tbuckley/cabot-search huggingface dataset:
NHS and the Health and Social Care Bill: end of Bevan's vision?
Authors: A. M Pollock
Journal: BMJ (2003)

Although the Labour government has repeatedly pledged its commitment to the NHS, its latest reforms pave the way for multiple providers of health care

The Health and Social Care (Community Health and Standards) Bill 2003 is the most controversial piece of legislation to come out of the government's 10 year strategy for the NHS in England.1 The bill, which abolishes government control of NHS trusts by turning them into competing independent corporations called foundation trusts, is a major policy reversal. It could lead to considerable local variation in services and endangers one of the NHS's founding principles–to provide equal care for equal need.

The new bill allows both NHS and non-NHS bodies, including private companies, to apply to become foundation trusts. Although their principal purpose is to provide goods and services to the NHS, they will be able to carry out any type of business. With guaranteed independence from direct government control, their sole statutory general duty will be to operate “effectively, efficiently, and economically.” They will not have shareholders but will be expected to make and retain surpluses for new investment or for servicing loans raised on the financial markets.2 The scale of such borrowing will depend on their ability to make surpluses.3 The government has given them several new powers to generate surpluses (box 1). These powers, taken together with changes to the methods of allocating resources,4 threaten to destabilise the provision of health services and systematically widen inequalities of access to care.

In the face of growing opposition to the bill from the BMA, trade unions, and the public, the government claims that regulatory safeguards in the bill will protect the core principles of universality and access on the basis of need (see bmj.com). However, as we show below, careful scrutiny shows that …
The Phylogenetic Position of Myxozoa: Exploring Conflicting Signals in Phylogenomic and Ribosomal Data Sets
Authors: N. M. Evans, M. T. Holder, M. S. Barbeitos, B. Okamura, P. Cartwright
Journal: Molecular Biology and Evolution (2010)

Myxozoans are a diverse group of microscopic endoparasites that have been the focus of much controversy regarding their phylogenetic position. Two dramatically different hypotheses have been put forward regarding the placement of Myxozoa within Metazoa. One hypothesis, supported by ribosomal DNA (rDNA) data, place Myxozoa as a sister taxon to Bilateria. The alternative hypothesis, supported by phylogenomic data and morphology, place Myxozoa within Cnidaria. Here, we investigate these conflicting hypotheses and explore the effects of missing data, model choice, and inference methods, all of which can have an effect in placing highly divergent taxa. In addition, we identify subsets of the data that most influence the placement of Myxozoa and explore their effects by removing them from the data sets. Assembling the largest taxonomic sampling of myxozoans and cnidarians to date, with a comprehensive sampling of other metazoans for 18S and 28S nuclear rDNA sequences, we recover a well-supported placement of Myxozoa as an early diverging clade of Bilateria. By conducting parametric bootstrapping, we find that the bilaterian placement of Buddenbrockia could not alone be explained by long-branch attraction. After trimming a published phylogenomic data set, to circumvent problems of missing data, we recover the myxozoan Buddenbrockia plumatellae as a medusozoan cnidarian. In further explorations of these data sets, we find that removal of just a few identified sites under a maximum likelihood criterion employing the Whelan and Goldman amino acid substitution model changes the placement of Buddenbrockia from within Cnidaria to the alternative hypothesis at the base of Bilateria. Under a Bayesian criterion employing the CAT model, the cnidarian placement is more resilient to data removal, but under one test, a well-supported early diverging bilaterian position for Buddenbrockia is recovered. Our results confirm the existence of two relatively stable placements for myxozoans and demonstrate that conflicting signal exists not only between the two types of data but also within the phylogenomic data set. These analyses underscore the importance of careful model selection, taxon and data sampling, and in-depth data exploration when investigating the phylogenetic placement of highly divergent taxa.
Emergence of community-associated methicillin resistant Staphylococcus aureus in Hawaii, 2001–2003
Authors: Concepcion F. Estivariz, Sarah Y. Park, Jeffrey C. Hageman, Jeffrey Dvorin, Marian M. Melish, Rose Arpon, Pat Coon, Susan Slavish, Mary Kim, Linda K. McDougal, Bette Jensen, Sigrid McAllister, David Lonsway, George Killgore, Paul E. Effler, Daniel B. Jernigan
Journal: Journal of Infection (2006)
Characterization of a phenotypically and functionally distinct subset of large granular lymphocytes (pit cells) in rat liver sinusoids
Authors: Karin Vanderkerken, Luc Bouwens, Eddie Wisse
Journal: Hepatology (1990)

Pit cells, or large granular lymphocytes, with natural tumoricidal activity are found in the sinusoids of normal rat liver. Hepatic large granular lymphocytes are heterogeneous and can be subdivided into two subsets. These subsets were compared with peripheral-blood large granular lymphocytes and were found to differ phenotypically and functionally. Phenotypical differences included lower expression of the asialo-GM1 marker of natural killer cells, lower cellular density and many more small cytoplasmic granules in hepatic large, granular lymphocytes. Low-density hepatic large, granular lymphocytes were five to eight times more cytotoxic than blood large, granular lymphocytes on a per-cell basis as measured against YAC-1 cells and colon carcinoma cells. In addition, hepatic large, granular lymphocytes were able to lyse P-815 target cells, which are resistant to blood natural killer cells. Large, granular lymphocytes isolated from the liver also contained a subset with intermediate phenotypical and functional characteristics, possibly representing a transitional form between blood and "liver-specific" large, granular lymphocytes. The liver thus contains a specific population of highly activated or further differentiated large granular lymphocytes.
Transitions in Illicit Drug Use Status Over 3 Years: A Prospective Analysis of a General Population Sample
Authors: Wilson M. Compton, Deborah A. Dawson, Kevin P. Conway, Marc Brodsky, Bridget F. Grant
Journal: American Journal of Psychiatry (2013)

The authors examined 3-year transitions among nonuse, asymptomatic use, and problem use of illicit drugs for U.S. adults in the general household population.Data were from the nationally representative National Epidemiologic Survey on Alcohol and Related Conditions, a study of 34,653 adults interviewed twice, 3 years apart. Respondents were categorized on three mutually exclusive categories of baseline drug status: past-year nonusers (N=32,675), past-year asymptomatic drug users (N=861), and past-year symptomatic drug users (N=1,117). Symptomatic drug use, or problem use, was defined as presence of one or more symptoms that operationalize DSM-IV drug abuse and dependence criteria. The authors assessed sociodemographic, health, substance use, and psychiatric covariates for association with 3-year transitions to different status categories.Among baseline nonusers, 95.4% continued to be nonusers at follow-up, 2.1% became asymptomatic users, and 2.5% developed problem use. Among baseline asymptomatic users, 66.6% had stopped using drugs at follow-up, 14.3% continued to be asymptomatic users, and 19.1% had developed problem use. Nearly half (49.0%) of those with problem use at baseline had stopped using drugs at follow-up, 10.9% had transitioned to asymptomatic use, and 40.1% continued to have problem use. Younger age, male sex, white race, and not being married were associated with progression from nonuse to use or problem use, as were alcohol and tobacco use and disorders, major depression, and schizotypal, borderline, and narcissistic personality disorders. Panic disorder and avoidant personality disorder were associated with less progression.Transitions in drug use status are common. The finding that alcohol and tobacco variables and co-occurring psychopathology are important correlates of transitions suggests the value of addressing all co-occurring disorders and substance use in patient assessments and treatment planning, both to prevent adverse transitions and to promote positive transitions.
24-hour blood pressure monitoring and clinical differentiations in patients with bronchial asthma
Authors: Nina Karoli, Anna Roschina, Andrey Rebrov
Journal: European Respiratory Journal (2013)

The aim of present study was to elucidate of special characteristics of 24-hour blood pressure (BP) monitoring in patients with asthma. We study 84 patients with stable asthma and self-reported arterial hypertension (AH).  Patient with was divided to 2 groups: with stable (19 pts) and non-stable (65 pts) AH. First group of patients had previously reported BP elevated and high systolic and/or diastolic BP by  24-hour BP monitoring  . Patients in second group had  previously reported BP elevated in asthma attacks, asthma exacerbations, but by  24-hour BP monitoring mean  24-hour systolic BP  .   The patients in two groups not differ by sex, age (47,60±9,68 and 47,06±11,06 yr), BMI and spirometry parameter.  The second group of patients had less AH duration then pts with stable AH (p  Patient with non-stable AH had correlation between night depression of systolic BP and FEV1 (r=0,56, p  We founded of special characteristics of 24-h BP and influence of obstructive symptoms on these parameters in patient with asthma.
Uptake and degradation of Curosurf after tracheal administration to newborn and adult rabbits
Authors: A Alberti, A Pettenazzo, GB Enzi, A Palamidese, C Mapp, P Ventura, A Baritussio
Journal: European Respiratory Journal (1998)

This paper examines the removal from the airways of Curosurf, a commercial surfactant derived from porcine lungs, administered at pharmacological concentrations to newborn or adult animals. Curosurf was labelled by the addition of radioactive dipalmitoyl phosphatidylcholine (DPPC) and administered intratracheally to newborn and adult rabbits at a dose of 200 mg x kg(-1) body weight. The disappearance of DPPC from the airways and its appearance in alveolar macrophages, lung parenchyma, lamellar bodies, serum, liver, kidneys and brain was then studied for 24-48 h. The in vitro degradation of Curosurf DPPC by alveolar macrophages was also studied. During the first 3 h after instillation, large amounts of Curosurf left the airways and became associated with tissue, indicating that it mixed rapidly with the endogenous pools of surfactant. A fraction of administered DPPC became associated with the lamellar bodies, suggesting that Curosurf can be recycled. Curosurf administration did not stop the secretion of endogenous surfactant. Very little intact radioactive DPPC could be recovered at any time in alveolar macrophages, however, macrophages have the ability, in vitro, to degrade Curosurf. Newborn rabbits lose Curosurf from the lungs at a slower rate than adult rabbits. One and two days after instillation, organic extracts from the liver, kidney, brain and serum contained small but measurable amounts of radioactivity. These results indicate that Curosurf rapidly enters the pathways of surfactant metabolism and that alveolar macrophages may play an important role in the catabolism of Curosurf.
Activation of cardiac sympathetic afferents during coronary occlusion. Evidence for reflex activation of sympathetic nervous system during transmural myocardial ischemia in the dog.
Authors: A J Minisi, M D Thames
Journal: Circulation (1991)

BACKGROUND Left ventricular sympathetic afferent nerves are located mainly in superficial epicardial layers. Reflex excitatory responses mediated by sympathetic afferent nerves have been observed during myocardial ischemia in cats and humans but not in dogs. Previous canine studies have induced ischemia by occlusion of a coronary artery. Extensive collateral circulation in the canine heart may limit ischemia of epicardial layers during simple coronary occlusion, resulting in little stimulation of sympathetic afferent nerves and minimal reflex excitatory responses. METHODS AND RESULTS In anesthetized dogs with sinoaortic and vagal deafferentation, we determined whether reflex sympathoexcitatory responses mediated by sympathetic afferents occurred during transmural myocardial ischemia. Reflex sympathoexcitation was quantitated by direct recording from either efferent renal (n = 20) or cardiac (n = 5) sympathetic nerves. Responses of arterial pressure and efferent sympathetic nerve activity were measured during simple occlusion of the anterior descending artery (LAD alone) and during LAD occlusion with a circumflex stenosis (LAD + CIRC). This circumflex stenosis was adjusted to abolish coronary vasodilator reserve without reducing basal flow. We observed significantly greater reflex increases in renal (32 +/- 5%) and cardiac (58 +/- 15%) nerve activity during LAD + CIRC than during LAD alone (14 +/- 6% and 8 +/- 7%, respectively). Reflex changes in renal nerve activity during LAD + CIRC were abolished by interruption of cardiac sympathetic afferent pathways (n = 5). In eight experiments, myocardial blood flow was measured during the two coronary occlusions. These experiments confirmed that LAD + CIRC elicited more transmural ischemia in the LAD distribution than did LAD alone. However, these experiments also revealed that LAD + CIRC elicited endocardial ischemia in the circumflex distribution. In five additional experiments, regional sympathetic deafferentation of the posterior left ventricle by epicardial application of 88% phenol along the atrioventricular groove had no significant effect on renal nerve responses to LAD + CIRC (36 +/- 5% increase before phenol versus 31 +/- 3% increase after phenol). These results indicate that endocardial ischemia in the circumflex distribution did not contribute to the reflex increases in nerve activity that were noted during LAD + CIRC. CONCLUSIONS Reflex sympathoexcitation mediated by cardiac sympathetic afferents can be elicited in dogs. However, these responses are significant only during ischemia that is transmural and involves the superficial epicardial layers of the left ventricle.
Anaphylaxis from Passive Transfer of Peanut Allergen in a Blood Product
Authors: Joannes F.M. Jacobs, Joseph L. Baumert, Paul P. Brons, Irma Joosten, Stef J. Koppelman, Elisabeth C.M. van Pampus
Journal: New England Journal of Medicine (2011)

Anaphylactic transfusion reactions from passive transfer of IgE have been documented, but a case is now reported in which the eliciting factor was a food allergen in peanuts ingested by blood donors before donation.
In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. Delivery of ribosome-inactivating proteins to spleen and lymph node T cells.
Authors: N L Letvin, L V Chalifoux, K A Reimann, J Ritz, S F Schlossman, J M Lambert
Journal: Journal of Clinical Investigation (1986)

The selective delivery in vivo of a T lymphocyte-specific monoclonal antibody and immunotoxin conjugates to T cells in lymph node and spleen was assessed in rhesus monkeys. A transient coating of all T lymphocytes in the lymph nodes and spleens of healthy rhesus monkeys could be achieved after infusion of unconjugated anti-T11. Because derivatized antibody is cleared more rapidly than unconjugated antibody, it was necessary to infuse a higher dose of immunotoxin than antibody alone to achieve saturation of the lymphocyte binding sites with anti-T11. When sufficient antibody-toxin conjugate was infused, toxin was readily demonstrable on lymph node and spleen T cells by 16 h after infusion. This demonstration that toxins can be successfully delivered with specificity to target T cell populations in the monkey suggests that killing of restricted cell populations in vivo should be feasible.
A phase II study of single-agent docetaxel in patients with metastatic esophageal cancer
Authors: K. Muro, T. Hamaguchi, A. Ohtsu, N. Boku, K. Chin, I. Hyodo, H. Fujita, W. Takiyama, T. Ohtsu
Journal: Annals of Oncology (2004)

To evaluate the activity and toxicity of docetaxel in patients with metastatic esophageal cancer.Eligible patients had histologically confirmed carcinoma of the esophagus with measurable metastatic sites according to Response Evaluation Criteria in Solid Tumors (RECIST). Patients were either chemotherapy-naïve or previously treated with one regimen of chemotherapy. Docetaxel 70 mg/m(2) was administered intravenously over 1-2 h, every 21 days.Of 52 patients enrolled in this study, three were excluded because they did not receive docetaxel due to worsening condition after enrollment. Thirty-six patients had received prior platinum-based chemotherapy. The majority of patients (94%) had squamous cell carcinoma. Ten of 49 evaluable patients [20%; 95% confidence interval (CI) 10-34%] showed a partial response. Of the 10 partial responses, six patients had received prior platinum-based chemotherapy. Grade 3 or 4 neutropenia was noted in 43 of 49 patients (88%), and nine of 49 patients (18%) developed febrile neutropenia. Twenty-eight of 49 patients (57%) required lenograstim. Grade 3 anorexia and fatigue occurred in nine (18%) and six (12%) patients, respectively. Median survival time was 8.1 months (95% CI 6.6-11.3) and the 1-year survival rate was 35% (95% CI 21-48%).Docetaxel as a single agent is effective in esophageal cancer, but careful management of neutropenia is needed.
Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation
Authors: Adlen Foudi, Daniel J. Kramer, Jinzhong Qin, Denise Ye, Anna-Sophie Behlich, Scott Mordecai, Frederic I. Preffer, Arnaud Amzallag, Sridhar Ramaswamy, Konrad Hochedlinger, Stuart H. Orkin, Hanno Hock
Journal: The Journal of Experimental Medicine (2014)

The zinc finger transcriptional repressor Gfi-1b is essential for erythroid and megakaryocytic development in the embryo. Its roles in the maintenance of bone marrow erythropoiesis and thrombopoiesis have not been defined. We investigated Gfi-1b’s adult functions using a loxP-flanked Gfi-1b allele in combination with a novel doxycycline-inducible Cre transgene that efficiently mediates recombination in the bone marrow. We reveal strict, lineage-intrinsic requirements for continuous adult Gfi-1b expression at two distinct critical stages of erythropoiesis and megakaryopoiesis. Induced disruption of Gfi-1b was lethal within 3 wk with severely reduced hemoglobin levels and platelet counts. The erythroid lineage was arrested early in bipotential progenitors, which did not give rise to mature erythroid cells in vitro or in vivo. Yet Gfi-1b−/− progenitors had initiated the erythroid program as they expressed many lineage-restricted genes, including Klf1/Eklf and Erythropoietin receptor. In contrast, the megakaryocytic lineage developed beyond the progenitor stage in Gfi-1b’s absence and was arrested at the promegakaryocyte stage, after nuclear polyploidization, but before cytoplasmic maturation. Genome-wide analyses revealed that Gfi-1b directly regulates a wide spectrum of megakaryocytic and erythroid genes, predominantly repressing their expression. Together our study establishes Gfi-1b as a master transcriptional repressor of adult erythropoiesis and thrombopoiesis.
THE COMPARATIVE EFFECTS OF COMA DOSES OF AMORPHOUS INSULIN ADMINISTERED INTRAVENOUSLY AND SUBCUTANEOUSLY TO PSYCHOTIC PATIENTS
Authors: IRVING C. SHERMAN, JOHN C. MERGENER, ABRAHAM A. LOW
Journal: American Journal of Psychiatry (1941)

1. In a group of 13 schizophrenic patients the blood sugar fell more promptly in response to coma doses of amorphous insulin given intravenously than to those given subcutaneously. 2. The fall in blood sugar in response to coma doses of insulin given intravenously occurs at about the same rate as in response to small doses—e.g., 10 units. In the latter case the blood sugar returns to normal values rapidly, whereas in the former it stays low for a prolonged time, so that coma ensues. 3. The only practical advantage of the intravenous administration of insulin is the shortening of the pre-coma period. 4. There was no appreciable difference in the coma doses required between the two methods of administration. 5. There was no significant difference in the complications resulting from the two methods of injection. 6. Spontaneous emergence from coma produced by intravenous insulin is rare.
Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts.
Authors: S K Sanders, P A Giblin, P Kavathas
Journal: The Journal of Experimental Medicine (1991)

The lymphocyte differentiation marker CD8 acts as a coreceptor with the T cell receptor (TCR) during recognition of peptide presented by major histocompatibility complex (MHC) class I molecules. The functions of CD8 in the TCR complex are thought to be signaling through the association of CD8 with the protein tyrosine kinase p56lck and adhesion to MHC class I through the alpha 3 domain. While the ability of the CD8 alpha/alpha homodimer to bind to classical MHC class I molecules has been shown, it is unclear whether CD8 can also bind nonclassical molecules. Of particular interest is human histocompatibility leukocyte antigen (HLA)-G which is expressed on placental cytotrophoblast cells. These cells do not express HLA-A, -B and -C molecules. In this report, we demonstrate that CD8 can bind to HLA-G. It is possible, therefore, that a cell bearing CD8 may interact with HLA-G-expressing cells.
Adiponectin acts as an anti-inflammatory cytokine on human lung macrophages
Authors: Hélène Salvator, Stanislas Grassin-Delyle, Charlotte Abrial, Emmanuel Naline, Marion Brollo, Philippe Devillier
Journal: European Respiratory Journal (2013)

Adiponectin (APN) is an adipokine, mostly released by adipocytes, involved in the inflammatory status observed in obese subjects.  Lung macrophages were isolated from tissues obtained after surgical resection for cancer. Macrophages were treated with LPS (10 ng/ml), Poly I:C (10 µg/ml) and IL-4 (10 ng/ml) in presence or not of APN (3-10-30 µg/ml). LPS and Poly I:C are agonists that guide macrophages towards an M1-classical state of activation while IL-4 promotes an M2-alternative state. Cytokines were measured by ELISA in supernatants after 24 hours culture. In addition APN was measured in supernatants of lung parenchymal explants after 24h culture. Results were obtained from preparations on 4-9 different patients.  APN concentration-dependently reduced LPS-induced release of CCL2, CXCL10, CCL4 and CXCL1; the reduction with APN 10µg/ml was respectively -73±11%, -61.5 ±16%, -56±7% and -68±8.5 %.  Similarly, APN 10 µg/ml reduced Poly I:C-induced release of CCL2, CXCL10, CCL4 and CXCL1, respectively : -64.4±10%, -78±8%, -84±9% and -44.4±8.4%  Finally, APN also decreased IL4-induced release of M2 cytokines: CCL13 (-96±1%) and CCL18 (-77.4±3.6%).  Otherwise, the basal concentration of APN in lung parenchymal supernantants was 144±30 ng/ml corresponding to an estimated concentration of 43.2 µg/ml of interstitial tissue. This measure was not modulated by LPS.  APN, at concentrations close to that in lung parenchyma, was able to reduce cytokine production in human lung macrophages stimulated either by LPS, Poly I:C or IL4, suggesting that APN may be involved in the regulation of lung inflammation.