tbuckley/cabot-search huggingface dataset:
Patient Advocacy in Clinical Ethics Consultation
Authors: Lisa M. Rasmussen
Journal: The American Journal of Bioethics (2012)

The question of whether clinical ethics consultants may engage in patient advocacy in the course of consultation has not been addressed, but it highlights for the field that consultants' allegiances, and the boundaries of appropriate professional practice, must be better understood. I consider arguments for and against patient advocacy in clinical ethics consultation, which demonstrate that patient advocacy is permissible, but not central to the practice of consultation. I then offer four recommendations for consultants who engage in patient advocacy, and consider the implications of this issue for the field.1
STATe-of-the-Art Approach: Using Oligonucleotide Decoys to Target the “Undruggable”
Authors: Priya Koppikar, Jacqueline Bromberg
Journal: Cancer Discovery (2012)

Abstract Summary: Sen and colleagues have shown for the first time the clinical application of an oligonucleotide decoy targeting the oncogenic transcription factor STAT3 for the treatment of head and neck tumors. Intratumoral injection of decoy effectively reduced the activity of STAT3 as evidenced by a decrease in several of its transcriptional targets. However, its low bioavailability makes them unacceptable for systemic therapy. Cyclization of the STAT3 decoy markedly increased its half-life while preserving specificity and showed significant antitumor activity upon systemic delivery in preclinical models of head and neck cancer. These findings have broad therapeutic implications for the treatment of many malignancies. Cancer Discov; 2(8); 670–2. ©2012 AACR. Commentary on Sen et al., p. 694.
Dose-dependent in vitro effect of recombinant human DNase on rheological and transport properties of cystic fibrosis respiratory mucus
Authors: JM Zahm, S Girod de Bentzmann, E Deneuville, C Perrot-Minnot, A Dabadie, F Pennaforte, M Roussey, S Shak, E Puchelle
Journal: European Respiratory Journal (1995)

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis (CF) respiratory mucus, to improve pulmonary function and to reduce the risk of respiratory tract infectious exacerbations, but its effect on mucus transportability has not so far been investigated. The dose-dependent effect of rhDNase was analysed in vitro on mucus transport rate (tr) by ciliary activity and by simulated cough (cough transport (ct)), as well as on mucus viscosity and surface properties. Purulent CF sputa (n = 15) were incubated for 30 min at 37 degrees C with either rhDNase at three different concentrations (final concentrations 0.2, 2 or 20 micrograms.ml-1 of mucus) or placebo. No significant dose-dependent effect of rhDNase on the mucociliary transport rate was observed when the samples wer statistically analysed together. However, in the larger group of mucus samples (n = 11) with a low initial mucociliary transport rate, the latter was improved at each rhDNase concentration (tr0.2 = 0.69, tr2 = 0.88 and tr20 = 0.87) as compared to placebo (trp = 0.58). In the smaller group of mucus samples (n = 4) with high initial transport rate, a decrease in mucociliary transport rate was observed, particularly at the highest concentration rhDNase assayed, i.e. 20 micrograms.ml-1 of mucus (tr20 = 0.58) as compared to placebo (trp = 0.86). The mucus cough transport was increased by rhDNase (ct0.2 = 25 mm, ct2 = 27.5 mm and ct20 = 31 mm) as compared to placebo (ctp = 23.5 mm).(ABSTRACT TRUNCATED AT 250 WORDS)
Factors that influence practice nurses to promote physical activity.
Authors: N McDowell, J McKenna, P J Naylor
Journal: British Journal of Sports Medicine (1997)

OBJECTIVE: To investigate what factors may influence practice nurses to promote physical activity. METHODS: Postal questionnaires were sent to all practice nurses in the county of Avon, UK in 1994. Specifically, the questionnaire survey explored whether patient, provider, and practice factors influenced practice nurses promotion behaviour. In addition, the stages of change model was used to measure current levels of promoting behaviour. RESULTS: A response rate of 80.9% was achieved. Over 80% of the sample reported currently promoting physical activity to some degree. "Promoting" nurses more frequently followed up all (new, established or targeted) patients' activity progress when compared with "restricted promoting" nurses (P &lt; 0.05). Nurses who engaged in regular exercise were more likely to encourage physical activity as a treatment than "irregularly active" nurses (P &lt; 0.05) for five of six clinical groups with the single exception of people with diabetes. CONCLUSIONS: This study shows that the two stage measures (activity promotion and personal behaviour) of the health care professional are associated with important differences in patient and practice factors for physical activity promotion. Further investigations into the content and quality of delivery are required before planning strategies to develop physical activity in the general practice.
Raynaud's phenomenon
Authors: J Belch
Journal: Cardiovascular Research (1997)

Raynaud's phenomenon (RP) may affect as many 20–30% of young women [1] and have an overall prevalence in the population of approximately 10% [2]. In the UK RP is the blanket term used to describe any form of cold related vasospasm and can be further subdivided into Raynaud's syndrome (RS) where there is an associated disorder and primary Raynaud's disease (RD) where there is not. In the USA the terminology most used is primary RP and secondary RP. Australasia uses RP and RS interchangeably and thus care must be taken with literature comparisons to ensure the different terminologies are used in a standard fashion. Most workers define their population in terms of CTD association, otherwise at the start of each paper and until a standard nomenclature is accepted, this practice should continue. By far the largest group of patients presenting to their primary care physician are those with the primary disorder. However, recent studies have shown that the phenomenon may pre-date systemic illness by up to two decades. Since the development of sensitive laboratory procedures, we now know that more than half of the patients referred to hospital because of RP will have an associated systemic disease [1, 3, 4]. There is a wide spectrum of disease associated with RS including those reported in the mystery cases (i.e., drug-induced RS), that associated with thromboangiitis obliterans and with occupational vibration exposure. The best recognised of the associated disorders are the connective tissue disorders (CTDs) and RS of occupational origin (Table 1).

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Table 1 
Conditions associated with Raynaud's phenomenon



RS accompanies systemic sclerosis (SSC) in 95% of cases and also in the majority of patients with mixed connective tissue disease (MCTD) (85%). Between 10–45% of patients with systemic lupus erythematosus also suffer vasospastic attacks as do 33% of Sjogren's syndrome patients …
Effect of Angiosonography to Monitor Response During Imatinib Treatment in Patients with Metastatic Gastrointestinal Stromal Tumors
Authors: Ugo De Giorgi, Camillo Aliberti, Giorgio Benea, Matteo Conti, Maurizio Marangolo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Gastrointestinal stromal tumor (GIST) metastases are typically intra-abdominal and hypervascular. We assessed the effect of angiosonography with a second-generation contrast agent to monitor response during imatinib treatment in patients with metastatic KIT+ GIST. Experimental Design: Ten consecutive patients with known advanced KIT+ GIST were investigated with angiosonography and computerized tomography (CT). We also monitored the serum levels of the major angiogenic growth factor, vascular endothelial growth factor. Results: Angiosonography showed a reduction in tumor vascularization of liver metastases during imatinib treatment in all cases. We observed a reduction in tumor vascularization before a reduction in tumor size. The tumor perfusion appeared reduced in the central part of the liver metastases. With a median follow-up of 18 months (range 3-33), a reduction in tumor vascularization was initially observed in all patients, but progressive disease was documented in four patients following imatinib treatment. CT documented tumor response according to standardized criteria in six patients, stable disease in four, and progressive disease according to angiosonography. The reduction of tumor perfusion at angiosonography correlated with the pseudocystic appearance at CT. The “nodule(s) within a mass” pattern of recurrence occurred in two patients with no difference observed between angiosonography and CT. Early decreasing serum vascular endothelial growth factor levels were observed in the two cases with higher pretreatment levels. Conclusions: Imatinib could induce antiangiogenic and/or antivascular effects in GIST, and this effect could be easily monitored with angiosonography. Angiosonography might be a useful complement for monitoring the therapeutic effect of imatinib in these patients.
Hotspots of mammalian chromosomal evolution
Authors: Jeffrey A Bailey, Robert Baertsch, W James Kent, David Haussler, Evan E Eichler
Journal: Genome biology (2004)

Chromosomal evolution is thought to occur through a random process of breakage and rearrangement that leads to karyotype differences and disruption of gene order. With the availability of both the human and mouse genomic sequences, detailed analysis of the sequence properties underlying these breakpoints is now possible.
Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape
Authors: Amar Gajjar, Daniel C. Bowers, Matthias A. Karajannis, Sarah Leary, Hendrik Witt, Nicholas G. Gottardo
Journal: Journal of Clinical Oncology (2015)

Pediatric neuro-oncology has undergone an exciting and dramatic transformation during the past 5 years. This article summarizes data from collaborative group and institutional trials that have advanced the science of pediatric brain tumors and survival of patients with these tumors. Advanced genomic analysis of the entire spectrum of pediatric brain tumors has heralded an era in which stakeholders in the pediatric neuro-oncology community are being challenged to reconsider their current research and diagnostic and treatment strategies. The incorporation of this new information into the next-generation treatment protocols will unleash new challenges. This review succinctly summarizes the key advances in our understanding of the common pediatric brain tumors (ie, medulloblastoma, low- and high-grade gliomas, diffuse intrinsic pontine glioma, and ependymoma) and some selected rare tumors (ie, atypical teratoid/rhabdoid tumor and CNS primitive neuroectodermal tumor). The potential impact of this new information on future clinical protocols also is discussed. Cutting-edge genomics technologies and the information gained from such studies are facilitating the identification of molecularly defined subgroups within patients with particular pediatric brain tumors. The number of evaluable patients in each subgroup is small, particularly in the subgroups of rare diseases. Therefore, international collaboration will be crucial to draw meaningful conclusions about novel approaches to treating pediatric brain tumors.
THE PUBLIC HEALTH INFRASTRUCTURE AND OUR NATION'S HEALTH
Authors: Edward L. Baker, Margaret A. Potter, Deborah L. Jones, Shawna L. Mercer, Joan P. Cioffi, Lawrence W. Green, Paul K. Halverson, Maureen Y. Lichtveld, David W. Fleming
Journal: Annual Review of Public Health (2005)

Threats to Americans' health-including chronic disease, emerging infectious disease, and bioterrorism-are present and growing, and the public health system is responsible for addressing these challenges. Public health systems in the United States are built on an infrastructure of workforce, information systems, and organizational capacity; in each of these areas, however, serious deficits have been well documented. Here we draw on two 2003 Institute of Medicine reports and present evidence for current threats and the weakness of our public health infrastructure. We describe major initiatives to systematically assess, invest in, rebuild, and evaluate workforce competency, information systems, and organizational capacity through public policy making, practical initiatives, and practice-oriented research. These initiatives are based on applied science and a shared federal-state approach to public accountability. We conclude that a newly strengthened public health infrastructure must be sustained in the future through a balancing of the values inherent in the federal system.
Higher Frequencies of GARP+CTLA-4+Foxp3+ T Regulatory Cells and Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Are Associated with Impaired T-Cell Functionality
Authors: Suresh Kalathil, Amit A. Lugade, Austin Miller, Renuka Iyer, Yasmin Thanavala
Journal: Cancer Research (2013)

Abstract The extent to which T-cell–mediated immune surveillance is impaired in human cancer remains a question of major importance, given its potential impact on the development of generalized treatments of advanced disease where the highest degree of heterogeneity exists. Here, we report the first global analysis of immune dysfunction in patients with advanced hepatocellular carcinoma (HCC). Using multi-parameter fluorescence-activated cell sorting analysis, we quantified the cumulative frequency of regulatory T cells (Treg), exhausted CD4+ helper T cells, and myeloid-derived suppressor cells (MDSC) to gain concurrent views on the overall level of immune dysfunction in these inoperable patients. We documented augmented numbers of Tregs, MDSC, PD-1+–exhausted T cells, and increased levels of immunosuppressive cytokines in patients with HCC, compared with normal controls, revealing a network of potential mechanisms of immune dysregulation in patients with HCC. In dampening T-cell–mediated antitumor immunity, we hypothesized that these processes may facilitate HCC progression and thwart the efficacy of immunotherapeutic interventions. In testing this hypothesis, we showed that combined regimens to deplete Tregs, MDSC, and PD-1+ T cells in patients with advanced HCC restored production of granzyme B by CD8+ T cells, reaching levels observed in normal controls and also modestly increased the number of IFN-γ producing CD4+ T cells. These clinical findings encourage efforts to restore T-cell function in patients with advanced stage disease by highlighting combined approaches to deplete endogenous suppressor cell populations that can also expand effector T-cell populations. Cancer Res; 73(8); 2435–44. ©2013 AACR.
Response of primary glioblastoma cells to therapy is patient specific and independent of cancer stem cell phenotype
Authors: Shaun D. Fouse, Jean L. Nakamura, C. David James, Susan Chang, Joseph F. Costello
Journal: Neuro-Oncology (2013)

Glioblastoma multiforme (GBM) contains a population of cells that exhibit stem cell phenotypes. These cancer stem cells (CSCs) may be a source of therapeutic resistance, although support for this important concept is limited. We determined whether early-passage GBM CSCs respond differently than patient-matched, genotypically similar non-CSCs to clinically relevant single or serial doses of temozolomide (TMZ), radiation therapy (XRT), or alternating TMZ treatment and XRT, which is the standard of care for GBM patients. Despite the phenotypic differences, including the presence of stem cell markers and formation of intracranial tumors, the CSCs and matched non-CSCs were equally resistant to TMZ in a majority of patients, using 2 independent assays. TMZ response was consistent with methylated O6-DNA methylguanine-methyltransferase (MGMT) and MGMT protein levels in both culture types. In contrast, CSCs were unexpectedly more responsive to XRT compared with matched non-CSCs from 2 patients despite having relatively equal resistance to TMZ. However, for the majority of culture pairs from individual patients, responses in CSCs were indistinguishable from non-CSC cultures. In our patient-matched primary cultures, response to TMZ was tightly linked to the individual tumor's MGMT status and independent of their phenotypic differences. TMZ and XRT together revealed no additive benefit compared with monotherapy for either culture type, in contrast to the notion that the CSC population is more resistant to XRT. If the tumor cell response in vitro mirrors therapeutic response in larger patient cohorts, these rapid assays in primary cultures could allow ­empirical selection of efficacious therapeutic agents on a patient-specific basis.
Global incidence of oesophageal cancer by histological subtype in 2012
Authors: Melina Arnold, Isabelle Soerjomataram, Jacques Ferlay, David Forman
Journal: Gut (2014)

<h3>Objective</h3> The two major histological types of oesophageal cancer—adenocarcinoma (AC) and squamous cell carcinoma (SCC)—are known to differ greatly in terms of risk factors and epidemiology. To date, global incidence estimates for individual subtypes are still lacking. This study for the first time quantified the global burden of oesophageal cancer by histological subtype. <h3>Design</h3> Where available, data from Cancer Incidence in Five Continents Vol. X (CI5X) were used to compute, age-specific, sex-specific and country-specific proportions of AC and SCC. Nine regional averages were computed for countries without CI5X data. The proportions were then applied to all oesophageal cancer cases from GLOBOCAN 2012 and age-standardised incidence rates calculated for both histological types. <h3>Results</h3> Worldwide, an estimated 398 000 SCCs and 52 000 ACs of the oesophagus occurred in 2012, translating to incidence rates of 5.2 and 0.7 per 100 000, respectively. Although SCCs were most common in South-Eastern and Central Asia (79% of the total global SCC cases), the highest burden of AC was found in Northern and Western Europe, Northern America and Oceania (46% of the total global AC cases). Men had substantially higher incidence than women, especially in the case of AC (male to female ratio AC: 4.4; SCC: 2.7). <h3>Conclusions</h3> These first global estimates of oesophageal cancer incidence by histology suggested a high concentration of AC in high-income countries with men being at much greater risk. This quantification of incidence will aid health policy makers to plan appropriate cancer control measures in the future.
Induction of Broad Cytotoxic T Cells by Protective DNA Vaccination Against Marburg and Ebola
Authors: Devon J Shedlock, Jenna Aviles, Kendra T Talbott, Gary Wong, Stephan J Wu, Daniel O Villarreal, Devin JF Myles, Maria A Croyle, Jian Yan, Gary P Kobinger, David B Weiner
Journal: Molecular Therapy (2013)

Marburg and Ebola hemorrhagic fevers have been described as the most virulent viral diseases known to man due to associative lethality rates of up to 90%. Death can occur within days to weeks of exposure and there is currently no licensed vaccine or therapeutic. Recent evidence suggests an important role for antiviral T cells in conferring protection, but little detailed analysis of this response as driven by a protective vaccine has been reported. We developed a synthetic polyvalent-filovirus DNA vaccine against Marburg marburgvirus (MARV), Zaire ebolavirus (ZEBOV), and Sudan ebolavirus (SUDV). Preclinical efficacy studies were performed in guinea pigs and mice using rodent-adapted viruses, whereas murine T-cell responses were extensively analyzed using a novel modified assay described herein. Vaccination was highly potent, elicited robust neutralizing antibodies, and completely protected against MARV and ZEBOV challenge. Comprehensive T-cell analysis revealed cytotoxic T lymphocytes (CTLs) of great magnitude, epitopic breadth, and Th1-type marker expression. This model provides an important preclinical tool for studying protective immune correlates that could be applied to existing platforms. Data herein support further evaluation of this enhanced gene-based approach in nonhuman primate studies for in depth analyses of T-cell epitopes in understanding protective efficacy. Marburg and Ebola hemorrhagic fevers have been described as the most virulent viral diseases known to man due to associative lethality rates of up to 90%. Death can occur within days to weeks of exposure and there is currently no licensed vaccine or therapeutic. Recent evidence suggests an important role for antiviral T cells in conferring protection, but little detailed analysis of this response as driven by a protective vaccine has been reported. We developed a synthetic polyvalent-filovirus DNA vaccine against Marburg marburgvirus (MARV), Zaire ebolavirus (ZEBOV), and Sudan ebolavirus (SUDV). Preclinical efficacy studies were performed in guinea pigs and mice using rodent-adapted viruses, whereas murine T-cell responses were extensively analyzed using a novel modified assay described herein. Vaccination was highly potent, elicited robust neutralizing antibodies, and completely protected against MARV and ZEBOV challenge. Comprehensive T-cell analysis revealed cytotoxic T lymphocytes (CTLs) of great magnitude, epitopic breadth, and Th1-type marker expression. This model provides an important preclinical tool for studying protective immune correlates that could be applied to existing platforms. Data herein support further evaluation of this enhanced gene-based approach in nonhuman primate studies for in depth analyses of T-cell epitopes in understanding protective efficacy.
What does brain damage tell us about the mechanisms of sleep?
Authors: B M Evans
Journal: Journal of the Royal Society of Medicine (2002)

Much is now known about the factors that influence the timing of sleep onset, such as the circadian rhythm and the length of time since a previous sleep1. There is also information about hormonal factors that influence sleeping and waking and the cerebral areas associated with them2. Less is known about the nerve fibres and cells involved in transferring the function of the brain and the body from a state of wakefulness to sleep and back again at least every twenty-four hours. This paper outlines what is known about these neural processes and suggests that information about them can be derived from the normal brain and also the damaged brain.