Predicting suicides after outpatient mental health visits in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).

The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded

An XML transfer schema for exchange of genomic and genetic mapping data: implementation as a web service in a Taverna workflow

<p>Abstract</p> <p>Background</p> <p>Genomic analysis, particularly for less well-characterized organisms, is greatly assisted by performing comparative analyses between different types of genome maps and across species boundaries. Various providers publish a plethora of on-line resources collating genome mapping data from a multitude of species. Datasources range in scale and scope from small bespoke resources for particular organisms, through larger web-resources containing data from multiple species, to large-scale bioinformatics resources providing access to data derived from genome projects for model and non-model organisms. The heterogeneity of information held in these resources reflects both the technologies used to generate the data and the target users of each resource. Currently there is no common information exchange standard or protocol to enable access and integration of these disparate resources. Consequently data integration and comparison must be performed in an <it>ad hoc </it>manner.</p> <p>Results</p> <p>We have developed a simple generic XML schema (GenomicMappingData.xsd – GMD) to allow export and exchange of mapping data in a common lightweight XML document format. This schema represents the various types of data objects commonly described across mapping datasources and provides a mechanism for recording relationships between data objects. The schema is sufficiently generic to allow representation of any map type (for example genetic linkage maps, radiation hybrid maps, sequence maps and physical maps). It also provides mechanisms for recording data provenance and for cross referencing external datasources (including for example ENSEMBL, PubMed and Genbank.). The schema is extensible via the inclusion of additional datatypes, which can be achieved by importing further schemas, e.g. a schema defining relationship types. We have built demonstration web services that export data from our ArkDB database according to the GMD schema, facilitating the integration of data retrieval into Taverna workflows.</p> <p>Conclusion</p> <p>The data exchange standard we present here provides a useful generic format for transfer and integration of genomic and genetic mapping data. The extensibility of our schema allows for inclusion of additional data and provides a mechanism for typing mapping objects via third party standards. Web services retrieving GMD-compliant mapping data demonstrate that use of this exchange standard provides a practical mechanism for achieving data integration, by facilitating syntactically and semantically-controlled access to the data.</p

Prevalence and correlates of 30-day suicidal ideation and intent: Results of the South African National Student Mental Health Survey

Background. Although suicide prevention is recognised as a priority among university students in South Africa (SA), it is unclear what proportion of students require urgent indicated interventions and what the characteristics are of these students. Objective. To assess the prevalence and sociodemographic correlates of 30-day suicidal ideation, frequency of ideation and self-reported intention to act on ideation in the next year among a national sample of SA university students. Methods. Self-report cross-sectional data were collected online from students (N=28 268) at 17 universities across SA as part of the national student mental health survey. Students reported suicidal ideation in the past 30 days, frequency of ideation and intention to act on ideation in the next year. Data were weighted within institutions by gender and population group, and across the four main types of universities (historically white, historically disadvantaged, technical and distance learning) to correct for response rate discrepancies. Prevalence was estimated with these weighted in the total sample and across types of universities. Poisson regression with robust error variances was used to investigate associations of sociodemographic characteristics with ideation and intention to act on suicidal ideation. Results are reported as relative risks (RRs) with design-based 95% confidence intervals (CIs). Results. Thirty-day prevalence of suicidal ideation was 24.4% (standard error (SE) 0.3), with 2.1% (SE 0.1) and 4.1% (SE 0.1), respectively, reporting suicidal ideation all/almost all the time, or most of the time. A total of 1.5% (SE 0.1) of respondents reported being very likely to act on their suicidal ideation, while 3.9% (SE 0.2) were somewhat likely, 8.7% (SE 0.2) were not very likely and 85.8 (SE 0.5) either reported no suicidal ideation or that they were not at all likely to act on this ideation. Risk of suicidal ideation with high intent in the total sample was elevated among females (RR 1.9, 95% CI 1.3 - 2.7) and gender non-conforming students (RR 4.3, 95% CI 1.4 - 13.0) relative to males, black African students compared with white students (RR 3.6, 95% CI 1.9 - 7.1), students whose parents did not progress to secondary school compared with students whose parents had a university education (RR 1.6, 95% CI 1.0 - 2.5) and sexual minority students compared with heterosexual students (RR 1.9, 95% CI 1.3 - 2.6). Among students with 30-day ideation (controlling for frequency of ideation), only two of these predictors of high intent remained significant: identifying as black African (RR 2.7, 95% CI 1.4 - 5.1), and having parents with less than secondary education (RR 1.5, 95% CI 1.0 - 2.1). Conclusion. Scalable suicide prevention interventions are needed to reach the large number of SA students who report suicidal ideation with intent

The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene.

Neuregulin-1 (NRG1) is both a candidate oncogene and a candidate tumour suppressor gene. It not only encodes the heregulins and other mitogenic ligands for the ERBB family, but also causes apoptosis in NRG1-expressing cells. We found that most breast cancer cell lines had reduced or undetectable expression of NRG1. This included cell lines that had translocation breaks in the gene. Similarly, expression in cancers was generally comparable to or less than that in various normal breast samples. Many non-expressing cell lines had extensive methylation of the CpG island at the principal transcription start site at exon 2 of NRG1. Expression was reactivated by demethylation. Many tumours also showed methylation, whereas normal mammary epithelial fragments had none. Lower NRG1 expression correlated with higher methylation. Small interfering RNA (siRNA)-mediated depletion of NRG1 increased net proliferation in a normal breast cell line and a breast cancer cell line that expressed NRG1. The short arm of chromosome 8 is frequently lost in epithelial cancers, and NRG1 is the most centromeric gene that is always affected. NRG1 may therefore be the major tumour suppressor gene postulated to be on 8p: it is in the correct location, is antiproliferative and is silenced in many breast cancers

Electro-Magnetic Nucleon Form Factors and their Spectral Functions in Soliton Models

It is demonstrated that in simple soliton models essential features of the electro-magnetic nucleon form factors observed over three orders of magnitude in momentum transfer $t$ are naturally reproduced. The analysis shows that three basic ingredients are required: an extended object, partial coupling to vector mesons, and relativistic recoil corrections. We use for the extended object the standard skyrmion, one vector meson propagator for both isospin channels, and the relativistic boost to the Breit frame. Continuation to timelike $t$ leads to quite stable results for the spectral functions in the regime from the 2- or 3-pion threshold to about two rho masses. Especially the onset of the continuous part of the spectral functions at threshold can be reliably determined and there are strong analogies to the results imposed on dispersion theoretic approaches by the unitarity constraint.Comment: 24 pages, (RevTeX), 5 PS-figures; Data points in fig.2 and corresponding references added. Final version, to be published in Z.Physik

Change in quality of life and their predictors in the long-term follow-up after group cognitive behavioral therapy for social anxiety disorder: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Social anxiety disorder (SAD) is one of the most common anxiety disorders. The efficacy of cognitive behaviour therapy (CBT) has been examined but to date its effects on Quality of Life (QoL) have not been appropriately evaluated especially in the long term.</p> <p>The study aimed to examine, in the long term, what aspects of Quality of Life (QoL) changed among social anxiety disorder (SAD) patients treated with group cognitive behaviour therapy (CBT) and what predictors at baseline were associated with QoL.</p> <p>Methods</p> <p>Outpatients diagnosed with SAD were enrolled into group CBT, and assessed at follow-ups for up to 12 months in a typical clinical setting. QoL was evaluated using the Short Form 36. Various aspects of SAD symptomatology were also assessed. Each of the QoL domains and scores on symptomatology were quantified and compared with those at baseline. Baseline predictors of QoL outcomes at follow-up were investigated.</p> <p>Results</p> <p>Fifty-seven outpatients were enrolled into group CBT for SAD, 48 completed the whole program, and 44 and 40 completed assessments at the 3-month and 12-month follow-ups, respectively. All aspects of SAD symptomatology and psychological subscales of the QoL showed statistically significant improvement throughout follow-ups for up to 12 months. In terms of social functioning, no statistically significant improvement was observed at either follow-up point except for post-treatment. No consistently significant pre-treatment predictors were observed.</p> <p>Conclusions</p> <p>After group CBT, SAD symptomatology and some aspects of QoL improved and this improvement was maintained for up to 12 months, but the social functioning domain did not prove any significant change statistically. Considering the limited effects of CBT on QoL, especially for social functioning, more powerful treatments are needed.</p

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio

Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Minimal residual disease (MRD), where leukemic cell levels are lower than the morphologic detection threshold, is the most important prognostic factor for acute lymphoblastic leukemia (ALL) relapse during first-line chemotherapy treatment and is standard of care in treatment monitoring and decision making. Limited data are available on the prognostic value of MRD response after relapse. We evaluated the relationship between MRD response and outcomes in blinatumomab-treated adults with relapsed/refractory (R/R) B-cell precursor ALL. Of 90 patients with complete remission (CR) or CR with partial hematologic recovery (CRh), 64 (71.1%) achieved a complete MRD response (no detectable individual rearrangements of immunoglobulin/T-cell receptor genes by polymerase chain reaction [PCR] at a minimum sensitivity level of 10-4). Eleven patients had MRD <10-4. Therefore, overall, 75 (83.3%) experienced an MRD response (no detectable MRD or detectable MRD) measured by PCR within the first 2 treatment cycles. Overall survival (OS) and relapse-free survival (RFS) were significantly longer in patients who achieved CR/CRh and MRD response (median, 20.6 and 9.0 months, respectively) compared with CR/CRh patients without MRD response (median, 12.5 and 2.3 months, respectively). In conclusion, longer durations of OS and RFS associated with MRD response support the value of achieving MRD response and its use as a prognostic factor for blinatumomab treatment in R/R ALL. This trial was registered at www.clinicaltrials.gov as #NCT01466179