Simulating chemistry using quantum computers

The difficulty of simulating quantum systems, well-known to quantum chemists, prompted the idea of quantum computation. One can avoid the steep scaling associated with the exact simulation of increasingly large quantum systems on conventional computers, by mapping the quantum system to another, more controllable one. In this review, we discuss to what extent the ideas in quantum computation, now a well-established field, have been applied to chemical problems. We describe algorithms that achieve significant advantages for the electronic-structure problem, the simulation of chemical dynamics, protein folding, and other tasks. Although theory is still ahead of experiment, we outline recent advances that have led to the first chemical calculations on small quantum information processors.Comment: 27 pages. Submitted to Ann. Rev. Phys. Che

Motor onset and diagnosis in Huntington disease using the diagnostic confidence level

Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine-adenine-guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington's Disease Rating Scale. HD progression from unimpaired to impaired motor function, as well as the progression from motor impairment to diagnosis, was associated with the linear effect of age and CAG repeat length. Specifically, for every 1-year increase in age, the risk of transition in diagnostic confidence level increased by 11% (95% CI 7-15%) and for one repeat length increase in CAG, the risk of transition in diagnostic confidence level increased by 47% (95% CI 27-69%). Findings show that CAG repeat length and age increased the likelihood of the first onset of motor impairment as well as the age at diagnosis. Results suggest that more accurate estimates of HD onset age can be obtained by incorporating the current status of diagnostic confidence level into predictive models

Mothers after gestational diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: study protocol for a randomized controlled trial

Background:Gestational diabetes mellitus (GDM) is defined as glucose intolerance with its onset or first recognition during pregnancy. Post-GDM women have a life-time risk exceeding 70% of developing type 2 diabetes mellitus (T2DM). Lifestyle modifications reduce the incidence of T2DM by up to 58% for high-risk individuals.Methods/Design:The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial aiming to assess the effectiveness of a structured diabetes prevention intervention for post-GDM women. This trial has an intervention group participating in a diabetes prevention program (DPP), and a control group receiving usual care from their general practitioners during the same time period. The 12-month intervention comprises an individual session followed by five group sessions at two-week intervals, and two follow-up telephone calls. A total of 574 women will be recruited, with 287 in each arm. The women will undergo blood tests, anthropometric measurements, and self-reported health status, diet, physical activity, quality of life, depression, risk perception and healthcare service usage, at baseline and 12 months. At completion, primary outcome (changes in diabetes risk) and secondary outcome (changes in psychosocial and quality of life measurements and in cardiovascular disease risk factors) will be assessed in both groups.Discussion:This study aims to show whether MAGDA-DPP leads to a reduction in diabetes risk for post-GDM women. The characteristics that predict intervention completion and improvement in clinical and behavioral measures will be useful for further development of DPPs for this population.</span

Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: individual-patient-data meta-analysis of randomized trials

Background: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims: We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods: We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results: Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions: An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality

The Green Bank Ammonia Survey (GAS): First Results of NH3 mapping the Gould Belt

We present an overview of the first data release (DR1) and first-look science from the Green Bank Ammonia Survey (GAS). GAS is a Large Program at the Green Bank Telescope to map all Gould Belt star-forming regions with $A_V \gtrsim 7$ mag visible from the northern hemisphere in emission from NH$_3$ and other key molecular tracers. This first release includes the data for four regions in Gould Belt clouds: B18 in Taurus, NGC 1333 in Perseus, L1688 in Ophiuchus, and Orion A North in Orion. We compare the NH$_3$ emission to dust continuum emission from Herschel, and find that the two tracers correspond closely. NH$_3$ is present in over 60\% of lines-of-sight with $A_V \gtrsim 7$ mag in three of the four DR1 regions, in agreement with expectations from previous observations. The sole exception is B18, where NH$_3$ is detected toward ~ 40\% of lines-of-sight with $A_V \gtrsim 7$ mag. Moreover, we find that the NH$_3$ emission is generally extended beyond the typical 0.1 pc length scales of dense cores. We produce maps of the gas kinematics, temperature, and NH$_3$ column densities through forward modeling of the hyperfine structure of the NH$_3$ (1,1) and (2,2) lines. We show that the NH$_3$ velocity dispersion, ${\sigma}_v$, and gas kinetic temperature, $T_K$, vary systematically between the regions included in this release, with an increase in both the mean value and spread of ${\sigma}_v$ and $T_K$ with increasing star formation activity. The data presented in this paper are publicly available.Comment: 33 pages, 27 figures, accepted to ApJS. Datasets are publicly available: https://dataverse.harvard.edu/dataverse/GAS_DR

A progress report of the IFCC Committee for Standardization of Thyroid Function Tests

BACKGROUND: The IFCC Committee for Standardization of Thyroid Function Tests aims at equivalence of laboratory test results for free thyroxine (FT4) and thyrotropin (TSH). OBJECTIVES: This report describes the phase III method comparison study with clinical samples representing a broad spectrum of thyroid disease. The objective was to expand the feasibility work and explore the impact of standardization/harmonization in the clinically relevant concentration range. METHODS: Two sets of serum samples (74 for FT4, 94 for TSH) were obtained in a clinical setting. Eight manufacturers participated in the study (with 13 FT4 and 14 TSH assays). Targets for FT4 were set by the international conventional reference measurement procedure of the IFCC; those for TSH were based on the all-procedure trimmed mean. The manufacturers recalibrated their assays against these targets. RESULTS: All FT4 assays were negatively biased in the mid- to high concentration range, with a maximum interassay discrepancy of approximately 30%. However, in the low range, the maximum deviation was approximately 90%. For TSH, interassay comparability was reasonable in the mid-concentration range, but worse in the pathophysiological ranges. Recalibration was able to eliminate the interassay differences, so that the remaining dispersion of the data was nearly entirely due to within-assay random error components. The impact of recalibration on the numerical results was particularly high for FT4. CONCLUSIONS: Standardization and harmonization of FT4 and TSH measurements is feasible from a technical point of view. Because of the impact on the numerical values, the implementation needs careful preparation with the stakeholders

Forward Global Photometric Calibration of the Dark Energy Survey

Many scientific goals for the Dark Energy Survey (DES) require calibration of optical/NIR broadband $b = grizY$ photometry that is stable in time and uniform over the celestial sky to one percent or better. It is also necessary to limit to similar accuracy systematic uncertainty in the calibrated broadband magnitudes due to uncertainty in the spectrum of the source. Here we present a "Forward Global Calibration Method (FGCM)" for photometric calibration of the DES, and we present results of its application to the first three years of the survey (Y3A1). The FGCM combines data taken with auxiliary instrumentation at the observatory with data from the broad-band survey imaging itself and models of the instrument and atmosphere to estimate the spatial- and time-dependence of the passbands of individual DES survey exposures. "Standard" passbands are chosen that are typical of the passbands encountered during the survey. The passband of any individual observation is combined with an estimate of the source spectral shape to yield a magnitude $m_b^{\mathrm{std}}$ in the standard system. This "chromatic correction" to the standard system is necessary to achieve sub-percent calibrations. The FGCM achieves reproducible and stable photometric calibration of standard magnitudes $m_b^{\mathrm{std}}$ of stellar sources over the multi-year Y3A1 data sample with residual random calibration errors of $\sigma=5-6\,\mathrm{mmag}$ per exposure. The accuracy of the calibration is uniform across the $5000\,\mathrm{deg}^2$ DES footprint to within $\sigma=7\,\mathrm{mmag}$. The systematic uncertainties of magnitudes in the standard system due to the spectra of sources are less than $5\,\mathrm{mmag}$ for main sequence stars with $0.5<g-i<3.0$.Comment: 25 pages, submitted to A

Astrometric calibration and performance of the Dark Energy Camera

We characterize the ability of the Dark Energy Camera (DECam) to perform relative astrometry across its 500~Mpix, 3 deg^2 science field of view, and across 4 years of operation. This is done using internal comparisons of ~4x10^7 measurements of high-S/N stellar images obtained in repeat visits to fields of moderate stellar density, with the telescope dithered to move the sources around the array. An empirical astrometric model includes terms for: optical distortions; stray electric fields in the CCD detectors; chromatic terms in the instrumental and atmospheric optics; shifts in CCD relative positions of up to ~10 um when the DECam temperature cycles; and low-order distortions to each exposure from changes in atmospheric refraction and telescope alignment. Errors in this astrometric model are dominated by stochastic variations with typical amplitudes of 10-30 mas (in a 30 s exposure) and 5-10 arcmin coherence length, plausibly attributed to Kolmogorov-spectrum atmospheric turbulence. The size of these atmospheric distortions is not closely related to the seeing. Given an astrometric reference catalog at density ~0.7 arcmin^{-2}, e.g. from Gaia, the typical atmospheric distortions can be interpolated to 7 mas RMS accuracy (for 30 s exposures) with 1 arcmin coherence length for residual errors. Remaining detectable error contributors are 2-4 mas RMS from unmodelled stray electric fields in the devices, and another 2-4 mas RMS from focal plane shifts between camera thermal cycles. Thus the astrometric solution for a single DECam exposure is accurate to 3-6 mas (0.02 pixels, or 300 nm) on the focal plane, plus the stochastic atmospheric distortion.Comment: Submitted to PAS

A whole blood gene expression-based signature for smoking status

BACKGROUND: Smoking is the leading cause of preventable death worldwide and has been shown to increase the risk of multiple diseases including coronary artery disease (CAD). We sought to identify genes whose levels of expression in whole blood correlate with self-reported smoking status. METHODS: Microarrays were used to identify gene expression changes in whole blood which correlated with self-reported smoking status; a set of significant genes from the microarray analysis were validated by qRT-PCR in an independent set of subjects. Stepwise forward logistic regression was performed using the qRT-PCR data to create a predictive model whose performance was validated in an independent set of subjects and compared to cotinine, a nicotine metabolite. RESULTS: Microarray analysis of whole blood RNA from 209 PREDICT subjects (41 current smokers, 4 quit ≤ 2 months, 64 quit > 2 months, 100 never smoked; NCT00500617) identified 4214 genes significantly correlated with self-reported smoking status. qRT-PCR was performed on 1,071 PREDICT subjects across 256 microarray genes significantly correlated with smoking or CAD. A five gene (CLDND1, LRRN3, MUC1, GOPC, LEF1) predictive model, derived from the qRT-PCR data using stepwise forward logistic regression, had a cross-validated mean AUC of 0.93 (sensitivity=0.78; specificity=0.95), and was validated using 180 independent PREDICT subjects (AUC=0.82, CI 0.69-0.94; sensitivity=0.63; specificity=0.94). Plasma from the 180 validation subjects was used to assess levels of cotinine; a model using a threshold of 10 ng/ml cotinine resulted in an AUC of 0.89 (CI 0.81-0.97; sensitivity=0.81; specificity=0.97; kappa with expression model = 0.53). CONCLUSION: We have constructed and validated a whole blood gene expression score for the evaluation of smoking status, demonstrating that clinical and environmental factors contributing to cardiovascular disease risk can be assessed by gene expression

Rubidium and potassium levels are altered in Alzheimer's disease brain and blood but not in cerebrospinal fluid

Loss of intracellular compartmentalization of potassium is a biochemical feature of Alzheimer's disease indicating a loss of membrane integrity and mitochondrial dysfunction. We examined potassium and rubidium (a biological proxy for potassium) in brain tissue, blood fractions and cerebrospinal fluid from Alzheimer's disease and healthy control subjects to investigate the diagnostic potential of these two metal ions. We found that both potassium and rubidium levels were significantly decreased across all intracellular compartments in the Alzheimer's disease brain. Serum from over 1000 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), showed minor changes according to disease state. Potassium and rubidium levels in erythrocytes and cerebrospinal fluid were not significantly different according to disease state, and rubidium was slightly decreased in Alzheimer's disease patients compared to healthy controls. Our data provides evidence that contrasts the hypothesized disruption of the blood-brain barrier in Alzheimer's disease, with the systemic decrease in cortical potassium and rubidium levels suggesting influx of ions from the blood is minimal and that the observed changes are more likely indicative of an internal energy crisis within the brain. These findings may be the basis for potential diagnostic imaging studies using radioactive potassium and rubidium tracers