116 research outputs found

    Special Issue “International Conference of Spirituality in Healthcare. Creating Space for Spirituality in Healthcare,”—Trinity College Dublin 2017

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    This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).This is an editorial of a Special Issue pertaining to the “International Conference of Spirituality in Healthcare. Creating a Space for Spirituality in Healthcare” Trinity College Dublin 2017. This was the third International Spirituality in Healthcare Conference hosted by Trinity College Dublin, with future annual conferences planned. This conference has provided a space to facilitate clinicians, healthcare practitioners and academics to present and debate current issues with this domain. This editorial summarises some of the papers that have been published arising from that conference.publishedVersio

    Synthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16)

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    A highly conserved region of 21 amino acids flanked by cysteine residues, contained within a larger repeated domain, has been proposed to be the antibody-binding site in the ovarian cancer biomarker CA125 (MUC16). In this study solid-phase peptide synthesis with Fmoc protection chemistry was used to assemble a 21-mer peptide corresponding to the most frequently occurring antibody binding sequence in CA125. Potentially significant sequence variants were also synthesized. Peptide secondary structure was investigated using Fourier transform infrared spectroscopy, revealing the consensus sequence peptide to be largely unstructured at physiological pH whether the cysteine residues were reduced or were oxidized to form an intramolecular disulfide bond. Substitution of serine for proline at position 8 (P8S) results in ÎČ-sheet formation in peptides involved in intramolecular disulfide bonds. This ÎČ-sheet structure does not persist in peptides incapable of intramolecular disulfide bonding because of sequence nor in peptides treated with the reducing agent dithiothreitol. In CA125, P8S is predicted to occur in ~25% of repeat domains, suggesting that this structural motif is a non-negligible contributor to overall structure and function. These findings suggest that future structural characterization efforts of CA125 should be especially mindful of the amino acid sequence and oxidation state of the protein

    Competing risks of death in women treated with adjuvant aromatase inhibitors for early breast cancer on NCIC CTG MA.27

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    Baseline patient and tumor characteristics differentially affected type of death in the MA.17 placebo-controlled letrozole trial where cardiovascular death was not separately identified. The MA.27 trial allowed competing risks analysis of breast cancer (BC), cardiovascular, and other type (OT) of death. MA.27 was a phase III adjuvant breast cancer trial of exemestane versus anastrozole. Effects of baseline patient and tumor characteristics were tested for whether factors were associated with (1) all cause mortality and (2) cause-specific mortality. We also fit step-wise forward cause-specific-adjusted models. 7576 women (median age 64 years; 5417 (72 %) < 70 years and 2159 (28 %) ≄ 70 years) were enrolled and followed for median 4.1 years. The 432 deaths comprised 187 (43 %) BC, 66 (15 %) cardiovascular, and 179 (41 %) OT. Five baseline factors were differentially associated with type of death. Older patients had greater BC (p = 0.03), cardiovascular (p < 0.001), and other types (p < 0.001) of mortality. Patients with pre-existing cardiovascular history had worse cardiovascular mortality (p < 0.001); those with worse ECOG performance status had worse OT mortality (p < 0.001). Patients with T1 tumors (p < 0.001) and progesterone receptor positive had less BC mortality (p < 0.001). Fewer BC deaths occurred with node-negative disease (p < 0.001), estrogen receptor-positive tumors (p = 0.001), and without adjuvant chemotherapy (p = 0.005); worse cardiovascular mortality (p = 0.01), with trastuzumab; worse OT mortality, for non-whites (p = 0.03) and without adjuvant radiotherapy (p = 0.003). Overall, 57 % of deaths in MA.27 AI-treated patients were non-breast cancer related. Baseline patient and tumor characteristics differentially affected type of death with women 70 or older experiencing more non-breast cancer death

    Assessing secondary attack rates among household contacts at the beginning of the influenza A (H1N1) pandemic in Ontario, Canada, April-June 2009: A prospective, observational study

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    <p>Abstract</p> <p>Background</p> <p>Understanding transmission dynamics of the pandemic influenza A (H1N1) virus in various exposure settings and determining whether transmissibility differed from seasonal influenza viruses was a priority for decision making on mitigation strategies at the beginning of the pandemic. The objective of this study was to estimate household secondary attack rates for pandemic influenza in a susceptible population where control measures had yet to be implemented.</p> <p>Methods</p> <p>All Ontario local health units were invited to participate; seven health units volunteered. For all laboratory-confirmed cases reported between April 24 and June 18, 2009, participating health units performed contact tracing to detect secondary cases among household contacts. In total, 87 cases and 266 household contacts were included in this study. Secondary cases were defined as any household member with new onset of acute respiratory illness (fever or two or more respiratory symptoms) or influenza-like illness (fever plus one additional respiratory symptom). Attack rates were estimated using both case definitions.</p> <p>Results</p> <p>Secondary attack rates were estimated at 10.3% (95% CI 6.8-14.7) for secondary cases with influenza-like illness and 20.2% (95% CI 15.4-25.6) for secondary cases with acute respiratory illness. For both case definitions, attack rates were significantly higher in children under 16 years than adults (25.4% and 42.4% compared to 7.6% and 17.2%). The median time between symptom onset in the primary case and the secondary case was estimated at 3.0 days.</p> <p>Conclusions</p> <p>Secondary attack rates for pandemic influenza A (H1N1) were comparable to seasonal influenza estimates suggesting similarities in transmission. High secondary attack rates in children provide additional support for increased susceptibility to infection.</p

    Essentials in Accident and Emergency Medicine Radiation Injury: Response and Treatment

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    The discovery of radiation has enabled great healthcare advances as well as catastrophic injury. This paper reviews major historical incidents of public radiation exposure and the evolution of standards affecting today’s public and health care workers. Current patient care and response assessment to radiation exposure are reviewed. The strengths of modern radiation therapy and the need for continuous process improvements to ensure optimal patient care and secure safe environments are identified. The discovery of radiation has brought significant scientific achievements as well as catastrophic injury

    The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

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    The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

    Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer

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    BACKGROUND The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS We performed a prospective trial involving 9427 women with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≀1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy

    Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

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    BACKGROUND The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS We performed a prospective trial involving 10,273 women with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary node–negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease–free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease–free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease–free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local–regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease–free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor–positive, HER2-negative, axillary node–negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger
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