bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteopontin, a Key Mediator Expressed by Senescent Pulmonary Vascular Cells in Pulmonary Hypertension
Authors: Saker Mirna , Lipskaia Larissa , Marcos Elisabeth , Abid Shariq , Parpaleix Aurelien , Houssaini Amal , Validire Pierre , Girard Philippe , Noureddine Hiba , Boyer Laurent , Vienney Nora , Amsellem Valerie , Marguerit Laurent , Maitre Bernard , Derumeaux Geneviève , Dubois-Rande Jean-Luc , Jourdan-Lesaux Claude , Delcroix Marion , Quarck Rozenn , Adnot Serge 
Published: July 2016

Objective—
Senescent pulmonary artery smooth muscle cells (PA-SMCs) may contribute to the pathogenesis of pulmonary hypertension by producing secreted factors. The aim of this study was to explore the role in pulmonary hypertension of extracellular matrix proteins released by senescent PA-SMCs.

Approach and Results—

Polymerase chain reaction array analysis of human PA-SMCs undergoing replicative senescence revealed osteopontin upregulation, which mediated the stimulatory effect of senescent PA-SMC media and matrix on PA-SMC growth and migration. Osteopontin was upregulated in lungs from patients with chronic obstructive pulmonary disease or idiopathic pulmonary arterial hypertension. Prominent osteopontin immunostaining was noted in PA-SMCs that also stained for p16 at sites of vascular hypertrophy, and lung osteopontin levels correlated closely with age. Compared with younger mice, 1-year-old mice displayed higher lung osteopontin levels, right ventricular systolic pressure, pulmonary vessel muscularization, and numbers of PA-SMCs stained for p16 or p21 and also for osteopontin. No such changes with age were observed in osteopontin
−/−
mice, which developed attenuated pulmonary hypertension during hypoxia. Compared with cultured PA-SMCs from young mice, PA-SMCs from 1-year-old mice grew faster; a similar fast growth rate was seen with PA-SMCs from young mice stimulated by matrix or media from old mice. Differences between old/young mouse PA-SMC growth rates were suppressed by antiosteopontin antibodies. PA-SMCs from osteopontin
−/−
mice grew more slowly than did wild-type PA-SMCs; they were stimulated by wild-type PA-SMCs media and matrix, and this effect was stronger with PA-SMCs from older versus younger mice.

Conclusions—
Osteopontin is a key mediator released by senescent PA-SMCs and contributing to pulmonary hypertension progression.
Impact of Hypothermia Initiation and Duration on Perihemorrhagic Edema Evolution After Intracerebral Hemorrhage
Authors: Volbers Bastian , Herrmann Sabrina , Willfarth Wolfgang , Lücking Hannes , Kloska Stephan P. , Doerfler Arnd , Huttner Hagen B. , Kuramatsu Joji B. , Schwab Stefan , Staykov Dimitre 
Published: July 2016

Background and Purpose—
Intracerebral hemorrhage (ICH) causes high morbidity and mortality. Recently, perihemorrhagic edema (PHE) has been suggested as an important prognostic factor. Therapeutic hypothermia may be a promising therapeutic option to treat PHE. However, no data exist about the optimal timing and duration of therapeutic hypothermia in ICH. We examined the impact of therapeutic hypothermia timing and duration on PHE evolution.

Methods—
In this retrospective, single-center, case–control study, we identified patients with ICH treated with mild endovascular hypothermia (target temperature 35°C) from our institutional database. Patients were grouped according to hypothermia initiation (early: days 1–2 and late: days 4–5 after admission) and hypothermia duration (short: 4–8 days and long: 9–15 days). Patients with ICH matched for ICH volume, age, ICH localization, and intraventricular hemorrhage were identified as controls. Relative PHE, temperature, and intracranial pressure course were analyzed. Clinical outcome on day 90 was assessed using the modified Rankin scale (0–3=favorable and 4–6=poor).

Results—

Thirty-three patients with ICH treated with hypothermia and 37 control patients were included. Early hypothermia initiation led to relative PHE decrease between admission and day 3, whereas median relative PHE increased in control patients (−0.05 [interquartile range, −0.4 to 0.07] and 0.07 [interquartile range, −0.07 to 0.26], respectively;
P
=0.007) and patients with late hypothermia initiation (0.22 [interquartile range 0.12–0.27];
P
=0.037). After day 3, relative PHE increased in all groups without difference. Outcome was not different between patients treated with hypothermia and controls.

Conclusions—
Early hypothermia initiation after ICH onset seems to have an important impact on PHE evolution, whereas our data suggest only limited impact later than day 3 after onset.
Global Soil Moisture Estimation by Assimilating AMSR-E Brightness Temperatures in a Coupled CLM4–RTM–DART System
Authors: Zhao Long , Yang Zong-Liang , Hoar Timothy J. 
Published: July 2016

Abstract
Very few frameworks exist that estimate global-scale soil moisture through microwave land data assimilation (DA). Toward this goal, such a framework has been developed by linking the Community Land Model, version 4 (CLM4), and a microwave radiative transfer model (RTM) with the Data Assimilation Research Testbed (DART). The deterministic ensemble adjustment Kalman filter (EAKF) within DART is utilized to estimate global multilayer soil moisture by assimilating brightness temperature observations from the Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E). A 40-member ensemble of Community Atmosphere Model, version 4.0 (CAM4.0), reanalysis is adopted to drive CLM4 simulations. Space-specific, time-invariant microwave parameters are precalibrated to minimize uncertainties in RTM. Besides, various methods are designed to upscale AMSR-E observations for computational efficiency and time shift CAM4.0 forcing to facilitate global daily assimilations. A series of experiments are conducted to quantify the DA sensitivity to microwave parameters, choice of assimilated observations, and different CLM4 updating schemes. Evaluation results indicate that the newly established CLM4–RTM–DART framework improves the open-loop CLM4-simulated soil moisture. Precalibrated microwave parameters, rather than their default values, can ensure a more robust global-scale performance. In addition, updating near-surface soil moisture is capable of improving soil moisture in deeper layers (0–30 cm), while simultaneously updating multilayer soil moisture fails to obtain intended improvements. Future work is needed to address the systematic bias in CLM4 that cannot be fully covered through the ensemble spread in CAM4.0 reanalysis.
A Finescale Radar Examination of the Tornadic Debris Signature and Weak-Echo Reflectivity Band Associated with a Large, Violent Tornado
Authors: Houser Jana Lesak , Bluestein Howard B. , Snyder Jeffrey C. 
Published: July 2016

AbstractHigh-resolution data of the tornadic debris signature (TDS) and weak-echo reflectivity band (WRB) associated with a large, violent tornado on 24 May 2011 in central Oklahoma are examined using a rapid-scan, X-band, polarimetric, mobile Doppler radar. Various characteristics of these features and their evolution are examined over time intervals of 20 s or less. The formation of the TDS, debris fallout, and inhomogeneities in the TDS structure, are analyzed from volumetric and single-elevation observations. Constant-radius vertical cross sections of Doppler velocity, reflectivity, and copolar cross-correlation coefficient are compared at various times during the tornado’s life cycle; from them it is found that the weak echo column (WEC) is considerably narrower than the TDS and the WEC is confined to the strong gradient of Doppler velocities in the tornado’s core. The TDS of the mature tornado extends radially outward, bound approximately by the 40 m s−1 radial isodop.Rapid-scan, near-surface data were collected for a period of 6 min, during which 2-s single-elevation PPI updates at 1° were available at heights below 100 m above radar level. During this period, a WRB associated with a visually observed horizontal vortex developed east of the tornado, along the leading edge of the secondary rear-flank gust front, as the tornado was rapidly intensifying. A relationship was noted between reduced radar-observed reflectivity and increased radar-observed radial convergence/divergence in the vicinity of the horizontal vortex as it strengthened. This feature is qualitatively analyzed and hypotheses explaining its generation and structure are discussed.
Exploring the Obstacles to Implementing Economic Mechanisms to Stimulate Antibiotic Research and Development
Authors: Baraldi Enrico , Ciabuschi Francesco , Leach Ross , Morel Chantal M. , Waluszewski Alexandra 
Published: July 2016

This Article examines the potential stakeholder-related obstacles hindering the implementation of mechanisms to re-ignite the development of novel antibiotics. Proposed economic models and incentives to drive such development include: Public Funding of Research and Development (“R&D”), Tax Incentives, Milestone Prizes, End Payments, Intellectual Property (“IP”) and Exclusivity Extensions, Pricing and Reimbursement Incentives, Product Development Partnerships (“PDPs”), and the Options Market for Antibiotics model. Drawing on personal experience and understanding of the antibiotic field, as well as stakeholder consultation and numerous expert meetings within the DRIVE-AB project and Uppsala Health Summit 2015, the Authors identify obstacles attributable to the following actors: Universities and Research Institutes, Small and Medium-sized Enterprises (“SMEs”), Large Pharmaceutical Companies, Marketing Approval Regulators, Payors, Healthcare Providers, National Healthcare Authorities, Patients, and Supranational Institutions.The analysis also proposes a characterization and ranking of the difficulty associated with implementing the reviewed mechanisms. Public Funding of R&D, Pricing and Reimbursement Incentives, and PDPs are mechanisms expected to meet highly systemic barriers (i.e., obstacles across the entire antibiotic value chain), imposing greater implementation challenges in that they require convincing and involving several motivationally diverse actors in order to have much effect.
The Economic Theory of Patent Protection and Pandemic Influenza Vaccines
Authors: Eccleston-Turner Mark 
Published: July 2016

The creation of new vaccines is one of the key challenges in the battle against global infectious diseases. Therefore, creating the optimal conditions for innovation in vaccines is one of the most important roles law may undertake in this battle. In relation to pharmaceuticals, the economic theory of patent protection is commonly cited by industry and in the academic literature to justify the patenting of life-saving medicines and vaccines. The economic theory of patent protection holds that innovation occurs due to patents protecting the research and development investment made by the innovator. Proponents of this theory claim that without patents such innovation in medicines and vaccines would occur at a significantly reduced rate. This Article considers the applicability of the economic theory of patent protection to pandemic influenza vaccines. This Article examines a number of factors relevant to patent law, theory, and innovation including: the patent landscape for pandemic influenza vaccines; the market dominance enjoyed by manufacturers; the actual risk posed by imitators making generic vaccines if patent protection were not in place; and, the licensing and regulatory provisions for creating generic vaccines.According to the economic theory of patent protection, a patent incentivizes innovation by providing an innovator with a temporary monopoly regarding their innovation, and by protecting them from the threat posed by imitators who wish to make a cheap replica of the product. However, even without a patent, pandemic influenza vaccine manufacturers are in this position. Due to economies of scale and the complicated regulatory and licensing frameworks relevant to bringing a pandemic influenza vaccine to market, manufacturers are at little to no risk from generic imitators. Moreover, there is a very strong incentive to innovate because pandemic influenza vaccine manufacturers are selling a product for which demand exceeds supply to a captive market of nations and organizations, each of which is hoping to secure as much vaccine as possible. The unique conditions associated with pandemic influenza vaccines appear to provide more of an incentive to innovate and research in this field than the fact that the innovations can be patented.
Interventions for Reducing Hospital Readmission Rates: The Role of Hospice and Palliative Care
Authors: Cherlin Emily J. , Brewster Amanda L. , Curry Leslie A. , Canavan Maureen E. , Hurzeler Rosemary , Bradley Elizabeth H. 
Published: July 2016

Background: Despite evidence that enrollment with hospice services has the potential to reduce hospital readmission rates, previous research has not examined exactly how hospitals may promote the appropriate use of hospice and palliative care for their discharged patients. Therefore, we sought to explore the strategies used by hospitals to increase the use of hospice and palliative care for patients at risk of readmission. Methods: We conducted a secondary analysis of qualitative data from a study of hospitals that were participating in the State Action on Avoidable Readmissions (STAAR) initiative, a quality improvement collaborative. We used data attained from 46 in-depth interviews conducted during 10 hospital site visits using a standard discussion guide and protocol. We used a grounded theory approach using the constant comparative method to generate recurrent and unifying themes. Results: We found that a positive effect for hospitals participating in the STAAR initiative was enhanced engagement in efforts to promote greater use of hospice and palliative care as a possible method of reducing unplanned readmissions, the central goal of the STAAR initiative. Hospital staff described strategies to increase the use of hospice and palliative care that included (1) designing and implementing tracking systems to identify patients most at risk of being readmitted, (2) providing education about hospice and palliative care to family, internal and external clinical groups, and (3) establishing closer links to posthospital settings. Conclusion: National efforts to reduce rehospitalizations may result in improved integration of hospice and palliative care for patients who are at risk of readmission.
Extra Virgin Olive Oil Improves Oxidative Stress, Functional Capacity, and Health-Related Psychological Status in Patients With Fibromyalgia
Authors: Rus Alma , Molina Francisco , Ramos Manuel Miguel , Martínez-Ramírez María Josefa , del Moral María Luisa 
Published: July 2016

Objectives: Fibromyalgia (FM) is a chronic disease that imposes physical, psychological, and social limitations. We have reported that oxidative stress may play a role in the pathophysiology of FM. Olive oil has been shown to be effective treatment against the oxidative stress associated with several diseases. The aim of this study was to investigate the effect of olive oil on oxidative stress and health-related parameters in FM. Methods: This preliminary study was performed on blood samples of 23 women diagnosed with FM who consumed 50 ml of organic olive oil daily for 3 weeks. Subjects were randomized into two groups: one ingested extra virgin olive oil (EVOO) and the other refined olive oil (ROO), which have different antioxidant content. The patients’ oxidative (lipid, protein, and DNA oxidation) and antioxidative (antioxidant enzyme activities and compounds) profiles were examined before and after the treatment period. Functional capacity and physical and mental health status were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and the Physical Component (PCS-12) and Mental Component Summaries (MCS-12) of the Short Form-12 Health Survey, respectively. Results: Significant differences were found in pre–post change between the EVOO and ROO groups for protein carbonyls, lipid peroxidation, and FIQ and MCS-12 scores. Differences between groups approached statistical significance for oxidative DNA damage and levels of the antioxidant compound zinc. Conclusions: EVOO may protect women with FM against oxidative stress in addition to improving functional capacity and health-related psychological status. Findings suggest that olive oil may be a valuable therapeutic support in FM.
Factors Associated With Inadequate Effectiveness of a Multidisciplinary Disease Management Program in Heart Failure Patients Stratified by Galectin 3 Level
Authors: Liu Min-Hui , Wang Chao-Hung , Chiou Ai-Fu , Yang Ning-I , Kuo Li-Tang 
Published: July 2016

Objective: This study investigated whether multidisciplinary disease management programs (MDPs) exert the same effects in heart failure (HF) patients across risk levels stratified by galectin-3 (Gal-3) level and what factors are associated with inadequate effectiveness of MDP. Methods: We used a longitudinal follow-up design based on a previous randomized trial. A total of 355 stabilized hospitalized HF patients were enrolled. The effects of MDP on death and HF-related rehospitalization were analyzed according to Gal-3 levels. Results: During the 4-year follow-up, Gal-3 levels predicted mortality and composite events ( p < .001). Multivariable analysis demonstrated the event-lowering effect of MDP (hazard ratio [HR] = 0.49, p = .001 for death and HR = 0.50, p < .001 for composite events). However, the effect of MDP was inadequate for those with high Gal-3 levels (≥17.9 ng/ml), whose 4-year composite event rate was 43% in the MDP arm. Further analysis showed that, in patients with Gal-3 ≥ 17.9 ng/ml, the independent factors associated with a high composite event rate were no MDP, older age, worse New York Heart Association functional class, no angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use, higher predischarge natriuretic peptide levels, and wider QRS complexes. Conclusions: The effectiveness of MDP for HF patients at high risk was inadequate. Our findings identified the characteristics of these MDP nonresponders. Better integration of advanced care plans based on strategies guided by Gal-3 level is needed to improve care quality.
Telehealth clinics increase access to care for adults with cystic fibrosis living in rural and remote Western Australia
Authors: Wood Jamie , Mulrennan Siobhain , Hill Kylie , Cecins Nola , Morey Sue , Jenkins Sue 
Published: July 2016

Introduction A significant proportion (15%, n = 28) of the adults with cystic fibrosis (CF) in Western Australia (WA) live in rural and remote areas and have difficulty accessing specialist care at the state adult CF centre, located in Perth. We aimed to increase access by offering telehealth clinics, and evaluate the impact on health outcomes. Methods Telehealth clinics were offered via videoconference over a 12-month period, with uptake and satisfaction measured at the end of the intervention. Participants could still attend in person clinics at the CF centre if requested. Other outcomes comprised healthcare utilisation (HCU), spirometry, weight and health-related quality of life. Results In 21 participants, total clinic visits increased from 46 (median (range) per participant 2 (0–6)) in the 12-month period preceding the study to 100 (5 (2–8), p < 0.001) during the intervention. Of the 100 clinics in total, 66 were delivered via telehealth. Satisfaction with telehealth was high and most (94%) participants agreed that telehealth is a good way to deliver CF care. An increase in intravenous antibiotic days (incident rate ratio (IRR) 2.3, p = 0.03) and hospital admission days (IRR 3.7, p = 0.01) was observed. There was an improvement in the vitality domain of the Cystic Fibrosis Questionnaire – Revised ( p < 0.05). Discussion Telehealth had good uptake and increased clinic attendance in adults with CF living in rural and remote WA, and had high satisfaction amongst participants. The increase in HCU, resulting from increased detection and treatment of exacerbations, may improve long-term outcomes in this population.
How I treat hepatitis C virus infection in patients with hematologic malignancies
Authors: Torres Harrys A. , McDonald George B. 
Published: July 2016

AbstractHepatitis C virus (HCV) infection is not uncommon in cancer patients. Over the past 5 years, treatment of chronic HCV infection in patients with hematologic malignancies has evolved rapidly as safe and effective direct-acting antivirals (DAAs) have become the standard-of-care treatment. Today, chronic HCV infection should not prevent a patient from receiving cancer therapy or participating in clinical trials of chemotherapy because most infected patients can achieve virologic cure. Elimination of HCV from infected cancer patients confers virologic, hepatic, and oncologic advantages. Similar to the optimal therapy for HCV-infected patients without cancer, the optimal therapy for HCV-infected patients with cancer is evolving rapidly. The choice of regimens with DAAs should be individualized after thorough assessment for potential hematologic toxic effects and drug-drug interactions. This study presents clinical scenarios of HCV-infected patients with hematologic malignancies, focusing on diagnosis, clinical and laboratory presentations, complications, and DAA therapy. An up-to-date treatment algorithm is presented.
Management algorithm for failed gastric pull up reconstruction of laryngopharyngectomy defects: Case report and review of the literature
Authors: Butskiy Oleksandr , Anderson Donald W. , Prisman Eitan 
Published: July 2016

Background Gastric pull up remains a popular reconstructive option for pharyngoesophagectomy defects extending to thoracic inlet. Gastric necrosis is a dreaded complication of gastric pull up reconstruction and few studies report on management of this complication. MEDLINE, EMBASE, and Web of Science™ databases were searched for publications in the last 25 years on gastric pull up reconstruction following pharyngoesophagectomy. The rates of complications related to gastropharyngeal anastomosis were extracted, and methods of managing gastric necrosis were noted. Forty seven case series were identified reporting on the use of gastric pull up for reconstruction of pharyngoesophageal defects. Mortality rate varied from 0 to 33 % with a weighted average of 8.6 %. In 39 % of patients, mortality was either caused or directly related to failure of the gastropharyngeal anastomosis. The reported rate of gastric necrosis ranged from 0 to 24 % resulting in a 28 % mortality. Options for managing gastric necrosis included: temporary cervical diversion, free jejunum flap, colonic interposition, tubed radial forearm flap, deltopectoralis and pectoralis myocutaneous flaps. Case presentation We present the first case of an anterolateral thigh flap rescue of gastric necrosis after gastric pull up reconstruction. The case report is followed by a review of literature on management of gastric pull up failures. Conclusion Based on the extracted information, we propose an algorithm for managing gastric pull up failure following pharyngoesophageal reconstruction.