A Crystallographic Map of the Transition from B-DNA to A-DNA

The transition between B- and A-DNA was first observed nearly 50 years ago. We have now mapped this transformation through a set of single-crystal structures of the sequence d(GGCGCC)(2), with various intermediates being trapped by methylating or brominating the cytosine bases. The resulting pathway progresses through 13 conformational steps, with a composite structure that pairs A-nucleotides with complementary B-nucleotides serving as a distinct transition intermediate. The details of each step in the conversion of B- to A-DNA are thus revealed at the atomic level, placing intermediates for this and other sequences in the context of a common pathway

Beyond Ads: Sequential Decision-Making Algorithms in Law and Public Policy

We explore the promises and challenges of employing sequential decision-making algorithms - such as bandits, reinforcement learning, and active learning - in law and public policy. While such algorithms have well-characterized performance in the private sector (e.g., online advertising), their potential in law and the public sector remains largely unexplored, due in part to distinct methodological challenges of the policy setting. Public law, for instance, can pose multiple objectives, necessitate batched and delayed feedback, and require systems to learn rational, causal decision-making policies, each of which presents novel questions at the research frontier. We highlight several applications of sequential decision-making algorithms in regulation and governance, and discuss areas for needed research to render such methods policy-compliant, more widely applicable, and effective in the public sector. We also note the potential risks of such deployments and describe how sequential decision systems can also facilitate the discovery of harms. We hope our work inspires more investigation of sequential decision making in law and public policy, which provide unique challenges for machine learning researchers with tremendous potential for social benefit.Comment: Version 1 presented at Causal Inference Challenges in Sequential Decision Making: Bridging Theory and Practice, a NeurIPS 2021 Worksho

Progressive Multifocal Leukoencephalopathy in AIDS: Proton MR Spectroscopy Patterns of Asynchronous Lesions Confirmed by Serial Diffusion-Weighted Imaging and Apparent Diffusion Coefficient Mapping

Progressive multifocal leukoencephalopathy (PML) is a rare disease that occurs mainly in immunocompromised patients. Despite the progressive nature of the disease, the changes on MRI during the disease course - which may help in monitoring the disease process - have seldom been reported. Here we describe a patient with polymerase-chain-reaction-proven PML examined using serial diffusion-weighted imaging (DWI) and apparent-diffusion-coefficient mapping. Magnetic resonance spectroscopy (MRS) revealed that the demyelinating process was more active without significant neuronal loss at the newer and advancing edge of a lesion than in the older central part of the lesion. This case shows that MRI findings such as DWI and MRS may improve the diagnosis and the understanding of the pathophysiology of PML

Socioeconomic status and modification of atherosclerotic cardiovascular disease risk prediction: Epidemiological analysis using data from the Atherosclerosis Risk In Communities study

OBJECTIVE: Examine whether the relationship between the pooled cohort equations (PCE) predicted 10-year risk for atherosclerotic cardiovascular disease (ASCVD) and absolute risk for ASCVD is modified by socioeconomic status (SES). DESIGN: Population-based longitudinal cohort study-Atherosclerosis Risk in Communities (ARIC)-investigating the development of cardiovascular disease across demographic subgroups. SETTING: Four communities in the USA-Forsyth County, North Carolina, Jackson, Mississippi, suburbs of Minneapolis, Minnesota and Washington County, Maryland. PARTICIPANTS: We identified 9782 ARIC men and women aged 54-73 without ASCVD at study visit 4 (1996-1998). PRIMARY OUTCOME MEASURES: Risk ratio (RR) differences in 10-year incident hospitalisations or death for ASCVD by SES and PCE predicted 10-year ASCVD risk categories to assess for risk modification. SES measures included educational attainment and census-tract neighbourhood deprivation using the Area Deprivation Index. PCE risk categories were 0%-5%, \u3e5%-10%, \u3e10%-15% and \u3e15%. SES as a prognostic factor to estimate ASCVD absolute risk categories was further investigated as an interaction term with the PCE. RESULTS: ASCVD RRs for participants without a high school education (referent college educated) increased at higher PCE estimated risk categories and was consistently \u3e1. Results indicate education is both a risk modifier and delineates populations at higher ASCVD risk independent of PCE. Neighbourhood deprivation did modify association but was less consistent in direction of effect. However, for participants residing in the most deprived neighbourhoods (referent least deprived neighbourhoods) with a PCE estimated risk \u3e10%-15%, risk was significantly elevated (RR 1.65, 95% CI 1.05 to 2.59). Education and neighbourhood deprivation inclusion as an interaction term on the PCE risk score was statistically significant (likelihood ratio p≤0.0001). CONCLUSIONS: SES modifies the association between PCE estimated risk and absolute risk of ASCVD. SES added into ASCVD risk prediction models as an interaction term may improve our ability to predict absolute ASCVD risk among socially disadvantaged populations

New Mechanism for Electronic Energy Relaxation in Nanocrystals

The low-frequency vibrational spectrum of an isolated nanometer-scale solid differs dramatically from that of a bulk crystal, causing the decay of a localized electronic state by phonon emission to be inhibited. We show, however, that an electron can also interact with the rigid translational motion of a nanocrystal. The form of the coupling is dictated by the equivalence principle and is independent of the ordinary electron-phonon interaction. We calculate the rate of nonradiative energy relaxation provided by this mechanism and establish its experimental observability.Comment: 4 pages, Submitted to Physical Review

Optical modeling and polarization calibration for CMB measurements with ACTPol and Advanced ACTPol

The Atacama Cosmology Telescope Polarimeter (ACTPol) is a polarization sensitive upgrade to the Atacama Cosmology Telescope. Located at an elevation of 5190 m, ACTPol measures the Cosmic Microwave Background (CMB) temperature and polarization with arcminute-scale angular resolution. Calibration of the detector angles is a critical step in producing maps of the CMB polarization. Polarization angle offsets in the detector calibration can cause leakage in polarization from E to B modes and induce a spurious signal in the EB and TB cross correlations, which eliminates our ability to measure potential cosmological sources of EB and TB signals, such as cosmic birefringence. We present our optical modeling and measurements associated with calibrating the detector angles in ACTPol.Comment: 12 pages, 8 figures, conference proceedings submitted to Proceedings of SPIE; added reference in section 2 and merged repeated referenc

The impact of varying the number and selection of conditions on estimated multimorbidity prevalence::a cross-sectional study using a large, primary care population dataset

Background: Multimorbidity prevalence rates vary considerably depending on the conditions considered in the morbidity count, but there is no standardised approach to the number or selection of conditions to include. Methods and findings: We conducted a cross-sectional study using English primary care data for 1,168,260 participants who were all people alive and permanently registered with 149 included general practices. Outcome measures of the study were prevalence estimates of multimorbidity (defined as ≥2 conditions) when varying the number and selection of conditions considered for 80 conditions. Included conditions featured in ≥1 of the 9 published lists of conditions examined in the study and/or phenotyping algorithms in the Health Data Research UK (HDR-UK) Phenotype Library. First, multimorbidity prevalence was calculated when considering the individually most common 2 conditions, 3 conditions, etc., up to 80 conditions. Second, prevalence was calculated using 9 condition-lists from published studies. Analyses were stratified by dependent variables age, socioeconomic position, and sex. Prevalence when only the 2 commonest conditions were considered was 4.6% (95% CI [4.6, 4.6] p < 0.001), rising to 29.5% (95% CI [29.5, 29.6] p < 0.001) considering the 10 commonest, 35.2% (95% CI [35.1, 35.3] p < 0.001) considering the 20 commonest, and 40.5% (95% CI [40.4, 40.6] p < 0.001) when considering all 80 conditions. The threshold number of conditions at which multimorbidity prevalence was >99% of that measured when considering all 80 conditions was 52 for the whole population but was lower in older people (29 in >80 years) and higher in younger people (71 in 0- to 9-year-olds). Nine published condition-lists were examined; these were either recommended for measuring multimorbidity, used in previous highly cited studies of multimorbidity prevalence, or widely applied measures of “comorbidity.” Multimorbidity prevalence using these lists varied from 11.1% to 36.4%. A limitation of the study is that conditions were not always replicated using the same ascertainment rules as previous studies to improve comparability across condition-lists, but this highlights further variability in prevalence estimates across studies. Conclusions: In this study, we observed that varying the number and selection of conditions results in very large differences in multimorbidity prevalence, and different numbers of conditions are needed to reach ceiling rates of multimorbidity prevalence in certain groups of people. These findings imply that there is a need for a standardised approach to defining multimorbidity, and to facilitate this, researchers can use existing condition-lists associated with highest multimorbidity prevalence

Mechanical design and development of TES bolometer detector arrays for the Advanced ACTPol experiment

The next generation Advanced ACTPol (AdvACT) experiment is currently underway and will consist of four Transition Edge Sensor (TES) bolometer arrays, with three operating together, totaling ~5800 detectors on the sky. Building on experience gained with the ACTPol detector arrays, AdvACT will utilize various new technologies, including 150mm detector wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors includes a feedhorn array of stacked silicon wafers which form a spline profile leading to each pixel. This is then followed by a waveguide interface plate, detector wafer, back short cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured from high purity copper and then gold plated. In addition to the detector array assembly, the array package also encloses cryogenic readout electronics. We present the full mechanical design of the AdvACT high frequency (HF) detector array package along with a detailed look at the detector array stack assemblies. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modified to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT arrays with pre-existing ACTPol infrastructure.Comment: 9 pages, 5 figures, SPIE Astronomical Telescopes and Instrumentation conference proceeding