tbuckley/cabot-search huggingface dataset:
Early Prevention of Antisocial Personality: Long-Term Follow-Up of Two Randomized Controlled Trials Comparing Indicated and Selective Approaches
Authors: Stephen Scott, Jackie Briskman, Thomas G. O’Connor
Journal: American Journal of Psychiatry (2014)

Antisocial personality is a common adult problem that imposes a major public health burden, but for which there is no effective treatment. Affected individuals exhibit persistent antisocial behavior and pervasive antisocial character traits, such as irritability, manipulativeness, and lack of remorse. Prevention of antisocial personality in childhood has been advocated, but evidence for effective interventions is lacking.The authors conducted two follow-up studies of randomized trials of group parent training. One involved 120 clinic-referred 3- to 7-year-olds with severe antisocial behavior for whom treatment was indicated, 93 of whom were reassessed between ages 10 and 17. The other involved 109 high-risk 4- to 6-year-olds with elevated antisocial behavior who were selectively screened from the community, 90 of whom were reassessed between ages 9 and 13. The primary psychiatric outcome measures were the two elements of antisocial personality, namely, antisocial behavior (assessed by a diagnostic interview) and antisocial character traits (assessed by a questionnaire). Also assessed were reading achievement (an important domain of youth functioning at work) and parent-adolescent relationship quality.In the indicated sample, both elements of antisocial personality were improved in the early intervention group at long-term follow-up compared with the control group (antisocial behavior: odds ratio of oppositional defiant disorder=0.20, 95% CI=0.06, 0.69; antisocial character traits: B=-4.41, 95% CI=-1.12, -8.64). Additionally, reading ability improved (B=9.18, 95% CI=0.58, 18.0). Parental expressed emotion was warmer (B=0.86, 95% CI=0.20, 1.41) and supervision was closer (B=-0.43, 95% CI=-0.11, -0.75), but direct observation of parenting showed no differences. Teacher-rated and self-rated antisocial behavior were unchanged. In contrast, in the selective high-risk sample, early intervention was not associated with improved long-term outcomes.Early intervention with severely antisocial children for whom treatment is indicated may prevent the development of antisocial personality in adolescence and may improve academic performance. In contrast, early intervention with selective high-risk samples may be ineffective.
Interferon- augments eosinophil adhesion-inducing activity of endothelial cells
Authors: T. Kobayashi, Y. Takaku, A. Yokote, H. Miyazawa, T. Soma, K. Hagiwara, M. Kanazawa, M. Nagata
Journal: European Respiratory Journal (2008)

Viral infections induce exacerbations of asthma. One of the earliest host responses to viral infections is the production of innate cytokines including type I interferons (IFNs), such as IFN-β, which may act to modify airway inflammation. The objective of the present study was to investigate whether IFN-β modifies the eosinophil adhesion-inducing activity of endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with IFN-β for 24 h in the presence or absence of tumour necrosis factor (TNF)-α. Eosinophils were isolated from the peripheral blood of healthy volunteers. The ability of the IFN-β-stimulated HUVEC monolayers to induce eosinophil adhesion was assessed according to the eosinophil peroxidase assay. Eosinophil adhesion to HUVECs was significantly augmented by IFN-β in the presence of TNF-α but not in its absence. The augmented adhesion was inhibited by anti-α 4 integrin monoclonal antibody (mAb) or anti-β 2 integrin mAb. IFN-β significantly enhanced the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 on HUVECs in the presence of TNF-α. Interferon-β can augment the adhesiveness of endothelial cells to eosinophils, mainly through the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. This action of interferon-β may contribute to the intensification of airway inflammation in asthma that is associated with exacerbations induced by viral infections.
Aspirin, Nonaspirin Nonsteroidal Anti-inflammatory Drug, and Acetaminophen Use and Risk of Invasive Epithelial Ovarian Cancer: A Pooled Analysis in the Ovarian Cancer Association Consortium
Authors: B. Trabert, R. B. Ness, W.-H. Lo-Ciganic, M. A. Murphy, E. L. Goode, E. M. Poole, L. A. Brinton, P. M. Webb, C. M. Nagle, S. J. Jordan, H. A. Risch, M. A. Rossing, J. A. Doherty, M. T. Goodman, G. Lurie, S. K. Kjaer, E. Hogdall, A. Jensen, D. W. Cramer, K. L. Terry, A. Vitonis, E. V. Bandera, S. Olson, M. G. King, U. Chandran, H. Anton-Culver, A. Ziogas, U. Menon, S. A. Gayther, S. J. Ramus, A. Gentry-Maharaj, A. H. Wu, C. L. Pearce, M. C. Pike, A. Berchuck, J. M. Schildkraut, N. Wentzensen
Journal: JNCI Journal of the National Cancer Institute (2014)

Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. We analyzed pooled data from 12 population-based case–control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91). Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.
But what would a balanced approach look like?
Authors: David Dunning
Journal: Behavioral and Brain Sciences (2004)

Krueger &amp; Funder (K&amp;F) could have gone further to sketch out a more comprehensive vision of “balanced” psychology. The triumphs and travails of other sciences (e.g., economics) provide clues about the advantages and pitfalls of pursuing such an approach. Perhaps introducing more positivity into psychology may involve asking how people can do better, not how well they do already.
Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer
Authors: H. K. Gan, B. You, G. R. Pond, E. X. Chen
Journal: JNCI Journal of the National Cancer Institute (2012)

In designing phase III randomized clinical trials (RCTs), the expected magnitude of the benefit of the experimental therapy (δ) determines the number of patients required and the number of person-years of follow-up. We conducted a systematic review to evaluate how reliably δ approximates the observed benefit ( B ) in RCTs that evaluated cancer treatment. RCTs evaluating systemic therapy in adult cancer patients published in 10 journals from January 1, 2005, through December 31, 2009, were identified. Data were extracted from each publication independently by two investigators. The related-samples Sign test was used to determine whether the median difference between δ and B was statistically significant in different study subsets and was two-sided. A total of 253 RCTs met the eligibility criteria and were included in the analysis. Regardless of whether benefit was defined as proportional change (median difference between δ and B = −13.0%, 95% confidence interval [CI] = −21.0% to −8.0%), absolute change (median difference between δ and B = −8.0%, 95% CI = −9.9% to −5.1%), or median increase in a time-to-event endpoint (median difference between δ and B = −1.4 months, 95% CI = −2.1 to −0.8 months), δ was consistently and statistically significantly larger than B ( P < .001, for each, respectively). This relationship between δ and B was independent of year of publication, industry funding, management by cooperative trial groups, type of control arm, type of experimental arm, disease site, adjuvant treatment, or treatment for advanced disease, and likely contributed to the high proportion of negative RCTs (158 [62.5%] of 253 studies). Investigators consistently make overly optimistic assumptions regarding treatment benefits when designing RCTs. Attempts to reduce the number of negative RCTs should focus on more realistic estimations of δ. Increased use of interim analyses, certain adaptive trial designs, and better biological characterization of patients are potential ways of mitigating this problem.
Preferential Tumor Targeting and Selective Tumor Cell Cytotoxicity of 5-[131/125I]Iodo-4′-Thio-2′-Deoxyuridine
Authors: Agnieszka Morgenroth, Sandra Deisenhofer, Gerhard Glatting, Falk H-G. Kunkel, Cornelia Dinger, Boris Zlatopolskiy, Andreas T.J. Vogg, Thomas Kull, Sven N. Reske
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Auger electron emitting radiopharmaceuticals are attractive for targeted nanoirradiation therapy, provided that DNA of malignant cells is selectively addressed. Here, we examine 5-[123/125/131I]iodo-4′-thio-2′-deoxyuridine (ITdU) for targeting DNA in tumor cells in a HL60 xenograft severe combined immunodeficient mouse model. Experimental Design: Thymidine kinase and phosphorylase assays were done to determine phosphorylation and glycosidic bond cleavage of ITdU, respectively. The biodistribution and DNA incorporation of ITdU were determined in severe combined immunodeficient mice bearing HL60 xenografts receiving pretreatment with 5-fluoro-2′-deoxyuridine (FdUrd). Organ tissues were dissected 0.5, 4, and 24 h after radioinjection and uptake of [131I]ITdU (%ID/g tissue) was determined. Cellular distribution of [125I]ITdU was imaged by microautoradiography. Apoptosis and expression of the proliferation marker Ki-67 were determined by immunohistologic staining using corresponding paraffin tissue sections. Results: ITdU is phosphorylated by thymidine kinase 1 and stable toward thymidylate phosphatase-mediated glycosidic bond cleavage. Thymidylate synthase-mediated deiodination of [123/125/131I]ITdU was inhibited with FdUrd. Pretreatment with FdUrd increased preferentially tumor uptake of ITdU resulting in favorable tumor-to-normal tissue ratios and tumor selectivity. ITdU was exclusively localized within the nucleus and incorporated into DNA. In FdUrd-pretreated animals, we found in more than 90% of tumor cells apoptosis induction 24 h postinjection of ITdU, indicating a highly radiotoxic effect in tumor cells but not in cells of major proliferating tissues. Conclusion: ITdU preferentially targets DNA in proliferating tumor cells and leads to apoptosis provided that the thymidylate synthase is inhibited.
Efficacy of a 1-week, once-daily regimen of terbinafine 1% cream in the treatment of tinea cruris and tinea corporis
Authors: Nardo Zaias, Brian Berman, Carlos N. Cordero, Alfred Hernandez, Coleman Jacobson, Larry Millikan, Rosa Rojas, Irene de la Rosa, Violette Villars, Jay E. Birnbaum
Journal: Journal of the American Academy of Dermatology (1993)
Structural Basis for the Static Mechanical Properties of the Aortic Media
Authors: HARVEY WOLINSKY, SEYMOUR GLAGOV
Journal: Circulation Research (1964)

The arrangement and interrelation of the structural components of the rabbit aorta were studied by light and electron microscopy. Segments of abdominal aorta were restored to in vivo length and fixed in formalin or osmic acid while intraluminal pressures ranging from 0 to 200 mm Hg were maintained by a constant pressure perfusion apparatus. Transverse, longitudinal, and tangential sections of vessels fixed at various distending pressures were examined. Micrometric measurements included vessel diameters and wall thickness, thickness and waviness of elastin lamellae and interlamellar distances. With increasing pressures below the diastolic value, aortic radius increased and wall thickness decreased rapidly. Waviness of the tubular elastin lamellae decreased uniformly throughout the wall. Interlamellar distances decreased uniformly and markedly. Lamellar thicknesses decreased uniformly but much less than interlamellar distances. A fine fibrillary elastin network connected the thick lamellae. Collagen fibers showed no definite pattern of orientation. At and above diastolic pressure radius and wall thickness changed little with increasing pressures. Elastin lamellae were straight and interlamellar distances were uniform; the fibrils of the interlamellar elastin net were arranged obliquely. Collagen fibers were arranged nearly circumferentially. Collagen and elastin fibers were closely intermingled in the narrow interlamellar space but no collagen-elastin connections were obserevd. The mechanical properties and organization of the collagen and elastin components of the aortic media indicate that the wall normally functions as a "two-phase" material. At and above physiological pressures, circumferentially aligned collagen fibers of high tensile strength and relatively high modulus of elasticity bear most of the stressing force. Elastin lamellae and fibrils of relatively low modulus of elasticity distribute stressing forces uniformly. Attempts to assess the role of medial pressure and tension gradients in the pathogenesis of aortic disease must take into account the special mechanical properties of this "two-phase" material.
Percutaneous ethanol injection for small hepatocellular carcinoma: Therapeutic efficacy based on 20-year observation
Authors: Masaaki Ebara, Shinichiro Okabe, Kazuhiko Kita, Nobuyuki Sugiura, Hiroyuki Fukuda, Masaharu Yoshikawa, Fukuo Kondo, Hiromitsu Saisho
Journal: Journal of Hepatology (2005)
The Unfolded Protein Response and Integrated Stress Response to Anoxia
Authors: Tomasz Rzymski, Adrian L. Harris
Journal: Clinical Cancer Research (2007)

The lack of oxygen delivery to tumor cells has profound consequences for tumor growth and correlates with poor prognosis. Some tumors contain regions of very severe hypoxia called anoxia, which constitutes a functionally different state to hypoxia. In response to anoxia, mammalian cells induce coordinated cytoprotective programs that are critical for tumor survival: the unfolded protein response and integrated stress response. Therefore, targeting additional components of anoxic pathways, besides the hypoxia-inducible response, may be effective for future anticancer therapies.
Characterizing linkage disequilibrium and evaluating imputation power of human genomic insertion-deletion polymorphisms
Authors: James T Lu, Yi Wang, Richard A Gibbs, Fuli Yu
Journal: Genome biology (2012)

Indels are an important cause of human variation and central to the study of human disease. The 1000 Genomes Project Low-Coverage Pilot identified over 1.3 million indels shorter than 50 bp, of which over 890 were identified as potentially disruptive variants. Yet, despite their ubiquity, the local genomic characteristics of indels remain unexplored.Herein we describe population- and minor allele frequency-based differences in linkage disequilibrium and imputation characteristics for indels included in the 1000 Genomes Project Low-Coverage Pilot for the CEU, YRI and CHB+JPT populations. Common indels were well tagged by nearby SNPs in all studied populations, and were also tagged at a similar rate to common SNPs. Both neutral and functionally deleterious common indels were imputed with greater than 95% concordance from HapMap Phase 3 and OMNI SNP sites. Further, 38 to 56% of low frequency indels were tagged by low frequency SNPs. We were able to impute heterozygous low frequency indels with over 50% concordance. Lastly, our analysis also revealed evidence of ascertainment bias. This bias prevents us from extending the applicability of our results to highly polymorphic indels that could not be identified in the Low-Coverage Pilot.Although further scope exists to improve the imputation of low frequency indels, our study demonstrates that there are already ample opportunities to retrospectively impute indels for prior genome-wide association studies and to incorporate indel imputation into future case/control studies.
Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections
Authors: Geraldine Taylor, Michelle Thom, Stefania Capone, Angiolo Pierantoni, Efrain Guzman, Rebecca Herbert, Elisa Scarselli, Federico Napolitano, Alessandro Giuliani, Antonella Folgori, Stefano Colloca, Riccardo Cortese, Alfredo Nicosia, Alessandra Vitelli
Journal: Science Translational Medicine (2015)

Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract disease in children and the elderly for which there is still no effective vaccine. We have previously shown that PanAd3-RSV, which is a chimpanzee adenovirus-vectored vaccine candidate that expresses a secreted form of the HRSV F protein together with the N and M2-1 proteins of HRSV, is immunogenic in rodents and nonhuman primates, and protects mice and cotton rats from HRSV challenge. Because the extent to which protection demonstrated in rodent models will translate to humans is unclear, we have exploited the calf model of bovine RSV (BRSV) infection, which mimics HRSV disease in children more closely than do experimental models of unnatural laboratory hosts, to evaluate the safety and efficacy of the PanAd3-RSV vaccine. We show that PanAd3-RSV alone and in combination with a modified vaccinia Ankara expressing the same HRSV antigens (MVA-RSV) induced neutralizing antibodies and cellular immunity in young seronegative calves and protected against upper and lower respiratory tract infection and pulmonary disease induced by heterologous BRSV challenge. There was no evidence either of enhanced pulmonary pathology or of enhanced respiratory disease in vaccinated calves after BRSV challenge. These findings support the continued evaluation of the vectored RSV vaccines in man.
Symptomatic Extranodal Rosai-Dorfman Disease Treated With Steroids, Radiation, and Surgery
Authors: Sachin S. Saboo, Jyothi P. Jagannathan, Katherine M. Krajewski, Kevin O'Regan, Jason L. Hornick, David C. Fisher, Nikhil Ramaiya
Journal: Journal of Clinical Oncology (2011)
Amputation and Mortality in New-Onset Diabetic Foot Ulcers Stratified by Etiology
Authors: Probal K. Moulik, Robert Mtonga, Geoffrey V. Gill
Journal: Diabetes Care (2003)

Foot ulcers and their complications are an important cause of morbidity and mortality in diabetes. The present study aims to examine the long-term outcome in terms of amputations and mortality in patients with new-onset diabetic foot ulcers in subgroups stratified by etiology.Patients presenting with new ulcers (duration <1 month) to a dedicated diabetic foot clinic between 1994 and 1998 were studied. Outcomes were determined until March 2000 (or death) from podiatry, hospital, and district registers. Baseline clinical examination was done to classify ulcers as neuropathic, ischemic, or neuroischemic. Five-year amputation and mortality rates were derived from Kaplan-Meier survival analysis curves.Of the 185 patients studied, 41% had peripheral vascular disease (PVD) and 61% had neuropathy; 45%, 16%, and 24% of patients had neuropathic, ischemic, and neuroischemic ulcers, respectively. The mean follow-up period was 34 months (range 1-65) including survivors and patients who died during the study period. Five-year amputation rates were higher for ischemic (29%) and neuroischemic (25%) than neuropathic (11%) ulcers. Five-year mortality was 45%, 18%, and 55% for neuropathic, neuroischemic, and ischemic ulcers, respectively. Mortality was higher in ischemic ulcers than neuropathic ulcers. On multivariate regression analysis, only increasing age predicted shorter survival time.All types of diabetic foot ulcers are associated with high morbidity and mortality. The increased mortality appears to be independent of factors increasing ulcer risk-that is, neuropathy and PVD-in patients with established foot ulcers.
Role of the Parasite-Derived Prostaglandin D2 in the Inhibition of Epidermal Langerhans Cell Migration during Schistosomiasis Infection
Authors: Véronique Angeli, Christelle Faveeuw, Olivier Roye, Josette Fontaine, Elisabeth Teissier, André Capron, Isabelle Wolowczuk, Monique Capron, François Trottein
Journal: The Journal of Experimental Medicine (2001)

Epidermal Langerhans cells (LCs) play a key role in immune defense mechanisms and in numerous immunological disorders. In this report, we show that percutaneous infection of C57BL/6 mice with the helminth parasite Schistosoma mansoni leads to the activation of LCs but, surprisingly, to their retention in the epidermis. Moreover, using an experimental model of LC migration induced by tumor necrosis factor (TNF)-α, we show that parasites transiently impair the departure of LCs from the epidermis and their subsequent accumulation as dendritic cells in the draining lymph nodes. The inhibitory effect is mediated by soluble lipophilic factors released by the parasites and not by host-derived antiinflammatory cytokines, such as interleukin-10. We find that prostaglandin (PG)D2, but not the other major eicosanoids produced by the parasites, specifically impedes the TNF-α–triggered migration of LCs through the adenylate cyclase–coupled PGD2 receptor (DP receptor). Moreover, the potent DP receptor antagonist BW A868C restores LC migration in infected mice. Finally, in a model of contact allergen-induced LC migration, we show that activation of the DP receptor not only inhibits LC emigration but also dramatically reduces the contact hypersensitivity responses after challenge. Taken together, we propose that the inhibition of LC migration could represent an additional stratagem for the schistosomes to escape the host immune system and that PGD2 may play a key role in the control of cutaneous immune responses.