A dilution effect without dilution: When missing evidence, not non-diagnostic evidence, is judged inaccurately.

When asked to combine two pieces of evidence, one diagnostic and one non-diagnostic, people show a dilution effect: the addition of non-diagnostic evidence dilutes the overall strength of the evidence. This non-normative effect has been found in a variety of tasks and has been taken as evidence that people inappropriately combine information. In a series of five experiments, we found the dilution effect, but surprisingly it was not due to the inaccurate combination of diagnostic and non-diagnostic information. Because we have objectively correct answers for our task, we could see that participants were relatively accurate in judging diagnostic evidence combined with non-diagnostic evidence, but overestimated the strength of diagnostic evidence alone. This meant that the dilution effect - the gap between diagnostic evidence alone and diagnostic evidence combined with non-diagnostic evidence - was not caused by dilution. We hypothesized that participants were filling in "missing" evidence in a biased fashion when presented with diagnostic evidence alone. This hypothesis best explained the experimental results.

Effects of oral environment on frailty: particular relevance of tongue pressure.

PURPOSE: Oral frailty or the loss of oral functionality can be a symptomatic precursor of overall frailty. Previous studies have suggested that decreased tongue pressure causes a decline in ingesting and swallowing function and poor nutrition. This study investigated what factor(s) contribute to tongue pressure, thereby leading to frailty. PATIENTS AND METHODS: For the purposes of the present study, 467 residents of Hirosaki city in northern Japan aged≥60 years who completed a questionnaire about frailty and underwent an intraoral assessment, which included number of teeth, presence or absence of periodontitis, tongue pressure, and oral diadochokinesis (ODK) were recruited. RESULTS: Of the 467 participants with complete data sets, frailty was identified in 13 (7.5%) of 173 males and in 34 (11.6%) of 294 females. Significantly fewer teeth, lower tongue pressure, and a reduced diadochokinetic syllable rate were more prevalent among frail than among healthy residents. Multivariable logistic regression analysis revealed that age, body mass index, number of teeth, and tongue pressure significantly contributed to frailty, whereas ODK did not. Multiple regression analysis showed that tongue pressure was positively associated with muscle index and number of teeth. CONCLUSION: The results of the present study suggest that fewer teeth and lower tongue pressure, but not ODK function, are risk factors for developing overall frailty among older residents.

Resolving the so-called "probabilistic paradoxes in legal reasoning" with Bayesian networks.

Examples of reasoning problems such as the twins problem and poison paradox have been proposed by legal scholars to demonstrate the limitations of probability theory in legal reasoning. Specifically, such problems are intended to show that use of probability theory results in legal paradoxes. As such, these problems have been a powerful detriment to the use of probability theory - and particularly Bayes theorem - in the law. However, the examples only lead to 'paradoxes' under an artificially constrained view of probability theory and the use of the so-called likelihood ratio, in which multiple related hypotheses and pieces of evidence are squeezed into a single hypothesis variable and a single evidence variable. When the distinct relevant hypotheses and evidence are described properly in a causal model (a Bayesian network), the paradoxes vanish. In addition to the twins problem and poison paradox, we demonstrate this for the food tray example, the abuse paradox and the small town murder problem. Moreover, the resulting Bayesian networks provide a powerful framework for legal reasoning.

Efficacy and safety of hangeshashinto for treatment of GERD refractory to proton pump inhibitors : Usual dose proton pump inhibitors plus hangeshashinto versus double-dose proton pump inhibitors: randomized, multicenter open label exploratory study.

BACKGROUND: Proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) leads to a clinical decline in the quality of life (QOL). Therefore, new treatment options are needed. We performed a multicenter, randomized, parallel-group exploratory trial to determine the efficacy of hangeshashinto (HST) in patients with PPI-refractory GERD. METHODS: We enrolled 78 patients with PPI-refractory GERD for standard PPI regimens for at least 4 weeks and randomly assigned patients to receive either a combination of usual dose of rabeprazole (10 mg/day) + HST (7.5 g/day; HST group) or a double dose of rabeprazole (20 mg/day; double-dose PPI group). The primary end points were the extent of improvement in FSSG (Frequency Scale for the Symptoms of GERD) score and the change over time in FSSG score. RESULTS: There was no significant difference in terms of the improvement degree of the FSSG score between the two groups. Although the total FSSG score and reflux syndrome score decreased significantly for both groups over time (p < 0.001), the acid-related dyspepsia (ARD) score decreased significantly in the HST group from 1 week after drug administration (p < 0.05), indicating an improvement in the condition earlier than in the double-dose PPI group. Moreover, in examinations concerning BMI and age, the HST group had a significantly higher improvement degree of ARD score in patients with BMI < 22 (p < 0.05) and aged < 65 years (p < 0.05) than the double-dose PPI group. CONCLUSIONS: HST may be beneficial for patients with PPI-refractory GERD, particularly in non-obese and non-elderly patients with dyspepsia symptoms.

Dynamic integration of conceptual information during learning.

The development and application of concepts is a critical component of cognition. Although concepts can be formed on the basis of simple perceptual or semantic features, conceptual representations can also capitalize on similarities across feature relationships. By representing these types of higher-order relationships, concepts can simplify the learning problem and facilitate decisions. Despite this, little is known about the neural mechanisms that support the construction and deployment of these kinds of higher-order concepts during learning. To address this question, we combined a carefully designed associative learning task with computational model-based functional magnetic resonance imaging (fMRI). Participants were scanned as they learned and made decisions about sixteen pairs of cues and associated outcomes. Associations were structured such that individual cues shared feature relationships, operationalized as shared patterns of cue pair-outcome associations. In order to capture the large number of possible conceptual representational structures that participants might employ and to evaluate how conceptual representations are used during learning, we leveraged a well-specified Bayesian computational model of category learning [1]. Behavioral and model-based results revealed that participants who displayed a tendency to link experiences in memory benefitted from faster learning rates, suggesting that the use of the conceptual structure in the task facilitated decisions about cue pair-outcome associations. Model-based fMRI analyses revealed that trial-by-trial integration of cue information into higher-order conceptual representations was supported by an anterior temporal (AT) network of regions previously implicated in representing complex conjunctions of features and meaning-based information.

Multialternative decision by sampling: A model of decision making constrained by process data.

Sequential sampling of evidence, or evidence accumulation, has been implemented in a variety of models to explain a range of multialternative choice phenomena. But the existing models do not agree on what, exactly, the evidence is that is accumulated. They also do not agree on how this evidence is accumulated. In this article, we use findings from process-tracing studies to constrain the evidence accumulation process. With these constraints, we extend the decision by sampling model and propose the multialternative decision by sampling (MDbS) model. In MDbS, the evidence accumulated is outcomes of pairwise ordinal comparisons between attribute values. MDbS provides a quantitative account of the attraction, compromise, and similarity effects equal to that of other models, and captures a wider range of empirical phenomena than other models. (PsycINFO Database Record

Design of a Hypersensitive pH-Sensory System Created by a Combination of Charge Neutralization and Aggregation-Induced Emission (AIE).

In our bodies, a slight pH change causes remarkable activation or serious damage in the biological processes and continuously keeps biological homeostasis. Detection of such a slight pH change has been a constant demand in searching for unusual biological events. In this paper, we demonstrate a novel pH sensory system that has been achieved through a combination of charge neutralization by a slight pH change with aggregation-induced emission (AIE). We selected a cyano-functionalized oligo(phenylene-vinylene) (cyanoOPV) backbone for AIE and introduced ammonium-tethered boronic acid groups as a pH-dependent function. The self-assembling of these dyes (OPV-Cn) was readily achieved by pH-dependent charge neutralization at the neutral pH region. This sensory system showed unusually sensitive pH responsiveness in a narrow pH range. Moreover, this pH change was observed in a biologically important neutral pH region. We therefore believe that this system is broadly applicable to detect the slight pH change occurring in the biological events.

A Chiral Recognition System Orchestrated by Self-Assembly: Molecular Chirality, Self-Assembly Morphology, and Fluorescence Response.

The newly developed oligophenylenevinylene (OPV)-based fluorescent (FL) chiral chemosensor (OPV-Me) for the representative enantiomeric guest, 1,2-cyclohexanedicarboxylic acid (1,2-CHDA: RR- and SS-form) showed the high chiral discrimination ability, resulting in the different aggregation modes of OPV-Me self-assembly: RR-CHDA directed the fibrous supramolecular aggregate, whereas SS-CHDA directed the finite aggregate. The consequent FL intensity toward RR-CHDA was up to 30 times larger than that toward SS-CHDA. Accordingly, highly enantioselective recognition was achieved. Application to the chirality sensing was also possible: OPV-Me exhibited a linear relationship between the FL intensity and the enantiomeric excess through the morphological development of stereocomplex aggregates. These results clearly show that the chiral recognition ability is manifested by the amplification cascade of the chirality difference through self-assembly.

Oral conditions and dysphagia in Japanese, community-dwelling middle- and older- aged adults, independent in daily living.

PURPOSE: Prevention, early detection and effective rehabilitation of dysphagia are important issues to be considered in an aging society. Previous studies have shown conflicting findings regarding the association between dysphagia and its potential risk factors, including age, malnutrition, oral conditions, lifestyle and medical history. Herein, we assessed the prevalence and association of dysphagia with potential risk factors in 50- to 79-year-old adults dwelling in a community in Japan. PATIENTS AND METHODS: In this study, there were 532 participants (185 males and 347 females). Participants who responded positively to the question "Do you sometimes choke on drinks/food such as tea and soup?" or those who presented with abnormal repetitive saliva swallowing test findings were diagnosed with dysphagia. The data collected from these participants included the following: number of teeth, occurrence of oral dryness, age, body mass index, serum albumin concentration, smoking, drinking and exercise habits, presence of diseases, such as diabetes mellitus and hypertension, and questions from the Mini-Mental State Examination. RESULTS: Dysphagia was observed in 33 males (17.8%) and 76 females (21.9%). To explore the effect of the potential risk factors on the prevalence of dysphagia, a model was built by multivariate logistic regression analysis. Using the forced entry method, oral dryness (odds ratio [OR] =3.683 and P=0.003 in males; OR =1.797 and P=0.032 in females) and the number of teeth (OR =0.946 and P=0.038 in males) were found to be significantly related to dysphagia. CONCLUSION: This cross-sectional study demonstrated associations between oral conditions and dysphagia. Factors such as oral dryness and number of teeth may contribute to dysphagia more so than aging, lifestyle and comorbidity in community-dwelling adults over the age of 50.

Photoresponsive Nanosheets of Polyoxometalates Formed by Controlled Self-Assembly Pathways.

Anionic Keggin polyoxometalates (POMs) and ether linkage-enriched ammonium ions spontaneously self-assemble into rectangular ultrathin nanosheets in aqueous media. The structural flexibility of the cation is essential to form oriented nanosheets; as demonstrated by single-crystal X-ray diffraction measurements. The difference in initial conditions exerts significant influence on selecting for self-assembly pathways in the energy landscape. Photoillumination of the POM sheets in pure water causes dissolution of reduced POMs, which allowed site-specific etching of nanosheets using laser scanning microscopy. By contrast, photoetching was suppressed in aqueous AgNO3 and site-selective deposition of silver nanoparticles occurred as a consequence of electron transfer from the photoreduced POMs to Ag+ ions on the nanosheet surface.

Cohelical Crossover Network by Supramolecular Polymerization of a 4,6-Acetalized ß-1,3-Glucan Macromer.

Natural polysaccharides represent a renewable resource whose effective utilization is of increasing importance. Chemical modification is a powerful tool to transform them into processable materials but usually sacrifices the original structures and properties of value. Here we introduce a chemical modification of Curdlan, a ß-1,3-glucan, via 4,6-acetalization. This modification has successfully combined a helix-forming ability of Curdlan with new solubility in organic media. Furthermore, it has operationalized efficient cohelical crossovers (CCs) among the helices to demonstrate the formation of an extensive supramolecular network that goes well beyond the nanoscopic regime, allowing for preparation of flexible self-supporting films with macroscopic dimensions. This protocol, which is now viewed as supramolecular polymerization of a helical polysaccharide macromer, can add a new dimension to "polysaccharide nanotechnology", opening a door for the creation of unconventional polymer materials based on the cohelical crossover network (CCN).

Adaptive Self-Assembly Behavior Restrained by Supramolecular Crystallization and Molecular Recognition.

The control over supramolecular interactions and obtaining information beyond the molecular scale is an extended challenge. The intriguing self-assembly of a perylene-3,4,9,10-tetracarboxylic acid diimide (PDI)-based novel bolaamphiphilic probe is experienced within an artificial environment that is restrained by using supramolecular crystallization and molecular recognition. The bolaamphiphile with a hydrophilic [18]-azacrown ether ring produced nanoaggregates due to differing solubilities in organic and aqueous media. A structural evolution was observed in the presence of alkali metal ions as guests. The metal complexes form a pseudo-cationic structure, which is further involved in an ionic self-assembly with biomolecules, thus resulting new spectroscopic information on the dye self-assembly. The overarching aim of this study is to emphasize the importance of the concept of supramolecular adaptability, which has been used to establish an environment-friendly behavior based on noncovalent forces, thus leading to the evolution of new assembly structures and photophysical properties.

Instantaneous Conventions.

Humans can communicate even with few existing conventions in common (e.g., when they lack a shared language). We explored what makes this phenomenon possible with a nonlinguistic experimental task requiring participants to coordinate toward a common goal. We observed participants creating new communicative conventions using the most minimal possible signals. These conventions, furthermore, changed on a trial-by-trial basis in response to shared environmental and task constraints. Strikingly, as a result, signals of the same form successfully conveyed contradictory messages from trial to trial. Such behavior is evidence for the involvement of what we term joint inference, in which social interactants spontaneously infer the most sensible communicative convention in light of the common ground between them. Joint inference may help to elucidate how communicative conventions emerge instantaneously and how they are modified and reshaped into the elaborate systems of conventions involved in human communication, including natural languages.

Eye Movements in Strategic Choice.

In risky and other multiattribute choices, the process of choosing is well described by random walk or drift diffusion models in which evidence is accumulated over time to threshold. In strategic choices, level-k and cognitive hierarchy models have been offered as accounts of the choice process, in which people simulate the choice processes of their opponents or partners. We recorded the eye movements in 2 × 2 symmetric games including dominance-solvable games like prisoner's dilemma and asymmetric coordination games like stag hunt and hawk-dove. The evidence was most consistent with the accumulation of payoff differences over time: we found longer duration choices with more fixations when payoffs differences were more finely balanced, an emerging bias to gaze more at the payoffs for the action ultimately chosen, and that a simple count of transitions between payoffs-whether or not the comparison is strategically informative-was strongly associated with the final choice. The accumulator models do account for these strategic choice process measures, but the level-k and cognitive hierarchy models do not. © 2015 The Authors. Journal of Behavioral Decision Making published by John Wiley & Sons Ltd.

Conformation Control of a Conjugated Polymer through Complexation with Bile Acids Generates Its Novel Spectral and Morphological Properties.

Control of higher-order polymer structures attracts a great deal of interest for many researchers when they lead to the development of materials having various advanced functions. Among them, conjugated polymers that are useful as starting materials in the design of molecular wires are particularly attractive. However, an equilibrium existing between isolated chains and bundled aggregates is inevitable and has made their physical properties very complicated. As an attempt to simplify this situation, we previously reported that a polymer chain of a water-soluble polythiophene could be isolated through complexation with a helix-forming polysaccharide. More recently, a covalently self-threading polythiophene was reported, the main chain of which was physically protected from self-folding and chain-chain π-stacking. In this report, we wish to report a new strategy to isolate a water-soluble polythiophene and to control its higher-order structure by a supramolecular approach: that is, among a few bile acids, lithocholate can form stoichiometric complexes with cationic polythiophene to isolate the polymer chain, and the higher-order structure is changeable by the molar ratio. The optical and morphological studies have been thoroughly performed, and the resultant complex has been applied to the selective recognition of two AMP structural isomers.

Emergent Molecular Recognition through Self-Assembly: Unexpected Selectivity for Hyaluronic Acid among Glycosaminoglycans.

Oligophenylenevinylene (OPV)-based fluorescent (FL) chemosensors exhibiting linear FL responses toward polyanions were designed. Their application to FL sensing of glycosaminoglycans (heparin: HEP, chondroitin 4-sulfate: ChS, and hyaluronic acid: HA) revealed that the charge density encoded as the unit structure directs the mode of OPV self-assembly: H-type aggregate for HEP with 16-times FL increase and J-type aggregate for HA with 93-times FL increase, thus unexpectedly achieving the preferential selectivity for HA in contrast to the conventional HEP selective systems. We have found that the integral magnitude of three factors consisting of binding mechanism, self-assembly, and FL response can amplify the structural information on the target input into the characteristic FL output. This emergent property has been used for a novel molecular recognition system that realizes unconventional FL sensing of HA, potentially applicable to the clinical diagnosis of cancer-related diseases.

Amplified fluorescence emission of bolaamphiphilic perylene-azacrown ether derivatives directed towards molecular recognition events.

Long-term creative approaches have been considered in the design of molecular probes to overcome the quenching effect of important dyes in an aqueous medium. Using the rational donor-acceptor based design principle, we demonstrate herein the different fluorescence states of a non-conjugated symmetrical perylene-azacrown ether system in a solution, from the molecular to the aggregated states. The ethylene-spacer is exceptionally capable of fluorescence enhancement, even in the aggregated state (organic nanoparticle, ONPs, 44 nm), overcoming the quenching effect on changing the solvent from tetrahydrofuran to water. The ONPs with crown ether receptors at the surface show colloidal stability in an aqueous solution. Furthermore, an improved fluorescent state is developed via ONPs-polymer (protamine, Pro) hybridization. Supramolecular interactions between the crown ring and the guanidinium group in Pro play an important role in the ONPs-Pro hybrid formation. The decorated fluorescent hybrid state is finally used as a nano-probe for sensing heparin via the turn-OFF mechanism. The decoration method is further generalized by recognition of the nucleotides. Herein, we detail the bottom-up approach to the molecular design and development of the different fluorescent states of a useful probe. Most excitingly, this new approach is very general and adaptive to facile detection.

Time-course of Serum Pro-inflammatory Cytokines and Chemokines Levels Observed in Granulomatosis with Polyangiitis: A Case Report.

A 77-year-old man visited our hospital with chief complaints of difficulty in hearing, nasal discharge and fever. The patients was diagnosed with otitis media, and his fever continued at approximately 38°C despite the administration of clarithromycin. After that, dyspnea on exertion developed and chest X-ray examination indicated multiple infiltrative shadows. PR3-ANCA levels were high (238-fold of the normal levels), and granulomatosis with polyangiitis (GPA) was diagnosed on the basis of clinical symptoms, laboratory results, and pathological findings. Thus, remission induction therapy was initiated with prednisolone and cyclophosphamide, following which symptoms and imaging findings rapidly improved. Blood concentrations of tumor necrosis factor-α, interleukin-8, and growth-related oncogene that had been measured since before treatment decreased over time with the improvement of lesions following treatment.

Tailoring of the desired selectivity and the turn-on detection range in a self-assembly-based fluorescence sensory system.

This study demonstrates how to control the selectivity and the turn-on detection range toward the tailoring of an assembly-based fluorescence (FL) sensory system. Assembly-based FL chemosensors composed of oligophenylenevinylene with a varied number of guanidinium receptors (G2, G4 and G6) were newly developed, and their FL response to nucleotides (AMP, ADP and ATP) was investigated. Indeed, G6 exhibited FL emission via self-assembly with ATP. More importantly, the FL response of G6 showed markedly improved selectivity for ATP over ADP and a broadly extended detection range of ATP concentration under adjusted salt conditions. The salt effect on the FL response revealed the competitive binding interactions affecting the subsequent self-assembly process. These studies have unveiled the pivotal binding mechanisms operating in the self-assembly process, which tailor the performance level of the assembly-based sensory system. We believe that this study offers a new design principle of an assembly-based FL chemosensor with high selectivity and the appropriate detection range, being different from the conventional key-and-lock system.

Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis.

The loss of homeostasis of essential metals is associated with various diseases, including neurodegenerative diseases. Previous studies have shown that the levels of zinc (Zn) are significantly higher in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Zn transporters and metallothioneins tightly control intracellular and extracellular Zn levels. This study investigated the protein levels of ZnT, a Zn transporter family, in ALS patients and model mice. The mRNA expression of ZnT1, -3, -4, -5, -6, -7, and -10 was assessed in the spinal cords of human control subjects. ZnT3 and ZnT6 protein levels were significantly diminished in the spinal cords of sporadic ALS patients compared with controls. Furthermore, immunohistochemical staining demonstrated decreased ZnT3 and ZnT6 immunoreactivity in the ventral horn of the spinal cords in ALS patients. Moreover, immunohistochemical analysis revealed that all ZnTs expressed in the spinal cords were localized in a distinct subset of motor neurons. In addition, ZnT3 and ZnT6 protein levels were not altered in SOD1 (G93A) mutant transgenic mice before or after the onset of ALS symptoms compared with controls. These results suggest that ZnT3 and ZnT6 protein levels are decreased in the spinal cords of sporadic ALS patients; however, this did not occur merely via loss of motor neurons.