tbuckley/cabot-search huggingface dataset:
Somatically mutated forms of a major anti-p-azophenylarsonate antibody variable region with drastically reduced affinity for p-azophenylarsonate. By-products of an antigen-driven immune response?
Authors: T Manser, B Parhami-Seren, MN Margolies, ML Gefter
Journal: The Journal of Experimental Medicine (1987)

The pivotal role played by antigen in the clonal selection of B cells for initial participation in an immune response is well established. Antigen selective mechanisms ensure that antigen-binding antibodies are produced during all stages of the immune response. However, antibodies that lack specificity for the immunogen might also be produced during the course of an antigen-driven immune response . It has been suggested that, through idiotype-antiidiotype network interactions within the immune system, production of antibodies that lack specificity for the immunogen but that share idiotopes with antigen-binding antibodies could result (1). In addition, data obtained by a number of investigators suggest that somatic mutation of antibody V region genes occurs at a rate of 10(-3)/basepair/cell division in B cells participating in an immune response (2, 3). One outcome of such V region structural alteration could be antibodies that lack, or have drastically reduced affinity for the immunogen . We sought to identify and characterize some of the antibody by-products of the antigen-driven immune response that are expected to be created by the mechanisms described above.
Screening for Colorectal Cancer: A Targeted, Updated Systematic Review for the U.S. Preventive Services Task Force
Authors: Evelyn P. Whitlock, Jennifer S. Lin, Elizabeth Liles, Tracy L. Beil, Rongwei Fu
Journal: Annals of Internal Medicine (2008)

Background: In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended colorectal cancer screening for adults 50 years of age or older but concluded that evidence was insufficient to prioritize among screening tests or evaluate newer tests, such as computed tomographic (CT) colonography. Purpose: To review evidence related to knowledge gaps identified by the 2002 recommendation and to consider community performance of screening endoscopy, including harms. Data Sources: MEDLINE, Cochrane Library, expert suggestions, and bibliographic reviews. Study Selection: Eligible studies reported performance of colorectal cancer screening tests or health outcomes in average-risk populations and were at least of fair quality according to design-specific USPSTF criteria, as determined by 2 reviewers. Data Extraction: Two reviewers verified extracted data. Data Synthesis: Four fecal immunochemical tests have superior sensitivity (range, 61% to 91%), and some have similar specificity (97% to 98%), to the Hemoccult II fecal occult blood test (Beckman Coulter, Fullerton, California). Tradeoffs between superior sensitivity and reduced specificity occur with high-sensitivity guaiac tests and fecal DNA, with other important uncertainties for fecal DNA. In settings with sufficient quality control, CT colonography is as sensitive as colonoscopy for large adenomas and colorectal cancer. Uncertainties remain for smaller polyps and frequency of colonoscopy referral. We did not find good estimates of community endoscopy accuracy; serious harms occur in 2.8 per 1000 screening colonoscopies and are 10-fold less common with flexible sigmoidoscopy. Limitation: The accuracy and harms of screening tests were reviewed after only a single application. Conclusion: Fecal tests with better sensitivity and similar specificity are reasonable substitutes for traditional fecal occult blood testing, although modeling may be needed to determine all tradeoffs. Computed tomographic colonography seems as likely as colonoscopy to detect lesions 10 mm or greater but may be less sensitive for smaller adenomas. Potential radiation-related harms, the effect of extracolonic findings, and the accuracy of test performance of CT colonography in community settings remain uncertain. Emphasis on quality standards is important for implementing any operator-dependent colorectal cancer screening test.
Sports Ultrasound: a fundamental skill for sports medicine fellows moving forward
Authors: Rob Monaco
Journal: British Journal of Sports Medicine (2015)

The American Medical Society for Sports Medicine (AMSSM) has released a timely and comprehensive revision to its curriculum for ultrasound (US) training for fellowship programmes.1 It is a substantial improvement from the original 2010 document and creates a high standard for programmes. It confirms AMSSM's strong position that Sports US is a fundamental skill for providers moving forward. The document’s primary aim is to provide a pathway by which a sports medicine fellow can obtain sufficient Sports US training to become proficient in its outlined core competencies. Completion of this Sports US curriculum fulfils the American Institute of Ultrasound in Medicine's (AIUM) requirements to perform a musculoskeletal (MSK) US examination, and the pre-requisites for the American Registry for Diagnostic Medical Sonography's (ARDMS) MSK sonography certification examination. This curriculum is a key document as the field continues to deal with critical matters affecting sports medicine practitioners such as US certifications, accreditation, third party payer issues and the significant changes occurring in the graduate medical education process.

The document provides an excellent framework for fellowships to implement this curriculum through a variety of teaching modalities. They have skilfully outlined the basic structures and procedures to be learnt. One can argue on the inclusion/exclusion of some structures, but this would most likely vary by practitioner and be unlikely to achieve a full consensus. …
Dr John Wall
Authors: Keith M. Lindgren
Journal: JAMA (1979)

THE NAME Dr John Wall is familiar to all acquainted with English Worcester porcelain. The first and most famous period of manufacture in the Worcester Porcelain Co (now known as the Worcester Royal Porcelain Co, Ltd) has long borne the eponym of one of its founders, Dr John Wall. Notably, Dr Wall was a man best known in his day as a skilled physician. In fact, at the time of his death approximately 200 years ago in 1776, his memorial in Bath Abbey paid tribute to his talents in the "study and practice of a profession most beneficial to mankind"1 but made no mention of his association with the Worcester Porcelain Co. It is ironic that collectors of porcelain have remembered him, and the history of medicine has passed him by. Yet, his medical contributions were not trivial, and he was probably the first physician to offer autopsy evidence that
Europe plans to strengthen surveillance system for medical devices, MPs are told
Authors: A. O'Dowd
Journal: BMJ (2012)

A stronger system throughout Europe for checking medical devices and implants and how they are performing is likely to be agreed in revised regulations.

MPs on the parliamentary Science and Technology Committee heard some hints of what changes are coming from various witnesses on 13 June as part of their inquiry into regulation of medical implants.

The inquiry follows the scandal last year over discredited and now bankrupt French manufacturer Poly Implant Prosthese (PIP), which used non-medical grade silicone in breast implants that were given to around 47 000 women in the UK.1 2

Jacqueline Minor, director of consumer affairs at the European Commission, giving evidence, spoke about the commission’s plan to review the directives that make up the current medical device regulatory framework in Europe.

“These directives have been …
Homoeolog-specific retention and use in allotetraploid Arabidopsis suecica depends on parent of origin and network partners
Authors: Peter L Chang, Brian P Dilkes, Michelle McMahon, Luca Comai, Sergey V Nuzhdin
Journal: Genome biology (2010)

Allotetraploids carry pairs of diverged homoeologs for most genes. With the genome doubled in size, the number of putative interactions is enormous. This poses challenges on how to coordinate the two disparate genomes, and creates opportunities by enhancing the phenotypic variation. New combinations of alleles co-adapt and respond to new environmental pressures. Three stages of the allopolyploidization process - parental species divergence, hybridization, and genome duplication - have been well analyzed. The last stage of evolutionary adjustments remains mysterious. Homoeolog-specific retention and use were analyzed in Arabidopsis suecica (As), a species derived from A. thaliana (At) and A. arenosa (Aa) in a single event 12,000 to 300,000 years ago. We used 405,466 diagnostic features on tiling microarrays to recognize At and Aa contributions to the As genome and transcriptome: 324 genes lacked Aa contributions and 614 genes lacked At contributions within As. In leaf tissues, 3,458 genes preferentially expressed At homoeologs while 4,150 favored Aa homoeologs. These patterns were validated with resequencing. Genes with preferential use of Aa homoeologs were enriched for expression functions, consistent with the dominance of Aa transcription. Heterologous networks - mixed from At and Aa transcripts - were underrepresented. Thousands of deleted and silenced homoeologs in the genome of As were identified. Since heterologous networks may be compromised by interspecies incompatibilities, these networks evolve co-biases, expressing either only Aa or only At homoeologs. This progressive change towards predominantly pure parental networks might contribute to phenotypic variability and plasticity, and enable the species to exploit a larger range of environments.
Differential Effects of Neuropeptide Y on the Growth and Vascularization of Neural Crest–Derived Tumors
Authors: Joanna Kitlinska, Ken Abe, Lydia Kuo, Jennifer Pons, Muchieh Yu, Lijun Li, Jason Tilan, Lindsay Everhart, Edward W. Lee, Zofia Zukowska, Jeffrey A. Toretsky
Journal: Cancer Research (2005)

Abstract Neuropeptide Y (NPY) is a sympathetic neurotransmitter recently found to be potently angiogenic and growth promoting for endothelial, vascular smooth muscle and neuronal cells. NPY and its cognate receptors, Y1, Y2 and Y5, are expressed in neural crest–derived tumors; however, their role in regulation of growth is unknown. The effect of NPY on the growth and vascularization of neuroendocrine tumors was tested using three types of cells: neuroblastoma, pheochromocytoma, and Ewing's sarcoma family of tumors (ESFT). The tumors varied in expression of NPY receptors, which was linked to differential functions of the peptide. NPY stimulated proliferation of neuroblastoma cells via Y2/Y5Rs and inhibited ESFT cell growth by Y1/Y5-mediated apoptosis. In both tumor types, NPY receptor antagonists altered basal growth levels, indicating a regulatory role of autocrine NPY. In addition, the peptide released from the tumor cells stimulated endothelial cell proliferation, which suggests its paracrine angiogenic effects. In nude mice xenografts, exogenous NPY stimulated growth of neuroblastoma tumors, whereas it increased apoptosis and reduced growth of ESFT. However, in both tumors, NPY treatment led to an increase in tumor vascularization. Taken together, this is the first report of NPY being a growth-regulatory factor for neuroendocrine tumors, acting both by autocrine activation of tumor cell proliferation or apoptosis and by angiogenesis. NPY and its receptors may become targets for novel approaches in the treatment of these diseases, directed against both tumor cell proliferation and angiogenesis.
Randomised trial of once- or twice-daily MMX mesalazine for maintenance of remission in ulcerative colitis
Authors: M A Kamm, G R Lichtenstein, W J Sandborn, S Schreiber, K Lees, K Barrett, R Joseph
Journal: Gut (2008)

Maintenance treatment in ulcerative colitis should be as convenient as possible, to increase the chance of compliance. MMX mesalazine is a once-daily, high-strength (1.2 g/tablet) formulation of 5-aminosalicylic acid. This study evaluated the safety and efficacy of MMX mesalazine dosed once or twice daily as maintenance therapy in patients with ulcerative colitis.This multicentre, randomised, open-label trial enrolled patients with strictly defined clinical and endoscopic remission, immediately following an episode of mild to moderate ulcerative colitis. Patients were randomised to MMX mesalazine 2.4 g/day as a single (2x1.2 g tablet) or divided dose (1x1.2 g tablet twice daily) for 12 months.174 patients (37.9%; safety population n = 459) experienced 384 adverse events, the majority of which were mild or moderate in intensity. Eighteen patients (3.9%), nine in each group, experienced a total of 22 serious adverse events (10 in the once-daily and 12 in the twice-daily group). Most serious adverse events were gastrointestinal, experienced by 5 patients in the once-daily and 4 in the twice-daily group. At month 12, 64.4% (efficacy population, n = 451) of patients in the once-daily and 68.5% of patients in the twice-daily group were in clinical and endoscopic remission (p = 0.351). At month 12, 88.9% and 93.2% in each group, respectively, had maintained clinical remission (were relapse free).MMX mesalazine 2.4 g/day administered as a single or divided dose demonstrated a good safety profile, was well tolerated and was effective as maintenance treatment. High clinical and endoscopic remission rates can be achieved with once-daily dosing.NCT00151944.
Structure, expression, and genetic linkage of the mouse BCM1 (OX45 or Blast-1) antigen. Evidence for genetic duplication giving rise to the BCM1 region on mouse chromosome 1 and the CD2/LFA3 region on mouse chromosome 3.
Authors: Y W Wong, A F Williams, S F Kingsmore, M F Seldin
Journal: The Journal of Experimental Medicine (1990)

The mouse BCM1 (OX45, Blast-1) antigen has been cDNA cloned and sequenced to provide data supporting the view that BCM1, LFA3, and CD2 constitute a subgroup within the Ig superfamily. Mouse BCM1 is widely expressed on leukocytes and is likely to be anchored to the cell surface by a glycosyl-phosphatidylinositol anchor, as is the case for rat and human BCM1 antigen. Genetic linkage studies by recombination and pulse field analysis showed the BCM1 locus (Bcm-1) to be on distal mouse chromosome 1 and to be linked within 1,600 kb to the locus for an ATPase alpha chain gene (Atpa-3). A similar relationship was established between the human BCM1 locus (BCM1) and ATP1A2, and other markers on chromosome 1q. Conservation of genomic organization within a segment of human chromosome 1q and mouse chromosome 1 was demonstrated. A similar situation is seen in the region of the CD2 and LFA3 genes between mouse chromosome 3 and human chromosome 1p. Furthermore, the CD2/LFA3 genes are linked within 580 kb to Atpa-1/ATP1A1 genes to provide a parallel situation to the linkage between Bcm-1/BCM1 and Atpa-3/ATP1A2 on chromosomes 1 (mouse) and 1q (human). Taken together, the data suggest duplication of a chromosome region including the precursors of the genes for BCM1, CD2, and LFA3, and the ATPase genes to give rise to the linkage groups now observed. The duplicated regions may have stayed together on chromosome 1 in the human (with the insertion of a centromere), while in the mouse, the genetic regions are proposed to have become dispersed in the formation of chromosomes 1 and 3. CD2 and LFA3 are more dissimilar in sequence than BCM1 and LFA3, and if the precursors of the CD2 and LFA3 loci formed before the proposed chromosome segment duplication, then a gene encoding a recognizer molecule for BCM1 may exist in linkage with Bcm-1/BCM1 on chromosome 1 (mouse) and 1q (human).
Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients.
Authors: C L Shapiro, P H Hardenbergh, R Gelman, D Blanks, P Hauptman, A Recht, D F Hayes, J Harris, I C Henderson
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess the cardiac effects of two different cumulative doses of adjuvant doxorubicin and radiation therapy (RT) in breast cancer patients. PATIENTS AND METHODS Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyclophosphamide (500 mg/ m2) and doxorubicin (45 mg/m2) administered by intravenous bolus every 21 days. One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable in 276 patients (92%), with a median follow-up time of 6.0 years (range, 0.5 to 19.4). RESULTS The estimated risk (95% confidence interval) of cardiac events per 100 patient-years was significantly higher for CA10 than for CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P=.02]. The risk of cardiac events in CA5 patients, irrespective of the cardiac RT dose-volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study. In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P &lt; .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT. CONCLUSION Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT, was not associated with a significant increase in the risk of cardiac events. Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events. This appears to be especially true in patients treated with higher dose-volumes of cardiac RT. Larger studies with longer follow-up periods are needed to confirm these results.
Providing High-Quality and Affordable Intensive Care to Patients With Cancer: The Forgotten Brick in the Steep Wall of Costs Throughout the Cancer Care Continuum
Authors: Márcio Soares, Jorge I.F. Salluh
Journal: Journal of Clinical Oncology (2014)

TO THEEDITOR: The article by Shih et al 1 summarized the activities of the workshop entitled “Delivering Affordable Cancer Care in the 21st Century” led by the National Cancer Policy Forum of the Institute of Medicine. We congratulate the authors for such work that, as remarked by themselves, describes the challenges posed by the increasing costs of cancer care as being exemplary of those facing the health care system as whole, driven significantly by an aging population. Many concerns regarding the implications of the overuse and/or inappropriate use of screening and therapeutic strategies (in particular, the new therapies and technologies) for the costs of cancer care were raised by the authors. In addition, there is urgent need for improvements in supportive care for these patients. In this sense, the growing demand for intensive care represents another critical and forgotten facet of a complex problem. Intensive care–related costs in the United States (estimated at $82 billion in 2005) account for 13% of hospital expenditures and approximately 1% of the gross domestic product. 2 Although many targets to improve the provision of supportive care for patients with cancer were addressed, the discussion was restricted to palliative care. Nonetheless, intensive care units (ICUs) are essential for the supportive care of patients with cancer; up to one in five patients admitted to ICUs have cancer. 3 It is well known that survival of critically ill patients with cancer has improved significantly in recent years, even in the case of respiratory failure or severe infection. 3 In contrast, many patients with cancer are still inappropriately admitted to the ICU at the end of life. 4 However, because triage procedures are inaccurate even in specialized centers, 5 the broadening of ICU admission policies has been recommended by experts worldwide. 3 For all these reasons, the provision of intensive care to an increasing number of patients with cancer deserves to be included in any future agenda of care planning for these patients. Along this lines, future investigations should address the roles of fast-track postoperative care, planned recovery tracks, dehospitalization programs, rehabilitation, and hospice-based care for patients with cancer who survive ICU stays. Meanwhile, close collaboration between oncologists and intensivists coupled with the need to document patient preferences for aggressive therapies and end-of-life issues at the time of ICU admission are essential to avoid either depriving patients who may benefit from life-sustaining treatments or, conversely, inappropriately prolonging the end of life. Integrating palliative and intensive care is paramount to achieving high-quality and affordable supportive care that will meet the needs of patients, family members, care providers, and society.
Psychiatric Care of Federal Prisoners
Authors: LOREN H. ROTH, FRANK R. ERVIN
Journal: American Journal of Psychiatry (1971)

Data from a thorough review of the records of 1,154 prisoners in the federal penitentiary at Lewisburg, Pa., indicated that the psychiatric morbidity within this group was about 20 percent. The bulk of psychiatric effort with the prisoners studied took place at the pretrial or immediate posttrial stage; very few inmates were seen again specifically for treatment. The authors believe that more effort should be devoted to the psychiatric evaluation and treatment of the convicted offender; among other benefits, this may be an efficient method of screening for and preventing future violent behavior.
Toxicological Bases for the Setting of Health-Related Air Pollution Standards
Authors: M. Lippmann, R. B. Schlesinger
Journal: Annual Review of Public Health (2000)

▪ Abstract The development of air pollution standards ideally involves the integration of data from the disciplines of epidemiology, controlled clinical studies, and animal toxicology. Epidemiological studies show statistical associations between health outcomes and exposure; they cannot establish a definite cause-effect relationship. The utility of toxicological studies is to establish this relationship. Recently, there was simultaneous promulgation of a new National Ambient Air Quality Standard (NAAQS) for particulate matter &lt;2.5 μm in aerodynamic diameter (PM 2.5 ) and a revised NAAQS for ozone (O 3 ). The O 3 NAAQS was based, in part, on a sound foundation of toxicological data from controlled exposure studies in humans and animals. It also relied on epidemiological studies of hospital admissions for respiratory diseases. Such studies also served as important bases for the new PM 2.5 NAAQS. However, the most influential bases for the PM NAAQS were the numerous and generally consistent epidemiological studies that associated exposure with premature mortality in susceptible subpopulations and the inability of numerous hypothesized confounding factors to negate the associations. Using ozone and PM as examples, this paper discusses the scientific basis for NAAQS promulgations in situations in which the underlying database differed greatly in the extent of toxicological support.
Bilingual inner speech as the medium of cross-modular retrieval in autobiographical memory
Authors: Robert W. Schrauf
Journal: Behavioral and Brain Sciences (2002)

Carruthers’ notion that natural language(s) might serve as the medium of non-domain-specific, propositionally based inferential thought is extended to the case of effortful retrieval of autobiographical memory among bilinguals. Specifically, the review suggests that the resources of bilingual inner speech might play a role in the cyclical activation of information from various informational domains during memory retrieval.