tbuckley/cabot-search huggingface dataset:
Child custody contests in historical perspective
Authors: A P Derdeyn
Journal: American Journal of Psychiatry (1976)

The author reviews the historical background of interparental child custody disputes. The father's superior right to custody in the nineteenth century continued the English common law tradition, but in the twentieth century the mother's claim became superior to the father's, reflecting women's generally increasing rights and the assumption that women are better suited to caring for children. Partly as a result of recent cultural changes leading to a beginning equalization of parental rights and partly because of greater concern for children, courts are starting to focus more on children's emotional needs. It is likely that courts will increasingly call on psychiatrists and other mental health professionals for help in making their decisions.
Medical Marijuana, Physicians, and State Law
Authors: George J. Annas
Journal: New England Journal of Medicine (2014)

Interview with Prof. George Annas on the tension between federal and state marijuana laws and the role of physicians. (09:17)Download Drug Enforcement Administration agents have told some Massachusetts doctors that they must sever ties with new medical-marijuana dispensaries or give up their DEA registration. But there's a difference between acting as a physician and acting as a marijuana entrepreneur.
IMPACT OF AGE ON THE MODES OF DUAL ANTIPLATELET THERAPY CESSATION: ANALYSIS FROM THE PARIS (PATTERNS OF NON-ADHERENCE TO ANTI-PLATELET REGIMENS IN STENTED PATIENTS) REGISTRY
Authors: Shunsuke Aoi, Jennifer Yu, Samantha Sartori, Usman Baber, Cono Ariti, Timothy Henry, David Cohen, David Moliterno, Stuart Pocock, C. Michael Gibson, Thomas Stuckey, Peter Berger, Ioannis Iakovou, Ron Waksman, James Hermiller, Roxana Mehran
Journal: Journal of the American College of Cardiology (2015)
Abstract 4500: Clinical significance of survivin expression in urothelial carcinoma of the bladder
Authors: Yuan-Hung Wang, Hsiao-Yen Hsieh, Cheng-Da Hsu, Chun-Liang Tung, Kun-Hung Shen, Cheng-Hung Shen
Journal: Cancer Research (2012)

Abstract Objective: Survivin is one of the inhibitors of apoptosis protein family and plays an important role in carcinogenesis. Survivin also has been reported to be related with poor clinical outcome in various malignancies. The aim of this study is to examine the association between survivin expression and clinical outcome in urothelial carcinoma of the bladder. Materials and methods: A total of 56 histopathologically confirmed urothelial carcinoma of bladder (UCB) patients were recruited from the Department of Urology of Chiayi Christian Hospital and Chi-Mei Medical Center from August 2006 to May 2007. Immunohistochemistry (IHC) analysis was performed to determine the expression level of survivin in tumor and adjacent normal tissues. One normal human urothelial cell: HUC4449 and nine urothelial carcinoma cell lines which are TSGH8301, 5637, BFTC905, BFTC909, HT1376, TCC SUP, J82, T24 and HT1197 for survivin mRNA analysis by quantitative real-time PCR. The –31 C/G polymorphism in survivin gene was determined using PCR-RFLP method. The effects of a higher expression level of survivin on disease-free survival (DFS) and overall survival (OS) were estimated using Cox proportional hazard models. Results: The frequency of low, moderate and higher expression of survivin in tumor tissues of UCB were 16.1%, 39.3% and 44.6%, respectively. The frequency of high expression of survivin was significantly higher in muscle-invasive tumors (66.6%) than in non-muscle invasive tumors (34.2%) (P=0.042). The frequency of high expression of survivin was significantly higher in poor-differentiated (85.7%) than in moderate- differentiated tumors (30.8%) (P= 0.0014). The survivin mRNA expression (Log2 fold change were 3.41∼5.30) in various grade (G2-G4) urothelium carcinoma cell lines were all higher than normal human urothelial cell. Moreover, the higher frequency of risk genotypes (C/C+C/G) was observed in median and high survivn expression groups. In a multivariate analysis, high survivin expression was predictive of inferior OS (HR= 12.3, P=0.02). Conclusion: These findings suggest that the high expression of survivin is not only associated with tumor stage and grade of tumors but also may be predictive of inferior overall survival of urothelail carcinoma of the bladder. Keywords: survivin; bladder; urothelial carcinoma; immunohistochemistry, disease-free survival; overall survival Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4500. doi:1538-7445.AM2012-4500
Genetic testing and insurance
Authors: E Smyth, E Anderson, M Steel, G H Hall, W T Hamilton
Journal: BMJ (1994)

Complicated by polygenic diseases

EDITOR, - We commend the recent attempt to address the issue of genetic testing and insurance.1 Given the differences between the health care systems in the United States and Britain, however, we believe that the editorial should have had British authors. Though the situation for life insurance may be similar on both sides of the Atlantic, that for health insurance is very different as in Britain health care is available to all through the NHS regardless of any additional insurance a person may hold.

Too little mention was made of the complex issues of polygenic and multifactorial diseases. Perhaps these were beyond the scope of such a short editorial, but, because of the speed of recent technological advances, particularly in cancer genetics, this subject warrants further discussion. In the near future it will be possible to identify people who carry a gene or …
TEMPORAL AND SPACIAL EVOLUTION OF CLONES IN 400 LOW GRADE GLIOMAS IN JAPAN
Authors: A. Natsume, H. Suzuki, S. Ogawa, T. Wakabayashi
Journal: Neuro-Oncology (2014)

BACKGROUND: Low grade gliomas (LGGs) account for approximately half of all gliomas. Although LGGs typically show slower tumor progression and generally better clinical outcomes than high-grade gliomas, their clinical course is invariably indolent and most patients ultimately succumb to death. In contrast to high-grade tumors, our knowledge about the genetic lesions and clonal evolution in LGG is still incomplete. METHODS: To obtain a complete registry of gene mutations involved in LGG pathogenesis and their role in clonal evolution, we performed whole exome sequencing (WES) of paired tumor/normal DNA from 54 cases with LGG. Clonal evolution in LGG was investigated using paired primary/relapsed tumor specimens from 9 cases as well as multiple tumor specimens (median 5) from 4cases. We further performed deep-sequencing of common mutational targets identified by WES and SNP array analysis among a large cohort of 327 LGG cases. RESULTS: Major mutational targets detected in WES included not only previously known mutational genes, including IDH1/2, TP53, ATRX, CIC, FUBP1 and NOTCH1, as well as multiple components of the PI3K pathway and the SWI/SNF complex. Multi-sampling analysis revealed regional and special heterogeneity of LGG. According to the observed variant allele frequencies (VAFs), mutations of IDH1/2 and 1p19q co-deletion were thought to exist in the major clone, representing truncal mutations in most cases., In contrast, mutations in TP53, ATRX, CIC and FUBP1 were more often identified in one or more phylogenic branches in different subclones and involved in parallel evolution, where different mutations of the same genes were found at different time points in different locations. mutations in IDH1/2 were found in 78.6%. 1p19q co-deletion (43.1%), and TP53 mutations (34.6%) with or without ATRX mutations were mutually exclusive with common IDH mutations. VAFs of coexisting IDH1/2 and 1p19q co-deletion were approximately the same, whereas mutations in other genes tended to show lower VAFs than those of IDH1/2. CONCLUSIONS: Combined, our findings revealed two major, mutually exclusive patterns in clonal evolution in LGG; in some cases IDH1/2 mutations and 1p19q co-deletions were trunchal events, followed by CIC, FUBP1, and other mutations in subsequent phylogenic branches. In other cases, predated by the founder IDH1/2 mutations, mutations in TP53 and ATRX seemed to predominate tumor populations later. SECONDARY CATEGORY: Epidemiology & Cancer Control.
OC-063 The severity of hepatic ischaemia-reperfusion injury is associated with acute kidney injury following donation after brain death liver transplantation
Authors: J A Leithead, M J Armstrong, C Corbett, M Andrew, C Kothari, B K Gunson, P Muiesan, J W Ferguson
Journal: Gut (2012)

<h3>Introduction</h3> Donation after Cardiac Death liver transplant recipients have an increased frequency of acute kidney injury (AKI) during the immediate post-operative period and in these patients peak peri-operative aspartate amino-transferase (AST), a surrogate marker of hepatic ischaemia-reperfusion injury (IRI), is the only variable associated with renal dysfunction (Leithead <i>et al Am J Transplant</i> 2012). This suggests that hepatic IRI may play a critical role in the pathogenesis of AKI after liver transplantation. The aim of this study was to determine if graft injury is also associated with renal dysfunction following Donation after Brain Death (DBD) liver transplantation. <h3>Methods</h3> Single-centre study of 290 patients who underwent first whole DBD liver transplantation for chronic liver disease 01/2007–06/2011. Peak peri-operative serum AST was recorded as a marker of hepatic IRI. AKI was defined according to the RIFLE criteria: peak serum creatinine ≥2 times baseline. <h3>Results</h3> The median peak peri-operative AST was 1307 U/l. Peak AST correlated well with the histological grading of IRI on “time zero” allograft biopsy (p=0.007). The median peak peri-operative creatinine was 125 (IQR 91–191) μmol/l. The median percentage change in creatinine from baseline was +49 (IQR 12–119). 36.9% of patients developed AKI, of whom 58.9% required renal replacement therapy. Patient survival was reduced in the AKI group (AKI, 82.8%; no AKI, 95.5%, estimated 1-year survival; log rank p=0.001). On univariate analysis peak AST correlated with both peak creatinine (r=0.259, p&lt;0.001) and peak change in creatinine from baseline (r=0.309, p&lt;0.001). Median peak AST was higher in AKI patients (1755 vs 1158 U/l; p&lt;0.001). The incidence of AKI was 25.7%, 41.0% and 75.0% for patients with a peak AST of &lt;1500, 1500–3000 and ≥3000 U/l, respectively (p&lt;0.001). On multiple logistic regression analysis the variables associated with AKI were black ethnicity (p=0.043), pre-transplant MELD (p=0.047), pre-transplant refractory ascites (p=0.047), intra-operative red cell concentrate requirements (p&lt;0.001), peri-operative sepsis (p&lt;0.001) and peak peri-operative AST (p&lt;0.001). <h3>Conclusion</h3> Hepatic IRI demonstrates a strong relationship with peri-operative AKI in DBD liver transplant recipients. Hepatic IRI may therefore play an important and modifiable role in the pathogenesis of renal dysfunction in this setting. <h3>Competing interests</h3> None declared.
Protective Effects of Aspirin against Acute Myocardial Infarction and Death in Men with Unstable Angina
Authors: H. Daniel Lewis, James W. Davis, Donald G. Archibald, William E. Steinke, Thomas C. Smitherman, James E. Doherty, Harold W. Schnaper, Martin M. LeWinter, Esteban Linares, J. Maurice Pouget, Subhash C. Sabharwal, Elliot Chesler, Henry DeMots
Journal: New England Journal of Medicine (1983)

We conducted a multicenter, double-blind, placebo-controlled randomized trial of aspirin treatment (324 mg in buffered solution daily) for 12 weeks in 1266 men with unstable angina (625 taking aspirin and 641 placebo). The principal end points were death and acute myocardial infarction diagnosed by the presence of creatine kinase MB or pathologic Q-wave changes on electrocardiograms. The incidence of death or acute myocardial infarction was 51 per cent lower in the aspirin group than in the placebo group: 31 patients (5.0 per cent) as compared with 65 (10.1 per cent); P = 0.0005. Nonfatal acute myocardial infarction was 51 per cent lower in the aspirin group: 21 patients (3.4 per cent) as compared with 44 (6.9 per cent); P = 0.005. The reduction in mortality in the aspirin group was also 51 per cent — 10 patients (1.6 per cent) as compared with 21 (3.3 per cent) — although it was not statistically significant; P = 0.054. There was no difference in gastrointestinal symptoms or evidence of blood loss between the treatment and control groups. Our data show that aspirin has a protective effect against acute myocardial infarction in men with unstable angina, and they suggest a similar effect on mortality. (N Engl J Med 1983; 309:396–403.)
Dysphagia in Patients with the Post-Polio Syndrome
Authors: Barbara C. Sonies, Marinos C. Dalakas
Journal: New England Journal of Medicine (1991)

Dysphagia may develop in some patients many years after an attack of acute paraltic poliomyelitis. To identify clinical or subclinical signs of oropharyngeal dysfunction, we examined 32 patients (mean age, 48.9 years) with the post-polio syndrome (defined by new weakness in the limbs). Of the 32 patients, 14 had symptoms of new swallowing difficulties, and 18 were asymptomatic in this respect; 12 had a history of bulbar involvement during acute poliomyelitis. Swallowing function was assessed objectively by ultrasonography, videofluoroscopy, and an oral motor index score for 10 components of oral function.
1087 THERAPEUTIC EFFECT OF S-ADENOSYLMETHIONINE ON LIVER TUMOR DEVELOPMENT IN MURINE INFLAMMATION-MEDIATED MODEL IS ASSOCIATED WITH INCREASED EXPRESSION OF TUMOR SUPPRESSOR GENES AND CELL CYCLE ARREST
Authors: E. Stoyanov, G. Ludwig, L. Mizrahi, D. Olam, T. Schnitzer- Perlman, H. Cedar, E. Galun, D. Goldenberg
Journal: Journal of Hepatology (2013)
Carotid-Artery Intima and Media Thickness as a Risk Factor for Myocardial Infarction and Stroke in Older Adults
Authors: Daniel H. O'Leary, Joseph F. Polak, Richard A. Kronmal, Teri A. Manolio, Gregory L. Burke, Sidney K. Wolfson
Journal: New England Journal of Medicine (1999)

The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease.
Association of Hypokalemia, Aldosteronism, and Renal Cysts
Authors: Vicente E. Torres, William F. Young, Kenneth P. Offord, Robert R. Hattery
Journal: New England Journal of Medicine (1990)

The recognition of renal cysts in two patients with chronic hypokalemia and the renal effects of hypokalemia in certain species of animals prompted this study of the possible association of hypokalemia and renal cysts in patients with primary aldosteronism or primary renal potassium wasting.
FRI0241 Which ra patients end up starting which biologic? a nationwide assessment of differential channelling to biological treatments in sweden 2006-2011
Authors: J. Askling, S. Ernestam, H. Forsblad-d'Elia, R. von Vollenhoven, L. Jacobsson, C. Turesson, T. Frisell
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Over the past years, many new biologics have been introduced for the treatment of RA. In clinical practice, treatment guidelines and perceived or established differences between available biologics lead to a non-random allocation of treatment, the magnitude of which is seldom quantified but essential for a correct understanding of their comparative effectiveness and safety. In Sweden, national treatment guidelines for RA suggest the use of TNF inhibitors (with no inter-drug preference) as first biologic, but the use of non-anti TNF biologics (with no inter-drug preference) in case of contra-indications or non-response to TNF-inhibitors. <h3>Objectives</h3> To assess differences in baseline characteristics across biologics. <h3>Methods</h3> Data on biological treatment, RA characteristics, demographics, and comorbidities among RA patients initiating biological therapies were identified in the nationwide Swedish Biologics Register (ARTIS) 2006-2011 (estimated coverage around 90%, and through linkage to the nationwide and virtually complete Swedish Patient Register. Initiators of biological therapies were stratified by type of biologic and by previous use of any biologic. <h3>Results</h3> There were only moderate differences with respect to demographics and RA characteristics (Table). These differences were larger between drugs than between initiators of a given drug as first vs. later biologic. In contrast, we noted large differences in the prevalence of comorbidities across different biologics, with higher load of co-morbidities among patients initiating non-antiTNF biologics as their first biologic. <h3>Image/graph</h3> <h3>Conclusions</h3> We observed clear channeling, notably a higher prevalence of comorbidities in patients for whom non-anti-TNF biologics were chosen. There were smaller differences between initiators of older and newer anti-TNF drugs. We speculate that the observed channeling is related to perceived safety and effectiveness. Studies of comparative effectiveness and safety of different biologics must factor in, and be interpreted in light of, this channeling which is as pronounced among subsets of initiators of a particular biologic as between different biologics. <h3>Acknowledgements</h3> ARTIS has agreements with Abbott, BMS, Merck, Sobi, AstraZeneca, Pfizer, and Roche <b>Disclosure of Interest</b>: None Declared
Abstract 1226: The AH receptor plays a key role in mediating IL6 production in head and neck tumor cell lines
Authors: Brett DiNatale, Gary H. Perdew
Journal: Cancer Research (2010)

Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor conventionally viewed as binding exogenous ligands and mediating gene transcription through DNA binding. Our research has uncovered various structurally distinct ligands, both exogenous and endogenous, that are capable of binding the AHR. We have also recently shown that combinatorial treatment of human breast and cervical cancer cell lines with an AHR ligand and an inflammatory signal results in synergistic induction of interleukin 6 (IL6). Squamous cell cancer of the head and neck is an umbrella term for malignancies developing in numerous locations, including the pharynx, larynx, tongue, and oral cavity. These tumors are often aggressive in nature, with high rates of metastasis to regional lymph nodes. Treatment has historically included radical or modified neck dissection to remove lymph nodes and frequent adjuvant chemotherapy and/or radiation therapy. IL6 production within HNSCC microenvironments both by cancer cells and by tumor-infiltrating macrophages has been shown to correlate with invasive, proliferative, and anti-apoptotic abilities of HNSCC cells, as well as human disease prognosis and recurrence rates. In studying a number of HNSCC cell lines, we have found many to have relatively high basal IL6 production. Using HNSCC2095 as an example, the AHR dependency of basal IL6 production was shown by means of siRNA-mediated AHR knockdown, as well as mediation of basal IL6 transcription following treatment with an AHR antagonist. ChIP assays reveal a significant level of basal AHR occupancy at the IL6 promoter, and antagonist treatment leads to dismissal of the AHR and a combination of coactivators. Similarly, AHR dismissal results in higher occupancy of transcriptional repressors. Key activators lost with AHR dismissal include p65, HDAC3, and BRG1. Following AHR dismissal, an increased presence of dimethylated histone H3 and HDAC1 occurs; both of which are typically repressive. Dismissal of the AHR from the IL6 promoter also leads to a decrease in the IL6-induced STAT3 signaling feedback loop seen in HNSCC lines. Constitutively active STAT3 has been examined as a therapeutic target in HNSCC due to its ability to increase tumor growth and anti-apoptotic effects. Our research shows that AHR binding to the IL6 promoter in HNSCC lines is required for constitutive cytokine production and plays a key role in STAT3 activation. These findings highlight the AHR as a potential target in mediating the autocrine loop of pro-growth signaling in human head and neck cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1226.
OT3-01-01: Randomized Phase II Study of Fulvestrant Versus Fulvestrant Plus Bortezomib in Postmenopausal Women with Estrogen Receptor (ER) Positive, Aromatase-Inhibitor (AI) Resistant Metastatic Breast Cancer (MBC): New York Cancer Consortium Trial P8457.
Authors: KB Adelson, G Raptis, J Sparano, D Germain
Journal: Cancer Research (2011)

Abstract Background: Bortezomib ia proteasome inhibitor that enhances fulvestrant-mediated aggregation of the ER in the cytoplasm without blocking ER degradation in the nucleus in ER+ human breast cancer cell lines, thereby promoting cytoplasmic ER aggresomes which activate a sustained unfolded protein response leading to apoptotic cell death; the combination also induces tumor regression in a tamoxifen resistant T47D-cyclin D1 xenograft model more effectively than either agent alone (Clin Cancer Res 2011; 17: 2292–2300). Hypothesis: We hpothesize that the combination of fulvestrant and bortezomib will be more effective than fulvestrant alone in ER+, AI-resistant MBC. Trial design: This is an open-label randomized phase II design in which patients with MBC are randomized to receive fulvestrant alone (500 mg IM day −14, day +1, and day +14 during cycle 1, then 500 mg every 4 weeks on day +1 during cycle 2 and thereafter) or in combination with bortezomib (1.6 mg/m2 IV days +1, +8, +15 every cycle). Stratification factors for randomization include performance status (ECOG 0 vs. 1–2), measurable disease (yes vs. no), and prior chemotherapy for MBC (yes vs. no). Patients who progress on fulvestrant alone may cross over to the combination. Eligibility criteria: Postmenopausal women with ER+, Her2-negative, MBC who have progressive disease during AI therapy for metastatic disease, or relapse while receiving adjuvant AI therapy. Up to one prior chemotherapy regimen for metastatic disease is permitted. Specific aims: Primary Objective: To determine if the addition of bortezomib to fulvestrant significantly improves median progression-free survival (PFS), defined as the time from cycle 1, day 1 of therapy until disease progression or death from any cause. Secondary Objectives: To determine: (1) adverse event rates in both arms, (2) the clinical benefit rate (CBR — objective response [by RECIST 1.1] and/or progression free at 24 weeks), (3) the objective response and CBR after crossover from fulvestrant to fulvestrant plus bortezomib. Translational Objectives: To perform an exploratory analysis of the effects of the combination on intratumoral nuclear/cytoplasmic ER ratio, unfolded protein response (BiP), apoptotis (cleaved caspase 3, Bc1-2 phospho JNK.) Statistical methods: he median PFS for patients receiving fulvestrant alone is expected to be approximately 5.4 months based upon patients with AI-resistant disease enrolled on the CONFIRM trial ( J Clin Oncol 2010; 28: 4594–4600). The trial is designed to detect a 70% improved in median PFS to 9.0 months (alpha=0.10, beta =0.10), which will require 59 eligible patients in each arm. Present accrual and target accrual: 24/118 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-01.