bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preishöhenmissbrauch bei Arzneimitteln
Authors: Schuhmacher Florian , Holzweber Stefan 
Published: February 2019

Zusammenfassung
In letzter Zeit sind zahlreiche Fälle hoher Preise und drastischer Preiserhöhungen bei Arzneimitteln bekannt geworden und auch in den Fokus der Wettbewerbsbehörden gerückt. Dabei besteht in Märkten für Arzneimittel naturgemäß ein Spannungsverhältnis zwischen hohen Preisen und Innovationsanreizen. Hohe Preise, die durch neue Arzneimittelprodukte erzielt werden sollen, bewirken einerseits Anreize zur Investition in F&E, andererseits ist aufgrund der geringen Nachfrageelastizität bei zum Teil essentiellen Arzneimitteln die Festsetzung sehr hoher Preise möglich. Diese werden je nach Erstattungssystem von Systemen der gesetzlichen Krankenversicherung übernommen oder direkt den Patienten verrechnet. Die zentrale Herausforderung besteht demnach darin, eine Grenze festzulegen, welche hohe, jedoch kartellrechtlich zulässige Preise von marktmissbräuchlichen Preisen trennt. Schwierigkeiten ergeben sich im pharmazeutischen Bereich allerdings bereits aus der Prüfung der marktbeherrschenden Stellung. Diese wird auf Arzneimittelmärkten nicht unwesentlich durch die Macht am Nachfragemarkt beeinflusst, die sich aus den unterschiedlichen regulatorischen Maßnahmen und der staatlichen Preisfestsetzungen der einzelnen Mitgliedsstaaten ergibt. Die Festlegung der Grenze von zulässigen und gleichzeitig innovationsfördernden Preisen bedarf in diesem Sektor daher der Berücksichtigung mehrerer Faktoren und erfordert eine detaillierte Analyse. Der folgende Beitrag geht diesen Fragen nach und entwickelt im Rahmen von Art. 102 AEUV ein Konzept der Prüfung eines Preishöhenmissbrauchs bei der Festlegung der Abgabepreise durch den Hersteller.
Duration of Initial Empirical Antibiotic Therapy and Outcomes in Very Low Birth Weight Infants
Authors: Ting Joseph Y. , Roberts Ashley , Sherlock Rebecca , Ojah Cecil , Cieslak Zenon , Dunn Michael , Barrington Keith , Yoon Eugene W. , Shah Prakesh S. ,   on behalf of the Canadian Neonatal Network Investigators
Published: February 2019

BACKGROUND:
Overuse of antibiotics can facilitate antibiotic resistance and is associated with adverse neonatal outcomes. We studied the association between duration of antibiotic therapy and short-term outcomes of very low birth weight (VLBW) (&lt;1500 g) infants without culture-proven sepsis.

METHODS:
We included VLBW infants admitted to NICUs in the Canadian Neonatal Network between 2010–2016 who were exposed to antibiotics but did not have culture-proven sepsis in the first week. Antibiotic exposure was calculated as the number of days an infant received antibiotics in the first week of life. Composite primary outcome was defined as mortality or any major morbidity (severe neurologic injury, retinopathy of prematurity, necrotizing enterocolitis, chronic lung disease, or hospital-acquired infection).

RESULTS:
Of the 14 207 included infants, 21% (n = 2950), 38% (n = 5401), and 41% (n = 5856) received 0, 1 to 3, and 4 to 7 days of antibiotics, respectively. Antibiotic exposure for 4 to 7 days was associated with higher odds of the composite outcome (adjusted odds ratio 1.24; 95% confidence interval [CI] 1.09–1.41). Each additional day of antibiotic use was associated with 4.7% (95% CI 2.6%–6.8%) increased odds of composite outcome and 7.3% (95% CI 3.3%–11.4%) increased odds in VLBW infants at low risk of early-onset sepsis (born via cesarean delivery, without labor and without chorioamnionitis).

CONCLUSIONS:
Prolonged empirical antibiotic exposure within the first week after birth in VLBW infants is associated with increased odds of the composite outcome. This practice is a potential target for antimicrobial stewardship.
Hematologic Complications of Immune Checkpoint Inhibitors
Authors: Davis Elizabeth J. , Salem Joe-Elie , Young Arissa , Green Jennifer R. , Ferrell P. Brent , Ancell Kristin K. , Lebrun-Vignes Benedicte , Moslehi Javid J. , Johnson Douglas B. 
Published: February 2019

Abstract

Immune checkpoint inhibitors have improved outcomes for patients with numerous hematological and solid cancers. Hematologic toxicities have been described, but the spectrum, timing, and clinical presentation of these complications are not well understood. We used the World Health Organization's pharmacovigilance database of individual-case-safety-reports (ICSRs) of adverse drug reactions, VigiBase, to identify cases of hematologic toxicities complicating immune checkpoint inhibitor therapy. We identified 168 ICSRs of immune thrombocytopenic purpura (ITP), hemolytic anemia (HA), hemophagocytic lymphohistiocytosis, aplastic anemia, and pure red cell aplasia in 164 ICSRs. ITP (n = 68) and HA (n = 57) were the most common of these toxicities and occurred concomitantly in four patients. These events occurred early on treatment (median 40 days) and were associated with fatal outcome in 12% of cases. Ipilimumab-based therapy (monotherapy or combination with anti-programmed death-1 [PD-1]) was associated with earlier onset (median 23 vs. 47.5 days, p = .006) than anti-PD-1/programmed death ligand-1 monotherapy. Reporting of hematologic toxicities has increased over the past 2 years (98 cases between January 2017 and March 2018 vs. 70 cases before 2017), possibly because of increased use of checkpoint inhibitors and improved recognition of toxicities. Future studies should evaluate incidence of hematologic toxicities, elucidate risk factors, and determine the most effective treatment algorithms.

Key Points
Immune-mediated hematologic toxicities are a potential side effect of immune checkpoint inhibitors (ICIs). Providers should monitor complete blood counts during treatment with ICIs. Corticosteroids are the mainstay of treatment for immune-mediated hematologic toxicities. Further research is needed to define patient-specific risk factors and optimal management strategies for hematologic toxicities.
The Role of Radiation Oncology in Immuno-Oncology
Authors: Meng Xiangjiao , Feng Rui , Yang Lian , Xing Ligang , Yu Jinming 
Published: February 2019

Abstract

Despite the promising efficacy of immunotherapy in some patients, many other patients are resistant. The synergistic effect of radiotherapy (RT) in combination with immunotherapy reported in case reports and clinical trials has piqued the interest of radiologists in investigating the underlying mechanisms and efficacy of the combination in preclinical and clinical trials. To date, the reported data are limited to small-sized samples, trials lacking a comparison arm, and trials using diverse immunotherapies, various radiation doses, and fractionations. There are just a few studies comparing the efficacy of immunotherapy and radiotherapy to that of conventional therapies or different combinations. Radiologists should design and conduct clinical trials wisely to confirm the efficacy of the combination, particularly the abscopal effect, identify the best combination of various immunotherapeutic drugs and different radiation models for patients, identify the best sequence of the combination, determine the optimal timing of the combination, select the target site and volume, lower adverse effects, and explore predictive models to identify patients who may benefit from the combination therapy. We expect that these clinical trials performed by radiologists will offer definitive evidence for the wide use of the combination of RT and immunotherapy in clinical practice.
INTERNATIONAL MARKET EXPANSION
Authors: Volodin Yu. V. , Podkovyrov P. A. 
Published: February 2019

In article various theoretical aspects of an exit of the companies on the foreign markets are considered. Influence of globalization on productivity of the companies is considered, ways and factors of a choice of strategy of an exit to the world market are analysed. The behavioural and cultural aspects influencing strategy of an exit to the world market are analysed. The analysis of strategy of the companies which have entered the foreign markets, is carried out taking into account the previous researches in this area.The following conclusions became result of research: 1) globalization positively influences the companies as the market increases, however the small companies and the companies in emerging markets lose in competitive fight; 2) the companies with considerable experience are inclined to choose strategy of opening of own enterprise while the organizations without similar experience prefer export or joint venture in the host country territory; 3) the strategy choice with a bigger involvement of resources is directly proportional to knowledge of culture of the country to which there is a company. At entry into the market with other culture smooth adaptation is necessary for successful realization of strategy. At last, people are inclined to make behavioural mistakes, and knowledge of them and continuous control will help to achieve successful results; 4) for an exit and successful work in the foreign markets of the company important not only to possess competences, but also to be able to protect them and to keep in time; 5) on the market with high political and investment risks, and also adverse economic conditions of the company are inclined to choose strategy with the minimum investment of money (franchizes, licensing).
OPERATING EXPENSES FOR LARGE AMERICAN AIR CARRIERS
Authors: Manvelidze A. B. 
Published: February 2019

Indicators of prime cost and profitability of passenger traffic on the example of statistics of American Airlines, Delta Airlines and United Airlines. Initial information for researches is accepted according to the financial and statistical analysis of airlines of the. Indicators of cost of transportations and profitability during noticeable reduction of prices of aviation fuel in 2014-2016 are compared. The main attention is paid to the analysis of fleet (park) of planes and changesin separate items of expenditure. The algorithm of calculation of cost of transportations on types of planes according to the statistical account is offered. In calculations it is considered that in air-transport branch of the USA statistical account of factor flight cost on the aerial vehicle types is kept. The share of factor flight cost makes to 50%. Indirect expenses are distributed by a settlement way. Prime cost a chair kilometer on straight lines and indirect items of expenditure of narrow-body planes 737-800/900 and A319/320/321 at range of 2000 km makes from 8,8 to 11 cents. On the ranges, over 2000 km, prime cost decreases to 7,7–8,3 cents.Prime cost a chair kilometer of planes 757-200/300, and widebody 767-300, 777-300, A330-200/300 at range of 3000–5000 km by calculation makes 6,8–7,8 cents for a chair km. Prime cost at ranges over 6000 km makes a chair kilometer of widebody planes 777-200/300, 787-800/900, A330-200/300 from 6,0 to 6,7 cent for a chair km
Characteristic Study of the MCM-41 Modified with Zn by Direct Synthesis
Authors: Hasanah Nur , Sutarno Sutarno , Kunarti Eko Sri 
Published: February 2019

<div class="WordSection1"><p>Modification of MCM-41 with zinc (Zn) by direct synthesis has been attempted. The aims of this research were (i) to show morphology of MCM-41, (ii) to know the optimal ratio of Si/Zn in MCM-41 modification, and (iii) to know crystallinity and pore diameter of MCM-41 and MCM-41 modified by Zn. Zn metal added to MCM-41 matrix by direct synthesis used zinc nitrate as precursor with ratio Si/Zn variation. Zn added by <em>direct synthesis</em> to get larger diameter without changing the structure of MCM-41. Characterization of material was used XRD, FTIR, TEM, and N<sub>2</sub> adsorption. Characterization of MCM-41 with TEM show that material has spherical shape with uniform pore morphology. The result of XRD show that synthesized MCM-41 has good crystallinity with three peaks observed specific to MCM-41. Ratio of Si/Zn optimal to modification MCM-41 is Si/Zn= 100. Modified MCM-41 show decrease in crystallinity and increase pore diameter that is 35.58 Ǻ compared with MCM-41 with pore diameter 31.42 Ǻ.</p><p> </p><p> </p></div>
Gluteal Fibrosis and Its Surgical Treatment
Authors: Alves Kristin , Katz Jeffrey N. , Sabatini Coleen S. 
Published: February 2019

Background:
The objective of this study was to analyze the literature regarding the diagnosis, pathogenesis, and prevalence of gluteal fibrosis (GF) and the outcomes of treatment.

Methods:
We searched PubMed, Embase, and Cochrane literature databases, from database inception to December 15, 2016. We used the following search terms including variants: “contracture,” “fibrosis,” “injections,” “injections, adverse reactions," “gluteal,” and “hip.” All titles and abstracts of potentially relevant studies were scanned to determine whether the subject matter was potentially related to GF, using predefined inclusion and exclusion criteria. If the abstract had subject matter involving GF, the paper was selected for review if full text was available. Only papers including ≥10 subjects who underwent surgical treatment were included in the systematic analysis. Data abstracted included the number of patients, patient age and sex, the type of surgical treatment, the method of outcome measurement, and outcomes and complications.

Results:
The literature search yielded 2,512 titles. Of these, 82 had a focus on GF, with 50 papers meeting the inclusion criteria. Of the 50 papers reviewed, 18 addressed surgical outcomes. The surgical techniques in these papers included open, minimally invasive, and arthroscopic release and radiofrequency ablation. Of 3,733 operatively treated patients in 6 reports who were evaluated on the basis of the criteria of Liu et al., 83% were found to have excellent results. Few papers focused on the incidence, prevalence, and natural history of GF, precluding quantitative synthesis of the evidence in these domains.

Conclusions:
This study provided a systematic review of surgical outcomes and a summary of what has been reported on the prevalence, diagnosis, prognosis, and pathogenesis of GF. Although GF has been reported throughout the world, it requires further study to determine the exact etiology, pathogenesis, and appropriate treatment. Surgical outcomes appear satisfactory.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Visit Duration Does Not Correlate with Perceived Physician Empathy
Authors: Kortlever Joost T.P. , Ottenhoff Janna S.E. , Vagner Gregg A. , Ring David , Reichel Lee M. 
Published: February 2019

Background:
Perceived physician empathy is a strong driver of patient satisfaction. We assessed the influence of wait time, time spent with the surgeon, and surgeon stress level on the way patients rated surgeon empathy.

Methods:
One hundred and fourteen patients visiting 1 of 6 participating surgeons were prospectively enrolled in the study. We recorded patient demographics and assessed the patient rating of perceived physician empathy. Time waiting for the surgeon and time spent with the surgeon were measured with use of ambulatory tracking systems and by research assistants with stopwatches outside the patient rooms. Patient ratings of surgeon empathy were assessed with use of the Jefferson Scale of Patient’s Perceptions of Physician Empathy (JSPPPE), and surgeon stress level was assessed with use of the Perceived Stress Score short form. The mean wait time was 30 ± 18 minutes, and the mean time spent with the surgeon was 8.7 ± 5.3 minutes. Two separate multilevel linear regression models were used to compare factors associated with the JSPPPE and time spent with the surgeon.

Results:
Neither time spent with the surgeon nor wait time was independently associated with perceived physician empathy; being male, having at least a post-college graduate degree, and higher self-reported surgeon stress levels were independently associated with less perceived empathy. More time spent with the surgeon was independently associated with lower self-reported surgeon stress levels; follow-up visits and visits for a traumatic condition were independently associated with less time spent with the surgeon.

Conclusions:
The results of the present study show that improved communication strategies, rather than shorter wait time or increased time spent with the patient, may increase patient satisfaction. This should be a focus of future research.
Technology Focus: Seismic
Authors: Egan Mark S. 
Published: February 2019

Technology Focus
Last year saw continued contraction in the seismic data-acquisition industry. This included both onshore and offshore operations. Most notably, WesternGeco exited land and marine data acquisition. (In the case of marine, WesternGeco sold all of its vessels, facilities, and technologies to Shearwater GeoServices.) Ironically, it was just 1 year ago when I discussed in this column the new and exciting acquisition-related advances in the industry that had been developed for the purpose of better data sampling.
With this drop in acquisition business, it is not surprising that there were fewer seismic data-acquisition papers published in SPE proceedings. Nevertheless, several excellent SPE papers covered important acquisition and processing topics. One of the papers deals with the current state of the art for addressing marine challenges. This is described with a 3D case history from the Gulf of Thailand. Another paper deals with leading-edge techniques that were used in a recent onshore 3D survey in Abu Dhabi. And a third paper showcases the application of a relatively new technology, distributed acoustic sensing (DAS). DAS is rapidly finding a home in vertical-seismic-profile surveys and in unconventional programs. Indeed, this third paper deals with a DAS study performed in the Marcellus Shale.
Offsetting the drop in the number of acquisition papers was a proportionate increase in the number of SPE papers that covered other important seismic topics. These included inversion and reservoir characterization, 4D interpretation, seismic for carbonate plays, and machine learning. (Similar to what is happening in other industries, machine learning is receiving tremendous attention now in the seismic world.) Though industry fluctuations may affect our areas of specialty, there will always be room for improvement driven by innovation.
Recommended additional reading at OnePetro: www.onepetro.org.
SPE 189888 Seismic Attributes Application for the Distributed Acoustic Sensing Data for the Marcellus Shale: New Insights to Cross-Stage Flow Communication by Payam Kavousi Ghahfarokhi, West Virginia University, et al.
SPE 192948 How Broadband, High-Density, Full-Azimuth, and Point-Source Point-Receiver Acquisition Improves Seismic Interpretation in Onshore Abu Dhabi by Sheikha Al-Naqbi, ADNOC Onshore, et al.
SPE 192956 Comparing Seismic Inversion Methods on a Carbonate Reservoir: A Case Study From the Mishrif Reservoir, Rumaila Field, Iraq by Olabode Joseph Olatoke, BP, et al.
SPE 192927 Effect of Seismic Acquisition and Processing Techniques in Challenging Subsurface Imaging, Block G11/48, Gulf of Thailand by Phansakorn Kaewprain, Mubadala
Gas Mass Transport Model for Microfractures Considering the Dynamic Variation of Width in Shale Reservoirs
Authors: Zeng Fanhui , Peng Fan , Guo Jianchun , Rui Zhenhua , Xiang Jianhua 
Published: February 2019

Summary
Microfractures are commonly observed in shale reservoirs. During the shale gas–production process, stress sensitivity induces a change in the width of the microfractures, which is a significant factor that affects shale gas mass transport. By using research methods based on desorption theory and elastic–plastic mechanics, a shale gas mass transport model that considers the dynamic variations in the microfracture width is established in this paper. This model comprehensively fuses the surface diffusion model, slip flow model, Knudsen diffusion model, and cubic grid model. The reliability of this model is verified using molecular simulations, which do not include surface diffusion. The shale gas is considered as pure methane. Then, the different contributions of the gas mass transport mechanisms to the total mass transport are discussed in detail. The results demonstrate the following findings: (1) The studied flows are well–simulated by the proposed model. (2) Stress sensitivity results in a decrease in gas mass transport when the formation pressure exceeds 3.4 MPa, and the minimum value is approximately 0.45 times smaller than that when the width change is not considered. Moreover, stress sensitivity results in an increase in gas mass transport when the formation pressure is lower than 3.4 MPa, and the maximum value is approximately 4.5 times higher than that when the width change is not considered. (3) Shale gas mass transport is positively associated with the Young's modulus and Poisson's ratio, whereas it is negatively associated with the microfracture compressibility. When the formation pressure is less than 4 MPa, shale gas transport is positively correlated with the desorption capacity, whereas when the formation pressure exceeds 4 MPa, the effect of different desorption capacities on gas transport is nearly consistent. (4) When the microfracture width is at nanoscale and the reservoir pressure is lower than 15 MPa, surface diffusion has an obvious effect on the shale gas mass transport process. When the contribution of surface diffusion to the total shale gas mass transport is relatively small, the contributions of slip flow and Knudsen flow to shale gas mass transport exhibit the trend of “shifting each other.” When the surface diffusion contribution is larger, a reduction in its contribution leads to simultaneous initial increases in the contributions of slip flow and Knudsen flow to shale gas mass transport, and then these flows begin “shifting each other.”