All Numbers Are Not Equal: An Electrophysiological Investigation of Small and Large Number Representations

Behavioral and brain imaging research indicates that human infants, humans adults, and many nonhuman animals represent large nonsymbolic numbers approximately, discriminating between sets with a ratio limit on accuracy. Some behavioral evidence, especially with human infants, suggests that these representations differ from representations of small numbers of objects. To investigate neural signatures of this distinction, event-related potentials were recorded as adult humans passively viewed the sequential presentation of dot arrays in an adaptation paradigm. In two studies, subjects viewed successive arrays of a single number of dots interspersed with test arrays presenting the same or a different number; numerical range (small numerical quantities 1–3 vs. large numerical quantities 8–24) and ratio difference varied across blocks as continuous variables were controlled. An early-evoked component (N1), observed over widespread posterior scalp locations, was modulated by absolute number with small, but not large, number arrays. In contrast, a later component (P2p), observed over the same scalp locations, was modulated by the ratio difference between arrays for large, but not small, numbers. Despite many years of experience with symbolic systems that apply equally to all numbers, adults spontaneously process small and large numbers differently. They appear to treat small-number arrays as individual objects to be tracked through space and time, and large-number arrays as cardinal values to be compared and manipulated.Psycholog

Near-Infrared Spectroscopy Shows Right Parietal Specialization for Number in Pre-Verbal Infants

Bilateral regions of the intraparietal sulcus (IPS) appear to be functionally selective for both rudimentary non-symbolic number tasks and higher-level symbolic number tasks in adults and older children. Furthermore, the ability to mentally represent and manipulate approximate non-symbolic numerical quantities is present from birth. These factors leave open whether the specialization of the IPS develops through the experience of learning a symbolic number system or if it is already specialized before symbolic number acquisition. Using the newly emerging technique of functional Near-Infrared Spectroscopy (fNIRS) over left and right parietal and lateral occipital regions, we show right parietal specialization for number in 6-month-old infants. These results extend the current literature in three ways: by successfully implementing an event-related NIRS design in infants, by showing parietal specialization for number occurs before the acquisition of language, and by suggesting number representation may be initially right lateralized and become bilateral through experience.Psycholog

A comparison of forward and backward pp pair knockout in 3He(e,e'pp)n

Measuring nucleon-nucleon Short Range Correlations (SRC) has been a goal of the nuclear physics community for many years. They are an important part of the nuclear wavefunction, accounting for almost all of the high-momentum strength. They are closely related to the EMC effect. While their overall probability has been measured, measuring their momentum distributions is more difficult. In order to determine the best configuration for studying SRC momentum distributions, we measured the $^3$He$(e,e'pp)n$ reaction, looking at events with high momentum protons ($p_p > 0.35$ GeV/c) and a low momentum neutron ($p_n< 0.2$ GeV/c). We examined two angular configurations: either both protons emitted forward or one proton emitted forward and one backward (with respect to the momentum transfer, $\vec q$). The measured relative momentum distribution of the events with one forward and one backward proton was much closer to the calculated initial-state $pp$ relative momentum distribution, indicating that this is the preferred configuration for measuring SRC.Comment: 8 pages, 9 figures, submitted to Phys Rev C. Version 2 incorporates minor corrections in response to referee comment

Measurement of the neutron F2 structure function via spectator tagging with CLAS

We report on the first measurement of the F2 structure function of the neutron from semi-inclusive scattering of electrons from deuterium, with low-momentum protons detected in the backward hemisphere. Restricting the momentum of the spectator protons to < 100 MeV and their angles to < 100 degrees relative to the momentum transfer allows an interpretation of the process in terms of scattering from nearly on-shell neutrons. The F2n data collected cover the nucleon resonance and deep-inelastic regions over a wide range of Bjorken x for 0.65 < Q2 < 4.52 GeV2, with uncertainties from nuclear corrections estimated to be less than a few percent. These measurements provide the first determination of the neutron to proton structure function ratio F2n/F2p at 0.2 < x < 0.8 with little uncertainty due to nuclear effects.Comment: 6 pages, 3 page

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies