Feature engineering and a proposed decision-support system for systematic reviewers of medical evidence

Objectives: Evidence-based medicine depends on the timely synthesis of research findings. An important source of synthesized evidence resides in systematic reviews. However, a bottleneck in review production involves dual screening of citations with titles and abstracts to find eligible studies. For this research, we tested the effect of various kinds of textual information (features) on performance of a machine learning classifier. Based on our findings, we propose an automated system to reduce screeing burden, as well as offer quality assurance. Methods: We built a database of citations from 5 systematic reviews that varied with respect to domain, topic, and sponsor. Consensus judgments regarding eligibility were inferred from published reports. We extracted 5 feature sets from citations: alphabetic, alphanumeric +, indexing, features mapped to concepts in systematic reviews, and topic models. To simulate a two-person team, we divided the data into random halves. We optimized the parameters of a Bayesian classifier, then trained and tested models on alternate data halves. Overall, we conducted 50 independent tests. Results: All tests of summary performance (mean F3) surpassed the corresponding baseline, P<0.0001. The ranks for mean F3, precision, and classification error were statistically different across feature sets averaged over reviews; P-values for Friedman's test were .045, .002, and .002, respectively. Differences in ranks for mean recall were not statistically significant. Alphanumeric+ features were associated with best performance; mean reduction in screening burden for this feature type ranged from 88% to 98% for the second pass through citations and from 38% to 48% overall. Conclusions: A computer-assisted, decision support system based on our methods could substantially reduce the burden of screening citations for systematic review teams and solo reviewers. Additionally, such a system could deliver quality assurance both by confirming concordant decisions and by naming studies associated with discordant decisions for further consideration. © 2014 Bekhuis et al

Systemic Sclerosis is Linked to Psoriasis and May Impact on Patients' Survival: A Large Cohort Study.

Although skin manifestations are quite common in systemic sclerosis (SSc), a link between SSc and psoriasis (PsO) has been poorly investigated. We assessed the Clalit medical database in a cohort study to compare the prevalence of PsO between SSc-patients and SSc-free controls. We also evaluated the SSc-related autoantibodies' role in the co-existence of the two conditions. Survival analysis was performed using both univariate (Kaplan-Meier, log-rank test) and multivariate (Cox proportional-hazards technique) analyses. Our cohort of 2,431 SSc-patients was age- and gender-matched with 12,710 controls (case-control match 1:5.2). There were 150 (1.2%) cases of PsO among controls and 47 (1.9%) among SSc-patients (p = 0.0027). A SSc diagnosis was an independent risk factor for PsO with an odds ratio (OR) of 2.16 (95%CI 1.38-3.39, p = 0.0008). Among SSc-patients, 98.6% with PsO were antinuclear antibodies (ANA)-negative. In terms of survival, the mortality rate in SSc-patients with PsO was lower than SSc without PsO (14.9% vs. 26%, p < 0.0001). At the multivariate-analysis, SSc-patients with PsO compared to SSc-patients without PsO had an OR for death of 0.44 (95%CI 0.19-0.99, p < 0.05). SSc is independently associated with PsO. The cases with concurrent PsO and SSc are almost exclusively ANA-negative and may exhibit a better survival

The Social and Political Dimensions of the Ebola Response: Global Inequality, Climate Change, and Infectious Disease

The 2014 Ebola crisis has highlighted public-health vulnerabilities in Liberia, Sierra Leone, and Guinea – countries ravaged by extreme poverty, deforestation and mining-related disruption of livelihoods and ecosystems, and bloody civil wars in the cases of Liberia and Sierra Leone. Ebola’s emergence and impact are grounded in the legacy of colonialism and its creation of enduring inequalities within African nations and globally, via neoliberalism and the Washington Consensus. Recent experiences with new and emerging diseases such as SARS and various strains of HN influenzas have demonstrated the effectiveness of a coordinated local and global public health and education-oriented response to contain epidemics. To what extent is international assistance to fight Ebola strengthening local public health and medical capacity in a sustainable way, so that other emerging disease threats, which are accelerating with climate change, may be met successfully? This chapter considers the wide-ranging socio-political, medical, legal and environmental factors that have contributed to the rapid spread of Ebola, with particular emphasis on the politics of the global and public health response and the role of gender, social inequality, colonialism and racism as they relate to the mobilization and establishment of the public health infrastructure required to combat Ebola and other emerging diseases in times of climate change

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Design, baseline characteristics, and retention of African American light smokers into a randomized trial involving biological data

<p>Abstract</p> <p>Background</p> <p>African Americans experience significant tobacco-related health disparities despite the fact that over half of African American smokers are light smokers (use ≤10 cigarettes per day). African Americans have been under-represented in smoking cessation research, and few studies have evaluated treatment for light smokers. This paper describes the study design, measures, and baseline characteristics from <it>Kick It at Swope III </it>(KIS-III), the first treatment study of bupropion for African American light smokers.</p> <p>Methods</p> <p>Five hundred forty African American light smokers were randomly assigned to receive bupropion (150mg bid) (n = 270) or placebo (n = 270) for 7 weeks. All participants received written materials and health education counseling. Participants responded to survey items and provided blood samples for evaluation of phenotype and genotype of CYP2A6 and CYP2B6 enzymes involved in nicotine and bupropion metabolism. Primary outcome was cotinine-verified 7-day point prevalence smoking abstinence at Week 26 follow-up.</p> <p>Results</p> <p>Of 2,628 individuals screened, 540 were eligible, consented, and randomized to treatment. Participants had a mean age of 46.5 years and 66.1% were women. Participants smoked an average of 8.0 cigarettes per day, had a mean exhaled carbon monoxide of 16.4ppm (range 1-55) and a mean serum cotinine of 275.8ng/ml. The mean Fagerström Test for Nicotine Dependence was 3.2, and 72.2% of participants smoked within 30 minutes of waking. The average number of quit attempts in the past year was 3.7 and 24.2% reported using pharmacotherapy in their most recent quit attempt. Motivation and confidence to quit were high.</p> <p>Conclusion</p> <p>KIS-III is the first study designed to examine both nicotine and bupropion metabolism, evaluating CYP2A6 and CYP2B6 phenotype and genotype in conjunction with psychosocial factors, in the context of treatment of African American light smokers. Of 1629 smokers screened for study participation, only 18 (1.1%) were ineligible to participate in the study because they refused blood draws, demonstrating the feasibility of recruiting and enrolling African American light smokers into a clinical treatment trial involving biological data collection and genetic analyses. Future evaluation of individual factors associated with treatment outcome will contribute to advancing tailored tobacco use treatment with the goal of enhancing treatment and reducing health disparities for African American light smokers.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="URL">NCT00666978</a></p

The Incidence and Predictors of Solid- and Hematological Malignancies in Patients with Giant Cell Arteritis: A Large Real-World Database Study

Background: The association between giant cell arteritis (GCA) and malignancies had been widely investigated with studies reporting conflicting results. Therefore, in this study, we aimed to investigate this association using a large nationwide electronic database. Methods: This study was designed as a retrospective cohort study including GCA patients first diagnosed between 2002–2017 and age, sex and enrollment time-matched controls. Follow-up began at the date of first GCA-diagnosis and continued until first diagnosis of malignancy, death or end of study follow-up. Results: The study enrolled 7213 GCA patients and 32,987 age- and sex-matched controls. The mean age of GCA diagnosis was 72.3 (SD 9.9) years and 69.1% were women. During the follow-up period, 659 (9.1%) of GCA patients were diagnosed with solid malignancies and 144 (2.0%) were diagnosed with hematologic malignancies. In cox-multivariate-analysis the risk of solid- malignancies (HR = 1.12 [95%CI: 1.02–1.22]), specifically renal neoplasms (HR = 1.60 [95%CI: 1.15–2.23]) and sarcomas (HR = 2.14 [95%CI: 1.41–3.24]), and the risk of hematologic malignancies (HR = 2.02 [95%CI: 1.66–2.47]), specifically acute leukemias (HR = 1.81 [95%CI: 1.06–3.07]), chronic leukemias (HR = 1.82 [95%CI: 1.19–2.77]), Hodgkin’s lymphomas (HR = 2.42 [95%CI: 1.12–5.20]), non-Hodgkin’s-lymphomas (HR = 1.66: [95%CI 1.21–2.29]) and multiple myeloma(HR = 2.40 [95%CI: 1.63–3.53]) were significantly increased in GCA patients compared to controls. Older age at GCA-diagnosis (HR = 1.36 [95%CI: 1.25–1.47]), male-gender (HR = 1.46 [95%CI: 1.24–1.72]), smoking (HR = 1.25 [95%CI: 1.04–1.51]) and medium-high socioeconomic status (HR = 1.27 [95%CI: 1.07–1.50]) were independently associated with solid malignancy while age (HR = 1.47 [95%CI: 1.22–1.77]) and male-gender (HR = 1.61 [95%CI: 1.14–2.29]) alone were independently associated with hematologic- malignancies. Conclusion: our study demonstrated higher incidence of hematologic and solid malignancies in GCA patients. Specifically, leukemia, lymphoma, multiple myeloma, kidney malignancies, and sarcomas. Age and male gender were independent risk factors for hematological malignancies among GCA patients, while for solid malignancies, smoking and SES were risk factors as well

Investigating hyper-vigilance for social threat of lonely children

The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs

Epstein Barr Virus-positive large T-cell lymphoma presenting as acute appendicitis 17 years after cadaveric renal transplant: a case report

<p>Abstract</p> <p>Introduction</p> <p>The majority of post-transplant lymphoproliferative disorders in renal transplant patients are of the B-cell phenotype, while the T-cell phenotype is rare. We report a case of Epstein Barr Virus-positive, T-cell lymphoma in a renal transplant patient, presenting unusually as acute appendicitis.</p> <p>Case presentation</p> <p>A 45-year-old Hispanic male renal transplant patient presented with right-side abdominal pain 17 years after transplant. The laboratory studies were unremarkable. Laparoscopic exploration showed an inflamed appendix so a laparoscopic appendectomy was performed. Pathology of the appendix showed large cells positive for CD3, CD56 and Epstein Barr Virus-encoded RNA staining, and negative for CD20 and CD30. The tissue tested positive for T-cell receptor gene rearrangement by polymerase chain reaction analysis. Treatment management involved reduction of immunosuppression and initiation of chemotherapy with cisplatin, etoposide, gemcitabine, and solumedrol followed by cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone). He recovered and the allo-grafted kidney is fully functional.</p> <p>Conclusion</p> <p>We report a rare case of post-renal transplant large T-cell lymphoma, with an unusual presentation of acute appendicitis and Epstein Barr Virus-positivity, which responded well to chemotherapy.</p