tbuckley/cabot-search huggingface dataset:
PTH-124 Action Learning sets to Support Specialist Screening Practitioners
Authors: V Breen
Journal: Gut (2013)

<h3>Introduction</h3> Bowel Screening Wales (BSW) have undertaken a pilot to provide evidence which will consider the benefits of Action Learning Sets to Support Specialist Screening Practitioners. <h3>Methods</h3> Action Learning Sets (ALS) are a powerful problem-solving process widely used in nursing and other organisations to help staff develop their own skills in resolving workplace issues by using enhanced communication in a group setting. It can help build teams, support individuals, develop self awareness, promote professional development and improve leadership skills. Allocating time for one-to-one meetings for clinical supervision can be difficult to maintain. ALS could be developed to enable SSP peer-group learning. A pilot will commence in one LAC in January 2013 and will create a mechanism for setting up action learning, enabling discussion of the options and the practicalities of setting up ALS. A Bowel Screening Wales, Regional Nurse would take on the initial facilitator role. This would help to ensure progress is maintained and to encourage and shape ALS, with a view totraining up internal facilitators for future sets in other LACs. The ALS would become self facilitating but this would only be done once the SSP’s are experienced in the methodology. Those involved in the pilot would need to agree how the ALS pilot will be evaluated, one possibility would be to ask members to write a reflective account of their experience of participating and how it influenced their practise and professional development. <h3>Results</h3> The feedback from the results will be considered and the process consent process modified accordingly. The results of the pilot will help BSW focus on finding out how ALS could enable SSP peer-group learning, development and support providing peer supervision, identifying strategies for leading service developments and providing a focus for problem solving and reflection workplace issues. Also needing consideration is how the pilot, if successful, could be conveyed to other SSP’s working within Bowel Screening Wales, SSP’s working within other UK Bowel Screening Programmes and other Specialist Nurses working within the symptomatic service. <h3>Conclusion</h3> ALS for SSP’s would ensure continuous professional development and could represent an empowering approach for SSP’s advanced practise, helping them to develop their own practical solutions to workplace problems and issues. ALS is a dynamic and evolving group process. The approach would require commitment but ALS is a relatively straight forward way of improving individual SSP and team working. It aims to be of benefit to the organisation and the individual SSP. <h3>Disclosure of Interest</h3> None Declared.
DISCHARGE HOME HEALTH REFERRAL IS ASSOCIATED WITH HIGHER POST-DISCHARGE 30-DAY ALL-CAUSE READMISSION AND ALL-CAUSE MORTALITY AMONG OLDER MEDICARE BENEFICIARIES HOSPITALIZED FOR HEART FAILURE
Authors: Chakradhari Inampudi, Helen Sheriff, Sijian Zhang, Charity Morgan, Christine Ritchie, Marc Blackman, Prakash Deedwania, Gregg Fonarow, Javed Butler, Wen-Chih Wu, Wilbert Aronow, Ross Fletcher, Richard Allman, Ali Ahmed
Journal: Journal of the American College of Cardiology (2016)
The Maltreatment Syndrome in Children
Authors: Vincent J. Fontana, Denis Donovan, Raymond J. Wong
Journal: New England Journal of Medicine (1963)

WITHIN the last several years there has been a medical awareness of a major pediatric problem involving childhood neglect and physical abuse. The infliction of willful injuries to children is not a new entity but has existed since the beginning of time. Only recently has there been an apparent increased incidence of "battered" children reported in the medical literature and noted by child-protective agencies. Before these reports, this pediatric syndrome of the maltreated child has for the most part been unsuspected and has gone unrecognized by the medical profession. Little or no information on the subject is available in the . . .
FRI0452 Determinants factors of sleep disturbances in spondylarthritis
Authors: W. B. bousselmi, I. M. mahmoud, O. S. saidène, H. S. sahli, R. T. tekaya, L. A. abdelmoula, L. C. chaabouni, R. Z. zouari
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Literature data suggest that sleep disturbances are prevalent among patients with Spondylarthritis (Spa) and have a close correlation with pain and psychological status. <h3>Objectives</h3> our study was designed first to evaluate sleep disturbances in patients with Spa and to compare the results to a population of healthy subjects. Secondly, to assess the association of sleep disturbance with demographic variables, pain, tiredness, disease-specific variables, functional status in Spa patients. <h3>Methods</h3> This is a case-control Transversal Study that included 70 patients with Spa and 50 healthy subjects. The demographic and clinical characteristics of the patients were collected (The BASDAI (Bath ankylosing spondylitis disease activity index), the BASFI (Bath ankylosing spondylitis functionnal index), the BASMI (Bath ankylosing spondylitis metrological index), BAS G (Bath ankylosing spondylitis Global index), the BASRI (bath ankylosing spondylitis radiology index). Depression or anxiety was evaluated by the HAD (hospital anxiety and depression scale) and quality of life was assessed by the SF36(Summary physical (PCS) and mental (MCS) component measure). Sleep quality was evaluated by sleep scale from the medical outcomes study. The 12 items of the MOS Sleep Scale measure sleep parameters across six domains (sleep disturbance, sleep adequacy, sleep quantity, somnolence, snoring and shortness of breath, or headache). <h3>Results</h3> There were 65% men and 35% women. Age ranged from 16 to 74 years with an average of 40,6 years. Disease mean duration was 10,75±9 years. Mean Pain-VAS was 65 mm and mean Tiredness-VAS was 56 mm. Mean BASDAI score was 45%, mean BASFI score 44,7% and mean BASG-s score 55%. The mean BASMI score was 4,76 and the mean BASRI score was 4,43. Mean HADS score was 15,9. Sleep disturbance is correlated with the VAS pain (p = 0.027), the VAS fatigue (p = 0.006), the BASDAI (p = 0.03), the BASFI(p=0,048), the BASG (p = 0.01), the HAD (0.002 ) and inversely correlated with PCS(p=0,02) and MCS(p=0,006). The quantity of sleep is inversely correlated with the VAS pain (p = 0.005), the VAS fatigue, BASDAI (p = 0.02), the BASG (p = 0.002), the HAD (p = 0.004) and Lesquene index (p = 0.015) and correlated to the PCS(p=0,042) and MCS(P=0,002). The results for the comparative study of sleep disturbances between spa and healthy and are summarized in the table <h3>Conclusions</h3> our study suggests that sleep disturbances are frequent and severe in the Spa. Our findings suggest that multiple factors are associated with polysomnographic sleep disturbances including disease activity, fatigue, hips involvement and anxiety and depression. <h3>Disclosure of Interest</h3> None Declared
Abstract DDT01-01: Preclinical profile of AZD4547: A selective inhibitor of FGF-receptors 1, 2, and 3
Authors: Nigel A. Brooks
Journal: Cancer Research (2011)

Abstract The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling axis comprises 18 ligands which exert their actions via 4 transmembrane tyrosine kinase receptors. FGFs signaling though their cognate receptors play an important role in normal organ, vascular and skeletal development. Deregulation of FGFR signaling through genetic modification or overexpression of the receptors (or their ligands) has been observed in numerous tumor settings, whilst the FGF/FGFR axis also plays an important role in driving tumor angiogenesis. A growing body of data demonstrates that inhibition of FGFR signaling can result in antiproliferative and/or proapoptotic effects, both in vitro and in vivo, thus confirming the validity of FGFR as a cancer therapeutic target. AZD4547 is a small molecule inhibitor which competes with ATP for binding to FGF receptors 1, 2 and 3, thus inhibiting autophosphorylation and downstream signaling. Using in vitro kinase assays, we demonstrate that AZD4547 is a potent inhibitor of FGFR's 1,2 and 3 with IC50 values of 0.2, 2.5 and 1.8 nM respectively. AZD4547 is also highly selective vs. a panel of over 70 other kinases (no activity at 10 μM) and importantly vs. kinase insert domain receptor (KDR) (&amp;gt;120-fold window in cellular assays vs. FGFR2). In vitro treatment of a large panel of cell lines (&amp;gt;100, representing several tumor types) with AZD4547 resulted in varying antiproliferative responses, the most potent of which were almost exclusively confined to those cell-lines in which FGFR signaling was deregulated by either gene amplification, mutation or translocation. Treatment of these sensitive cell lines with AZD4547 for 1 hr, demonstrated potent inhibition of phosphorylation of FGF receptors and downstream substrates including pFRS2α and p44/42 MAPK. The antiproliferative effects of AZD4547 appear to be cell line dependent and vary between potent G1-phase cell cycle arrest and apoptotic induction. Chronic in vivo dosing of AZD4547 up to 12.5 mg/kg qd was well tolerated and resulted in dose-dependent growth inhibition in KMS11 (FGFR3 translocated, multiple myeloma) and Snu16 (FGFR2 amplified, gastric) tumour xenograft models. This in vivo antitumor activity is correlated with exposure to AZD4547 and associated pharmacodynamic modulation of phospho-FGFR and downstream substrates. In addition to the single-agent efficacy, combining of AZD4547 with cytotoxic agents, currently used for the treatment of gastric cancer patients, revealed enhanced growth inhibition of Snu-16 xenografts. Collectively, these data confirm the suitability of AZD4547 as a potent and selective agent for the therapeutic treatment of tumors with deregulated FGF/FGFR signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr DDT01-01. doi:10.1158/1538-7445.AM2011-DDT01-01
Abstract 1158: Multiple molecular targeting effects by miR-7 in EGFR tyrosine kinase inhibitor-resistant lung cancer xenograft models
Authors: Kammei Rai, Nagio Takigawa, Sachio Ito, Katsuyuki Kiura, Tateji Yasuda, Kenji Shimizu, Mitsune Tanimoto
Journal: Cancer Research (2011)

Abstract Background and Purpose: Since T790M secondary mutation in exon 20 restores the affinity of ATP to the ATP binding site of mutated EGFR, the oncogene addiction by EGFR pathway is presumed to sustain in the EGFR tyrosine kinase inhibitor (TKI)-resistant cells harboring T790M. MicroRNA-7 (miR-7) was reported to regulate signaling pathway by targeting EGFR, IRS-1 and RAF1. We previously showed that miR-7 had potential tumor suppressor effect by binding 3′-untranslated region of EGFR mRNA in vitro as predicted in silico, which could be observed in xenograft model using gefitinib-resistant lung cancer cell line (RPC-9) carrying a secondary mutation T790M from EGFR mutated (delE746-A750 in exon 19) PC-9 cell line (#4041, Annual AACR meeting, 2010). We explored the efficacy and further mechanisms in other lung cancer cell lines and xenograft models. Material and Methods: H3255 harboring L858R and H1975 carrying both L858R mutation in exon 21 and T790M mutation in exon 20 were used as EGFR addicted cell lines, while A549 was used as the cell line driven by not EGFR but KRAS. Each anti-proliferation effect was evaluated at 60 hours after transfection of miR-7 by the cell count assay. As EGFR-TKI resistant xenograft models, we selected H1975. Two million cells were injected s.c. into the backs of the athymic mice. After confirming the tumor formation of 7 mm in the diameter, we injected 3μg of control siRNA expressing plasmid and miR-7 expressing plasmid weekly into the each tumor by using optimized cationic liposome. Protein expression was determined by Western blotting. Results: Significant growth inhibition by miR-7 was observed in the H3255 cells (p = 0.006) and H1975 cells (p = 0.004), while inhibition in A549 cells was likely to be moderate (p =0.07). Total EGFR was decreased and phosphorylation of AKT was suppressed in all cell lines by the treatment, moreover, total IRS-1 and total RAF-1 were also suppressed. Marked anti-proliferative effect in H1975 xenograft model was observed after treatment. The tumor sizes between the control mice and the treated mice were significantly different on day 19 (714% vs 154%, p=0.02). Total EGFR, IRS-1 and RAF-1 were suppressed in the tumors of H1975 and RPC-9 one day after injection of miR-7. Conclusion: MiR-7 by non-viral weekly delivery in two typical xenograft models of EGFR-TKI resistant cell lines was effective through downregulating EGFR, IRS-1, and RAF-1. The treatment with miR-7 expressing plasmid may be promising for the EGFR-TKI-resistant lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1158. doi:10.1158/1538-7445.AM2011-1158
Abstract 3581: Long-term results of organ sparing surgical treatments of precancerous cervical lesions in Mongolia
Authors: Avirmed Damdin, Amarsanaa Jazag
Journal: Cancer Research (2012)

Abstract Background: Cervical cancer is the most common cancer in female reproductive system. Since introduction of diagnostic modalities like Pap-tests, the detection pre-cancerous cervical lesions CIN1, CIN2 and CIN3 have increased dramatically. Early detection of pre-cancerous lesions enables performance of organ sparing treatments like LEEP, conization and cryotherapy. Aim: Since there are no studies in the field of organ sparing treatment of cervical cancer, we decided analyze the results of such treatments and calculate the: 1. Five year survival of patients underwent organ sparing surgical procedures 2. Fertility and reproductive function of these patients Method: LEEP (n-63), knife conization (n-22) and trachelectomy (total removal of cervix) (n-15) was performed in women of reproductive age (25-35 years old) at National Cancer Center. The treatment results were followed for 5 years and statistical analysis of survival and reproductive function were analyzed. Results: 87.7% of patients with CINI lesions had LEEP, 12.3 % had knife conization and 0% had trachelectomy. 44.4% of patients with CINI lesions had LEEP, 55.6 % had knife conization and 0% had trachelectomies respectively. For CINIII 6.2% of patients had LEEP, 0% had knife conization and 93% had trachelectomy. We performed organ sparing treatment in 100 patients, out of which 10% had cancer recurrence in LEEP treatment, 9.1% in knife conization and 0% in trachelectomy. Complications of hemorrhage were observed in 14% of patients, cervical tube obstruction in 3% and deterioration of chronic inflammations in 13% respectively. After the organ sparing treatment, menstrual cycle was normal in 75% of the all patients, 65% reached pregnancy. 9.2% of patients who reached pregnancy had stillbirth, 12.3% had abortion, and 78.5% had normal delivery. 80.4% of patients with pregnancy had natural labors, while19.6% of patients had caesarean sections respectively. Conclusion: in Mongolia, LEEP, knife conization and trachelectomy methods are used since 2000. But the treatment results were not reported so far. 10% of patients treated by LEEP and 9.1% of patients treated by knife conization had tumor recurrence. Thus our treatment efficiency is above 90%. Up to 20% of patients had complications ranging from bleeding to cervical tube obstruction. We conclude that organ sparing cancer treatment allows better QOL (quality of life) for the patients and provides opportunity to have children. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3581. doi:1538-7445.AM2012-3581
OP0272 Abatacept is highly effective in inhibiting T cell priming but fails to induce T cell tolerance after primary antigen encounter
Authors: A. Patakas, S.G. Nadler, J.M. Brewer, I.B. McInnes, P. Garside
Journal: Annals of the Rheumatic Diseases (2013)

A 10-year-old girl with no nasal or respiratory symptoms developed a headache lasting a few hours. The next day she became totally blind in the right eye and over 5 days vision in the left eye deteriorated to bare light perception. The diagnosis of a sphenoid sinus mucocele was made radiologically and drainage via an endonasal sphenoidectomy produced 12 ml of brownish fluid. Endoscopic biopsy of the wall confirmed the diagnosis of a mucocele. Steroid treatment was given postoperatively, but vision recovered to 6/12 in the left eye only. The importance of urgent clinical diagnosis and treatment is stressed.
Abstract 3928: KU-0060019, a novel small molecule inhibitor of ATM
Authors: Kerry F. Shea, Mark Albertella, Julia Bárdos, Michael A. Batey, Aaron Cranston, Nicola Curtin, Roger Griffin, Alan Lau, Keith Menear, David Newell, Mark O'Connor, Caroline Richardson, Louise Jones, Graeme Smith, Pia Thömmes, Yan Zhao, Niall Martin
Journal: Cancer Research (2010)

Abstract Ataxia telangiectasia mutated (ATM) is an important serine/threonine kinase involved in the DNA damage response and cell cycle checkpoint control. The 350kDa protein is a member of the PI3-kinase like kinase (PIKK) family and is mutated in the neurodegenerative disorder, Ataxia telangiectasia. ATM exists in the inactive form as a dimer but following DNA damage is phosphorylated at a serine residue at position 1981 and dissociates to become an active monomer. It detects DNA double strand breaks (DSBs) through the Mre11/Rad50/NBS1 (MRN) complex and signals this information downstream to the cell cycle machinery, for example by the phosphorylation of p53 (Ser15) and Chk2 (Thr68). ATM is a key signalling molecule for DNA double strand breaks that can regulate the homologous recombination repair pathway. Inhibition of ATM activity sensitises cells to the cytotoxic effects of DNA damaging agents such as some chemotherapies or ionising radiation that either directly or indirectly induce double stand breaks. Here we present the biological profile of KU-0060019, a potent and specific novel small molecule inhibitor of ATM kinase activity. The compound has an IC50 value against the enzyme of 5 nM with above 1 μM IC50 value against DNA-PK and inhibits cellular phosphorylation of p53 at serine 15 with an EC50 value of 150 nM. It sensitises cells to chemotherapeutics, in particular topoisomerase II inhibitors, as well as radiotherapeutics in vitro in a variety of cancer cell lines. We also demonstrate potentiation of chemotherapeutics in in vivo mouse xenograft tumour models. Using the novel ATM inhibitor KU-0060019 these studies demonstrate the potential of targeting ATM as a sensitising mechanism by a small molecule in cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3928.
THE ROLE OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS (ICDS) IN PATIENTS WITH A LEFT VENTRICULAR ASSIST DEVICE (LVAD): A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Divyang Patel, Vic Hasselblad, Chetan Patel, Sean Pokorney, Emily Zeitler, Joseph Rogers, James Daubert, Prateeti Khazanie, Albert Sun, Robert Mentz, Donald Hegland, Adrian Hernandez, Sana Al-Khatib
Journal: Journal of the American College of Cardiology (2016)
The Fall and Rise of Carotid Endarterectomy in the United States and Canada
Authors: Jack V. Tu, Edward L. Hannan, Geoffrey M. Anderson, Karey Iron, Keyi Wu, Karen Vranizan, A. John Popp, Kevin Grumbach
Journal: New England Journal of Medicine (1998)

Randomized clinical trials have demonstrated the efficacy of carotid endarterectomy in the prevention of stroke when the procedure is performed in regional centers of surgical excellence. However, the relative effects of these studies on the rates of carotid endarterectomy in the United States and Canada have been unclear.
Abstract 4744: Development of an immunoproteasome fluorescent substrate: A functional proteomics tool
Authors: Na-Ra Lee, Kimberly C. Carmony, Ying Wu, Zachary Miller, Kyung-Bo Kim
Journal: Cancer Research (2012)

Abstract Introduction: This research was conducted to develop the first immunoproteasome fluorescent substrate. The immunoproteasome is an alternate form of the constitutive proteasome with distinct catalytic subunits. While immunoproteasomes appear to generate peptides for MHC class I antigen presentation, their functions are still not completely understood. Antibody-based studies have shown that immunoproteasome catalytic subunits are expressed in a variety of cancers, suggesting they may play important roles in this disease. However, antibodies bind both active and inactive subunits, rendering these studies incapable of correlating immunoproteasome activity with disease progression. Although fluorescent peptide substrates are widely used to monitor proteasome activity, those currently available are cleaved by both forms of the proteasome. Therefore, fluorescent substrates selectively cleaved by the immunoproteasome are needed to correlate their activity with cancer progression. Experimental Procedures: The fluorescent substrate was synthesized by replacing the epoxyketone pharmacophore of the immunoproteasome-selective inhibitor YU-102 with a 7-amino-4-methylcoumarin (AMC) fluorogenic moiety. The rates of hydrolysis of the resulting substrate, YU-102-AMC, by both purified constitutive proteasomes and immunoproteasomes were evaluated by monitoring the release of AMC over time. Hydrolysis of this substrate was also investigated in T1 and T2 cell lysates. Data Summary: The structure of the fluorescent substrate YU-102-AMC was confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy. YU-102-AMC was preferentially cleaved by purified immunoproteasomes in comparison with purified constitutive proteasomes. This preferential cleavage by immunoproteasomes was confirmed in lysates of cancer cell lines T1 and T2. Conclusions: We have successfully developed YU-102-AMC, an immunoproteasome fluorescent substrate which facilitates quantification of immunoproteasome activity in cancer cell lysates. This substrate will be utilized to examine a correlation between immunoproteasome activity and cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4744. doi:1538-7445.AM2012-4744