Use of an integrated clinical trial database to evaluate the effect of timing of drotrecogin alfa (activated) treatment in severe sepsis

INTRODUCTION: Several studies have indicated that early identification and treatment of patients with severe sepsis using standard supportive care improves outcomes. Earlier treatment with drotrecogin alfa (activated) (DrotAA) may also improve outcomes in severe sepsis. Using a recently constructed integrated severe sepsis database, our objectives in this study were to describe the influence of baseline clinical characteristics on timing of DrotAA treatment in patients with severe sepsis, to evaluate the efficacy of DrotAA with respect to timing of administration, and to examine the association between early intervention with DrotAA and patient outcomes, using adjustments for imbalances. METHODS: The database comprises data from 4,459 patients with severe sepsis (DrotAA, n = 3,228; placebo, n = 1,231) included in five clinical trials conducted in tertiary care institutions in 28 countries. Placebo data came only from randomized trials, whereas data for the DrotAA group came from randomized (PROWESS) and open-label/observational (ENHANCE) trials. RESULTS: Increased time-to-treatment with DrotAA was significantly associated with more organ dysfunction, greater need of mechanical ventilation, vasopressor use, or recent surgery. Earlier treatment was associated with higher baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Adjusted and unadjusted survival analyses suggested that compared with placebo, DrotAA treatment provided a potential survival benefit, regardless of time to treatment. Survival curves of DrotAA patients treated early compared with those treated late began to separate at 14 days. By 28 days, patients treated earlier had higher survival than those treated later (76.4% versus 73.5%, p = 0.03). Sepsis-induced multiorgan dysfunction was the most common cause of death followed by refractory shock and respiratory failure. Modeling of the treatment effect, as a function of time to treatment, suggested increased benefit with earlier treatment. CONCLUSION: Using an integrated database of five severe sepsis trials and appropriate statistical adjustments to reduce sources of potential bias, earlier treatment with DrotAA seemed to be associated with a lower risk-adjusted mortality than later treatment. These data suggest that earlier treatment with DrotAA may provide most benefit for appropriate patients

The low-energy limit of AdS(3)/CFT2 and its TBA

We investigate low-energy string excitations in AdS3 × S3 × T4. When the worldsheet is decompactified, the theory has gapless modes whose spectrum at low energies is determined by massless relativistic integrable S matrices of the type introduced by Al. B. Zamolodchikov. The S matrices are non-trivial only for excitations with identical worldsheet chirality, indicating that the low-energy theory is a CFT2. We construct a Thermodynamic Bethe Ansatz (TBA) for these excitations and show how the massless modes’ wrapping effects may be incorporated into the AdS3 spectral problem. Using the TBA and its associated Y-system, we determine the central charge of the low-energy CFT2 to be c = 6 from calculating the vacuum energy for antiperiodic fermions — with the vacuum energy being zero for periodic fermions in agreement with a supersymmetric theory — and find the energies of some excited states

Finite-gap equations for strings on AdS_3 x S^3 x T^4 with mixed 3-form flux

We study superstrings on AdS_3 x S^3 x T^4 supported by a combination of Ramond-Ramond and Neveu-Schwarz-Neveu-Schwarz three form fluxes, and construct a set of finite-gap equations that describe the classical string spectrum. Using the recently proposed all-loop S-matrix we write down the all-loop Bethe ansatz equations for the massive sector. In the thermodynamic limit the Bethe ansatz reproduces the finite-gap equations. As part of this derivation we propose expressions for the leading order dressing phases. These phases differ from the well-known Arutyunov-Frolov-Staudacher phase that appears in the pure Ramond-Ramond case. We also consider the one-loop quantization of the algebraic curve and determine the one-loop corrections to the dressing phases. Finally we consider some classical string solutions including finite size giant magnons and circular strings.Comment: 44 pages, 3 figures. v2: references and a discussion about perturbative results adde

Excited State Dynamics of Bistridentate and Trisbidentate RuII Complexes of Quinoline-Pyrazole Ligands

Three homoleptic ruthenium(II) complexes, [Ru(Q3PzH)3]2+, [Ru(Q1Pz)3]2+, and [Ru(DQPz)2]2+, based on the quinoline-pyrazole ligands, Q3PzH (8-(3-pyrazole)-quinoline), Q1Pz (8-(1-pyrazole)-quinoline), and DQPz (bis(quinolinyl)-1,3-pyrazole), have been spectroscopically and theoretically investigated. Spectral component analysis, transient absorption spectroscopy, density functional theory calculations, and ligand exchange reactions with different chlorination agents reveal that the excited state dynamics for Ru(II) complexes with these biheteroaromatic ligands differ significantly from that of traditional polypyridyl complexes. Despite the high energy and low reorganization energy of the excited state, nonradiative decay dominates even at liquid nitrogen temperatures, where triplet metal-to-ligand-charge-transfer emission quantum yields range from 0.7 to 3.8%, and microsecond excited state lifetimes are observed. In contrast to traditional polypyridyl complexes where ligand exchange is facilitated by expansion of the metal-ligand bonds to stabilize a metal-centered state, photoinduced ligand exchange occurs in the bidentate complexes despite no substantial MC state population, while the tridentate complex is extremely photostable despite an activated decay route, highlighting the versatile photochemistry of nonpolypyridine ligands.\ua0\ua9 2019 American Chemical Society

Classical integrability and quantum aspects of the AdS(3) x S(3) x S(3) x S(1) superstring

In this paper we continue the investigation of aspects of integrability of the type IIA AdS(3) x S(3) x S(3) x S(1) and AdS(3) x S(3) x T(4) superstrings. By constructing a one parameter family of flat connections we prove that the Green-Schwarz string is classically integrable, at least to quadratic order in fermions, without fixing the kappa-symmetry. We then compare the quantum dispersion relation, fixed by integrability up to an unknown interpolating function h(lambda), to explicit one-loop calculations on the string worldsheet. For AdS(3) x S(3) x S(3) x S(1) the spectrum contains heavy, as well as light and massless modes, and we find that the one-loop contribution differs depending on how we treat these modes showing that similar regularization ambiguities as appeared in AdS(4)/CFT(3) occur also here.Comment: 29 pages; v2: updated references and acknowledgmen

Light-cone gauge Hamiltonian for AdS_4 x CP^3 superstring

It is developed the phase-space formulation for the Type IIA superstring on the AdS_4 x CP^3 background in the kappa-symmetry light-cone gauge for which the light-like directions are taken from the D=3 Minkowski boundary of AdS_4. After fixing bosonic light-cone gauge the superstring Hamiltonian is expressed as a function of the transverse physical variables and in the quadratic approximation corresponds to the light-cone gauge-fixed IIA superstring in flat space.Comment: 12 pages, LaTeX; v2 minor improvements of the text, misprints corrected, reference added; v3: missing terms in Eqs.(8),(53) and (56) adde

Depression, anxiety, and psychological distress among caregivers of young children in rural Lesotho: Associations with food insecurity, household death and parenting stress

Good mental health is a critical resource for mothers and caregivers of young children, given the central role of mental health in enabling responsive caregiving. However, fulfilling caregiving responsibilities under challenging circumstances such as extreme poverty, food insecurity, and gender inequality intensifies vulnerability to poor mental health. Previous research focuses on mental health of mothers, while in many LMICs children are cared for by other caregivers, such as grandparents. We examined the prevalence of mental health problems among primary caregivers of young children in rural Lesotho, and investigated factors associated with these mental health problems. We analysed baseline data from a cluster randomised controlled trial, where all caregivers with children between 1 and 5 years old across 34 villages were invited to participate. The analysis included mental health data from 781 caregivers of 998 children. We assessed caregiver mental health using three self-report screening instruments. Univariate and multivariate regression modelling tested associations between caregiver, child and household variables and (1) depression symptoms (PHQ-9), (2) anxiety symptoms (GAD-7), (3) psychological distress (SRQ-20), (4) suicidal ideation and (5) help-seeking for mental health. This study reported a high prevalence of symptoms of psychological distress (46.2%), depression (25.7%), anxiety (17.1%) and suicidal ideation (27.5%) among caregivers. Greater prevalence was associated with food insecurity, parenting stress or recent death in the family/household. Older caregivers reported higher rates of psychological distress and depression, while younger caregivers reported higher rates of anxiety. Suicidal ideation was associated with greater food insecurity and parenting stress, and lower caregiver education. Our findings support the need to address intersecting public health issues to improve conditions for caregivers in these settings. Targeting modifiable risk factors such as food insecurity among individuals within a society who carry disproportionate burdens of caregiving should be prioritised, especially in contexts of scarcity, where mental health is not prioritised