tbuckley/cabot-search huggingface dataset:
Likened to pike in German
Authors: M. Ranta
Journal: BMJ (2011)

The lognormal diffusion process is mathematically tractable and incorporates the kind of continuous random evolution of the price by small increments that seems to characterize most security prices. But market microstructure studies have shown that a lognormal diffusion does not describe very well price formation at the shortest intervals. This is especially true of short-term bond returns. Bond price changes are mostly small, but the tails of the distribution are fatter than the lognormal allows and occasional non-diffusive jumps do seem to occur. Also, the intervals between price changes vary considerably in length. Alternative distributions have been proposed, but they do not have the convenient mathematical properties of the lognormal, so implementation can be challenging. Hainaut and MacGilchrist propose using the normal inverse Gaussian (NIG) distribution that arises from a particular Lévy process and develop a lattice implementation for pricing. A pentanomial tree incorporates the NIG by matching its first four moments. In a simulation exercise, the NIG consistently outperforms the lognormal, largely due to its ability to capture skewness in returns. <b>TOPICS:</b>Derivatives, statistical methods, simulations
HIV-1 Tat and heparan sulfate proteoglycan interaction: a novel mechanism of lymphocyte adhesion and migration across the endothelium
Authors: Chiara Urbinati, Stefania Nicoli, Mauro Giacca, Guido David, Simona Fiorentini, Arnaldo Caruso, Massimo Alfano, Luca Cassetta, Marco Presta, Marco Rusnati
Journal: Blood (2009)
Altered MicroRNA Processing in Heritable Pulmonary Arterial Hypertension
Authors: Kylie M. Drake, Deborah Zygmunt, Lori Mavrakis, Phyllis Harbor, Lingli Wang, Suzy A. Comhair, Serpil C. Erzurum, Micheala A. Aldred
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Heritable pulmonary arterial hypertension (HPAH) is primarily caused by mutations of the bone morphogenetic protein (BMP) type-II receptor (BMPR2). Recent identification of mutations in the downstream mediator Smad-8 (gene, SMAD9) was surprising, because loss of Smad-8 function in canonical BMP signaling is largely compensated by Smad-1 and -5. We therefore hypothesized that noncanonical pathways may play an important role in PAH.To determine whether HPAH mutations disrupt noncanonical Smad-mediated microRNA (miR) processing.Expression of miR-21, miR-27a, and miR-100 was studied in pulmonary artery endothelial (PAEC) and pulmonary artery smooth muscle cells (PASMC) from explant lungs of patients with PAH.SMAD9 mutation completely abrogated miR induction, whereas canonical signaling was only reduced by one-third. miR-21 levels actually decreased, suggesting that residual canonical signaling uses up or degrades existing miR-21. BMPR2 mutations also led to loss of miR induction in two of three cases. HPAH cells proliferated faster than other PAH or controls. miR-21 and miR-27a each showed antiproliferative effects in PAEC and PASMC, and PAEC growth rate after BMP treatment correlated strongly with miR-21 fold-change. Overexpression of SMAD9 corrected miR processing and reversed the hyperproliferative phenotype.HPAH-associated mutations engender a primary defect in noncanonical miR processing, whereas canonical BMP signaling is partially maintained. Smad-8 is essential for this miR pathway and its loss was not complemented by Smad-1 and -5; this may represent the first nonredundant role for Smad-8. Induction of miR-21 and miR-27a may be a critical component of BMP-induced growth suppression, loss of which likely contributes to vascular cell proliferation in HPAH.
The State We're In
Authors: M. Bartley
Journal: BMJ (1995)

Will Hutton Cape, pounds sterling16.99, pp 352 ISBN 0 224 03688 2

The early economists were not only concerned about money. They called themselves “political economists,” and were concerned with the whole complex of social and political institutions that make it possible to have markets at all. Will Hutton has returned to this tradition.

There are two ways of looking at the present ills of the advanced industrial economies. One is that the Keynesian policies which ironed out wild economic fluctuations in the postwar period are no longer viable because their price is too high in terms of inflation and workers' militancy. In a state of full employment, workers got too …
There Is No Such Thing as a Psychiatric Disorder/Disease/Chemical Imbalance
Authors: Fred Baughman
Journal: PLoS Medicine (2006)

I am a disease monger.I teach primary care doctors how to identify bipolar disorder.Worse yet, I take money from pharmaceutical companies for doing so.I use it to subsidize my practice so that I can treat patients with no insurance, or little money, who now account for over a third of my patients-in part because the pharmaceutical companies have drained so much money out of the health-care system.Ironic, isn't it?My Web site PsychEducation.org(http:⁄⁄www.psycheducation.org) is number one on Google for searches on "bipolar II."See if you think it looks like disease mongering.Hundreds of people have written thanking me for explaining bipolar II and the concept of a bipolar spectrum, indicating that this new perspective really helps them understand their long-standing symptoms.To my immediate recall, none have complained about being led astray by an overbroad interpretation of bipolarity.Notice that, just like Mr. Moynihan, one of the guest editors of your April 2006 series of articles on disease mongering [1], I could be mongering even now, as I too have a new book.At least I'm not trying to attract attendees to my conference.Tricky, isn't it.Has there been an oversimplifi cation in this analysis?(PsychEducation.org
Adaptative response of alpha- and beta-glucosidase kinetics along the villi of rat self-filling jejunal blind loops.
Authors: S Gutschmidt, F Sandforth, H Menge, E O Riecken
Journal: Gut (1982)

Four and 12 days after the construction of self-filling jejunal blind loops in the rat, the apparent Km- and Vmax-values of lactase/beta-glucosidase and neutral alpha-glucosidase were determined by in-situ quantitative enzyme histochemistry, and changes in the villus-crypt architecture of the mucosa were examined by microdissection. The results were compared with corresponding data from sham-operated controls. The kinetics data were obtained from the base and the transition zone between medium and apical villus third by the use of a microdensitometric technique. The apparent Vmax of lactase/beta-glucosidase is significantly smaller than in the control rats at both measuring sites of the villi and even decreases from day 4 to day 12. The apparent Vmax of neural alpha-glucosidase is not affected, and thus the same increase in enzyme activity along the villi as in the controls is observed. The apparent Km of this enzyme, however, is already significantly increased on day 4 at both villus positions in the blind loops. A pronounced increase in villus surface area is detected in the blind loops as a result of an increase in crypt cell proliferation. The results indicate that enzymatic adaptation in the self-filling blind loops of rat jejunum exhibits different patterns for brush border alpha- and beta-glucosidases and is at least in part accomplished independently of the pronounced mucosal transformation occurring in this experimental condition.
Case-control studies: advantages and disadvantages
Authors: P. Sedgwick
Journal: BMJ (2014)

Researchers investigated the risk factors associated with the development of pulmonary tuberculosis in Russia. A case-control study was performed in the city of Samara, 700 miles south east of Moscow. Cases were 334 consecutive adults diagnosed as having culture confirmed pulmonary tuberculosis at any of the city’s specialist tuberculosis clinics between 1 January 2003 and 31 December 2003. For each case, a control matched for year of birth and sex, and with no history of tuberculosis, was sampled randomly from a registry of the general population of Samara city. A questionnaire was used to collect information retrospectively about potential risk factors before and during the development of pulmonary tuberculosis. Controls were asked about exposure to risk factors before the index date for their matched case—that is, the date when tuberculosis was diagnosed.1

The researchers reported that the most important risk factors associated with the development of pulmonary tuberculosis were raw milk and unemployment.

Which of the following statements, if any, are true?

Statement b is true, whereas a , c, and d are false.

The purpose of the study was to establish those risk factors associated with the development of pulmonary …
The rubber ear
Authors: Des Spence
Journal: BMJ (2008)

The male lead singers of US rock bands of the 1980s—with their frizzy, long blond hair and pink make-up—were the prettiest girls on television. Their screaming guitar solos and the wailing backing vocals were a rock abomination, although the greatest danger lay in listening to their lyrics. Listening, however, is the doctor’s mantra. I have spent the past decade teaching undergraduates how to listen. I have suffered the tantrums of medical school actors who clearly resented the bit part of …
Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects
Authors: Kanji Uchida, Koh Nakata, Takuji Suzuki, Maurizio Luisetti, Masato Watanabe, Diana E. Koch, Carrie A. Stevens, David C. Beck, Lee A. Denson, Brenna C. Carey, Naoto Keicho, Jeffrey P. Krischer, Yoshitsugu Yamada, Bruce C. Trapnell
Journal: Blood (2009)
The "Two-Step" Exercise Electrocardiogram in Functional Heart Disturbances and in Organic Heart Disease: The Use of Ergotamine Tartrate
Authors: ARTHUR M. MASTER, LEON PORDY, JOSEPH KOLKER, MORTIMER J. BLUMENTHAL
Journal: Circulation (1950)

Patients with functional cardiac disturbances, including chest pain, may present electrocardiographic abnormalities (pronounced RS-T depressions and T-wave inversions) after the "2-step" exercise test which are indistinguishable from those found in organic heart disease. Ergotamine tartrate was employed intravenously in conjunction with "2-step" tests in 10 cases for the objective differentiation of functional from organic heart involvement. However, ergotamine was found to be contraindicated as a routine for this purpose because of its anginal-provoking properties. We have substituted dihydroergecornine (DHO-180), a newer, safer ergot alkaloid, in our further investigation of this problem.
Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma
Authors: William W. Lockwood, Raj Chari, Bradley P. Coe, Kelsie L. Thu, Cathie Garnis, Chad A. Malloff, Jennifer Campbell, Ariane C. Williams, Dorothy Hwang, Chang-Qi Zhu, Timon P. H. Buys, John Yee, John C. English, Calum MacAulay, Ming-Sound Tsao, Adi F. Gazdar, John D. Minna, Stephen Lam, Wan L. Lam
Journal: PLoS Medicine (2010)

Background Traditionally, non-small cell lung cancer is treated as a single disease entity in terms of systemic therapy. Emerging evidence suggests the major subtypes—adenocarcinoma (AC) and squamous cell carcinoma (SqCC)—respond differently to therapy. Identification of the molecular differences between these tumor types will have a significant impact in designing novel therapies that can improve the treatment outcome. Methods and Findings We used an integrative genomics approach, combing high-resolution comparative genomic hybridization and gene expression microarray profiles, to compare AC and SqCC tumors in order to uncover alterations at the DNA level, with corresponding gene transcription changes, which are selected for during development of lung cancer subtypes. Through the analysis of multiple independent cohorts of clinical tumor samples (>330), normal lung tissues and bronchial epithelial cells obtained by bronchial brushing in smokers without lung cancer, we identified the overexpression of BRF2, a gene on Chromosome 8p12, which is specific for development of SqCC of lung. Genetic activation of BRF2, which encodes a RNA polymerase III (Pol III) transcription initiation factor, was found to be associated with increased expression of small nuclear RNAs (snRNAs) that are involved in processes essential for cell growth, such as RNA splicing. Ectopic expression of BRF2 in human bronchial epithelial cells induced a transformed phenotype and demonstrates downstream oncogenic effects, whereas RNA interference (RNAi)-mediated knockdown suppressed growth and colony formation of SqCC cells overexpressing BRF2, but not AC cells. Frequent activation of BRF2 in >35% preinvasive bronchial carcinoma in situ, as well as in dysplastic lesions, provides evidence that BRF2 expression is an early event in cancer development of this cell lineage. Conclusions This is the first study, to our knowledge, to show that the focal amplification of a gene in Chromosome 8p12, plays a key role in squamous cell lineage specificity of the disease. Our data suggest that genetic activation of BRF2 represents a unique mechanism of SqCC lung tumorigenesis through the increase of Pol III-mediated transcription. It can serve as a marker for lung SqCC and may provide a novel target for therapy. Please see later in the article for the Editors' Summary
Evidence of protein transduction but not intercellular transport by proteins fused to HIV tat in retinal cell culture and in vivo
Authors: Siobhan M Cashman, David J Morris, Rajendra Kumar-Singh
Journal: Molecular Therapy (2003)

The human immunodeficiency virus type-1 Tat protein is known to exit virally infected cells and enter the nucleus of adjacent uninfected cells. This property has been mapped to an 11-amino-acid protein transduction domain (PTD). When the PTD of Tat is fused to heterologous proteins and added exogenously to cells, the fusion peptide is able to demonstrate protein transduction across plasma membranes. Recent reports indicate that endogenously expressed Tat fusion peptides can demonstrate intercellular transport and improve biodistribution of therapeutic protein in the context of adenovirus vectors. Intercellular transport and protein transduction have not been observed in some studies and in the former have been attributed to an artifact of fixation. We have attempted to resolve these studies using an approach that unambiguously distinguishes cells that express Tat fusion protein from those that receive it from their environment. We find no evidence of intercellular transport in the context of an adenovirus vector in cell culture or in vivo. Instead, we find that Tat fusion peptides are down regulated in terms of expression not only in the context of adenovirus vectors, but also when expressed from transfected plasmid DNA. However, when Tat fusion peptides are released from cells by degradation of the plasma membrane, the fusion peptides demonstrate protein transduction without the need for cell fixation, indicating a unidirectional transport of Tat fusion proteins across the plasma membrane. Our data are consistent with previously reported studies and help to explain the apparently different results obtained from several different laboratories.
A Freakish Occurrence
Authors: N. C. Lake
Journal: BMJ (1945)

ERYTHEMA NODOSUM AND TUBERCULOSIS MEDBRIALJOURNAL 287 definite family history; but the child frequently visited a house where somebody had a bad cough and swollen glands in the neck.Case 8.-Boy, 6 years; referred because a lodger in the house had been found suffering from pulmonary tuberculosis with a positive sputum.The left tonsillar gland was enlarged, and a tuberculin patch test was found positive for human and bovine tests.A chest film showed a primary complex on the left side.He had had an attack of erythema nodosum in Jan:, 1944, diagnosed as rheumatism.Case 9.-Boy, 7 years; referred with erythema nodosum, corneal ulcers, and phlyctenular conjunctivitis.Tuberculin patch test posi- tive for both human and bovine tests.A chest film showed an enlarged right hilar gland, suggesting a primary complex.Rhonchi were heard in the right lung, and there has been loss of weight.He visits a house where one of the family died of tuberculosis.
Instantaneous and delayed ventricular arrhythmias after reperfusion of acutely ischemic myocardium: evidence for multiple mechanisms.
Authors: E Kaplinsky, S Ogawa, E L Michelson, L S Dreifus
Journal: Circulation (1981)

To characterize the electrophysiologic properties of the ventricular arrhythmias occurring dur- ing reperfusion after acute coronary artery ligation, a study was undertaken to correlate the time course of appearance of such arrhythmias with specific electrophysiologic mechanisms.Thirty-seven dogs survived 30- minute ligations of the left descending coronary artery, and all had either instantaneous (onset at 0-1 minute) or delayed (onset at 2-7 minutes) ventricular arrhythmias on reperfusion.Local electrograms recorded from ischemic myocardium were markedly abnormal after 30 minutes of coronary artery ligation, but rapidly returned to approximately normal within 1-2 minutes after reperfusion.Instantaneous reperfusion ventricular arrhythmias occurred in the midst of the recovery process when fragmented activity was recorded on elec- trograms from the ischemic area.This activity increased in amplitude, was of long duration (i.e., spanning diastole) and was associated with the occurrence of ventricular fibrillation in 24 of 37 dogs.By 3 minutes after reperfusion, all electrical activity was again synchronous and inscribed completely within the QRS complex.However, in eight of 19 dogs that survived the initial reperfusion period, including six resuscitated from ventricular fibrillation, there was a second surge of ventricular arrhythmias that was independent of diastolic or asynchronous electrical activity.In contrast to the instantaneous reperfusion ventricular arrhythmias, the delayed arrhythmias (2-7 minutes after reperfusion) were associated with electrophysiologic properties characteristic of enhanced automaticity and only infrequently (one of eight dogs) degenerated to ventricular fibrillation.Although the incidence of ventricular arrhythmias during the antecedent period of coronary artery ligation and the occurrence of instantaneous reperfusion arrhythmias were closely correlated, the delayed ven- tricular arrhythmias of reperfusion and those occurring during the antecedent coronary artery ligation period were not correlated.Distinct electrophysiologic mechanisms are apparently associated with a specific time course of appearance and with the severity of ventricular arrhythmias that occur when blood flow is suddenly restored to acutely ischemic myocardium.
Baroreflex Failure -- A Diagnostic Challenge
Authors: William M. Manger
Journal: New England Journal of Medicine (1993)

In this issue of the Journal, Robertson et al.1 admirably characterize a poorly understood and rarely recognized syndrome, baroreflex failure. The hallmark of this syndrome is marked lability of blood pressure, with systolic and diastolic hypertension and tachycardia (usually lasting 3 to 30 minutes, but sometimes persisting for several days) alternating at times with hypotension and relative bradycardia24. Some patients may have sustained hypertension with periods of lability. The rarity of baroreflex failure is evidenced by its identification in only 11 of 500 patients referred to the Autonomic Dysfunction Center at Vanderbilt University for autonomic or blood-pressure problems . . .
932-90 Transient Adenosine Infusion and Washout Before Ischemia Protects the Heart Against Metabolic Damage During Ischemia and Reperfusion, but Does not Attenuate Stunning in Pigs – Comparison with Ischemic Preconditioning
Authors: Ryoji Yokota, Hisayoshi Fujiwara, Masami Miyamae, Masaru Tanaka, Kenzo Yamasaki, Shuji Itoh, Keiko Koga, Yoichi Yabuuchi, Shigetake Sasayama
Journal: Journal of the American College of Cardiology (1995)
Insulin for Toddlers With Difficult Diabetes
Authors: Rajiv Goonetilleke, Melanie Pollitzer, Nick Mann
Journal: Diabetes Care (2004)

Effective control of blood glucose in toddlers with diabetes can be difficult for a variety of reasons. Unpredictable eating patterns with changes in the timing of meals and quantities eaten, as well as different levels of activity, are the major factors that impact on blood glucose levels at this age.

The Diabetes Control and Complications Trial showed the importance of good glycemic control in reducing complications of diabetes (1). Twice-daily insulin regimens with an intermediate-acting insulin such as isophane often result in unacceptable hypoglycemia in young children. We wish to describe two patients <3 years of age treated with a premeal short-acting analog insulin in conjunction with glargine insulin …
The first seizure and its management in adults and children
Authors: Bernd Pohlmann-Eden, Ettore Beghi, Carol Camfield, Peter Camfield
Journal: BMJ (2006)

This review presents a comprehensive approach to children and adults with a first seizure, an event that may have profound emotional, social, and vocational consequences.

A first “grand mal” convulsion is frightening, yet prospective, population-based studies indicate that we all face an 8-10% lifetime risk of one seizure1 and a 3% chance of epilepsy.2 It seems likely that everyone could have a seizure if a particular set of circumstances occur—but some people have a lower seizure threshold than others. A first seizure caused by an acute disturbance of brain function (acute symptomatic or provoked) is unlikely to recur (3-10%). If a first seizure is unprovoked, however, meta-analyses suggest that 30-50% will recur; and after a second unprovoked seizure, 70-80% will recur, justifying the diagnosis of epilepsy (a tendency for recurrent seizures).3–5

When a person presents to the healthcare system with a first seizure, it is almost always a convulsive seizure, either generalised or focal. Other seizure types such as absence or complex partial seizures typically occur several times before the person or family become concerned.

We reviewed all literature listed in PubMed under the headings “first seizure” and “initial seizure.” Two of us have helped to develop a practice parameter on treatment of a first seizure in children, and all of us have conducted prospective studies of first seizures. We are unaware of any systematic (Cochrane) review of this topic. All references cited were judged to give strong evidence.

The differential diagnosis for a first seizure is wide. Most important in our experience are syncope (including breath holding and pallid syncope), transient ischaemic attacks, metabolic encephalopathy (including hypoglycaemia or electrolyte disturbance), sleep walking, night terrors, complex migraines, cardiac arrhythmias, and pseudoseizures. “Convulsive syncope” presents a particular challenge when syncope provokes a post-anoxic convulsion. A detailed …
US drug maker is challenged over decision to force patients to use new version of drug as patent expiry looms
Authors: O. Dyer
Journal: BMJ (2014)

New York state’s attorney general, Eric Schneiderman, has launched a federal antitrust suit against the drug company Actavis and its recently acquired subsidiary Forest Laboratories, over their plan to force patients to switch to a new extended release version of the Alzheimer’s drug Namenda (memantine).

Forest announced in February that it would stop manufacturing the twice daily Namenda this summer, offering instead a new once daily drug, Namenda XR. Namenda’s patent is due to expire in July 2015, which would normally trigger a sharp drop in sales as cheaper generic versions flooded the market. But Forest said that it hoped to maintain its market share by engineering what is known in the industry as a “forced switch” to Namenda XR, whose patent is …