Smartphone-based safety planning and self-monitoring for suicidal patients: Rationale and study protocol of the CASPAR (Continuous Assessment for Suicide Prevention And Research) study

Background: It remains difficult to predict and prevent suicidal behaviour, despite growing understanding of the aetiology of suicidality. Clinical guidelines recommend that health care professionals develop a safety plan in collaboration with their high-risk patients, to lower the imminent risk of suicidal behaviour. Mobile health applications provide new opportunities for safety planning, and enable daily self-monitoring of suicide-related symptoms that may enhance safety planning. This paper presents the rationale and protocol of the Continuous Assessment for Suicide Prevention And Research (CASPAR) study. The aim of the study is two-fold: to evaluate the feasibility of mobile safety planning and daily mobile self-monitoring in routine care treatment for suicidal patients, and to conduct fundamental research on suicidal processes. Methods: The study is an adaptive single cohort design among 80 adult outpatients or day-care patients, with the main diagnosis of major depressive disorder or dysthymia, who have an increased risk for suicidal behaviours. There are three measurement points, at baseline, at 1 and 3 months after baseline. Patients are instructed to use their mobile safety plan when necessary and monitor their suicidal symptoms daily. Both these apps will be used in treatment with their clinician. Conclusion: The results from this study will provide insight into the feasibility of mobile safety planning and self-monitoring in treatment of suicidal patients. Furthermore, knowledge of the suicidal process will be enhanced, especially regarding the transition from suicidal ideation to behaviour

QCD Coherence and the Top Quark Asymmetry

Coherent QCD radiation in the hadroproduction of top quark pairs leads to a forward--backward asymmetry that grows more negative with increasing transverse momentum of the pair. This feature is present in Monte Carlo event generators with coherent parton showering, even though the production process is treated at leading order and has no intrinsic asymmetry before showering. In addition, depending on the treatment of recoils, showering can produce a positive contribution to the inclusive asymmetry. We explain the origin of these features, compare them in fixed-order calculations and the Herwig++, Pythia and Sherpa event generators, and discuss their implications.Comment: 28 pages, 11 figures, 2 table

Precision on leptonic mixing parameters at future neutrino oscillation experiments

We perform a comparison of the different future neutrino oscillation experiments based on the achievable precision in the determination of the fundamental parameters theta_{13} and the CP phase, delta, assuming that theta_{13} is in the range indicated by the recent Daya Bay measurement. We study the non-trivial dependence of the error on delta on its true value. When matter effects are small, the largest error is found at the points where CP violation is maximal, and the smallest at the CP conserving points. The situation is different when matter effects are sizable. As a result of this effect, the comparison of the physics reach of different experiments on the basis of the CP discovery potential, as usually done, can be misleading. We have compared various proposed super-beam, beta-beam and neutrino factory setups on the basis of the relative precision of theta_{13} and the error on delta. Neutrino factories, both high-energy or low-energy, outperform alternative beam technologies. An ultimate precision on theta_{13} below 3% and an error on delta of < 7^{\circ} at 1 sigma (1 d.o.f.) can be obtained at a neutrino factory.Comment: Minor changes, matches version accepted in JHEP. 30 pages, 9 figure

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain

This is the final version of the article. Available from Springer Nature via the DOI in this record.Functional neuroimaging, using genetically-encoded Ca(2+) sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.This work was funded by the Biological and Biotechnology Research Council (CASE studentship BB/L502510/1, with AstraZeneca Safety Health and Environment), and by the University of Exeter and AstraZeneca

Coherent Parton Showers with Local Recoils

We outline a new formalism for dipole-type parton showers which maintain exact energy-momentum conservation at each step of the evolution. Particular emphasis is put on the coherence properties, the level at which recoil effects do enter and the role of transverse momentum generation from initial state radiation. The formulated algorithm is shown to correctly incorporate coherence for soft gluon radiation. Furthermore, it is well suited for easing matching to next-to-leading order calculations.Comment: 24 pages, 3 figure

Non-standard interactions versus non-unitary lepton flavor mixing at a neutrino factory

The impact of heavy mediators on neutrino oscillations is typically described by non-standard four-fermion interactions (NSIs) or non-unitarity (NU). We focus on leptonic dimension-six effective operators which do not produce charged lepton flavor violation. These operators lead to particular correlations among neutrino production, propagation, and detection non-standard effects. We point out that these NSIs and NU phenomenologically lead, in fact, to very similar effects for a neutrino factory, for completely different fundamental reasons. We discuss how the parameters and probabilities are related in this case, and compare the sensitivities. We demonstrate that the NSIs and NU can, in principle, be distinguished for large enough effects at the example of non-standard effects in the $\mu$-$\tau$-sector, which basically corresponds to differentiating between scalars and fermions as heavy mediators as leading order effect. However, we find that a near detector at superbeams could provide very synergistic information, since the correlation between source and matter NSIs is broken for hadronic neutrino production, while NU is a fundamental effect present at any experiment.Comment: 32 pages, 5 figures. Final version published in JHEP. v3: Typo in Eq. (27) correcte

Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites

Background: Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. microRNAs are small non-coding RNA molecules that regulate target mRNAs and we set out to investigate whether they play a role in the infection event. Results: microRNAs differentially expressed during the early post-infective stages of Brugia pahangi L3 were identified by microarray analysis. One of these, bpa-miR-5364, was selected for further study as it is upregulated ~12-fold at 24 hours post-infection, is specific to clade III nematodes, and is a novel member of the let-7 family, which are known to have key developmental functions in the free-living nematode Caenorhabditis elegans. Predicted mRNA targets of bpa-miR-5364 were identified using bioinformatics and comparative genomics approaches that relied on the conservation of miR-5364 binding sites in the orthologous mRNAs of other filarial nematodes. Finally, we confirmed the interaction between bpa-miR-5364 and three of its predicted targets using a dual luciferase assay. Conclusions: These data provide new insight into the molecular mechanisms underpinning the transmission of third stage larvae of filarial nematodes from vector to mammal. This study is the first to identify parasitic nematode mRNAs that are verified targets of specific microRNAs and demonstrates that post-transcriptional control of gene expression via stage-specific expression of microRNAs may be important in the success of filarial infection

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives