2,208 research outputs found
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
The origins of quark-hadron duality: How does the square of the sum become the sum of the squares?
Bloom-Gilman duality demonstrates empirically that the electroproduction of
's at low momentum transfers averages smoothly around the scaling curve
measured at large momentum transfers. The latter is proportional to the sum of
the squares of the constituent charges whereas the former involves the coherent
excitation of resonances and is driven by the square of summed constituent
charges. We determine the minimal necessary conditions for this equality to be
realised so that duality can occur and consider the implications for a range of
processes that may be studied soon at CEBAF.Comment: 9 page
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
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
All Who Wander: On the Prevalence and Characteristics of Multi-community Engagement
Although analyzing user behavior within individual communities is an active
and rich research domain, people usually interact with multiple communities
both on- and off-line. How do users act in such multi-community environments?
Although there are a host of intriguing aspects to this question, it has
received much less attention in the research community in comparison to the
intra-community case. In this paper, we examine three aspects of
multi-community engagement: the sequence of communities that users post to, the
language that users employ in those communities, and the feedback that users
receive, using longitudinal posting behavior on Reddit as our main data source,
and DBLP for auxiliary experiments. We also demonstrate the effectiveness of
features drawn from these aspects in predicting users' future level of
activity.
One might expect that a user's trajectory mimics the "settling-down" process
in real life: an initial exploration of sub-communities before settling down
into a few niches. However, we find that the users in our data continually post
in new communities; moreover, as time goes on, they post increasingly evenly
among a more diverse set of smaller communities. Interestingly, it seems that
users that eventually leave the community are "destined" to do so from the very
beginning, in the sense of showing significantly different "wandering" patterns
very early on in their trajectories; this finding has potentially important
design implications for community maintainers. Our multi-community perspective
also allows us to investigate the "situation vs. personality" debate from
language usage across different communities.Comment: 11 pages, data available at
https://chenhaot.com/pages/multi-community.html, Proceedings of WWW 2015
(updated references
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
Locality of quark-hadron duality and deviations from quark counting rules above resonance region
We show how deviations from the dimensional scaling laws for exclusive
processes may be related to a breakdown in the locality of quark-hadron
duality. The essential principles are illustrated in a pedagogic model of a
composite system with two spinless charged constituents, for which a dual
picture for the low-energy resonance phenomena and high-energy scaling behavior
can be established. We introduce the concept of "restricted locality" of
quark-hadron duality and show how this results in deviations from the pQCD
quark counting rules above the resonance region. In particular it can be a
possible source for oscillations about the smooth quark counting rule, as seen
e.g. in the 90-degree differential cross sections for .Comment: The way to present Eqs. (2), (4), (7) are changed while physics
contents and calculations are left intact; Additional explanations for the
forward and large-angle duality are added; Three more references are
included; Version to appear on Phys. Rev. Let
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
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