Generalized Convexity and Inequalities

Let R+ = (0,infinity) and let M be the family of all mean values of two numbers in R+ (some examples are the arithmetic, geometric, and harmonic means). Given m1, m2 in M, we say that a function f : R+ to R+ is (m1,m2)-convex if f(m1(x,y)) < or = m2(f(x),f(y)) for all x, y in R+ . The usual convexity is the special case when both mean values are arithmetic means. We study the dependence of (m1,m2)-convexity on m1 and m2 and give sufficient conditions for (m1,m2)-convexity of functions defined by Maclaurin series. The criteria involve the Maclaurin coefficients. Our results yield a class of new inequalities for several special functions such as the Gaussian hypergeometric function and a generalized Bessel function.Comment: 17 page

Psychiatric blood biomarkers: avoiding jumping to premature negative or positive conclusions

Blood biomarkers may provide a scientifically useful and clinically usable peripheral signal in psychiatry, as they have been doing for other fields of medicine. Jumping to premature conclusions, negative or positive, can create confusion in this field. Reproducibility is a hallmark of good science. We discuss some recent examples from this dynamic field, and show some new data in support of previously published biomarkers for suicidality (SAT1, MARCKS and SKA2). Methodological clarity and rigor in terms of biomarker discovery, validation and testing is needed. We propose a set of principles for what constitutes a good biomarker, similar in spirit to the Koch postulates used at the birth of the field of infectious diseases

Precision medicine for suicidality: from universality to subtypes and personalization

Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a ‘liquid biopsy’ approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies. Such markers may reflect and/or be a proxy for the core biology of suicide. We were successful in this endeavor, using a comprehensive stepwise approach, leading to a wealth of findings. Steps 1, 2 and 3 were discovery, prioritization and validation for tracking suicidality, resulting in a Top Dozen list of candidate biomarkers comprising the top biomarkers from each step, as well as a larger list of 148 candidate biomarkers that survived Bonferroni correction in the validation step. Step 4 was testing the Top Dozen list and Bonferroni biomarker list for predictive ability for suicidal ideation (SI) and for future hospitalizations for suicidality in independent cohorts, leading to the identification of completely novel predictive biomarkers (such as CLN5 and AK2), as well as reinforcement of ours and others previous findings in the field (such as SLC4A4 and SKA2). Additionally, we examined whether subtypes of suicidality can be identified based on mental state at the time of high SI and identified four potential subtypes: high anxiety, low mood, combined and non-affective (psychotic). Such subtypes may delineate groups of individuals that are more homogenous in terms of suicidality biology and behavior. We also studied a more personalized approach, by psychiatric diagnosis and gender, with a focus on bipolar males, the highest risk group. Such a personalized approach may be more sensitive to gender differences and to the impact of psychiatric co-morbidities and medications. We compared testing the universal biomarkers in everybody versus testing by subtypes versus personalized by gender and diagnosis, and show that the subtype and personalized approaches permit enhanced precision of predictions for different universal biomarkers. In particular, LHFP appears to be a strong predictor for suicidality in males with depression. We also directly examined whether biomarkers discovered using male bipolars only are better predictors in a male bipolar independent cohort than universal biomarkers and show evidence for a possible advantage of personalization. We identified completely novel biomarkers (such as SPTBN1 and C7orf73), and reinforced previously known biomarkers (such as PTEN and SAT1). For diagnostic ability testing purposes, we also examined as predictors phenotypic measures as apps (for suicide risk (CFI-S, Convergent Functional Information for Suicidality) and for anxiety and mood (SASS, Simplified Affective State Scale)) by themselves, as well as in combination with the top biomarkers (the combination being our a priori primary endpoint), to provide context and enhance precision of predictions. We obtained area under the curves of 90% for SI and 77% for future hospitalizations in independent cohorts. Step 5 was to look for mechanistic understanding, starting with examining evidence for the Top Dozen and Bonferroni biomarkers for involvement in other psychiatric and non-psychiatric disorders, as a mechanism for biological predisposition and vulnerability. The biomarkers we identified also provide a window towards understanding the biology of suicide, implicating biological pathways related to neurogenesis, programmed cell death and insulin signaling from the universal biomarkers, as well as mTOR signaling from the male bipolar biomarkers. In particular, HTR2A increase coupled with ARRB1 and GSK3B decreases in expression in suicidality may provide a synergistic mechanistical corrective target, as do SLC4A4 increase coupled with AHCYL1 and AHCYL2 decrease. Step 6 was to move beyond diagnostics and mechanistical risk assessment, towards providing a foundation for personalized therapeutics. Items scored positive in the CFI-S and subtypes identified by SASS in different individuals provide targets for personalized (psycho)therapy. Some individual biomarkers are targets of existing drugs used to treat mood disorders and suicidality (lithium, clozapine and omega-3 fatty acids), providing a means toward pharmacogenomics stratification of patients and monitoring of response to treatment. Such biomarkers merit evaluation in clinical trials. Bioinformatics drug repurposing analyses with the gene expression biosignatures of the Top Dozen and Bonferroni-validated universal biomarkers identified novel potential therapeutics for suicidality, such as ebselen (a lithium mimetic), piracetam (a nootropic), chlorogenic acid (a polyphenol) and metformin (an antidiabetic and possible longevity promoting drug). Finally, based on the totality of our data and of the evidence in the field to date, a convergent functional evidence score prioritizing biomarkers that have all around evidence (track suicidality, predict it, are reflective of biological predisposition and are potential drug targets) brought to the fore APOE and IL6 from among the universal biomarkers, suggesting an inflammatory/accelerated aging component that may be a targetable common denominator

Direct Observation of Quark-Hadron Duality in the Free Neutron F\u3csub\u3e2\u3c/sub\u3e Structure Function

Using the recently published data from the BONuS(Barely Off-shell Nucleon Structure) experiment at Jefferson Lab, which utilized a spectator tagging technique to extract the inclusive electron-free neutron scattering cross section, we obtain the first direct observation of quark-hadron duality in the neutron F2 structure function. The data are used to reconstruct the lowest few (N = 2, 4, and 6) moments of F2 in the three prominent nucleon resonance regions, as well as the moments integrated over the entire resonance region. Comparison with moments computed from global parametrizations of parton distribution functions suggest that quark-hadron duality holds locally for the neutron in the second and third resonance regions down to Q2 approximate to 1 GeV2, with violations possibly up to 20% observed in the first resonance region

Significance of solutions of the inverse Biot-Savart problem in thick superconductors

The evaluation of current distributions in thick superconductors from field profiles near the sample surface is investigated theoretically. A simple model of a cylindrical sample, in which only circular currents are flowing, reduces the inversion to a linear least squares problem, which is analyzed by singular value decomposition. Without additional assumptions about the current distribution (e.g. constant current over the sample thickness), the condition of the problem is very bad, leading to unrealistic results. However, any additional assumption strongly influences the solution and thus renders the solutions again questionable. These difficulties are unfortunately inherent to the inverse Biot-Savart problem in thick superconductors and cannot be avoided by any models or algorithms

Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs

We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic

Moments of the Proton F2 Structure Function at Low Q2

The Q^2 dependence of inclusive electron-proton scattering F_2 structure function data in both the nucleon resonance region and the deep inelastic region, at momentum transfers below 5 (GeV/c)^2, is investigated. Moments of F_2 are constructed, down to momentum transfers of Q^2 ~ 0.1 (GeV/c)^2. The second moment is only slowly varying with Q^2 down to Q^2 ~ 1 (GeV/c)^2, which is a reflection of duality. Below Q^2 of 1 (GeV/c)^2, the Q^2 dependence of the moments is predominantly governed by the elastic contribution, whereas the inelastic channels still seem governed by local duality.Comment: 11 page paper, 1 LaTeX file, 10 postscript figure file

Processing fluency scale development for consumer research

Processing fluency or the subjective experience of ease that consumers can experience when processing information is a prominent construct in consumer research. Despite its prevalence, however, its measurement has been inconsistent. The present research addresses this methodological gap in literature by developing and testing a scale for assessing the subjective experience of processing fluency. This scale demonstrates strong evidence of convergent and discriminant validity, reliability, and nomological validity across different processing fluency manipulations and marketing contexts. Use of this scale will allow marketing practitioners and academicians to consistently measure a psychological state that is known to have ubiquitous effects on downstream consumer outcomes including trust, attitude, and choice. Researchers can administer this four-item scale by having participants indicate their agreement (1 = strongly disagree, 7 = strongly agree) on whether a given marketing communication (e.g., ad copy) is (a) difficult to process, (b) difficult to read, (c) takes a long time to process, and (d) difficult to understand