Mental health care: perceptions of people with schizophrenia and their carers

The current study aims to discover the opinions of patients and their (informal and formal) carers concerning the mental health care of individuals with long term schizophrenic disorders within different contexts and cultures. It's a qualitative study with focus groups, in which 6 research centers (from Argentina, Brazil, Chile, Spain, England and Venezuela) participated. Eight focus groups were conducted in each center, totaling 303 individuals in 46 groups. The data were analyzed with the aid of the Qualitative Solutions and Research/Non-numerical Unstructured Data Indexing program (QSR NUD*IST 4.0). The perception regarding the quality of care is influenced by the professional-patient relationship and the availability of resources. Poor quality of care is also perceived as discrimination. People with schizophrenia in general consider themselves to be ostracized by professionals and services and lacking in more humanized care. In the contexts in which community care is less advanced, the complaints center on resources and services that do not meet demands. On the other hand, in more developed contexts criticism centers more on the attitude of the professionals and the professional-patient relationship. Over and above the need for resources and services, people with schizophrenia require more humanized health care

Decomposing socio-economic inequality in colorectal cancer screening uptake in England

Colorectal cancer (CRC) is the second largest cause of cancer death in the UK. Since 2010, CRC screening based on Faecal Occult Blood testing has been offered by the NHS in England biennially to all persons age 60-69 years. Several studies have demonstrated a gradient in uptake using area-level markers of socio-economic status (SES), but few have examined the individual-level contributors to the gradient. We aimed to quantify the extent of SES inequality in CRC screening uptake in England using individual-level data, and to identify individual factors associated with this inequality. We used data from 1833 participants (aged 61-69) in Wave 5 (collected in years 2010/11) of the English Longitudinal Study of Ageing (ELSA) eligible for having been sent at least one CRC screening invitation. Uptake was defined by self-report of ever having been screened as part of the National Screening Programme. We assessed socio-economic inequality using the corrected concentration index of uptake against SES rank, which was derived by regressing a range of SES markers against net non-pension household wealth. Other demographic and health-related variables were included in the analysis. Factors associated with inequality were measured using concentration index decomposition. There was a significant pro-rich gradient in screening uptake (concentration index: 0.16, 95% CI:0.11-0.22), mostly explained within our model by differences in non-pension wealth (38.7%), partner screening status (15.9%), sickness/disability (13.5%), and health literacy (8.5%). Interventions aimed at reducing inequalities in CRC screening uptake should focus on improving acceptability of screening in populations with low levels of education and literacy barriers

Non-universal gauge boson Z′Z' and the spin correlation of top quark pair production at e−e+e^{-}e^{+} colliders

In the off-diagonal basis, we discuss the contributions of the non-universal gauge boson $Z'$ predicted by the topcolor-assisted technicolor ($TC2$) model to the spin configurations and the spin correlation observable of the top quark pair production via the process $e^{-}e^{+}\to t\bar{t}$. Our numerical results show that the production cross sections for the like-spin states, which vanish in the standard model, can be significantly large as $M_{Z'}\approx \sqrt{S}$. With reasonable values of the $Z'$ mass $M_{Z'}$ and the coupling parameter $k_{1}$, $Z'$ exchange can generate large corrections to the spin correlation observable.Comment: 16 pages, 5 figure

Prediction of lethal and synthetically lethal knock-outs in regulatory networks

The complex interactions involved in regulation of a cell's function are captured by its interaction graph. More often than not, detailed knowledge about enhancing or suppressive regulatory influences and cooperative effects is lacking and merely the presence or absence of directed interactions is known. Here we investigate to which extent such reduced information allows to forecast the effect of a knock-out or a combination of knock-outs. Specifically we ask in how far the lethality of eliminating nodes may be predicted by their network centrality, such as degree and betweenness, without knowing the function of the system. The function is taken as the ability to reproduce a fixed point under a discrete Boolean dynamics. We investigate two types of stochastically generated networks: fully random networks and structures grown with a mechanism of node duplication and subsequent divergence of interactions. On all networks we find that the out-degree is a good predictor of the lethality of a single node knock-out. For knock-outs of node pairs, the fraction of successors shared between the two knocked-out nodes (out-overlap) is a good predictor of synthetic lethality. Out-degree and out-overlap are locally defined and computationally simple centrality measures that provide a predictive power close to the optimal predictor.Comment: published version, 10 pages, 6 figures, 2 tables; supplement at http://www.bioinf.uni-leipzig.de/publications/supplements/11-01

Phenomenology of the nMSSM from colliders to cosmology

Low energy supersymmetric models provide a solution to the hierarchy problem and also have the necessary ingredients to solve two of the most outstanding issues in cosmology: the origin of dark matter and baryonic matter. One of the most attractive features of this framework is that the relevant physical processes are related to interactions at the weak scale and therefore may be tested in collider experiments in the near future. This is true for the Minimal Supersymmetric Standard Model (MSSM) as well as for its extension with the addition of one singlet chiral superfield, the so-called nMSSM. It has been recently shown that within the nMSSM an elegant solution to both the problem of baryogenesis and dark matter may be found, that relies mostly on the mixing of the singlet sector with the Higgs sector of the theory. In this work we review the nMSSM model constraints from cosmology and present the associated collider phenomenology at the LHC and the ILC. We show that the ILC will efficiently probe the neutralino, chargino and Higgs sectors, allowing to confront cosmological observations with computations based on collider measurements. We also investigate the prospects for a direct detection of dark matter and the constraints imposed by the current bounds of the electron electric dipole moment in this model.Comment: 44 pp, 10 figures; Fig.9 replaced; discussion on CP violation extended and references added; few minor additions in text about details of the cut

Unparticle physics in top pair signals at the LHC and ILC

We study the effects of unparticle physics in the pair productions of top quarks at the LHC and ILC. By considering vector, tensor and scalar unparticle operators, as appropriate, we compute the total cross sections for pair production processes depending on scale dimension d_{\U}. We find that the existence of unparticles would lead to measurable enhancements on the SM predictions at the LHC. In the case of ILC this may become two orders of magnitude larger than that of SM, for smaller values of d_\U, a very striking signal for unparticles.Comment: 19 pages, 9 figures, analysis for ILC has been adde

The ansamycin antibiotic, rifamycin SV, inhibits BCL6 transcriptional repression and forms a complex with the BCL6-BTB/POZ domain

BCL6 is a transcriptional repressor that is over-expressed due to chromosomal translocations, or other abnormalities, in ~40% of diffuse large B-cell lymphoma. BCL6 interacts with co-repressor, SMRT, and this is essential for its role in lymphomas. Peptide or small molecule inhibitors, which prevent the association of SMRT with BCL6, inhibit transcriptional repression and cause apoptosis of lymphoma cells in vitro and in vivo. In order to discover compounds, which have the potential to be developed into BCL6 inhibitors, we screened a natural product library. The ansamycin antibiotic, rifamycin SV, inhibited BCL6 transcriptional repression and NMR spectroscopy confirmed a direct interaction between rifamycin SV and BCL6. To further determine the characteristics of compounds binding to BCL6-POZ we analyzed four other members of this family and showed that rifabutin, bound most strongly. An X-ray crystal structure of the rifabutin-BCL6 complex revealed that rifabutin occupies a partly non-polar pocket making interactions with tyrosine58, asparagine21 and arginine24 of the BCL6-POZ domain. Importantly these residues are also important for the interaction of BLC6 with SMRT. This work demonstrates a unique approach to developing a structure activity relationship for a compound that will form the basis of a therapeutically useful BCL6 inhibitor

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research

The Citation Field of Evolutionary Economics

Evolutionary economics has developed into an academic field of its own, institutionalized around, amongst others, the Journal of Evolutionary Economics (JEE). This paper analyzes the way and extent to which evolutionary economics has become an interdisciplinary journal, as its aim was: a journal that is indispensable in the exchange of expert knowledge on topics and using approaches that relate naturally with it. Analyzing citation data for the relevant academic field for the Journal of Evolutionary Economics, we use insights from scientometrics and social network analysis to find that, indeed, the JEE is a central player in this interdisciplinary field aiming mostly at understanding technological and regional dynamics. It does not, however, link firmly with the natural sciences (including biology) nor to management sciences, entrepreneurship, and organization studies. Another journal that could be perceived to have evolutionary acumen, the Journal of Economic Issues, does relate to heterodox economics journals and is relatively more involved in discussing issues of firm and industry organization. The JEE seems most keen to develop theoretical insights