bluuebunny/crossref_metadata_2025_split huggingface dataset:
RESPONSES TO DISCLOSURE OF DOMESTIC VIOLENCE IN THE ED
Authors: McGarry Julie , Hinsliff-Smiith Kathryn , Kench Selecia , Miller Philip 
Published: August 2014

Objectives & BackgroundSignificant numbers of people attend ED either as a direct result of domestic violence and abuse (DVA) or related admissions, for example self-harm (Boyleet al, 2006, Boursnell and Prosser, 2010). However, effective management remains problematic and as Gibbons (2011) has highlighted DVA often goes unreported by ED staff. The recent National Institute of Health and Care Excellence (NICE) (2014) guidanceDomestic violence and abuse […]has identified that front line health care professionals will have a pivotal role and responsibility in the management of DVA in the future. The aim of our research therefore was to gather evidence regarding current practice in the recognition and management of DVA within ED in order to develop recommendations for service development through the following questions:How are survivors of DVA currently identified and managed within the ED?What systems can be put into place to maximize recognition and effective support within this context?MethodsA qualitative exploratory study involving in-depth interviews with ED clinical staff (n=11) and focus groups with survivors of domestic abuse (n=6) who had attended ED in order to understand experiences and identify factors influencing effective recognition and assessment within ED. A pre-piloted aide memoire was used to guide the interviews and focus groups. Data were analyzed using Framework (Ritchie and Lewis, 2012).ResultsInterviews identified a number of themes with clinical staff highlighting that it was emotionally and professionally ‘challenging' to manage disclosure, expressed anxiety about ‘wanting to do the right thing' and were cognizant of the organizational constraints of ‘managing time'. Survivors had first-hand experience of ED attendance and discussed how they did not disclose to ED staff for a number of reasons including guilt about repeated ED attendance as a result of their injuries and ‘time wasting', not being able to respond to staff advice to ‘leave abusive partners' and the lack of opportunity ‘privacy' within the ED environment.ConclusionA number of barriers exist including cultural and organizational structures which mediate against effective assessment and support. The recent NICE (2014) guidelines provide a potential platform to transform effective assessment and support for survivors by ED staff. Findings of the study and implications for service and practice development will form the basis of the presentation.
PAEDIATRIC TRAUMATIC CARDIAC ARREST: DATA FROM THE JOINT THEATRE TRAUMA REGISTRY
Authors: Hillman Christopher M , Rickard Annette , Rawlins Matthew , Smith Jason 
Published: August 2014

Objectives & BackgroundTraumatic cardiac arrest (TCA) in children is associated with poor survival (<5% in the majority of studies) and even worse neurological outcome.Since 2003, over 600 seriously injured local national children have been treated at deployed UK military medical treatment facilities during the Iraq and Afghanistan conflicts. A number of these were in cardiac arrest after sustaining traumatic injuries.Mechanism of InjuryMechanismIED13GSW7MVC4Drowning4Other (RPG, UXO)4Total32Trauma care has continually advanced during the recent conflicts, leading to many unexpected survivors (1). The objective of this study was to define outcomes from paediatric TCA in this cohort.MethodsA retrospective database review was undertaken using the Joint Theatre Trauma Registry. This includes UK military, coalition military, civilians, and local security forces personnel who prompted trauma team activation. However, all children in this series were local nationals. All children aged less than 18 years who presented between January 2003 and April 2014, and who underwent CPR, were included.Results32 children with TCA were included. The mechanisms of injury were IED (improvised explosive device), GSW (gunshot wound), MVC (motor vehicle collision), drowning and others (rocket propelled grenade, unexploded ordnance) – see Table 1. 4 children survived to discharge from the medical treatment facility (12.5%), though no data are available regarding the long-term neurological outcome in these patients. Further analyses, in particular with regard to injury patterns and life saving interventions, are underway.ConclusionOutcomes from this cohort show better survival rates in paediatric traumatic cardiac arrest compared to the most other studies. The reason for this is not known, although this mirrors the unexpected survivors previously reported in recent military series. Further work is necessary to define the optimal management of paediatric patients in TCA.
Simulation of end-member scenarios of density-driven flow: prediction of dolostone geobody dimensions using COMSOL
Authors: Pal Mayur , Taberner Conxita , Tueckmantel Christian 
Published: August 2014

Abstract
Density-driven flows occur in nature and are initiated by density contrast. Salinity and temperature differences are remarkably effective in initiating density-driven flow, which may instigate convective flow. In turn, convective flow is seen by many authors as key for solute and mass transport, which are important processes controlling dolomitization.
Two key dolomitization models rely on the application of density-driven flow concepts: (1) dolomitization by shallow or deep reflux of hypersaline brines in coastal ramp settings; and (2) fault-related dolomitization by the inflow of deep-seated fluids. These dolomitization scenarios are evaluated in this paper to infer plausible architecture, geobody dimensions and rock property distributions of dolomitic reservoirs. Since dolomitization processes may also alter porosity and permeability of the host lithology, changes in these properties are also discussed.
This contribution focuses on the application of numerical models to assess the applicability of specific dolomitization models/mechanisms in different geological scenarios. We discuss end-member results of flow simulations using the numerical code COMSOL. This software has been chosen to model these processes as it provides a multiphysics framework for solving coupled systems, as in the case of brine reflux and geothermal convection.
Our results provide a useful insight to the dynamic propagation of the limestone–dolomite front through fingering effects. The dolomite geobodies/patterns generated with the help of numerical simulation compare favourably with dolomite geobodies seen in outcrops. This study shows that during the dolomitization process the shape, the extent of propagation of the limestone–dolomite front and the rock properties (porosity and permeability) of the dolomitized reservoir are mainly influenced by the ‘contaminant’ source initiating dolomitization: that is, the magnesium-rich brine density in the case of brine reflux and the heat flux intensity in the case of geothermal reflux circulation.
Abstract BL-2: Brinker Award Lecture: Older Women and Breast Cancer: Challenges and Opportunities
Authors: Muss HB 
Published: August 2014

Abstract
In the United States and other developed nations breast cancer incidence and mortality rates rise dramatically with increasing age. This fact, coupled with the aging of the U.S population is leading to a tsunami of older women with breast cancer. Most oncologists lack training in geriatrics and the frequent comorbidities in older patients along with a new diagnosis of breast cancer makes treatment selection challenging. Little data from clinical trials are available to guide physicians in treatment selection and a paucity of geriatricians makes it difficult to develop comprehensive treatment plans for many older patients. Newer tools that are validated, fast, and user-friendly are now available to help busy clinicians do meaningful geriatric assessments which are necessary for evaluating the medical, functional, cognitive, psychological, and social status of older patients. Such tools can be used to accurately estimate survival in older patients and more recently to predict chemotherapy related toxicity. For older patients, maintenance of independent living and cognitive function are their major goals and such preferences must be taken into consideration when planning treatment. Older women, like younger women, are interested in body image and when possible should be offered breast preservation with lumpectomy and radiation. In some older women treated with lumpectomy and adjuvant endocrine therapy for small tumors that are hormone-receptor positive and lower grade, breast radiation may be omitted with only a small increase in the risk of in-breast recurrence. The majority of older patients with early stage breast cancer have hormone receptor positive, HER-2 negative breast cancers and are excellent candidates for endocrine therapy. The major issue in these patients is defining the potential added value of chemotherapy. Elders with HER-2 positive tumors may be good candidates for chemotherapy and trastuzumab, while for many with “triple-negative” lesions, chemotherapy is the option of choice. Older patients with metastatic breast cancer whose tumors have progressed after endocrine therapy can be considered for palliative chemotherapy and many single agent regimens are well tolerated in this setting. In these patients, making sure they are offered “structured” palliative care as part of their treatment program is integral to maximizing quality of life and possibly even prolonging survival. Lastly, eligible elders should be offered clinical trials participation. Although getting elders on trials remains a challenge, it's essential we work diligently on recruitment so as to obtain meaningful data on outcomes and toxicities of newer treatment regimens. Opportunities for trials of all types abound, not only for testing new treatments, but for defining interventions that minimize toxicity and loss of function. All of us in oncology will need to learn how to care for older cancer patients to provide them with optimal treatment.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr BL-2.
Abstract MS1-3: Clinical Development of mTOR Inhibitors in Breast Cancer
Authors: André F 
Published: August 2014

Abstract
mTOR is a serine/threonine kinase involved in cancer cell metabolism and protein synthesis. mTOR induces phosphorylation of estrogen receptor and resistance to endocrine therapy in preclinical models. Based on this rationale, clinical trials have evaluated whether first generation of mTOR inhibitors could reverse resistance to endocrine therapy. Two randomized trials, including one registration trial, have reported that everolimus improves progression-free survival in patients resistant to non-steroidal aromatase inhibitors. These data are consistent with a phase II randomized trial performed in the neoadjuvant setting. One large phase III trial performed with temsirolimus failed, mainly due to dose intensity of the drug and patient population. Overall, these finding suggest that rapalogs could reverse resistance to endocrine therapy. These data open several avenues in the field of breast cancer.
First, two trials are starting that evaluate the efficacy of everolimus in the adjuvant setting. These trials evaluate everolimus either frontline or after 2–3 years of endocrine therapy.
Second, rapalogs are being tested in other breast cancer subtypes including Her2-overexpressing breast cancers and triple negative breast cancers. Indeed, mTOR has been shown to be involved in trastuzumab resistance in preclinical studies. Early trials have suggested that mTOR inhibition could reverse trastuzumab resistance. mTOR inhibitors have also been shown to synergize with cisplatin in preclinical models, and this combination is currently being evaluated in a phase II randomized trial.
Finally, several mechanisms of resistance to rapalogs have been identified. This includes positive feedback loops and lack of optimal bioactivity on p4EBP1. Rapalogs indeed mediate activating feedback loops that in turn induce a paradoxical activation of kinase pathways. Based on this observation, several trials have started that evaluate the combination between Rapalogs and IGF1R inhibitors. Preliminary results from phase I trial suggest that this combination is active in ER+/highly proliferative disease. Although they induce optimal inhibition of pS6K, several studies have reported that rapalogs could be suboptimal to inhibit p4EBP1, a protein downstream of mTORC1. 4EBP1 is involved in protein synthesis. Second generation mTOR inhibitors (mTORC1/C2 inhibitors) present an increased bioactivity on 4EBP1, in addition to avoid mTORC2-mediated feedback loop. This second generation mTOR inhibitor is being tested in early phase trials.
Overall, rapalogs have opened the path for the development of mTOR inhibitors in the field of breast cancer. This will further improve outcome by exploring new indications and by developing strategies to reverse resistance. Finally, the development of mTOR inhibitors will dramatically increase our knowledge on the role of metabolism and protein translation in cancer progression.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr MS1-3.
Abstract OT1-1-12: NSABP FB-7 Trial: A Phase II Randomized Clinical Trial Evaluating Neoadjuvant Therapy Regimens with Weekly Paclitaxel and Neratinib or Trastuzumab or Neratinib and Trastuzumab Followed by Doxorubicin and Cyclophosphamide with Postoperative Trastuzumab in Women with Locally Advanced HER2-Positive Breast Cancer
Authors: Lu J , Jacobs SA , Buyse ME , Paik S , Wolmark N 
Published: August 2014

Abstract
Neratinib is an oral, small molecule which acts as an irreversible inhibitor of the pan ErbB receptor tyrosine kinase. Dual ErbB blockade combined with chemotherapy improves efficacy in Her-2 positive breast cancer. Both NeoALTTO (Lancet 2012) and Neosphere (Lancet Oncol 2012) trials demonstrated higher pCR for Her-2 positive breast cancer receiving dual anti-Her-2 neoadjuvant blockade therapy. The purpose of this trial is to determine the activity and safety profile of Neratinib as mono-blockade or in combination with Trastuzumab as dual blockade in neoadjuvant therapy of locally advanced breast cancer (stage IIB, III A, B and C).
Methods: This NSABP Foundation Research Program study (FB-7) is designed as a Phase II, multi-center, three arm clinical trial for patients with Her-2 positive locally advanced breast cancer. 126 patients will be enrolled. The initial two- arm study of Neratinib or Trastuzumab in combination with Paclitaxel began in December 2010. 30 patients were enrolled by December of 2011 at which time the study was placed on hold awaiting the recommended phase II dose of the three drug combination, Neratinib, Trastuzamab and Paclitaxel (NSABP FB-8 trial), which is a Phase I dose-escalation study in women with metastatic Her-2 positive breast cancer. The amended FB −7 trial is now a three arm trial of weekly Paclitaxel and Neratinib or Trastuzumab or Neratinib and Trastuzumab for 4 cycles followed by Doxorubicin and Cyclophosphamide for 4 cycles prior to surgical resection. Patients will then receive postoperative Trastuzumb to complete one total year of Her-2 blockade therapy. The primary goal of this study is to determine the pathologic complete response in breast and axillary lymph nodes following completion of neoadjuvant therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-12.
Abstract OT2-2-02: Prospective multicentre study evaluating the effect of impaired tamoxifen metabolization on efficacy in breast cancer patients receiving tamoxifen in the neo-adjuvant or metastatic setting - The CYPTAM-BRUT 2 trial.
Authors: Lintermans A , Dieudonné A-S , Blomme C , Lambrechts D , Wildiers H , Christiaens M-R , Timmerman D , Van Calster B , Decloedt J , Berteloot P , Joerger M , Zaman K , Dezentjé V , Neven P 
Published: August 2014

Abstract
Background: Tamoxifen is often used for the prevention and treatment of hormone receptor positive breast cancer. It is metabolized in the liver through cytochrome P450 (CYP) enzymes to more active metabolites, of which endoxifen is considered the most important. It is known that certain genetic variants in CYP enzymes result in lower serum endoxifen levels, but their effect on tamoxifen efficacy is not yet clear as results remain contradictory.
Trial design: CYPTAM-BRUT 2 is a prospective multicentre open label single arm non randomized observational trial approved by the UZ Leuven Ethics Committee. Eligibility criteria are postmenopausal women with estrogen receptor positive invasive breast cancer receiving tamoxifen as first line therapy in the metastatic or neo-adjuvant setting. Prior adjuvant endocrine therapy is allowed if there is more than 12 months after completion of the adjuvant therapy.
Primary endpoint is the relation between endoxifen levels and objective response rate. Secondary endpoints are the relation between endoxifen levels and the proportion of patients who are failure-free at 6 months, clinical benefit, tolerability of tamoxifen and the predictive value of the tamoxifen activity score, based on the presence of genetic variants and CYP inhibiting drugs. Patients with bone-only lesions will only be included in the analysis of the secondary endpoints.
The trial is designed to show an improvement of the objective tumor response rate from 5% in patients with an unfavorable endoxifen profile (steady-state concentrations &lt; 90nM) to 20% in patients with a favorable endoxifen profile (steady-state concentrations ≥ 90nM). With a type I error of 5% and a power of 90%, 231 patients have to be included into the study. The main secondary study endpoint is progression-free survival (PFS) at 6 months. With a total number 260 patients eligible for PFS, the study has a power of 80% to detect a 20% improvement of PFS at 6 months (i.e. from 50% to 70%) in patients with a favorable endoxifen as compared to patients with an unfavorable endoxifen profile, and a type-I error of 5%.
Patient accrual: Total sample size is 260 and currently 202 patients from 22 participating centres in Belgium and Switzerland are included (May 2012).
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-2-02.
Abstract OT2-3-10: Phase II study of panitumumab, nab-paclitaxel, and carboplatin for patients with primary inflammatory breast cancer (IBC) without HER2 overexpression
Authors: Willey JS , Alvarez RH , Valero V , Lara JM , Parker CA , Hortobagyi GN , Ueno NT 
Published: August 2014

Abstract
Background: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. The outcome for patients with IBC is bleak despite multimodality treatment approaches. 10-year disease-free survival rates after combined anthracycline and taxane-containing chemotherapy, surgery, and radiation are only 20%–25%. Our recent study found EGFR overexpression, a predictive factor of poor outcome, in 12 of 40 (30%) patients with IBC. Panitumumab has shown activity against EGFR overexpressing breast cancer xenograft model.
Trial design: This is a single center, open-label, phase II study to evaluate the safety and efficacy of panitumumab in combination with preoperative chemotherapy. The treatment regimen consists panitumumab 2.5 mg/Kg given intravenously alone for the first week, followed by weekly panitumumab, nab-paclitaxel (100mg/m2) and carboplatin (2 AUC) (PNC) for 12 weeks. Patients then will receive 5-FU, epirubicin, and cyclophosphamide (FEC) every 3 weeks for 4 cycles prior to surgery.
Eligibility criteria: 1) Histological confirmation of breast carcinoma with pathologic evidence of dermal lymphatic invasion and clinical diagnosis of IBC, including diffuse erythema, heat, ridging, and peau d'orange; 2) Normal HER2 expression; 3) No prior therapies for IBC; 4) Adequate hematologic, cardiac, renal and hepatic functions.
Specific aims: 1) Primary objective is to determine the pathologic complete response (pCR) rate in patients with primary IBC without HER2 overexpression; 2) Secondary objectives are to determine the disease-free survival (DFS), overall survival (OS), the safety and tolerability of PNC regimens and the correlates of pathologic response rate and EGFR expression level.
Statistical methods: 1) Previous studies have shown that this IBC patient population achieved a 13% pCR rate on the standard of care. We assume a beta (0.26, 1.74) prior distribution for the pCR rate. This prior distribution has a mean of 13% and a standard deviation of 19%. 2) We will stop the trial early if P (pCR rate &gt;/= 13%) is &lt; 0.01. If we determine that there is less than a 1% chance that the pCR rate is 13% or more we will consider stopping the trial. 3) Once we have completed the study we will estimate the pCR rate with a 90% credible interval. If we have pCR in 4 of the 40 patients (10%), then our 90% credible interval for the pCR rate will be 4.0–19.6%. If we have pCR in 8 of the 40 patients (20%), then our 90% credible interval for the pCR rate will be 10.6–30.4%. We will also report the posterior probability that the pCR rate is 13% or more. For example, if we have pCR in 8 of the 40 patients (20%), then the probability that the pCR rate is 13% or more is 0.869.
Present accrual and target accrual: To date, 13 patients have been enrolled. Target accrual is 40 patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-3-10.