Executive Function Variance in a School-Based Behavioral Screener

The implementation of school-wide behavior supports is considered typical educational practice. A main component of school-wide behavior support is the systematic screening for behavioral and emotional problems. Students\u27 ability to utilize executive functions greatly affects both academic and social success and it is associated with behavior and emotional problems (Lehto, Juujarvi, Kooistra, & Pulkkinen, 2003). This study uses a sample of fourth grade students to analyze the relationship between executive function skills and a screening measure of behavior. This study will examine if deficits in executive function may account for variance in the first level of behavior support screening systems. This may help educators understand the relationship between behavior screening results and executive functions, and possibly explain how social and emotional difficulties may be affected by deficits in executive functions

TAK1 and TBK1 are Differentially Required by GMP- and LMPP-like Leukemia Stem Cells

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow. Aside from the M3 subtype (PML-RARA+), AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a 2-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine. Despite 60-70% of patients achieving complete remission (CR), at least half of CR-achieving patients experience relapse within 3 years from their diagnosis. Additionally, 30-40% of patients present with refractory AML, experiencing little to no benefit from frontline treatment. AML relapses when a pool of undetectable, CTx-resistant leukemia stem cells (LSCs) survives & proliferates after frontline CTx [1]. Notably, the poor performance status of many AML patients precludes use of the standard CTx regimen; while reduced-intensity CTx still offers therapeutic benefit, it is less effective at killing LSCs and, as a result, relapse is more likely. Goardon, et al. determined that AML patients harbor two types of LSCs: granulocyte-macrophage progenitor (GMP)-like LSCs and FLT3+ lymphoid-primed multipotential progenitor (LMPP)-like LSCs [2]. Eradication of both types of LSCs is necessary to maintain CR in AML. Our group and others have established that ~40% of AML patients express upregulated Toll-like receptor (TLR) signaling (TLR+). TLR+ disease is associated with specific genetic abnormalities, such as MLL rearrangements (MLL-r+), and is inversely associated with prognosis (Figure 1) [3,4]. TLR+ AML represents a challenging, treatment-sparse subset of an already difficult-to-treat disease. To study TLR+ AML, we utilize an MLL-r+ model using the MLL-AF9 oncogene. We have also demonstrated that both GMP- and LMPP-like LSCs require TLR-associated Ser/Thr protein kinases for their survival [5-7]. Specifically, GMP-like LSCs require TAK1 and LMPP-like LSCs require TBK1. The loss of either Tak1 or Tbk1 ablates the corresponding LSC pool and enriches for the opposite LSC pool in vitro and in vivo. Recently, our group determined that the genetic loss of Tak1 sensitizes mouse AML cells to TBK1 blockade in vitro. Strikingly, the loss of Tbk1 also seems to extend overall survival (OS) despite causing extramedullary AML. While mice given Tbk1NULL AML cells develop a subcutaneous tumor of AML cells (chloroma) near the pelvis, they survive longer than mice given control (Tbk1WT) AML cells. The clinical significance is unknown, but these data support our impression that the loss of Tbk1 forces AML cells to differentiate; this should be therapeutically favorable, as inducing the differentiation of AML cells is an effective treatment strategy. Theoretically, chloromas may form in Tbk1NULL AML due to the enrichment of GMP-like LSCs, which express higher levels of chemokine receptors. We hypothesize that the differentiation & eradication of LSCs can be induced by blocking TAK1/TBK1 in combination with standard CTx (and possibly targeted agents like Mylotarg®, Venclexta®, and/or Xospata®). We propose TAK1/TBK1 parallel blockade as augmentation to standard CTx, ideally allowing for a dose-reduction of CTx & promoting improved patient outcomes

NN Core Interactions and Differential Cross Sections from One Gluon Exchange

We derive nonstrange baryon-baryon scattering amplitudes in the nonrelativistic quark model using the ``quark Born diagram" formalism. This approach describes the scattering as a single interaction, here the one-gluon-exchange (OGE) spin-spin term followed by constituent interchange, with external nonrelativistic baryon wavefunctions attached to the scattering diagrams to incorporate higher-twist wavefunction effects. The short-range repulsive core in the NN interaction has previously been attributed to this spin-spin interaction in the literature; we find that these perturbative constituent-interchange diagrams do indeed predict repulsive interactions in all I,S channels of the nucleon-nucleon system, and we compare our results for the equivalent short-range potentials to the core potentials found by other authors using nonperturbative methods. We also apply our perturbative techniques to the N$\Delta$ and $\Delta\Delta$ systems: Some $\Delta\Delta$ channels are found to have attractive core potentials and may accommodate ``molecular" bound states near threshold. Finally we use our Born formalism to calculate the NN differential cross section, which we compare with experimental results for unpolarised proton-proton elastic scattering. We find that several familiar features of the experimental differential cross section are reproduced by our Born-order result.Comment: 27 pages, figures available from the authors, revtex, CEBAF-TH-93-04, MIT-CTP-2187, ORNL-CCIP-93-0

The distinct category of healthcare associated bloodstream infections

<p>Abstract</p> <p>Background</p> <p>Bloodstream infections (BSI) have been traditionally classified as either community acquired (CA) or hospital acquired (HA) in origin. However, a third category of healthcare-associated (HCA) community onset disease has been increasingly recognized. The objective of this study was to compare and contrast characteristics of HCA-BSI with CA-BSI and HA-BSI.</p> <p>Methods</p> <p>All first episodes of BSI occurring among adults admitted to hospitals in a large health region in Canada during 2000-2007 were identified from regional databases. Cases were classified using a series of validated algorithms into one of HA-BSI, HCA-BSI, or CA-BSI and compared on a number of epidemiologic, microbiologic, and outcome characteristics.</p> <p>Results</p> <p>A total of 7,712 patients were included; 2,132 (28%) had HA-BSI, 2,492 (32%) HCA-BSI, and 3,088 (40%) had CA-BSI. Patients with CA-BSI were significantly younger and less likely to have co-morbid medical illnesses than patients with HCA-BSI or HA-BSI (p < 0.001). The proportion of cases in males was higher for HA-BSI (60%; p < 0.001 vs. others) as compared to HCA-BSI or CA-BSI (52% and 54%; p = 0.13). The proportion of cases that had a poly-microbial etiology was significantly lower for CA-BSI (5.5%; p < 0.001) compared to both HA and HCA (8.6 vs. 8.3%). The median length of stay following BSI diagnosis 15 days for HA, 9 days for HCA, and 8 days for CA (p < 0.001). Overall the most common species causing bloodstream infection were <it>Escherichia coli, Staphylococcus aureus</it>, and <it>Streptococcus pneumoniae</it>. The distribution and relative rank of importance of these species varied according to classification of acquisition. Twenty eight day all cause case-fatality rates were 26%, 19%, and 10% for HA-BSI, HCA-BSI, and CA-BSI, respectively (p < 0.001).</p> <p>Conclusion</p> <p>Healthcare-associated community onset infections are distinctly different from CA and HA infections based on a number of epidemiologic, microbiologic, and outcome characteristics. This study adds further support for the classification of community onset BSI into separate CA and HCA categories.</p

Prostaglandin E2 Regulates AMPA Receptor Phosphorylation and Promotes Membrane Insertion in Preoptic Area Neurons and Glia during Sexual Differentiation

Sexual differentiation of the rodent brain is dependent upon the organizing actions of the steroid hormone, estradiol. In the preoptic area, a brain region critical for the expression of adult reproductive behavior, there are twice as many dendritic spine synapses per unit length on newborn male neurons compared to female neurons and this sex difference correlates with the expression of adult male copulatory behavior. The sex difference in the POA is achieved via estradiol's upregulation of the membrane-derived lipid signaling molecule prostaglandin E2 (PGE2); PGE2 is necessary and sufficient to masculinize both dendritic spine density and adult sexual behavior in rats. We have previously shown that PGE2 activates EP2 and EP4 receptors which increases protein kinase A (PKA) activity and that masculinized dendritic spine density and sex behavior are both dependent upon PKA as well as activation of AMPA type glutamate receptors. In the current experiments, we build upon this signaling cascade by determining that PGE2 induces phosphorylation of the AMPA receptor subunit, GluR1, which leads to increased AMPA receptor insertion at the membrane. Treating female pups on the day of birth with PGE2 induced the phosphorylation of GluR1 at the PKA-sensitive site within 2 hours of treatment, an effect that was blocked by co-administration of the PKA/AKAP inhibitor, HT31 with PGE2. Brief treatment of mixed neuronal/glial POA cultures with PGE2 or the cAMP/PKA stimulator, forskolin, increased membrane associated GluR1 in both neurons and glia. We speculate that PGE2 induced increases in AMPA receptor associated with the membrane underlies our previously observed increase in dendritic spine density and is a critical component in the masculinization of rodent sex behavior

Phylogeography of red muntjacs reveals three distinct mitochondrial lineages

Background: The members of the genus Muntiacus are of particular interest to evolutionary biologists due to their extreme chromosomal rearrangements and the ongoing discussions about the number of living species. Red muntjacs have the largest distribution of all muntjacs and were formerly considered as one species. Karyotype differences led to the provisional split between the Southern Red Muntjac (Muntiacus muntjak) and the Northern Red Muntjac (M. vaginalis), but uncertainties remain as, so far, no phylogenetic study has been conducted. Here, we analysed whole mitochondrial genomes of 59 archival and 16 contemporaneous samples to resolve uncertainties about their taxonomy and used red muntjacs as model for understanding the evolutionary history of other species in Southeast Asia. Results: We found three distinct matrilineal groups of red muntjacs: Sri Lankan red muntjacs (including the Western Ghats) diverged first from other muntjacs about 1.5 Mya; later northern red muntjacs (including North India and Indochina) and southern red muntjacs (Sundaland) split around 1.12 Mya. The diversification of red muntjacs into these three main lineages was likely promoted by two Pleistocene barriers: one through the Indian subcontinent and one separating the Indochinese and Sundaic red muntjacs. Interestingly, we found a high level of gene flow within the populations of northern and southern red muntjacs, indicating gene flow between populations in Indochina and dispersal of red muntjacs over the exposed Sunda Shelf during the Last Glacial Maximum. Conclusions: Our results provide new insights into the evolution of species in South and Southeast Asia as we found clear genetic differentiation in a widespread and generalist species, corresponding to two known biogeographical barriers: The Isthmus of Kra and the central Indian dry zone. In addition, our molecular data support either the delineation of three monotypic species or three subspecies, but more importantly these data highlight the conservation importance of the Sri Lankan/South Indian red muntjac

Priorities to Promote Participant Engagement in the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network.

BACKGROUND: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network\u27s research. METHODS: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network\u27s research priorities in participant engagement: (i) a brainstorming exercise to elicit potential priorities; (ii) a 2-day virtual meeting to discuss priorities; (iii) recommendations from the PE-CGS External Advisory Panel to refine priorities; and (iv) a virtual meeting to set priorities. RESULTS: Nearly 150 PE-CGS stakeholders engaged in the process. Five priorities were set: (i) tailor education and communication materials for participants throughout the research process; (ii) identify measures of participant engagement; (iii) identify optimal participant engagement strategies; (iv) understand cancer disparities in the context of cancer genomics research; and (v) personalize the return of genomics findings to participants. CONCLUSIONS: PE-CGS is pursuing these priorities to meaningfully engage diverse and underrepresented patients with cancer and posttreatment cancer survivors as participants in cancer genomics research and, subsequently, generate new discoveries. IMPACT: Data from PE-CGS will be shared with the broader scientific community in a manner consistent with participant informed consent and community agreement

Nursing sensitive outcomes in patients with rheumatoid arthritis: A systematic literature review

© 2017 Elsevier Ltd Background Although rheumatology nursing has been shown to be effective in managing patients with rheumatoid arthritis, patient outcomes sensitive to nursing interventions (nursing sensitive outcomes) have not been systematically studied. Objectives The objective of this study was to identify and delineate relevant patient outcomes measured in studies that reported nursing interventions in patients with rheumatoid arthritis. Design A systematic search was conducted from 1990 to 2016. Inclusion criteria were (i) patients with rheumatoid arthritis, (ii) adult population age ≥16 years, (iii) nurse as part of the care team or intervention delivery, (iv) primary research only, (v) English language, and (vi) quantitative studies with nursing sensitive outcomes. Data sources Medline, CINAHL, Ovid nursing, Cochrane library and PsycINFO databases were searched for relevant studies. Review methods Using the predetermined inclusion/exclusion criteria, nine reviewers working in pairs assessed the eligibility of the identified studies based on titles and abstracts. Papers meeting the inclusion criteria were retrieved and full texts were further assessed. Critical Appraisal Skills Programme tools were used to assess the quality of the included studies. Data on nursing sensitive outcomes were extracted independently by two reviewers. The Outcome Measures in Rheumatology comprehensive conceptual framework for health was used to contextualise and present findings. Results Of the 820 articles retrieved, 7 randomised controlled trials and 3 observational studies met the inclusion criteria. Seventeen nursing sensitive outcomes were identified (disease activity, clinical effects, pain, early morning stiffness duration, fatigue, patient safety issues, function, knowledge, patient satisfaction, confidence in care received, mental health status, self-efficacy, patient attitude/perception of ability to control arthritis, quality of life, health utility, health care resources, death). These fitted into 10 health intervention domains in keeping with the pre-specified conceptual framework for health: disease status, effectiveness, safety, function, knowledge, satisfaction, psychological status, quality of life, cost, death. A total of 59 measurement instruments were identified comprising patient reported outcome measures (n = 31), and biologic measures and reports (n = 28). Conclusions This review is notable in that it is the first to have identified, and reported, a set of multidimensional outcome measures that are sensitive to nursing interventions in rheumatology specifically. Further research is required to determine a core set of outcomes to be used in all rheumatology nursing intervention studies

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration