bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors
Authors: Leijen Suzanne , van Geel Robin M.J.M. , Pavlick Anna C. , Tibes Raoul , Rosen Lee , Razak Albiruni R. Abdul , Lam Raymond , Demuth Tim , Rose Shelonitda , Lee Mark A. , Freshwater Tomoko , Shumway Stuart , Liang Li Wen , Oza Amit M. , Schellens Jan H.M. , Shapiro Geoffrey I. 
Published: September 2016

PurposeAZD1775 is a WEE1 kinase inhibitor targeting G2 checkpoint control, preferentially sensitizing TP53-deficient tumor cells to DNA damage. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of oral AZD1775 as monotherapy or in combination with chemotherapy in patients with refractory solid tumors.Patients and MethodsIn part 1, patients received a single dose of AZD1775 followed by 14 days of observation. In part 2, patients received AZD1775 as a single dose (part 2A) or as five twice per day doses or two once per day doses (part 2B) in combination with one of the following chemotherapy agents: gemcitabine (1,000 mg/m2), cisplatin (75 mg/m2), or carboplatin (area under the curve, 5 mg/mL⋅min). Skin biopsies were collected for pharmacodynamic assessments. TP53 status was determined retrospectively in archival tumor tissue.ResultsTwo hundred two patients were enrolled onto the study, including nine patients in part 1, 43 in part 2A (including eight rollover patients from part 1), and 158 in part 2B. AZD1775 monotherapy given as single dose was well tolerated, and the maximum-tolerated dose was not reached. In the combination regimens, the most common adverse events consisted of fatigue, nausea and vomiting, diarrhea, and hematologic toxicity. The maximum-tolerated doses and biologically effective doses were established for each combination. Target engagement, as a predefined 50% pCDK1 reduction in surrogate tissue, was observed in combination with cisplatin and carboplatin. Of 176 patients evaluable for efficacy, 94 (53%) had stable disease as best response, and 17 (10%) achieved a partial response. The response rate in TP53-mutated patients (n = 19) was 21% compared with 12% in TP53 wild-type patients (n = 33).ConclusionAZD1775 was safe and tolerable as a single agent and in combination with chemotherapy at doses associated with target engagement.
Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non–Clear Cell Renal Cell Carcinoma
Authors: Voss Martin H. , Molina Ana M. , Chen Ying-Bei , Woo Kaitlin M. , Chaim Joshua L. , Coskey Devyn T. , Redzematovic Almedina , Wang Patricia , Lee William , Selcuklu S. Duygu , Lee Chung-Han , Berger Michael F. , Tickoo Satish K. , Reuter Victor E. , Patil Sujata , Hsieh James J. , Motzer Robert J. , Feldman Darren R. 
Published: September 2016

Purpose The decreased effectiveness of single-agent targeted therapies in advanced non–clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing. Results Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology ( P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit. Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.
“Little Big Things”: A Qualitative Study of Ovarian Cancer Survivors and Their Experiences With the Health Care System
Authors: Long Roche Kara , Angarita Ana M. , Cristello Angelica , Lippitt Melissa , Haider Adil H. , Bowie Janice V. , Fader Amanda N. , Tergas Ana I. 
Published: September 2016

Purpose: Navigation of a complex and ever-changing health care system can be stressful and detrimental to psychosocial well-being for patients with serious illness. This study explored women’s experiences with navigating the health care system during treatment for ovarian cancer. Methods: Focus groups moderated by trained investigators were conducted with ovarian cancer survivors at an academic cancer center. Personal experiences with cancer treatment, provider relationships, barriers to care, and the health care system were explored. Sessions were audiotaped, transcribed, and coded by using grounded theory. Subsequently, one-on-one interviews were conducted to further evaluate common themes. Results: Sixteen ovarian cancer survivors with a median age of 59 years participated in the focus group study. Provider consistency, personal touch, and patient advocacy positively affected the care experience. Treatment with a known provider who was well acquainted with the individual’s medical history was deemed an invaluable aspect of care. Negative experiences that burdened patients, referred to as the “little big things,” included systems-based challenges, which were scheduling, wait times, pharmacy, transportation, parking, financial, insurance, and discharge. Consistency, a care team approach, effective communication, and efficient connection to resources were suggested as ways to improve patients’ experiences. Conclusion: Systems-based challenges were perceived as burdens to ovarian cancer survivors at our institution. The role of a consistent, accessible care team and efficient delivery of resources in the care of women with ovarian cancer should be explored further.
A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs
Authors: Haslem Derrick S. , Van Norman S. Burke , Fulde Gail , Knighton Andrew J. , Belnap Tom , Butler Allison M. , Rhagunath Sharanya , Newman David , Gilbert Heather , Tudor Brian P. , Lin Karen , Stone Gary R. , Loughmiller David L. , Mishra Pravin J. , Srivastava Rajendu , Ford James M. , Nadauld Lincoln D. 
Published: September 2016

Purpose: The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. Patients and Methods: We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). Results: The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). Conclusion: These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.
Case Article—ABCtronics: Manufacturing, Quality Control, and Client Interfaces
Authors: Adhikari Arnab , Biswas Indranil , Bisi Arnab 
Published: September 2016

Teaching statistics in an undergraduate or a graduate business administration course, business analytics course, or engineering program remains a challenging task for the instructors. Often students fail to comprehend the real-life application of statistical concepts with the help of disconnected textbook examples. This failure inspires scholars to develop case studies on statistical theories in real-life industry backgrounds or realistic industrial settings. Recognizing the students’ difficulty to understand the diverse statistical concepts in a realistic setting, we design a case study in an industrial background to facilitate students’ learning. It is constructed by drawing inspiration from real-life business scenarios in the context of the integrated chip manufacturing industry. It helps to bridge the gap between theoretical understanding and practical application. The case starts with introducing various probability distributions and gradually incorporates intricate concepts of statistics like sampling distribution, hypothesis testing, and regression models in realistic scenarios. Each assignment question enables the teacher to engage in the in-depth discussion regarding the applications of different statistical concepts about business problems of integrated chip manufacturing. Also, it involves the application of the software tools for solving statistical problems. This case article demonstrates different usages of the case, ranging from a common thread for classroom discussion throughout the course to a class reading for providing a holistic approach to understanding and applying different statistical concepts in real-life scenarios by the end of the course.Case Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
Case Article—U.S. Army Deployment to the Middle East
Authors: Dillenburger Steven P. 
Published: September 2016

This paper describes a modeling and simulation case study relating to Army platoons deploying to the Middle East. The study tasks students with analyzing routes for deploying troops travel through in an effort to decrease the average time a soldier spends in transit. Students with little simulation experience are able to become familiar with modeling software. Student groups are instructed to identify where bottlenecks occur in the queuing system and to find creative solutions to alleviate those bottlenecks. Additionally, the case study illustrates the concepts of input and output analysis, random numbers, random variate generation, and probability distributions. Case Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
Analisis kesesuaian dan daya dukung ekowisata bahari Pulau Sebesi, Provinsi Lampung
Authors: Johan Yar 
Published: September 2016

Abstract. The Sebesi Island has coral reefs, mangrove and seagrass ecosystems, and therefore this island has the potenticy to be developed as a tourism destination object. The objectives of the present study were to analysis the suitability and carrying of Sebesi Island for for marine ecotourism activities of diving and snorkeling. The primary data were collected through field sampling, direct observation of field conditions, questionnaires and interviews. The secondary data were collected from previous studies, journals, technical reports and related agencies. The results showed that the Sebesi Island was suitable for diving and snorkeling activities (S2 category) with the carrying capacity for diving and snorkeling activities were 2,394 person/day and 2,489 person/day, respectively.Keywords: coral reef, marine ecotourism, suitability, carrying capacity, Sebesi Island Abstrak. Pulau Sebesi berpotensi untuk dikembangkan menjadi salah satu Objek Daerah Tujuan Wisata (ODTW). Ekosistem Pulau Sebesi sebagian besar merupakan ekosistem terumbu karang, mangrove dan lamun. Penelitian tentang analisis kesesuaian dan daya dukung ekowisata bahari Pulau Sebesi Provinsi Lampung bertujuan mengkaji kesesuaian kawasan Pulau Sebesi untuk kegiatan ekowisata bahari yaitu diving dan snorkeling dan menganalisis daya dukung (carryng capacity) kawasan Pulau Sebesi. Pengumpulan data primer dilakukan melalui sampling, observasi langsung di lapangan, kuisioner, wawancara terbuka/langsung dan wawancara mendalam di lokasi penelitian. Data sekunder dikumpulkan dengan penelusuran berbagai pustaka, dan instansi terkait. Hasil penelitian menunjukkan bahwa jenis kegiatan ekowisata bahari diving dan snorkling termasuk dalam kategori sesuai (S2), dengan daya dukung kawasan 2.394/hari orang untuk diving dan 2.489 orang/hari untuk snorkling.Kata kunci: terumbu karang, ekowisata bahari, kesesuaian, daya dukung, Pulau Sebesi
Hubungan parameter fisika-kimia perairan dengan kelimpahan plankton di Samudera Hindia bagian Barat Daya
Authors: Novia Rani , . Adnan , Ramadhan Ritonga Irwan 
Published: September 2016

Abstract. The aims of this research was to examine the water quality parameters and plankton abundance and its relationships in the Southwestern of Indian Ocean. This is a quantitative descriptive research. Planktons were sampled using plankton net, and water samples were taken using Conductivity, Temperature, Depth (CTD) where the water samples colleted in the Nansen Bottle No. 1 (surface water) at seven sampling stations. The results showed that there were 25 species of planktons belonging into seven classes, i.e., Bacillariophyceae, Ciliate, Crustacea, Cyanobacteria, Dinophyceae, Flagellata, and Maxillopoda. The highest value of abundance of plankton was found at station 6 with 7255 ind. L-1, the value of diversity index of plankton was at moderate category, and there was no predominant species was occurred in the community. Bivariate correlation analysis results of Person's showed that the temperature and Dissolved Oxygen (DO) were positively correlated to the plankton abudance, while pH, conductivity, TDS, salinity were negatively correlated with abundances of plankton.Keywords: Abundance of plankton, linkages, water quality, Indian Ocean of Southwestern Abstrak. Penelitian ini bertujuan untuk mengetahui jenis dan kelimpahan plankton dan kualitas air serta hubungan antara kelimpahan plankton dengan parameter fisika-kimia perairan di Samudera Hindia bagian Barat Daya. Penelitian ini merupakan penelitian deskriptif kuantitatif, pengambilan sampel plankton menggunakan plankton net, dan sampel air menggunakan CTD (Conductivity, Temperature Depth) dimana sampel air yang diambil pada botol nansen No. 1 (sampel air permukaan) pada 7 titik stasiun. Hasil penelitian ditemukan 25 spesies plankton yang termasuk ke dalam 7 kelas, yaitu Bacillariophyceae, Ciliata, Crustacea, Cyanobacteria, Dinophyceae, Flagellata, dan Maxillopoda. Kelimpahan plankton tertinggi terdapat pada stasiun 6 dengan 7255 ind/L, indeks keragaman plankton pada kondisi sedang, dan tidak terjadi dominasi spesies dalam komunitas. Hasil analisis korelasi Bivariate Person’s menunjukkan suhu dan DO (Dissolved Oxygen) berkorelasi positif terhadap kelimpahan plankton, sedangkan pH, konduktifitas, TDS, salinitas berkorelasi negative dengan kelimpahan plankton. Kata kunci: Kelimpahan Plankton, Keterkaitan, Kualitas air, Samudera Hindia bagian Barat Daya
Risk factors for cefotaxime resistance in children with pneumonia
Authors: Sucipta Anak Agung Made , Subanada Ida Bagus , Wahab Samik 
Published: September 2016

Background Pneumonia is a health problem in developingcountries, often caused by bacterial agents. The 'Widespreaduse of cefotaxime, a third􀁒generation of cephalosporin, may leadto increased incidence of resistance to this antibiotic. Severalstudies have reported on risk factors associated v.ith resistanceto cefotaxime.Objective To identify risk factors for cefotaxime resistance inchildren 'With pneumonia.Methods We performed a case􀁒control study at Sanglah Hospitalbetween January 2006􀁒December 2010. The case group includedchildren with blood culture􀁒positive pneumonia and resistanceto cefotaxime by sensitivity test. The control group was selectedfrom the same population as the case group, but the bacteriaisolated from these subjects were sensitive to cefotaxime. Wetested the folloMng risk factors for resistance to cefotaxime:age :53 years, microorganism species, history of antimicrobialuse, and history of hospitalization within the prior 3 months.Chi square test and logistic regression analysis were performedto determine any associations between the four potential riskfactors and resistance to cefotaxime. A P<0.05 was consideredto be statistically significant.Results Univariate analysis showed that the risk factors forresistance to cefotaxime were history of antimicrobial use in theprior 3 months (OR 2.79; 95%CI 1.40 to 5.55; P􀁓O.OOI) andhistory of hospitalization Mthin the prior 3 months (OR 5.57;95%CI 1.95 to 15.87; P=<O.OOOl). By multivariate analysis,risk factors associated Mth resistance to cefotaxime were historyof antimicrobial use in the prior 3 months (OR 2.4; 95%CI 1.18to 4.86; P=0.015), history of hospitalization within the prior 3months (OR 4.7; 95%CI 1.62 to 13.85; P􀁓0.004), and historyof breast feeding for less than 2 months (OR 2.3; 95%CI 1.0 to5.4; P􀁓0.042).Conclusion History of antimicrobial use and history ofhospitalization within the prior 3 monthsweresignificantrisk factors for resistance to cefotaxime in children Mth pneumonia.[Paediatr Indanes. 2012;52:255-9].
Recht im Kalten Krieg. Das Bundesverfassungsgericht, die deutsche Teilung und die politische Kultur der frühen Bundesrepublik
Authors: Gehrig Sebastian 
Published: September 2016

Zusammenfassung
Das Bundesverfassungsgericht wurde bis zum Bau der Berliner Mauer zu einem zentralen Ort der Verhandlung westdeutscher Staatsverständnisse. Zwischen 1951 und 1958 kodifizierten die Richter juristische Definitionen nationaler Identität. Das Bundesverfassungsgericht nahm durch wegweisende Urteile an der Neudefinition von Ideen der Nation, des Staates und der Gesellschaft teil, welche die politische Kultur der frühen Bundesrepublik nachhaltig prägen sollten. Zugleich verliehen die Urteile diesen politischen Neubestimmungen durch deren Aufladung mit der Autorität des Rechts und der Rechtsstaatlichkeit zusätzliches Gewicht. In der Entscheidung hochpolitscher Fragen zur Westbindung und dem Staatsschutz der jungen Republik war das Bundesverfassungsgericht jedoch nicht frei von politischen Einflüssen und dem Antikommunismus des frühen Kalten Kriegs. Das Bundesverfassungsgericht weitete in diesem Kontext seinen Einfluss auf die westdeutsche Rechtslandschaft gegen Widerstände der Bundesregierung, der Gerichtsbarkeit und der Staatsrechtslehre entscheidend aus. Im Kampf der Ideologien wuchs der Idee der Rechtsstaatlichkeit darüber hinaus zunehmende Bedeutung im Propagandakrieg um staatliche Legitimität zwischen den beiden deutschen Staaten zu. Das Bundesverfassungsgericht nahm somit durch Stellungnahmen zur Frage der Staatskontinuität vom Deutschen Reich zur Bundesrepublik und der juristischen Ausformulierung der Konzepte der freiheitlich-demokratischen Grundordnung und streitbaren Demokratie maßgeblich Anteil an der Etablierung der Staatsräson des „Provisoriums“ Bundesrepublik.
Lynx1 Limits Dendritic Spine Turnover in the Adult Visual Cortex
Authors: Sajo Mari , Ellis-Davies Graham , Morishita Hirofumi 
Published: September 2016

Dendritic spine turnover becomes limited in the adult cerebral cortex. Identification of specific aspects of spine dynamics that can be unmasked in adulthood and its regulatory molecular mechanisms could provide novel therapeutic targets for inducing plasticity at both the functional and structural levels for robust recovery from brain disorders and injuries in adults. Lynx1, an endogenous inhibitor of nicotinic acetylcholine receptors, was previously shown to increase its expression in adulthood and thus to limit functional ocular dominance plasticity in adult primary visual cortex (V1). However, the role of this “brake” on spine dynamics is not known. We examined the contribution of Lynx1 on dendritic spine turnover before and after monocular deprivation (MD) in adult V1 with chronicin vivoimaging using two-photon microscopy and determined the spine turnover rate of apical dendrites of layer 5 (L5) and L2/3 pyramidal neurons in adult V1 of Lynx1 knock-out (KO) mice. We found that the deletion of Lynx1 doubled the baseline spine turnover rate, suggesting that the spine dynamics in the adult cortex is actively limited by the presence of Lynx1. After MD, adult Lynx1-KO mice selectively exhibit higher rate of spine loss with no difference in gain rate in L5 neurons compared with control wild-type counterparts, revealing a key signature of spine dynamics associated with robust functional plasticity in adult V1. Overall, Lynx1 could be a promising therapeutic target to induce not only functional, but also structural plasticity at the level of spine dynamics in the adult brain.SIGNIFICANCE STATEMENTDendritic spine turnover becomes limited in the adult cortex. In mouse visual cortex, a premier model of experience-dependent plasticity, we found that the deletion of Lynx1, a nicotinic “brake” for functional plasticity, doubled the baseline spine turnover in adulthood, suggesting that the spine dynamics in the adult cortex is actively limited by Lynx1. After visual deprivation, spine loss, but not gain rate, remains higher in adult Lynx1 knock-out mice than in control wild-type mice, revealing a key signature of spine dynamics associated with robust functional plasticity. Lynx1 would be a promising target to induce not only functional, but also structural plasticity at the level of spine dynamics in adulthood.