tbuckley/cabot-search huggingface dataset:
Abstract 5426: Assessing factors predictive of response to ADCs for companion diagnostic strategies
Authors: Joseph S. Krueger, Holger Lange, Steve Potts, David Young
Journal: Cancer Research (2014)

Abstract One premise of antibody-drug conjugates (ADC) is that the bound mAb-antigen complex on the cell surface will internalize and be metabolized by lysosomal proteases to release the free drug. Thus, the efficacy of an ADC is dependent not only on the presence of cell surface antigens, but also in-tact delivery of the conjugated drug, and an active pathway of receptor-mediated endocytosis. On a cellular level, the biological mechanisms behind receptor internalization and turnover have not been elucidated for novel therapeutic targets. On a tissue level, vascularization and hypoxic profile will affect delivery of the antibody into the tissue. Varying expression of the antibody target within the tissue (antigen density) will also affect the uptake of the ADC. Furthermore, the extracellular stability of the ADC may be affected by the activity of the various proteases in the tumor microenvironment (TME), outside of the lysozome. These concepts are critical for efficacy, and thus are especially important for companion diagnostic approaches (CDx) meant to predict response to ADCs. Thus, a predictive assay which would account not only for the degree of cell surface expression of the target, but also receptor internalization and potential effects of tumor microenvironment is required. To answer this need, Flagship Biosciences has invented several proprietary approaches for measuring critical properties of the therapeutic target on the cell surface or inside the cell, as well as properties of the TME which could be used to understand and predict efficacy to an ADC using FFPE biopsies. These quantitative pathology approaches are based on image analysis approaches which been designed specifically for ADC CDx programs to answer these critical questions: 1) Defining cell surface target expression independent of cytoplasmic expression; 2) Estimating receptor flux (turnover, internalization) based on staining profile; 3) Assessing critical factors in the TME which may affect delivery of the in-tact drug to the intracellular target; 4) Assaying vascular properties which may affect delivery of the drug; and 5) Heterogeneity of the target within a tumor. We are able to provide these as discrete evaluations or multiplex these evaluations for an integrative answer which can be derived from a typical clinical biopsy. Incorporation of these novel tools will enable ADC developers to create efficacy and patient stratification paradigms which incorporate the critical biological endpoints unique to ADCs. Citation Format: Joseph S. Krueger, Holger Lange, Steve Potts, David Young. Assessing factors predictive of response to ADCs for companion diagnostic strategies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5426. doi:10.1158/1538-7445.AM2014-5426
Acute Pulmonary Disease Caused by Phenytoin
Authors: JOHN R. MICHAEL
Journal: Annals of Internal Medicine (1981)

Acute pulmonary disease may occur as part of the hypersensitivity angitis produced by phenytoin sodium. The clinical features of the pulmonary involvement are fever, dyspnea, hypoxemia, and bilateral radiographic infiltrates. The pathologic process is an interstitial pneumonitis that appears reversible with cessation of the drug and treatment with corticosteroids.
Simple and rapid enzyme‐linked immunosorbent assay for the detection of hemoglobin C[α<sub>2</sub>β<sub>2</sub>6(A3)Glu → Lys] in cord blood using a monoclonal antibody
Authors: M. Shyamala, Charles R. Kiefer, Hugo Moscoso, Fred A. Garver
Journal: American Journal of Hematology (1990)

Abstract We have generated a murine hybridoma that secretes a monoclonal antibody (mAb) that is highly specific for hemoglobin C (HbC) [α 2 ß 2 6(A3)Glu→Lys] and shows no cross reactivity with HbA 2 , HbF 2 , HbS, HbE, or Hb O‐Arab. Using this antibody, we developed a simple and rapid enzyme linked immunosorbent assay (ELISA) technique for the detection of HbC in both adult and cord blood. The assay can be carried out using either whole blood samples or hemolysates. With as little as 10 μl/well of whole blood or 5 μg Hb/well of hemolysates, and, with dilutions of the antibody up to 10 −5 we were able to detect HbC unequivocally in cord blood samples. The ELISA procedure could detect HbC in proportions as low as 0.01%. This simple diagnostic test represents a technological advance in Hb identification and can easily be used for mass screening (96 samples in less than 45 min) to detect HbC. Furthermore, this assay, when employed in conjunction with an mAb specific for β6GLU of HbA, allows the discrimination between HbC homozygotes, heterozygotes, and normals.
Spatial frames for motor control would be commensurate with spatial frames for vision and proprioception, but what about control of energy flows?
Authors: Christopher C. Pagano, Geoffrey P. Bingham
Journal: Behavioral and Brain Sciences (1995)

Abstract The model identifies a spatial coordinate frame within which the sensorimotor apparatus produces movement. Its spatial nature simplifies its coupling with spatial reference frames used concurrently by vision and proprioception. While the positional reference frame addresses the performance of spatial tasks, it seems to have little to say about movements involving energy expenditure as the principle component of the task.
How relevant are fluid cognition and general intelligence? A developmental neuroscientist's perspective on a new model
Authors: Marko Wilke
Journal: Behavioral and Brain Sciences (2006)

Blair boldly proposes a model integrating different aspects of intelligence. Its real-life value can be put to the test by using programs designed to develop children's abilities in areas predicted to be crucial for minimizing adverse outcome. Until support from such programs is available, the model is an interesting hypothesis, albeit with remarkable possible repercussions. As such, it seems worthy of further development.
Comment on: Draznin et al. Pathways to Quality Inpatient Management of Hyperglycemia and Diabetes: A Call to Action. Diabetes Care 2013;36:1807–1814
Authors: Ketan Dhatariya, Mike Sampson, Chris Walton, Gerry Rayman, Esther Walden, Tracy Kelly
Journal: Diabetes Care (2013)

The initiative taken by the PRIDE investigators is to be commended and fully supported (1). They correctly identify gaps in the knowledge of how to manage inpatient dysglycemia, in particular hyperglycemia. However, as discussed recently by one of us, while there is plenty of evidence to show that hyperglycemia is associated with poor outcomes in hospitalized patients, there is almost no data to show that correcting the hyperglycemia is beneficial (2). The data that do exist are limited to cardiac surgery, which represent a small minority of hospitalized patients, while the data from the intensive care population are inconclusive.

In the U.K., three major organizations, the Association …
CANCER OF THE PROSTATE IN INFANTS AND CHILDREN
Authors: Matthew H. Griswold
Journal: JAMA (1952)

The average age at the time of admission to Connecticut hospitals of patients with malignant tumors of the prostate is about 70 years. Sarcoma of the prostate seems to be rare<sup>1</sup>and can occur at any age, although there is evidence that it has a predilection for the younger age groups, about 25% occurring within the first decade.<sup>2</sup>True cancer of the prostate, carcinoma, is seldom seen in infants and children, but other forms of malignant tumors may develop.<sup>3</sup> <h3>REPORT OF CASES</h3><h3>Case 1.—</h3> On July 22, 1944, a 2-year-old infant was admitted to a Connecticut hospital because of complete retention of urine. The history indicated that one month prior to admission the child suddenly began to complain of burning and frequency of urination. No previous history of urinary disturbance could be obtained. The child had learned to control his bladder. At that time the family physician
Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma
Authors: Iris Helfrich, Inka Scheffrahn, Sönke Bartling, Joachim Weis, Verena von Felbert, Mark Middleton, Masahi Kato, Süleyman Ergün, Hellmut G. Augustin, Dirk Schadendorf
Journal: The Journal of Experimental Medicine (2013)

Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor beta, and the late-stage maturity marker alpha smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this.
Classification of Cancer Patients
Authors: Edwin B. Cox
Journal: JAMA (1979)

APPROPRIATE description and classification of the clinical features of the patient with cancer are important prerequisites to clinical management and interpretation of treatment results. Classification serves at least three important functions. First, it is used to provide a prognosis for the individual patient, to establish a basis on which the patient, his family, and the physician may discuss the anticipated course of the disease. A second related use of classification is to guide the physician in his choice of therapy and assist the patient in understanding the potential benefits and risks of alternate forms of treatment. Finally, classification facilitates the use of stratification techniques prior to treatment allocation in clinical trials so that relatively homogeneous subgroups are available for comparison on alternative treatments. A classification system should be chosen according to its ability to fulfill these functions. <h3>Drawbacks of Staging Systems</h3> Staging, or classification according to the anatomical extent of
Into the depths of ataxia
Authors: Harry T. Orr
Journal: Journal of Clinical Investigation (2004)

Ataxia is a lethal neurological disease characterized by incoordination, postural abnormalities, difficulties with gait, and problems with clarity of speech. The etiology of ataxia is divided equally between hereditary and sporadic forms. Regardless of cause, the cerebellar cortex is often a target in ataxia. Thus, how a disruption in cerebellar cortex might lead to ataxia is of considerable interest. A report in this issue of the JCI links ataxia to enhanced hyperexcitability of neurons in the deep cerebellar nuclei.
Individual differences in evolutionary perspective: The games people play
Authors: Diane S. Berry, Stan A. Kuczaj
Journal: Behavioral and Brain Sciences (2000)

The emphasis on individual differences in evolutionary theories is important and has not received adequate attention. Strategic Pluralism makes a major contribution by addressing these issues, but like other evolutionary models (e.g., game theory) does not articulate the specific mechanisms underlying strategy selection. Specification of such mechanisms is an essential next step in the development of these models.
Veneers of Venereal Disease
Authors: C. N. Lester
Journal: JAMA (1965)

<h3>To the Editor:—</h3> I am moved to comment on the letter by Francis A. Pflum, MD, published inThe Journal, March 1, 1965 (<b>190</b>:767), under the title "Veneers of Venereal Disease." I think Dr. Pflum badly misses the essentials of the "campaign" against venereal disease and the "basic epidemiology." The basic epidemiologic principles of the control of any infectious disease are (1) prompt, adequate treatment of infected persons, and (2) equally prompt, rapid, and thorough investigation of source and spread. To these, in some instances of course, we add immunization of potential hosts, but this resource is not yet available for venereal disease. The most important single defect in the control of venereal disease at present is the failure of private physicians to report their cases and permit adequate interview of them for source and spread. If the average physician encounters a case of diptheria or smallpox, he is
How Sensitive is Sensitivity Training?
Authors: RALPH CRAWSHAW
Journal: American Journal of Psychiatry (1969)

The author describes three cases of emotional disturbance aggravated by sensitivity training. No quackery was detected, but the absence of ethical standards and an apparent abrogation of responsibility by the trainers and their sponsoring institutions was noted. A new process appears to be evolving under the guise of teaching, the author feels, which contributes to the destruction of freedom and attacks the substance of individual privacy and dignity.
Meta-analysis: Effect of Patient Self-testing and Self-management of Long-Term Anticoagulation on Major Clinical Outcomes
Authors: Hanna E. Bloomfield, Ange Krause, Nancy Greer, Brent C. Taylor, Roderick MacDonald, Indulis Rutks, Preetham Reddy, Timothy J. Wilt
Journal: Annals of Internal Medicine (2011)

Background: Anticoagulation with vitamin K antagonists reduces major thromboembolic complications in at-risk patients. With portable monitoring devices, patients can conduct their own international normalized ratio testing and dose adjustment at home. Purpose: To determine whether patient self-testing (PST), alone or in combination with self-adjustment of doses (patient self-management [PSM]), is associated with a reduction in thromboembolic complications and all-cause mortality without an increase in major bleeding events compared with usual care. Data Sources: MEDLINE and the Cochrane Central Register of Controlled Trials. Study Selection: Studies published in English from 1966 to October 2010 that enrolled outpatient adults receiving long-term (>3 months) oral anticoagulant therapy and that compared PST or PSM with care in a physician's office or an anticoagulation clinic were included. Data Extraction: Two investigators reviewed each article. Three investigators extracted data from articles that met inclusion criteria by using standardized data abstraction forms. Studies were assessed for quality, and the overall strength of evidence was rated for each clinical outcome. Data Synthesis: Twenty-two trials, with a total of 8413 patients, were included. In one half of the trials, fewer than 50% of potentially eligible persons successfully completed the training and agreed to be randomly assigned. Patients randomly assigned to PST or PSM had lower total mortality (Peto odds ratio [OR], 0.74 [95% CI, 0.63 to 0.87]), lower risk for major thromboembolism (Peto OR, 0.58 [CI, 0.45 to 0.75]), and no increased risk for a major bleeding event (Peto OR, 0.89 [CI, 0.75 to 1.05]). The strength of evidence was moderate for the bleeding and thromboembolism outcomes but low for mortality. Eight of 11 trials reported that patient satisfaction, quality of life, or both was better with PST or PSM than with usual care. Limitations: In one half of the trials, fewer than 50% of the potentially eligible patients were randomly assigned. Only 5 trials were considered high quality, and only 2 were conducted in the United States. No studies addressed whether PST or PSM is safe during the high-risk initiation phase. Conclusion: Compared with usual care, PST with or without PSM is associated with significantly fewer deaths and thromboembolic events, without increased risk for a serious bleeding event, for a highly selected group of motivated adult patients requiring long-term anticoagulation with vitamin K antagonists. Whether this care model is cost-effective and can be implemented successfully in typical U.S. health care settings requires further study. Primary Funding Source: U.S. Department of Veterans Affairs Health Services Research and Development Service.
Human rights and medical education
Authors: J. Leaning
Journal: BMJ (1997)

The Universal Declaration of Human Rights enters its 50th anniversary year in 1998. Around the world efforts are under way to celebrate this event and accelerate efforts to disseminate the contents of the declaration. These efforts are undertaken in recognition that progress has been at best uneven since that early morning of 10 December 1948 when the United Nations General Assembly formally adopted this document and thereby sought to enshrine in world consciousness a commitment to secure basic human rights around the world.

In 1948 there were 58 member nations of the UN; there are now 185. For this world community the declaration has acquired the status of international law and all governments can be held to its principles. Many other international treaties and charters have incorporated the language of the declaration or referred to it; and many national governments have included its language and principles in their constitutions.1

The declaration encompasses civil and political rights of individuals (in the first 21 articles); economic and social rights, including to health care (articles 22-27); and reciprocal obligations and constraints conferred by participation in a community (articles 28-30) (see p 1455).

There are several histories of this document which are relevant to those interested in the struggle to persuade human beings to find common ground and push off to higher reaches from it. Yet for the medical community in general, and for the subset who are medical students, the history is less crucial than is the fact of what this document now has become, 50 years from its making.

With astonishing durability it has withstood the test of time and has become the minimum consensus statement …
Three hundred years of the Royal College of Physicians of Edinburgh.
Authors: R H Girdwood
Journal: BMJ (1981)

During the week 6 to 11 September 1981 there will be celebra- tions in Edinburgh to commemorate the 300th anniversary of the granting to its college of physicians of a Royal Charter.Various related activities are taking place throughout the year, but over these six days, just after the Edinburgh Festival, arrangements have been made for a comprehensive programme of scientific and social events, starting with an ecumenical service in the historic Kirk of the Greyfriars.The next day the Lord Provost of Edinburgh will perform the opening ceremony, and Lady Antonia Fraser will inaugurate a historical symposium by giving a paper on "Charles II-the father of his people."Participants in the week's programme have been drawn not only from fellows and members but also from '*' representatives of other colleges and academies of medicine IVYthroughout the world, the University of Leiden, the Pharma- ceutical Society of Great Britain, the Royal Botanic Garden, and the Scottish Society of the History of Medicine.Each day _ there will be some form of entertainment, the Castle will be floodlit, and even the floral clock in Princes Street Gardens (fig 1) has been specially redesigned in honour of the occasion.FIG 1-Floral Clock, Edinburgh, 1981.In the seventeenth century, however, things did not run so smoothly, and, indeed, the physicians of Edinburgh were thwarted in their endeavours for more than 60 years.Early efforts to found a college
Effects of potassium iodide, colchicine and dapsone on the generation of polymorphonuclear leukocyte-derived oxygen intermediates
Authors: Y. MIYACHI, Y. NIWA
Journal: British Journal of Dermatology (1982)

Journal Article Effects of potassium iodide, colchicine and dapsone on the generation of polymorphonuclear leukocyte‐derived oxygen intermediates Get access Y. MIYACHI, Y. MIYACHI Department of Dermatology, Faculty of Medicine, Kyoto University, Sakyo‐ku, Kyoto 606 Search for other works by this author on: Oxford Academic Google Scholar Y. NIWA Y. NIWA Niwa Institute for Immunology, Kochi, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue 2, 1 August 1982, Pages 209–214, https://doi.org/10.1111/j.1365-2133.1982.tb00340.x Published: 01 August 1982 Article history Accepted: 04 November 1981 Published: 01 August 1982
Cicatricial pemphigoid treated with intravenous immunoglobulin
Authors: M.L. Urcelay, A. McQueen, W.S. Douglas
Journal: British Journal of Dermatology (1997)

Journal Article Cicatricial pemphigoid treated with intravenous immunoglobulin Get access M.L. Urcelay, M.L. Urcelay Department of Dermatology, Monklands Hospital, Airdrie, ML6 OJS, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. McQueen, A. McQueen Department of Dermatology, Monklands Hospital, Airdrie, ML6 OJS, U.K. Search for other works by this author on: Oxford Academic Google Scholar W.S. Douglas W.S. Douglas Department of Dermatology, Monklands Hospital, Airdrie, ML6 OJS, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 3, 1 September 1997, Pages 477a–477, https://doi.org/10.1111/j.1365-2133.1997.tb03770.x Published: 01 September 1997
Creating a Peaceful School Learning Environment: A Controlled Study of an Elementary School Intervention to Reduce Violence
Authors: Stuart W. Twemlow, Peter Fonagy, Frank C. Sacco, Martin L. Gies, Richard Evans, Russell Ewbank
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The impact of a manual-based antiviolence program on the learning climate in an elementary school over 4 years was compared with the outcome in a control school. METHOD: The two schools were matched for demographic characteristics. The intervention in the experimental school was based on zero tolerance for bullying; the control school received only regular psychiatric consultation. Disciplinary and academic achievement data were collected in both schools. RESULTS: The experimental school showed significant reductions in discipline referrals and increases in scores on standardized academic achievement measures. CONCLUSIONS: A low-cost antiviolence intervention that does not focus on individual pathology or interfere with the educational process may improve the learning environment in elementary schools.
Geoffrey Robert Peberdy
Authors: K. Schapira
Journal: BMJ (2002)

Former consultant psychiatrist Newcastle General Hospital (b Leicester 1921; q Dunelm 1937; DPM, MD, FRCPsych), d 11 August 2001.

Geoffrey served as a specialist psychiatrist in the Royal Army Medical Corps during the second world war and rose to the rank of major. He continued in psychiatry until his retirement in 1977. He had many research interests and published on a wide range of subjects, including psychosexual disorders, and hypnosis—which he used in his clinical work. In retirement he devoted his energy to church and village activities, and was an enthusiastic countryside guide. He leaves a wife, Mary; three daughters; and seven grandchildren.