bluuebunny/crossref_metadata_2025 huggingface dataset:
Endovascular Repair for Ruptured Abdominal Aortic Aneurysms has Improved Outcomes Compared to Open Surgical Repair
Authors: Portelli Tremont Jaclyn N. , Cha Andrew , Dombrovskiy Viktor Y. , Rahimi Saum A.
Published: March 2016

Introduction:

Ruptured abdominal aortic aneurysm (rAAA) remains a critical diagnosis, and research is needed to address outcomes following surgical repair. The purpose of this study was to compare nationwide outcomes for patients who received either endovascular repair (EVAR) or open surgical repair (OSAR) for rAAA.

Methods:

The Medicare Provider Analysis and Review file from 2005 to 2009 was used to identify patients diagnosed with rAAA and treated with either EVAR or OSAR. Those patients with both procedures were excluded. Primary outcomes included mortality, postoperative complications, and readmission rates. Secondary outcomes included hospital resource utilization and length of stay (LOS).

Results:

A total of 8480 patients with rAAA who underwent EVAR (n = 1939) or OSAR (n = 6541) were identified. On multivariate regression, the likelihood of dying in the hospital after OSAR compared to EVAR was significantly greater (odds ratio [OR] = 1.95; 95% confidence interval [CI] = 1.74-2.18). There was significantly greater frequency of postoperative complications after OSAR compared to EVAR (OR = 2.1, 95%CI = 1.86-2.37, P < .0001). Freedom from readmission after OSAR was significantly greater than that after EVAR. Total hospital cost for all services after EVAR was greater than that after OSAR (US$100 875 vs US$89 035; P < .0001), but intensive care unit (ICU) cost for EVAR was significantly less than that for OSAR (US$5516 vs US$8600; P < .0001). Total hospital and ICU LOS were shorter in EVAR compared to OSAR ( P < .0001 for both).

Discussion:

EVAR for rAAA has shown mortality benefits over OSAR as well as reduced ICU and total LOS. This data suggest EVAR is associated with a greater survival benefit, fewer postoperative complications, and may help improve hospital resource utilization.
Acquired Severe Disabilities and Complex Health Care Needs
Authors: Ballard Sarah L. , Dymond Stacy K.
Published: March 2016

This case study examined one high school student’s access to inclusive education and experiences in an inclusive English class after he acquired severe disabilities and complex health care needs from a nontraumatic brain injury. Multiple sources of data (i.e., interviews, field notes, and documents) were collected and analyzed to formulate understanding of the unique particularities of this intrinsic, naturalistic case. Findings were organized into four major themes: (a) school reentry and adjustment, (b) communication access, (c) social inclusion, and (d) curricular access and assessment. Analysis of these major themes revealed that the focus student had minimal access to an inclusive education due to delayed school reentry, incomplete assessment data, and limited professional knowledge of acquired brain injuries and inclusive education. The student’s experiences in the general education English classroom were predominantly characterized by limited access to communication and peer interactions, undefined learning priorities, and an overreliance on adult staff. Findings from this study suggest the need for additional research related to the prevalence of students with nontraumatic brain injury, supports needed by families and students post injury, professional training for school personnel, and the use of 1:1 paraprofessionals and nurses.
Organizing for Innovation Ambidexterity in Emerging Markets
Authors: Dunlap Denise , Parente Ronaldo , Geleilate José-Mauricio , Marion Tucker J.
Published: March 2016

Firms struggle to be ambidextrous in the sense of being able to successfully manage both new and incremental innovation activities simultaneously. Applying the knowledge-based view, we examine the important moderating influences of supplier involvement and foreignness on the relationship between innovation ambidexterity and performance. We test our hypotheses at the business-unit level of analysis in the emerging market of Brazil. We examine two types of innovation ambidexterity: the balanced dimension and the combined dimension. We found that firms possessing greater supplier involvement reap higher performance benefits from the combined dimension of innovation ambidexterity. Last, foreign subsidiaries also achieved higher levels of performance than domestic firms from the combined dimension of innovation ambidexterity.
Laparoscopic Confocal Laser Microscopy Without Fluorescent Injection
Authors: Ellebrecht David B. , Gebhard Maximilian P. E. , Horn Marco , Keck Tobias , Kleemann Markus
Published: March 2016

Introduction. Histological analysis of surgical specimen is the gold standard for cancer classification. In particular, frozen histological diagnosis of vague peritoneal spots or uncertain excision of tumors plays a crucial role for proceeding with or without change of the operation procedure. Confocal laser microscopy (CLM) enables in vivo and real-time high-resolution tissue analysis. To evaluate a novel technique of CLM without any fluorescent dye, this pilot ex vivo study demonstrates a CLM camera device for minimal invasive surgical approach. Methods. In 5 cases, a laparoscopic CLM camera was used for examining colon and rectum specimen. Images of nonmalignant and malignant intestinal mucosa were characterized in terms of specific signal-patterns. No fluorescent dye was used. Correlations to findings in conventional histology were systematically recorded and described. Results. Using this CLM camera device, it is possible to analyze colon specimen mucosa. Nonmalignant and malignant intestinal mucosa show specific signal patterns. Nonmalignant mucosa is defined by honeycomb structure. There is deregulated structure in colon and rectum carcinoma mucosa. The inside lumen is irregular. The radial border appears swollen with reduced contrast. Discussion. This pilot study shows that the assessment of colon mucosa with a prototype of CLM camera for minimally invasive surgical approach without any fluorescent dye is feasible. It is possible to differentiate between benign and malignant mucosa in colon specimen by easy to evaluate and reproducible parameters. These first steps of this pioneering achievement to establish CLM in minimal invasive surgical procedures show a great potential for a more reliable intraoperative evaluation of suspect foci.
Comparison of polarisation curves and chronoamperometry experiments of titanium with and without ultrasonic vibrations of the electrolyte
Authors: Leese Rebecca , Ivanov Atanas
Published: March 2016

Ultrasonic vibrations were applied to the electrolyte in polarisation curve and chronoamperometry to observe the effect of anodic dissolution with the aim to apply knowledge to electrochemical machining. The application of the ultrasonic vibrations to the electrolyte allowed the dissolution potential to be lowered considerably and the machining rates were increased.
Design and analysis of a 2-degree-of-freedom flexure-based micro-motion stage
Authors: Du Yunsong , Li Tiemin , Jiang Yao , Wang Haitong
Published: March 2016

This article presents the mechanical design, dimensional optimization, finite element analysis, and experimentation of a 2-degree-of-freedom flexure-based micro-motion stage. The stage is composed of four parallel limbs with symmetrical configuration, and each limb is composed of two serially connected prismatic joints. The divided parts of flexure hinge thickness constituting the two prismatic joints are selected as two. Based on analytical models established in stiffness and dynamic analysis, the dimensional optimization is carried out to maximize the first resonance frequency. Finite element analysis is then adapted to verify the stiffness, workspace, and dynamic behavior. Finally, a prototype of the stage is manufactured and an experimental platform is set up. The experimental results show that the stage has a workspace range of 19.53 µm × 19.07 µm with a frequency of 1987 Hz, and the cross-coupling ratio between two axes is less than 1%. For high-frequency cooperative tracking experiments, a proportional–integral controller is implemented to compensate for the tracking errors. Finally, good tracking performance at high frequency is obtained, which validates the effectiveness of the micro-motion stage.
Queering Justice Thomas: Theories of Dignity in Obergefell
Authors: Viefhues-Bailey Ludger
Published: March 2016

The discourse of dignity constitutes one of the battlegrounds in the Supreme Court’s Obergefell decision imposing marriage equality. Whereas Justice Kennedy’s majority opinion celebrates the dignity of the institution of marriage, Justice Thomas’s dissent situates dignity outside of the purview of the state. I argue that a queer reading of Obergefell as response to the systemic racism in the US requires the theoretical position implied in Thomas’s view by mobilizing first a Kantian distinction between active citizens, passive citizens, and “savage” ungoverned bodies, and second Judith Butler’s politics of vulnerability.
Burnout and turnover intentions in Australian coaches as related to organisational support and perceived control
Authors: Kilo Rachel A , Hassmén Peter
Published: March 2016

Coach burnout and turnover intentions, as potentially modified by organisational support, perceived control, and coping strategies, were explored in a sample of 406 team and individual sport coaches. Multiple regression analyses revealed that higher perceived organisational support was associated with lower coach burnout scores. Further, coaches' internal locus of control and use of approach coping strategies predicted lower levels of burnout, especially reduced sense of accomplishment. Higher perceived organisational support was also a negative predictor of coaches' turnover intentions, whereas all three burnout dimensions were strong positive predictors. The focus of coach burnout literature has traditionally been on individual factors; this study shows that organisational factors also play an important role for understanding and preventing coach burnout and turnover. We therefore encourage sporting organisations to consider these findings and how they can work towards protecting their coaches against burnout and from leaving the organisation.
The value of global justice: Realism and moralism
Authors: Sleat Matt
Published: March 2016

It is a noticeable feature of the contemporary revival of interest in realist political thought that it has very much hesitated from exploring its implications for international political theory. This is interesting both because realism is one of the dominant intellectual traditions in international relations, but also as much of the recent debates surrounding global justice have engaged with themes that are at least germane to those of realism. This article will therefore try and extend some of the themes of realist political thought into the realm of global justice. While there might be several areas worth exploring, the focus here shall be on the realist emphasis on making sense of politics as a sphere of activity that has internal sources of normativity which cannot be reduced to moral first principles, the relationship between politics and legitimacy, and how these pose fundamental questions for the political nature of global justice. It ends by arguing that, viewed through the realist lens, the question of the legitimacy of international institutions should take greater priority in global justice debates insofar as this is fundamental to enabling us to understand justice in political and not exclusively moral terms.
Oral Baclofen Withdrawal Resulting in Progressive Weakness and Sedation Requiring Intensive Care Admission
Authors: Alvis Bret D. , Sobey Christopher M.
Published: March 2016

Baclofen is a common medication used as a muscle relaxant and antispasmodic. Baclofen-withdrawal syndrome has many symptoms such as sedation, somnolence, and weakness but can include psychological symptoms. We present a 62-year-old female whose oral baclofen was not continued at a skilled nursing facility after discharge following inpatient surgery that led to the development of altered mental status and respiratory insufficiency necessitating intensive care unit admission. Abrupt cessation of baclofen, no matter the mode of administration to the patient, can lead to baclofen-withdrawal syndrome.
Intraparenchymal hemorrhage from dural metastasis of breast cancer mimicking meningioma
Authors: Seki Syunsuke , Kamide Tomoya , Tamase Akira , Mori Kentaro , Yanagimoto Kunio , Nomura Motohiro
Published: March 2016

Intraparenchymal hemorrhage from dural metastasis of breast cancer is rare. A 54-year-old woman without a significant medical history showed altered consciousness and left hemiparesis. Radiological examination revealed an extra-axial mass in the right middle fossa with intraparenchymal hemorrhage and another mass invading the skull in the right parietal region. The pre-operative diagnosis was a sphenoid ridge meningioma presenting with intraparenchymal hemorrhage and another meningioma in the convexity. The tumors and hematoma were removed. Pathological findings of the tumors were compatible with adenocarcinoma. Systemic examination revealed breast cancer with metastasis to the spine. Although the radiological findings were similar to those of meningioma, a differential diagnosis of metastatic brain tumor with intraparenchymal hemorrhage should be taken into consideration.
Efficacy of Curcuma for Treatment of Osteoarthritis
Authors: Perkins Kimberly , Sahy William , Beckett Robert D.
Published: March 2016

The objective of this review is to identify, summarize, and evaluate clinical trials to determine the efficacy of curcuma in the treatment of osteoarthritis. A literature search for interventional studies assessing efficacy of curcuma was performed, resulting in 8 clinical trials. Studies have investigated the effect of curcuma on pain, stiffness, and functionality in patients with knee osteoarthritis. Curcuma-containing products consistently demonstrated statistically significant improvement in osteoarthritis-related endpoints compared with placebo, with one exception. When compared with active control, curcuma-containing products were similar to nonsteroidal anti-inflammatory drugs, and potentially to glucosamine. While statistical significant differences in outcomes were reported in a majority of studies, the small magnitude of effect and presence of major study limitations hinder application of these results. Further rigorous studies are needed prior to recommending curcuma as an effective alternative therapy for knee osteoarthritis.
Gastroprotective Effect of Combination of Hot Water Extracts of Licorice (Glycyrrhiza glabra), Pulasari Stem Bark (Alyxia reinwardtii), and Sembung Leaf (Blumea balsamifera) Against Aspirin-Induced Gastric Ulcer Model Rats
Authors: Nugroho Agung Endro , Wijayanti Agustin , Mutmainah Mutmainah , Susilowati Rina , Rahmawati Nuning
Published: March 2016

Licorice ( Glycyrrhiza glabra), Pulasari stem bark ( Alyxia reinwardtii) and Sembung leaf ( Blumea balsamifera) are traditionally used to treat gastrointestinal disorders. The aim of the study was to investigate gastroprotective effect of hot water extracts combination of those herbal against aspirin-induced gastric ulcer model in rats. The combination consisted of fixed doses of Licorice 273 mg/kg BW and Sembung leaf 457.5 mg/kg BW, and also consisted of Pulasari stem in various doses i.e. 100 mg/kg BW (first group), 200 mg/kg BW (second and sixth group) and 300 mg/kg BW (third group). The fourth grup rats received sucralfate 360 mg/kg BW. Ten minute after seven consecutive days of drug administration, the rats were induced with aspirin 450 mg/kg BW except sixth group rats. The fifth group rats only received aspirin without any protective agents. The number and area of gastric ulcers were evaluated macroscopically. Whereas, histopatological observation was used for evaluation of mucosal damage score, and the number of eosinophils and mast cells. In the study, herbal extracts combination markedly exhibited protective effects indicated by less number and smaller area of gastric ulcers in comparison to those of aspirin group ( P < 0.05). The score of mucosal damages were also decreased in herbal extracts combination groups. The number of eosinophils and mast cells of herbal combination groups were observed to be smaller than those of aspirin group ( P < 0.05). In conclusion, herbal combination of Licorice (Glycyrrhiza glabra), Pulasari stem bark (Alyxia reinwardtii) and Sembung leaf (Blumea balsamifera) is potential to develop as a gastroprotective agent.
Nutrition and Lifestyle Intervention on Mood and Neurological Disorders
Authors: Null Gary , Pennesi Luanne , Feldman Martin
Published: March 2016

This group study explored how an intervention of diet and lifestyle, including a vegan diet, fruit and vegetable juicing, nutritional supplements, regular exercise, and destressing techniques, would affect 27 subjects with anxiety, depression, poor memory, dementia, Alzheimer’s disease, Parkinson’s disease, history of stroke, or multiple sclerosis. Several subjects had overlapping conditions. Videotaped testimonials were obtained describing subjective results. Testimonials stated multiple benefits across all conditions addressed by the study, with subjects often reporting substantial benefits. These results demonstrate that an intervention of diet, juicing, supplements, exercise, and lifestyle may provide considerable benefits for all conditions addressed.
Instituting environmental sustainability and climate resilience into the governance process: Exploring the potential of new urban development schemes in India
Authors: Sharma Divya , Singh Seema
Published: March 2016

India is on the cusp of major transformation in terms of how it translates and directs urbanization. The recently announced flagship schemes of the Government of India – the ‘Smart Cities’ scheme, the Atal Mission for Rejuvenation and Urban Transformation (AMRUT) scheme, The Housing for All scheme – offer avenues for addressing some of the most daunting challenges that cities in India face today, including climate change impacts and disaster risks. While India has faced multiple climate-related hazards in the recent years, the frequency and intensity of extreme events on the Indian subcontinent has arguably begun to increase. While there have been clear entry points in the governance system and policy making through which the climate resilience agenda could have been integrated into urban development planning in Indian cities, it has not yet been done, largely due to the lack of realization of this very need among India’s decision makers. This paper discusses these issues in detail and outlines the gaps and challenges for bringing climate resilience into the mainstream agenda. Furthermore, it explores the possible avenues or entry points for integrating climate resilience into the urban development agenda through these schemes.
Methodological Aspects of Focus Groups in Health Research
Authors: Tausch Anja P. , Menold Natalja
Published: March 2016

Although focus groups are commonly used in health research to explore the perspectives of patients or health care professionals, few studies consider methodological aspects in this specific context. For this reason, we interviewed nine researchers who had conducted focus groups in the context of a project devoted to the development of an electronic personal health record. We performed qualitative content analysis on the interview data relating to recruitment, communication between the focus group participants, and appraisal of the focus group method. The interview data revealed aspects of the focus group method that are particularly relevant for health research and that should be considered in that context. They include, for example, the preferability of face-to-face recruitment, the necessity to allow participants in patient groups sufficient time to introduce themselves, and the use of methods such as participant-generated cards and prioritization.
The Kashmir Conflict: Multiple Fault Lines
Authors: Behera Navnita Chadha
Published: March 2016

The Kashmir conflict has acquired a multifaceted character. On the one hand, it involves national and territorial contestations between India and Pakistan and on the other, various political demands by religious, linguistic, regional and ethnic groups in both parts of the divided Kashmir that range from seeking affirmative discrimination, a separate political status within the state, to outright secession. Peace has eluded Kashmir so far because a state-centric peace process is at odds with its plural social realities and multiple fault lines. The article identifies the key challenges for the peace process that includes extending its outreach to all the local stakeholders in a multi-layered dialogue with a mandate to evolve political and institutional processes and mechanisms for addressing different—if not divergent—aspirations of its diverse communities, without undermining the plural character of its society. The prognosis in the foreseeable future entails a roller-coaster ride with no clear endgame in sight.
Mindanao: Nationalism, Jihadism and Frustrated Peace
Authors: Quimpo Nathan Gilbert
Published: March 2016

This article examines why the decades-old Moro insurgency in Mindanao, southern Philippines, has remained difficult to resolve, and how recent international developments, such as the jihadization of once secular ethno-nationalist movements and the rise of the Islamic State of Iraq and Syria (ISIS), have influenced it. The author argues that jihadism made significant inroads in the Moro nationalist struggle already in the 1990s, way before 9/11, and that since 2007, a more moderate Islamism has gained ascendancy. He argues further that the Moro insurgency has remained intractable because of grave errors committed by the Arroyo and Aquino administrations; recurrent outbursts of anti-Moro hysteria incited by demagogic politicians; and a continuing weak third-party role in the Mindanao peace process. He warns that the apparent collapse of the most recent peace pact between the government and the Moro Islamic Liberation Front (MILF) poses the danger of the possible rise of new ISIS-linked jihadist groups.
An exact solution for the calendering analysis of a third-order fluid
Authors: Sajid Muhammad , Ali Nasir , Javed Muhammad Asif
Published: March 2016

This paper presents the exact solution for calendering a third-order fluid under lubrication approximation. The solution obtained is valid for all values of the third-order fluid parameter. This exact solution is compared to the perturbation solution. The results show that the perturbation solution is valid for very small values of the third-order fluid parameter. Therefore, no significant deviation from the corresponding results of the Newtonian fluid is observed with the perturbation solution. The interesting quantities for mechanically designing a calendering system such as the force separating the two rolls and total power input into both rolls are calculated and shown graphically for large third-order fluid parameter. The material’s rheological features modify the pressure, flow characteristics, and all other operating variables significantly. In fact, the nip region pressure increases with increasing third-order fluid parameter. The exiting sheet thickness, power input, and roll separating force also increase with increasing third-order fluid parameter.
Interfacial polarization of disseminated conductive minerals in absence of redox-active species — Part 1: Mechanistic model and validation
Authors: Misra S. , Torres-Verdín C. , Revil A. , Rasmus J. , Homan D.
Published: March 2016

Electrically conductive mineral inclusions are commonly present in organic-rich mudrock and source-rock formations such as veins, laminations, rods, grains, flakes, and beds. Laboratory and subsurface electromagnetic (EM) measurements performed on geomaterials containing electrically conductive inclusions generally exhibit frequency dispersion due to interfacial polarization phenomena at host-inclusion interfaces. In the absence of redox-active species, surfaces of electrically conductive mineral inclusions are impermeable to the transport of charge carriers, inhibit the exchange of charges and behave as perfectly polarized (PP) interfaces under the influence of an externally applied EM field. Interfacial polarization phenomena involving charge separation, migration, accumulation/depletion, and relaxation around PP interfaces is referred to as PP interfacial polarization; it influences the magnitude and direction of the electric field and charge carrier migration in the geomaterial. We have developed a mechanistic model to quantify the complex-valued electrical conductivity response of geomaterials containing electrically conductive mineral inclusions, such as pyrite and magnetite, uniformly distributed in a fluid-filled, porous matrix made of nonconductive grains possessing surface conductance, such as silica and clay grains. The model first uses a linear approximation of the Poisson-Nernst-Planck equations of dilute solution theory to determine the induced dipole moment of a single isolated conductive inclusion and that of a single isolated nonconductive grain surrounded by an electrolyte. A consistent effective-medium formulation was then implemented to determine the effective complex-valued electrical conductivity of the geomaterial. Model predictions were in good agreement with laboratory measurements of multifrequency complex-valued electrical conductivity, relaxation time, and chargeability of mixtures containing electrically conductive inclusions.
Interfacial polarization of disseminated conductive minerals in absence of redox-active species — Part 2: Effective electrical conductivity and dielectric permittivity
Authors: Misra S. , Torres-Verdín C. , Revil A. , Rasmus J. , Homan D.
Published: March 2016

Hydrocarbon-bearing conventional formations, mudrock formations, and source-rock formations generally contain clays, pyrite, magnetite, graphitelike carbon, and/or other electrically conductive mineral inclusions. Under redox-inactive conditions, these inclusions give rise to perfectly polarized interfacial polarization (PPIP) when subjected to an external electric field. Effective electrical conductivity and dielectric permittivity of geomaterials containing such inclusions are frequency-dependent properties due to the electric-field-induced interfacial polarization and associated charge relaxation around host-inclusion interfaces. Existing resistivity interpretation techniques do not account for PPIP phenomena, and hence they can lead to inaccurate estimation of water saturation, total organic content, and conductivity of formation water based on subsurface galvanic resistivity, electromagnetic (EM) induction, and EM propagation measurements in the presence of conductive mineral inclusions. In the first paper of our two-part publication series, we derived a mechanistic electrochemical model, the PPIP model, and we validated a coupled model that integrates the PPIP model with a surface-conductance-assisted interfacial polarization (SCAIP) model to quantify the frequency-dependent electrical complex conductivity of geomaterials. We have used the PPIP-SCAIP model to evaluate the dependence of effective complex-valued conductivity of geologic mixtures on (1) frequency, (2) conductivity of the host medium, and (3) material, size, and the shape of inclusions. Notably, we have used the PPIP-SCAIP model to identify rock conditions that give rise to significant differences in effective conductivity and effective relative permittivity of conductive-inclusion-bearing mixtures from those of conductive-inclusion-free homogeneous media. For a mixture containing as low as a 5% volume fraction of disseminated conductive inclusions, the low-frequency effective conductivity of the mixture is in the range of [Formula: see text] to [Formula: see text] with respect to the host conductivity for frequencies between 100 Hz and 100 kHz. Further, the high-frequency effective relative permittivity of that mixture is in the range of [Formula: see text] to [Formula: see text] with respect to the host relative permittivity for frequencies between 100 kHz and 10 MHz.
Projected Gabor deconvolution
Authors: Gholami Ali
Published: March 2016

Gabor deconvolution consists of approximating a nonstationary problem as several stationary subproblems via the Gabor frame, solving each subproblem independently, and then recombining/projecting the subsolutions into an approximate solution to the original nonstationary problem. The approximations, however, cause inherent instability due to systematic errors that prevent the algorithm from converging to the true solution even for noise-free cases. Furthermore, the method will be time consuming when a nonlinear optimization is used for shaping the reflectivity structure. An alternative projected Gabor deconvolution is considered, which is based on the Gabor expansion. However, in contrast to the conventional form, in the new method, first the problem is projected into the time domain, and then an inversion is performed to obtain the final reflectivity. Compared with the Gabor deconvolution, the projected alternative (1) exhibits an improved convergence property, (2) is more efficient for sparse deconvolution because only a single optimization is required to be solved, and (3) is more flexible for incorporating prior information about noise and reflectivity structure via a least-squares method. Numerical tests using simulated and field data are presented showing that the new method generates more accurate and stable reflectivity models compared with the Gabor deconvolution.
Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine–DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial
Authors: Herrlinger Ulrich , Schäfer Niklas , Steinbach Joachim P. , Weyerbrock Astrid , Hau Peter , Goldbrunner Roland , Friedrich Franziska , Rohde Veit , Ringel Florian , Schlegel Uwe , Sabel Michael , Ronellenfitsch Michael W. , Uhl Martin , Maciaczyk Jaroslaw , Grau Stefan , Schnell Oliver , Hänel Mathias , Krex Dietmar , Vajkoczy Peter , Gerlach Rüdiger , Kortmann Rolf-Dieter , Mehdorn Maximilian , Tüttenberg Jochen , Mayer-Steinacker Regine , Fietkau Rainer , Brehmer Stefanie , Mack Frederic , Stuplich Moritz , Kebir Sied , Kohnen Ralf , Dunkl Elmar , Leutgeb Barbara , Proescholdt Martin , Pietsch Torsten , Urbach Horst , Belka Claus , Stummer Walter , Glas Martin
Published: March 2016

Purpose

In patients with newly diagnosed glioblastoma that harbors a nonmethylated O6-methylguanine–DNA methyltransferase promotor, standard temozolomide (TMZ) has, at best, limited efficacy. The GLARIUS trial thus explored bevacizumab plus irinotecan (BEV+IRI) as an alternative to TMZ.

Patients and Methods

In this phase II, unblinded trial 182 patients in 22 centers were randomly assigned 2:1 to BEV (10 mg/kg every 2 weeks) during radiotherapy (RT) followed by maintenance BEV (10 mg/kg every 2 weeks) plus IRI(125 mg/m2 every 2 weeks) or to daily TMZ (75 mg/m2) during RT followed by six courses of TMZ (150-200 mg/m2/d for 5 days every 4 weeks). The primary end point was the progression-free survival rate after 6 months (PFS-6).

Results

In the modified intention-to-treat (ITT) population, PFS-6 was increased from 42.6% with TMZ (95% CI, 29.4% to 55.8%) to 79.3% with BEV+IRI (95% CI, 71.9% to 86.7%; P <.001). PFS was prolonged from a median of 5.99 months (95% CI, 2.7 to 7.3 months) to 9.7 months (95% CI, 8.7 to 10.8 months; P < .001). At progression, crossover BEV therapy was given to 81.8% of all patients who received any sort of second-line therapy in the TMZ arm. Overall survival (OS) was not different in the two arms: the median OS was 16.6 months (95% CI, 15.4 to 18.4 months) with BEV+IRI and was 17.5 months (95% CI, 15.1 to 20.5 months) with TMZ. The time course of quality of life (QOL) in six selected domains of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ) –C30 and QLQ-BN20 (which included cognitive functioning), of the Karnofsky performance score, and of the Mini Mental State Examination score was not different between the treatment arms.

Conclusion

BEV+IRI resulted in a superior PFS-6 rate and median PFS compared with TMZ. However, BEV+IRI did not improve OS, potentially because of the high crossover rate. BEV+IRI did not alter QOL compared with TMZ.
Contemporary Locoregional Recurrence Rates in Young Patients With Early-Stage Breast Cancer
Authors: Aalders Kim C. , Postma Emily L. , Strobbe Luc J. , van der Heiden-van der Loo Margriet , Sonke Gabe S. , Boersma Liesbeth J. , van Diest Paul J. , Siesling Sabine , van Dalen Thijs
Published: March 2016

Purpose

The aim of this study was to evaluate contemporary rates of local recurrence (LR) and regional recurrence (RR) in young patients with breast cancer in relation to tumor biology as expressed by biomarker subtypes.

Patients and Methods

Women < 35 years of age who underwent surgery for primary unilateral invasive breast cancer between 2003 and 2008 were selected from the Netherlands Cancer Registry. Patients were categorized according to biomarker subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year risks of developing LR and regional lymph node recurrence were estimated by using Kaplan-Meier statistics.

Results

A total of 1,000 patients were identified, of whom 59% had a known subtype: 39% HR-positive/HER2-negative; 17% HR-positive/HER2-positive; 10% HR-negative/HER2-positive; and 34% HR-negative/HER2-negative (triple negative). Overall 5-year LR and RR rates were 3.5% and 3.7%, respectively. A decreasing trend for both rates was observed over time and was accompanied by a significant decrease in the risk of distant metastases (DM). LR occurred in 4.2%, RR in 6.1%, and DM in 17.8% of patients in 2003, and in 3.2%, 4.4%, and 10.0%, respectively, in 2008. LR and RR rates varied with biomarker subtype. These differences were borderline significant when analyzed for the entire study period (P = .056 and P = .014, respectively) and leveled off after the introduction of trastuzumab after 2005 (P = .24 and P = .42, respectively). Patients with lymph node metastases at the time of diagnosis had an increased risk of RR. The type of surgery performed—breast-conserving or mastectomy—did not influence rates of LR and RR.

Conclusion

Overall, the rates of LR and RR in young patients with early-stage breast cancer were relatively low and varied by biomarker subtype.
Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma
Authors: Korfel Agnieszka , Schlegel Uwe , Herrlinger Ulrich , Dreyling Martin , Schmidt Christian , von Baumgarten Luisa , Pezzutto Antonio , Grobosch Thomas , Kebir Sied , Thiel Eckhard , Martus Peter , Kiewe Philipp
Published: March 2016

Purpose

In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL).

Patients and Methods

Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week.

Results

Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF.

Conclusion

Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived.
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer
Authors: Tung Nadine , Lin Nancy U. , Kidd John , Allen Brian A. , Singh Nanda , Wenstrup Richard J. , Hartman Anne-Renee , Winer Eric P. , Garber Judy E.
Published: March 2016

Purpose

Testing for germline mutations in BRCA1/2 is standard for select patients with breast cancer to guide clinical management. Next-generation sequencing (NGS) allows testing for mutations in additional breast cancer predisposition genes. The frequency of germline mutations detected by using NGS has been reported in patients with breast cancer who were referred for BRCA1/2 testing or with triple-negative breast cancer. We assessed the frequency and predictors of mutations in 25 cancer predisposition genes, including BRCA1/2, in a sequential series of patients with breast cancer at an academic institution to examine the utility of genetic testing in this population.

Methods

Patients with stages I to III breast cancer who were seen at a single cancer center between 2010 and 2012, and who agreed to participate in research DNA banking, were included (N = 488). Personal and family cancer histories were collected and germline DNA was sequenced with NGS to identify mutations.

Results

Deleterious mutations were identified in 10.7% of women, including 6.1% in BRCA1/2 (5.1% in non-Ashkenazi Jewish patients) and 4.6% in other breast/ovarian cancer predisposition genes including CHEK2 (n = 10), ATM (n = 4), BRIP1 (n = 4), and one each in PALB2, PTEN, NBN, RAD51C, RAD51D, MSH6, and PMS2. Whereas young age (P < .01), Ashkenazi Jewish ancestry (P < .01), triple-negative breast cancer (P = .01), and family history of breast/ovarian cancer (P = .01) predicted for BRCA1/2 mutations, no factors predicted for mutations in other breast cancer predisposition genes.

Conclusion

Among sequential patients with breast cancer, 10.7% were found to have a germline mutation in a gene that predisposes women to breast or ovarian cancer, using a panel of 25 predisposition genes. Factors that predict for BRCA1/2 mutations do not predict for mutations in other breast/ovarian cancer susceptibility genes when these genes are analyzed as a single group. Additional cohorts will be helpful to define individuals at higher risk of carrying mutations in genes other than BRCA1/2.
From single genes to entire genomes: the search for a function of nuclear organization
Authors: Pueschel Ringo , Coraggio Francesca , Meister Peter
Published: March 2016

The existence of different domains within the nucleus has been clear from the time, in the late 1920s, that heterochromatin and euchromatin were discovered. The observation that heterochromatin is less transcribed than euchromatin suggested that microscopically identifiable structures might correspond to functionally different domains of the nucleus. Until 15 years ago, studies linking gene expression and subnuclear localization were limited to a few genes. As we discuss in this Review, new genome-wide techniques have now radically changed the way nuclear organization is analyzed. These have provided a much more detailed view of functional nuclear architecture, leading to the emergence of a number of new paradigms of chromatin folding and how this folding evolves during development.
H19 controls reactivation of the imprinted gene network during muscle regeneration
Authors: Martinet Clémence , Monnier Paul , Louault Yann , Benard Matthieu , Gabory Anne , Dandolo Luisa
Published: March 2016

The H19 locus controls fetal growth by regulating expression of several genes from the imprinted gene network (IGN). H19 is fully repressed after birth, except in skeletal muscle. Using loss-of-function H19Δ3 mice, we investigated the function of H19 in adult muscle. Mutant muscles display hypertrophy and hyperplasia, with increased Igf2 and decreased myostatin (Mstn) expression. Many imprinted genes are expressed in muscle stem cells or satellite cells. Unexpectedly, the number of satellite cells was reduced by 50% in H19Δ3 muscle fibers. This reduction occurred after postnatal day 21, suggesting a link with their entry into quiescence. We investigated the biological function of these mutant satellite cells in vivo using a regeneration assay induced by multiple injections of cardiotoxin. Surprisingly, despite their reduced number, the self-renewal capacity of these cells is fully retained in the absence of H19. In addition, we observed a better regeneration potential of the mutant muscles, with enhanced expression of several IGN genes and genes from the IGF pathway.
Development of the lymphatic system: new questions and paradigms
Authors: Semo Jonathan , Nicenboim Julian , Yaniv Karina
Published: March 2016

The lymphatic system is a blind-ended network of vessels that plays important roles in mediating tissue fluid homeostasis, intestinal lipid absorption and the immune response. A profound understanding of the development of lymphatic vessels, as well as of the molecular cues governing their formation and morphogenesis, might prove essential for our ability to treat lymphatic-related diseases. The embryonic origins of lymphatic vessels have been debated for over a century, with a model claiming a venous origin for the lymphatic endothelium being predominant. However, recent studies have provided new insights into the origins of lymphatic vessels. Here, we review the molecular mechanisms controlling lymphatic specification and sprouting, and we discuss exciting findings that shed new light on previously uncharacterized sources of lymphatic endothelial cells.
SEARCH OF NEW DESIGN SCHEMES OF GEARED AND DIRECT-DRIVE TRACTION MECHANISM OF LOCOMOTIVE WITH MASS PARTIAL SPRINGING
Authors: Стриженок Александр , Strizhenok Aleksandr , Воробьев Владимир , Vorobev Vladimir , Измеров Олег , Izmerov Oleg
Published: March 2016

The problem of search new design schemes of a traction mechanism for a locomotive with mass drive partial springing is under consideration. New design schemes are offered: a drive with a movable joint of a drive motor and an axial reducing gear and a drive with a disk motor with the separation of a stator and rotor. The authors offer to return to the development of supportframe drives with an axial reducing gear as it is simpler in manufacturing and assemblage on the basis of updated data of their operating modes. The authors also offer their own design of an integrated traction drive with a swivel of a motor and reducing gear which is simpler in manufacturing and assemblage as compared with the foreign analogues.

The introduction of nonsynchronous traction electric motors having a smaller mass and higher reliability as compared with commutator motors resulted in new designs of a supportaxial drive by foreign manufacturers and their introduction in the market of domestic rolling-stock. This work shows an attempt to determine possibilities to eliminate dependence mentioned by means of the analysis of basic problems in the development of supportaxial drive design and new structural scheme searches.
EFFECT OF MODIFIER FRACTIONAL COMPOSITION UPON ITS ASSIMILATION BY CAST IRON MELT TAKING INTO ACCOUNT DISSOLUTION PROCESS KINETICS
Authors: Болдырев Денис , Boldyrev Denis
Published: March 2016

The results of the theoretical researches on a modifier dispersity influence at cast iron melt vermiculiting working in a reaction chamber of a mold with the use of mathematical target setting for a flat crystal are shown.
PROSPECTS IN MOTOR CAR COMPACT LOADING IN RAILROAD CARS
Authors: Ожерельев Виктор , Ozherelev Viktor , Афонина Елена , Afonina Elena
Published: March 2016

Motor car competitiveness in markets distant from motor car manufacturing area depends on the value of logistics outgoings. A motor car compact loading in special railroad cars allows reducing considerably outgoings mentioned. According to a common loading order a railroad car capacity within the limits of extreme dimensions throughout the height is not completely used as it exceeds considerably a total height of two motor cars. In this connection it is possible to compact a loading layout only through the location of a motor car rear part of a front motor car under the engine jacket of it following motor car at their inclined fixation and longitudinal orientation. It allows stowing additionally two motor cars in every railroad car. The motor cars of some models cannot be stowed in two rows in one deck. It is caused with that a total width of two motor cars exceeds extreme dimensions of a railroad car allowed for railway operations. The problem could be solved, if motor car loading in every deck is carried out on load floorings the surfaces of which have a tilt from the center of a railroad car to its side walls. At the inclination of about 100 the projection on a horizontal plane of maximum cross dimension of a motor car on a level of passenger seats decreases by 25 mm. Space saving makes 50 mm on two parallel rows. As a result a two-row rail freightage of motor cars becomes possible in every motor car deck with the width 1680 mm common for products of Volzhsky Motor Car Works. At the expense of this way a length of haul economically feasible increases considerably.
SIMULATION OF SYSTEM OF ENERGY EFFICIENT DOUBLE-AREA VELOCITY CONTROL IN ASYNCHRONOUS DRIVE WITH MOMENT DIRECT CONTROL
Authors: Тарасов Алексей , Tarasov Aleksey , Конохов Дмитрий , Konokhov Dmitriy , Федяева Галина , Fedyaeva Galina , Сморудова Татьяна , Smorudova Tatyana
Published: March 2016

In the paper there are presented and tested energy-efficient algorithms of asynchronous drive control with the system of moment direct control on the basis of simulation. The algorithms are directed to the reduc-tion of stator current consumption and also to the maximum use of an engine on heating and power. With purpose of energy saving the electric drive system with direct moment control is supplied additionally with a special setting device of a stator flux linkage where the dependence of a stator flux linkage upon the moment of an asynchronous drive necessary to support an optimum angle between momentforming vectors is realized. A functional scheme of the system of an energy effective doublearea control of an asynchronous drive velocity with the direct control of a moment and an adjustable capacity limitation reflecting principles of functioning and an interrelation of system basic units is shown. To check-up the solutions offered there is developed a model of a traction electric drive system in the basic library of the bundled software Matlab Simulink, the results of its modeling confirm the effectiveness in the application of energy saving algorithms allowing the reduction of current consumption of the asynchronous traction electric drive by 7-10%