Phase-transitions induced by easy-plane anisotropy in the classical Heisenberg antiferromagnet on a triangular lattice: a Monte Carlo simulation

We present the results of Monte Carlo simulations for the antiferromagnetic classical XXZ model with easy-plane exchange anisotropy on the triangular lattice, which causes frustration of the spin alignment. The behaviour of this system is similar to that of the antiferromagnetic XY model on the same lattice, showing the signature of a Berezinskii-Kosterlitz-Thouless transition, associated to vortex-antivortex unbinding, and of an Ising-like one due to the chirality, the latter occurring at a slightly higher temperature. Data for internal energy, specific heat, magnetic susceptibility, correlation length, and some properties associated with the chirality are reported in a broad temperature range, for lattice sizes ranging from 24x24 to 120x120; four values of the easy-plane anisotropy are considered. Moving from the strongest towards the weakest anisotropy (1%) the thermodynamic quantities tend to the isotropic model behaviour, and the two transition temperatures decrease by about 25% and 22%, respectively.Comment: 11 pages, 13 figures (embedded by psfig), 3 table

Observations On the Potential Confinement of a Light Fermion

We consider possible dynamical models for a light fermion confined by a potential field. With the Dirac equation only Lorentz scalar confinement yields normalizable wavefunctions, while with the ``no pair'' variant of the Dirac equation only Lorentz vector confinement has normal Regge behaviour. A systematic investigation of Regge properties and phenomenological properties is carried out, including calculations of the Isgur-Wise function. We point out that the Isgur-Wise function provides a sensitive test of confinement models. In particular, the slope of the IW function at zero recoil point is found to be $\xi'(1)\simeq -0.90$ for the Dirac equation with scalar confinement, and $\xi'(1)\simeq -1.20$ for the no pair equation with vector confinement. Using heavy-light data alone we argue against scalar confinement.Comment: Latex (uses epsf macro), 25 pages of text, 12 postscript figures included. One reference is added and some typos are fixe

Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma

Development of anti-drug antibodies (ADAs) can interfere with therapeutic monoclonal antibodies and may lead to drug neutralisation and clinical disease progression. Measurement of circulating drug levels and development of ADAs in the setting of anti-programmed cell death-1 agent pembrolizumab has not been well-studied. Enzyme-linked immunosorbent assays were used to measure pembrolizumab drug level and ADAs in 41 patients with melanoma at baseline, Time-point 1 (3 weeks) and Time-point 2 (21 weeks). Assay results were related to patient demographics and clinical outcome data at 6 months. The median pembrolizumab drug level at 3 weeks was 237 ng/μL and did not correlate with age, sex or body surface area.17/41 patients had an ADA detected at any timepoint, with the highest prevalence at Timepoint 1 (median concentration = 17 ng/μL). The presence of an ADA did not correlate with clinical progression at 6 months. 3/41 (7%) of patients displayed a falling pembrolizumab drug level and rising ADA titre between Timepoint 1 and 2 suggestive of a neutralising ADA. Pembrolizumab drug levels and ADAs can be readily measured. The rates of total and treatment-emergent ADAs may be higher in "real-word" settings than those previously reported. Larger studies are needed to determine effect of neutralising ADAs on long-term clinical outcome

The double-edged effect of intergroup similarity: Muslim and Christian immigrants’ acculturation preferences on intergroup relations in Sweden

A 2x2x2 experiment examined effects of the acculturation orientations seen to be endorsed by immigrants (of two different religions) on intergroup relations in Sweden. Swedish majority participants (N = 448) read interviews with Iraqi immigrants in which the immigrants’ religion (Muslim vs. Christian), desired level of contact with the host society (high vs. low) and desire to maintain their own culture (high vs. low) were manipulated. Overall, immigrants who were perceived to favour contact elicited more favourable intergroup attitudes. Desire for contact also interacted with immigrants’ religion: contact among Muslim minorities increased majority members’ support for multiculturalism. In addition, majority members identified more with being Swedish when Christian minorities appeared to endorse contact and reject their heritage culture, which corresponds to an acculturation strategy of assimilation. These findings demonstrate the complex role of religious similarity in intergroup relations. Implications for future research are proposed

A unitary model for meson-nucleon scattering

In an effective Lagrangian model employing the K-matrix approximation we extract nucleon resonance parameters. To this end we analyze simultaneously all available data for reactions involving the final states $\pi N$, $\pi\pi N$, $\eta N$ and $K \Lambda$ in the energy range $m_N + m_{\pi} \le \sqrt s \le 1.9$ GeV. The background contributions are generated consistently from the relevant Feynman amplitudes, thus significantly reducing the number of free parameters.Comment: Revised version. 60 pages, 17 figures. Two figures and a short discussion (\pi N \to \eta N, K \Lambda amplitudes) added, typos and minor errors in the citations correcte

Pre-conception self-harm, maternal mental health and mother-infant bonding problems:a 20-year prospective cohort study

Background: Self-harm in young people is associated with later problems in social and emotional development. However, it is unknown whether self-harm in young women continues to be a marker of vulnerability on becoming a parent. This study prospectively describes the associations between pre-conception self-harm, maternal depressive symptoms and mother&ndash;infant bonding problems.MethodsThe Victorian Intergenerational Health Cohort Study (VIHCS) is a follow-up to the Victorian Adolescent Health Cohort Study (VAHCS) in Australia. Socio-demographic and health variables were assessed at 10 time-points (waves) from ages 14 to 35, including self-reported self-harm at waves 3&ndash;9. VIHCS enrolment began in 2006 (when participants were aged 28&ndash;29 years), by contacting VAHCS women every 6 months to identify pregnancies over a 7-year period. Perinatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale during the third trimester, and 2 and 12 months postpartum. Mother&ndash;infant bonding problems were assessed with the Postpartum Bonding Questionnaire at 2 and 12 months postpartum.ResultsFive hundred sixty-four pregnancies from 384 women were included. One in 10 women (9.7%) reported pre-conception self-harm. Women who reported self-harming in young adulthood (ages 20&ndash;29) reported higher levels of perinatal depressive symptoms and mother&ndash;infant bonding problems at all perinatal time points [perinatal depressive symptoms adjusted &beta; = 5.40, 95% confidence interval (CI) 3.42&ndash;7.39; mother&ndash;infant bonding problems adjusted &beta; = 7.51, 95% CI 3.09&ndash;11.92]. There was no evidence that self-harm in adolescence (ages 15&ndash;17) was associated with either perinatal outcome.ConclusionsSelf-harm during young adulthood may be an indicator of future vulnerability to perinatal mental health and mother&ndash;infant bonding problems.</jats:sec

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations

Alzheimer’s disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. While in animal models of AD pathology, soluble tau aggregates have been shown to disrupt neuronal function, it is unclear whether the tau species present in CSF will modulate neural activity. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. The method involves incubation of acutely-isolated wild-type mouse hippocampal brain slices with small volumes of diluted human CSF, followed by a suite of electrophysiological recording methods to evaluate their effects on neuronal function, from single cells through to the network level. Comparison of the toxicity profiles of the same CSF samples, with and without immuno-depletion for tau, has enabled a pioneering demonstration that CSF-tau potently modulates neuronal function. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input–output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future. Graphical Abstract: [Figure not available: see fulltext.

Checkpoint inhibition reduces the threshold for Drug-Specific T-Cell priming and increases the incidence of sulfasalazine hypersensitivity

An emerging clinical issue associated with immune-oncology agents is the collateral effects on the tolerability of concomitant medications. One report of this phenomenon was the increased incidence of hypersensitivity reactions observed in patients receiving concurrent immune checkpoint inhibitors (ICIs) and sulfasalazine (SLZ). Thus, the aim of this study was to characterize the T cells involved in the pathogenesis of such reactions, and recapitulate the effects of inhibitory checkpoint blockade on de-novo priming responses to compounds within in vitro platforms. A regulatory competent human dendritic cell/T-cell coculture assay was used to model the effects of ICIs on de novo nitroso sulfamethoxazole- and sulfapyridine (SP) (the sulfonamide component of SLZ) hydroxylamine-specific priming responses. The role of T cells in the pathogenesis of the observed reactions was explored in 3 patients through phenotypic characterization of SP/sulfapyridine hydroxylamine (SPHA)-responsive T-cell clones (TCC), and assessment of cross-reactivity and pathways of T-cell activation. Augmentation of the frequency of responding drug-specific T cells and intensity of the T-cell response was observed with PD-1/PD-L1 blockade. Monoclonal populations of SP- and SPHA-responsive T cells were isolated from all 3 patients. A core secretory effector molecule profile (IFN-γ, IL-13, granzyme B, and perforin) was identified for SP and SPHA-responsive TCC, which proceeded through Pi and hapten mechanisms, respectively. Data presented herein provides evidence that drug-responsive T cells are effectors of hypersensitivity reactions observed in oncology patients administered ICIs and SLZ. Perturbation of drug-specific T-cell priming is a plausible explanation for clinical observations of how an increased incidence of these adverse events is occurring

How fear of falling can increase fall-risk in older adults: Applying psychological theory to practical observations

This article was made available through the Brunel Open Access Fund.It is widely reported that fear of falling (FOF) has a profound and largely detrimental effect on balance performance in older adults. However, the mechanisms by which FOF influence postural stability are poorly understood. In the current article, we use psychological theory to explain FOF-related changes to postural control. First, we review literature describing associations between FOF and the 'stiffening' strategies observed during control of posture, including observations of eye and head movements. Second, we present a framework illustrating the interactions between increased age, FOF, and altered attentional processes, which in turn influence balance performance and fall-risk. Psychological theory predicts that anxiety can cause attentional bias for threatening and task-irrelevant stimuli and compromise the efficiency of working memory resources. We argue that while the adoption of stiffening strategies is likely to be beneficial in avoiding a loss of balance during simple postural tasks, it will ultimately compromise performance in dynamic and highly demanding functional tasks. The adoption of stiffening strategies leads to inadequate acquisition of the sensory information necessary to plan and execute dynamic and interactive movements. We conclude with some suggestions for future research.This research was supported by The Royal Society (IE131576) and British Academy (SG132820)