Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection.

Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p = 1.76⁎10(-5)) and IL-6 (p = 0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p = 0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection

Preoperative Parathyroid Needle Localization: A Minimally Invasive Novel Technique in Reoperative Settings

Background. Reoperative parathyroid surgery for primary hyperparathyroidism can be challenging. Numerous preoperative localization techniques have been employed to facilitate a more focused surgical exploration. This paper describes a novel, minimally invasive, and highly successful method of parathyroid localization. Methods. Patients with recurrent or persistent primary hyperparathyroidism underwent parathyroidectomy following CT scan or ultrasound-guided wire localization of the parathyroid. Accurate placement was confirmed by fine-needle aspiration with immunocytochemistry or PTH washout. The guide wire was left in situ to guide surgical excision of the gland. Curative resection was established by monitoring intact serum PTH levels after excision of the adenoma. Results. All ten patients underwent successful redo-targeted parathyroidectomy. Nine of the ten patients were discharged on the day of surgery. One patient was observed overnight due to transient postoperative hypocalcemia, which resolved with calcium supplementation. Conclusion. Placement of a localization wire via preoperative high-resolution ultrasound or CT can expedite reoperative parathyroid surgery. It allows identification of parathyroid adenoma via a minimally invasive approach, especially in cases where a sestamibi scan is inconclusive

Teaching Group Processes Through Multiple Group Leadership Opportunities in a Masters Level Counselor Education Program

Utilizing an experiential component in group work training is a prominent feature in Counselor Education programs. Although numerous models have been proposed, the vast majority offer limited explanations of incorporating the number of hours of group participation and observation recommended by the Professional Standards for the Training of Group Workers (ASGW, 2000). This article presents an experiential group training model with multiple opportunities for group leadership in a masters level Counselor Education program, and provides a description of common themes experienced by group-leaders-in-training as they progressed through the culminating feature which served as the capstone of this approach

HST/WFC3 Light Curve Confirms the Closest Exoplanet to Transit an M Dwarf is Terrestrial

Previous studies of the exoplanet LTT 1445Ac concluded that the light curve from the Transiting Exoplanet Survey Satellite (TESS) was consistent with both grazing and non-grazing geometries. As a result, the radius and hence density of the planet remained unknown. To resolve this ambiguity, we observed the LTT 1445 system for six spacecraft orbits of the Hubble Space Telescope (HST) using WFC3/UVIS imaging in spatial scan mode, including one partial transit of LTT 1445Ac. This imaging produces resolved light curves of each of the three stars in the LTT 1445 system. We confirm that the planet transits LTT 1445A and that LTT 1445C is the source of the rotational modulation seen in the TESS light curve, and we refine the estimate of the dilution factor for the TESS data. We perform a joint fit to the TESS and HST observations, finding that the transit of LTT 1445Ac is not grazing with 97% confidence. We measure a planetary radius of 1.10$_{-0.07}^{+0.10}$ R$_\oplus$. Combined with previous radial velocity observations, our analysis yields a planetary mass of $1.36\pm0.19$ M$_\oplus$ and a planetary density of 5.6$_{-1.5}^{+1.7}$ g cm$^{-3}$. LTT 1445Ac is an Earth analog with respect to its mass and radius, albeit with a higher instellation, and is therefore an exciting target for future atmospheric studies.Comment: Submitted to AJ. 9 pages, 7 figures, 3 table

An Automated Procedure to Identify Biomedical Articles that Contain Cancer-associated Gene Variants

The proliferation of biomedical literature makes it increasingly difficult for researchers to find and manage relevant information. However, identifying research articles containing mutation data, a requisite first step in integrating large and complex mutation data sets, is currently tedious, time-consuming and imprecise. More effective mechanisms for identifying articles containing mutation information would be beneficial both for the curation of mutation databases and for individual researchers. We developed an automated method that uses information extraction, classifier, and relevance ranking techniques to determine the likelihood of MEDLINE abstracts containing information regarding genomic variation data suitable for inclusion in mutation databases. We targeted the CDKN2A (p16) gene and the procedure for document identification currently used by CDKN2A Database curators as a measure of feasibility. A set of abstracts was manually identified from a MEDLINE search as potentially containing specific CDKN2A mutation events. A subset of these abstracts was used as a training set for a maximum entropy classifier to identify text features distinguishing relevant from not relevant abstracts. Each document was represented as a set of indicative word, word pair, and entity tagger-derived genomic variation features. When applied to a test set of 200 candidate abstracts, the classifier predicted 88 articles as being relevant; of these, 29 of 32 manuscripts in which manual curation found CDKN2A sequence variants were positively predicted. Thus, the set of potentially useful articles that a manual curator would have to review was reduced by 56%, maintaining 91% recall (sensitivity) and more than doubling precision (positive predictive value). Subsequent expansion of the training set to 494 articles yielded similar precision and recall rates, and comparison of the original and expanded trials demonstrated that the average precision improved with the larger data set. Our results show that automated systems can effectively identify article subsets relevant to a given task and may prove to be powerful tools for the broader research community. This procedure can be readily adapted to any or all genes, organisms, or sets of documents

Automated recognition of malignancy mentions in biomedical literature

BACKGROUND: The rapid proliferation of biomedical text makes it increasingly difficult for researchers to identify, synthesize, and utilize developed knowledge in their fields of interest. Automated information extraction procedures can assist in the acquisition and management of this knowledge. Previous efforts in biomedical text mining have focused primarily upon named entity recognition of well-defined molecular objects such as genes, but less work has been performed to identify disease-related objects and concepts. Furthermore, promise has been tempered by an inability to efficiently scale approaches in ways that minimize manual efforts and still perform with high accuracy. Here, we have applied a machine-learning approach previously successful for identifying molecular entities to a disease concept to determine if the underlying probabilistic model effectively generalizes to unrelated concepts with minimal manual intervention for model retraining. RESULTS: We developed a named entity recognizer (MTag), an entity tagger for recognizing clinical descriptions of malignancy presented in text. The application uses the machine-learning technique Conditional Random Fields with additional domain-specific features. MTag was tested with 1,010 training and 432 evaluation documents pertaining to cancer genomics. Overall, our experiments resulted in 0.85 precision, 0.83 recall, and 0.84 F-measure on the evaluation set. Compared with a baseline system using string matching of text with a neoplasm term list, MTag performed with a much higher recall rate (92.1% vs. 42.1% recall) and demonstrated the ability to learn new patterns. Application of MTag to all MEDLINE abstracts yielded the identification of 580,002 unique and 9,153,340 overall mentions of malignancy. Significantly, addition of an extensive lexicon of malignancy mentions as a feature set for extraction had minimal impact in performance. CONCLUSION: Together, these results suggest that the identification of disparate biomedical entity classes in free text may be achievable with high accuracy and only moderate additional effort for each new application domain

Trait urgency and gambling problems in young people by age: The mediating role of decision-making processes

Although the personality trait of urgency has been linked to problem gambling, less is known about psychological mechanisms that mediate the relationship between urgency and problem gambling. One individual variable of potential relevance to impulsivity and addictive disorders is age. The aims of this study were to examine: (i) a theoretical model associating urgency and gambling problems, (ii) the mediating effects of decision-making processes (operationalized as preference for small/immediate rewards and lower levels of deliberative decision-making); and (iii) age differences in these relationships. Participants comprised 986 students (64% male; mean age=19.51 years; SD=2.30) divided into three groups: 16-17 years, 18-21 years, and 22-25 years. All participants completed measures of urgency, problem gambling, and a delay-discounting questionnaire involving choices between a smaller amount of money received immediately and a larger amount of money received later. Participants were also asked to reflect on their decision-making process. Compared to those aged 16-17 years and 22-25 years, participants aged 18-21 years had a higher level of gambling problems and decreased scores on lower levels of deliberative decision-making. Higher levels of urgency were associated with higher levels of gambling problems. The association was mediated by a lower level of deliberative decision-making and preference for an immediate/small reward. A distinct pathway was observed for lower levels of deliberative decision-making. Young people who tend to act rashly in response to extreme moods, had lower levels of deliberative decision-making, that in turn were positively related to gambling problems. This study highlights unique decision-making pathways through which urgency trait may operate, suggesting that those developing prevention and/or treatment strategies may want to consider the model’s variables, including urgency, delay discounting, and deliberative decision-making

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

Genetic Variation in the IL-6

Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p=1.76⁎10-5) and IL-6 (p=0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p=0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection