bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014
Authors: Basu Bristi , Dean Emma , Puglisi Martina , Greystoke Alastair , Ong Michael , Burke Wendy , Cavallin Maria , Bigley Graham , Womack Christopher , Harrington Elizabeth A. , Green Stephen , Oelmann Elisabeth , de Bono Johann S. , Ranson Malcolm , Banerji Udai 
Published: March 2015

AbstractPurpose: AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown in vitro and in vivo efficacy across a range of preclinical human cancer models.Experimental Design: A rolling six-dose escalation was performed to define an MTD (part A), and at MTD a further cohort of patients was treated to further characterize toxicities and perform pre- and posttreatment biopsies (part B). AZD2014 was administered orally twice a day continuously. Flow cytometry, ELISA, and immunohistochemistry were used to quantify pharmacodynamic biomarkers. Pharmacokinetic analysis was carried out by mass spectrometry.Results: A total of 56 patients were treated across a dose range of 25 to 100 mg. The MTD was 50 mg twice daily. The dose-limiting toxicities were fatigue and mucositis. At the MTD, the most common adverse events (AE) were fatigue (78%), nausea (51%), and mucositis (49%), but these were equal to or greater than grade 3 in only 5% of patients. Drug levels achieved at the MTD (AUCss 6686 ng·h/mL, Cmax ss 1,664 ng/mL) were consistent with activity in preclinical models. A reduction in p-S6 levels and Ki67 staining was observed in 8 of 8 and 5 of 9 evaluable paired biopsy samples. Partial responses were seen in a patient with pancreatic cancer and a patient with breast cancer, who were found to have a PDGFR and ERBB2 mutation, respectively.Conclusions: The recommended phase II dose for further evaluation of AZD2014 is 50 mg twice daily, and at this dose it has been possible to demonstrate pharmacologically relevant plasma concentrations, target inhibition in tumor, and clinical responses. Clin Cancer Res; 21(15); 3412–9. ©2015 AACR.
SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-Associated Cancer
Authors: Ida Satoshi , Ozaki Nobuyuki , Araki Kimi , Hirashima Kotaro , Zaitsu Yoko , Taki Katsunobu , Sakamoto Yasuo , Miyamoto Yuji , Oki Eiji , Morita Masaru , Watanabe Masayuki , Maehara Yoshihiko , Yamamura Ken-ichi , Baba Hideo , Ohmuraya Masaki 
Published: March 2015

Abstract
Colorectal cancer is a major cause of deaths due to cancer; therefore, research into its etiology is urgently needed. Although it is clear that chronic inflammation is a risk factor for colorectal cancer, the details remain uncertain. Serine protease inhibitor, Kazal type 1 (SPINK1) is mainly produced in pancreatic acinar cells. However, SPINK1 is expressed in various cancers and in inflammatory states, such as colon cancer and inflammatory bowel disease. There are structural similarities between SPINK1 and epidermal growth factor (EGF). Hence, it was hypothesized that SPINK1 functions as a growth factor for tissue repair in inflammatory states, and if prolonged, acts as a promoter for cell proliferation in cancerous tissues. Here, immunohistochemical staining for SPINK1 was observed in a high percentage of colorectal cancer patient specimens and SPINK1 induced proliferation of human colon cancer cell lines. To clarify its role in colon cancer in vivo, a mouse model exposed to the colon carcinogen azoxymethane and nongenotoxic carcinogen dextran sodium sulfate revealed that Spink3 (mouse homolog of SPINK1) is overexpressed in cancerous tissues. In Spink3 heterozygous mice, tumor multiplicity and tumor volume were significantly decreased compared with wild-type mice. These results suggest that SPINK1/Spink3 stimulates the proliferation of colon cancer cells and is involved in colorectal cancer progression.
Implications: Evidence suggests that SPINK1 is an important growth factor that connects chronic inflammation and cancer. Mol Cancer Res; 13(7); 1130–8. ©2015 AACR.
High-Density Lipoprotein-Cholesterol, Daily Estradiol and Progesterone, and Mammographic Density Phenotypes in Premenopausal Women
Authors: Flote Vidar G. , Frydenberg Hanne , Ursin Giske , Iversen Anita , Fagerland Morten W. , Ellison Peter T. , Wist Erik A. , Egeland Thore , Wilsgaard Tom , McTiernan Anne , Furberg Anne-Sofie , Thune Inger 
Published: March 2015

AbstractHigh-density lipoprotein-cholesterol (HDL-C) may influence the proliferation of breast tumor cells, but it is unclear whether low HDL-C levels, alone or in combination with cyclic estrogen and progesterone, are associated with mammographic density, a strong predictor of breast cancer development. Fasting morning serum concentrations of HDL-C were assessed in 202 premenopausal women, 25 to 35 years of age, participating in the Norwegian Energy Balance and Breast Cancer Aspects (EBBA) I study. Estrogen and progesterone were measured both in serum, and daily in saliva, throughout an entire menstrual cycle. Absolute and percent mammographic density was assessed by a computer-assisted method (Madena), from digitized mammograms (days 7–12). Multivariable models were used to study the associations between HDL-C, estrogen and progesterone, and mammographic density phenotypes. We observed a positive association between HDL-C and percent mammographic density after adjustments (P = 0.030). When combining HDL-C, estradiol, and progesterone, we observed among women with low HDL-C (&lt;1.39 mmol/L), a linear association between salivary 17β-estradiol, progesterone, and percent and absolute mammographic density. Furthermore, in women with low HDL-C, each one SD increase of salivary mid-menstrual 17β-estradiol was associated with an OR of 4.12 (95% confidence intervals; CI, 1.30–13.0) of having above-median percent (28.5%), and an OR of 2.5 (95% CI, 1.13–5.50) of having above-median absolute mammographic density (32.4 cm2). On the basis of plausible biologic mechanisms linking HDL-C to breast cancer development, our findings suggest a role of HDL-C, alone or in combination with estrogen, in breast cancer development. However, our small hypothesis generating study requires confirmation in larger studies. Cancer Prev Res; 8(6); 535–44. ©2015 AACR.
Policies Allowing Family Presence During Resuscitation and Patterns of Care During In-Hospital Cardiac Arrest
Authors: Goldberger Zachary D. , Nallamothu Brahmajee K. , Nichol Graham , Chan Paul S. , Curtis J. Randall , Cooke Colin R. 
Published: March 2015

Background—
A growing number of hospitals have begun to implement policies allowing for family presence during resuscitation (FPDR). However, the overall safety of these policies and their effect on resuscitation care is unknown.

Methods and Results—
We conducted an observational cohort study of 252 hospitals in the United States with 41 568 adults with cardiac arrest. Multivariable hierarchical regression models were used to evaluate patterns of care at hospitals with and without an FPDR policy. Primary outcomes included return of spontaneous circulation and survival to discharge. Secondary outcomes included resuscitation quality, interventions, and facility-reported potential resuscitation systems errors. There were no significant differences in facility characteristics between hospitals with and without an FPDR policy, nor were there significant differences in return of spontaneous circulation (adjusted risk ratio, 1.02; 95% confidence interval, 0.95–1.06) or survival to discharge (adjusted risk ratio, 1.05; 95% confidence interval, 0.95–1.15). There was a small, borderline significant decrease in the mean time to defibrillation at hospitals with an FPDR policy compared with hospitals without the policy (mean difference, 0.32 minutes; 95% confidence interval, −0.01 to 0.64). Resuscitation quality, interventions, and facility-reported potential resuscitation systems errors did not meaningfully differ between hospitals with and without an FPDR policy.

Conclusions—
Hospitals with an FPDR policy generally have no statistically significant differences in outcomes and processes of care as hospitals without this policy, suggesting such policies may not negatively affect resuscitation care. Further study is warranted about the direct effect of FPDR attempts on adult patients with an in-hospital cardiac arrest and their families.
High-Temporal Resolution Polarimetric X-Band Doppler Radar Observations of the 20 May 2013 Moore, Oklahoma, Tornado
Authors: Kurdzo James M. , Bodine David J. , Cheong Boon Leng , Palmer Robert D. 
Published: March 2015

Abstract
On 20 May 2013, the cities of Newcastle, Oklahoma City, and Moore, Oklahoma, were impacted by a long-track violent tornado that was rated as an EF5 on the enhanced Fujita scale by the National Weather Service. Despite a relatively sustained long track, damage surveys revealed a number of small-scale damage indicators that hinted at storm-scale processes that occurred over short time periods. The University of Oklahoma (OU) Advanced Radar Research Center’s PX-1000 transportable, polarimetric, X-band weather radar was operating in a single-elevation PPI scanning strategy at the OU Westheimer airport throughout the duration of the tornado, collecting high spatial and temporal resolution polarimetric data every 20 s at ranges as close as 10 km and heights below 500 m AGL. This dataset contains the only known polarimetric radar observations of the Moore tornado at such high temporal resolution, providing the opportunity to analyze and study finescale phenomena occurring on rapid time scales. Analysis is presented of a series of debris ejections and rear-flank gust front surges that both preceded and followed a loop of the tornado as it weakened over the Moore Medical Center before rapidly accelerating and restrengthening to the east. The gust front structure, debris characteristics, and differential reflectivity arc breakdown are explored as evidence for a “failed occlusion” hypothesis. Observations are supported by rigorous hand analysis of critical storm attributes, including tornado track relative to the damage survey, sudden track shifts, and a directional debris ejection analysis. A conceptual description and illustration of the suspected failed occlusion process is provided, and its implications are discussed.
The determination of absorbance and scattering coefficients for photochromic composition with the application of the black and white background method
Authors: Viková Martina , Vik Michal 
Published: March 2015

Fresnel's postulates and equations of energy transfer, including approximate Kubelka – Munk theory, also allow the determination of other optical parameters for measured materials as for example absorbance coefficient k and scattering coefficients. In the case of colorants it is possible to determine molar coefficient ε0 by absorption spectrophotometry and Lambert – Beer Law from a calibration set with a different concentration of specific substance. If we use recommended solvents for the photochromic pigments, from the capsules the pigments not only flood out, but also use additives (HALS). This situation results in turbid solution, where use of Lambert – Beer Law is problematic from point of their turbidity. An advantage for the case of finalized photochromic pigments applied on the textile or other substrates in determination of absorption k and scattering s coefficients is the black and white background method.
Successful Patient Diabetes Education in the Emergency Department
Authors: Lewis Vicki R. , Benda Natalie , Nassar Carine , Magee Michelle 
Published: March 2015

Purpose The purpose of this study was to examine the effect of diabetes self-management education (DSME) provided in a large urban emergency department (ED) by a certified diabetes educator using a “learner-centered” approach to teaching survival skills. It was hypothesized that an intervention providing learner-centered education in the ED would significantly improve diabetes knowledge and self-management skills. Methods Participants were patients who presented to the ED with uncontrolled blood glucose with type 2 diabetes mellitus (T2DM). A learner-centered DSME approach was developed. Baseline knowledge and skills were assessed in the ED with a 5-question test and a request to demonstrate meter and insulin injection technique. Education focused on identified gaps in knowledge and skills and incorporated an opportunity for the patient to exercise control in the treatment process. At outpatient follow-up, knowledge retention was assessed with the same 5-question test, and skills again were tested. Results Patients with T2DM who were provided learner-centered DSME in the ED demonstrated a significant increase in knowledge-related test scores on all questions at follow-up. Significantly fewer patients required meter and insulin injection instruction postintervention, compared to the baseline. Conclusion Study results provide evidence supporting the effectiveness of learner-centered DSME delivered in the ED at imparting critical knowledge and skills to patients with T2DM.
The meaning of home at the end of life: A video-reflexive ethnography study
Authors: Collier Aileen , Phillips Jane L , Iedema Rick 
Published: March 2015

Background: While ‘home’ is cited most frequently as being the preferred place of death, most people will die in institutions. Yet, the meaning and significance of home for people nearing the end of life has not been fully explored. Aim: The aim of this article is to critically examine the meaning of home for dying patients and their families. Design: The qualitative study used video-reflexive ethnography methods. Data were collected and analysed over an 18-month period. Setting/participants: Participants were recruited from two Australian sites: a palliative care day hospital and an acute hospital. Participants included patients with a prognosis of 6 months or less ( n = 29), their nominated family member(s) ( n = 5) and clinicians ( n = 36) caring for them. Patients and families were ‘followed’ through care settings including the palliative care unit and into their own homes. Results: Whether or not participants deemed space(s) safe or unsafe was closely related to the notion of home. Six themes emerged concerning this relationship: ‘No place like home’; ‘Safety, home and the hospital’; ‘Hospital “becomes” home’; ‘Home “becomes” hospital’; ‘Hospital and “connections with home”’; and ‘The built environment’. Conclusion: Home is a dynamic concept for people nearing the end of life and is concerned with expression of social and cultural identity including symbolic and affective connections, as opposed to being merely a physical dwelling place or street address. Clinicians caring for people nearing the end of life can foster linkages with home by facilitating connections with loved ones and meaningful artefacts.
A scoping review of bereavement risk assessment measures: Implications for palliative care
Authors: Sealey Margaret , Breen Lauren J , O’Connor Moira , Aoun Samar M 
Published: March 2015

Background: Palliative care standards and policies recommend that bereavement support be provided to family caregivers, yet uncertainty surrounds whether support currently offered by palliative care services throughout developed countries meets caregiver needs. The public health model of bereavement support, which aligns bereavement support needs with intervention, may address this gap between policy and practice. Aim: The aim was to review the literature to identify bereavement risk assessment measures appropriate for different points in the caring and bereavement trajectories, evaluate their psychometric properties and assess feasibility for use in palliative care. Design: A scoping review was systematically undertaken following Arksey and O’Malley’s methodological framework. Data sources: PsycINFO, CINAHL, PubMed and Cochrane Reviews databases, as well as grey literature including Internet searches of Google, World Health Organization, CareSearch, the Grey Literature Report and OAIster were searched. Bereavement organisations and palliative care websites, reference lists in obtained articles and grief and bereavement handbooks were also scrutinised. Results: Of 3142 records screened, 356 records yielded 70 grief measures. In all, 19 measures published between 1982 and 2014 were identified for inclusion in this review, and categorised for use with family caregivers at three points in time – before the patient’s death ( n = 5), in the period following the death ( n = 10) and for screening of prolonged or complex grief ( n = 4). The majority had acceptable psychometric properties; feasibility for use in palliative care varied substantially. Conclusion: This review is an important preliminary step in improving the assessment of bereavement risk and, consequently, better bereavement outcomes for palliative care family caregivers.
Interventions for bereaved parents following a child’s death: A systematic review
Authors: Endo Kaori , Yonemoto Naohiro , Yamada Mitsuhiko 
Published: March 2015

Background: A child’s death is one of the most stressful events that parents and siblings may experience. Interventions for bereaved families following a child’s death have been examined over the last several decades. However, there is little high-quality evidence to support any rationale for determining optimal interventions for bereaved parents and siblings. Aim: This study objectives were to evaluate the efficacy of interventions for bereaved parents and siblings following a child’s death, to collect empirical evidence of the quality of these intervention studies, and to identify methodological challenges. Design: A systematic review of data from randomized controlled trials of interventions for parents or siblings bereaved after a child loss. Data sources: We searched MEDLINE (from 1949), PsycINFO (from 1806), and CINAHL (from 1806) databases for key terms and checked the reference lists of potentially relevant articles. Results: We identified nine articles describing eight eligible trials from which we extracted data. The four types of intervention included support groups, counseling, psychotherapy, and crisis intervention. Most intervention trials showed some effect on participants in at least one outcome measure. However, we identified many severe methodological issues and outcome sets in these trials. Conclusion: Very little evidence of sufficient quality is available to confirm the effects of intervention measures on bereaved parents and siblings following a child’s death. Well-designed randomized controlled trials are needed to improve our understanding of the efficacy and implementation of interventions targeting bereaved parents and siblings.
A J2–J3 approach in plastic and damage description of ductile materials
Authors: Cortese Luca , Coppola Tommaso , Campanelli Flavia , Broggiato Giovanni B 
Published: March 2015

This paper illustrates a methodology to improve the description of the plastic behavior and the fracture prediction for ductile materials under complex loading conditions. To this purpose, a plasticity model and a damage estimation model are proposed. The former, differently from the classic J2 plasticity theory, takes into account the effect of the third deviatoric invariant on the plastic flow. The latter assumes that damage accumulation is governed by both stress triaxiality and deviatoric parameters, and takes advantage of the new plasticity formulation. The two models rely on the same theoretical foundation, where a specific function is invoked to describe the subsequent yield surfaces and the damage accumulation up to fracture. Both have been implemented into a commercial finite element code via user subroutines. Three steel alloys have been tested under very different stress states: tensile tests on smooth and round notched bars, plane strain tests, torsion tests, and combined tension–torsion tests on hollow and solid cylindrical bars have been executed. For the last ones, several tension—torsion-loading ratios have been applied. These kinds of tests allow to explore a wide domain of the governing parameters for both models. The experimental results from tensile and torsion tests are used to calibrate the proposed plasticity model and the damage model; combined tests are used for validation purposes. The experimental–numerical comparison of global quantities made by using a standard plasticity approach confirms the need for a more accurate plastic description in the large strain range. The proposed plasticity model is able to provide a very good match until fracture for all tests available. Moreover, the damage model has the potential to take into account the experimental evidence, predicting the fracture initiation accurately. In particular, its validation by using tension–torsion tests shows to be really significant.
Heparin Reexposure in Patients With a History of Heparin-Induced Thrombocytopenia
Authors: Dhakal Prajwal , Giri Smith , Pathak Ranjan , Bhatt Vijaya Raj 
Published: March 2015

Objectives: Patients with a history of heparin-induced thrombocytopenia (HIT), who require subsequent anticoagulation, have limited options. Rechallenge with unfractionated heparin (UFH) has been reported but may be associated with a risk of recurrence of HIT. The objective of this study was to determine the safety of heparin reexposure in patients with a history of HIT. Methods: Using several search terms, all cases of heparin reexposure in patients with HIT indexed in MEDLINE (English language only) by June 2014 were reviewed. The bibliography of each relevant article was searched for additional reports. In cases of multiple reexposures, each reexposure was identified as a separate instance of reexposure during analysis. Results: A total of 136 patients with a history of HIT had 141 instances of heparin reexposure. Cardiac (76%) and vascular surgeries (11%) were the most common indications. Antiplatelet factor 4/heparin antibodies were positive in 63% of evaluable cases before reexposure. Preexposure plasma exchange (11%) and postexposure nonheparin anticoagulants (63%) were frequently utilized. Complications with heparin reexposure included recurrence of HIT (2.1%, 95% confidence interval 0.73%-6.07%) and bleeding (2.1%). Conclusion: Intraoperative heparin reexposure in patients with a history of HIT has a small risk of developing HIT recurrence. The use of preexposure plasma exchange in patients with positive antiplatelet factor 4/heparin antibody and postexposure nonheparin anticoagulants arguably may have reduced the risk of recurrence of HIT.