay of neutral kaons into two charged pions. Observation of such an asymmetry is direct proof of CP violation. A fit to the asymmetry enabled a determination of the parameter-eta+- to be made, yielding the result \textbackslash{}eta+-\textbackslash{} = {[}2.32 +/- 0.14 (stat. ) +/- 0.03 (syst.)] X 10(-3) and phi+- = 42.3-degrees +/- 4.4-degrees (stat.) +/- 0.4-degrees (syst. ), with an additional uncertainty of +/-1.0-degrees due to the error on the present published value of DELTA-m, the K(L)0-K(S)0 mass difference. The magnitudes of both statistical and systematic errors will be significantly reduced in the future.}

Objective To study differences between subjects with Alzheimer disease (AD) and cognitively intact control subjects, with respect to brain histologic markers of AD, and the relationship of those markers in the AD group to severity of dementia, age at death, sex, and apolipoprotein E genotype. Setting Washington University Alzheimer's Disease Research Center, St Louis, Mo. Design and Subjects Consecutive neuropathologic series of 224 prospectively studied volunteer research subjects, 186 with dementia of the Alzheimer type (DAT) or "incipient" DAT and confirmed to have AD by postmortem examination and 13 cognitively intact subjects, confirmed to lack postmortem findings of AD. Main Outcome Measures Brain densities (number per square millimeter) of senile plaques and neurofibrillary tangles, extent of cerebral amyloid angiopathy, cortical Lewy bodies, and apolipoprotein E genotype. Results Neocortical neurofibrillary tangle densities were substantially correlated with dementia severity, and to a greater degree than was true for senile plaque densities. When infarcts, hemorrhages, and Parkinson disease changes coexisted with AD, neurofibrillary tangle and senile plaque densities were lower. Plaque-predominant AD was found in a greater proportion of subjects with milder than more severe dementia. Entorhinal cortical Lewy bodies were no more frequent in plaque-predominant AD than in the remaining AD cases. Increasing age at death was negatively correlated with dementia severity and densities of senile plaques and neurofibrillary tangles. The apolipoprotein E ϵ4 allele frequency was greater in AD than in control subjects but decreased with increasing age. After controlling for dementia severity, senile plaque densities were only weakly related to ϵ4 allele frequency, and only in hippocampus. However, the degree of cerebral amyloid angiopathy was clearly related to ϵ4 allele frequency. Among subjects diagnosed during life as having DAT or incipient DAT, only 7% were found to have a neuropathologic disorder other than AD causing their dementia. Conclusions (1) The order of the strength of relationships between densities of histologic markers and dementia severity in AD is neurofibrillary tangles greater than cored senile plaques greater than total senile plaques. (2) Advanced age at death is associated with somewhat less severe dementia and fewer senile plaques and neurofibrillary tangles. (3) Plaque-predominant AD may represent a developmental stage in AD. (4) Despite a substantial effect of apolipoprotein E ϵ4 as a risk factor for AD, on decreasing the age at AD onset, and increasing the amount of cerebral amyloid angiopathy, its effect on senile plaque densities is variable and complex, being confounded with age, dementia severity, and methodologic differences. (5) Stringent clinical diagnostic criteria for DAT, even in the very mild stage, and senile plaque–based neuropathologic criteria for AD are highly accurate.