tbuckley/cabot-search huggingface dataset:
Asylum seekers and refugees in Britain: What brings asylum seekers to the United Kingdom?
Authors: A. Burnett
Journal: BMJ (2001)

This is the first in a series of three articles 

Asylum seekers and refugees have been the subject of much media and political attention over recent months, but they are often misrepresented. In the first paper in this series we discuss the reasons that cause people to go into exile and the situation in which they find themselves as refugees in the United Kingdom. In subsequent papers we will examine the health needs of refugees, appropriate care and responses, the specific health effects of torture and organised violence, the needs of health workers, and the structural organisation of health services.

The term refugee is used to include people at all stages of the asylum process. The various definitions of refugee status are given in the box below.

#### Definitions of refugee status

Asylum seeker—asylum claim submitted, awaiting Home Office decision

Refugee status (accepted as a refugee under the Geneva Convention)—given leave to remain in the UK for four years, and can then apply for settled status (Indefinite leave to remain, see below). Eligible for family reunion for one spouse and all children under 18 years

Indefinite leave to remain (ILR)—given permanent residence in Britain indefinitely. Eligible for family reunion only if able to support family without recourse to public funding

Exceptional leave to remain (ELR)—the Home Office accepts there are strong reasons why the person should not return to the country of origin and grants the right to stay in Britain for four years. Expected to return if the home country situation improves. Ineligible for family reunion

Refusal—the person has a right of appeal, within strict time limits

Britain, as a signatory to the 1951 Geneva Convention, and for many years before this, has offered asylum to those fleeing from persecution and violence. Under the terms of the Convention, a refugee is defined as any person …
A novel sodium bicarbonate cotransporter-like gene in an ancient duplicated region: SLC4A9 at 5q31.
Authors: Leonard Lipovich, Eric D Lynch, Ming K Lee, Mary-Claire King
Journal: Genome biology (2001)

Sodium bicarbonate cotransporter (NBC) genes encode proteins that execute coupled Na+ and HCO3- transport across epithelial cell membranes. We report the discovery, characterization, and genomic context of a novel human NBC-like gene, SLC4A9, on chromosome 5q31.SLC4A9 was initially discovered by genomic sequence annotation and further characterized by sequencing of long-insert cDNA library clones. The predicted protein of 990 amino acids has 12 transmembrane domains and high sequence similarity to other NBCs. The 23-exon gene has 14 known mRNA isoforms. In three regions, mRNA sequence variation is generated by the inclusion or exclusion of portions of an exon. Noncoding SLC4A9 cDNAs were recovered multiple times from different libraries. The 3' untranslated region is fragmented into six alternatively spliced exons and contains expressed Alu, LINE and MER repeats. SLC4A9 has two alternative stop codons and six polyadenylation sites. Its expression is largely restricted to the kidney. In silico approaches were used to characterize two additional novel SLC4A genes and to place SLC4A9 within the context of multiple paralogous gene clusters containing members of the epidermal growth factor (EGF), ankyrin (ANK) and fibroblast growth factor (FGF) families. Seven human EGF-SLC4A-ANK-FGF clusters were found.The novel sodium bicarbonate cotransporter-like gene SLC4A9 demonstrates abundant alternative mRNA processing. It belongs to a growing class of functionally diverse genes characterized by inefficient highly variable splicing. The evolutionary history of the EGF-SLC4A-ANK-FGF gene clusters involves multiple rounds of duplication, apparently followed by large insertions and deletions at paralogous loci and genome-wide gene shuffling.
Systematic review of dietary intervention trials to lower blood total cholesterol in free-living subjects Commentary: Dietary change, cholesterol reduction, and the public health---what does meta-analysis add?
Authors: J L Tang, J M Armitage, T Lancaster, C A Silagy, G H Fowler, H A W Neil, G. D. Smith, S. Ebrahim
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives:</b> To estimate the efficacy of dietary advice to lower blood total cholesterol concentration in free-living subjects and to investigate the efficacy of different dietary recommendations. <b>Design:</b> Systematic overview of 19 randomised controlled trials including 28 comparisons. <b>Subjects:</b> Free-living subjects. <b>Interventions:</b> Individualised dietary advice to modify fat intake. <b>Main outcome measure:</b> Percentage difference in blood total cholesterol concentration between the intervention and control groups. <b>Results:</b> The percentage reduction in blood total cholesterol attributable to dietary advice after at least six months of intervention was 5.3% (95% confidence interval 4.7% to 5.9%). Including both short and long duration studies, the effect was 8.5% at 3 months and 5.5% at 12 months. Diets equivalent to the step 2 diet of the American Heart Association were of similar efficacy to diets that aimed to lower total fat intake or to raise the polyunsaturated to saturated fatty acid ratio. These diets were moderately more effective than the step 1 diet of the American Heart Association (6.1% <i>v</i> 3.0% reduction in blood total cholesterol concentration; P&lt;0.0001). On the basis of reported food intake, the targets for dietary change were seldom achieved. The observed reductions in blood total cholesterol concentrations in the individual trials were consistent with those predicted from dietary intake on the basis of the Keys equation. <b>Conclusions:</b> Individualised dietary advice for reducing cholesterol concentration is modestly effective in free-living subjects. More intensive diets achieve a greater reduction in serum cholesterol concentration. Failure to comply fully with dietary recommendations is the likely explanation for this limited efficacy. <h3>Key messages</h3> Results from metabolic ward studies suggest that dietary change can reduce blood cholesterol concentrations by up to 15% In free-living subjects the standard step 1 diet of the American Heart Association lowers cholesterol concentration by about 3%, and about another 3% can be achieved with more intensive diets Difficulties in complying with the prescribed dietary change explain the failure to achieve the expected reductions in cholesterol concentrations It is important to be realistic about the reductions in cardiovascular risk that can be achieved by individual dietary counselling
Abstract 695: Significant Hypertrophy and Reduced Systolic Function Predict Intramyocardial Fibrosis in Patients with Hypertrophic Cardiomyopathy Undergoing Cardiac Magnetic Resonance Imaging
Authors: Ronen Rubinshtein, James F Glockner, Bernard J Gersh, Philip A Araoz, Michael J Ackerman, A J Tajik, Steve R Ommen
Journal: Circulation (2008)

Background: Contrast enhanced magnetic resonance imaging (CE-MRI) is a useful tool to define cardiac morphology, systolic function, and the presence of late gadolinium enhancement (LGE). In patients (pts) with hypertrophic cardiomyopathy (HCM), LGE may represent intra-myocardial fibrosis. We explored the association between left ventricular (LV) morphology and function to the presence and amount of LGE in pts with HCM. Methods: 424 HCM pts (age = 55 ± 16 years, 41% females), without prior history of septal ablation/myectomy, underwent CE-MRI (GE 1.5T) during a 6-year period. LV volumes, diameter, ejection fraction (EF), septal shape and thickness, and the presence of obstructive physiology were assessed from standard steady state free precession pulse sequences. The presence and amount of LGE were traced from a dynamic post contrast inversion recovery pulse sequence. Morphologic and functional findings were then compared with presence and amount of LGE. Results: Over half of the pts [239/424 (56%)] had LGE, most commonly localizing to RV insertion points [174/239 pts, (73%)]. The extent of LGE ranged from 0.4–65% of LV mass. Univariate (morphologic) predictors of LGE were: reverse curve septal shape [OR = 7.8, (95% CI, 3.9–15.6)], septal thickness ≥ 16 mm (OR = 4.5, 2.4–8.2), LV mass ≥ 150 grams (OR = 2.6, 1.7–3.8)], LVEF&lt;50% (OR = 4.6, 1.3–16), and presence of obstructive physiology (OR = 1.8, 1.02–3). The percentage of LV mass involved with LGE increased with higher LV mass, increased septal wall thickness, and decreasing LVEF (Spearman rank = 0.2– 0.4, p&lt;0.0001 for all). Multivariate analysis (adjusting for all morphologic and functional parameters) showed that septal thickness ≥ 16mm (p = 0.0001), LV mass ≥ 150 grams (p = 0.01) and LVEF &lt; 50% (p = 0.02) were independent predictors of LGE on CE-MRI. Conclusions: LGE, as determined by CE-MRI, was seen in over half of the patients with HCM. Decreased LVEF, increased septal thickness, and increased LV mass were associated with the presence of LGE. The clinical and prognostic impact of these morphological features warrants further investigation.
Metformin mediated AMPK activation inhibits translation initiation in breast cancer cells
Authors: Ryan Dowling, Mahvash Zakikhani, Nahum Sonenberg, Michael Pollak
Journal: Cancer Research (2007)

4470   The antidiabetic drug metformin lowers blood glucose by decreasing hepatic gluconeogenesis and stimulating glucose uptake in muscle. Some of the beneficial effects of metformin have been linked to the activation of the AMP activated protein kinase (AMPK) in muscle, adipose tissue, and liver, but effects of metformin on normal or transformed epithelial cells have not been well characterized. Upon activation, AMPK phosphorylates a number of effector proteins leading to the activation of ATP generating pathways, and the inhibition of ATP consuming pathways, such as protein synthesis. AMPK mediates its effects on protein synthesis through inhibition of the serine/threonine kinase, mTOR (mammalian target of rapamycin). mTOR is a major regulator of mRNA translation, and its effects on protein synthesis are mediated by two of its direct targets: the eIF4E binding proteins (4E-BPs) and the S6 protein kinase (S6K1), which are involved in regulating mRNA translation initiation. Inappropriate activation of mTOR can lead to increased cell growth, proliferation and neoplasia. Therefore, the inhibition of mTOR is being explored as a potential anti-cancer therapy.  Recently we demonstrated ( Cancer Research  66:10269, 2006) that metformin inhibited the growth of breast cancer cells through the activation of AMPK. To extend this, we studied the effects of metformin on protein synthesis. Cells were treated with increasing doses of metformin for 24 hours and overall cellular translation was assessed by incorporation of  35  S  methionine. In the breast cancer cell line MCF-7, metformin treatment led to a 30% decrease in protein synthesis. More specifically, the effect of metformin on cap-dependent translation was examined using a bicistronic reporter assay. Under these conditions, metformin caused a dose dependent decrease in cap-dependent translation, with a maximal inhibition of 40% at a dose of 20 mM. Polysome profile analysis also indicated an inhibition of translation initiation as metformin treatment of MCF-7 cells led to a decrease in heavy polysomes and a concomitant increase in the amount of 80S monosomes. The effects of metformin on translation were specifically mediated by AMPK, as treatment of cells with the AMPK inhibitor Compound C reversed the inhibition of protein synthesis. Furthermore, MDAMB-231 cells, which lack the AMPK regulator LKB1, were unaffected by metformin treatment. The effect of metformin on cellular translation was associated with mTOR inhibition and a decrease in the phosphorylation of ribosomal protein S6, and 4E-BP1.  These results demonstrate that metformin-mediated AMPK activation leads to an inhibition of mTOR and a reduction in translation initiation, thus providing a mechanism for direct inhibition of cancer cell growth, separate from any growth inhibition that may relate to metformin-induced reduction of insulin levels  in vivo .
Ethical debate: Doctoring malaria, badly: the global campaign to ban DDT DDT for malaria control should not be banned Commentary: Reduction and elimination of DDT should proceed slowly
Authors: A. Attaran, R. Maharaj, R. Liroff
Journal: BMJ (2000)

Doctoring malaria, badly: the global campaign to ban DDTThe treaty on persistent organic pollutants-POPs-will be finalised at the United Nations Environment Programme meeting in Johannesburg, 4-9 December.One proposal is to ban DDT, still used by many countries for controlling the mosquitoes that spread malaria.It should not be banned, argue Amir Attaran and Rajendra Maharaj, specialists in malariology and also international development and law-there's no evidence that spraying with DDT harms anyone.The issue is not straightforward, says Richard Liroff, director of the World Wildlife Fund's alternatives to DDT project; the treaty raises a series of equity challenges.
Cytokinesis failure in RhoA-deficient mouse erythroblasts involves actomyosin and midbody dysregulation and triggers p53 activation
Authors: Diamantis G. Konstantinidis, Katie M. Giger, Mary Risinger, Suvarnamala Pushkaran, Ping Zhou, Phillip Dexheimer, Satwica Yerneni, Paul Andreassen, Ursula Klingmüller, James Palis, Yi Zheng, Theodosia A. Kalfa
Journal: Blood (2015)
Abstract 17743: Calcific Uremic Arteriolopathy is Characterized by Increased Arteriolar Bone Morphogenetic Protein Signaling
Authors: Pawina Jiramongkolchai, Sagar U Nigwekar, Rosalynn M Nazarian, Rajeev Malhotra, Kenneth D Bloch, Ravi I Thadhani, Donald B Bloch
Journal: Circulation (2014)

Background: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a subcutaneous vasculopathy associated with calcification of the medial layer of arterioles leading to thrombosis and skin necrosis. CUA is almost exclusively seen in patients with end-stage chronic kidney disease and is usually fatal. Bone morphogenetic protein (BMP) signaling plays an important role in the calcification of large- and mid-sized arteries. We hypothesized that BMP signaling is increased in the subcutaneous arterioles of patients with CUA.

Methods: Formalin-fixed, paraffin-embedded, skin biopsies were obtained from ten patients with CUA and four patients without the disease. Vascular calcification was assessed using Von Kossa histochemical staining. To detect evidence for activation of BMP signaling, tissue sections were stained with antibodies directed against phosphorylated SMADs 1 and 5 (p-SMAD1/5).

Results: Von Kossa staining detected calcification in the medial layer of arterioles in the skin tissue specimens from all patients with CUA. Robust p-SMAD1/5 staining was detected adjacent to the arteriolar calcification in all 10 CUA patients. Neither calcification nor p-SMAD1/5 immunoreactivity was detected in arterioles in control samples (see Figure).

Conclusions: The results of this study provide evidence that increased BMP signaling contributes to the pathogenesis of CUA. Inhibition of BMP signaling is a promising approach to the treatment of this life-threatening disease.

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Abstract 3959: Impact of Aortic Valve Replacement on Survival of Patients With Severe Aortic Stenosis With Low Transvalvular Gradient and Preserved Left Ventricular Ejection Fraction
Authors: Giuseppe Tarantini, Elisa Covolo, Massimo Napodano, Claudio Bilato, Nicola Gasparetto, Enrico Favaretto, Chiara Fraccaro, Angelo Ramondo, Renato Razzolini, Gino Gerosa, Sabino Iliceto
Journal: Circulation (2009)

Background Severe aortic stenosis (SAS) with low transvalvular gradients (LTG), normal left ventricular ejection fraction (LVEF) is often misdiagnosed, leading to the undertreatment of patients bec...
Abstract 4259: The radiogenomic landscape of cancer
Authors: Mohamed Abazeed, Drew Adams, Pablo Tamayo, Matthew Meyerson, Peter Hammerman, Stuart Schreiber
Journal: Cancer Research (2014)

Abstract Radiotherapy is the mainstay of treatment for many solid malignancies. Despite this, there have not been extensive systematic analyses of the correlation between therapeutic sensitivity and genomic parameters. To accelerate discovery of patient-matched radiotherapy, or precision radiotherapeutics, systematic approaches are needed to identify specific genetic features that confer radiotherapeutic resistance and target these features with small-molecule drugs. We have quantitatively measured the sensitivity of 533 genomically characterized cancer cell lines to radiation, uncovering novel and established genetic, lineage, chromosomal copy number, and gene-expression-based dependencies. We show that small molecules that target genetic alterations driving therapeutic resistance effect genotype selective radiosensitization, establishing a preclinical basis for personalized therapeutic regimens. This dataset is an important resource that can be used to develop novel therapeutic hypotheses and to accelerate discovery of drugs given concurrently with radiation matched to patients by their cancer genotype, thereby enhancing efficacy and limiting toxicity in the context of a new approach of precision radiotherapy. Citation Format: Mohamed Abazeed, Drew Adams, Pablo Tamayo, Matthew Meyerson, Peter Hammerman, Stuart Schreiber. The radiogenomic landscape of cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4259. doi:10.1158/1538-7445.AM2014-4259
Dose and plasma levels of nortriptyline and chlorpromazine in delusionally depressed adolescents and of nortriptyline in nondelusionally depressed adolescents
Authors: B Geller, T B Cooper, Z Q Farooki, E C Chestnut
Journal: American Journal of Psychiatry (1985)

Eight adolescents with major depressive disorder were treated with nortriptyline and six adolescents with delusional depression were treated with combined nortriptyline and chlorpromazine. Dose and plasma levels of nortriptyline for the two groups were compared. The delusional group receiving combined drug treatment needed significantly less nortriptyline than did the nondelusional group receiving only nortriptyline to obtain similar mean steady state plasma levels of the drug. The mean plasma chlorpromazine levels were quite low.
Overexpression of MnSOD induces mitochondrial depolarization and p53-dependent senescence
Authors: Andrea Mohr, Lars Behrend, Ralf M. Zwacka
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4986 

The mitochondrial enzyme Manganese Superoxide Dismutase (MnSOD) is known to suppress cell growth in different tumor cell lines. However, the molecular mechanism of this growth retarding effect is not fully understood. Here, we show that overexpression of MnSOD slows down growth of HCT116 human colorectal cancer cells by induction of cellular senescence. MnSOD overexpression causes up-regulation of p53 and its transcriptional target the cyclin-dependent kinase inhibitor p21. Adenoviral mediated knock-down of p53 by RNAi rescues MnSOD overexpressing clones from growth retardation. Accordingly, the overexpression of MnSOD in HCTp53-/- does not lead to senescence, whereas in HCTp21-/- we found induction of senescence by forced expression of MnSOD. These results indicate a pivotal role of p53, but not p21 in the observed effects. Analysis of the mitochondrial membrane potential revealed reduced polarization in MnSOD over expressing cells. In addition, depolarization of the mitochondrial membrane by mitochondrial inhibitors like rotenone or antimycin A lead colorectal cancer cells into p53-dependent senescence. Our data indicate that uncoupling of the electrochemical gradient by increased MnSOD activity gives rise to p53 up-regulation and induction of senescence. This novel mitochondrial-mediated mechanism of tumor suppression might enable strategies that allow reactivation of cellular aging in tumor cells.
Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma
Authors: Alfred L. Garfall, Marcela V. Maus, Wei-Ting Hwang, Simon F. Lacey, Yolanda D. Mahnke, J. Joseph Melenhorst, Zhaohui Zheng, Dan T. Vogl, Adam D. Cohen, Brendan M. Weiss, Karen Dengel, Naseem D.S. Kerr, Adam Bagg, Bruce L. Levine, Carl H. June, Edward A. Stadtmauer
Journal: New England Journal of Medicine (2015)

A patient with refractory multiple myeloma received an infusion of CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative chemotherapy (melphalan, 140 mg per square meter of body-surface area) and autologous stem-cell transplantation. Four years earlier, autologous transplantation with a higher melphalan dose (200 mg per square meter) had induced only a partial, transient response. Autologous transplantation followed by treatment with CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at the most recent evaluation, 12 months after treatment. This response was achieved despite the absence of CD19 expression in 99.95% of the patient's neoplastic plasma cells. (Funded by Novartis and others; ClinicalTrials.gov number, NCT02135406.).
Managing status epilepticus
Authors: M T E Heafield
Journal: BMJ (2000)

Status epilepticus is a medical emergency familiar to accident and emergency departments, acute medical wards, and intensive care units. It is defined as a continuous seizure lasting for at least 30 minutes,1 or two or more discrete seizures between which the patient does not recover consciousness, and in the 15-30 patients per 100 000 per year who present in status epilepticus mortality may be as high as 10%. The longer seizures persist the more difficult they are to control and the higher the mortality,2 with an increase in neuronal damage and chronic epilepsy. Until recently phenytoin has been the drug of choice for managing prolonged seizures, but it has to be given intravenously and major side effects are common. Fosphenytoin is a prodrug of phenytoin, recently licensed in the United Kingdom, that seems to offer several advantages over its parent.

Status epilepticus is challenging to treat and may be difficult to diagnose. In early status epilepticus patients usually have visible tonic-clonic seizures, although motor-convulsive activity can decline. Diagnosis may require electroencephalographic monitoring, because some …
Pre-transplant thymic function is associated with the risk of cytomegalovirus disease after solid organ transplantation
Authors: I. Gracia-Ahufinger, S. Ferrando-Martínez, M. Montejo, M.C. Muñoz-Villanueva, S. Cantisán, A. Rivero, R. Solana, M. Leal, J. Torre-Cisneros
Journal: Clinical Microbiology and Infection (2015)