Out-of-Hospital Cardiac Arrest Bystander Defibrillator Search Time and Experience With and Without Directional Assistance: A Randomized Simulation Trial in a Community Setting

INTRODUCTION: Probability of survival after out-of-hospital cardiac arrest (OHCA) doubles when a bystander initiates cardiopulmonary resuscitation and uses an automated external defibrillator (AED) rapidly. National, state, and community efforts have increased placement of AEDs in public spaces; however, bystander AED use remains less than 2% in the United States. Little is known about the effect of giving bystanders directional assistance to the closest public access AED. METHODS: We conducted 35 OHCA simulations using a life-sized manikin with participants aged 18 through 65 years who searched for public access AEDs in 5 zones on a university campus. Zones varied by challenges to pedestrian AED acquisition and number of fixed AEDs. Participants completed 2 searches-first unassisted and then with verbal direction to the closest AED-and we compared AED delivery times. We conducted pretest and posttest surveys. RESULTS: In all 5 zones, the median time from simulated OHCA onset to AED delivery was lower when the bystander received directional assistance. Time savings (minutes:seconds) varied by zone, ranging from a median of 0:53 (P = 0.14) to 3:42 (P = 0.02). Only 3 participants immediately located the closest AED without directional assistance; more than half reported difficulty locating an AED. CONCLUSIONS: These findings may inform strategies to ensure that AEDs are consistently marked and placed in visible, accessible locations. Continued emphasis on developing strategies to improve lay bystanders' ability to locate and use AEDs may improve AED retrieval times and OHCA outcomes

Rare functional variants associated with antidepressant remission in Mexican-Americans: short title: antidepressant remission and pharmacogenetics in Mexican-Americans

Introduction: Rare genetic functional variants can contribute to 30-40% of functional variability in genes relevant to drug action. Therefore, we investigated the role of rare functional variants in antidepressant response. Method: Mexican-American individuals meeting the Diagnostic and Statistical Manual-IV criteria for major depressive disorder (MDD) participated in a prospective randomized, double-blind study with desipramine or fluoxetine. The rare variant analysis was performed using whole-exome genotyping data. Network and pathway analyses were carried out with the list of significant genes. Results: The Kernel-Based Adaptive Cluster method identified functional rare variants in 35 genes significantly associated with treatment remission (False discovery rate, FDR <0.01). Pathway analysis of these genes supports the involvement of the following gene ontology processes: olfactory/sensory transduction, regulation of response to cytokine stimulus, and meiotic cell cycleprocess. Limitations: Our study did not have a placebo arm. We were not able to use antidepressant blood level as a covariate. Our study is based on a small sample size of only 65 Mexican-American individuals. Further studies using larger cohorts are warranted. Conclusion: Our data identified several rare functional variants in antidepressant drug response in MDD patients. These have the potential to serve as genetic markers for predicting drug response. Trial Registration: ClinicalTrials.gov NCT00265291.Ma-Li Wong, Mauricio Arcos-Burgos, Sha Liu, Alice W. Licinio, Chenglong Yu, Eunice W.M. Chin, Wei-Dong Yao, Xin-Yun Lu, Stefan R. Bornstein, Julio Licini

Highly conserved interaction profiles between clinically relevant mutants of the cytomegalovirus CDK-like kinase pUL97 and human cyclins: functional significance of cyclin H

The complex host interaction network of human cytomegalovirus (HCMV) involves the regulatory protein kinase pUL97, which represents a viral cyclin-dependent kinase (CDK) ortholog. pUL97 interacts with the three human cyclin types T1, H, and B1, whereby the binding region of cyclin T1 and the pUL97 oligomerization region were both assigned to amino acids 231-280. We further addressed the question of whether HCMVs harboring mutations in ORF-UL97, i.e., short deletions or resistance-conferring point mutations, are affected in the interaction with human cyclins and viral replication. To this end, clinically relevant UL97 drug-resistance-conferring mutants were analyzed by whole-genome sequencing and used for genetic marker transfer experiments. The recombinant HCMVs indicated conservation of pUL97-cyclin interaction, since all viral UL97 point mutants continued to interact with the analyzed cyclin types and exerted wild-type-like replication fitness. In comparison, recombinant HCMVs UL97 Δ231-280 and also the smaller deletion Δ236-275, but not Δ241-270, lost interaction with cyclins T1 and H, showed impaired replication efficiency, and also exhibited reduced kinase activity. Moreover, a cellular knock-out of cyclins B1 or T1 did not alter HCMV replication phenotypes or pUL97 kinase activity, possibly indicating alternative, compensatory pUL97-cyclin interactions. In contrast, however, cyclin H knock-out, similar to virus deletion mutants in the pUL97-cyclin H binding region, exhibited strong defective phenotypes of HCMV replication, as supported by reduced pUL97 kinase activity in a cyclin H-dependent coexpression setting. Thus, cyclin H proved to be a very relevant determinant of pUL97 kinase activity and viral replication efficiency. As a conclusion, the results provide evidence for the functional importance of pUL97-cyclin interaction. High selective pressure on the formation of pUL97-cyclin complexes was identified by the use of clinically relevant mutants

Collinear cluster tripartition as sequential binary fission in the 235^{235}U(nth_{\rm th},f) reaction

The mechanism leading to the formation of the observed products of the collinear cluster tripartition is carried out within the framework of the model based on the dinuclear system concept. The yield of fission products is calculated using the statistical model based on the driving potentials for the fissionable system. The minima of potential energy of the decaying system correspond to the charge numbers of the products which are produced with large probabilities in the sequential fission (partial case of the collinear cluster tripartition) of the compound nucleus. The realization of this mechanism supposes the asymmetric fission channel as the first stage of sequential mechanism. It is shown that only the use of the driving potential calculated by the binding energies with the shell correction allows us to explain the yield of the true ternary fission products. The theoretical model is applied to research collinear cluster tripartition in the reaction $^{235}$U(n$_{\rm th}$,f). Calculations showed that in the first stage of this fission reaction, the isotopes $^{82}$Ge and $^{154}$Nd are formed with relatively large probabilities and in the second stage of sequential fission of the isotope Nd mainly Ni and Ge are formed. This is in agreement with the yield of the isotope $^{68}$Ni which is observed as the product of the collinear cluster tripartition in the experiment.Comment: 20 pages, 9 figure

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

Optimization of blood handling and peripheral blood mononuclear cell cryopreservation of low cell number samples

Background: Rural/remote blood collection can cause delays in processing, reducing PBMC number, viability, cell composition and function. To mitigate these impacts, blood was stored at 4 °C prior to processing. Viable cell number, viability, immune phenotype, and Interferon-γ (IFN-γ) release were measured. Furthermore, the lowest protective volume of cryopreservation media and cell concentration was investigated. Methods: Blood from 10 individuals was stored for up to 10 days. Flow cytometry and IFN-γ ELISPOT were used to measure immune phenotype and function on thawed PBMC. Additionally, PBMC were cryopreserved in volumes ranging from 500 µL to 25 µL and concentration from 10 × 10⁶ cells/mL to 1.67 × 10⁶ cells/mL. Results: PBMC viability and viable cell number significantly reduced over time compared with samples processed immediately, except when stored for 24 h at RT. Monocytes and NK cells significantly reduced over time regardless of storage temperature. Samples with >24 h of RT storage had an increased proportion in Low-Density Neutrophils and T cells compared with samples stored at 4 °C. IFN-γ release was reduced after 24 h of storage, however not in samples stored at 4 °C for >24 h. The lowest protective volume identified was 150 µL with the lowest density of 6.67 × 10⁶ cells/mL. Conclusion: A sample delay of 24 h at RT does not impact the viability and total viable cell numbers. When long-term delays exist (>4 d) total viable cell number and cell viability losses are reduced in samples stored at 4 °C. Immune phenotype and function are slightly altered after 24 h of storage, further impacts of storage are reduced in samples stored at 4 °C.Christopher M. Hope, Dao Huynh, Ying Ying Wong, Helena Oakey, Griffith Boord Perkins, Trung Nguyen, Sabrina Binkowski, Minh Bui, Ace Y.L. Choo, Emily Gibson, Dexing Huang, Ki Wook Kim, Katrina Ngui, William D. Rawlinson, Timothy Sadlon, Jennifer J. Couper, Megan A.S. Penno, Simon C. Barry, and on behalf of the ENDIA Study Grou

Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the vascular effects of infection in pediatric stroke study.

Background and purposeAlthough arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.MethodsVascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.ResultsCases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78).ConclusionsClinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke

Internal representations of smell in the Drosophila brain

Recent advances in sensory neuroscience using Drosophila olfaction as a model system have revealed brain maps representing the external world. Once we understand how the brain's built-in capability generates the internal olfactory maps, we can then elaborate how the brain computes and makes decision to elicit complex behaviors. Here, we review current progress in mapping Drosophila olfactory circuits and discuss their relationships with innate olfactory behaviors

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements