tbuckley/cabot-search huggingface dataset:
Lymphangioplasty--The Fate of Silk
Authors: H. Hartley, R. A. K. Harper
Journal: BMJ (1937)

The current low volatility environment keeps trading costs low. But what if volatility increases? In this paper, we discuss how an increase in volatility will affect execution strategies and estimate its impact on portfolio trading costs. We derive our estimates by simulating the Goldman Sachs PortX algorithm. PortX derives the optimum execution strategy by balancing the cost-risk trade-off and therefore allows us to examine how an increase in volatility changes the optimum strategy. Our simulations suggest that doubling volatility will increase the expected trading cost on large cap portfolios by 20% to 25% (depending on trading aggressiveness) and by almost 50% on small cap portfolios. In our simulations, doubling volatility increases trading costs both directly (for a fixed execution horizon) and indirectly: the resulting increase in execution risk reduces the optimum execution horizon further increasing trading costs. <b>TOPICS:</b>Exchanges/markets/clearinghouses, volatility measures, portfolio construction
MECHANISMS OF IMPAIRED WATER EXCRETION IN ADRENAL AND PITUITARY INSUFFICIENCY. III. THE EFFECT OF EXTRACELLULAR OR PLASMA VOLUME EXPANSION, OR BOTH, ON THE IMPAIRED DIURESIS*
Authors: Ralph E. Cutler, Charles R. Kleeman, Jerry Koplowitz, Morton H. Maxwell, J. Thomas Dowling
Journal: Journal of Clinical Investigation (1962)

Earlier studies suggest that cortisol and related glucocorticoids correct the impaired water diuresis of primary and secondary adrenal insufficiency by a direct effect upon the diluting segment of the nephron (1-4); however, no one has conclusively demonstrated that a sustained positive water balance in the adrenal-insufficient patient completely inhibits the secretion of antidiuretic hormone (ADH). Although osmotic inhibition of the release of ADH may be normal in adrenal insufficiency, the human or animal in this state may have a distorted volume stimulus that prevents complete inhibition. Recent studies have demonstrated that contraction or redistribution of both vascular and extracellular volumes can cause the continued secretion of ADH in the water-loaded subject (5, 6). Blood loss, quiet standing, venous congestion of the lower extremities, and positive pressure breathing are all events that may produce this contraction or redistribution. Since the adrenal-insufficient patient is hypo
Chronic unexplained hypertransaminasemia may be caused by occult celiac disease
Authors: Maria Teresa Bardella, Maurizio Vecchi, Dario Conte, Ersilio Del Ninno, Mirella Fraquelli, Stefania Pacchetti, Eliseo Minola, Marina Landoni, Bruno Mario Cesana, Roberto De Franchis
Journal: Hepatology (1999)

In a subset of patients attending liver units, a chronic increase in serum transaminases may remain of undetermined cause despite thorough investigations. On the other hand, elevated levels of serum transaminases have been reported in about 40% of adult celiac patients. To evaluate the prevalence of subclinical celiac disease in patients with chronic unexplained hypertransaminasemia in comparison with that in the general population (0.5%), 140 consecutive patients with chronic increases of serum transaminases levels of unknown cause were tested for antigliadin and antiendomysium IgA antibodies. All patients with positive antibody tests were offered upper gastrointestinal endoscopy with distal duodenal biopsy. Thirteen patients (9.3%, 95% confidence interval 5. 0-15.4) had positive antigliadin and antiendomysium antibodies. The prevalence of antibodies was 17% in women and 5.4% in men (8/47 vs. 5/93 respectively; relative risk 3.2, 95% confidence interval 1.1-9. 1). Distal duodenal biopsy performed in all but one of the patients showed mild villous atrophy with increased intraepithelial lymphocytes in three cases, subtotal villous atrophy in six, and total villous atrophy in three. The prevalence of celiac disease in the patient group was significantly higher than that in the general population (P <.001) with a relative risk of 18.6 (95% confidence interval 11.1-31.2). On the basis of the present findings, screening for celiac disease is an important tool in the initial diagnostic work-up of patients with chronic unexplained hypertransaminasemia.
Evolution of the mammalian G protein α subunit multigene family
Authors: Thomas M. Wilkie, Debra J. Gilbert, Anne S. Olsen, Xiao–Ning Chen, Thomas T. Amatruda, Julie R. Korenberg, Barbara J. Trask, Pieter de Jong, Randall R. Reed, Melvin I. Simon, Nancy A. Jenkins, Neal G. Copeland
Journal: Nature Genetics (1992)
Validity and Responsiveness of the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales in the Pediatric Inpatient Setting
Authors: Arti D. Desai, Chuan Zhou, Susan Stanford, Wren Haaland, James W. Varni, Rita M. Mangione-Smith
Journal: JAMA Pediatrics (2014)

Validated patient-reported outcomes responsive to clinical change are needed to evaluate the effectiveness of quality improvement interventions.To evaluate responsiveness, construct validity, and predictive validity of the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales in the pediatric inpatient setting.Prospective, cohort study of parents and caregivers of patients 1 month to 18 years old (n = 4637) and patients 13 to 18 years old (n = 359) admitted to Seattle Children's Hospital between October 1, 2011, and December 31, 2013. Of 7184 eligible participants invited to complete the survey, 4637 (64.5%) completed the PedsQL on admission, and of these 2694 (58.1%) completed the follow-up survey 2 to 8 weeks after discharge.Responsiveness was assessed by calculating improvement scores (difference between follow-up and admission scores). Construct validity was examined by comparing the mean improvement scores for known groups differing by medical complexity. Predictive validity was assessed using Poisson regression to examine associations among admission scores, prolonged length of stay (≥3 days), and 30-day readmissions or emergency department (ED) return visits. Similar models examined the association between improvement scores and risk for 30-day readmissions or ED return visits.The mean (SD) PedsQL improvement scores (scale, 0-100) were 22.1 (22.7) for total, 29.4 (32.4) for physical, and 17.1 (21.0) for psychosocial. The mean PedsQL total improvement scores were lower for patients with medically complex conditions compared with patients without chronic conditions (13.7 [95% CI, 11.6-15.8] vs. 24.1 [95% CI, 22.4-25.7], P < .001). A 10-point decrement in the PedsQL total admission score below the established community-based mean was associated with an increase in risk for prolonged length of stay (15% [95% CI, 13%-17%]), 30-day readmissions (8% [95% CI, 3%-14%]), and ED return visits (13% [95% CI, 6%-20%]). A 5-point decrement in the PedsQL total improvement score below the study sample mean improvement score was associated with an increase in risk for 30-day readmissions or ED return visits (9% [95% CI, -1% to 19%]).The PedsQL demonstrated responsiveness, construct validity, and predictive validity in hospitalized pediatric patients. The PedsQL may be a useful patient-reported outcome for hospital-based clinical effectiveness research.
Mutations of epigenetic regulators and of the spliceosome machinery in therapy-related myeloid neoplasms and in acute leukemias evolved from chronic myeloproliferative diseases
Authors: M T Voso, E Fabiani, L Fianchi, G Falconi, M Criscuolo, R Santangelo, P Chiusolo, S Betti, F D'Alo', S Hohaus, V De Stefano, G Leone
Journal: Leukemia (2012)
Platelet-Derived Transforming Growth Factor-β Down-Regulates NKG2D Thereby Inhibiting Natural Killer Cell Antitumor Reactivity
Authors: Hans-Georg Kopp, Theresa Placke, Helmut Rainer Salih
Journal: Cancer Research (2009)

Natural killer (NK) cells play an important role in cancer immunosurveillance and may prevent tumor progression and metastasis due to their ability to mediate direct cellular cytotoxicity and by releasing immunoregulatory cytokines, which shape adaptive immune responses. Their reactivity is governed by various activating and inhibitory molecules expressed on target cells and reciprocal interactions with other hematopoietic cells such as dendritic cells. In mice, thrombocytopenia inhibits metastasis, and this is reversed by NK cell depletion, suggesting that platelets are an important additional player in NK cell-tumor interaction. Moreover, it has been shown that metastasizing tumor cells do not travel through the blood alone but are rapidly coated by platelets. However, the knowledge about the molecular mechanisms by which platelets influence NK cells is fragmentary at best. Here we show that platelet-derived soluble factors, secreted on coating of tumor cells or after stimulation with classic platelet agonists, impair NK cell antitumor reactivity resulting in diminished granule mobilization, cytotoxicity, and IFN-gamma production. The impaired NK cell reactivity was not due to induction of apoptosis but mediated by down-regulation of the activating immunoreceptor natural killer group 2, member D (NKG2D) on NK cells by platelet-derived transforming growth factor beta (TGF-beta). Neutralization of TGF-beta in platelet releasate not only prevented NKG2D down-regulation but also restored NK cell antitumor reactivity. Thus, our data elucidate the molecular basis of the previously described influence of platelets on NK cell antitumor reactivity and suggest that therapeutic intervention in tumor cell-platelet interaction and the resulting TGF-beta release by platelets may serve to enhance antitumor immunity.
CHRONIC DIALYSIS: SELECTION AND SUCCESS
Authors: HARRY S. ABRAM
Journal: Annals of Internal Medicine (1968)

Letters and Comments1 August 1968CHRONIC DIALYSIS: SELECTION AND SUCCESSHARRY S. ABRAM, M.D.HARRY S. ABRAM, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-69-2-402 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: I wish to raise two points in Schupak, Sullivan, and Lee's presentation, "Chronic Hemodialysis in 'Unselected' Patients" (Ann. Intern. Med. 67: 708, 1967), in which the investigators mislead the reader:1. The patients were not "unselected" and indeed went through a selection process, utilizing four criteria (including the patient being "likely to cooperate in his own care") and requiring the "unanimous" decision of "a small group of physicians" (in other words a selection committee). Of 34 patients evaluated 8 were rejected, 4 for failing "to give any indication that they were likely to cooperate" (details not given).... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: HARRY S. ABRAM, M.D.Affiliations: University of Virginia Medical Center Charlottesville, Va. 22901 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1968Volume 69, Issue 2Page: 402-403KeywordsMedical dialysis ePublished: 1 December 2008 Issue Published: 1 August 1968 PDF downloadLoading ...
Lack of Normal Association Between Cerebellar Volume and Neuropsychological Functions in First-Episode Schizophrenia
Authors: Philip R. Szeszko, Faith Gunning-Dixon, Robert S. Goldman, John Bates, Manzar Ashtari, Peter J. Snyder, Jeffrey A. Lieberman, Robert M. Bilder
Journal: American Journal of Psychiatry (2003)

Functional neuroimaging studies have identified a role for the cerebellum in the neuropsychology of schizophrenia. Few studies, however, have examined the relationship between cerebellar size and neuropsychological functioning in schizophrenia. The authors' goal was to examine this relationship in patients and healthy comparison subjects.Total cerebellar volume was computed from magnetic resonance images in 48 male and 33 female patients experiencing a first episode of schizophrenia and in 14 male and nine female healthy comparison subjects. Patients and comparison subjects completed a comprehensive neuropsychological assessment encompassing six domains of functioning: executive, motor, language, visuospatial, memory, and attention. A global domain of functioning was computed as the mean of these six domains.Larger cerebellar volume correlated significantly with better global functioning in healthy subjects but not among patients with schizophrenia; this relationship was significantly stronger in healthy subjects than in patients. Additional analyses revealed significant associations between cerebellar volume and visuospatial, executive, and memory functions in healthy volunteers but not among patients.The cerebellum plays a role in higher cognitive functions in healthy individuals, and normal associations between cerebellar size and function are absent in patients experiencing a first episode of schizophrenia. These findings are consistent with neurobiological models implicating the cerebellum in the pathogenesis of schizophrenia.
Abstract 1041: Epigenetic regulation of BRAF-HDAC complex in presence of trichostatin A, 5-aza-2′-deoxycytidine and cisplatin in ovarian cancer
Authors: Fanliang Meng, Mei Zhong, Guigin Sun, Yanhong Yu, Molly A. Brewer
Journal: Cancer Research (2012)

Abstract Objective: To investigate the regulation of the subunits of BRAF-HDAC complex, a gene transcription repression complex, which regulates the interaction of histone methylation, histone acetylation, DNA methylation and DNA repair in response to chemotherapy in ovarian cancer cell lines with different treatment strategies. We hypothesized that combining different epigenetic modifiers with low dose Cisplatin would result in an optimal therapeutic regime for ovarian cancer. Materials and Methods: Two epigenetic modifiers Trichostatin A (TSA), a histone deacetylase inhibitor and 5-aza-2′- deoxycytidine (Decitabine), a demethylating agent were evaluated in different doses alone and in combination with Cisplatin on the expression of subunits of BRAF-HDAC complex, histone methylation, acetylation and the associated pathways affected. Three cell lines, A2780, Hey and SKOV3 were used. Spheroids were grown in serum free medium and injected IP in SCID mice. Western blots confirmed protein expression. Results: Different combinations of TSA, Decitabine and low dose Cisplatin significantly inhibited the expression of the subunits LSD1 and CoREST in the BRAF-HDAC complex, two proteins which together demethylate H3K4 and H3K9. The BRAF-HDAC complex cofactor subunit BRAF35 was also significantly suppressed by the combination treatment. The BRAF-HDAC complex subunit repressor increased significantly after combined treatment. indicating that the combination of TSA, Decitabine and Cisplatin suppresses the expression of H3K4 and H3K9 methylation and increases the expression of Histone H3 lys9/14 and Histone H4 ser1/lys5/lys8/lys12 acetylation. Along with these methylation and acetylation changes, we found a decrease in epithelial-mesenchymal transition, cancer cell proliferation, chemoresistance and pluripotency. Spheroid formation was decreased in vitro and there was no tumor formation in SCID mice in presence of these epigenetic modifiers and low dose Cisplatin. Conclusions: The combination of epigenetic modifiers and low dose Cisplatin can regulate and modify the expression of subunits of BRAF-HDAC complex, resulting in decreased expression of tri- and di- methylated H3K4 and H3K9 and increased acetylation of Histone H3 and H4, subsequently modifying the tumor biology and tumorigenicity of these ovarian cancer cell lines. Further investigation of these mechanisms could provide the development of more effective and less toxic treatment for ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1041. doi:1538-7445.AM2012-1041
What do families and professional organisations really think about assisted dying?
Authors: S. Kenwright
Journal: BMJ (2013)

Noble highlights some dilemmas around assisted dying for the terminally ill, but—despite his personal anecdotes—there is little hard evidence about how families pressurise patients into making clinical decisions, let alone whether these pressures agree with the wishes of the patient.1 

Families generally push for more aggressive treatment, even when this seems inappropriate medically. We …
Abstract P1-02-02: Processing of GPNMB by ADAM-10 in Breast Tumors Releases an Extracellular Domain with Angiogenic Properties
Authors: AAN Rose, MG Annis, Z Dong, F Pepin, M Hallett, M Park, P. Siegel
Journal: Cancer Research (2010)

Abstract Background: Glycoprotein non-metastatic B (GPNMB), also known as Osteoactivin, is a cell surface bound, transmembrane protein that is expressed in 41-74% of breast cancers. We have shown that it promotes migration, invasion and metastasis of breast cancer cells, that it is associated with shorter recurrence-free and overall survival times, and that it is most commonly expressed among breast tumors of the basal/triple-negative subtypes. Patients with basal/triple-negative breast cancer have aggressive disease and are not amenable to currently available targeted therapies. For these reasons GPNMB is an attractive target for therapeutic intervention in breast cancer; indeed, a GPNMB-targeted antibody-drug conjugate (CDX-011) has shown impressive clinical response among patients with GPNMB-positive breast cancer and is being investigated in Phase IIb clinical trials. Despite its promise as a therapeutic target in breast cancer, little is known about the functional role of GPNMB the primary tumor microenvironment. Materials and Methods: We have employed 66cl4 murine mammary carcinoma cells and human BT549 breast cancer cells to investigate the effects of GPNMB on tumor growth and angiogenesis, respectively in vivo. Control and GPNMB-expressing tumors were analyzed using immunohistochemistry for degree of proliferation apoptosis and angiogenesis. To better characterize functionally important domains of GPNMB we employed immunoblot and ELISA analyses to assess levels of full length, intact GPNMB and shed GPNMB ectodomain in breast cancer cells. Transient siRNA-mediated knockdown studies were used to identify sheddases responsible for GPNMB shedding. Finally, we employed in vitro migration assays to assess function of the shed extracellular domain (ECD) of GPNMB. Results: In this study we show that GPNMB promotes the outgrowth of mammary tumors in vivo and enhances their microvascular density. In an effort to investigate the functional domains of GPNMB that are responsible for this pro-angiogenic effect, we found that that the extracellular domain (ECD) of GPNMB is constitutively shed in breast cancer cells and show that this ECD is capable of inducing endothelial migration. Finally, we have implicated a disintegrin and metalloprotease-10 (ADAM10) as a novel sheddase responsible for liberation GPNMB ectodomain. Conclusion: In this study we have described ADAM10-mediated shedding of GPNMB ECD - a protein fragment that induces endothelial cell migration - as a novel mechanism by which GPNMB can promote angiogenesis in breast cancer. Further efforts to characterize the effect of GPNMB on endothelial cell function will be discussed. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-02.
The Risks Associated with Teenage Abortion
Authors: Willard Cates, Kenneth F. Schulz, David A. Grimes
Journal: New England Journal of Medicine (1983)

The risks of morbidity and mortality affect a teenager's choice between termination of a pregnancy through induced abortion and continuation of the pregnancy. To identify these risks, we analyzed information from two separate sets of data collected by the Centers for Disease Control: that of the Joint Program for the Study of Abortion, a multicenter prospective study of nearly 165,000 legally induced abortions; and that of a national surveillance of abortion-related mortality. The rates of major complications associated with abortions in teenagers were 1 to 3 per 1000 suction-curettage procedures and approximately 13 per 1000 saline-administration procedures. The death-to-case rate for teenage women was 1.3 per 100,000 procedures. When the data on procedures were adjusted according to gestational age, teenagers generally had lower rates of morbidity and mortality from induced abortion than older women. (N Engl J Med 1983; 309:621–4.)
Gamma-secretase: from pathogenesis to therapeutics
Authors: Yueming Li
Journal: Molecular Neurodegeneration (2012)

Background Presenilin (PS) is the catalytic subunit of g-secretase and mutations in this protein cause familial Alzheimer’s Disease (FAD). Moreover, g-secretase has emerged as an appealing drug target for Alzheimer’s disease (AD) and cancer due to its central role in the generation of Ab peptides and the regulation of Notch signaling. g-Secretase is composed of at least four subunits: PS, Nicastrin, Aph1 and Pen2; with a total of 19 putative transmembrane domains.
Sexual Dysfunction in Diabetes Mellitus
Authors: ALAN SACERDOTE
Journal: Annals of Internal Medicine (1980)

Letters1 July 1980Sexual Dysfunction in Diabetes MellitusALAN SACERDOTE, M.D., SHELDON J. BLEICHER, M.D.ALAN SACERDOTE, M.D.Search for more papers by this author, SHELDON J. BLEICHER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-1-147_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In reading the February supplement on diabetic autonomic neuropathy, we were struck by two major differences between the diabetic cases of Dr. Ellenberg (1) and ours.The first difference is in the prevalence of sexual dysfunction in diabetic females. For the past 5 months we have held weekly inpatient diabetes education classes; during the first few weeks we echoed categorical statements (1, 2) that diabetic neuropathy does not affect female sexual function. This statement was so frequently objected to by patients that we have stopped making it. In interviews, diabetic women who complained of sexual dysfunction invariably...References1. ELLENBERG M. Sexual function in diabetic patients. Ann Intern Med. 1980;92(Part 2):331-3. LinkGoogle Scholar2. KOLODNY R. Sexual dysfunction in diabetic females. Diabetes. 1971;20:557-9. CrossrefMedlineGoogle Scholar3. SALWAYWHITEHEADFINNEGANKARUNANAYAKABARNETTPAYNE JLJADR. Effects of myo-inositol on peripheral-nerve function in diabetes. Lancet. 1978;2:1282-4. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ALAN SACERDOTE, M.D.; SHELDON J. BLEICHER, M.D.Affiliations: The Brooklyn Hospital Brooklyn, NY 11201 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDiabetes mellitus and female sexuality 1 July 1980Volume 93, Issue 1_Part_1Page: 147-147KeywordsDiabetes mellitusInpatientsNeuropathySexual dysfunction ePublished: 1 December 2008 Issue Published: 1 July 1980 PDF downloadLoading ...