tbuckley/cabot-search huggingface dataset:
Qualitative research methodologies: ethnography
Authors: S. Reeves, A. Kuper, B. D. Hodges
Journal: BMJ (2008)

The previous articles (there were 2 before this 1) in this series discussed several methodological approaches commonly used by qualitative researchers in the health professions. This article focuses on another important qualitative methodology: ethnography. It provides background for those who will encounter this methodology in their reading rather than instructions for carrying out such research. Ethnography is the study of social interactions, behaviours, and perceptions that occur within groups, teams, organisations, and communities. Its roots can be traced back to anthropological studies of small, rural (and often remote) societies that were undertaken in the early 1900s, when researchers such as Bronislaw Malinowski and Alfred Radcliffe-Brown participated in these societies over long periods and documented their social arrangements and belief systems. This approach was later adopted by members of the Chicago School of Sociology (for example, Everett Hughes, Robert Park, Louis Wirth) and applied to a variety of urban settings in their studies of social life. The central aim of ethnography is to provide rich, holistic insights into people’s views and actions, as well as the nature (that is, sights, sounds) of the location they inhabit, through the collection of detailed observations and interviews. As Hammersley states, “The task [of ethnographers] is to document the culture, the perspectives and practices, of the people in these settings. The aim is to ‘get inside’ the way each group of people sees the world.”1 Box 1 outlines the key features of ethnographic research. #### Box 1 Key features of ethnographic research2
Epidermal Growth Factor Receptor–Targeted Cytotoxin Inhibits Neointimal Hyperplasia In Vivo
Authors: Christopher J. Pastore, Jeffrey M. Isner, Patricia A. Bacha, Marianne Kearney, J. Geoffrey Pickering
Journal: Circulation Research (1995)

Abstract Smooth muscle cell accumulation is a key feature of restenosis that may be inhibited by the delivery of receptor-targeted cytotoxins. DAB 389 EGF is a recombinant fusion protein in which the receptor-binding domain of diphtheria toxin has been replaced by human epidermal growth factor (EGF). We investigated the effectiveness of DAB 389 EGF to inhibit neointimal hyperplasia in the balloon-injured rat carotid artery. Incubation of rat carotid arteries with 125 I-labeled EGF revealed extensive EGF binding sites in the neointima of balloon-injured arteries. Sixty rats subsequently received either saline or DAB 389 EGF (total dose, 0.15 mg) delivered immediately following balloon injury either systemically, via 14-day continuous osmotic pump infusion, or locally, via 30-minute intraluminal incubation. The effect of both treatment strategies was measured 2 weeks after injury by cross-sectional morphometric analysis of intimal area, the ratio of intimal/medial area (I/M), and the percent luminal narrowing (%LN). In addition, proliferative activity was assessed by immunostaining for the presence of the proliferating cell nuclear antigen (PCNA). Compared with controls, systemic delivery of fusion toxin significantly reduced intimal area, I/M, and %LN by 40%, 40%, and 29%, respectively. However, these rats exhibited 2% weight loss, indicating mild systemic toxicity. Local, intraluminal administration of DAB 389 EGF yielded a more pronounced reduction in intimal area, I/M, and %LN by 74%, 79%, and 72%, respectively. This inhibitory effect was preserved at 3 weeks postinjury, and PCNA immunostaining of locally treated arteries revealed a virtual absence of proliferative activity in the neointima and media at this timepoint. In contrast to systemically treated rats, rats receiving fusion toxin locally gained weight at a rate similar to controls, indicating avoidance of systemic toxicity. We conclude that DAB 389 EGF is a potent inhibitor of neointimal hyperplasia in vivo and that whereas an inhibitory effect may be achieved by systemic delivery, local delivery appears to be more potent, avoids systemic toxicity, and thus represents a feasible strategy to preempt restenosis.
Practice nurse health checks for adults with intellectual disabilities: a cluster-design, randomised controlled trial
Authors: Sally-Ann Cooper, Jill Morrison, Linda M Allan, Alex McConnachie, Nicola Greenlaw, Craig A Melville, Marion C Baltzer, Laura A McArthur, Claire Lammie, Gordon Martin, Eleanor A D Grieve, Elisabeth Fenwick
Journal: The Lancet Psychiatry (2014)
Evidence for marked disproportionate myocardial dysfunction in the septum in hypertensive left ventricular hypertrophy
Authors: R.W.W. Biederman, M. Doyle, A. Young, S. Thrupp, E. Kortright, G. Perry, J. Bella, R. Devereux, S. Oparil, G.M.S. Oparil, G.M. Pohost, L.J. Dell'Italia
Journal: Journal of the American College of Cardiology (1998)
Evidence Does Not Support Clinically Significant Lenalidomide-CCI-779 Interaction via P-Glycoprotein
Authors: Nianhang Chen, Claudia Kasserra, Gondi Kumar, Maria Palmisano
Journal: Journal of Clinical Oncology (2011)

studies. 4 We acknowledge that routine adjuvant chemotherapy for pT1/pT2 tumors is not standard, but this was exactly the justification for performing a controlled trial in which only the experimental (p53 altered) group received the treatment.A concern regarding toxicity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) was also raised; however, only one neutropenic fever was observed in patients treated with MVAC in this trial (data not shown).Furthermore, there are little data that indicated that serious toxicity is any worse with MVAC in the modern supportive care era than with typical regimens used for adjuvant therapy of patients with breast or colorectal cancer patients.We agree that the potential predictive value of p53 alteration for DNA damaging chemotherapy is not disproven by our data, 5 but like Dizdar and Demirci, 1 we suggest that any additional such studies be conducted in the context of a more comprehensive evaluation of the p53 DNA damage response pathway and perhaps other predictive biomarkers.Finally, although we agree that testing of predictive biomarkers for systemic therapy of bladder cancer may be more efficient in the neoadjuvant setting, we point out that there are significant complexities with the pathologic end points that such a trial would require, not the least of which is that none have been formally demonstrated to be a surrogate end point.
Systems Pharmacology to Predict Drug Toxicity: Integration Across Levels of Biological Organization
Authors: Jane P.F. Bai, Darrell R. Abernethy
Journal: The Annual Review of Pharmacology and Toxicology (2012)

To achieve sensitive and specific mechanism-based prediction of drug toxicity, the tools of systems pharmacology will be integrated using structured ontological approaches, analytics, mathematics, and statistics. Success of this effort is based on the assumption that a systems network that consists of drug-induced perturbations of physiological functions can be characterized. This network spans the hierarchy of biological organization, from gene to mRNA to protein to intracellular organelle to cell to organ to organism. It is populated with data from each of these levels of biological organization. These data, from disparate sources, include the published literature, drug development archives of all approved drugs and drug candidates that did not complete development, and various toxicity databases and adverse event reporting systems. The network contains interrelated genomics, transcriptomics, and metabolomics data, as well as organ and physiological functional data that are derived from the universe of information that describes and analyzes drug toxicity. Here we describe advances in bioinformatics, computer sciences, next-generation sequencing, and systems biology that create the opportunity for integrated systems pharmacology–based prediction of drug safety.
Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial
Authors: Mohammod J Chisti, Mohammed A Salam, Jonathan H Smith, Tahmeed Ahmed, Mark A C Pietroni, K M Shahunja, Abu S M S B Shahid, Abu S G Faruque, Hasan Ashraf, Pradip K Bardhan, None Sharifuzzaman, Stephen M Graham, Trevor Duke
Journal: The Lancet (2015)
Willis's Cerebri Anatome
Authors: William Feindel
Journal: Journal of the Royal Society of Medicine (2003)

The admirers of Thomas Willis are indebted to Dr O'Connor (March 2003 JRSM1) for adding further evidence that Cerebri Anatome (1664) reflects the religious and political practices of mid-17th-century England. Keele previously noted that the dedication of this famous book can leave no reasonable doubt that Willis carried through all his great work on the anatomy of the brain in a deeply religious spirit. Like William Harvey before him Willis saw nothing incongruous between religious sincerity and anatomical investigation.2 Willis dedicated all three of his works on the anatomy, pathology and clinical disorders of the nervous system to Gilbert Sheldon, Archbishop of Canterbury and his patron, patient and friend. After a devoted and pious life, his body was laid to rest in Westminster Abbey, a fitting tribute to the founder of neurology.3,4
Toll-Like Receptor 9 Affects Severity of IgA Nephropathy
Authors: Hitoshi Suzuki, Yusuke Suzuki, Ichiei Narita, Masashi Aizawa, Masao Kihara, Takahiro Yamanaka, Tatsuya Kanou, Hiroyasu Tsukaguchi, Jan Novak, Satoshi Horikoshi, Yasuhiko Tomino
Journal: Journal of the American Society of Nephrology (2008)

Environmental pathogens are suspected to aggravate renal injury in IgA nephropathy (IgAN), but neither underlying mechanisms nor specific exogenous antigens have been identified. In this study, a genome-wide scan of ddY mice, which spontaneously develop IgAN, was performed, and myeloid differentiation factor 88 (MyD88) was identified as a candidate gene for progression of renal injury (chi(2) = 21.103, P = 0.00017). For evaluation of the potential influence of environmental pathogens on progression of renal injury, ddY mice were housed in either conventional or specific pathogen-free conditions. Expression of genes encoding toll-like receptors (TLR) and the signaling molecule MyD88 were quantified by real-time reverse transcription-PCR in splenocytes. Although the housing conditions did not affect the prevalence of IgAN, the severity of renal injuries was higher in the conventionally housed group. Mice that had IgAN and were housed in conventional conditions had higher levels of TLR9 and MyD88 transcripts than mice that had IgAN and were housed in specific pathogen-free conditions. Furthermore, nasal challenge with CpG-oligodeoxynucleotides, which are ligands for TLR9, aggravated renal injury, led to strong Th1 polarization, and increased serum and mesangial IgA. For investigation of whether these results may be generalizable to humans, single-nucleotide polymorphisms in the TLR9 and MyD88 genes were analyzed in two cohorts of patients with IgAN; an association was observed between TLR9 polymorphisms and disease progression. In summary, these findings suggest that activation of the TLR9/MyD88 pathway by common antigens may affect the severity of IgAN.
Class II histocompatibility antigen expression in human melanocytes transformed by Harvey murine sarcoma virus (Ha-MSV) and Kirsten MSV retroviruses.
Authors: A P Albino, A N Houghton, M Eisinger, J S Lee, R R Kantor, A I Oliff, L J Old
Journal: The Journal of Experimental Medicine (1986)

Human melanocytes infected with Ki-MSV or Ha-MSV, but not amphotropic MuLV, undergo a series of transformation-related changes that are characteristic of malignant melanoma. These are (a) expression of Ia antigens, in particular DP, DQ, and DR class II histocompatibility gene products, (b) a transformed morphology and ability to grow in soft agar, and (c) a 5-10-fold increase in the cell surface expression of GD3 ganglioside. However, other characteristics of melanoma, such as independence from specific growth factors and loss of adenosine deaminase binding protein were not observed. We conclude that viral ras oncogenes initiate early transformation events in melanocytes, and that Ia antigen expression is a transformation marker in this system.
Predictors of blood pressure fall with continuous positive airway pressure (CPAP) treatment of obstructive sleep apnoea (OSA)
Authors: G V Robinson, B A Langford, D M Smith, J R Stradling
Journal: Thorax (2008)

Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality. Randomised controlled trials have shown that, on average, treatment of OSA with continuous positive airway pressure (CPAP) reduces blood pressure (BP) by 3-5 mm Hg, although with considerable variation between individuals. No predictors of the change in BP with CPAP have been convincingly identified. This prospective study aimed to determine predictors of BP change, which might provide an insight into the aetiology of the raised BP seen in untreated OSA.Eighty-six patients with daytime hypersomnolence warranting treatment with CPAP were recruited. 24 h mean BP (24 hMBP), subjective sleepiness, fasting venous blood samples and anthropometric measurements were assessed at baseline and after 6 months of CPAP treatment.The mean (SD) 24 hMBP fell at 6 months from 101.0 (10.3) mm Hg to 96.1 (9.1) mm Hg (change -4.92 mm Hg (95% CI -2.8 to -7.1)). The Epworth Sleepiness Score (ESS) fell from a median of 16 (IQR 12-18) to 4 (2-7) with a mean fall of 9.7 (95% CI 8.6 to 10.8). Several factors correlated with the fall in 24 hMBP but, after allowing for the baseline 24 hMBP, only the fall in ESS and the body mass index (BMI) remained significant independent predictors (p = 0.006 and 0.007, respectively). There was also a correlation between the fall in 24 hMBP and the fall in pulse rate (r = 0.44, p<0.001). Baseline severity of OSA, overnight hypoxia, caffeine intake or being on antihypertensive drugs were not independent predictors of a fall in 24 hMBP.Improvement in hypersomnolence and the BMI are independent correlates of the fall in 24 hMBP following CPAP therapy. Markers of initial OSA severity did not predict the fall in 24 hMBP. This suggests that sleep fragmentation and its effects may be more important than hypoxia in the pathogenesis of the hypertension associated with human sleep apnoea.
Myocardial Structure and Function Differ in Systolic and Diastolic Heart Failure
Authors: Loek van Heerebeek, Attila Borbély, Hans W.M. Niessen, Jean G.F. Bronzwaer, Jolanda van der Velden, Ger J.M. Stienen, Wolfgang A. Linke, Gerrit J. Laarman, Walter J. Paulus
Journal: Circulation (2006)

To support the clinical distinction between systolic heart failure (SHF) and diastolic heart failure (DHF), left ventricular (LV) myocardial structure and function were compared in LV endomyocardial biopsy samples of patients with systolic and diastolic heart failure.Patients hospitalized for worsening heart failure were classified as having SHF (n=22; LV ejection fraction (EF) 34+/-2%) or DHF (n=22; LVEF 62+/-2%). No patient had coronary artery disease or biopsy evidence of infiltrative or inflammatory myocardial disease. More DHF patients had a history of arterial hypertension and were obese. Biopsy samples were analyzed with histomorphometry and electron microscopy. Single cardiomyocytes were isolated from the samples, stretched to a sarcomere length of 2.2 microm to measure passive force (Fpassive), and activated with calcium-containing solutions to measure total force. Cardiomyocyte diameter was higher in DHF (20.3+/-0.6 versus 15.1+/-0.4 microm, P<0.001), but collagen volume fraction was equally elevated. Myofibrillar density was lower in SHF (36+/-2% versus 46+/-2%, P<0.001). Cardiomyocytes of DHF patients had higher Fpassive (7.1+/-0.6 versus 5.3+/-0.3 kN/m2; P<0.01), but their total force was comparable. After administration of protein kinase A to the cardiomyocytes, the drop in Fpassive was larger (P<0.01) in DHF than in SHF.LV myocardial structure and function differ in SHF and DHF because of distinct cardiomyocyte abnormalities. These findings support the clinical separation of heart failure patients into SHF and DHF phenotypes.
Effectiveness of Bystander-Initiated Cardiac-Only Resuscitation for Patients With Out-of-Hospital Cardiac Arrest
Authors: Taku Iwami, Takashi Kawamura, Atsushi Hiraide, Robert A. Berg, Yasuyuki Hayashi, Tatsuya Nishiuchi, Kentaro Kajino, Naohiro Yonemoto, Hidekazu Yukioka, Hisashi Sugimoto, Hiroyuki Kakuchi, Kazuhiro Sase, Hiroyuki Yokoyama, Hiroshi Nonogi
Journal: Circulation (2007)

Background— Previous animal and clinical studies suggest that bystander-initiated cardiac-only resuscitation may be superior to conventional cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrests. Our hypothesis was that both cardiac-only bystander resuscitation and conventional bystander CPR would improve outcomes from out-of-hospital cardiac arrests of ≤15 minutes’ duration, whereas the addition of rescue breathing would improve outcomes for cardiac arrests lasting &gt;15 minutes. Methods and Results— We carried out a prospective, population-based, observational study involving consecutive patients with emergency responder resuscitation attempts from May 1, 1998, through April 30, 2003. The primary outcome measure was 1-year survival with favorable neurological outcome. Multivariable logistic regression analysis was performed to evaluate the relationship between type of CPR and outcomes. Among the 4902 witnessed cardiac arrests, 783 received conventional CPR, and 544 received cardiac-only resuscitation. Excluding very-long-duration cardiac arrests (&gt;15 minutes), the cardiac-only resuscitation yielded a higher rate of 1-year survival with favorable neurological outcome than no bystander CPR (4.3% versus 2.5%; odds ratio, 1.72; 95% CI, 1.01 to 2.95), and conventional CPR showed similar effectiveness (4.1%; odds ratio, 1.57; 95% CI, 0.95 to 2.60). For the very-long-duration arrests, neurologically favorable 1-year survival was greater in the conventional CPR group, but there were few survivors regardless of the type of bystander CPR (0.3% [2 of 624], 0% [0 of 92], and 2.2% [3 of 139] in the no bystander CPR, cardiac-only CPR, and conventional CPR groups, respectively; P &lt;0.05). Conclusions— Bystander-initiated cardiac-only resuscitation and conventional CPR are similarly effective for most adult out-of-hospital cardiac arrests. For very prolonged cardiac arrests, the addition of rescue breathing may be of some help.
Rose succeeds where Wilson fails
Authors: Jerry Hirsch
Journal: Behavioral and Brain Sciences (1999)

Rose's accomplishment in combining ontological unity with epistemological diversity contrasts it with Wilson's failure in overemphasizing the former and not appreciating the latter. This commentary cites the two most authoritative discussions of the inapplicability of heritability to human data, corrects several historical errors or inaccuracies in genetics, and criticizes the characterizations of Jacques Loeb and Robert Plomin.
Inhibition of ADP Ribosylation Prevents and Cures <i>Helicobacter</i>-Induced Gastric Preneoplasia
Authors: Isabella M. Toller, Matthias Altmeyer, Esther Kohler, Michael O. Hottiger, Anne Müller
Journal: Cancer Research (2010)

Abstract Gastric adenocarcinoma develops as a consequence of chronic inflammation of the stomach lining that is caused by persistent infection with the bacterium Helicobacter pylori. Gastric carcinogenesis progresses through a sequence of preneoplastic lesions that manifest histologically as atrophic gastritis, intestinal metaplasia, and dysplasia. We show here in several preclinical models of Helicobacter-induced atrophic gastritis, epithelial hyperplasia, and metaplasia that the inhibition of ADP ribosylation by the small-molecule inhibitor PJ34 not only prevents the formation of gastric cancer precursor lesions, but also efficiently reverses preexisting lesions. PJ34 exerts its chemopreventive and therapeutic effects by impairing Helicobacter-specific T-cell priming and TH1 polarization in the gut-draining mesenteric lymph nodes. The subsequent infiltration of pathogenic T cells into the gastric mucosa and the ensuing gastric T cell–driven immunopathology are prevented efficiently by PJ34. Our data indicate that PJ34 directly suppresses T-cell effector functions by blocking the IFN-γ production of mesenteric lymph node T cells ex vivo. Upon exposure to PJ34, purified T cells failed to synthesize ADP-ribose polymers and to activate the transcription of genes encoding IFN-γ, interleukin 2, and the interleukin 2 receptor α chain in response to stimuli such as CD3/CD28 cross-linking or phorbol 12-myristate 13-acetate/ionomycin. The immunosuppressive and chemoprotective effects of PJ34 therefore result from impaired T-cell activation and TH1 polarization, and lead to the protection from preneoplastic gastric immunopathology. In conclusion, ADP-ribosylating enzymes constitute novel targets for the treatment of Helicobacter-associated gastric lesions predisposing infected individuals to gastric cancer and may also hold promise for the treatment of other T cell–driven chronic inflammatory conditions and autoimmune pathologies. Cancer Res; 70(14); 5912–22. ©2010 AACR.
Influence of the Coanda effect on color Doppler jet area and color encoding. In vitro studies using color Doppler flow mapping.
Authors: K Chao, V A Moises, R Shandas, T Elkadi, D J Sahn, R Weintraub
Journal: Circulation (1992)

We studied surface adherence and its effects on color Doppler jet areas and color encoding in an in vitro model with a noncompliant receiving chamber into which a steady flow jet was directed parallel to either a straight or a curved surface adjacent to and 4 mm away from the inflow orifice (1.50 mm2) with the control condition being a free jet matched for flow rates and driving pressures. Jets were imaged perpendicular to the plane of the surface, the plane in which most clinical images of jet-surface interactions are obtained. Ten different flow rates ranging from 0.13 to 0.30 l/min were used. Surface-adherent jet areas were smaller than control jets for every driving pressure-volume combination (paired t test, p less than 0.01). Computer analysis of color Doppler images showed more green and blue (reverse flow) pixels on the surface side of the adherent jets than the control jets (p less than 0.05), suggesting that viscous energy loss and flow deceleration and reversal play a role in the jet-surface interaction. Analysis of variance demonstrated that linear regression slopes of flow rate versus jet area for surface jets were lower (slopes, 11-21 cm2/l/min; r = 0.95-0.97) than those for the control (slope, 33 cm2/l/min; r = 0.97) (p less than 0.0001). Surface adherence (Coanda effect) influences jet size and color encoding, causing smaller color Doppler jet areas and greater variance and reverse velocity encoding.