tbuckley/cabot-search huggingface dataset:
Effects of Branch Length Uncertainty on Bayesian Posterior Probabilities for Phylogenetic Hypotheses
Authors: Bryan Kolaczkowski, Joseph W. Thornton
Journal: Molecular Biology and Evolution (2007)

In Bayesian phylogenetics, confidence in evolutionary relationships is expressed as posterior probability—the probability that a tree or clade is true given the data, evolutionary model, and prior assumptions about model parameters. Model parameters, such as branch lengths, are never known in advance; Bayesian methods incorporate this uncertainty by integrating over a range of plausible values given an assumed prior probability distribution for each parameter. Little is known about the effects of integrating over branch length uncertainty on posterior probabilities when different priors are assumed. Here, we show that integrating over uncertainty using a wide range of typical prior assumptions strongly affects posterior probabilities, causing them to deviate from those that would be inferred if branch lengths were known in advance; only when there is no uncertainty to integrate over does the average posterior probability of a group of trees accurately predict the proportion of correct trees in the group. The pattern of branch lengths on the true tree determines whether integrating over uncertainty pushes posterior probabilities upward or downward. The magnitude of the effect depends on the specific prior distributions used and the length of the sequences analyzed. Under realistic conditions, however, even extraordinarily long sequences are not enough to prevent frequent inference of incorrect clades with strong support. We found that across a range of conditions, diffuse priors—either flat or exponential distributions with moderate to large means—provide more reliable inferences than small-mean exponential priors. An empirical Bayes approach that fixes branch lengths at their maximum likelihood estimates yields posterior probabilities that more closely match those that would be inferred if the true branch lengths were known in advance and reduces the rate of strongly supported false inferences compared with fully Bayesian integration.
The effect of recombinant interleukin‐8 on eosinophils’ and neutrophils’ migration <i>in vivo</i> and <i>in vitro</i>
Authors: M. Bocheńska‐Marciniak, M. Kupczyk, P. Górski, P. Kuna
Journal: Allergy (2003)

Background: Interleukin‐8 (IL‐8) is a chemokine that causes chemotaxis of neutrophils, eosinophils and lymphocytes in vitro ; however, its role as a chemoattractant in allergic inflammation is unclear. The objective of this study was to investigate the effect of nasal instillation of IL‐8 on the influx of inflammatory cells. Methods: Twelve patients suffering from seasonal allergic rhinitis hypersensitive to grass pollens, with average age 30.1 ± 2.67 years were challenged both with diluent for IL‐8 and IL‐8 on a subsequent day, in two phases: before the pollen season (unprimed mucosa) and during the season (primed mucosa). The number of neutrophils, eosinophils and myeloperoxydase (MPO) levels in the nasal fluid collected after IL‐8 or placebo challenge were determined. Results: Challenge with IL‐8 of primed nasal mucosa induced a significant influx of neutrophils (29 × 10 4 cells/ml at 0.5 h, 251 × 10 4 at 2 h and 334 × 10 4 at 3 h). Number of eosinophils in comparison with diluent challenge was not significant. There was no difference in MPO levels in the nasal lavage between IL‐8 and diluent challenge of unprimed and primed mucosa. We did not find the relationship between MPO levels and the neutrophils number in the lavage (rank Spearman factor, R S = 0.258, P = 0.42). Conclusion: We have demonstrated that IL‐8 causes influx of neutrophils but not eosinophils into nasal mucosa in vivo . MPO level seems to be of little value as a marker of neutrophil influx into nasal mucosa.
Health reforms won't work without major changes, say King's Fund and BMA
Authors: A. Gulland
Journal: BMJ (2011)

The health think tank the King’s Fund and the British Medical Association have both urged the government to radically rethink its Health and Social Care Bill, with the BMA reiterating its view that it should be withdrawn.

The health bodies make the calls in submissions to the NHS Future Forum, the body conducting the government’s listening exercise on NHS reform, which is due to end next week.

In its submission the BMA states: “It is clear from the deep seated concerns expressed by stakeholders across the health sector in recent months that the legislation is fundamentally flawed.”

The King’s Fund doesn’t call for withdrawal of the bill but says that it needs major overhaul to deliver the …
Excretion of Cephaloridine and Cephalothin in Patients with Renal Impairment
Authors: Calvin M. Kunin, Nuzhet Atuk
Journal: New England Journal of Medicine (1966)

THE cephalosporins are a group of antibiotics isolated from Cephalosporium acremonium in 1945.1 Cephalothin, a semisynthetic derivation of one of these, cephalosporin C, came into general clinical use in 1964. This compound has gained widespread acceptance because of its penicillin-like activity against a wide variety of bacteria, general resistance to staphylococcal penicillinase, low serum protein binding, minimum crossallergenic relation to the penicillins and limited side reactions and toxicity.2 3 4 5 It is poorly absorbed by the oral route and requires parenteral injection. Cephalothin is rapidly excreted into the urine. The major metabolite is a relatively inactive desacetyl analogue.6 Substitution of a pyridine . . .
Effect of wall shear rate on thrombogenesis in microvessels of the rat mesentery.
Authors: M Sato, N Ohshima
Journal: Circulation Research (1990)

The role of hemodynamics on platelet thrombus formation was studied in venules and arterioles of the rat mesentery. Thrombus formation was induced by the fluorescent dye/light method for examination of the following factors: 1) the effect of wall shear rate on thrombus initiation, 2) the effect of wall shear rate on the growth of thrombi, and 3) the relation between platelet thrombus initiation and intraluminal velocity profile. The range of wall shear rate was up to approximately 1,000 1/sec in venules and from 640 to 2,900 1/sec in arterioles. Platelet thrombus initiation occurred more rapidly at higher wall shear rate in venules and at lower wall shear rate in arterioles. Thrombus initiation time was shortest around a wall shear rate of 900 1/sec in venules and around 700 1/sec in arterioles. Thrombus growth rate in venules was greatest at a wall shear rate of 1,500-2,000 1/sec. Thrombus initiation and its relation to blood flow was also examined in branched and curved microvessels. In these vessels platelet thrombi were also first initiated at the sites of higher wall shear rate in venules and of lower wall shear rate in arterioles.
Hyperlipemia Following Sulfonylurea Therapy in Young Diabetics
Authors: Joseph C. Shipp, Francis C. Wood, Alexander Marble
Journal: JAMA (1964)

PATIENTS with untreated diabetes mellitus often demonstrate some elevations of plasma lipids. The increased blood concentrations of free fatty acids (FFA), triglycerides, cholesterol, and phospholipids usually return to normal with treatment which improves glucose utilization. This report describes the occurrence of severe hyperlipemia associated with lipemia retinalis and xanthomatosis in certain diabetic patients treated with sulfonylurea compounds. In each instance, the control of the patient's hyperglycemia by the sulfonylurea was inadequate. These observations emphasize the importance of adequate follow-up of carbohydrate metabolism in patients treated with oral hypoglycemic agents. <h3>Methods</h3> Venous blood was drawn while the patient was in the fasting state unless otherwise noted. Blood glucose was determined by the method of Somogyi,<sup>1</sup>total lipids by the method of Folch,<sup>2</sup>FFA by the method of Dole,<sup>3</sup>cholesterol by the method of Abell,<sup>4</sup>and phospholipids by the method of Sperry.<sup>5</sup>Patients were hospitalized during the
ANGIOTENSINOGEN M235T GENETIC VARIANTS IN THE SUSCEPTIBILITY OF HYPERTENSION: EFFECTS ON ENDOTHELIAL FUNCTION AND ARTERIAL STIFFNESS
Authors: Emmanouel Androulakis, Dimitris Tousoulis, Antigoni Miliou, Nikolaos Papageorgiou, Chatzistamatiou Evaggelos, George Moustakas, Anna-Maria Kampoli, Kostas Toutouzas, Stella Brili, Eleftherios Tsiamis, Ioannis Kallikazaros
Journal: Journal of the American College of Cardiology (2011)
Trichorhinophalangeal syndrome type I and systemic lupus erythematosus with complement C4A homozygous null alleles in the same family.
Authors: S R Dahlqvist, B Lundstrom, G Holmgren
Journal: Annals of the Rheumatic Diseases (1989)

A three generation family from northern Sweden with both trichorhinophalangeal syndrome type I (TRP I) and systemic lupus erythematosus (SLE)-like syndrome with complement C4 homozygous null alleles is described. Five family members in three generations were affected by the TRP I syndrome, indicating autosomal dominant inheritance. Two members had clinical and laboratory signs of SLE and two other members SLE-like syndrome. All living family members in the first and second generation had homozygous C4A null alleles. In three of the adults the two syndromes occurred simultaneously, probably in this family by coincidence.
Extrahepatic conditions associated with primary biliary cirrhosis
Authors: Ricardo Moreno-Otero, María Trapero-Marugán
Journal: Hepatology (2009)

We read with great interest the updated American Association for the Study of Liver Diseases practice guidelines on primary biliary cirrhosis (PBC) and congratulate the authors for their comprehensive review and, in particular, for their clear discussion of special cases and patients with overlap syndrome and for exhaustive and practical approaches to therapy.1 However, we consider being familiar with the common extrahepatic manifestations of this disease to be of the upmost clinical relevance in medical practice. PBC is often associated with other diseases or syndromes, many of which are considered to be mediated by immunological mechanisms and some of which are classified within the spectrum of collagen vascular diseases. Accordingly, with the striking defects of immune regulation found in these patients, it has been proposed that PBC can be classified as a model autoimmune disease.2-5 Furthermore, although PBC is primarily a disease of the liver, there can be extrahepatic manifestations of this disease. The prevalence of other diseases in patients with PBC varies in different series between 15% and 100%. This wide variation in prevalence may be due, at least in part, to whether associated diseases that were subclinical were diagnosed and included in published series. More than 84% of PBC patients have been reported to exhibit features of at least one nonhepatic autoimmune disease sometime during the clinical course, and in about 40% of PBC cases, evidence of two or more nonhepatic autoimmune diseases can be found.6 It has been suggested that some of the more frequently associated diseases share a common pathogenic mechanism with PBC. In contrast, most of the rare associations of PBC with other diseases have been described in isolated case reports. In such reports, it is uncertain whether an association is related to a common pathogenic factor or is purely fortuitous. In conclusion, the occurrence of associated disorders with immunological features that do not primarily affect the liver provides support for the hypothesis that PBC is a systemic disease with an autoimmune basis. In individual patients, either PBC or another autoimmune disease may be clinically silent, so the true incidence of the association of PBC with other disorders having immunological features will be apparent only if appropriate tests for relevant asymptomatic diseases are conducted. Multicenter, prospective studies are warranted. Ricardo Moreno-Otero* , María Trapero-Marugán* , * Hepatogastroenterology Department, Hospital Universitario de La Princesa, Autonomous University of Madrid, Madrid, Spain, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
What's in a name change? Visual prediction makes extrapolation real and functional
Authors: Beena Khurana
Journal: Behavioral and Brain Sciences (2008)

Abstract Nijhawan redraws our attention to the problem of accurately perceiving an ever-changing visual world via a sensory system that has finite and significant communication times. The quandary is compelling and stark, but the suggestion that the visual system can compensate for these transmission delays by extrapolating the present is not so unequivocal. However, in this current airing of contradictory issues, accounts, and findings, Nijhawan trades spatial extrapolation – a rather specific concept introduced earlier (in Nijhawan 1994) for visual prediction – a far more expansive notion that forces the issue of both the perceived reality and functional significance of compensation.
CHANGES IN LV CONTRACTILITY AND DYSSYNCHRONY AFTER 12 MONTHS OF RESYNCHRONIZATION THERAPY ON SUBSEQUENT OUTCOMES: MADIT-CRT
Authors: Anne-Catherine Pouleur, Dorit Knappe, Amil Shah, Elyse Foster, Wojciech Zareba, Ilan Goldenberg, Mary Brown, Marc A. Pfeffer, Arthur J. Moss, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2011)
Early life origins of asthma
Authors: James E. Gern, Robert F. Lemanske, William W. Busse
Journal: Journal of Clinical Investigation (1999)

It is increasingly clear that the seeds of the asthmatic diathesis are planted early in life, possibly in utero. The cellular and molecular events that are responsible for these important disease processes are only now being identified. Genetic factors play a crucial role. In addition, the in utero microenvironment and neonatal immune system are now appreciated to be intrinsically skewed toward a Th2 (rather than Th1) immune response. When the genetically predisposed individual then encounters key environmental factors, an immune/inflammatory response ensues that ultimately directs the development of allergic disease and, through processes not fully defined, focuses these immune-regulated inflammatory responses into the lower airway (Figure ​(Figure22).



Figure 2

The early life origins can be divided into a number of phases. Early life events can lead to the development of a Th2-like environment, which is influenced by infections (Th1) rather than allergen exposure, diet, and certain respiratory infections. The ...



A variety of levels of investigation suggest that there are crucial temporal windows in babies and children during which these important patient-environment interactions need to occur for full disease expression, and that a variety of agents, including respiratory infections, diet, and toxin exposure, can all interact to regulate the final phenotype. The culmination of these multiple events is the development of Th2-like inflammation, bronchial hyperresponsiveness, and air flow obstruction/clinical asthma. The appreciation that these events begin early in life has refined our thought processes regarding disease pathogenesis, and has provided new experimental targets for investigators. Hopefully, an enhanced understanding of the pathogenesis of childhood asthma will provide the types of insights that will allow us to think in terms of primary disease prevention rather than the present goal of secondary symptom amelioration.
Lente Carbohydrate: A Newer Approach to the Dietary Management of Diabetes
Authors: David J A Jenkins
Journal: Diabetes Care (1982)

The dietary fiber hypothesis has stimulated interest in the possibility that the glycemic response to carbohydrate foods may be reduced by modifying gastrointestinal events to produce sustained-release or “lente” carbohydrate. Associated with this interest, a new branch of pharmacology has been developed involving the use of purified fiber preparations and enzyme inhibitors. These measures, together with the selection of diets containing foods that naturally release their carbohydrate products of digestion slowly, may contribute a useful facet to diabetic management in the future.
Group A β-Hemolytic Streptococcal Pharyngitis—Results of Treatment With Lincomycin
Authors: Ham Jackson
Journal: JAMA (1965)

A controlled study was done to determine the effectiveness of lincomycin in treating pharyngitis due to group A β-hemolytic streptococcus. Included in the study were 870 patients with either a positive culture or a clinical disease serious enough to warrant treatment with antibiotics. They were allocated alternately to a lincomycin-treated group (429 patients) or to a penicillin-treated control group (441 patients). Initial cultures were positive for group A β-hemolytic streptococci in 140 of the lincomycin group and 125 of the penicillin group. Followup cultures on these patients were negative in 131 (93%) of those treated with lincomycin and 111 (89%) of those treated with penicillin. The lincomycin was as effective as penicillin, acceptable in all dosage forms, and had a low incidence of side effects.
Fifteenth International Congress of Medicine.
Authors: Miguel Bombarda
Journal: JAMA (1904)

Dr. John A. Wyeth, New York City, has sent us a letter which he has received from Prof. Miguel Bombarda, secretary-general of the International Congress of Medicine to be held at Lisbon in 1906. Dr. Wyeth expresses the hope that the unpleasant experiences of our delegates at Madrid will not deter us from taking an interest in the Lisbon congress. He suggests that it would be well for The Journal of the Association to inaugurate this movement by printing at this time this invitation. A translation of the letter referred to is as follows: Lisbon, Dec. 22, 1903. <h3>Sir and most honored confrère:</h3> —At the last international congress at Madrid, Lisbon was designated as the place of meeting of the Fifteenth International Congress of Medicine, and the medical profession of Portugal, appreciating the great honor conferred on it, accepted with pleasure the decision of the representatives of the various countries
Lipid Treatment Assessment Project 2
Authors: David D. Waters, Carlos Brotons, Cheng-Wen Chiang, Jean Ferrières, JoAnne Foody, J. Wouter Jukema, Raul D. Santos, Juan Verdejo, Michael Messig, Ruth McPherson, Ki-Bae Seung, Lisa Tarasenko
Journal: Circulation (2009)

Background— Information about physicians’ adherence to cholesterol management guidelines remains scant. The present survey updates our knowledge of lipid management worldwide. Methods and Results— Lipid levels were determined at enrollment in dyslipidemic adult patients on stable lipid-lowering therapy in 9 countries. The primary end point was the success rate, defined as the proportion of patients achieving appropriate low-density lipoprotein cholesterol (LDL-C) goals for their given risk. The mean age of the 9955 evaluable patients was 62±12 years; 54% were male. Coronary disease and diabetes mellitus had been diagnosed in 30% and 31%, respectively, and 14% were current smokers. Current treatment consisted of a statin in 75%. The proportion of patients achieving LDL-C goals according to relevant national guidelines ranged from 47% to 84% across countries. In low-, moderate-, and high-risk groups, mean LDL-C was 119, 109, and 91 mg/dL and mean high-density lipoprotein cholesterol was 62, 49, and 50 mg/dL, respectively. The success rate for LDL-C goal achievement was 86% in low-, 74% in moderate-, and 67% in high-risk patients (73% overall). However, among coronary heart disease patients with ≥2 risk factors, only 30% attained the optional LDL-C goal of &lt;70 mg/dL. In the entire cohort, high-density lipoprotein cholesterol was &lt;40 mg/dL in 19%, 40 to 60 mg/dL in 55%, and &gt;60 mg/dL in 26% of patients. Conclusions— Although there is room for improvement, particularly in very-high-risk patients, these results indicate that lipid-lowering therapy is being applied much more successfully than it was a decade ago.
Bacteria directed to produce insulin in test application of genetic code
Authors: Phil Gunby
Journal: JAMA (1978)

Putting the genetic code to the test, California researchers have synthesized genes that "instruct" an enfeebled laboratory strain of<i>Escherichia coli</i>(EK-1) to produce the two amino acid chains of insulin. When these peptide chains are separated from the enzyme to which they are attached, purified, and mixed together, the result is a chemical structure identical to human insulin. Making the announcement are scientists from City of Hope National Medical Center at Duarte, Calif, near Los Angeles, and the research and development laboratories of Genentech, Inc, in South San Francisco. Genentech funded the work. A long-range development program now is beginning, "aimed at the eventual commercial production of human insulin" by this means. Because the precise sequence of amino acids in insulin is known, the researchers said, they were able to select nucleotides that code for each of these amino acids and "design the necessary genes on paper." Then, using
Beta-adrenergic-mediated influences on microscopic conduction in epicardial regions overlying infarcted myocardium.
Authors: G Zuanetti, R H Hoyt, P B Corr
Journal: Circulation Research (1990)

Slowing in conduction and functional block in the epicardial tissue overlying a region of transmural necrosis are pivotal in the genesis of many lethal arrhythmias during the healing phase of myocardial infarction. The mechanisms responsible for these alterations in conduction in the epicardial region have not been completely elucidated. In the present study, the microscopic abnormalities in conduction were investigated in vitro using high-density mapping with 224 bipolar electrodes (interelectrode distance, 350 microns) in isolated epicardial tissue excised from the hearts of dogs 2 weeks after anterior myocardial infarction. Seven epicardial tissue slices (group 1) exhibited uninterrupted sequential activation after stimulation at the basic cycle length as well as after premature stimuli. Four tissues (group 2) demonstrated microscopic alterations in conduction both during basic drive and premature stimuli, with the extent of conduction delay dependent on the stimulation site. In three tissues (group 3), the activation sequence was normal during the basic drive but became abnormal after premature stimulation, with the appearance of functional block in the direction transverse to fiber orientation. Superfusion with isoproterenol (10(-6) M) did not significantly modify resting membrane potential, amplitude, or maximum rate change of voltage (Vmax) of phase 0 depolarization but decreased action potential duration. Isoproterenol did not alter the activation sequence during basic drive, but it reduced the slowing in conduction elicited by premature stimulation in group 1 (p less than 0.01 in the transverse direction), alleviated microcircuitous conduction in group 2, and prevented the occurrence of functional block in tissues in group 3. Despite this salutary effect on conduction velocity, arrhythmias occurred after isoproterenol because of focal activity (three of 14, 21%) or reentry (one of 14, 7%) at very short coupling intervals of premature stimulation. These findings indicate that microscopic abnormalities in conduction occur in response to premature stimulation in epicardial regions overlying an infarct, eliciting conduction block that is more prone to occur in the direction transverse to fiber orientation and is dependent on the direction of activation. beta-Adrenergic stimulation prevents or attenuates the alterations in the pattern of activation elicited by premature stimulation. However, this potential beneficial effect of beta-adrenergic stimulation is offset by the occurrence of focal activity and reentry at short coupling intervals of premature stimulation.