bluuebunny/crossref_metadata_2025 huggingface dataset:
Supportive measures to enhance clinical trial data management in oncology community network practices.
Authors: Johnson Elizabeth Anne , Andersen Jay C. , Smith Sandy , Patel Bharat , Night Susan S. , Steckel Lauren
Published: September 2018

38

Background: As an innovative industry leader of Research Site Management Organizations, US Oncology Research (USOR) sought to develop a best practice to support over 65 community practice network sites to comply with Sponsor data entry expectations. Efforts led by the Clinical Trial Manager (CTM) focused on bringing research site awareness to priority data, Sponsor deadlines, and weekly performance feedback via the ‘Healthy Data Habits Pathway’. Methods: The Healthy Data Habits Pathway was created to define the role of CTM involvement in data management operations on behalf of USOR. In collaboration with Sponsor, the USOR CTM reviewed data management reports weekly for data entry trends. Results: Two separate oncology clinical trials (different Sponsors) implemented the Pathway with renal and breast oncology indications. The renal trial demonstrated an almost 90% reduction in total query count for 8 sites in 7 months while the breast trial reported 7 of 14 sites (50%) meeting Sponsor goal of 20 or fewer total queries in 13 weeks. Interventions included emailed notifications, site manager calls, and weekly CTM-Sponsor collaboration teleconferences. Conclusions: Clinical research Sponsors and sites both strive towards maintaining data integrity in an ever-evolving atmosphere of complex oncology trials and increasingly-detailed data capture requirements. Implementation of Pathway interventions increases site and Sponsor engagement in daily data management operations. [Table: see text]
Real-world genetic testing patterns in metastatic colorectal cancer: Balancing adoption challenges with performance efficiency.
Authors: Casebeer Adrianne Waldman , Long Charron , Drzayich Jankus Dana Angela , Racsa Patrick , Rogstad Teresa , Loy Bryan A. , De Souza Jonas A.
Published: September 2018

46

Background: Evaluation of real-world data regarding genetic testing for metastatic colorectal cancer (mCRC) highlights the successes and challenges of precision medicine. Guidelines recommend genetic testing to inform mCRC treatment choice. However, there is a lack of real-world evidence regarding genetic testing patterns, including adoption and efficiency. Methods: This retrospective analysis identified adult patients with newly diagnosed mCRC (2015-2106), Medicare Advantage coverage with a pharmacy benefit (MAPD), and claims evidence of CRC-related genetic testing. Inclusion required diagnosis of colon/rectal cancer on ≥2 medical claims and new metastatic disease. Paid and unpaid claims identified genetic testing, which was classified as limited RAS, extended KRAS/NRAS, limited + extended, and BRAF. Efficiency was measured as time-to-testing and time-to-treatment once testing was performed. Results: The study included 4,408 patients with mCRC and MAPD, with a median age of 72 years. Evidence of limited +/- extended testing was noted for 667 (15.1%) of patients. Of these, 78.3% initiated CRC treatment. Limited, extended, and limited + extended testing was observed for 51.7%, 4.5% and 43.8% of patients, respectively. BRAF was observed for 46.4%, 23.3% and 63.7% of patients with limited, extended, or limited + extended testing, respectively. For the 69.2% of patients tested prior to treatment, the median number of days between mCRC diagnosis and first genetic test was 6 [range: 0-31] days, with 25 [13-46] days between testing and treatment. When treatment preceded testing, the median number of days from treatment to test was 72.0 [20-251]. Of patients with > 1 genetic test, most patients had all tests on the same day (96.9%) or within 7 days (97.8%) of diagnosis, with no differences by type of testing. Conclusions: Per guidelines, mCRC-related genetic testing was completed efficiently after diagnosis and prior to treatment initiation for most patients. Genetic testing rates remain low, perhaps indicating barriers to scaling precision medicine. Ongoing research to explore ways to expedite adoption of precision medicine, while maintaining its efficiency, is needed.
Enhanced compliance with appropriate antiemetic prescribing guidelines by utilizing a medically integrated pharmacy antiemetic therapeutic interchange protocol.
Authors: Wilfong Lalan S. , Portnoy Carla , Hoverman J. Russell , Wallace Kathryn , Schwartz Jim R. , Dave Neal , Mikan Sabrina Q. , Patt Debra A.
Published: September 2018

55

Background: Appropriate antiemetic prescribing remains an unmet need in patients receiving emetogenic chemotherapy. Non-compliance with standard antiemetic guidelines is well reported, and a focus of the American Society of Clinical Oncology Choosing Wisely campaign. Using our medically integrated pharmacies, a community oncology practice sought to maximize compliance with national guidelines by minimizing the use of NK1 inhibitors for low and minimally emetogenic regimens and optimizing medications for highly emetogenic regimens per NCCN guidelines. Methods: A retrospective review of a medically integrated pharmacy antiemetic therapeutic interchange policy. Trained oncology pharmacists imbedded within 2 cancer centers evaluated all new chemotherapy orders to determine the level of emetogenicity per NCCN guidelines. Pharmacists then used a guideline compliant prespecified therapeutic interchange protocol to adjust the antiemetic medications. Patient education to enhance medication compliance was performed by the pharmacists, nurses, and in one on one treatment review sessions with an advance practice provider. Results: Of 271 low to minimally emetogenic regimens, 99% did not receive an NK1 inhibitor on the first cycle. Of 367 highly emetogenic regimens, 97% appropriately received guideline based therapy. Additionally, the use of olanzapine was non-existent in the practice prior to this protocol and increased to 55% of patients with highly emetogenic regimens. Conclusions: We demonstrated that a therapeutic interchange policy with a medically integrated pharmacist shows enhanced compliance with guideline based antiemetic medication usage. This system also allows rapid uptake of changes in supportive care guidelines such as rapid adoption of olanzapine. Efficacy results of this protocol will be reported separately.
Predicting acute care use following the initiation of systemic therapy for solid tumors.
Authors: Grant Robert C , Moineddin Rahim , Yao Zhan , Powis Melanie Lynn , Croxford Ruth , Grunfeld Eva , Kukreti Vishal , Krzyzanowska Monika K.
Published: September 2018

6

Background: Emergency department (ED) visits and hospitalizations are undesirable and costly. We developed and validated the PROACCT (PRediction Of Acute Care use during Cancer Treatment) score to predict at least one acute care visit during the first 30 days (AC30) after initiating systemic therapy for cancer. Methods: Using administrative data, we identified patients in Ontario with the 18 most common solid tumors who started systemic treatment from July 1, 2014 to June 30, 2015. Southwestern and Northeastern Ontario formed the development and validation cohorts, respectively. We created a score to predict AC30 using multivariate logistic regression in the development cohort. Combinations of tumor sites and regimens were grouped into quintiles based on AC30. The score was assessed in the validation cohort. Results: AC30 occurred in 23% (4438/19359) of patients. Eleven factors predicted AC30 and formed the score: tumor site and regimen (2nd quintile: 2; 3rd-4th: 3; 5th: 4), recent ED visit (2), recent palliative radiation (1), rural residence (1) and Edmonton Symptom Assessment Scale anxiety (4+: 1), lack of appetite (4+: 1), pain (4+: 1), and wellbeing (4+: 1). Among the 204 tumor-regimen combinations, tumors with poor prognoses, such as pancreatic and lung, and platinum- and taxane-containing regimens, carried the highest risk for AC30. The score had moderate discrimination (c-statistic 0.65; P< 0.001) and strong calibration (Table) in the validation cohort. Conclusions: PROACCT identifies factors that predict AC30 in patients starting systemic treatment for solid tumors and could be incorporated into electronic health records to select patients for preventative interventions. [Table: see text]
Burdensome transitions on cancer decedents treated in different health care systems at the end of life.
Authors: Gidwani Risha
Published: September 2018

7

Background: Cancer decedents often experience intensive and unnecessary medical care in the months prior to death. We evaluated whether cancer patients treated by a purchasing system with fee-for-service incentives (Medicare) experience a greater number of burdensome transitions in the last 6 months of life compared to those treated by a system in which care is directly provided by salaried clinicians (Veterans Health Administration, or VA). Methods: We evaluated Fee-for-Service (FFS) Medicare and VA data from FY 2010-2014 for the population of veteran cancer decedents who died from solid tumor, as assessed by National Death Index data (n = 97,955). Burdensome transitions were defined as ED visits or hospital admission in the last 6 months of life. Veterans were allocated to the system (i.e., Medicare, VA) in which they received the most overall healthcare. We modeled outcomes using hierarchical logistic regression, with month nested within patient. Models adjusted for variables previously shown to influence veteran selection into Medicare versus VA, comorbidity burden, and time trends. Results: In adjusted analyses, veterans treated by Medicare were significantly more likely to experience an ED visit in the last 6 months of life compared to veterans treated by VA (aOR = 1.37, 95% CI 1.26-1.49, p < 0.001). Adjusted analyses also revealed veterans treated by Medicare were significantly more likely to experience a hospital stay in the last 6 months of life compared to veterans treated by VA (aOR 1.28, 95% CI 1.17-1.40, p < 0.001). Conclusions: Patients dying of metastatic solid tumor who were treated under FFS Medicare were more likely to have ED visits or hospital stays in the last six months of life those treated by VA. As VA shifts more towards purchasing care in the community for its veterans, they may be at greater risk of experiencing burdensome transitions in the last months of life.[Table: see text]
A review of oncologic therapeutic phase III clinical trial literature: Exploring the reporting of clinical trial data of older patients with cancer.
Authors: BrintzenhofeSzoc Karlynn , Shahrokni Armin , Canin Beverly E. , Parker Ira Russell , Krok-Schoen Jessica L. , Koll Thuy , MacKenzie Amy R. , Lund Jennifer Leigh , Hsu Christine D , Pan Kathy , Vankina Ritika
Published: September 2018

70

Background: With demographic shifts leading to an aging cancer population, the American Society of Clinical Oncology (ASCO) has recommended that journal editors improve the reporting of clinical trial data specific to older adults. This study aimed to assess the current reporting status of clinical trial data regarding older adults with cancer. Methods: This was a review of oncologic therapeutic phase-3 clinical trial data published from 07/01/2016-06/30/2017. Based on a keyword search of EMBASE and PubMed, 929 manuscripts were identified. Removing duplicates (n = 116) and articles that did not meet this study’s cancer inclusion criteria (n = 589), a total of 224 were identified. In the pilot phase there was 85% agreement among the reviewers. Results: Thus far, 197 papers (88%), have been independently reviewed with 118 evaluated by more than one reviewer. Reviewed papers were published in 57 journals including Journal of Clinical Oncology (28, 14.2%), Lancet Oncology (25, 12.7%), and NEJM (20, 10.2%). Much of the literature focused upon the following cancer sites: Breast (33, 16.7%), Lung (27, 13.7%), Colorectal (18, 9.1%), and Prostate (12, 6.1%). 175 articles included inclusion/exclusion criteria, 32 (16.2%) had upper age exclusion criteria. Age was presented in 184 articles and data was stratified by age in 84 (42.6%). Age stratification of effectiveness and toxicity were presented in the results section in 65 (38.2%) and 21 (14.4%). Effectiveness by age was in the discussion section in 37 (18.8%) and toxicity by age in 16 (8.1%). Reviewers could not determine the proportion of study participants who were older adults in 111 articles (56.2%). In the remainder of the articles, the proportion ranged from 0% to 81%, except one in which all participants were older adults. Conclusions: A slim minority of phase-3 oncologic clinical trials included and discussed age-referenced results regarding the effectiveness and toxicity of treatments in older adults. Clinical investigators and journal editors should consider the ASCO recommendation and increase the reporting of oncologic clinical trial data specific to older adults.
Using ASCO QOPI and the QTP as an improvement model in a small safety net cancer center.
Authors: Simmons Crystal , Power Steve
Published: September 2018

78

Background: Organizational change is challenging in a well-resourced large academic cancer center. Such challenges are greater in a resource-constrained safety net cancer center. This project sought to learn how the combination of ASCO QOPI data submission and the Quality Training Program (QTP) could assist JPS with implementing a quality improvement project. Methods: The results from QOPI data submissions for Fall 2016 and Spring 2017 indicated opportunity in the area of oral chemotherapy education. This was prioritized due to increasing use of oral chemotherapy and relatively poor adherence data nationally 1,2. The team recognized the relatively low sample size in the QOPI results and supplemented the data with additional abstraction to validate the original hypothesis. Following the structure provided by the QTP enabled JPS to focus its limited resources on understanding the existing process and formally interrogating it to determine the key causes of the problem. Additional information was obtained from the provider team via the use of an online survey. The team found that no single intervention would achieve the goals of improving the metric to above the QOPI mean they implemented small changes over time. These included reducing variation in ordering processes by defaulting to an electronic method; adding the Via oral chemotherapy protocols to the EMR; and developing and deploying a pre-chemotherapy checklist. The team learned that continual reinforcement and inquiry was necessary to ensure the effectiveness of some interventions. Results: Post-implementation results revealed improvements beyond the targeted measure. Approaching the problem systematically and methodically deploying solutions, the team observed improvements in multiple related oral chemotherapy QOPI measures. Conclusions: Meaningful change can result from the ASCO QOPI data and QTP combination in a safety net cancer center. Projects need to start small and remain focused. Challenges to implementing QI in a resource limited environment remain; however, these can be addressed with a methodical approach and strong support from leadership.
Opportunities for improving cancer care management through primary care-oncology relationships.
Authors: Tsui Jennifer , Howard Jenna , Miller William L. , O'Malley Denalee M. , Hudson Shawna V. , Rubinstein Ellen , Bator Alicja , Crabtree Benjamin F
Published: September 2018

80

Background: Improvements in the management of care transitions between primary care and oncology are critical for achieving optimal care quality and outcomes for cancer patients and survivors. We examine relationships between innovative PC practices and oncologists to inform and strengthen PC-oncology interfaces in diverse healthcare settings. Methods: Comparative case studies of 14 innovative PC practices throughout the United States examined strategies for providing cancer survivorship care. Field researchers observed each practice for 10-12 days, recording fieldnotes and conducting key informant and formal, semi-structured interviews with clinicians and staff. We extracted all data related to PC-oncology relationships and then collaboratively identified patterns to characterize these relationships through an inductive “immersion/crystallization” analysis process. Results: Nine of the 14 practices discussed either formal or informal PC-oncology relationships. Nearly all practices with existing formal PC-oncology relationships were embedded within healthcare systems. Private, independent practices had more informal relationships between individual PC physicians and specific oncologists. Practices with formal relationships noted ease of communication and transfer of patient information, timeliness in patient referrals, and direct access to oncologists; while practices with informal relationships noted the benefits of having close engagement with specific oncologists. Regardless of relationship type, remaining challenges include lack of clarity about roles during cancer treatment and beyond. Conclusions: With the rapid transformation of U.S. healthcare towards system ownership of primary care practices, efforts are needed to integrate the strengths of both formal and informal PC-oncology relationships to improve care for cancer patients and survivors.
Valued outcomes in the cancer experience: Patient priorities and control.
Authors: Zaleta Alexandra Katherine , McManus Shauna , Miller Melissa F , Yuen Eva , Stein Kevin , Hurley Karen , Shockney Lillie D. , Goldberger Sara , Golant Mitch , Buzaglo Joanne S.
Published: September 2018

84

Background: In the era of value-based cancer care, identifying what is important to cancer survivors, and their perceived control over these experiences, can inform shared decision-making and support quality care. We examined cancer patient priorities and control to guide the development of a new measure of patient value, Valued Outcomes in the Cancer Experience (VOICE). Methods: 459 cancer patients completed an online survey and rated level of importance and control over 54 value items (0 = not at all; 4 = very much). Items of most and least importance, items with most and least control, and rating discrepancies (importance-control) were identified. Bivariate associations with socio-demographics were examined. Results: Participants were 86% non-Hispanic White; mean age = 60 years, SD= 10; 38% breast cancer, 18% blood, 9% lung, 9% prostate; mean time since diagnosis = 6.5 years, SD= 6; 22% metastatic. Items of highest importance (quite a bit to very much) included, “Having your health care team (HCT) talk to you in a way that makes sense to you” (99% of participants); “Making decisions for yourself” (99%); “Talking honestly with your HCT about your illness” (99%). Participants reported the most control over, “Talking honestly with your HCT about your illness” (89%); “Making decisions for yourself” (88%), “Understanding your illness” (84%). Greatest discrepancies were, “Having your illness not get worse or come back” (96% Important; 27% Control); “Having energy to do things that are important to you (98% Important; 41% Control); “Being able to afford medical expenses” (96% Important; 49% Control); “Having a death free from suffering” (91% Important; 40% Control); “Having your medical providers communicate with each other about your care” (94% Important; 44% Control). Greater importance/control discrepancies were associated with lower income, unemployment due to disability, and poorer health ( ps < .05). Conclusions: Cancer patients experience notable discrepancies between personal priorities and their ability to control these experiences, suggesting key areas for intervention and support. Next steps include psychometric assessment to refine the VOICE scale to guide clinical and research efforts to improve patient care outcomes.
Understanding the value of clinical survivorship programs.
Authors: Gilmore Katherine Ramsey , Palos Guadalupe R. , Chapman Patricia , Lewis-Patterson Paula A. , Rodriguez Maria Alma
Published: September 2018

86

Background: Various models of care exist for the growing number of cancer survivors; yet little is known about the value or the difference in the models’ costs. We sought to assess the professional billing and reimbursements of 2 models of survivorship care; a) oncologist-led and b) advanced practice providers (APPs). Methods: Data were collected from 6 disease specific survivorship clinics, genitourinary, gynecology, head and neck, lymphoma, melanoma, and thyroid. Billing data was obtained to determine the professional billing and reimbursement amounts for these visits over one fiscal year. Comparisons were made between the APP and oncologists average salaries to determine costs per model. Clinic FTE salaries were based on the amount of time an APP devoted to a survivorship activities with 33% fringe benefits added to salaries. Oncologists’ salaries were based on the annual average faculty salary by department including fringe. Results: Billing data of 4,255 outpatient survivorship visits across the six clinics from 09/1/2016 - 8/31/2017 were abstracted. Table 1 summarizes the percentage (%) of professional reimbursement by model of care, oncologist versus APP and survivorship clinic. Conclusions: These data indicate that the advanced practice providers' model of survivorship care was financially more efficient than the oncologist model. Further research is warranted to compare the clinical effectiveness of these models and their impact on patients' outcomes related to their quality of life and satisfaction with care.[Table: see text]
Imaging progression-free survival: How much does it matter to patients?
Authors: O'Donnell Jennifer , Robinson Andrew George , Booth Christopher M. , Koven Rachel , Eisenhauer Elizabeth A. , Brundage Michael Donald
Published: September 2018

99

Background: Progression-free survival (PFS) is often used as a clinical trials outcome for evaluating new therapies for solid tumors. While PFS is a validated surrogate for overall survival (OS) or quality of life (QOL) in some settings, it is increasingly used in contexts where surrogacy is not established. The end point is a composite of survival, symptomatic progression, and imaging-only progression. The intrinsic value of asymptomatic (imaging-only) progression from the patient perspective is not known. Methods: Patients with advanced metastatic cancer (lung, colorectal, or ovarian) who had completed at least 3 months of chemotherapy and were attending a routine ambulatory clinic were recruited and participated in a structured discrete choice trade-off exercise. The interview guide and visual aids were developed by a multidisciplinary team including patient representatives. Participants were provided with a hypothetical clinical scenario and associated treatment options. Treatment options presented had the same OS time but longer time to imaging progression and were associated with various levels of toxicity and treatment time. A sliding scale was used for duration of imaging-only PFS to determine each patient’s willingness to trade longer time for a given level of toxicity. Results: 20 (11M, 9F) patients participated in interviews (Nov 2017 - Jun 2018). Given the scenario 85% (n = 17) of patients chose treatment with less toxicity and treatment duration even if associated with a shorter imaging-only PFS. Two patients chose a trade-off for a more toxic treatment with an increase in imaging PFS by 18 months and 24 months respectively. One patient chose to always opt for most aggressive treatment irrespective of PFS benefit and toxicity. Conclusions: Patients with metastatic cancer currently being treated with palliative chemotherapy overwhelmingly considered imaging-only PFS to be of low value when it was associated with increased toxicity but not with longer OS. In situations where surrogacy for OS and QOL has not been established, endpoints that de-emphasise the importance of imaging are required.
Transmitting the Memory of a Medieval Heretic
Authors: Dubois Danielle C.
Published: September 2018

Modern scholars have assumed that after Marguerite Porete was condemned for heresy in 1310 she disappeared from the historical record. However, the discovery of references to Porete in François de Belleforest's Grandes annales (1579) and Henri de Sponde's Annales ecclesiastici (1641) overturns this narrative and shows that these historians were responsible for reintroducing her story to the French public. Porete offered a powerful symbol that bolstered their vision of religion and state history, a vision that emphasized the purity of the Gallican Church and the role of the state in preserving its integrity in the face of heresy. Their shaping of the memory of Porete as a heretical Beguine expands our knowledge of book history, early modern research practices, and the dissemination of historical knowledge.

On a longtemps supposé qu'après sa condamnation pour hérésie en 1310, Marguerite Porete avait disparu de l'histoire. Cependant, la découverte de références à Porete dans les Grandes annales de François de Belleforest (1579) et les Annales ecclesiastici de Henri de Sponde (1641) dément cette hypothèse et montre que ces historiens ont réintroduit son histoire au public français. Marguerite Porete constituait un puissant symbole pour leur vision de l'histoire religieuse et étatique qui renforçait l'importance de la pureté de l'Eglise gallicane, ainsi que le rôle que devait assumer l'Etat pour maintenir l'intégrité de l'Eglise face aux hérésies. Leur façonnage de la mémoire de Porete en tant que béguine hérétique jette la lumière sur l'histoire du livre, les pratiques de recherche à l'époque de la Renaissance, ainsi que la diffusion de connaissances historiques.
Plasma membrane damage caused by Listeriolysin O is not repaired through endocytosis of the membrane pore
Authors: Skalman Lars Nygård , Holst Mikkel R. , Larsson Elin , Lundmark Richard
Published: September 2018

Endocytic mechanisms have been suggested to be important for plasma membrane repair in response to pore-forming toxins such as Listeriolysin O (LLO), which form membrane pores that disrupts cellular homeostasis. Yet, little is known about the specific role of distinct endocytic machineries in this process. Here, we have addressed the importance of key endocytic pathways, and developed reporter systems for real-time imaging of the endocytic response to LLO pore formation. We found that loss of clathrin-independent endocytic pathways negatively influenced the efficiency of membrane repair. However, we did not detect any increased activity of these pathways, or co-localisation with the toxin or markers of membrane repair, suggesting that they were not directly involved in removal of LLO pores from the plasma membrane. In fact, markers of clathrin-independent carriers (CLICs) were rapidly disassembled in the acute phase of membrane damage due to Ca2+ influx, followed by a reassembly about 2 min after pore formation. We propose that these endocytic mechanisms might influence membrane repair by regulating the plasma membrane composition and tension, but not via direct internalisation of LLO pores.
A nonalcoholic fatty liver disease model in human induced pluripotent stem cell-derived hepatocytes, created by endoplasmic reticulum stress-induced steatosis
Authors: Parafati Maddalena , Kirby R. Jason , Khorasanizadeh Sepideh , Rastinejad Fraydoon , Malany Siobhan
Published: September 2018

Hepatic steatosis, a reversible state of metabolic dysregulation, can promote the onset of nonalcoholic steatohepatitis (NASH), and its transition is thought to be critical in disease evolution. The association between endoplasmic reticulum (ER) stress response and hepatocyte metabolism disorders prompted us to characterize ER stress-induced hepatic metabolic dysfunction in human induced pluripotent stem cell-derived hepatocytes (hiPSC-Hep), to explore regulatory pathways and validate a phenotypic in vitro model for progression of liver steatosis. We treated hiPSC-Hep with a ratio of unsaturated and saturated fatty acids in the presence of an inducer of ER stress to synergistically promote triglyceride accumulation and dysregulate lipid metabolism. We monitored lipid accumulation by high-content imaging and measured gene regulation by RNA sequencing and reverse transcription quantitative PCR analyses. Our results show that ER stress potentiated intracellular lipid accumulation by 5-fold in hiPSC-Hep in the absence of apoptosis. Transcriptome pathway analysis identified ER stress pathways as the most significantly dysregulated of all pathways affected. Obeticholic acid dose dependently inhibited lipid accumulation and modulated gene expression downstream of the farnesoid X receptor. We were able to identify modulation of hepatic markers and gene pathways known to be involved in steatosis and nonalcoholic fatty liver disease (NAFLD), in support of a hiPSC-Hep disease model that is relevant to clinical data for human NASH. Our results show that the model can serve as a translational discovery platform for the understanding of molecular pathways involved in NAFLD, and can facilitate the identification of novel therapeutic molecules based on high-throughput screening strategies.
Modeling the effect of ascites-induced compression on ovarian cancer multicellular aggregates
Authors: Klymenko Yuliya , Wates Rebecca B. , Weiss-Bilka Holly , Lombard Rachel , Liu Yueying , Campbell Leigh , Kim Oleg , Wagner Diane , Ravosa Matthew J. , Stack M. Sharon
Published: September 2018

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. EOC dissemination is predominantly via direct extension of cells and multicellular aggregates (MCAs) into the peritoneal cavity, which adhere to and induce retraction of peritoneal mesothelium and proliferate in the submesothelial matrix to generate metastatic lesions. Metastasis is facilitated by the accumulation of malignant ascites (500 ml to >2 l), resulting in physical discomfort and abdominal distension, and leading to poor prognosis. Although intraperitoneal fluid pressure is normally subatmospheric, an average intraperitoneal pressure of 30 cmH2O (22.1 mmHg) has been reported in women with EOC. In this study, to enable experimental evaluation of the impact of high intraperitoneal pressure on EOC progression, two new in vitro model systems were developed. Initial experiments evaluated EOC MCAs in pressure vessels connected to an Instron to apply short-term compressive force. A Flexcell Compression Plus system was then used to enable longer-term compression of MCAs in custom-designed hydrogel carriers. Results show changes in the expression of genes related to epithelial-mesenchymal transition as well as altered dispersal of compressed MCAs on collagen gels. These new model systems have utility for future analyses of compression-induced mechanotransduction and the resulting impact on cellular responses related to intraperitoneal metastatic dissemination.

This article has an associated First Person interview with the first authors of the paper.
A transgenic minipig model of Huntington's disease shows early signs of behavioral and molecular pathologies
Authors: Askeland Georgina , Rodinova Marie , Štufková Hana , Dosoudilova Zaneta , Baxa Monika , Smatlikova Petra , Bohuslavova Bozena , Klempir Jiri , Nguyen The Duong , Kuśnierczyk Anna , Bjørås Magnar , Klungland Arne , Hansikova Hana , Ellederova Zdenka , Eide Lars
Published: September 2018

Huntington's disease (HD) is a monogenic, progressive, neurodegenerative disorder with currently no available treatment. The Libechov transgenic minipig model for HD (TgHD) displays neuroanatomical similarities to humans and exhibits slow disease progression, and is therefore more powerful than available mouse models for the development of therapy. The phenotypic characterization of this model is still ongoing, and it is essential to validate biomarkers to monitor disease progression and intervention. In this study, the behavioral phenotype (cognitive, motor and behavior) of the TgHD model was assessed, along with biomarkers for mitochondrial capacity, oxidative stress, DNA integrity and DNA repair at different ages (24, 36 and 48 months), and compared with age-matched controls. The TgHD minipigs showed progressive accumulation of the mutant huntingtin (mHTT) fragment in brain tissue and exhibited locomotor functional decline at 48 months. Interestingly, this neuropathology progressed without any significant age-dependent changes in any of the other biomarkers assessed. Rather, we observed genotype-specific effects on mitochondrial DNA (mtDNA) damage, mtDNA copy number, 8-oxoguanine DNA glycosylase activity and global level of the epigenetic marker 5-methylcytosine that we believe is indicative of a metabolic alteration that manifests in progressive neuropathology. Peripheral blood mononuclear cells (PBMCs) were relatively spared in the TgHD minipig, probably due to the lack of detectable mHTT. Our data demonstrate that neuropathology in the TgHD model has an age of onset of 48 months, and that oxidative damage and electron transport chain impairment represent later states of the disease that are not optimal for assessing interventions.

This article has an associated First Person interview with the first author of the paper.
Mesoporous Metal Catalysts Templated on Clay Nanotubes
Authors: Glotov Aleksandr , Stavitskaya Anna , Chudakov Yaroslav , Ivanov Evgenii , Huang Wei , Vinokurov Vladimir , Zolotukhina Anna , Maximov Anton , Karakhanov Eduard , Lvov Yuri
Published: September 2018

Halloysite is a natural tubular aluminosilicate clay of ca. 50 nm diameter and 0.5–1.5 micrometers in length. The nanoarchitectural modification of halloysite inner/outer surfaces can be achieved through supramolecular and covalent interactions exploiting its different inside/outside chemistry (Al2O3/SiO2). The tubular morphology makes halloysite a prospective nanotemplate for core-shell structured mesoporous catalysts. Catalytic metals can be incorporated on the nanotubes’ outer surface or in the inner lumens with selective metal binding. 2–5 nm diameter Au, Ag, Pt, Pd, Co, Ru, Cu-Ni, Fe2O3, CoxBy, CdS, and CdxZn1−xS particles were templated on halloysite. In this work, CdS and Ru-containing halloysite based nanocatalysts were synthesized via modification with organic ligands and microwave-assisted wetness ion impregnation. The catalytic hydrogenation of benzene and its homologues as well as phenol was performed. The impacts of the core-shell architecture, the metal particle size and seeding density were optimized for high reaction efficiency. An efficient Co-halloysite catalyst was formed using azines as ligands, and it contained 16 wt. % of cobalt with hydrogen evolution rate of 3.0 L/min × g(cat). The mesocatalysts produced are based on a safe and cheap natural clay nanomaterial and may be scaled-up for industrial applications.
Synthesis and Photophysical and Electrochemical Properties of Structural Isomers of Pyrazine-Based D-π-A-π-D Fluorescent Dyes
Authors: Enoki Toshiaki , Ohshita Joji , Ooyama Yousuke
Published: September 2018

The structural isomers of D-π-A-π-D fluorescent dyes 2,5-PD and 2,6-PD which are substituted with two diphenylamine-thienylcarbazole moieties (electron-donating and π-conjugated unit) on 2,5- and 2,6-positions of a pyrazine ring (electron-withdrawing unit) have been developed. It was found that the structural isomers 2,5-PD and 2,6-PD show a significant solvatofluorochromism (λem = 513–614 and 480–588 nm for 2,5-PD and 2,6-PD, respectively). The photophysical and electrochemical measurements, and density functional theory calculations reveal that 2,5-substituted pyrazine dye 2,5-PD possesses stronger photoabsorption and fluorescence properties in a longer wavelength region and at a lower LUMO energy level, compared to the 2,6-substituted structural isomer 2,6-PD.
Nanoporous CeO2 Supports Prepared from Amorphous Alloys: Enhanced Catalytic Performance for Hydrogen Generation from Formic Acid
Authors: Nozaki Ai , Yamashita Ayane , Fujiwara Ryosuke , Ueda Chiyako , Yamamoto Hiroaki , Morishita Masao
Published: September 2018

Nanoporous CeO2 samples as supports were prepared by chemical dealloying Ce-Al amorphous alloy, followed by synthesis of Au-Pd/CeO2 catalysts. The synthesized Au-Pd/CeO2 catalysts showed higher catalytic activity for hydrogen generation from formic acid than catalysts using supports prepared from a crystalline alloy precursor.
Social Networks as Contract Enforcement: Evidence from a Lab Experiment in the Field
Authors: Chandrasekhar Arun G. , Kinnan Cynthia , Larreguy Horacio
Published: September 2018

Lack of well-functioning formal institutions leads to reliance on social networks to enforce informal contracts. Social proximity and network centrality may affect cooperation. To assess the extent to which networks substitute for enforcement, we conducted high-stakes games across 34 Indian villages. We randomized subjects’ partners and whether contracts were enforced to estimate how partners’ relative network position differentially matters across contracting environments. While socially close pairs cooperate even without enforcement, distant pairs do not. Individuals with more central partners behave more cooperatively without enforcement. Capacity for cooperation in the absence of contract enforcement therefore depends on the subjects’ network position. (JEL C93, D86, K12, O15, O17, Z13)
Does Electoral Competition Curb Party Favoritism?
Authors: Curto-Grau Marta , Solé-Ollé Albert , Sorribas-Navarro Pilar
Published: September 2018

We study whether incumbents facing uncontested elections channel public spending toward co–partisan officials more than is the case of incumbents that are worried about reelection. We draw on data on capital transfers allocated by Spanish regions to local governments during 1995–2007. Using a regression discontinuity design, we document strong and robust effects. We find that a mayor belonging to the party of the regional president obtains twice the amount in grants received by an opposition’s mayor. This effect is much greater for regional incumbents that won the previous election by a large margin, but it disappears for highly competitive elections. (JEL D72, H76)
Foreign Rivals Are Coming to Town: Responding to the Threat of Foreign Multinational Entry
Authors: Bao Cathy Ge , Chen Maggie Xiaoyang
Published: September 2018

How do domestic firms respond to the threat of foreign competition? This paper quantifies foreign competition threats by exploiting news of potential multinational investments from over 35,000 media outlets around the world. Using firm–specific measures of foreign competition threat, the analysis shows that domestic firms respond by upgrading productivity, raising innovation, and altering product composition. However, there is a U–shape relationship between initial productivity and productivity growth where the right and left tails upgrade productivity through innovation and product dropping, respectively. These responses constitute an economically important source of gains and convey new implications for the timing of economic policies. (JEL D24, F23, L25, L82, O30)
ДИСКУРСИВНЫЕ РЕПРЕЗЕНТАЦИИ «ЦИФРОВОГО ПОКОЛЕНИЯ» И СМЕНА ПАРАДИГМЫ ОБРАЗОВАНИЯ
Authors: Sheypak Svetlana Alexandrovna
Published: September 2018

В статье проводится анализ функционирования в современном российском образовательном дискурсе сформировавшейся в начале 2000-х гг. и ставшей устойчивой, несмотря на ее критику, тенденции описывать взаимоотношения субъектов образовательного процесса в терминах «цифрового поколения», «цифровых аборигенов» и «цифровых иммигрантов». Анализ репрезентаций «цифрового поколения» демонстрирует использование в риторике конфликта между учащимися и преподавателями постколониальных и маркетинговых дискурсивных практик. Показано, как эти репрезентации используются в образовательном дискурсе для обоснования смены парадигмы образования для «цифрового поколения». Однако сопоставление дискурсивных репрезентаций «цифрового поколения» с социальными практиками, в которых реализуется цифровая компетентность современных пользователей доказывает необоснованность этих репрезентаций и их негативное влияние на завышенную самооценку и невысокую мотивацию подростков при формировании цифровой компетентности. В заключении обосновывается необходимость разработки новой парадигмы образования в результате исследований, выявляющих реальный уровень цифровой компетентности учащихся и сопоставляющих его с академическими и профессиональными требованиями, предъявляемыми к развитию цифровой компетентности.Цель. В статье рассматривается обоснованность смены парадигмы образования на основе дискурсивных репрезентаций «цифрового поколения».Метод или методология проведения работы. Методы критического дискурс-анализа позволяют сопоставить дискурсивные репрезентации «цифрового поколения» в научном и медийном образовательном дискурсе и социальные практики, выявленные в результате эмпирических исследований, посвященных описанию цифровой компетентности современных интернет-пользователей. По ключевым словам «аборигены», «иммигранты», «цифровое поколение» были отобраны для анализа репрезентации отношений учащихся и преподавателей, воспроизводящиеся в 2014–2017 гг. в медийном и научном дискурсах.Результаты. Выявлены противоречия между репрезентациями «цифрового поколения» в научных и медийных дискурсивных практиках и реальным уровнем его цифровой компетентности.Область применения результатов. Результаты исследования обосновывают необходимость развития эмпирических и теоретических исследований социальных практик, в которых реализуется цифровая компетентность субъектов образовательного процесса, как основы для разработки новой парадигмы образования в условиях цифровой коммуникации.
СРЕДА КАК ФАКТОР ПРОФЕССИОНАЛЬНОГО СТАНОВЛЕНИЯ СТУДЕНТА
Authors: Voyko Roman Aleksandrovich
Published: September 2018

Цель: На основе анализа научной литературы раскрывающей вопросы профессионального становления студентов в высшей школе обосновать возможность рассмотрения среды как фактора и средства профессионального становления студента в высшей школе в логике средового подхода в образовании.Метод или методология проведения работы: Теоретический анализ психолого-педагогической, социологической и философской литературы, мысленное моделирование.Результаты: Представлена и обоснована логика рассмотрения среды как фактора профессионального становления студента вышей школы с позиций средового подхода в образовании.Область применения результатов: Система высшего образования.
THE APPLICATION OF AHP METHOD FOR SUPPLIER SELECTION OF BANGLADESH’S JUTE INDUSTRY: FROM THE PERSPECTIVE OF BOTH PUBLIC AND PRIVATE SECTORS
Authors: Rahman Mustafizur , Haldar Shuvo
Published: September 2018

In the competitive global business market, selection of the best supplier plays a vital role for the survival of any manufacturing company. The selection of a good supplier can make it possible for a company to reach the top position in the market. On the other side, the selection of a poor supplier can lead a company to a lower market position or even shutdown. As a developing country, Bangladesh has many very small and extremely large manufacturing companies where supplier selection is not seriously considered. These companies are selecting suppliers in the traditional way by giving priority to cost and quality, which acts as an impediment to their development. In this paper, the Analytic Hierarchy Process (AHP) method is applied in order to find the best supplier for the jute industry in Bangladesh. The study compares the application process of the method from both the public and private sector perspectives. For this purpose, the data are collected from a government factory named “Jessore Jute Industries Ltd” and a private factory named “Ahyan Jute Mills” and their present strategies are compared. This paper recommends to these jute industries that the use of the AHP method in selecting the best supplier can be effective and efficient.
WAREHOUSE RISK ASSESSMENT USING INTERVAL VALUED INTUITIONISTIC FUZZY AHP
Authors: Cebi Selcuk , Ilbahar Esra
Published: September 2018

Warehouses are essential components of a supply chain management system. Any malfunction in warehouses may have an important effect on the subsequent operations of a firm. For example, an accident that occurs in a warehouse can damage the operations of the company as well as the health of the employees. In this paper, critical operations at a warehouse are considered in terms of occupational health and safety. The originality of the paper is that the proposed approach provides a new perspective on warehouse risk assessment. It is the first time a method involving interval valued intuitionistic fuzzy Analytical Hierarchy Process (IVIF-AHP) and a new risk assessment table is utilized to evaluate and categorize the risks in warehouses. As a result of the proposed risk assessment method, hazards in warehouses are categorized as insignificant, marginal, or catastrophic.
Dental prevention in children with cleft deformities
Authors: Kalra Aneesh , Bhujel Nabina , Vaidyanathan Mina
Published: September 2018

Children born with a cleft lip and/or palate are at increased risk of experiencing dental problems compared with the population without clefts. 1 This article explores the amount of preventive dental advice parents receive for their children with cleft lip and/or palate by healthcare professionals and whether there is a need to focus more on preventive measures.
Whistle-Blowing as a Form of Digital Resistance: State Crimes and Crimes Against the State
Authors: Colvin Naomi
Published: September 2018

Whistle-blowing has always been an important vector of resistance to state crimes, and technology has produced a new generation of digitally mediated truthtelling, which is novel in its provision of source material, its systemic critique and the breadth of its impact. International standards and national legal frameworks increasingly acknowledge the importance of whistle-blowers, but those whose disclosures challenge the state are often excluded from emerging standards of protection. The repercussions for those excluded include restrictions on freedom of expression pursued through the courts and the rhetorical framing of truthtelling as a crime against the state. Ultimately, if whistle-blowers' revelations about state crimes are to hit home, their status as human rights defenders needs to be asserted.
The Syrian Archive: A Methodological Case Study of Open-Source Investigation of State Crime Using Video Evidence from Social Media Platforms
Authors: Deutch Jeff , Habal Hadi
Published: September 2018

This article begins with the underlying assumption that data and the designing of informational infrastructure is not neutral; rather, that the acts of tagging, indexing, aggregating and defining of data and data categories are inherently political acts. How and whether information is collected, archived, categorized, and eventually published are further political choices that necessitate critical review, rather than being taken at face value. Taking a self-reflective approach, the objective of this article is to develop a methodological understanding of online-based open-source human rights investigations, with a particular focus on the Syrian Archive. This article aims to align with the work of other scholars investigating the new field of online open-source intelligence and big data analysis, particularly that by human rights organizations, as well as with scholars in the field of data ethics, digital rights and privacy, statactivism, and science and technology studies. Providing empirical and qualitative evidence on the potential of online-based open-source data collection in this context will address a crucial gap in the current literature.