bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Hand-Foot Skin Reaction and Quality of Life Questionnaire: An Assessment Tool for Oncology
Authors: Anderson Roger T. , Keating Karen N. , Doll Helen A. , Camacho Fabian 
Published: June 2015

AbstractBackground.Skin toxicity (hand-foot syndrome/hand-foot skin reaction, HFS/R) related to antineoplastic therapy is a significant issue in oncology practice, with potentially large impacts on health-related quality of life (HRQL).Materials and Methods.A patient-reported questionnaire, the hand-foot skin reaction and quality of life (HF-QoL) questionnaire was developed to measure the HFS/R symptoms associated with cancer therapeutic agents and their effect on daily activities. The validity and reliability of the HF-QoL questionnaire was tested in a randomized trial of capecitabine with sorafenib/placebo in 223 patients with locally advanced/metastatic breast cancer. Other measures completed included patient ratings of condition severity, the Functional Assessment of Cancer Therapy-Breast cancer (FACT-B), and the clinician-rated National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0, hand-foot skin reaction grade. The psychometric properties of the HF-QoL tested included structural validity, internal consistency, construct validity, discriminant validity, and responsiveness. Finally, the minimal clinically important difference (MCID) was estimated.Results.The HF-QoL instrument comprises a 20-item symptom scale and an 18-item daily activity scale. Each scale demonstrated excellent measurement properties and discriminated between NCI-CTCAE grade and patient-rated condition severity with large effect sizes. The daily activity scale had excellent internal consistency and correlated with the FACT-B and HF-QoL symptom scores. Both HF-QoL scale scores increased linearly with increasing patient-rated condition severity. The MCIDs were estimated as 5 units for daily activities and 8 units for symptoms mean scores.Conclusion.The HF-QoL was sensitive to symptoms and HRQL issues associated with HFS/R among participants treated with capecitabine with and without sorafenib. The HF-QoL appears suitable for assessing the HRQL impairment associated with HFS/R to cancer therapies.Implications for Practice:Skin toxicity related to anticancer therapies is a significant issue in oncology practice. Several newer agents, as well as older therapies, are associated with the skin toxicity known as hand-foot skin reaction (HFSR) or hand-foot syndrome (HFS). This study describes the development and validation of a brief, patient-reported questionnaire (the hand-foot skin reaction and quality of life questionnaire) supporting its suitability for use in clinical research to aid in early recognition of symptoms, to evaluate the effectiveness of agents for HFS/R treatment within clinical trials, and to evaluate the impact of these treatments on HFS/R-associated patients' health-related quality of life.
Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers
Authors: Flaherty Keith T. , Hamilton Betty K. , Rosen Mark A. , Amaravadi Ravi K. , Schuchter Lynn M. , Gallagher Maryann , Chen Helen , Sehgal Chandra , O'Dwyer Peter J. 
Published: June 2015

Abstract

Background.
Vascular endothelial growth factor and platelet-derived growth factor signaling in the tumor microenvironment appear to cooperate in promoting tumor angiogenesis.

Patients and Methods.
We conducted a phase I trial combining bevacizumab (i.v. every 2 weeks) and imatinib (oral daily). Once a recommended phase II dose combination was established, a phase II trial was initiated in patients with metastatic melanoma. A Simon 2-stage design was used with 23 patients required in the first stage and 41 patients in total should the criteria to proceed be met. We required that 50% of the patients be progression-free at 16 weeks. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and power Doppler ultrasonography were performed in patients with metastatic tumors amenable to imaging with these methods at baseline and after 4 weeks.

Results.
A total of 17 patients were accrued to 4 dose and combination levels. Bevacizumab 10 mg/kg every 2 weeks could be safely combined with imatinib 800 mg daily. Common toxicities included fatigue, nausea, vomiting, edema, proteinuria, and anemia, but were not commonly severe. A total of 23 patients with metastatic melanoma (48% with American Joint Commission on Cancer stage M1c; median age, 63 years) were enrolled in the first stage of phase II. The 16-week progression-free survival rate was 35%, leading to termination of phase II after the first stage. In the small subset of patients who remained on study with lesions evaluable by DCE-MRI, significant decreases in tumor vascular permeability were noted, despite early disease progression using the Response Evaluation Criteria In Solid Tumors.

Conclusion.
Bevacizumab and imatinib can be safely combined at the maximum doses used for each agent. We did not observe significant clinical activity with this regimen in melanoma patients.

Implications for Practice:
Vascular endothelial growth factor (VEGF)-targeted antiangiogenic therapy has proven clinical efficacy as a standalone therapy in renal cell carcinoma and glioblastoma multiforme. Also, enhancement of conventional cytotoxic chemotherapy efficacy has been observed in colorectal, non-small-cell lung, breast, and ovarian cancers. Optimal strategies to cotarget angiogenic cytokines combined with VEGF have not been defined. It was found that bevacizumab could be safely combined with imatinib, which was used as a platelet-derived growth factor receptor inhibitor in our study. High-dose imatinib-related edema was not observed when paired with bevacizumab. This regimen might be suitable for further investigation in other cancers but apparently not in melanoma.
The acid taste of climate change: 20th century acidification is re‐emerging during a climatic extreme event
Authors: Schweiger Andreas H. , Audorff Volker , Beierkuhnlein Carl 
Published: June 2015

The current state of an ecosystem results from the complex interaction of abiotic and biotic drivers jointly influenced by their dynamics and the legacy of a systems' history. Negative synergies between emerging climatically extreme events and past environmental impacts are expected to shift ecological communities to alternative stable states or towards hysteretic successional trajectories. However, knowledge on mutual effects of environmental stressors is scarce especially for not experimentally controlled, natural ecosystems.We investigated the effect of a prolonged drought and heat wave occurred during 2003 on the short‐term vegetation responses of forest springs, a waterlogged type of ecosystem which is highly abundant in Central European siliceous mountains. These landscapes experienced strong impairment by 20th century atmospheric acidification. For different levels of acidification, we investigated plant community composition and water chemistry of 57 springs before (1996) during (2003) and after (2004–2006) the summer of 2003 and quantified ecological resilience and elasticity related to this extreme event for single plant species and species assemblages of whole communities.The extreme dry and hot summer 2003 significantly decreased discharge, increased water temperature and affected water chemistry of the investigated springs. Ecological resilience and elasticity against the climatic extreme event differed significantly between communities dependent on their previous impact by acidification. Springs which were less affected by acidification performed higher resilience and elasticity than strongly acidified springs.Our study shows that strong negative synergies between emerging climatic extreme events and past environmental impairments occur on landscape scale. Hitherto, such interactions between climate change, hydrochemistry, and the responses of ecosystems have been neglected.
Assisted History Matching for Fractured Reservoirs by Use of Hough-Transform-Based Parameterization
Authors: Lu Le , Zhang Dongxiao 
Published: June 2015

Summary
Successful production in fractured reservoirs is significantly dependent on knowledge of the location, orientation, and conductivity of the fractures. Early water breakthrough can be prevented and sweep efficiency can be improved with the help of comprehensive and accurate information of fracture distributions. However, it is a challenge to estimate fracture distributions by conventional-history-matching methods because of the complexity of such reservoirs. Although there has been great progress in assisted-history-matching techniques during the last 2 decades, estimating fracture distributions in fractured reservoirs is still inefficient because of the strong heterogeneity and spatial discontinuity of model parameters. The performance of assisted-history-matching methods, such as the ensemble Kalman filter, can be significantly degraded by the non-Gaussian distributions of the parameters, such as effective permeability and porosity. On the other hand, although the geometric shapes of fractures may be generated properly at the initial step, they are difficult to preserve after updating, which results in geologically unrealistic fracture-distribution maps. In this study, we develop an assisted-history-matching method for fractured reservoirs with a Hough-transform-based parameterization. The facies maps of fractured reservoirs are parameterized into Hough-function fields in a discrete Hough space, whereas each gridblock in the Hough domain represents a fracture defined by its two Cartesian coordinates: angle θ of its normal and ρ of its algebraic distance from the origin in the flow domain. The length and axial position of the fractures are defined by two additional parameters on the same grid. The Hough-function value of each gridblock in the Hough domain is used as the indicator of the existence of the fracture in the facies map. When this parameterization is implemented in assisted history matching, the parameter fields in the Hough space, instead of the facies maps, are updated conditional on the production history. An inverse transform is performed to generate facies maps for the reservoir simulator. Pointwise prior information, such as known fractures discovered from well-log data, as well as the statistics of fracture orientation, can be honored by the inverse transform throughout the history-matching process. Applications and the effectiveness of this method are demonstrated by 2D synthetic-waterflooding examples. The fracture distributions in reference fields are identified by this method, and updated models are capable of providing improved predictions for prolonged periods of production.
Metabolic Effects of Exercise Training Among Fitness-Nonresponsive Patients With Type 2 Diabetes: The HART-D Study
Authors: Pandey Ambarish , Swift Damon L. , McGuire Darren K. , Ayers Colby R. , Neeland Ian J. , Blair Steven N. , Johannsen Neil , Earnest Conrad P. , Berry Jarett D. , Church Timothy S. 
Published: June 2015

OBJECTIVETo evaluate the impact of exercise training (ET) on metabolic parameters among participants with type 2 diabetes mellitus (T2DM) who do not improve their cardiorespiratory fitness (CRF) with training.RESEARCH DESIGN AND METHODSWe studied participants with T2DM participating in the Health Benefits of Aerobic and Resistance Training in Individuals With Type 2 Diabetes (HART-D) trial who were randomized to a control group or one of three supervised ET groups for 9 months. Fitness response to ET was defined as a change in measured peak absolute oxygen uptake (ΔVO2peak, in liters per minute) from baseline to follow-up. ET participants were classified based on ΔVO2peak into fitness responders (ΔVO2peak ≥5%) and nonresponders (ΔVO2peak &lt;5%), and changes in metabolic profiles were compared across control, fitness responder, and fitness nonresponder groups.RESULTSA total of 202 participants (mean age 57.1 ± 7.9 years, 63% women) were included. Among the exercise groups (n = 161), there was substantial heterogeneity in ΔVO2peak; 57% had some improvement in CRF (ΔVO2peak &gt;0), with only 36.6% having a ≥5% increase in VO2peak. Both fitness responders and nonresponders (respectively) had significant improvements in hemoglobin A1c and measures of adiposity (ΔHbA1c: −0.26% [95% CI −0.5 to −0.01] and −0.26% [−0.45 to −0.08]; Δwaist circumference: −2.6 cm [−3.7 to −1.5] and −1.8 cm [−2.6 to −1.0]; Δbody fat: −1.07% [−1.5 to −0.62] and −0.75% [−1.09 to −0.41]). No significant differences were observed in the degree of change of these metabolic parameters between fitness responders and nonresponders. Control group participants had no significant changes in any of these metabolic parameters.CONCLUSIONSET is associated with significant improvements in metabolic parameters irrespective of improvement in cardiorespiratory fitness.
Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism
Authors: Daniele Giuseppe , Winnier Deidre , Mari Andrea , Bruder Jan , Fourcaudot Marcel , Pengou Zuo , Tripathy Devjit , Jenkinson Christopher , Folli Franco 
Published: June 2015

OBJECTIVE
A gene mutation of the Wnt/β-catenin signaling cascade is present in rare patients with the insulin resistance syndrome. Sclerostin is a circulating peptide inhibiting Wnt/β-catenin signaling. Our aims were to evaluate serum sclerostin in subjects with prediabetes and to analyze its relationship with insulin resistance and β-cell function.

RESEARCH DESIGN AND METHODS
We performed a cross-sectional study including 43 healthy normal glucose-tolerant (NGT) individuals and 79 individuals with impaired glucose regulation (IGR), which included subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG-IGT, undergoing oral glucose tolerance test (OGTT) and dual-energy X-ray absorptiometry. A subgroup of 18 with NGT and 30 with IGR also underwent a euglycemic–hyperinsulinemic clamp with tracer.

RESULTS
Sclerostin levels were higher in IGR compared with NGT (50.8 ± 2.4 vs. 38.7 ± 2.3 pmol/L; P = 0.01), positively correlated with HOMA-insulin resistance (IR) (r = 0.62; P &lt; 0.001), and negatively correlated with insulin-mediated total body glucose disposal (r = −0.40; P &lt; 0.001). Fasting endogenous glucose production (EGP) and hepatic and adipose tissue insulin resistance indexes were positively correlated with sclerostin levels (r = 0.48, r = 0.62, and r = 0.61, respectively; P &lt; 0.001). Fasting and OGTT insulin clearance were inversely correlated with sclerostin serum levels (r = −0.52 and r = −0.44, respectively; both P &lt; 0.001). Sclerostin levels were not correlated with β-cell function parameters. In multiple linear regression analysis, the addition of sclerostin levels to the traditional risk factors for insulin resistance improved the r2 associated with HOMA-IR (r2 change: 0.055; F change: 28.893; P = 0.001) and insulin-mediated total body glucose disposal (r2 change: 0.059; F change: 4.938; P = 0.033).

CONCLUSIONS
Sclerostin levels are increased in individuals with prediabetes and correlated with insulin resistance in skeletal muscle, liver, and adipose tissue. The correlation between sclerostin and insulin clearance at fasting state and during OGTT is novel; thus, studies are needed to explore the potential causal relationship.
Refinements of the Medicare Outpatient Therapy Annual Expenditure Limit Policy
Authors: Amico Peter , Pope Gregory C. , Pardasaney Poonam , Silver Ben , Dever Jill A. , Meadow Ann , West Pamela 
Published: June 2015

Background
A Medicare beneficiary's annual outpatient therapy expenditures that exceed congressionally established caps are subject to extra documentation and review requirements. In 2011, these caps were $1,870 for physical therapy and speech-language pathology combined and $1,870 for occupational therapy separately.

Objective
This article considers the distributional effects of replacing current cap policy with equal caps by therapy discipline (physical therapy, occupational therapy, and speech-language pathology) or a single combined cap, and risk adjusting the physical therapy cap using beneficiary characteristics and functional status.

Methods
Alternative therapy cap policies are simulated with 100% Medicare claims for 2011 therapy users (N=4.9 million). A risk-adjusted cap for annual physical therapy expenditures is calculated from a quantile regression estimated on a sample of physical therapy users with diagnoses and clinician assessments of functional ability merged to their claims (n=4,210).

Results
Equal discipline-specific caps of $1,710 each for physical therapy, occupational therapy, and speech-language pathology result in the same aggregate Medicare expenditures above the caps as 2011 cap policy. A single combined-disciplines cap of $2,485 also results in the same aggregate expenditures above the cap. Risk adjustment varies the physical therapy cap by as much as 5 to 1 across beneficiaries and equalizes the probability of exceeding the physical therapy cap across diagnosis and functional status groups.

Limitations
One limitation of the study was the assumption of no behavioral response on the part of beneficiaries or providers to a change in cap policy. Additionally, analysis of risk adjusting the therapy caps was limited by sample size.

Conclusions
Equal discipline-specific caps for physical therapy, occupational therapy, and speech-language pathology are more equitable to high users of both physical therapy and speech-language pathology than current cap policy. Separating the physical therapy and speech-language pathology caps is a change that policy makers could consider. Risk adjustment of the therapy caps is a first step in incorporating beneficiary need for services into Medicare outpatient therapy payment policy.
De la villa antique à l’établissement alto-médiéval de la Maladrerie à Saillans (Drôme). Permanences et mutations jusqu’au VIIIe siècle.
Authors: Le Roy Ludovic , Berdeaux-Le Brazidec Marie-Laure , Malignas Adrien , Rovira Núria 
Published: June 2015

De la villa antigua al establecimiento alto-medieval de la Maladrerie en Saillans (Drôme). Permanencia y mutaciones hasta el siglo VIII.
Este artículo presenta los resultados de las excavaciones preventivas efectuadas en el sitio de La Maladrerie en Saillans (Drôme). Permitió elevar a la luz una parte de un amplio y rico establecimiento ocupado, sin cesar, desde la época galo-romana hasta la alta Edad Media. El interés de los descubrimientos reposa sobre el excelente estado de conservación de los vestigios comprendidos entre los siglos IV hasta VIII y sobre las formas arquitectónicas originales que pudieron ser observadas : hábitats, acondicionamientos domésticos, papel de las antiguas construcciones en la selección hecha por los edificadores de los primeros siglos de la Edad Media. El estudio presentado permite al mismo tiempo documentar un sector todavía ampliamente desconocido, el del valle de la Drôme, abordar la vida y la economía del sitio e ilustrar una problemática recurrente en el sur de Francia, la de la transición entre una finca galo-romana y las ocupaciones de la Edad Antigua tardía y de la alta Edad Media.
Vestiges et traces troglodytiques médiévaux autour de Tarascon-sur-Ariège
Authors: Guillot Florence 
Published: June 2015

Middle Ages troglodytic vestiges and traces around Tarascon-sur-Ariège.
An archaeological prospect using climbing techniques allowed to visit again all the cave porches located around Tarascon in the Ariège high valley, the heart of the north face of the Pyrenees. The research was focused on the vestiges of historical eras : those of the XIIth-XIVth centuries have been particularly numerous to be identified. This is a troglodytism, evidently eclectic, but finally poorly marked by pastoral habits. The porches, most of them in high parts, have been first of all strong, defensive and watching points, under the dependence of the Counts of Foix and associated within a network to a vast fortified glacis, including also outdoor castra isolated from the civil world as well as “ bourgs castraux” or fortified boroughs .
L’éternel retour du sweating system ?
Authors: Barraud de Lagerie Pauline 
Published: June 2015

Cet article éclaire l’histoire de la « responsabilité des commettants » en traçant un lien entre la tragédie de l’incendie de l’usine Triangle Shirtwaist, à New York en 1911, et le récent drame de l’effondrement du Rana Plaza, au Bangladesh en 2013. Il apparaît ainsi que, dès le sweating system du XIX e siècle, les défenseurs des travailleurs ont pointé du doigt la responsabilité de ceux qui, sans exercer une contrainte directe sur la main-d’œuvre, tirent néanmoins profit de son exploitation. Mais si le problème des mauvaises conditions de travail a alors été principalement réglé par d’autres moyens que la responsabilisation des commettants, la lutte anti-sweatshop dans le cadre des échanges mondialisés se caractérise en revanche aujourd’hui par un recours quasi exclusif à l’exercice d’une pression sur les donneurs d’ordre.
Responsabilité sociale et implication territoriale contemporaine de Michelin à Clermont-Ferrand : une réactualisation du système d’encadrement paternaliste du début du XX e siècle ?
Authors: Zanetti Thomas 
Published: June 2015

La firme Michelin, multinationale qui rassemble plus de 110 000 salariés dans le monde, a toujours maintenu son siège social dans la ville où elle est née : Clermont-Ferrand. L’entreprise est ainsi caractérisée par un degré élevé d’ancrage territorial qui trouve ses origines dans la mise en œuvre, durant la première moitié du XX e siècle, d’un système paternaliste d’encadrement de la force de travail. En résulte l’existence d’une organisation sociale spécifique au service de la production, qui va perdurer jusque dans les années 1990. Depuis deux décennies, Michelin fait face à la nécessité d’attirer une main-d’œuvre hautement qualifiée. La firme a ainsi défini une nouvelle stratégie d’encadrement de la force de travail qui s’inspire notamment du concept de responsabilité sociale des entreprises (RSE). Ce dernier traduirait alors un effort de perpétuation du capitalisme et des profits qu’il génère, qui, dans le cas de Michelin, s’exprimerait à travers l’émergence d’un « capitalisme territorial ».