bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II trial of nivolumab (nivo) plus ipilimumab (ipi) in patients with SMARCB1-deficient kidney malignancies.
Authors: Msaouel Pavlos , Slack-Tidwell Rebecca , Tannir Nizar M.
Published: March 2019

TPS677

Background: The potent tumor suppressor SMARCB1 (also known as INI-1, hSNF5, or BAF47) is inactivated in all cases of renal medullary carcinoma (RMC) and renal cell carcinoma unclassified with medullary phenotype (RCCU-MP), as well as most malignant rhabdoid tumors (MRT) of the kidney. Although rare, these kidney malignancies are highly lethal and often occur in young patients. The role of immune checkpoint inhibitor therapy remains to be prospectively defined in tumors harboring SMARCB1 defects. Although a case report noted efficacy of single-agent Nivo in a patient with RMC (Beckermann et al J Immunother Cancer, 2017), there were no durable responses in subsequent cases (Sodji et al. J Immunother Cancer, 2017). We hypothesize that the combination of anti-PD1 (Nivo) with anti-CTLA4 (Ipi) immune checkpoint inhibitor therapy will lead to more potent antitumor responses compared to those reported with single-agent Nivo. Methods: This single-arm phase II trial will test the efficacy of Nivo + Ipi in up to 30 patients with SMARCB1-negative RMC, RCCU-MP, and adult-onset kidney MRTs. Any number of prior therapies is allowed. Patients will be treated with Ipi 1 mg/kg + Nivo 3 mg/kg every 3 weeks x4 doses followed by maintenance Nivo 480 mg every 4 weeks for up to 2 years. Ongoing monitoring for safety and futility will be implemented per the method of Thall et al. (Stat Med, 1995; 14:357-79) using cohorts of 10 patients each. The primary endpoint is objective response rate (ORR) and the trial objective is to achieve a similar or greater ORR compared with the historical ORR of 29% achieved in our institution using conventional cytotoxic chemotherapies. Secondary endpoints include progression-free survival, overall survival, and disease control rate. To evaluate potential biomarkers for treatment response, correlative analyses will be performed in tumor tissue and peripheral blood samples obtained i) pre- treatment (baseline) up to 6 weeks (42 days) prior to initiation of treatment on Day 1, ii) after completion of the combination therapy (Nivo + Ipi) phase, and iii) upon disease progression. At the time of the abstract submission, 2 patients have been enrolled on this study. Clinical trial information: NCT03274258.
RENAVIV: A randomized phase III, double-blind, placebo-controlled study of pazopanib with or without abexinostat in patients with locally advanced or metastatic renal cell carcinoma.
Authors: Aggarwal Rahul Raj , Thomas Scott , Hauke Ralph J. , Nordquist Luke T. , Munster Pamela N.
Published: March 2019

TPS681

Background: Abexinostat is a pan-histone deacetylase (HDAC) inhibitor that has shown promising activity in prior pre-clinical studies and early phase clinical trials. A phase 1b study of pazopanib plus abexinostat (Aggarwal et al. J Clin Oncol 2017) demonstrated strikingly durable responses in patients (pts) with clear cell renal cell carcinoma (RCC), including one patient with previously refractory disease with ongoing response for > 5 years’ duration. Induction of histone acetylation in peripheral blood mononuclear cells (PBMCs) was associated with durable treatment response. We hypothesize that the addition of abexinostat to pazopanib will significantly improve outcomes in patients with clear cell RCC. Methods: RENAVIV is a global, randomized, double-blind, placebo-controlled, two arm phase 3 study of pazopanib plus abexinostat versus pazopanib plus placebo, in pts with locally advanced or metastatic RCC with clear cell component. Up to one prior line of immunotherapy is allowed. Prior VEGF-targeting tyrosine kinase inhibitor treatment is prohibited. Stratification factors include: 1) Prior immunotherapy (yes/no) and 2) prognostic group (good, intermediate, poor). Pts randomized to pazopanib + placebo have the option of crossing over to receive pazopanib plus abexinostat at the time of disease progression. The primary endpoint is PFS by independent review committee. Secondary endpoints include PFS by investigator assessment, overall survival, safety, objective response rate (ORR), duration of response, patient-reported quality of life, and outcomes in cross-over population. Planned correlative studies include association between histone acetylation and HDAC expression in PBMCs with clinical outcomes. The total planned accrual is 413 pts, estimated to provide 90% power to detect a hazard ratio of 0.67 in the comparison of PFS between experimental versus control arms, with an overall two-sided type I error rate of 0.025. A pre-specified minimum of 50% of patients are required to have received prior immunotherapy. The first patient was enrolled in October 2018. Clinical trial information: NCT03592472.
Phase Ib (COSMIC-021) trial of cabozantinib (C) in urothelial carcinoma (UC) or C in combination with atezolizumab (A) in patients (pts) with UC, castrate resistant prostate cancer (CRPC) or renal cell carcinoma (RCC).
Authors: Pal Sumanta K. , Vaishampayan Ulka N. , Castellano Daniel E. , Necchi Andrea , Van Herpen Carla M.L.- , Ramsingh Giridharan , Loriot Yohann , Agarwal Neeraj
Published: March 2019

TPS683

Background: C is an inhibitor of tyrosine kinases involved in tumor growth, angiogenesis, and immune regulation, including MET, VEGFR, and TAM kinases (Tyro3, AXL, MER). Preclinical and clinical studies suggest that C promotes an immune-permissive tumor environment which may enhance response to immune checkpoint inhibitors (ICI) such as the anti-PD-L1 mAb, A. C is approved for pts with advanced RCC and has shown encouraging clinical activity in combination with a PD-1 targeting mAb in RCC, UC, and CRPC (Nadal et al 2017). A is approved for pts with advanced UC after prior platinum-containing chemo and for chemo-naïve pts with platinum ineligible UC or PD-L1+ cisplatin ineligible UC. Combination of C with A may enhance treatment efficacy in pts with genitourinary (GU) cancers. Here, we present the study design of an ongoing phase 1b trial of C + A which includes cohorts with advanced RCC, UC, and CRPC. Methods: This global multicenter, phase 1b, open-label trial will assess the safety, tolerability, activity, and pharmacokinetics of C or C + A (NCT03170960). The study comprises a dose-escalation stage and an expansion stage. The dose-escalation stage (3+3 design) is completed. C 40 mg qd + 1200 mg A q3w is the recommended dose for the expansion stage. In the expansion stage, 18 cohorts (each 30 pts) will be enrolled including 7 cohorts with GU cancers: (1) treatment naïve clear cell RCC; (2) non-clear cell RCC, treatment naïve or following systemic anticancer therapy; (3) UC after prior platinum-based therapy; (4) treatment naïve cisplatin-ineligible UC; (5) treatment naïve cisplatin-eligible UC; (6) UC after prior ICI therapy and (7) CRPC after prior enzalutamide and/or abiraterone. In addition, an exploratory cohort (30 pts) will evaluate single agent 60 mg C in pts with UC after prior ICI therapy. Pts will continue treatment as long as they experience clinical benefit per investigator or until unacceptable toxicity. The primary objective of the expansion stage is the objective response rate per RECIST 1.1 per investigator for each cohort. Secondary objectives will assess safety including immune related AEs. Clinical trial information: NCT03170960.
PROSPER: A phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients with localized renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN 8143).
Authors: Harshman Lauren Christine , Puligandla Maneka , Haas Naomi B. , Allaf Mohamad , Drake Charles G. , McDermott David F. , Signoretti Sabina , Cella David , Gupta Rajan T. , Shuch Brian M. , Choueiri Toni K. , Lara Primo , Kapoor Anil , Heng Daniel Yick Chin , Jewett Michael A.S. , Master Viraj A. , Michaelson M. Dror , Leibovich Bradley C. , Maskens Deb , Carducci Michael Anthony ,   On behalf of the PROSPER RCC Investigators
Published: March 2019

TPS684

Background: The anti-PD-1 antibody nivo improves overall survival in metastatic RCC and is well tolerated. There is no standard adjuvant systemic therapy that increases overall survival (OS) over surgery alone for non-metastatic RCC. Priming the immune system prior to surgery with anti-PD-1 has shown an OS benefit compared to a pure adjuvant approach in mouse solid tumor models. The PROSPER RCC trial aims to improve clinical outcomes by priming the immune system prior to nephrectomy with neoadjuvant nivo and continued engagement with adjuvant blockade in patients with high risk M0 RCC compared to surgery alone. Methods: This global, unblinded, phase 3 National Clinical Trials Network study is currently accruing patients with clinical stage ≥T2 or node positive M0 RCC of any histology. Tumor biopsy prior to randomization is mandatory to ensure RCC and permits in depth correlative science. The investigational arm will receive two doses of nivo 240mg prior to surgery followed by adjuvant nivo for 9 months (q2 wks x 3 mo followed by 480mg q4 wks x 6 mo). The control arm will undergo standard nephrectomy followed by observation. Randomized patients are stratified by clinical T stage, node positivity, and histology. To enhance accrual and patient quality of life, key upcoming amendments are being instituted. These include biopsy only in the nivo arm, allowance of oligometastatic disease and bilateral renal masses that can be fully resected/ablated, and change of nivo dosing to q4 wks (1 neoadj; 9 adj). With accrual of 766 patients, there is 84.2% power to detect a 14.4% absolute benefit in recurrence-free survival (RFS) at 5 years assuming the ASSURE historical control of ~56% to 70% (HR = 0.70). The study is also powered to evaluate a significant increase in overall survival (HR 0.67). Safety, feasibility, and quality of life endpoints critical to adjuvant therapy considerations are incorporated. PROSPER RCC embeds a wealth of translational work aimed at investigating the impact of the baseline immune milieu, the changes induced by neoadjuvant anti-PD-1 priming, and how both correlate with clinical outcomes. Clinical trial information: NCT03055013.
A phase II open-label study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pretreated with one immune-checkpoint inhibitor: The BREAKPOINT trial.
Authors: Verzoni Elena , Bearz Alessandra , De Giorgi Ugo , Nole Franco , Porta Camillo , Ratta Raffaele , Claps Melanie , Pagani Filippo , Martinetti Antonia , Cova Agata , Rivoltini Licia , De Braud Filippo G. , Procopio Giuseppe
Published: March 2019

TPS685

Background: First-line treatment landscape of metastatic renal cell carcinoma (mRCC) is evolving with strong evidence in favour of PD-1/PD-L1 combinations over tyrosine kinase inhibitors (TKIs). No prospective data about efficacy of TKIs post immune-checkpoint inhibitor (CPI) combinations are available. Among TKIs, cabozantinib has demonstrated progression-free survival (PFS) and overall survival (OS) benefit over everolimus in pre-treated mRCC patients (pts). Methods: Overall 49 mRCC pts who received a previous CPI (anti PD-1/PD-L1) will be treated with cabozantinib. Pts will be stratified according to Heng prognostic group, duration of first-line and type of previous therapy received (CPI+CPI or CPI+TKI or CPI+anti-VEGF or CPI monotherapy). Key inclusion criteria include: one previous treatment with a PD-1/PD-L1 inhibitor in first-line and histological diagnosis of clear-cell RCC. The primary endpoint is to assess the efficacy of cabozantinib based on PFS. Secondary endpoints include evaluation of OS, objective response rate and safety profile of the drug. Exploratory endpoints include evaluation of PD-L1 levels by immunohistochemistry in tumor samples; the analysis of the immunological signature/profile of tumor cells; the state of circulating immune cells, as well as the modulating activity of cabozantinib on systemic tumor immunity; the evaluation of bone formation and reabsorption markers in pts with or without bone involvement. Cabozantinib will be administered orally at a dose of 60 mg/day continuously until evidence of disease progression or onset of unacceptable toxicity. Statistical design: By the methodology of Brookmeyer and Crowley, assuming an accrual period of 18 months and a minimum follow-up of 10 months (mos), 49 pts are necessary to detect an increment of the median PFS time from 3.8 mos to 7.4 mos with a power of 90% and one-sided alpha of 5%. The large sample critical value detecting the increment of the PFS median survival time will be 5.54 mos. To date, 2 pts have been enrolled. Clinical trial information: NCT03463681.
Lively Up Your Ontology
Authors: Marks Laura U.
Published: March 2019

This essay brings a process approach to the One-Many problem as treated in Gilles Deleuze’s thought, by focusing on the work of Ṣadr al-Dīn Muhammad al-Shīrāzī (Shiraz, 1571–1640). First acknowledging Avicenna’s concept of the univocity of being (attributed to John Duns Scotus) that influenced Deleuze, this essay examines how later Islamic philosophy, only recently transmitted to the West, provides methods for a lively process-based ontology. It compares Ṣadrā’s process cosmology to those of Gottfried Wilhelm von Leibniz and Alfred North Whitehead and examines his critique of abstraction in light of tashkīk, systematic ambiguity or modulation. The essay argues that Ṣadrā’s influence can make generative contributions to Deleuzean thought in terms of process realism, tashkīk as disjunctive synthesis, immanent causality, singularity, and an optimistic, world-oriented approach. Ṣadrā’s work allows us to rethink the boundary between philosophy and theology, and the essay proposes means to de-transcendentalize religious philosophy, if necessary.
Can a Dog Really Be a Man’s Best Friend?
Authors: Laqueur Thomas , Nehamas Alexander
Published: March 2019

This essay is an exchange between friends and scholars Thomas Laqueur and Alexander Nehamas. Laqueur offers a number of possible answers to the question “Why is a dog a man’s best friend?” as he explicates and analyzes a varied historical record of archaeological evidence, philosophy, art, and literature. Laqueur builds on Aristotle’s conception of friendship as he explores what types of friendships we humans have with dogs and how such relationships may benefit both species. Nehamas responds to Laqueur’s text and Aristotle on philia as he traces the limits of human relationships with dogs as well as human friends.
“A Picture of Peace”
Authors: Sato Courtney
Published: March 2019

During the interwar period, internationalists declared Hawai‘i the “new Geneva” of the Pacific: a locus for regional diplomacy, social reform, and cross-cultural exchange. This article examines the Pan-Pacific Women’s Association (PPWA) as part of the emerging Honolulu-based Pan-Pacific internationalist movement. The PPWA enacted social reform grounded in ideals of antiracism, affective connection, and cross-cultural exchange. The article recuperates “friendship” in two ways: first, as a fundamental tenet of Pacific interwar internationalist praxis, and second, as an analytic attuned to internationalism’s entanglements with empire, race, gender, and sexuality. Despite the PPWA’s progressive antiracist liberal cosmopolitanism, the ideology and practice of international and interracial friendship often consolidated, rather than dismantled, hierarchies of race, nationality, class, gender, and sexuality.
The KRAB-zinc-finger protein ZFP708 mediates epigenetic repression at RMER19B retrotransposons
Authors: Seah Michelle K. Y. , Wang Yaju , Goy Pierre-Alexis , Loh Hui Mun , Peh Wen Jun , Low Diana H. P. , Han Brenda Y. , Wong Esther , Leong Ei Leen , Wolf Gernot , Mzoughi Slim , Wollmann Heike , Macfarlan Todd S. , Guccione Ernesto , Messerschmidt Daniel M.
Published: March 2019

Global epigenetic reprogramming is vital to purge germ cell-specific epigenetic features to establish the totipotent state of the embryo. This process transpires to be carefully regulated and is not an undirected, radical erasure of parental epigenomes. The TRIM28 complex has been shown to be crucial in embryonic epigenetic reprogramming by regionally opposing DNA demethylation to preserve vital parental information to be inherited from germline to soma. Yet the DNA-binding factors guiding this complex to specific targets are largely unknown. Here, we uncover and characterize a novel, maternally expressed, TRIM28-interacting KRAB zinc-finger protein: ZFP708. It recruits the repressive TRIM28 complex to RMER19B retrotransposons to evoke regional heterochromatin formation. ZFP708 binding to these hitherto unknown TRIM28 targets is DNA methylation and H3K9me3 independent. ZFP708 mutant mice are viable and fertile, yet embryos fail to inherit and maintain DNA methylation at ZFP708 target sites. This can result in activation of RMER19B-adjacent genes, while ectopic expression of ZFP708 results in transcriptional repression. Finally, we describe the evolutionary conservation of ZFP708 in mice and rats, which is linked to the conserved presence of the targeted RMER19B retrotransposons in these species.
Control of breathing and respiratory gas exchange in ducks native to high altitude in the Andes
Authors: Ivy Catherine M. , Lague Sabine L. , York Julia M. , Chua Beverly A. , Alza Luis , Cheek Rebecca , Dawson Neal J. , Frappell Peter B. , McCracken Kevin G. , Milsom William K. , Scott Graham R.
Published: March 2019

We examined the control of breathing and respiratory gas exchange in six species of high-altitude ducks that independently colonized the high Andes. We compared ducks from high-altitude populations in Peru (Lake Titicaca at ∼3800 m above sea level; Chancay River at ∼3000-4100 m) to closely related populations or species from low altitude. Hypoxic ventilatory responses were measured shortly after capture at the native altitude. In general, ducks responded to acute hypoxia with robust increases in total ventilation and pulmonary O2 extraction. O2 consumption rates were maintained or increased slightly in acute hypoxia, despite ∼1-2°C reductions in body temperature in most species. Two high-altitude taxa – yellow-billed pintail and torrent duck – exhibited higher total ventilation than their low-altitude counterparts, and yellow-billed pintail exhibited greater increases in pulmonary O2 extraction in severe hypoxia. In contrast, three other high-altitude taxa – ruddy duck, cinnamon teal, speckled teal – had similar or slightly reduced total ventilation and pulmonary O2 extraction than low-altitude relatives. Arterial O2 saturation (SaO2) was elevated in yellow-billed pintails at moderate levels of hypoxia, but there were no differences in SaO2 in other high-altitude taxa compared to their close relatives. This finding suggests that improvements in SaO2 in hypoxia can require increases in both breathing and haemoglobin-O2 affinity, because yellow-billed pintail was the only high-altitude duck with concurrent increases in both traits compared to its low-altitude relative. Overall, our results suggest that distinct physiological strategies for coping with hypoxia can exist across different high-altitude lineages, even among those inhabiting very similar high-altitude habitats.
Review of Molecular Engineering for Horizontal Molecular Orientation in Organic Light-Emitting Devices
Authors: Watanabe Yuichiro , Sasabe Hisahiro , Kido Junji
Published: March 2019

Organic light-emitting devices (OLEDs) are widely used in next-generation eco-friendly solid-state display and lighting technologies. Most key optoelectronic functions of organic films used in organic semiconductor devices are dependent on two important factors: the electronic properties of single molecules, and the molecular orientations. The molecular orientation has recently attracted considerable attention, and been recognized as a crucial parameter for determining key optoelectronic functions of organic devices, such as device lifetime, efficiency, ionization potential, and carrier mobility of semiconductor amorphous films. In this review, we discuss horizontal molecular orientation from a molecular engineering perspective considering the three essential layers of OLEDs: the hole transport layer, electron transport layer, and emissive layer. In addition, we address the future challenges of next-generation OLED materials.
High-Intensity Aerobic Exercise Acutely Increases Brain-derived Neurotrophic Factor
Authors: ROSS RYAN E. , SALADIN MICHAEL E. , GEORGE MARK S. , GREGORY CHRIS M.
Published: March 2019

Aerobic exercise (AEx) exerts antidepressant effects, although the neurobiological mechanisms underlying such effects are not well understood. Reduced brain-derived neurotrophic factor (BDNF) and elevated cortisol have been implicated in the pathophysiology of depression and appear to normalize with antidepressant treatment. Thus, BDNF and cortisol may serve as biological targets for developing AEx as an antidepressant treatment.

Purpose

This study examined the effects of AEx, of different intensities, on serum BDNF and cortisol in individuals with and without depression.

Methods

Thirteen participants with depression (10 females; age = 27.2 ± 6.9 yr; Montgomery–Äsberg Depression Rating Scale = 21.7 ± 4.7) and 13 control participants (10 females; age 27.2 ± 7.2 yr; Montgomery–Äsberg Depression Rating Scale = 0.5 ± 0.9) participated. Experimental visits consisted of 15 min of low-intensity cycling (LO) at 35% heart rate reserve, high-intensity cycling (HI) at 70% heart rate reserve, or sitting (CON). During each visit, blood samples were obtained at baseline, immediately postexercise (IP), and then every 15 min postexercise for 1 h (15P, 30P, 45P, and 60P). Group, condition, and time differences in BDNF and cortisol were assessed.

Results

There were no group differences in cortisol and BDNF. Secondary analysis revealed that BDNF increased in an intensity-dependent nature at IP, and cortisol was significantly elevated at 15P after HI. Changes in BDNF and cortisol showed significant linear relationships with changes in HR.

Conclusion

HI AEx can elicit acute, transient increases in BDNF and cortisol in young, healthy, and physically active, nondepressed and mild to moderately depressed individuals. This work suggests that AEx has potential to significantly affect the central nervous system function, and the magnitude of such effect may be directly driven by exercise intensity.
Comparison of auditory brainstem response and auditory steady state response audiometry by evaluating the hearing thresholds obtained in children with different severity of hearing loss
Authors: Aslam Muhammad Azeem , Javed Adeela , Moiz Abdul
Published: March 2019

Objectives: To compare the hearing thresholds obtained with auditory brainstem response (ABR) and auditory steady state response (ASSR) audiometry in children with hearing loss.

Methods: Hearing thresholds were obtained by ABR and ASSR in children who presented with suspicion of deafness at Ear, nose & throat department of Al-Nafees Medical College Hospital Islamabad, between January to August 2018. The mean hearing thresholds obtained by two tests were compared within each category of severity of deafness. Time taken by both tests was also compared.

Results: A total of 57 patients (114 ears) were included in the study. Among them 27 (47.4%) were male and 30 (52.6%) were female. The mean age of patients at presentation was 42 months (±30.9) with age range from one to 12 years. Mean hearing thresholds obtained by click ABR, chirp ABR, ASSR (1, 2, 4 kHz) & ASSR (0.5, 1, 2, 4 kHz) was 56.25 (±27.61), 58.88 (±27.44), 58.03 (±21.26) & 56.35 (±22.86) respectively. Mean thresholds were comparable between click ABR & ASSR (1, 2, 4 kHz) and between chirp ABR & ASSR (0.5, 1, 2, 4 kHz) in all degrees of hearing loss categories except in those patients with normal hearing thresholds. The mean time taken by clicks ABR, chirp ABR and ASSR were four minutes seven seconds, three minutes 15 seconds and 16 minutes and 7 seconds respectively.

Conclusions: Hearing thresholds obtained by ABR and ASSR are comparable in all categories of severity of hearing loss. The time taken by ABR is less as compared to ASSR.

How to cite this:Aslam MA, Javed A, Moiz A. Comparison of auditory brainstem response and auditory steady state response audiometry by evaluating the hearing thresholds obtained in children with different severity of hearing loss. Pak J Med Sci. 2019;35(2):320-324.   doi: https://doi.org/10.12669/pjms.35.2.688

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Efficacy of inverted internal limiting membrane flap for large idiopathic macular holes
Authors: Tayyab Haroon , Khan Asad Aslam , Jahangir Sana
Published: March 2019

Objective: To evaluate the effectiveness of inverted internal limiting membrane flap in large idiopathic macular holes.

Methods: Twelve patients diagnosed with idiopathic macular holes larger than 400um underwent 23 gauge Pars Plana Vitrectomy (PPV) with inverted internal limiting flap and gas tamponade at Al-Ehsan Eye Welfare Eye Hospital, Lahore from February 2017 to February 2018. All cases were diagnosed on Spectral Domain Optical Coherence Tomography (SD-OCT) and were followed up for 6 months. At every follow-up, best corrected visual acuity and SD-OCT was done.

Results: We achieved macular hole closure in 91.6% (11/12) patients with idiopathic macular holes larger than 400um. Five out of 12 patients underwent combined phacoemulsification and PPV. One patient has flat hole closure which was considered failure. One patient was excluded from the study due to per-operative flap loss. This patient was not included in final data analysis of 12 patients. There was statistically significant gain in best corrected visual acuity after successful macular hole closure. We did not report any untoward events during or in the post-operative period.

Conclusion: Inverted internal limiting flap is an effective method for repairing large macular holes.

How to cite this:Tayyab H, Khan AA, Jahangir S. Efficacy of inverted internal limiting membrane flap for large idiopathic macular holes. Pak J Med Sci. 2019;35(2):315-319. doi: https://doi.org/10.12669/pjms.35.2.689

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Two-Stage Invest–Defend Game: Balancing Strategic and Operational Decisions
Authors: Yolmeh Abdolmajid , Baykal-Gürsoy Melike
Published: March 2019

Protecting infrastructures and their users against terrorist attacks involves making both strategic and operational decisions in an organization’s hierarchy. Although usually analyzed separately, these decisions influence each other. To study the combined effect of strategic and operational decisions, we present a game-theoretic, two-stage model between a defender and an attacker involving multiple target sites. In the first stage, the defender (attacker) makes a strategic decision of allocating investment resources to target sites to improve the defense (attack) capabilities. We consider two cases for investments in the first stage: (1) unconstrained and (2) budget-constrained models. The investment allocations for each target site determine its detection probability. In the second stage, the players make operational decisions of which target site to defend or to attack. We distinguish between two games that arise in the second stage: the maximal damage game and the infiltration/harassment game. We prove that the solution to each game under budget constraints is unique. In fact, when the second-stage game is of the infiltration/harassment type, the invest–defend game has a unique closed-form solution that is very intuitive. The results reveal that an increase in defense investments at a target site decreases the probability of both defending and attacking that target. However, an increase in attack investments increases the probability of both defending and attacking that target. Similarly, an increase in the defender’s (attacker’s) investment efficiency leads to a decrease (increase) in investments of both the defender and the attacker. Finally, the model is applied to real data to obtain the equilibrium investment and defense strategies. The results from real data demonstrate that the attacker’s penalty from a failed attack is an important factor in determining the defender’s optimal distribution of investments and defense probabilities. The defender’s second-stage defense decisions complement the first-stage investment decisions; that is, among target sites that receive little or zero investment, the most important one is covered with a relatively high defense probability in the second stage. Moreover, as the attacker’s budget increases, the defense investments shift from less important sites to more important ones.
INVESTIGACIÓN SOBRE EL BURNOUT EN DOCENTES ESPAÑOLES: UNA REVISIÓN SOBRE FACTORES ASOCIADOS E INSTRUMENTOS DE EVALUACIÓN
Authors: Pinel Martínez Cristina , Pérez Fuentes María Del Carmen , Carrión Martínez José Juan
Published: March 2019

INTRODUCCIÓN. El estrés puede ser uno de los desencadenantes del burnout o síndrome del quemado, un trastorno caracterizado por un agotamiento físico, psicológico y emocional. Sin embargo, cuando hacemos referencia a los docentes, el estrés no es el único factor que puede preceder al burnout. Esto hace que sea importante realizar una búsqueda de información sobre los elementos considerados más estudiados respecto al burnout docente en sus diversas etapas, así como sobre los diferentes instrumentos existentes para la recogida de datos referentes a este fenómeno. Por esta razón, se persigue el objetivo de identificar y analizar los factores tenidos en cuenta en el estudio del burnout docente en España y determinar los principales instrumentos de medida utilizados para este propósito. MÉTODO. En esta revisión sistemática se consideraron las bases bibliográficas electrónicas Dialnet, Web of Science y ScienceDirect con los descriptores “burnout”, “maestr*”, “docen*”, “profesor*”, “educaci*” y “Españ*”, así como sus respectivas traducciones al inglés y los operadores booleanos “AND” y “OR”. Se encontraron un total de 2.969 documentos, seleccionando 35 para su estudio tras aplicar los criterios de inclusión y exclusión. RESULTADOS. Se enumeraron 52 factores divididos en 7 grupos (sociodemográficos, académicos, profesionales, contextuales, sociales, psicológicos y salud). La etapa más estudiada fue la educación secundaria (74,3%) y la que menos la universitaria (17,1%). El instrumento más utilizado sigue siendo el MBI “Maslach Burnout Inventory” de Maslach y Jakson (1989). Las variables que más se repiten son las sociodemográficas (94,4%), siendo el sexo (91,43%), la edad (77,14%) y la experiencia docente (34,29%) los factores que más interés generan. DISCUSIÓN. Esta revisión sistemática vislumbra una gran variabilidad en cuanto a los factores estudiados en relación con el burnout docente en España, creando la necesidad de investigar de manera más profunda y realizando comparaciones más exactas sobre este constructo.
MANUEL BARTOLOMÉ COSSÍO EN LA REVISTA PEDAGÓGICA ESCUELAS DE ESPAÑA (1929-1936)
Authors: Ortiz de Santos Rosa , Torrego Egido Luis
Published: March 2019

INTRODUCCIÓN. Manuel Bartolomé Cossío estuvo en el origen de gran parte de las iniciativas pedagógicas y de las reformas educativas que se llevaron a cabo a finales del siglo XIX y durante el primer tercio del siglo XX en el contexto escolar español. En este periodo afloraron títulos de prensa pedagógica que constituyeron un medio esencial de expresión, de formación docente y de difusión del conocimiento, con presencia de referentes de renovación pedagógica y de figuras esenciales de la educación y de la cultura del momento. Esta aportación analiza el tratamiento de Cossío en la revista Escuelas de España, publicada entre 1929 y 1936. MÉTODO. El trabajo parte de una exhaustiva revisión de la literatura científica sobre la figura e iniciativas de Cossío. El estudio se ha llevado a cabo mediante el proceso de investigación histórico-educativa, a través de la técnica de análisis documental de los 44 números que componen la revista. Las categorías de análisis nos han permitido abordar los textos escritos por Cossío, las referencias que se le hacen desde la publicación y su influencia en la misma. RESULTADOS. La presencia de Cossío en Escuelas de España es significativa desde el momento fundacional de la revista, aunque se observa un mayor tratamiento del pedagogo desde su fallecimiento en septiembre de 1935. DISCUSIÓN. Escuelas de España, como otras revistas de referencia, recoge importantes aspectos de la obra y de la personalidad de Cossío. Recuperar el tratamiento de personas influyentes en la historia de la educación de nuestro país a través del patrimonio histórico-educativo, como lo es la prensa pedagógica, nos ayuda a reconstruir la educación de un momento espacio-temporal determinado y contribuir a la historia de la educación y de la pedagogía.
The conundrum of transmitting embodied knowledge for intercultural performance: A case study
Authors: Coldiron Margaret
Published: March 2019

How is ‘embodied knowledge’ transmitted? Certainly, in most Asian traditional performance practice, it is dinned into the body of the disciple through daily repetition. Unlike many western performance techniques, for example classical ballet, the discipline and transformation of the body in Asian performance forms is not managed through abstracted exercises, but rather by learning whole roles. In Bali, the student imbibes technique through regular practice until tarian masuk – literally until the dance enters the body. As a beneficiary of this pedagogical method, I know what it feels like, and as a student of anatomy and kinesiology I have some intellectual understanding of the nervous and muscular processes that make the appropriate movement happen; but how is this ‘sensuous knowledge’ transmitted? This case study examines the author’s experience of directing a group of Western-trained actors using techniques of Balinese topéng for an intercultural production of the Greek tragedy Hippolytos. It explores the physical and philosophical challenges for those who would make intercultural work, and who must find appropriate and effective methodologies for developing new body practices – often in a very short period of time.
Breathing and growth: Performing with plants
Authors: Arlander Annette
Published: March 2019

In this article breathing as a practice and vegetal growth as a form of movement are discussed by first returning to some repeated performances for camera made in Helsinki in 2004–05 and a text written in 2008 describing them in relation to Luce Irigaray’s ideas on breathing. These are then looked at from a current perspective and related to Michael Marder’s ideas on the place of plants, of growth as one of the Aristotelian forms of movement and Marder’s challenge to the arts to consider the vegetal. Based on Irigaray’s and Marder’s joint suggestion, in ‘Thinking anew’, to learn from plants, this article proposes that one way to begin considering performing with plants as a somatic practice could be, simply, breathing with plants.
The audience experience of immersion through intersubjective embodiment in Sensuous Geographies (2003)
Authors: Han Seok Jin
Published: March 2019

This article analyses an immersive interactive installation Sensuous Geographies (2003), created by choreographer Sarah Rubidge in collaboration with composer Alistair MacDonald. It applies phenomenological philosophies to critical interpretations of audience participants’ embodied experience. Rubidge employs choreographic sensibilities in designing a performative human–computer interface where the participants create their own sonic signature through physical behaviours while interacting with each other. The digital sound emerges as the ‘dys-appearing body’, as philosopher Drew Leder terms it, because it becomes part of their doubled embodiment but is perceptible due to its otherness. Moreover, the emergent sound embodies the participant’s subjectivity, which develops out of inter-subjectivity, since it is not transparent for the participant him/herself but generated through the intertwinement of the self and others. The self-perception of the corporeal body is heightened through digital imagery, costumes, facial veils and tactile materials, which provide the participant with a more intuitive and embodying experience of the sonic environment.
Fibromyalgia and the Feldenkrais method: Action research examining the teacher–student dynamic in transfer of learning
Authors: Fortin Sylvie , Hardy Élise
Published: March 2019

This action research brought together a group of Feldenkrais teachers and two groups of primarily female students living with fibromyalgia. The aim of the study was to work together to develop ways to allow the students to transfer knowledge acquired during weekly Feldenkrais lessons into their everyday lives. Based on the analysis of the empirical data collected, the research team developed a theoretical model of transfer of learning that calls attention to the importance of the student–teacher dynamic in the transfer of learning process. While this process may be different for each person, we argue that it occurs in three identifiable stages: (1) learning about the Feldenkrais method in the classroom; (2) applying the content and/or pedagogy of the Feldenkrais classes in everyday life; and (3) integrating knowledge gained through Feldenkrais classes into various spheres of one’s life. Despite the positive testimonies obtained throughout this action research, the authors of this article emphasize that the Feldenkrais method should not be seen as a panacea. Emphasis on the first-person experience, which is the basis of the Feldenkrais method, may run the risk of depoliticizing the broader social forces that contribute to the production and reproduction of fibromyalgia.
Shin Somatics contact unwinding: Developing mindfulness through interpersonal relationship
Authors: Purvis Denise
Published: March 2019

The Shin Somatics practice, contact unwinding, is a mindful improvisation practice aimed at clearing the chakras and promoting self-healing through physical and energetic connection of a primary mover and supportive guide. Developed by Sondra Fraleigh, contact unwinding encourages a primary mover to respond to internal cues, as well as a supportive guide’s energetic and tactile guidance. The practice is unique in encouraging partners to be present-centred, communicate clearly and honestly through touch, and reflect verbally in a manner allowing both parties to increase self-awareness without judgement or projection. This article explores contact unwinding’s potential to develop both mindfulness and interpersonal skills through holding presence and matching through touch. Using mindfulness-based cognitive behavioural therapy as an exemplar, I suggest the practice’s potential benefit to individuals seeking relief from psychosomatic disorders.
Conservation intervention on an embroidery with beads on perforated cardboard: problems and solutions
Authors: Barros Luciana , Cruz António João , Loureiro Leonor
Published: March 2019

Perforated cardboard is a rigid material widely used during the second half of the 19th century as an embroidery support, but very little-known today. Intervention cases are rare, and so an intervention on a poor condition 1879 glass beads embroidered specimen is presented here. The intervention was a complex task, mainly due to the fragility of the object and the existence of different materials linked to each other, that did not allow the execution of treatments to which they are usually subjected when isolated. The most intricate operation was the simultaneous action of micro-consolidation and micro-infill. These involved the insertion of Japanese paper fibres and 4 % Tylose MH300 between the perforated paper layers, and the insertion of Japanese paper strips between the embroidery lines. For the embroidery housing, it was necessary simultaneously to avoid the most unfavourable conditions for both the preservation of the glass and the paper.
Between Rhetoric and Sophistry: The Puzzling Case of Plato’s Gorgias
Authors: Tusi Jacqueline
Published: March 2019

The case of Gorgias’ profession has been an object of ongoing dispute among scholars. This is mainly because in some dialogues Plato calls Gorgias a rhetorician, in others a sophist. The purpose of this article is to show that a solution only emerges in the Gorgias, where Plato presents Gorgias’ goals as a rhetorician and its associated arts. On this basis, Plato introduces a systematic division between genuine arts and fake arts, including rhetoric and sophistry, thereby identifying their conceptual differences and similarities. The paper concludes by arguing that Gorgias can be called both a rhetorician and a sophist, provided that the labeling is done from different perspectives.
Vertical integration approach for the intelligent Oil & Gas field
Authors: García Marcelo V. , Armentia Aintzane , Pérez Federico , Estévez Elisabet , Marcos Marga
Published: March 2019

The oil and gas industry envisions a smarter way of running their business where they can visualize their entire operation, call and retrieve production data effortlessly and seamlessly, collaborating across the entire enterprise to decrease production costs while increasing recovery. The so-called Intelligent Oil Field (IOF) promotes reference architectures and development approaches that improve the flexibility and efficiency of upstream and downstream process. In this sense, OPC UA provides local and remote access to plant information, allowing horizontal and vertical integration in a reliable, safe and efficient way. This article contributes an open IOF architecture for vertical integration based on cyber-physical production systems, configured under IEC 61499 and using OPC UA. Therefore, the proposal is suitable to achieve flexible manufacturing.
Transient receptor potential channels in the context of nociception and pain – recent insights into TRPM3 properties and function
Authors: Behrendt Marc
Published: March 2019

Potential harmful stimuli like heat, mechanical pressure or chemicals are detected by specialized cutaneous nerve fiber endings of nociceptor neurons in a process called nociception. Acute stimulation results in immediate protective reflexes and pain sensation as a normal, physiological behavior. However, ongoing (chronic) pain is a severe pathophysiological condition with diverse pathogeneses that is clinically challenging because of limited therapeutic options. Therefore, an urgent need exists for new potent and specific analgesics without afflicting adverse effects. Recently, TRPM3, a member of the superfamily of transient receptor potential (TRP) ion channels, has been shown to be expressed in nociceptors and to be involved in the detection of noxious heat (acute pain) as well as inflammatory hyperalgesia (acute and chronic pain). Current results in TRPM3 research indicate that this ion channel might not only be part of yet unraveled mechanisms underlying chronic pain but also has the potential to become a clinically relevant pharmacological target of future analgesic strategies. The aim of this review is to summarize and present the basic features of TRPM3 proteins and channels, to highlight recent findings and developments and to provide an outlook on emerging directions of TRPM3 research in the field of chronic pain.
Adiposity and adipocytokines: the moderator role of cardiorespiratory fitness and pubertal stage in girls
Authors: Brand Caroline , Leite Neiva , Lopes Wendell Arthur , Dias Arieli Fernandes , da Silva Larissa Rosa , Araujo Gaya Adroaldo Cezar , Mota Jorge , Cavaglieri Claudia Regina , Gaya Anelise Reis
Published: March 2019

Background

Cardiorespiratory fitness (CRF) and pubertal stages have been related to many health outcomes, including obesity and adipocytokines. Thus, the present study aimed to analyze the moderator role of CRF and pubertal stage in the relationship between adiposity and adipocytokines in girls.

Method

This cross-sectional study was performed with 42 pre-pubertal girls aged from 7 to 11 years and 54 post-pubertal girls aged from 13 to 17 years. Blood samples were collected to determine the serum levels of leptin and adiponectin, and then the leptin/adiponectin ratio (L/A ratio) was calculated. CRF, anthropometric and body composition indicators were assessed. For statistical analysis, descriptive statistics and several linear regression models were used. The moderation analysis was tested using the PROCESS macro.

Results

An interaction between body mass index (BMI) and CRF (β: –0.70; confidence interval [CI]: –1.29, –0.12), as well as between BMI and pubertal stage (β: 0.79; CI: 0.28, 1.30) with leptin, was found. Regarding the L/A ratio, an interaction was found only in BMI × CRF (β: –0.56; CI: –1.06, –0.06). Using a combined interaction (CRF and pubertal stage), the results showed a positive association between BMI with leptin and L/A ratio only in low CRF, pre-pubertal and post-pubertal stages.

Conclusion

This study suggests a protective role of high levels of CRF in the relationship between BMI and adipocytokines. Despite the effect of pubertal stage, the results suggest that youth should be engaged in physical activity in order to improve CRF levels and consequently improve cardiometabolic health.
Reproductive senescence in free-ranging North American elk Cervus elaphus Cervidae
Authors: Bender Louis C. , Piasecke Jessica R.
Published: March 2019

Successful production of calves is necessary for growth of North American elk (Cervus elaphus Linnaeus 1758) populations, but few studies have evaluated age-related effects on both the conception and survival of a calf to weaning in multiple free-ranging populations. Conception and survival of calves to weaning were both affected by maternal age, with old (age 9 and older) females showing reproductive senescence as compared to prime-aged (ages 2–8) females despite achieving similar or greater size and condition. Reproductive senescence in our free-ranging populations ultimately resulted in old females weaning fewer calves (0.42 calves/female) than did prime-aged females (0.64 calves/female). Other factors, especially maternal size, also influenced conception and survival to weaning, and these interacted with age in a consistent manner, i.e. larger females or females in better condition were more likely to conceive and successfully wean calves within each age class. Female age structure receives less consideration in ungulate management than does male age structure, despite demonstrated impacts on population productivity of multiple species because of reproductive senescence. Because of the large proportion of individuals in senesced age classes in elk populations, low productivity in populations may simply reflect female age structure, rather than other frequently hypothesized factors.
Focusing attention in populations of semi-autonomously operating sensing nodes
Authors: Hildmann Hanno , Almeida Miguel , Isakovic Abdel F. , Saffre Fabrice
Published: March 2019

Cognition and the cognitive processing of sensory information in biological entities is known to occur over multiple layers of processing. In the example of human vision there are a vast number of photo-receptors feeding into various layers of cells which pre-process the original information before it arrives to the brain (as biased data).We propose to use a mechanism known to theoretical biologists as a means to bring about adaptive selforganization in colonies of social insects, and to apply it to such early stage signal processing. The underlying mathematical model is simple, and in the coming years, robotics will move into an era when aggregating simple computation devices into massively large collectives becomes feasible, making it possible to actually build such distributed cognitive sensing systems.