Decreasing physical and verbal aggression in a brain injured nursing home resident

Following a traumatic brain injury, patients often suffer a series of psychological and psychiatric sequalae. This study presents the case of Mr. K, a 52-year-old brain-injured nursing home resident who exhibited problematic physical aggression and verbal abuse toward staff and residents. His problem behaviors were intertwined with an ethical issue involving a heterosexual relationship with another resident who also was brain injured. Following a functional assessment of antecedents and consequences, a differential reinforcement of other behavior (DRO) schedule was implemented. Specifically, the resident was rewarded with short-term and long-term reinforcers following periods of time during which behaviors other than the target behavior were emitted. Although the behavior plan was successful, it resulted in a more noticeable decrease in physically aggressive behaviors than verbally abusive behaviors. Implications include increasing awareness of use of behavior plans in nursing homes and of ethical and behavioral issues associated with sexuality among nursing home residents

Relativistic D-brane Scattering is Extremely Inelastic

We study the effects of quantum production of open strings on the relativistic scattering of D-branes. We find strong corrections to the brane trajectory from copious production of highly-excited open strings, whose typical oscillator level is proportional to the square of the rapidity. In the corrected trajectory, the branes rapidly coincide and remain trapped in a configuration with enhanced symmetry. This is a purely stringy effect which makes relativistic brane collisions exceptionally inelastic. We trace this effect to velocity-dependent corrections to the open-string mass, which render open strings between relativistic D-branes surprisingly light. We observe that pair-creation of open strings could play an important role in cosmological scenarios in which branes approach each other at very high speeds.Comment: 30 pages; added references and a comment about velocity-dependent masse

Beauty is Attractive: Moduli Trapping at Enhanced Symmetry Points

We study quantum effects on moduli dynamics arising from the production of particles which are light at special points in moduli space. The resulting forces trap the moduli at these points, which often exhibit enhanced symmetry. Moduli trapping occurs in time-dependent quantum field theory, as well as in systems of moving D-branes, where it leads the branes to combine into stacks. Trapping also occurs in an expanding universe, though the range over which the moduli can roll is limited by Hubble friction. We observe that a scalar field trapped on a steep potential can induce a stage of acceleration of the universe, which we call trapped inflation. Moduli trapping ameliorates the cosmological moduli problem and may affect vacuum selection. In particular, rolling moduli are most powerfully attracted to the points with the largest number of light particles, which are often the points of greatest symmetry. Given suitable assumptions about the dynamics of the very early universe, this effect might help to explain why among the plethora of possible vacuum states of string theory, we appear to live in one with a large number of light particles and (spontaneously broken) symmetries. In other words, some of the surprising properties of our world might arise not through pure chance or miraculous cancellations, but through a natural selection mechanism during dynamical evolution.Comment: 50 pages, 4 figures; v2: added references and an appendix describing a related classical proces

Metastable SUSY Breaking, de Sitter Moduli Stabilisation and K\"ahler Moduli Inflation

We study the influence of anomalous U(1) symmetries and their associated D-terms on the vacuum structure of global field theories once they are coupled to N=1 supergravity and in the context of string compactifications with moduli stabilisation. In particular, we focus on a IIB string motivated construction of the ISS scenario and examine the influence of one additional U(1) symmetry on the vacuum structure. We point out that in the simplest one-Kahler modulus compactification, the original ISS vacuum gets generically destabilised by a runaway behaviour of the potential in the modulus direction. In more general compactifications with several Kahler moduli, we find a novel realisation of the LARGE volume scenario with D-term uplifting to de Sitter space and both D-term and F-term supersymmetry breaking. The structure of soft supersymmetry breaking terms is determined in the preferred scenario where the standard model cycle is not stabilised non-perturbatively and found to be flavour universal. Our scenario also provides a purely supersymmetric realisation of Kahler moduli (blow-up and fibre) inflation, with similar observational properties as the original proposals but without the need to include an extra (non-SUSY) uplifting term.Comment: 38 pages, 8 figures. v2: references added, minor correction

Accidental Inflation in the Landscape

We study some aspects of fine tuning in inflationary scenarios within string theory flux compactifications and, in particular, in models of accidental inflation. We investigate the possibility that the apparent fine-tuning of the low energy parameters of the theory needed to have inflation can be generically obtained by scanning the values of the fluxes over the landscape. Furthermore, we find that the existence of a landscape of eternal inflation in this model provides us with a natural theory of initial conditions for the inflationary period in our vacuum. We demonstrate how these two effects work in a small corner of the landscape associated with the complex structure of the Calabi-Yau manifold P^4_[1,1,1,6,9] by numerically investigating the flux vacua of a reduced moduli space. This allows us to obtain the distribution of observable parameters for inflation in this mini-landscape directly from the fluxes.Comment: 40 pages, 11 figure

Modulating bone marrow hematopoietic lineage potential to prevent bone metastasis in breast cancer

The presence of disseminated tumor cells in breast cancer patient bone marrow aspirates predicts decreased recurrence-free survival. Although it is appreciated that physiological, pathological, and therapeutic conditions impact hematopoiesis, it remains unclear if targeting hematopoiesis presents opportunities for limiting bone metastasis. Using pre-clinical breast cancer models, we discovered that marrow from mice treated with the bisphosphonate zoledronic acid (ZA) are metastasis-suppressive. Specifically, ZA modulated hematopoietic myeloid/osteoclast progenitor cell (M/OCP) lineage potential to activate metastasis-suppressive activity. Granulocyte-colony stimulating factor (G-CSF) promoted ZA resistance by redirecting M/OCP differentiation. We identified M/OCP and bone marrow transcriptional programs associated with metastasis suppression and ZA resistance. Analysis of patient blood samples taken at random revealed that women with high plasma G-CSF experienced significantly worse outcome with adjuvant ZA than those with lower G-CSF levels. Our findings support discovery of therapeutic strategies to direct M/OCP lineage potential and biomarkers that stratify responses in patients at risk of recurrence

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation