tbuckley/cabot-search huggingface dataset:
Radiotherapy in Cancer of the Thoracic Oesophagus
Authors: J. A. C. Fleming
Journal: Thorax (1947)

The successful treatment of malignant tumours by radiotherapy is limited by technical and biological factors.TECHNICAL FACTORS Improvements in design and construction of apparatus, greater precision in the measure- ment of radiation dose not only on the body surface but also at depths below the surface, and the greater penetration of both gamma and x rays achieved by the use of larger quantities of radium and of x-ray units operating at higher voltages have all contributed to an ever-increasing efficiency in technique.Although there is room for further improvement, particularly since the recent advent of x-ray units operating at several million volts and awaiting full clinical trial, it has been possible for some time to deliver to any tumour a high dose of radiation with reasonable accuracy, irrespective of the position of that tumour in the body. BIOLOGICAL FACTORSIn spite of the important technical advances mentioned above, cure of cancer arising in deep-seated thoracic organs has seldom been achieved, because success is prejudiced by certain biological factors.These are chiefly the radiosensitivity and the extent of the tumour.That different types of tumour vary in their radiosensitivity has been well known for many years, but it is also apparent that a variation exists in the radiosensitivity of malignant growths which arise from similar epitheium; moreover, the investigations of Gltcksmann and Spear (1945) have shown that early disappearance of a squamous epithelioma, as a result of irradiation, may be followed by a recurrence due to the persistence in the irradi- ated stroma of resistant cells which later multiply.The publications of Gltilcksmann and Spear referred only to investigations carried out in relation to squamous epithelioma arising in certain accessible sites, but it is reasonable to assume that a similar factor operates in deep-seated cancer.The extent to which a tumour has spread when the patient is first examined is of great importance to the radiotherapist.Most epithelial tumours are of moderate radiosensitivity and require a heavy dose of radiation if lasting response is to be anticipated.When the cells of a deep-seated epithelial neoplasm have infiltrated into the adjacent tissues to such an extent that the volume of the growth does not exceed 70 to 100 c.cm., it is possible to deliver to this block of tissue a dose of radiation of a magnitude which would afford a chance of cure.As the volume of tissac requiring irradiation increases, the constitutional effects upon the patient resulting from such irradiation become increasingly severe, until a point is reached when it is not possible to deliver a lethal dose to the entire volume of tissue on July 19, 2023 by guest.
Group theory and geometric psychology
Authors: William C. Hoffman
Journal: Behavioral and Brain Sciences (2001)

The commentary is in general agreement with Roger Shepard's view of evolutionary internalization of certain procedural memories, but advocates the use of Lie groups to express the invariances of motion and color perception involved. For categorization, the dialectical pair is suggested. [Barlow; Hecht; Kubovy &amp; Epstein; Schwartz; Shepard; Todorovič]
Seeing the same GP each time can reduce emergency department attendance, review finds
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Enabling patients to see the same GP every time they visit their doctor’s surgery is associated with reduced emergency department attendance and fewer hospital admissions, a review has concluded.1

Researchers from the University of Bristol conducted a systematic review to try to identify features that could help stem the rise in unscheduled care in the United Kingdom. They looked at 48 studies from around the world that examined potential factors influencing emergency department visits and emergency admissions. The review, published in …
Age-Related Prevalence of Anal Cancer Precursors in Homosexual Men: The EXPLORE Study
Authors: Peter V. Chin-Hong, Eric Vittinghoff, Ross D. Cranston, Lynette Browne, Susan Buchbinder, Grant Colfax, Maria Da Costa, Teresa Darragh, Dana Jones Benet, Franklyn Judson, Beryl Koblin, Kenneth H. Mayer, Joel M. Palefsky
Journal: JNCI Journal of the National Cancer Institute (2005)

Infection with human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In the United States, the incidence of anal cancer among men who have sex with men (MSM) is higher than the incidence of cervical cancer among women. Anal squamous intraepithelial lesions (ASILs) are anal cancer precursors comprising low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). The prevalence of cervical cancer precursor lesions peaks at around 30 years of age. The age-related prevalence of ASILs in HIV-negative MSM is unknown.We conducted a cross-sectional analysis of the prevalence and determinants of ASILs in 1262 HIV-negative MSM aged 18-89 years recruited from four U.S. cities. Anal cytology and behavioral data were obtained. Anal HPV infection status was assessed by polymerase chain reaction. Independent predictors of ASILs were identified using logistic regression. All statistical tests were two-sided.The prevalences of LSILs and HSILs were 15% and 5%, respectively, and did not change with age. In a multivariable analysis, the risk of LSILs was associated with having more than five male receptive anal sex partners (P = .03), any use of poppers (alkyl nitrites) in the previous 6 months [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.1 to 2.5; P = .03] or use of injection drugs two or more times per month during the previous 6 months [OR = 19, 95% CI = 1.3 to 277; P = .03], older age at first receptive anal intercourse (P = .004), and infection with a greater number of HPV types (P < .001 for linear trend). The risk of HSILs was associated with any anal HPV infection (OR = 3.2, 95% CI = 1.1 to 9.4; P = .039) and infection with an increasing number of HPV types (P < .001 for linear trend).Sexually active HIV-negative MSM in all age groups have a high prevalence of ASILs, possibly reflecting their ongoing sexual exposure to HPV.
Bone Marrow NK1.1− and NK1.1+ T Cells Reciprocally Regulate Acute Graft versus Host Disease
Authors: Defu Zeng, David Lewis, Sussan Dejbakhsh-Jones, Fengshuo Lan, Marcos García-Ojeda, Richard Sibley, Samuel Strober
Journal: The Journal of Experimental Medicine (1999)

Sorted CD4+ and CD8+ T cells from the peripheral blood or bone marrow of donor C57BL/6 (H-2b) mice were tested for their capacity to induce graft-versus-host disease (GVHD) by injecting the cells, along with stringently T cell–depleted donor marrow cells, into lethally irradiated BALB/c (H-2d) host mice. The peripheral blood T cells were at least 30 times more potent than the marrow T cells in inducing lethal GVHD. As NK1.1+ T cells represented &amp;lt;1% of all T cells in the blood and ∼30% of T cells in the marrow, the capacity of sorted marrow NK1.1− CD4+ and CD8+ T cells to induce GVHD was tested. The latter cells had markedly increased potency, and adding back marrow NK1.1+ T cells suppressed GVHD. The marrow NK1.1+ T cells secreted high levels of both interferon γ (IFN-γ) and interleukin 4 (IL-4), and the NK1.1− T cells secreted high levels of IFN-γ with little IL-4. Marrow NK1.1+ T cells obtained from IL-4−/− rather than wild-type C57BL/6 donors not only failed to prevent GVHD but actually increased its severity. Together, these results demonstrate that GVHD is reciprocally regulated by the NK1.1− and NK1.1+ T cell subsets via their differential production of cytokines.
Whole System Demonstrator trial: policy, politics, and publication ethics
Authors: T. Greenhalgh
Journal: BMJ (2012)

Limitations listed for the Whole System Demonstrator trial of telehealth did not include close involvement of the funder in its design and execution. Under “Finances,” the authors state: “The Department of Health reviewed the protocol . . . and provided project manager support.”1

The Department of Health makes greater claims for its …
Distal phenylalanine modification for enhancing cellular delivery of fluorophores, proteins and quantum dots by cell penetrating peptides
Authors: E.J. Sayers, K. Cleal, N.G. Eissa, P. Watson, A.T. Jones
Journal: Journal of Controlled Release (2014)

For cell penetrating peptides (CPPs) to fulfil their promise as effective delivery vectors we need a better understanding of their mechanisms of cell binding and uptake. This is especially the case when they are linked to different types of cargo. Here we describe new studies based on our previous findings suggesting that, for peptide-CPP chimeras, distal hydrophobic residues upstream of the CPP sequence can have profound effects on the way they interact with cells. We studied peptides bearing an N-terminal Glycine or Phenylalanine linked via a neutral and flexible bridging group, SGSGSGSG, to three well-studied CPPs: octaarginine, penetratin and TP10. Using a combination of flow cytometry, live-cell imaging and image analysis we examined the effects of this single amino acid change on binding and uptake of Alexa488-fluorophore, bovine serum albumin and quantum dot cargoes. The influence of the glycine-phenylalanine switch for fluorophore delivery was most dramatic in TP10, increasing cellular uptake by 4.4 and 9.9 fold in non-adherent and adherent cells, respectively. Only penetratin showed effective uptake of bovine serum albumin with the phenylalanine variant showing an increase of 1.6 fold over the glycine variant. The uptake of quantum dots was most efficiently demonstrated by octaarginine, with the glycine variant increasing uptake 4.8 fold and the phenylalanine variant increasing uptake 9.5 fold over quantum dots alone. Overall the data demonstrate that hydrophobicity distal to the CPP could be utilised to enhance their capacity to bind to the cell membrane and deliver a range of macromolecules to the insides of cells.
Pindolol Augmentation of Selective Serotonin Reuptake Inhibitors: PET Evidence That the Dose Used in Clinical Trials Is Too Low
Authors: Eugenii A. Rabiner, Zubin Bhagwagar, Roger N. Gunn, Peter A. Sargent, Christopher J. Bench, Philip J. Cowen, Paul M. Grasby
Journal: American Journal of Psychiatry (2001)

Positron emission tomography (PET) was used to examine whether the dose of pindolol used to augment antidepressant medication achieves a significant occupancy of the serotonin type 1A (5-HT(1A)) autoreceptor in depressed patients receiving medication.The authors examined eight depressed patients on one of two regimes of pindolol (2.5 mg t.i.d. and 5.0 mg t.i.d.) with PET and [11C]WAY-100635.The 5-mg t.i.d. regime achieved a modest (19%) but significant occupancy of the 5-HT(1A) autoreceptor, while the regime used in the vast majority of clinical trials (2.5 mg t.i.d.) did not achieve a significant occupancy.The dose of pindolol used in clinical trials is suboptimal and may explain the inconsistent results. Therefore, a thorough test of pindolol's efficacy will necessitate doses higher than those used in present clinical trials.
The language of rheumatology. I: Nomenclature and coding.
Authors: D Symmons, S Sant
Journal: Annals of the Rheumatic Diseases (1996)

Effective communication is essential in an efficient health service.Increasingly, such communication involves the electronic transfer of data from one computer system to another.The Information Management Group (IMG) of the National Health Service (NHS) plans eventually to introduce an electronic patient record which will be accessible wherever the patient is treated.If this plan is to function effectively, then all patient based information collected within the NHS must be consistent, unambiguous, and exchangeable.Thus it has become important to consider very carefully the way in which medical terms are coded and then grouped.This paper deals with the development of a national thesaurus of agreed clinical terms (the Clinical Terms Project) and the assignment of computer codes (Read codes) to these terms.A subsequent paper will discuss the need for systems of classification (such as International Classification of Disease (ICD) 10) and grouping (such as healthcare resource groups) for statistical analysis, research, costing, and resource management.
Effect of adrenalectomy on transport in the rat medullary thick ascending limb.
Authors: J Work, R L Jamison
Journal: Journal of Clinical Investigation (1987)

Previous studies in adrenalectomized (Adx) rats suggest that aldosterone may regulate ion transport in the ascending portion of Helen's loop. In order to examine directly the effect of adrenalectomy on transport, medullary thick ascending limb (Mtal) segments were isolated from Adx, Adx replaced with aldosterone (Adx + Ald, 0.5 micrograms X 100 g X body wt X d), and control Sprague-Dawley rats. Both net sodium and net chloride fluxes were significantly less in the Mtal segments from Adx rats compared with those in the control or Adx + Ald group. Physiologic levels of exogenous aldosterone increased net sodium chloride flux toward control values in the Adx + Ald group. Net potassium flux was not different among the three groups. We conclude that adrenalectomy impairs reabsorptive NaCl but not K transport in the Mtal, and that aldosterone restores this process. This reabsorptive defect may contribute to the urinary concentrating and diluting abnormality associated with adrenal insufficiency.
miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes
Authors: Li Qian, Linda W. Van Laake, Yu Huang, Siyuan Liu, Michael F. Wendland, Deepak Srivastava
Journal: The Journal of Experimental Medicine (2011)

Acute myocardial infarction (MI) involves necrotic and apoptotic loss of cardiomyocytes. One strategy to salvage ischemic cardiomyocytes is to modulate gene expression to promote cell survival without disturbing normal cardiac function. MicroRNAs (miRNAs) have emerged as powerful regulators of multiple cellular processes, including apoptosis, suggesting that regulation of miRNA function could serve a cardioprotective function. In this study, we report that miR-24 (miRNA-24) expression is down-regulated in the ischemic border zone of the murine left ventricle after MI. miR-24 suppresses cardiomyocyte apoptosis, in part by direct repression of the BH3-only domain–containing protein Bim, which positively regulates apoptosis. In vivo expression of miR-24 in a mouse MI model inhibited cardiomyocyte apoptosis, attenuated infarct size, and reduced cardiac dysfunction. This antiapoptotic effect on cardiomyocytes in vivo was partially mediated by Bim. Our results suggest that manipulating miRNA levels during stress-induced apoptosis may be a novel therapeutic strategy for cardiac disease.
Understanding the Biological Basis of Autofluorescence Imaging for Oral Cancer Detection: High-Resolution Fluorescence Microscopy in Viable Tissue
Authors: Ina Pavlova, Michelle Williams, Adel El-Naggar, Rebecca Richards-Kortum, Ann Gillenwater
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Autofluorescence imaging is increasingly used to noninvasively identify neoplastic oral cavity lesions. Improving the diagnostic accuracy of these techniques requires a better understanding of the biological basis for optical changes associated with neoplastic transformation in oral tissue. Experimental Design: A total of 49 oral biopsies were considered in this study. The autofluorescence patterns of viable normal, benign, and neoplastic oral tissue were imaged using high-resolution confocal fluorescence microscopy. Results: The autofluorescence properties of oral tissue vary significantly based on anatomic site and pathologic diagnosis. In normal oral tissue, most of the epithelial autofluorescence originates from the cytoplasm of cells in the basal and intermediate regions, whereas structural fibers are responsible for most of the stromal fluorescence. A strongly fluorescent superficial layer was observed in tissues from the palate and the gingiva, which contrasts with the weakly fluorescent superficial layer found in other oral sites. Upon UV excitation, benign inflammation shows decreased epithelial fluorescence, whereas dysplasia displays increased epithelial fluorescence compared with normal oral tissue. Stromal fluorescence in both benign inflammation and dysplasia drops significantly at UV and 488 nm excitation. Conclusion: Imaging oral lesions with optical devices/probes that sample mostly stromal fluorescence may result in a similar loss of fluorescence intensity and may fail to distinguish benign from precancerous lesions. Improved diagnostic accuracy may be achieved by designing optical probes/devices that distinguish epithelial fluorescence from stromal fluorescence and by using excitation wavelengths in the UV range.
Anti-CD22 ligand-blocking antibody HB22.7 has independent lymphomacidal properties and augments the efficacy of90Y-DOTA-peptide-Lym-1 in lymphoma xenografts
Authors: Joseph M. Tuscano, Robert T. O'Donnell, Laird A. Miers, Linda A. Kroger, David L. Kukis, Kathleen R. Lamborn, Thomas F. Tedder, Gerald L. DeNardo
Journal: Blood (2003)
Flexible bronchoscopy via the laryngeal mask: a new technique.
Authors: C J McNamee, B Meyns, K M Pagliero
Journal: Thorax (1991)

Malignant tracheal tumours often cause airway obstruction and this may be aggravated by vocal cord paralysis due to invasion of the recurrent laryngeal nerve. Conventional endoscopic techniques performed under general anaesthesia do not give a simultaneous view of vocal cord function and the distal airways. The technique of bronchoscopy via the laryngeal mask allowed full assessment of the cause of stridor in a patient with a malignant tracheal tumour that was causing airways obstruction and vocal cord paralysis.
Neural Mechanisms for Interacting with a World Full of Action Choices
Authors: Paul Cisek, John F. Kalaska
Journal: Annual Review of Neuroscience (2010)

The neural bases of behavior are often discussed in terms of perceptual, cognitive, and motor stages, defined within an information processing framework that was originally inspired by models of human abstract problem solving. Here, we review a growing body of neurophysiological data that is difficult to reconcile with this influential theoretical perspective. As an alternative foundation for interpreting neural data, we consider frameworks borrowed from ethology, which emphasize the kinds of real-time interactive behaviors that animals have engaged in for millions of years. In particular, we discuss an ethologically-inspired view of interactive behavior as simultaneous processes that specify potential motor actions and select between them. We review how recent neurophysiological data from diverse cortical and subcortical regions appear more compatible with this parallel view than with the classical view of serial information processing stages.
Argentinean court upholds fines against GSK and two doctors for malpractice during vaccine trial
Authors: A. Garcia Rada
Journal: BMJ (2012)

An Argentinean court has dismissed an appeal by the drug company GlaxoSmithKline (GSK) and upheld a fine of 400 000 pesos (£61 000; €73 000; $93 000) for failing to properly monitor a trial of the multivalent pneumococcal conjugate vaccine Synflorix. 

The judge has also upheld fines against two local doctors of 300 000 pesos each. Miguel Tregnaghi, the main coordinator of the trial in Argentina, was fined for failing to comply with good practice in the development of a clinical trial, and Hector Abate, the main investigator in Mendoza, one of the three regions where the study took place, was fined for administrative irregularities during patient selection and the collection of informed consent.

The penalty, the maximum that can be applied under national regulations for serious misconduct and the highest ever relating to clinical trials in the country, was imposed in 2009 by the Argentinean National Administration of Drugs, Food and Medical Technology (ANMAT) after detecting irregularities in the recruitment of …
RETRACTED: Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial
Authors: Hervé Bonnefoi, Anil Potti, Mauro Delorenzi, Louis Mauriac, Mario Campone, Michèle Tubiana-Hulin, Thierry Petit, Philippe Rouanet, Jacek Jassem, Emmanuel Blot, Véronique Becette, Pierre Farmer, Sylvie André, Chaitanya R Acharya, Sayan Mukherjee, David Cameron, Jonas Bergh, Joseph R Nevins, Richard D Iggo
Journal: The Lancet Oncology (2007)
Home hospitalisation of exacerbated chronic obstructive pulmonary disease patients
Authors: C. Hernandez, A. Casas, J. Escarrabill, J. Alonso, J. Puig-Junoy, E. Farrero, G. Vilagut, B. Collvinent, R. Rodriguez-Roisin, J. Roca
Journal: European Respiratory Journal (2003)

It was postulated that home hospitalisation (HH) of selected chronic obstructive pulmonary disease (COPD) exacerbations admitted at the emergency room (ER) could facilitate a better outcome than conventional hospitalisation. To this end, 222 COPD patients (3.2% female; 71±10 yrs (mean±sd)) were randomly assigned to HH (n=121) or conventional care (n=101). During HH, integrated care was delivered by a specialised nurse with the patient's free-phone access to the nurse ensured for an 8‐week follow-up period. Mortality (HH: 4.1%; controls: 6.9%) and hospital readmissions (HH: 0.24±0.57; controls: 0.38±0.70) were similar in both groups. However, at the end of the follow-up period, HH patients showed: 1) a lower rate of ER visits (0.13±0.43 versus 0.31±0.62); and 2) a noticeable improvement of quality of life (Δ St George's Respiratory Questionnaire (SGRQ), −6.9 versus −2.4). Furthermore, a higher percentage of patients had a better knowledge of the disease (58% versus 27%), a better self-management of their condition (81% versus 48%), and the patient's satisfaction was greater. The average overall direct cost per HH patient was 62% of the costs of conventional care, essentially due to fewer days of inpatient hospitalisation (1.7±2.3 versus 4.2±4.1 days). A comprehensive home care intervention in selected chronic obstructive pulmonary disease exacerbations appears as cost effective. The home hospitalisation intervention generates better outcomes at lower costs than conventional care.
<i>Treponema pallidum</i> Major Sheath Protein Homologue Tpr K Is a Target of Opsonic Antibody and the Protective Immune Response
Authors: Arturo Centurion-Lara, Christa Castro, Lynn Barrett, Caroline Cameron, Maryam Mostowfi, Wesley C. Van Voorhis, Sheila A. Lukehart
Journal: The Journal of Experimental Medicine (1999)

We have identified a family of genes that code for targets for opsonic antibody and protective immunity in T. pallidum subspecies pallidum using two different approaches, subtraction hybridization and differential immunologic screening of a T. pallidum genomic library. Both approaches led to the identification of a polymorphic multicopy gene family with predicted amino acid homology to the major sheath protein of Treponema denticola. One of the members of this gene family, tpr K, codes for a protein that is predicted to have a cleavable signal peptide and be located in the outer membrane of the bacterium. Reverse transcription polymerase chain reaction analysis of T. pallidum reveals that Tpr K is preferentially transcribed in the Nichols strain of T. pallidum. Antibodies directed to purified recombinant variable domain of Tpr K can opsonize T. pallidum, Nichols strain, for phagocytosis, supporting the hypothesis that this portion of the protein is exposed at the surface of the treponeme. Immunization of rabbits with the purified recombinant variable domain of Tpr K provides significant protection against infection with the Nichols strain of T. pallidum. This gene family is hypothesized to be central to pathogenesis and immunity during syphilis infection.