Commentary on strategies for switching antipsychotics

Both the new generation of antipsychotics and the more traditional antipsychotic drugs produce an important and meaningful improvement in patients with schizophrenia, but most patients are neither cured nor free of symptoms. As a consequence, it is common to switch from one drug to another in the hope of obtaining a better response. All antipsychotic drugs produce some side effects, so switching can also be a tolerance issue. There are reports in the literature on the tactics of switching: abrupt discontinuation, cross tapering, starting a patient on a new drug while continuing with the old drug until the new drug has reached a steady state, or some variation on these tactics. In this issue, Ganguli et al. have carried out a randomized switching study, the data from which indicates the tactics that might be optimal. We put this paper into context, provide a critique and describe indications for switching

Visualizing the emergence of the pseudogap state and the evolution to superconductivity in a lightly hole-doped Mott insulator

Superconductivity emerges from the cuprate antiferromagnetic Mott state with hole doping. The resulting electronic structure is not understood, although changes in the state of oxygen atoms appear paramount. Hole doping first destroys the Mott state yielding a weak insulator where electrons localize only at low temperatures without a full energy gap. At higher doping, the 'pseudogap', a weakly conducting state with an anisotropic energy gap and intra-unit-cell breaking of 90\degree-rotational (C4v) symmetry appears. However, a direct visualization of the emergence of these phenomena with increasing hole density has never been achieved. Here we report atomic-scale imaging of electronic structure evolution from the weak-insulator through the emergence of the pseudogap to the superconducting state in Ca2-xNaxCuO2Cl2. The spectral signature of the pseudogap emerges at lowest doping from a weakly insulating but C4v-symmetric matrix exhibiting a distinct spectral shape. At slightly higher hole-density, nanoscale regions exhibiting pseudogap spectra and 180\degree-rotational (C2v) symmetry form unidirectional clusters within the C4v-symmetric matrix. Thus, hole-doping proceeds by the appearance of nanoscale clusters of localized holes within which the broken-symmetry pseudogap state is stabilized. A fundamentally two-component electronic structure11 then exists in Ca2-xNaxCuO2Cl2 until the C2v-symmetric clusters touch at higher doping, and the long-range superconductivity appears.Comment: See the Nature Physics website for the published version available at http://dx.doi.org/10.1038/Nphys232

An Immersive Virtual Reality Curriculum for Pediatric Hematology Clinicians on Shared Decision-making for Hydroxyurea in Sickle Cell Anemia

Although hydroxyurea (HU) is an effective treatment for sickle cell anemia, uptake remains low. Shared decision-making (SDM) is a recommended strategy for HU initiation to elicit family preferences; however, clinicians lack SDM training. We implemented an immersive virtual reality (VR) curriculum at 8 pediatric institutions to train clinicians on SDM that included counseling virtual patients. Clinicians’ self-reported confidence significantly improved following the VR simulations on all communication skills assessed, including asking open-ended questions, eliciting specific concerns, and confirming understanding (Ps≤0.01 for all). VR may be an effective method for educating clinicians to engage in SDM for HU

Economic factors influencing zoonotic disease dynamics: demand for poultry meat and seasonal transmission of avian influenza in Vietnam

While climate is often presented as a key factor influencing the seasonality of diseases, the importance of anthropogenic factors is less commonly evaluated. Using a combination of methods-wavelet analysis, economic analysis, statistical and disease transmission modelling-we aimed to explore the influence of climatic and economic factors on the seasonality of H5N1 Highly Pathogenic Avian Influenza in the domestic poultry population of Vietnam. We found that while climatic variables are associated with seasonal variation in the incidence of avian influenza outbreaks in the North of the country, this is not the case in the Centre and the South. In contrast, temporal patterns of H5N1 incidence are similar across these 3 regions: periods of high H5N1 incidence coincide with Lunar New Year festival, occurring in January-February, in the 3 climatic regions for 5 out of the 8 study years. Yet, daily poultry meat consumption drastically increases during Lunar New Year festival throughout the country. To meet this rise in demand, poultry production and trade are expected to peak around the festival period, promoting viral spread, which we demonstrated using a stochastic disease transmission model. This study illustrates the way in which economic factors may influence the dynamics of livestock pathogens

B-L Cosmic Strings in Heterotic Standard Models

E_{8} X E_{8} heterotic string and M-theory, when compactified on smooth Calabi-Yau manifolds with SU(4) vector bundles, can give rise to softly broken N=1 supersymmetric theories with the exact matter spectrum of the MSSM, including three right-handed neutrinos and one Higgs-Higgs conjugate pair of supermultiplets. These vacua have the SU(3)_{C} X SU(2)_{L} X U(1)_{Y} gauge group of the standard model augmented by an additional gauged U(1)_{B-L}. Their minimal content requires that the B-L symmetry be spontaneously broken by a vacuum expectation value of at least one right-handed sneutrino. The soft supersymmetry breaking operators can induce radiative breaking of the B-L gauge symmetry with an acceptable B-L/electroweak hierarchy. In this paper, it is shown that U(1)_{B-L} cosmic strings occur in this context, potentially with both bosonic and fermionic superconductivity. We present a numerical analysis that demonstrates that boson condensates can, in principle, form for theories of this type. However, the weak Yukawa and gauge couplings of the right-handed sneutrino suggests that bosonic superconductivity will not occur in the simplest vacua in this context. The electroweak phase transition also disallows fermion superconductivity, although substantial bound state fermion currents can exist.Comment: 41 pages, 5 figure

TOPOLOGICAL DEFECTS AND HIGHEST ENERGY COSMIC AND GAMMA RAYS

In this paper we review the hypothesis that a considerable part of the cosmic ray flux observed above about 10^{19}\eV may be produced by decaying or annihilating topological defects left over from phase transitions in the early universe at grand unification energy scales (\approx10^{16}\GeV). Possible signatures of cosmic ray producing defect models are discussed which could be tested experimentally in the near future. We thereby focus on model independent universal spectral properties of the predicted particle fluxes.Comment: 11 pages of uuencoded compressed postscript, including 3 figures, to be published in Space Science Reviews

The Phyre2 web portal for protein modeling, prediction and analysis

Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission

Neutrino masses from new generations

We reconsider the possibility that Majorana masses for the three known neutrinos are generated radiatively by the presence of a fourth generation and one right-handed neutrino with Yukawa couplings and a Majorana mass term. We find that the observed light neutrino mass hierarchy is not compatible with low energy universality bounds in this minimal scenario, but all present data can be accommodated with five generations and two right-handed neutrinos. Within this framework, we explore the parameter space regions which are currently allowed and could lead to observable effects in neutrinoless double beta decay, $\mu - e$ conversion in nuclei and $\mu \rightarrow e \gamma$ experiments. We also discuss the detection prospects at LHC.Comment: 28 pages, 4 figures. Version to be published. Some typos corrected. Improved figures 3 and

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions