tbuckley/cabot-search huggingface dataset:
Misleading, unscientific, and unjust: the United Kingdom's research assessment exercise
Authors: G. Williams
Journal: BMJ (1998)

Keen observers of Britain will know of our obsession with regularly occurring phenomena that involve large sums of money, balls, and disappointment. Two obvious examples are test match cricket and the national lottery. Another, just as parochial but with lessons for the global scientific community, is the research assessment exercise (RAE) run every four years by the Higher Education Funding Councils. The aim of the exercise is to measure research activity in British academic institutions and thus determine how the councils' research budget will be distributed among the country's universities.

#### Summary points

The aim of the research assessment exercise is to evaluate research success and determine central funding for academic units in the United Kingdom

The assessment criteria used are restrictive, flawed, and unscientific and produce a distorted picture of research activity that can threaten the survival of active and productive research units

The assessment exercise is also unaccountable, inefficient, time consuming, and expensive

The assessment exercise should be made objective, by basing it solely on each unit's total published output during the survey period; each publication would be scored for quality (using agreed criteria) and the unit's share of the work done

With a computerised spreadsheet, data could be collected easily and each unit's submission for assessment continually updated. The assessment scores could determine the national ranking of groups in each specialty, as well as the distribution of central funds to each unit

In the 1996 research assessment exercise each “unit of assessment” in each university was graded from 1 (research of little consequence) to 5 (research of international renown) and 5* (outstanding).1 In the “hospital based clinical medicine” unit of assessment (which includes all mainstream medical and surgical specialties) a grade 5* was awarded to two institutions, grade 5 to four, grade 4 to eight, grade 3a and 3b …
Regulation of Ion Channel Distribution at Synapses
Authors: S C Froehner
Journal: Annual Review of Neuroscience (1993)

A model of neuromuscular synaptogenesis predicts that factors released by the nerve, such as agrin, determine the time and site of AChR clustering. These factors are thought to bind to specific receptors on the muscle fiber and activate intracellular signaling pathways, which act ultimately on the AChR, on the postsynaptic cytoskeleton, or on proteins, such as the 43K protein, that link AChR to the cytoskeleton. This model is not yet entirely proven, but provides a clear framework for further studies. Clustering of sodium channels at the neuromuscular postsynaptic membrane may also involve interaction with the cytoskeleton, but the signaling molecules are not yet known. AChR clustering and sodium channel clustering are separable events, both in the molecules involved and in developmental timing. Ion channel clustering in the CNS is less well understood, but may have features in common with the neuromuscular model. For example, glycine receptors are associated with gephyrin, a protein that mediates linkage to synaptic microtubules, thus raising obvious analogies to muscle AChR and the 43K protein. It is unknown, however, if AChR clustering in neurons is regulated by mechanisms in common with muscle. Coclustering of ion channels at synapses, both across the synaptic gap and within the same postsynaptic site, is likely to be of major importance to synaptic modulation and integration. Alignment of postsynaptic receptors with presynaptic calcium channels is critical for rapid transmission, but is achieved by mechanisms not yet understood. According to current models, the codistribution of two types of glutamate receptors in the postsynaptic membrane on dendritic spines is important for initiation of LTP. It is reasonable to expect that the basic mechanisms currently being elucidated at the neuromuscular junction will lead to greater understanding of how the CNS uses ion channel distribution to modulate synaptic activity.
Postprandial Insulin Lispro: A new therapeutic option for type 1 diabetic patients
Authors: Guntram Schernthaner, Wolfgang Wein, Klaudia Sandholzer, Susanna Equiluz-Bruck, Peter C Bates, Martin A Birkett
Journal: Diabetes Care (1998)

For intensified insulin therapy of type 1 diabetes, bolus injection of regular human insulin 30-15 min before a meal is currently recommended. This randomized study is aimed to determine whether insulin lispro (LIS), a new insulin analog with a rapid onset of action, can provide comparable blood glucose (BG) control by injection after the meal.Eighteen type 1 diabetic subjects injected regular insulin (REG) at 40, 20, or 0 min before or LIS at 20 or 0 min before or 15 min after the start of a standardized test meal. BG excursions and area under the curve of BG excursions (AUC) at the six visits were compared by analysis of variance. Hypoglycemic events (BG < or = 2.78 mmol/l) were evaluated in relation to the achieved postprandial BG control.Mean AUC values were 2.00, 2.55, and 3.33 mmol.h.l-1 for REG given 40, 20, and 0 min before the test meal, respectively, and -2.19, -2.15, and 1.98 mmol.h.l-1 for LIS given 20 and 0 min before and 15 min after the start of the test meal, respectively. LIS injected 20 min (-20) or immediately (0) before the meal was significantly more effective in controlling postprandial BG excursion (P < 0.001) than any REG treatment. Postprandial injection of LIS (15) did not compromise postprandial BG control and resulted in less hypoglycemia. REG -40 and LIS -20 were associated with early hypoglycemia, but other hypoglycemic events were equally distributed among groups.The optimal time for bolus insulin injection was 20 min before the meal for REG and immediately before the meal for LIS. LIS injected immediately after a standard meal provided postprandial BG control at least as good as REG injected from 40 to 0 min before the meal. Postprandial injection of LIS is an attractive new therapeutic option.
Bad medicine: sports medicine
Authors: D. Spence
Journal: BMJ (2011)

At school I wore plimsolls for football, and I slipped and skidded across the mud in a drenched, freezing cotton T shirt. But when I returned to exercise 25 years later, sports science had banished plimsolls as a fashion accessory. I listened to the chatter of the exercising classes: shoes, insoles, isotonic drinks, physiotherapy, personal trainers, heart rate monitors, massive watches, diets, and massages. But for all their physical strength, sports people are the zenith of vulnerable neuroticism. And everything is gospel from the mouths of evangelical sports scientists, supported by a global …
Thyroid Carcinoma in the Newborn
Authors: M. D. Ross
Journal: BMJ (1964)

MEDIBSH 1659 intercostal muscles to provide either an adequate cough mechanism or augmented res- piratory excursion.(2) In cases of cord section between C.2 and C.6, upper trapezius fibres to operate voluntary finger flexion.In cases in which shoulder girdle and arm muscles have been spared but hand function is deficient, it is hoped that this defect may thus be remedied on a controlled voluntary basis.(3) Ultimately perhaps, by cross over from anterior deltoid fibres to hip flexors of oppo- site side, to provide a method of walking.-Iam, etc.,
Pathways Targeting Tumor Lymphangiogenesis
Authors: Christoph Wissmann, Michael Detmar
Journal: Clinical Cancer Research (2006)

Abstract Tumor metastasis to sentinel lymph nodes represents the first step of tumor dissemination in most human cancers and serves as a major prognostic indicator for disease progression. Recent studies have revealed that tumors can actively induce the formation of lymphatic vessels, and that tumor lymphangiogenesis is correlated with lymph node metastasis in experimental cancer models and in several types of human cancers. Metastatic tumor cells may continue to promote lymphatic vessel growth even after their metastasis to sentinel lymph nodes, likely promoting further cancer spread. Vascular endothelial growth factor-C (VEGF-C) and VEGF-D were the first specific lymphangiogenesis factors identified, acting predominantly via VEGF receptor-3 (VEGFR-3) that is expressed by lymphatic endothelial cells, and a large number of clinical studies have shown a correlation between tumor expression of VEGF-C or VEGF-D and lymph node metastasis. VEGFR-3 activation promotes lymphatic endothelial cell proliferation, migration, and survival via the extracellular signal-regulated kinase 1/2, the phosphatidylinositol 3-kinase/AKT, and the c-Jun NH2-terminal kinase 1/2 pathways. Additional tumor lymphangiogenesis factors have been recently identified, including VEGF-A. Importantly, blockade of the VEGFR-3 pathway by specific antibodies, by soluble receptor constructs, and by small molecule kinase inhibitors efficiently inhibits experimental tumor lymphangiogenesis and metastasis and might also represent a novel therapeutic avenue for the treatment of human cancers.
Chronic Erosive (Verrucous) Gastritis: A Study of 108 Patients
Authors: P. H. R. Green, D. Fevre, P. Barrett, J. Hunt, P. Gillespie, G. Nagy
Journal: Endoscopy (1977)

Chronic erosive gastritis (C.E.G.) is a gastric mucosal lesionwith characteristic radiological and endoscopic appearances. Pyloric gland hyperplasia is seen on histological examination of biopsy specimens. C.E.G. is uncommonly reported in the English literature. In reviewing 3,800 upper gastro-intestinal endoscopies from 1971--1976, 108 patients were diagnosed as having typical features of chronic erosive gastritis, an incidence of 2.8%. There was a significant association with duodenal ulceration and an overall male predominance. The lesion can also co-exist with gastric ulceration and has been observed as an incidental finding in patients examined urgently for upper gastro-intestinal bleeding. In this context C.E.G. should be distinguished from acute mucosal erosions. Symptoms may relate to the accompanying peptic ulceration, although dyspepsia epigastric pain, fullness and nausea may possibly occur with C.E.G. alone.
Acute effects of polychlorinated biphenyl-containing and -free transformer fluids on rat testicular steroidogenesis.
Authors: S A Andric, T S Kostic, S M Dragisic, N L Andric, S S Stojilkovic, R Z Kovacevic
Journal: Environmental Health Perspectives (2000)

Polychlorinated biphenyl (PCB)-based transformer fluids belong to a class of environmentally persistent mixtures with known toxic effects. Here, we studied the acute effects of Askarel (which contains Aroclor 1260) and two substitute transformer fluids (the silicone oil-based DC561 and the mineral oil-based ENOL C) on rat testicular steroidogenesis. Single intraperitoneal (ip; 10 mg/kg body weight) or bilateral intratesticular (itt; 25 microg/testis) injections of Askarel markedly decreased serum androgen levels 24 hr after administration. In acute testicular cultures from these animals, chorionic gonadotropin-stimulated progesterone and androgen productions were severely attenuated. When itt was injected or added in vitro, Askarel inhibited 3ss-hydroxysteroid dehydrogenase (3ssHSD), stimulated 17[alpha]-hydroxylase/lyase (P450c17), and did not affect 17ss-hydroxysteroid dehydrogenase in testicular postmitochondrial fractions. The ip-injected Askarel did not affect 3ssHSD, but inhibited P450c17, suggesting that a more intensive metabolism of peripherally injected Askarel reduces the circulating levels of active ingredients below the threshold needed for inhibition of 3ssHSD and generates a derivative that inhibits P450c17. In contrast to Askarel, itt-injection (25 microg/testis) of DC561 and ENOL C did not affect in vivo and in vitro steroidogenesis. These findings show the acute effects of Askarel, but not silicone and mineral oils, on testicular steroidogenesis.
Intracellular Calcium Disturbances Induced by Arsenic and Its Methylated Derivatives in Relation to Genomic Damage and Apoptosis Induction
Authors: Ana-Maria Florea, Ebenezer N. Yamoah, Elke Dopp
Journal: Environmental Health Perspectives (2005)

Arsenic and its methylated derivatives are contaminants of air, water, and food and are known as toxicants and carcinogens. Arsenic compounds are also being used as cancer chemotherapeutic agents. In humans, inorganic arsenic is metabolically methylated to mono-, di-, and trimethylated forms. Recent findings suggest that the methylation reactions represent a toxification rather than a detoxification pathway. In recent years, the correlation between arsenic exposure, cytotoxicity and genotoxicity, mutagenicity, and tumor promotion has been established, as well as the association of arsenic exposure with perturbation of physiologic processes, generation of reactive oxygen species, DNA damage, and apoptosis induction. Trivalent forms of arsenic have been found to induce apoptosis in several cellular systems with involvement of membrane-bound cell death receptors, activation of caspases, release of calcium stores, and changes of the intracellular glutathione level. It is well known that calcium ion deregulation plays a critical role in apoptotic cell death. A calcium increase in the nuclei might lead to toxic effects in the cell. In this review, we highlight the relationship between induced disturbances of calcium homeostasis, genomic damage, and apoptotic cell death caused by arsenic and its organic derivatives.
The Impact of the Internet on Cancer Outcomes
Authors: G. Eysenbach
Journal: CA A Cancer Journal for Clinicians (2003)

Each day, more than 12.5 million health-related computer searches are conducted on the World Wide Web. Based on a meta-analysis of 24 published surveys, the author estimates that in the developed world, about 39% of persons with cancer are using the Internet, and approximately 2.3 million persons living with cancer worldwide are online. In addition, 15% to 20% of persons with cancer use the Internet "indirectly" through family and friends. Based on a comprehensive review of the literature, the available evidence on how persons with cancer are using the Internet and the effect of Internet use on persons with cancer is summarized. The author distinguishes four areas of Internet use: communication (electronic mail), community (virtual support groups), content (health information on the World Wide Web), and e-commerce. A conceptual framework summarizing the factors involved in a possible link between Internet use and cancer outcomes is presented, and future areas for research are highlighted.
Detection of a Stomach Gastrointestinal Stromal Tumor in Situs Invertus by Gallium-67 Scintigraphy
Authors: Jong-Kang Lee, Yeu-Sheng Tyan
Journal: Clinical Nuclear Medicine (2006)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Approximately 70% of the tumors are found in the stomach, 20% to 30% are found in the small intestine, and less than 10% are found elsewhere in the gastrointestinal tract. An 80-year-old man with anemia underwent a whole-body tumor survey with Ga-67 citrate. Markedly increased uptake was observed in the right upper quadrant of the abdomen. Computed tomography (CT) showed situs invertus with a heterogeneous mass in the stomach and multiple rim-enhancing lesions in the liver. Histologic examination of an endoscopic biopsy specimen confirmed a gastrointestinal stromal tumor (GIST) of the stomach.
Serum Globulin Levels in Whites and Negroes
Authors: Harold Keltz, George W. Comstock
Journal: New England Journal of Medicine (1959)

FROM various parts of the world one gets reports of differing serum globulin values.1 2 3 4 5 The areas with a predominantly Negro population tend to have higher "normal," or usual, values than those with a predominantly white population. These differences have been ascribed to the prevalence of various chronic diseases, which presumably result in elevated globulin levels. However, Comens6 has demonstrated a significant difference between the levels of Negro and white patients in his hypertensive clinic in St. Louis, Missouri, a finding that suggests the possibility of a racial difference.As part of a study of the epidemiology of sarcoidosis, determinations of . . .
The European Union Biological Standardization Program: Detailed Characterization of GMP-produced Recombinant Bet v 1.0101 and Phl p 5.0109 as Candidate Reference Standards
Authors: M. Himly, A. Neubauer, P. Moingeon, O. Cromwell, R. van Ree, K. Buchheit, S. Vieths, F. Ferreira
Journal: Journal of Allergy and Clinical Immunology (2009)
MRI assessment of hemodynamic effects of angiopoietin-2 overexpression in a brain tumor model
Authors: Samuel Valable, Dauphou Eddi, Jean-Marc Constans, Jean-Sébastien Guillamo, Myriam Bernaudin, Simon Roussel, Edwige Petit
Journal: Neuro-Oncology (2009)

Despite treatment efforts, the median survival in patients with glioblastoma multiforme, the most aggressive form of glioma, does not extend beyond 12-15 months. One of the major pathophysiological characteristics of these tumors is their ability to induce active angiogenesis. Thus, based on the lack of efficient therapies, agents that inhibit angiogenesis are particularly attractive as a therapeutic option. However, it has been recently proposed that although specifically targeting vascular endothelial growth factor, the main angiogenic factor, certainly leads to significant tumor regression, it could also be followed by tumor relapses. In this case, angiogenesis is driven by alternate pathways that include other angiogenic factors. One possible strategy to overcome this therapeutic obstacle is to overexpress antivascular factors such as angiopoietin-2 (Ang2). Here, by using MRI and histological analysis, we studied the vascular events involved in glioma growth impairment induced by Ang2 overexpression. Our results show that an increase in Ang2 expression, during the tumor growth, leads to a significant decrease in tumor growth ( approximately 86%) along with an increase in the survival median ( approximately 70%) but does not modify the tumor vascular area or cerebral blood volume. However, tumor Ang2-derived blood vessels display an abnormal, enlarged morphology. We show that the presence of Ang2 leads to an enhancement of tumor perfusion and a decrease in tumor vessel permeability. Based on our MR image evaluations of hemodynamic tumor vessel changes, we propose that Ang2-derived tumor vessels lead to an inadequate oxygenation of the tumor tissue, leading to impairment in tumor growth.
Four compartment method: a simplified and cost-effective method of noncultured epidermal cell suspension for the treatment of vitiligo
Authors: R. Kumar, D. Parsad, C. Singh, S. Yadav
Journal: British Journal of Dermatology (2013)

Despite continued progress towards an elucidation of pathogenetic pathways in vitiligo, a definitive cure remains elusive. Noncultured epidermal cell suspension (NCECS) is emerging as the treatment of choice for surgical management of both stable and segmental vitiligo. NCECS is very effective in repigmenting stable vitiligo, but the technique requires an expert and the support of a laboratory facility.To investigate a simplified and more cost-effective method for NCECS.We simplified the conventional NCECS method and made it more cost-effective and simple enough to be performed in the clinic without laboratory equipment. We named this the four compartment (FC) method. Six patients with vitiligo were treated with this FC method.The FC method for NCECS is highly cost-effective and simple. Six patients with vitiligo were treated and the results showed marked to complete repigmentation in four patients and > 50% repigmentation in two patients in 3 months.The FC method is a cost-effective and simple procedure to prepare epidermal cell suspensions. In this modified method we showed that there is no need for pipette, tips, centrifuge tube and most importantly a centrifuge machine or any other expensive laboratory equipment.
Cross-linking of the dermo-epidermal junction of skin regenerating from keratinocyte autografts. Anchoring fibrils are a target for tissue transglutaminase.
Authors: M Raghunath, B Höpfner, D Aeschlimann, U Lüthi, M Meuli, S Altermatt, R Gobet, L Bruckner-Tuderman, B Steinmann
Journal: Journal of Clinical Investigation (1996)

Since transglutaminases create covalent gamma-glutamyl-epsilon-lysine cross-links between extracellular matrix proteins they are prime candidates for stabilizing tissue during wound healing. Therefore, we studied the temporo-spatial expression of transglutaminase activity in skin regenerating from cultured epithelial autografts in severely burned children by the specific incorporation of monodansylcadaverine into cryostat sections from skin biopsies obtained between 5 d to 17 mo after grafting. The dansyl label was subsequently immunolocalized in the epidermis, dermal connective tissue, and along the basement membrane. Incubation of cryosections of normal and regenerating skin with purified tissue transglutaminase confirmed the dermo-epidermal junction and the papillary dermis as targets for this enzyme and revealed that in regenerating skin transamidation of the basement membrane zone was completed only 4-5 mo after grafting. Immunoelectron microscopy revealed that three distinct regions on the central portion of anchoring fibrils were positive for monodansylcadaverine in normal skin which were negative during the initial phase of de novo formation of anchoring fibrils in regenerating skin. Biochemically, we identified collagen VII as potential substrate for tissue transglutaminase. Thus, tissue transglutaminase appears to play an important role not only in cross-linking of the papillary dermis but also of the dermo-epidermal junction in particular.
Role of adenosine in the sympathetic activation produced by isometric exercise in humans.
Authors: F Costa, I Biaggioni
Journal: Journal of Clinical Investigation (1994)

Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate increased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 96 +/- 25% (n = 6, P < 0.01) and MABP by 12 +/- 3 mmHg (P < 0.01). Adenosine produced forearm discomfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adenosine. Furthermore, adenosine receptor antagonism with intrabrachial theophylline (1 microgram/ml forearm per min) blocked the increase in MSNA (92 +/- 15% vs. 28 +/- 6%, n = 7, P < 0.01) and MABP (38 +/- 6 vs. 27 +/- 4 mmHg, P = 0.01) produced by isometric handgrip (30% of maximal voluntary contraction) in the infused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle afferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans.