New Detectors to Explore the Lifetime Frontier

Long-lived particles (LLPs) are a common feature in many beyond the Standard Model theories, including supersymmetry, and are generically produced in exotic Higgs decays. Unfortunately, no existing or proposed search strategy will be able to observe the decay of non-hadronic electrically neutral LLPs with masses above $\sim$ GeV and lifetimes near the limit set by Big Bang Nucleosynthesis (BBN), $c \tau \lesssim 10^7 - 10^8$~m. We propose the MATHUSLA surface detector concept (MAssive Timing Hodoscope for Ultra Stable neutraL pArticles), which can be implemented with existing technology and in time for the high luminosity LHC upgrade to find such ultra-long-lived particles (ULLPs), whether produced in exotic Higgs decays or more general production modes. We also advocate for a dedicated LLP detector at a future 100 TeV collider, where a modestly sized underground design can discover ULLPs with lifetimes at the BBN limit produced in sub-percent level exotic Higgs decays.Comment: 7 pages, 4 figures. Added more detail to discussion of backgrounds. Various minor clarifications. Results and conclusions unchange

Tonic And Phasic Inhibitory Mechanisms Mediating Sensorimotor Decision-Making In The Goldfish Auditory Startle Circuit

This work describes related studies of cellular and synaptic signaling mechanisms involved in the balance of excitation and inhibition in the goldfish auditory startle circuit. The general purpose of these experiments was to identify novel mechanisms that contribute to action selection at different stages of the motor control hierarchy. The methods applied to achieve this goal tested the effects of selective antagonists for target receptor systems on sound-evoked excitation and inhibition of startle. Chapter 2 describes a study of a poorly-understood serotonergic mechanism, the 5-HT5A receptor, that was not previously functionally characterized in native tissues or associated with neural or behavioral processes. Treatment with a selective 5-HT5A antagonist caused a 26.41 ± 3.98% reduction in sound-evoked excitation of startle. Subsequent experiments revealed that the 5-HT5A antagonist significantly reduced post-synaptic excitability in the Mauthner-cell (M-cell) neurons that initiate startle. Despite these effects, prepulse inhibition (PPI) of the startle response remained robustly intact after treatment with the 5-HT5A antagonist. The 5-HT5A receptor is thus not a likely mechanism for PPI, but does act as a selective modulator of startle excitability. A final series of experiments confirmed that the 5-HT5A antagonist reduced M-cell excitability by increasing Cl- conductance, likely by activating Cl- channels. Chapter 3 presents experiments focused on the inhibitory neurotransmitters that directly mediate the phasic inhibitory process elicited during PPI. Strychnine, a glycine receptor (GlyR) antagonist, caused an 87.43 ± 21.53% increase in sound-evoked excitation of startle, but PPI remained robustly intact, despite this. GlyRs thus likely mediate a tonic inhibitory process that was blocked by strychnine treatment, but glycinergic components of sound-evoked inhibition decayed too rapidly (\u3c50 \u3ems) to contribute to the prolonged time-course of PPI. In a parallel series of experiments, treatment with bicuculline, the GABAAR antagonist, caused similar increases in sound-evoked excitation (by 133.8 ± 10.3%) of startle, but the GABAAR antagonist also significantly reduced auditory PPI at inter-stimulus intervals of 100 ms and less. In sum, these findings indicate that glycine and GABA tonically inhibit the M-cell startle circuit, but GABA is also the primary effector mechanism for inhibitory signaling during PPI. In summary, three goals were accomplished. First, the thorough functional characterization of 5-HT5A provides a fully integrated serotonergic mechanism, and this appears to provide an ideal tool for selective potentiation of startle. Next, experiments with strychnine emphasize a short-lived role of GlyRs in sound-evoked (feed-forward) inhibition, and also act as mediators of a tonic inhibitory process that controls startle excitability. Last, experiments with bicuculline identify GABA as the inhibitory neurotransmitter that directly mediates PPI

Biodynamic Interfaces Are Essential for Human-Environment Interactions.

AbstractThe environment impacts human health in profound ways, yet few theories define the form of the relationship between human physiology and the environment. It is conjectured that such complex systems cannot interact directly, but rather their interaction requires the formation of an intermediary "interface." This position contrasts with current epidemiological constructs of causation, which implicitly assume that two complex systems transfer information directly while remaining separate entities. Further, it is contended that dynamic, process‐based interfaces incorporate components from all the interacting systems but exhibit operational independence. This property has many consequences, the foremost being that characteristics of the interface cannot be fully resolved by only studying the systems involved in the interaction. The interface itself must be the subject of inquiry. Without refocusing the attention on biodynamic interfaces, how the environment impacts health cannot be discerned. Also see the video abstract here https://youtu.be/XeyjeZeyo4o

Explicit criteria as clinical tools to minimize inappropriate medication use and its consequences

Polypharmacy and prescribing of potentially inappropriate medications (PIMs) are the key elements of inappropriate medication use (IMU) in older multimorbid people. IMU is associated with a range of negative healthcare consequences including adverse drug events and unplanned hospitalizations. Furthermore, prescribing guidelines are commonly derived from randomized controlled clinical trials which have specifically excluded older adults with multimorbidity. Consequently, indiscriminate application of single disease pharmacotherapy guidelines to older multimorbid patients can lead to increased risk of drug?drug interactions, drug?disease interactions and poor drug adherence. Both polypharmacy and PIMs are highly prevalent in older people and strategies to improve the quality and safety of prescribing, largely through avoidance of IMU, are needed. In the last 30?years, numerous explicit PIM criteria-based tools have been developed to assist physicians with medication management in clinically complex multimorbid older people. Very few of these PIM criteria sets have been tested as an intervention compared with standard pharmaceutical care in well-designed clinical trials. In this review, we describe the most widely used sets of explicit PIM criteria to address inappropriate polypharmacy with particular focus on STOPP/START criteria and FORTA criteria which have been associated with positive patient-related outcomes when used as interventions in recent randomized controlled trials

Structural studies of 1:1 quinone-hydroquinone complexes

The structures of the 1:1 quinone-hydroquinone complexes of 2-phenyl and of 2-(4'-chloro) phenylbenzoquinone have been studied by X-ray methods. A superficial study would indicate that the quinhydrones are centrosymmetric and belong to the space group P21/c. However, other evidence indicates that the true crystal structure may belong to either the space group P21 or to Pc, or that the crystal may contain regions that would coresspond to each of these two non-centrosymmetric space groups. Some possible consequences of such a structural arrangement are briefly discussed

Human Microbiome Mixture Analysis Using Weighted Quantile Sum Regression

: Studies of the health effects of the microbiome often measure overall associations by using diversity metrics, and individual taxa associations in separate analyses, but do not consider the correlated relationships between taxa in the microbiome. In this study, we applied random subset weighted quantile sum regression with repeated holdouts (WQSRSRH), a mixture method successfully applied to 'omic data to account for relationships between many predictors, to processed amplicon sequencing data from the Human Microbiome Project. We simulated a binary variable associated with 20 operational taxonomic units (OTUs). WQSRSRH was used to test for the association between the microbiome and the simulated variable, adjusted for sex, and sensitivity and specificity were calculated. The WQSRSRH method was also compared to other standard methods for microbiome analysis. The method was further illustrated using real data from the Growth and Obesity Cohort in Chile to assess the association between the gut microbiome and body mass index. In the analysis with simulated data, WQSRSRH predicted the correct directionality of association between the microbiome and the simulated variable, with an average sensitivity and specificity of 75% and 70%, respectively, in identifying the 20 associated OTUs. WQSRSRH performed better than all other comparison methods. In the illustration analysis of the gut microbiome and obesity, the WQSRSRH analysis identified an inverse association between body mass index and the gut microbe mixture, identifying Bacteroides, Clostridium, Prevotella, and Ruminococcus as important genera in the negative association. The application of WQSRSRH to the microbiome allows for analysis of the mixture effect of all the taxa in the microbiome, while simultaneously identifying the most important to the mixture, and allowing for covariate adjustment. It outperformed other methods when using simulated data, and in analysis with real data found results consistent with other study findings

Ariel - Volume 11 Number 3

Executive Editors Ellen Feldman Leonardo S. Nasca, Jr. Business Managers Barbara L. Davies Martin B. Getzow News Editor Hugh A. Gelabert Features Editor Aaron D. Bleznak CAHS Editor Joan M. Greco Editorial Page Editor Samuel Markind Photography Editor Todd Demmy Sports Editor Paul F. Mansfiel