Modulating attentional load affects numerosity estimation: evidence against a pre-attentive subitizing mechanism

Traditionally, the visual enumeration of a small number of items (1 to about 4), referred to as subitizing, has been thought of as a parallel and pre-attentive process and functionally different from the serial attentive enumeration of larger numerosities. We tested this hypothesis by employing a dual task paradigm that systematically manipulated the attentional resources available to an enumeration task. Enumeration accuracy for small numerosities was severely decreased as more attentional resources were taken away from the numerical task, challenging the traditionally held notion of subitizing as a pre-attentive, capacity-independent process. Judgement of larger numerosities was also affected by dual task conditions and attentional load. These results challenge the proposal that small numerosities are enumerated by a mechanism separate from large numerosities and support the idea of a single, attention-demanding enumeration mechanism

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

s-Process Abundances in Planetary Nebulae

The s-process should occur in all but the lower mass progenitor stars of planetary nebulae, and this should be reflected in the chemical composition of the gas which is expelled to create the current planetary nebula shell. Weak forbidden emission lines are expected from several s-process elements in these shells, and have been searched for and in some cases detected in previous investigations. Here we extend these studies by combining very high signal-to-noise echelle spectra of a sample of PNe with a critical analysis of the identification of the emission lines of Z>30 ions. Emission lines of Br, Kr, Xe, Rb, Ba, and Pb are detected with a reasonable degree of certainty in at least some of the objects studied here, and we also tentatively identify lines from Te and I, each in one object. The strengths of these lines indicate enhancement of s-process elements in the central star progenitors, and we determine the abundances of Br, Kr, and Xe, elements for which atomic data relevant for abundance determination have recently become available. As representative elements of the ``light'' and ``heavy'' s-process peaks Kr and Xe exhibit similar enhancements over solar values, suggesting that PNe progenitors experience substantial neutron exposure.Comment: 56 Pages, 6 figures, accepted for publication in ApJ This version corrects missing captions in Figure 1-3 and minor typo

Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

Switching Multiple Sclerosis Patients with Breakthrough Disease to Second-Line Therapy

BACKGROUND: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. METHODS: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. RESULTS: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p =  0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). CONCLUSIONS: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies

Allelic Exclusion and Peripheral Reconstitution by TCR Transgenic T Cells Arising From Transduced Human Hematopoietic Stem/Progenitor Cells

Transduction and transplantation of human hematopoietic stem/progenitor cells (HSPC) with the genes for a T-cell receptor (TCR) that recognizes a tumor-associated antigen may lead to sustained long-term production of T cells expressing the TCR and confer specific antitumor activity. We evaluated this using a lentiviral vector (CCLc-MND-F5) carrying cDNA for a human TCR specific for an HLA-A*0201-restricted peptide of Melanoma Antigen Recognized by T cells (MART-1). CD34+ HSPC were transduced with the F5 TCR lentiviral vector or mock transduced and transplanted into neonatal NSG mice or NSG mice transgenic for human HLA-A*0201 (NSG-A2). Human CD8+ and CD4+ T cells expressing the human F5 TCR were present in the thymus, spleen, and peripheral blood after 4–5 months. Expression of human HLA-A*0201 in NSG-A2 recipient mice led to significantly increased numbers of human CD8+ and CD4+ T cells expressing the F5 TCR, compared with control NSG recipients. Transduction of the human CD34+ HSPC by the F5 TCR transgene caused a high degree of allelic exclusion, potently suppressing rearrangement of endogenous human TCR-β genes during thymopoiesis. In summary, we demonstrated the feasibility of engineering human HSPC to express a tumor-specific TCR to serve as a long-term source of tumor-targeted mature T cells for immunotherapy of melanoma

Identification of Yeast Transcriptional Regulation Networks Using Multivariate Random Forests

The recent availability of whole-genome scale data sets that investigate complementary and diverse aspects of transcriptional regulation has spawned an increased need for new and effective computational approaches to analyze and integrate these large scale assays. Here, we propose a novel algorithm, based on random forest methodology, to relate gene expression (as derived from expression microarrays) to sequence features residing in gene promoters (as derived from DNA motif data) and transcription factor binding to gene promoters (as derived from tiling microarrays). We extend the random forest approach to model a multivariate response as represented, for example, by time-course gene expression measures. An analysis of the multivariate random forest output reveals complex regulatory networks, which consist of cohesive, condition-dependent regulatory cliques. Each regulatory clique features homogeneous gene expression profiles and common motifs or synergistic motif groups. We apply our method to several yeast physiological processes: cell cycle, sporulation, and various stress conditions. Our technique displays excellent performance with regard to identifying known regulatory motifs, including high order interactions. In addition, we present evidence of the existence of an alternative MCB-binding pathway, which we confirm using data from two independent cell cycle studies and two other physioloigical processes. Finally, we have uncovered elaborate transcription regulation refinement mechanisms involving PAC and mRRPE motifs that govern essential rRNA processing. These include intriguing instances of differing motif dosages and differing combinatorial motif control that promote regulatory specificity in rRNA metabolism under differing physiological processes

Production of Embryonic and Fetal-Like Red Blood Cells from Human Induced Pluripotent Stem Cells

We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications