Strategically managing learning during perceptual decision making

Making optimal decisions in the face of noise requires balancing short-term speed and accuracy. But a theory of optimality should account for the fact that short-term speed can influence long-term accuracy through learning. Here, we demonstrate that long-term learning is an important dynamical dimension of the speed-accuracy trade-off. We study learning trajectories in rats and formally characterize these dynamics in a theory expressed as both a recurrent neural network and an analytical extension of the drift-diffusion model that learns over time. The model reveals that choosing suboptimal response times to learn faster sacrifices immediate reward, but can lead to greater total reward. We empirically verify predictions of the theory, including a relationship between stimulus exposure and learning speed, and a modulation of reaction time by future learning prospects. We find that rats' strategies approximately maximize total reward over the full learning epoch, suggesting cognitive control over the learning process

On the molecules of numerical semigroups, Puiseux monoids, and Puiseux algebras

A molecule is a nonzero non-unit element of an integral domain (resp., commutative cancellative monoid) having a unique factorization into irreducibles (resp., atoms). Here we study the molecules of Puiseux monoids as well as the molecules of their corresponding semigroup algebras, which we call Puiseux algebras. We begin by presenting, in the context of numerical semigroups, some results on the possible cardinalities of the sets of molecules and the sets of reducible molecules (i.e., molecules that are not irreducibles/atoms). Then we study the molecules in the more general context of Puiseux monoids. We construct infinitely many non-isomorphic atomic Puiseux monoids all whose molecules are atoms. In addition, we characterize the molecules of Puiseux monoids generated by rationals with prime denominators. Finally, we turn to investigate the molecules of Puiseux algebras. We provide a characterization of the molecules of the Puiseux algebras corresponding to root-closed Puiseux monoids. Then we use such a characterization to find an infinite class of Puiseux algebras with infinitely many non-associated reducible molecules.Comment: 21 pages, 2 figure

Biodiversity assessment of tropical shelf eukaryotic communities via pelagic eDNA metabarcoding

Our understanding of marine communities and their functions in an ecosystem relies on the ability to detect and monitor species distributions and abundances. Currently, the use of environmental DNA (eDNA) metabarcoding is increasingly being applied for the rapid assessment and monitoring of aquatic species. Most eDNA metabarcoding studies have either focussed on the simultaneous identification of a few specific taxa/groups or have been limited in geographical scope. Here, we employed eDNA metabarcoding to compare beta diversity patterns of complex pelagic marine communities in tropical coastal shelf habitats spanning the whole Caribbean Sea. We screened 68 water samples using a universal eukaryotic COI barcode region and detected highly diverse communities, which varied significantly among locations, and proved good descriptors of habitat type and environmental conditions. Less than 15% of eukaryotic taxa were assigned to metazoans, most DNA sequences belonged to a variety of planktonic “protists,” with over 50% of taxa unassigned at the phylum level, suggesting that the sampled communities host an astonishing amount of micro‐eukaryotic diversity yet undescribed or absent from COI reference databases. Although such a predominance of micro‐eukaryotes severely reduces the efficiency of universal COI markers to investigate vertebrate and other metazoans from aqueous eDNA, the study contributes to the advancement of rapid biomonitoring methods and brings us closer to a full inventory of extant marine biodiversity

Environmental DNA reveals tropical shark diversity in contrasting levels of anthropogenic impact

Sharks are charismatic predators that play a key role in most marine food webs. Their demonstrated vulnerability to exploitation has recently turned them into flagship species in ocean conservation. Yet, the assessment and monitoring of the distribution and abundance of such mobile species in marine environments remain challenging, often invasive and resource-intensive. Here we pilot a novel, rapid and non-invasive environmental DNA (eDNA) metabarcoding approach specifically targeted to infer shark presence, diversity and eDNA read abundance in tropical habitats. We identified at least 21 shark species, from both Caribbean and Pacific Coral Sea water samples, whose geographical patterns of diversity and read abundance coincide with geographical differences in levels of anthropogenic pressure and conservation effort. We demonstrate that eDNA metabarcoding can be effectively employed to study shark diversity. Further developments in this field have the potential to drastically enhance our ability to assess and monitor elusive oceanic predators, and lead to improved conservation strategies

Non-invasive, vagus nerve stimulation to reduce ileus after colorectal surgery: protocol for a feasibility trial with nested mechanistic studies

Introduction Ileus is a common and distressing condition characterised by gut dysfunction after surgery. While a number of interventions have aimed to curtail its impact on patients and healthcare systems, ileus is still an unmet challenge. Electrical stimulation of the vagus nerve is a promising new treatment due to its role in modulating the neuro-immune axis through a novel anti-inflammatory reflex. The protocol for a feasibility study of non-invasive vagus nerve stimulation (nVNS), and a programme of mechanistic and qualitative studies, is described. Methods and analysis This is a participant-blinded, parallel-group, randomised, sham-controlled feasibility trial (IDEAL Stage 2b) of self-administered nVNS. One hundred forty patients planned for elective, minimally invasive, colorectal surgery will be randomised to four schedules of nVNS before and after surgery. Feasibility outcomes include assessments of recruitment and attrition, adequacy of blinding and compliance to the intervention. Clinical outcomes include bowel function and length of hospital stay. A series of mechanistic substudies exploring the impact of nVNS on inflammation and bowel motility will inform the design of the final stimulation schedule. Semistructured interviews with participants will explore experiences and perceptions of the intervention, while interviews with patients who decline participation will explore barriers to recruitment. Ethics and dissemination The protocol has been approved by the Tyne and Wear South National Health Service (NHS) Research Ethics Committee (19/NE/0217) on 2 July 2019. Feasibility, mechanistic and qualitative findings will be disseminated to national and international partners through peer-reviewed publications, academic conferences, social media channels and stakeholder engagement activities. The findings will build a case for or against progression to a definitive randomised assessment as well as informing key elements of study design. Trial registration number ISRCTN62033341

Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

A Streamlined DNA Tool for Global Identification of Heavily Exploited Coastal Shark Species (Genus Rhizoprionodon)

Obtaining accurate species-specific landings data is an essential step toward achieving sustainable shark fisheries. Globally distributed sharpnose sharks (genus Rhizoprionodon) exhibit life-history characteristics (rapid growth, early maturity, annual reproduction) that suggests that they could be fished in a sustainable manner assuming an investment in monitoring, assessment and careful management. However, obtaining species-specific landings data for sharpnose sharks is problematic because they are morphologically very similar to one another. Moreover, sharpnose sharks may also be confused with other small sharks (either small species or juveniles of large species) once they are processed (i.e., the head and fins are removed). Here we present a highly streamlined molecular genetics approach based on seven species-specific PCR primers in a multiplex format that can simultaneously discriminate body parts from the seven described sharpnose shark species commonly occurring in coastal fisheries worldwide. The species-specific primers are based on nucleotide sequence differences among species in the nuclear ribosomal internal transcribed spacer 2 locus (ITS2). This approach also distinguishes sharpnose sharks from a wide range of other sharks (52 species) and can therefore assist in the regulation of coastal shark fisheries around the world

In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.

BACKGROUND: The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape. METHODOLOGY/PRINCIPAL FINDINGS: Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages. CONCLUSIONS: We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies