Invoice from James Parker & Co. to Ogden Goelet

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Categorical differentiation of the unipolar and bipolar disorders

There has been a longstanding debate as to whether the bipolar disorders differ categorically or dimensionally, with some dimensional or spectrum models including unipolar depressive disorders within a bipolar spectrum model. We analysed manic/hypomanic symptom data in samples of clinically diagnosed bipolar I, bipolar II and unipolar patients, employing latent class analyses to determine if separate classes could be identified. Mixture analyses were also undertaken to determine if a unimodal, bimodal or a trimodal pattern was present. For both a refined 15-item set and an extended 30-item set of manic/hypomanic symptoms, our latent class analyses favoured three-class solutions, while mixture analyses identified trimodal distributions of scores. Findings argue for a categorical distinction between unipolar and bipolar disorders, as well as between bipolar I and bipolar II disorders. Future research should aim to consolidate these results in larger samples, particularly given that the size of the unipolar group in this study was a salient limitation

Emerging Pharmacotherapies for Adult Patients with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) treatment regimes are amongst the longest, most intensive and complex used in hematooncology. Despite this, while treatment of pediatric ALL is a success story, we are far from being able to ensure a durable response in adult ALL. This is not due to failure of induction therapy as a complete remission (CR) is achieved in over 90% of patients. However the challenge remains in ensuring a sustained remission. Furthermore in the face of relapsed disease, salvage therapies currently offer a poor chance of a good outcome. This article reviews the novel agents which show the most promise in the treatment of adult ALL

Disc reflection and a possible disc wind during a soft X-ray state in the neutron star low-mass X-ray binary 1RXS J180408.9-342058

1RXS J180408.9–342058 is a transient neutron star low-mass X-ray binary that exhibited a bright accretion outburst in 2015. We present $\textit{NuSTAR}$, $\textit{Swift}$, and $\textit{Chandra}$ observations obtained around the peak brightness of this outburst. The source was in a soft X-ray spectral state and displayed an X-ray luminosity of $L_\text{X}$ $\simeq$ (2–3) × 10$^{37}$($D$/5.8 kpc)$^2$ erg s$^{−1}$ (0.5–10 keV). The $\textit{NuSTAR}$ data reveal a broad Fe–K emission line that we model as relativistically broadened reflection to constrain the accretion geometry. We found that the accretion disc is viewed at an inclination of $i$ $\simeq$ 27$^{\circ}$–35$^{\circ}$ and extended close to the neutron star, down to $R_\text{in}$ $\simeq$ 5–7.5 gravitational radii ($\simeq$11–17 km). This inner disc radius suggests that the neutron star magnetic field strength is $B$ $\lesssim$ 2 × 10$^8$ G. We find a narrow absorption line in the $\textit{Chandra}$/HEG data at an energy of $\simeq$7.64 keV with a significance of $\simeq$4.8$\sigma$. This feature could correspond to blueshifted Fe $\small \text{XXVI}$ and arise from an accretion disc wind, which would imply an outflow velocity of $v_\text{out}$ $\simeq$0.086$c$ ($\simeq$25 800 km s$^{−1}$). However, this would be extreme for an X-ray binary and it is unclear if a disc wind should be visible at the low inclination angle that we infer from our reflection analysis. Finally, we discuss how the X-ray and optical properties of 1RXS J180408.9–342058 are consistent with a relatively small ($P_\text{orb}$ $\lesssim$ 3 h) binary orbit.ND is supported by an NWO/Vidi grant and an EU Marie Curie Intra-European fellowship under contract no. FP-PEOPLE-2013-IEF-627148. DA acknowledges support from the Royal Society. JCAMJ is supported by an Australian Research Council (ARC) Future Fellowship (FT140101082) and an ARC Discovery Grant (DP120102393). RW and AP are supported by an NWO/TOP grant, module 1, awarded to RW. COH is supported by an NSERC Discovery Grant. ATD is supported by an NWO/Veni grant. JWTH is supported by NWO/Vidi and ERC/starting (337062) grants

Optimal spaces for those living with dementia : principles and evidence

This paper represents a synthesis of diverse and disparate evidence in the research literature that provide insights into the impacts of aspects of the built environment on the wellbeing of those living with dementia. The individually focused findings are structured into a set of practical design parameters, driven by three overarching needs-driven design principles, namely: manageable cognitive load, clear sequencing, and appropriate level of stimulation. These needs are contextualized within a general model that suggests that action in any one area (such as the built environment) also has to take into account other key dimensions, namely any support from the caring / social environment and any pharmacological treatment. Addressing these elements holistically should maximize the opportunity to improve the quality of life of the individual. This paper, however, explicitly focuses on the built environment

New insights into the synergism of nucleoside analogs with radiotherapy

Nucleoside analogs have been frequently used in combination with radiotherapy in the clinical setting, as it has long been understood that inhibition of DNA repair pathways is an important means by which many nucleoside analogs synergize. Recent advances in our understanding of the structure and function of deoxycytidine kinase (dCK), a critical enzyme required for the anti-tumor activity for many nucleoside analogs, have clarified the mechanistic role this kinase plays in chemo- and radio-sensitization. A heretofore unrecognized role of dCK in the DNA damage response and cell cycle machinery has helped explain the synergistic effect of these agents with radiotherapy. Since most currently employed nucleoside analogs are primarily activated by dCK, these findings lend fresh impetus to efforts focused on profiling and modulating dCK expression and activity in tumors. In this review we will briefly review the pharmacology and biochemistry of the major nucleoside analogs in clinical use that are activated by dCK. This will be followed by discussions of recent advances in our understanding of dCK activation via post-translational modifications in response to radiation and current strategies aimed at enhancing this activity in cancer cells

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

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

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal