bluuebunny/crossref_metadata_2025 huggingface dataset:
Group sequential designs for negative binomial outcomes
Authors: Mütze Tobias , Glimm Ekkehard , Schmidli Heinz , Friede Tim
Published: May 2018

Count data and recurrent events in clinical trials, such as the number of lesions in magnetic resonance imaging in multiple sclerosis, the number of relapses in multiple sclerosis, the number of hospitalizations in heart failure, and the number of exacerbations in asthma or in chronic obstructive pulmonary disease (COPD) are often modeled by negative binomial distributions. In this manuscript, we study planning and analyzing clinical trials with group sequential designs for negative binomial outcomes. We propose a group sequential testing procedure for negative binomial outcomes based on Wald statistics using maximum likelihood estimators. The asymptotic distribution of the proposed group sequential test statistics is derived. The finite sample size properties of the proposed group sequential test for negative binomial outcomes and the methods for planning the respective clinical trials are assessed in a simulation study. The simulation scenarios are motivated by clinical trials in chronic heart failure and relapsing multiple sclerosis, which cover a wide range of practically relevant settings. Our research assures that the asymptotic normal theory of group sequential designs can be applied to negative binomial outcomes when the hypotheses are tested using Wald statistics and maximum likelihood estimators. We also propose two methods, one based on Student’s t-distribution and one based on resampling, to improve type I error rate control in small samples. The statistical methods studied in this manuscript are implemented in the R package gscounts, which is available for download on the Comprehensive R Archive Network (CRAN).
Neuropsychological Performance Patterns of Adult ADHD Subtypes
Authors: LeRoy Amy , Jacova Claudia , Young Caedy
Published: May 2018

Objective: Neuropsychological performance patterns associated with adult ADHD subtypes are unknown. The aim of the current systematic review was to identify and synthesize available literature regarding neuropsychological performance associated with adult ADHD subtypes. Method: Searches were completed using the databases PsycINFO and PubMed for studies published before March 2017 addressing adult ADHD subtypes and neuropsychological performance. Data characterizing the neuropsychological tests utilized in each study were obtained and sorted into eight domains. To summarize the results of all comparisons (ADHD subtype compared with control, or to each other), we counted the proportion of tests within each domain with significant group differences. Results/Conclusion: We deemed four domains informative in differentiating ADHD subtypes from controls. Of these, memory was the only domain that held promise in distinguishing ADHD-Inattentive and ADHD-Combined. Limitations of the available literature are highlighted and recommendations for future research are provided.
Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum
Authors: Schee Jie Ping , Viswanathan Shanthi
Published: May 2018

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.
Conversation analysis, publics, practitioners and citizen social science
Authors: Housley William
Published: May 2018

During the course of this short article, I respond and connect with insights and issues raised by the Conversational Rollercoaster (CR) and its relationship with conversation analysis (CA) and the public science of talk. I constructively engage with the innovative thinking and practice associated with this initiative. Finally, I consider how this might enhance a potential drive to connect ethnomethodology (EM) and CA to additional public and collaborative practices and interventions in the digital age.
Individual accountability in Irish credit institutions—Lessons to be learned from the United Kingdom’s Senior Managers’ Regime
Authors: Clarke Blanaid
Published: May 2018

This article examines the Senior Managers' Regime (SMR), the duty of responsibility and the offence relating to a decision causing a financial institution to fail introduced by the Financial Services (Banking Reform) Act 2013 to give legislative effect to the recommendations of the Parliamentary Commission on Banking Standards. The Commission had examined impediments to accountability in the wake of the LIBOR scandal. The article explores the value of introducing similar requirements and regulations in Ireland as a means of improving individual accountability and allaying public concern in light of the Irish Banking Crisis and the more recent tracker mortgage scandal. It concludes that in cases of mismanagement which is not deliberate or reckless, the Central Bank of Ireland's model of proactive and intensive supervision and enforcement might benefit from the utilization of a SMR enhanced administrative sanctions procedure alongside its Fitness and Probity Regime. However, the introduction of an offence in Ireland relating to a decision causing a financial institution to fail, while appearing to respond to a public desire to improve accountability, would give rise to a number of significant challenges particularly in relation to enforcement.
The Woven EndoBridge (WEB) as primary treatment for unruptured intracranial aneurysms
Authors: van Rooij Sanne BT , van Rooij Willem Jan , Peluso Jo P , Sluzewski Menno
Published: May 2018

Purpose

The intrasaccular flow disruptor Woven EndoBridge (WEB) device is developed for the treatment of wide-necked aneurysms without supportive devices. We used the WEB as primary treatment for unruptured aneurysms suitable for the device, regardless of neck size.

Methods

Between February 2015 and June 2017, 59 aneurysms in 51 patients were selectively treated with the WEB. There were 15 men and 36 women with a mean age of 59 years. Mean aneurysm size was 7.0 mm (range 3–22 mm). Of 59 aneurysms, 45 (76%) had a wide neck defined as ≥4 mm or dome-neck ratio ≤1.5. No stents or supporting balloons were used.

Results

Initial WEB position was judged good in all 59 unruptured aneurysms. One patient with a basilar tip aneurysm had a late thrombotic posterior cerebral artery occlusion by protrusion of the WEB over the artery. There were no procedural ruptures. Overall complication rate was 2.0% (1 of 51, 95% CI 0.01–11.3%). Imaging follow-up was available in 55 of 59 aneurysms (93%). At 3 months, 41 of 57 aneurysms (72%) were completely occluded, 12 (21%) had a neck remnant and 4 (7%) were incompletely occluded.

Conclusion

WEB treatment is safe and effective in selected unruptured aneurysms suitable for the device, regardless of neck size or location. There was no need for supportive devices. Three-quarters of all unruptured small aneurysms could be treated with the WEB. In our opinion, the WEB is a valuable alternative to coils, especially in wide-necked aneurysms.
Analysis on the location of green logistics park based on heuristic algorithm
Authors: Xu Yingjun , Jia Hongfei , Zhang Yikun , Tian Guodong
Published: May 2018

The location problem of logistics park is the basis of logistics network planning. The establishment of conventional logistics park location planning model requires consideration of multiple factors, including position relationships between site selection points and demand points, economic cost, service efficiency, and consumer satisfaction. “Green development concept” gradually leads the trend of social and economic development in the contemporary world. The green logistics park emerges as the requirement of era. There are obvious differences between the site selection rules and the location demand of the green logistics park with the conventional logistics park. On the basis of analyzing the evaluation indexes of green logistics park and the factors affecting the site selection, this article builds a single-objective decision model based on the comprehensive cost. The model sets transportation cost and environment cost as the objective function. In addition, according to the constraints of location and quantity of the proposed logistics park, the model is divided into four parts to refine, and the solving process based on hybrid particle algorithm and alternate location allocation heuristic algorithm is given. The model and algorithm are feasible by analyzing the numerical example. Finally, the green logistics park site selection scheme is designed. The location model that considers the single comprehensive cost target provides a simple and feasible decision method for the green logistics park location.
Acute myeloid leukemia chimeric antigen receptor T-cell immunotherapy: how far up the road have we traveled?
Authors: Tasian Sarah K
Published: May 2018

Chemotherapy resistance and relapse remain significant sources of mortality for children and adults with acute myeloid leukemia (AML). Further intensification of conventional cytotoxic chemotherapy is likely not feasible due to the severity of acute and long-term side effects upon normal tissues commonly induced by these drugs. Successful development and implementation of new precision medicine treatment approaches for patients with AML, which may improve leukemia remission and diminish toxicity, is thus a major priority. Tumor antigen-redirected chimeric antigen receptor (CAR) T-cell immunotherapies have induced remarkable responses in patients with relapsed or chemorefractory B-lymphoblastic leukemia, and similar strategies are now under early clinical study in adults with relapsed/refractory AML. However, potential on target/off tumor toxicity of AML CAR T-cell immunotherapies, notably aplasia of normal myeloid cells, may limit broader implementation of such approaches. Careful selection of optimal target antigens, consideration of toxicity mitigation strategies, and development of methodologies to circumvent potential CAR T-cell resistance are essential for successful implementation of cellular immunotherapies for patients with high-risk AML.
Inside help: An integrative review of champions in healthcare-related implementation
Authors: Miech Edward J , Rattray Nicholas A , Flanagan Mindy E , Damschroder Laura , Schmid Arlene A , Damush Teresa M
Published: May 2018

Background/aims:

The idea that champions are crucial to effective healthcare-related implementation has gained broad acceptance; yet the champion construct has been hampered by inconsistent use across the published literature. This integrative review sought to establish the current state of the literature on champions in healthcare settings and bring greater clarity to this important construct.

Methods:

This integrative review was limited to research articles in peer-reviewed, English-language journals published from 1980 to 2016. Searches were conducted on the online MEDLINE database via OVID and PubMed using the keyword “champion.” Several additional terms often describe champions and were also included as keywords: implementation leader, opinion leader, facilitator, and change agent. Bibliographies of full-text articles that met inclusion criteria were reviewed for additional references not yet identified via the main strategy of conducting keyword searches in MEDLINE. A five-member team abstracted all full-text articles meeting inclusion criteria.

Results:

The final dataset for the integrative review consisted of 199 unique articles. Use of the term champion varied widely across the articles with respect to topic, specific job positions, or broader organizational roles. The most common method for operationalizing champion for purposes of analysis was the use of a dichotomous variable designating champion presence or absence. Four studies randomly allocated of the presence or absence of champions.

Conclusions:

The number of published champion-related articles has markedly increased: more articles were published during the last two years of this review (i.e. 2015–2016) than during its first 30 years (i.e. 1980–2009). The number of champion-related articles has continued to increase sharply since the year 2000. Individual studies consistently found that champions were important positive influences on implementation effectiveness. Although few in number, the randomized trials of champions that have been conducted demonstrate the feasibility of using experimental design to study the effects of champions in healthcare.
Successful use of balloon tamponade in the management of postpartum hemorrhage in a case of bicornuate uterus
Authors: Khan Erum Saleem , Basharat Ayesha
Published: May 2018

Worldwide 50%–70% of all cases of maternal morbidity have been attributed to postpartum hemorrhage. This report discusses a case of bicornuate uterus in a term pregnancy. The delivery was by cesarean section, which was followed by massive postpartum hemorrhage, managed successfully with balloon tamponade. This is the second reported case of successful management of post partum hemorrhage in a bicornuate uterus with balloon tamponade. A 22-year-old primigravida at 39 weeks of gestational age presented with vaginal leaking of clear fluid. Cesarean section was done due to meconium stained liquor in early labor; with an incidental finding of bicornuate uterus followed by massive postpartum hemorrhage managed successfully with balloon tamponade. The use of uterine balloon tamponade as an effective method to control postpartum hemorrhage has been studied extensively, but use in cases of hemorrhage associated with uterine malformations has not been reported much in literature. Use of uterine balloon tamponade in case of uterine malformations has been highlighted in our case as an effective non-surgical method to control hemorrhage.
Symptomatic recurrent varicose veins due to primary avalvular varicose anomalies (PAVA): A previously unreported cause of recurrence
Authors: Whiteley Alice M , Holdstock Judith M , Whiteley Mark S
Published: May 2018

A 56-year-old woman presented in 2006 with symptomatic primary varicose veins in her right leg. Venous duplex ultrasonography at that time showed what appeared to be “neovascular tissue” around the saphenofemoral junction. However, there had been no previous trauma or surgery in this area. This appearance has subsequently been described as primary avalvular varicose anomalies. She underwent endovenous treatment at that time. In 2018, she presented with symptomatic recurrent varicose veins of the same leg. Venous duplex ultrasonography showed successful ablation of the great saphenous and anterior accessory saphenous veins. All of the recurrent venous reflux was arising from the primary avalvular varicose anomalies. This report shows that primary avalvular varicose anomalies is a previously unreported cause of recurrent varicose veins and leads us to suggest that if found, treatment of the primary avalvular varicose anomalies should be considered at the primary procedure.
Impact of nutritional status on pulmonary function after lung transplantation for cystic fibrosis
Authors: Staufer Katharina , Halilbasic Emina , Hillebrand Peter , Harm Solveig , Schwarz Stefan , Jaksch Peter , Kivaranovic Danijel , Klepetko Walter , Trauner Michael , Kazemi-Shirazi Lili
Published: May 2018

Background

Nutritional status is an important prognostic factor in patients with cystic fibrosis (CF) prior to lung transplantation.

Objective

To investigate the impact of nutritional status on pulmonary function in CF transplant recipients.

Methods

Adult double lung transplanted CF patients were consecutively included. The predictive value of nutritional status on lung function – measured by spirometry – was longitudinally assessed by body composition serially evaluated by a three‐compartment model bioelectrical impedance analysis (BIA) in comparison to body mass index (BMI).

Results

Overall, 147 spirometries and 147 BIAs were performed in 58 patients (59% female, median age: 30.1 years, median BMI: 19.6 kg/m2). Malnourished patients (BMI < 18.5 kg/m2; 27.6%) had a significantly reduced lung function compared to normal/overweight patients (forced expiratory volume in 1 second in percent (FEV1%pred), 57% vs 77%; p = 0.024). BMI, as well as the BIA parameters phase angle, total body water, fat free mass, body cell mass (BCM) and extracellular mass (ECM)/BCM ratio, were univariate predictors of FEV1%pred. When included in a linear mixed model, ECM/BCM ratio remained the only significant predictor of lung function (p = 0.012).

Conclusion

Nutritional status assessed by BIA predicted lung function in CF transplant recipients. Serial BIA measurements to monitor patients’ nutritional status might help to improve or maintain lung function.
Addressing the targeting range of the ABILHAND-56 in relapsing–remitting multiple sclerosis: A mixed methods psychometric study
Authors: Cleanthous Sophie , Strzok Sara , Pompilus Farrah , Cano Stefan , Marquis Patrick , Cohan Stanley , Goldman Myla D , Kresa-Reahl Kiren , Petrillo Jennifer , Castrillo-Viguera Carmen , Cadavid Diego , Chen Shih-Yin
Published: May 2018

Background

ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure’s limited measurement range and precision in higher-functioning multiple sclerosis patients.

Objective

The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients.

Methods

A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis.

Results

Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items.

Conclusion

The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.
Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson’s Disease: A Pilot Randomized Controlled Trial
Authors: Vergara-Diaz Gloria , Osypiuk Kamila , Hausdorff Jeffrey M , Bonato Paolo , Gow Brian J , Miranda Jose GV , Sudarsky Lewis R , Tarsy Daniel , Fox Michael D , Gardiner Paula , Thomas Cathi A , Macklin Eric A , Wayne Peter M
Published: May 2018

Objectives

To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson’s disease (PD) and to select outcomes most responsive to TC assessed during off-medication states.

Design

Two-arm, wait-list controlled RCT.

Settings

Tertiary care hospital.

Subjects

Thirty-two subjects aged 40–75 diagnosed with idiopathic PD within 10 years.

Interventions

Six-month TC intervention added to usual care (UC) versus UC alone.

Outcome Measures

Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson’s Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications.

Results

Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [−0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups.

Conclusions

Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.
Can Fetal Heart Rate Responses to Maternal Exercise Be Used for Antepartum Surveillance?
Authors: Petrikovsky Boris M. , Sichinava Lali , Swancoat Steven
Published: May 2018

The contraction stress test (CST) is currently the only modality used to test for placental insufficiency. It is rarely used due to possible complications. We propose a new test to assess placental reserves by measuring fetal heart rate (FHR) fetal responses to maternal exercise (FRME). A cohort of 640 term patients underwent FRME for accepted clinical indications. There was a total of 1680 tests, performed using a motorized treadmill in a moderate exercise regimen. Monitoring was provided by using standard Philips equipment (Avalon CTS and FM40). FRME was interpreted as negative (absence of decelerations, possible presence of accelerations), positive (presence of late decelerations or sustained bradycardia), or inconclusive. The results demonstrated 1506 tests were negative, 58 were positive, and 312 were inconclusive. If the test was negative, only 2% of the fetuses experienced adverse outcomes, versus 14%, when the test was positive. Positive tests were associated with 29% of category III FHR tracing, 11.6% of 5-minute Apgar score of less than 7, 9.8% admissions to the intensive care nursery, 2.2% of growth restrictions, and 1.2% of fetal or early neonatal demises. FRME if positive is associated with adverse perinatal outcome and could be included into the armamentarium of fetal testing.
A reinvestigation of holotype wadalite from Tadano, Fukushima Prefecture, Japan
Authors: Banno Yasuyuki , Bunno Michiaki , Tsukimura Katsuhiro
Published: May 2018

A reinvestigation of the type specimen of wadalite, ideally Ca12Al10Si4O32Cl6, from Tadano, Fukushima Prefecture, Japan, reveals that it has well-defined chemical sector zoning. The mineral occurs in skarn xenoliths in two-pyroxene andesite and forms tris-tetrahedral crystals up to 1 mm in size. The mineral is cubic,I¯43d, witha= 12.009(2) Å,V= 1731.8(8) Å3andZ= 2. The zoning is divided into two sectors, {21¯1} and {211}, on the basis of back-scattered-electron images. The {21¯1} sector is more enriched in Fe3+, Si, Mg and Cl, and depleted in Al than the {211} sector. The empirical formulae yielded by the averaged compositions for the {21¯1} and {211} sectors are: Ca12.01(Al7.88$\hbox{Fe}_{{\rm 0}{\rm. 99}}^{{\rm 3 +}} $Si4.51Mg0.56Ti0.05)Σ13.99O32.22Cl5.55and Ca12.05(Al8.42$\hbox{Fe}_{{\rm 0}{\rm. 85}}^{{\rm 3 +}} $Si4.20Mg0.44Ti0.04)Σ13.95O32.19Cl5.38, respectively. Compositional variations in the wadalite grains suggest that the Si contents are controlled mainly by the substitutionT(Al,Fe3+) +W□ ↔TSi +W(Cl,F). The presence of sector zoning suggests that the wadalite grew during rapid non-equilibrium crystallization.
Wrightite, K2Al2O(AsO4)2, a new oxo-orthoarsenate from the Second scoria cone, Northern Breakthrough, Great Fissure eruption, Tolbachik volcano, Kamchatka peninsula, Russia
Authors: Shablinskii Andrey P. , Filatov Stanislav K. , Vergasova Lidyua P. , Avdontseva Eugeniya Yu. , Moskaleva Svetlana V.
Published: May 2018

The new mineral wrightite, K2Al2O(AsO4)2, was found in 1983 at a fumarole on the Second scoria cone, Northern Breakthrough, Great Fissure eruption, Tolbachik volcano, Kamchatka peninsula, Russia, where it occurs as light yellow aggregates of transparent tabular crystals, with an average size of 0.05 mm × 0.03 mm × 0.005 mm. Wrightite is orthorhombic, space group Pnma, with the unit-cell parameters a = 8.230(5), b = 5.555(4), c = 17.584(1) Å, V = 803.9(6) Å3 and Z = 4 (from powder data). The empirical formula is (K1.69Na0.38)Σ2.07(Al1.80Fe0.24)Σ2.04As1.96O9. The crystal structure (R1 = 0.043) consists of Al2O(AsO4)2 layers in the ab plane with clusters of edge-sharing AlO6 octahedra. Each layer contains two independent isolated AsO4 tetrahedra and two AlO6 octahedra. AlO6 octahedra are linked by edges, forming zigzag chains along the b axis inside the Al–As layer. Eight- and six-coordinated K atoms are located in the interlayer space between Al2O(AsO4)2 layers. The mineral is biaxial (−), α =1.679(2), β =1.685(2), γ (calc.) =1.687; 2V(meas.) = 62(10)° (λ = 589 nm). The strongest lines in the powder X-ray diffraction pattern [d,Å(I)(hkl)] are: 8.77(36)(002); 4.458(17)(111); 4.010(19)(201,013); 3.875(19)(104) and 2.972(100)(015). The mineral was named in honour of Adrian Carl Wright, Emeritus Professor at the University of Reading, UK.
Multiplex Gene Profiling of Cell-Free DNA in Patients With Metastatic Melanoma for Monitoring Disease
Authors: Lin Selena Y. , Huang Sharon K. , Huynh Kelly T. , Salomon Matthew P. , Chang Shu-Ching , Marzese Diego M. , Lanman Richard B. , Talasaz AmirAli , Hoon Dave S.B.
Published: May 2018

Purpose

Hotspot blood cell-free DNA (cfDNA) biomarker assays have limited utility in profiling tumor heterogeneity and burden and in capturing regional metastasis with low disease burden in patients with melanoma. We investigated the utility of a sensitive 54–cancer gene digital next-generation sequencing approach targeting blood cfDNA single nucleotide variants (SNVs) and copy number amplification for monitoring disease in patients with melanoma with regional or distant organ metastasis (DOM).

Patients and Methods

A total of 142 blood samples were evaluated by digital next-generation sequencing across two patient cohorts. Cohort 1 contained 44 patients with stage II, III, or IV disease with matched tumor DNA at the time of surgery or DOM. Cohort 2 consisted of 12 overlapping patients who were longitudinally monitored after complete lymph node dissection to DOM.

Results

In cohort 1, cfDNA SNVs were detected in 75% of patients. Tumor-cfDNA somatic SNV concordance was 85% at a variant allele fraction of ≥ 0.5%. An SNV load (number of unique SNVs detected) of greater than two SNVs and an SNV burden (total cumulative SNV VAF) of > 0.5% were significantly associated with worse overall survival ( P < .05) in stage IV patients. In cohort 2, 98 longitudinal blood samples along with matched regional and distant metastases from 12 stage III patients were analyzed before complete lymph node dissection and throughout disease progression. cfDNA SNV levels correlated with tumor burden ( P = .019), enabled earlier detection of recurrence compared with radiologic imaging ( P < .01), captured tumor heterogeneity, and identified increasing SNVs levels before recurrence.

Conclusion

This study demonstrates significant utility for cfDNA profiling in patients with melanoma with regional and/or distant metastasis for earlier detection of recurrence and progression and in capturing tumor evolution and heterogeneity, thus impacting how patients with melanoma are monitored.
Effects of Molecular Heterogeneity on Survival of Patients With BRAFV600-Mutated Melanoma Treated With Vemurafenib With or Without Cobimetinib in the coBRIM Study
Authors: Wongchenko Matthew J. , Ribas Antoni , Ascierto Paolo A. , Dréno Brigitte , Maria di Giacomo Anna , Garbe Claus , Chang Ilsung , Hsu Jessie , Rooney Isabelle , Lu William , Koeppen Hartmut , Larkin James , Yan Yibing , McArthur Grant A.
Published: May 2018

Purpose

The treatment of advanced BRAFV600-mutated melanomas with BRAF inhibitors (BRAFi) has improved survival, but the efficacy of BRAFi varies among individuals and the development of acquired resistance to BRAFi through reactivation of mitogen-activated protein kinase (MAPK) signaling is common. We performed an exploratory, retrospective analysis to investigate the effects of BRAFV600 allelic balance, coexisting oncogene mutations, cell proliferation signaling levels, and loss of PTEN expression on progression-free survival (PFS) in patients in the phase III coBRIM study, which compared the combination of the MEK inhibitor cobimetinib with the BRAFi vemurafenib versus vemurafenib as monotherapy.

Methods

Baseline tumor samples from the intention-to-treat population were analyzed by targeted deep sequencing at a median coverage of 3,600× and by immunohistochemistry for cell proliferation markers, BRAFV600E, and PTEN. The association of these biomarkers with PFS was assessed by Cox proportional hazards modeling. Gene expression in relation to loss of PTEN was profiled by RNA sequencing in 205 patient samples and 42 BRAFV600-mutated melanoma cell lines.

Results

Neither BRAFV600 allelic balance nor coexisting mutations in the RAS/RAF/RTK pathway affected PFS in either treatment group. Increased baseline MAPK signaling and cell proliferation did not affect PFS in patients treated with cobimetinib combined with vemurafenib. PTEN loss was associated with reduced PFS in patients treated with vemurafenib alone but not in patients treated with cobimetinib combined with vemurafenib.

Conclusion

Deeper inhibition of the MAPK pathway through targeting of both MEK and BRAF may override the effects of tumor heterogeneity and improve PFS in all patients with advanced BRAFV600 melanoma.
Cacicas, Escribanos, and Landholders: Indigenous Women’s Late Colonial Mexican Texts, 1703–1832
Authors: Melton-Villanueva Miriam
Published: May 2018

Indigenous escribanos, notaries, based in the western part of what is now Mexico State, lived in small highland towns within the regions of Jilotepec and Metepec and wrote the documents studied here. They wrote the land sales, testaments, financial instruments, and powers of attorney for the women featured in this article. Their records described a cross-section of women participating in the civic work of their communities; identified cacicas, women of position in northern small towns (Jilotepec region) in the late colonial eighteenth-century; and showed the proportion of Nahua women who controlled land in southern small towns (Metepec region) within the extant early nineteenth-century testamentary record. Further, language data from these women’s records serve to restore local meanings of land and society. Taken together, the evidence disputes the narrative of decline and indicates escribanos, indigenous male officials, acknowledged and fostered women’s status and autonomy.
Peruvian Cocaine Tangles: Arrests and Assertions of Innocence in Ayacucho's Drug Trade, 1976–1981
Authors: Heilman Jaymie Patricia
Published: May 2018

Arrests for participation in the global cocaine trade surged in Peru during the 1970s. This article uses court cases to explore complaints in Ayacucho of wrongful arrests in the cocaine trade, examining claims of innocence, false confessions under torture, and police and judicial misconduct between 1976 and 1981. What emerges is a picture of abuse and lives upended by the cocaine trade's repression, often on dubious grounds. Ayacucho police routinely tortured during interrogations, engaging in the kinds of violence that became systematic during counterinsurgent warfare against the Shining Path and its presumed supporters. These cases reveal that many Ayacuchanos profoundly distrusted their police and court systems. That was especially true for impoverished—and predominantly rural and indigenous—men and women who could not afford lawyers or bribes. Ayacuchanos' devastating experiences of cocaine repression fueled anger toward the police, which Shining Path militants capitalized on early in their armed struggle.
Acts of Meditative Mind in “The Ruined Cottage”
Authors: Budick Sanford
Published: May 2018

The poetic work of “The Ruined Cottage” is carried out by acts of the “meditative mind” that Armytage identifies early in the poem (l. 81). The history of interpretation of the poem has been sorely vexed by Armytage’s closing statement, “I turned away / And walked along my way in happiness” (ll. 524–25). Far from standing alone, Armytage’s statement flows immediately from his repeated identification of a kind of “meditation” (l. 524). Contrary to Wordsworth’s later disclaimers, he learned much about this activity of meditative mind from Kant’s theories of the sublime. Edmund Husserl’s deepenings of aspects of these Kantian theories are apt for understanding what Wordsworth saw in Kant and what he achieved in “The Ruined Cottage,” going even beyond Kant—and Husserl as well. Wordsworth’s meditative activity produces, in practice, the distinctive consciousness—encompassing a difficult happiness—that is this poem’s greatest achievement. Coleridge, who was well aware of this achievement but resisted acknowledging it, provides important suggestions for locating it substantively, most specifically in Wordsworth’s Kantian engagement with Milton’s poetry.
The Effects of Exercise, Aspirin, and Celecoxib in an Atherogenic Environment
Authors: GRIMM HEATHER , KRETZSCHMAR JAN , COOK MARC D. , BROWN MICHAEL D.
Published: May 2018

Introduction

Optimal vascular function is a hallmark of cardiovascular health. Specifically, the balance of vasoconstricting and vasodilating substances is recognized as a marker of vascular health. One of the greatest challenges to vascular health and vasodilatory balance is tumor necrosis factor alpha (TNFα)-mediated inflammation. Uncovering effective strategies that maintain a vascular environment that is more vasodilatory and antithrombotic in the face of an inflammatory challenge is favorable.

Purpose

To test the ability of various antithrombotic and provasodilatory treatments, as well as combinations thereof, to prevent unfavorable changes in markers of endothelial dysfunction in human umbilical vein endothelial cells when presented with an inflammatory challenge.

Methods

Human umbilical vein endothelial cells were pretreated with exercise-like levels of laminar shear stress (LSS), aspirin, celecoxib, and their combination before a TNFα challenge. Western blot analysis as well as colorimetric assays were used to determine levels of endothelial nitric oxide synthase (eNOS) and prostacyclin (6-keto PGF1α)/thromboxane (TXB2) metabolite ratio, respectively.

Results

Neither aspirin nor celecoxib were effective in preventing TNFα-induced reduction in eNOS. Further, aspirin was unable to maintain baseline levels of prostacyclin/thromboxane ratio in the face of the inflammatory challenge. Laminar shear stress, aspirin/LSS combination, and celecoxib/LSS combination were all able to prevent TNFα-induced alterations in eNOS levels and prostacyclin/thromboxane ratio.

Conclusions

Effective strategies to maintain a healthy endothelium, and therefore resistance vessel health, need to include exercise-levels of shear stress to be effective.
ANALYTICAL ESTIMATION OF THE TECHNICAL CONDITION OF PLUNGER PAIR WHEN COMPLETED BY HYDRODENSITY
Authors: Казаков Юрий , Kazakov Yuriy , Иванов Владимир , Ivanov Vladimir
Published: May 2018

The paper considers the factors influencing the estimated indicator of the technical state of the plunger pairs, when they are equipped according to the hydrodensity. To determine the influence of factors on the estimated value of the plunger pair in terms of hydrodensity, a two-factor experiment was planned and implemented, and a mathematical model was obtained for the process of selecting plunger pairs as a set for hydro-densities. On the basis of the research, it is suggested to complete the plunger pairs as a set on the KI-759 device with a mathematical dependence to reduce the error.
THE TRANSFORMATION OF PROTEIN AND DIET ENERGY INTO MEAT PRODUCTION WHEN BULLS ARE FED BY SILAGE WITH BIOLOGICAL PRESERVAT
Authors: Фисенко Наталья , Fisenko Natal'y
Published: May 2018

The purpose of researches is increase of meat efficiency of bull-calves of black-motley breed through the use of canned green mass of alfalfa with Laxil and Silostan when harvesting haylage. The results of the evaluation of the effect of alfalfa haylage harvested with preservatives on the efficacy of bioconversion of nutrients and energy rations in meat products. Scientific and economic experience held in the SEC-farm «Alga» Chekmagushevsky district of the Republic of Bashkortostan. There are three trench silage from alfalfa. In one of them the food was laid with the application of the preservative Laxil, the second – and third Silostan – no preservatives. Laxil preservative was added at the rate of 1 liter per 15 tons of green mass, Silostan – 1 liter to 150 tons. The object of research was 45 bulls of black-and-white breed at the age of 9 months, of which three groups were formed: control and two experienced. Gobies control group received silage of alfalfa harvested without preservatives, and the animals of I and II experimental groups – silage, preserved by Laxil and Silostan. For studying of meat productivity and quality of meat of test bulls control slaughter of 3 bulls from each group was carried out. The results of the study indicate the superiority of calves of the experimental group over their counterparts from the control groups both in vivo and post-slaughter parameters. The results of the evaluation of the transformation of protein and energy feed in the production of bulls compared groups when grown for meat indicate that in the body of young I and II experimental groups were deposited a little more protein compared with peers from the control group.
ABOUT NEW GEARED ENGAGEMENT
Authors: Мудров Александр , Mudrov Aleksandr
Published: May 2018

An external geared engagement is proposed, in which a positive gear ratio, i.e. gear and wheel rotate in one direction. The development of transmission from theoretical studies to implementation in car differentials is shown. The new differential has a high blocking ratio (up to 8), which will increase the patency of cars on difficult-to-reach road sections. It is simple in design and has small dimensions. Transmission can be used in gearboxes and gearboxes where rotation reversal is required.
EFFICIENCY OF RESOURCE POTENTIAL USAGE: EVALUATION AND DIRECTIONS OF IMPROVEMENT
Authors: Богапова Мярьям , Bogapova Myar'yam , Дозорова Татьяна , Dozorova Tat'yana
Published: May 2018

Increasing the efficiency of resource potential usage is of particular importance, since it allows substantially increasing the level of resource use and the efficiency of the functioning of agricultural production. From this point of view, the study of theoretical, methodological and practical issues of assessing the resource potential, the effectiveness of its use allows us to substantiate the priority directions of the development of the agricultural sector of the economy and is extremely relevant. The research was conducted with the purpose of revealing the level of availability and the degree of efficiency of resource potential using of agricultural organizations in the Ulyanovsk region. To assess the availability of resource potential, the system of indicators was used: financial support, material security, labor supply, state support, cadastral value of agricultural land, humus content. The carried out regression modeling made it possible to identify three clusters of the region’s areas with varying degrees of efficiency in the use of the resource potential. The cluster trajectories of the study areas are analyzed, reflecting the dynamics of their distribution according to the traits under study: the typologies of the regions were analyzed according to statistical data for 2005, 2010, 2015. Based on the analysis, it can be noted that the regions of the Ulyanovsk region are rather heterogeneous according to the available resource potential of the agrarian sector of the economy and its implementation. Analysis of the dynamic characteristics of the resource potential use of the agrarian sector of the economy of the Ulyanovsk region showed that in 17 districts of the region during the analyzed period the cluster numbers did not change, which indicates stability in the current situation with the state and use of the resource potential. The article proposes the classification of agricultural organizations in terms of the level and effectiveness of using the resource potential and recommendations for increasing it for each cluster.
Complications of diabetes: Keeping an eye on retinopathy
Authors: Morris David
Published: May 2018

The threat to eyesight from diabetes is considerable and should be understood, writes David Morris
Improving TRANS4D’s model for vertical crustal velocities in Western CONUS
Authors: Snay Richard A. , Saleh Jarir , Pearson Chris F.
Published: May 2018

The “Transformations in Four Dimensions” (TRANS4D) software was developed to enable geospatial professionals and others to transform 3-D positional coordinates referred to one date to corresponding positional coordinates referred to another date. For this purpose, TRANS4D incorporates 3-D crustal velocity models for most of the United States and Canada. In this report, an improved model for the vertical velocity field of that part of the conterminous United States that resides west of longitude 107°W is introduced. A new estimation process was employed so that this newer velocity field would have a spatial resolution of 0.0625° × 0.0625° in latitude and longitude, whereas the spatial resolution of TRANS4D’s previous model for this area was 0.25° × 0.25°. The realized improvements benefited from the inclusion of repeated geodetic data at approximately 1300 new locations and from the longer time spans of repeated geodetic data at other locations. After removing that part of the current vertical velocity field due to the glacial isostatic adjustment associated with the Last Glacial Maximum, features of the remaining vertical velocity field are discussed in terms of ongoing geophysical processes. These processes include subduction in the Pacific Northwest, uplift along the San Andreas Fault System, and subsidence due to groundwater extraction in California’s Central Valley. They also include uplift within both the Yellowstone Caldera and the Long Valley Caldera, uplift near Hebgen Lake in Montana, and subsidence near Lassen Peak Volcano in California.
A Continuous-Time Distributed Algorithm for Solving a Class of Decomposable Nonconvex Quadratic Programming
Authors: Zhao Yan , Liu Qingshan
Published: May 2018

In this paper, a continuous-time distributed algorithm is presented to solve a class of decomposable quadratic programming problems. In the quadratic programming, even if the objective function is nonconvex, the algorithm can still perform well under an extra condition combining with the objective, constraint and coupling matrices. Inspired by recent advances in distributed optimization, the proposed continuous-time algorithm described by multi-agent network with consensus is designed and analyzed. In the network, each agent only accesses the local information of its own and from its neighbors, then all the agents in a connected network cooperatively find the optimal solution with consensus.
Event-Triggered Cluster Consensus of Leader-Following Linear Multi-Agent Systems
Authors: Xu Bin , He Wangli
Published: May 2018

This paper is concerned with cluster consensus of linear multi-agent systems via a distributed event-triggered control scheme. Assume that agents can be split into several clusters and a leader is associated with each cluster. Sufficient conditions are derived to guarantee the realization of cluster consensus by a feasible event-triggered controller if the network topology of each cluster has a directed spanning tree and the couplings within each cluster are sufficiently strong. Further, positive inner-event time intervals are ensured for the proposed event-triggered strategy to avoid Zeno behaviors. Finally, a numerical example is given to illustrate the effectiveness of the theoretical results.
Neighbors through Imperial Eyes: Depicting Babylonia in the Assyrian Campaign Reliefs
Authors: Seymour Michael
Published: May 2018

The Neo-Assyrian campaign reliefs are rich sources for understanding Assyrian ideas of empire, geography, and Assyria’s relationship to the wider world. They are also exceptions: the format of the later Assyrian campaign reliefs is in several respects so unusual in ancient Near Eastern art as to demand explanation. Not the least of the campaign reliefs’ unusual qualities is the extensive and often detailed depiction of foreign landscapes and people. This paper examines one instance of this phenomenon: the particular case of depictions of Babylonia and the far south in Assyrian campaign reliefs. Studies of the textual sources have done much to draw out the complex cultural and political relationship between Assyria and Babylonia in the eighth, seventh, and sixth centuries B.C., revealing tensions between an identification with the cities of the south and their venerable temples on the one hand, and the undeniable political and strategic problems posed by Babylonian rebellions against Assyrian rule on the other. It is argued that the campaign reliefs attempt to resolve this tension by presenting conquest and pacification as accomplished facts, and Babylonia’s abundance as an Assyrian imperial possession. It is also suggested that one function of the reliefs was to process historical victories into a larger, ahistorical image of Assyrian imperial success.
The Impact of Culture on Parental Perceptions about Autism Spectrum Disorders: Striving for Culturally Competent Practices
Authors: Barrio Brenda L. , Hsiao Yun-Ju , Prishker Nydia , Terry Callie
Published: May 2018

Despite the increasing number of children from culturally and linguistically diverse (CLD) backgrounds in the United States, limited research exists synthesizing what is known about the prevalence and diagnosis of autism spectrum disorder (ASD) in these communities. Children from culturally and linguistically diverse backgrounds are disproportionately diagnosed with ASD and, there is a need for practitioners and educators to be culturally competent at addressing challenges and practices related to ASD for children and youth. The purpose of this paper is to review the literature related to parental perspectives on ASD, in children from a wide range of culturally diverse backgrounds to provide information and resources to practitioners about the importance to strive for cultural competence in practice-related work.
Illusory Gains from Privatizing Social Security when Reform is Politically Unstable
Authors: Bielecki Marcin , Makarski Krzysztof , Tyrowicz Joanna
Published: May 2018

With compulsory funded public social security systems, pension savings constitute a large stock of assets. In this paper we consider an economy populated by overlapping generations, which may decide about abolishing the funded system and replacing it with the pay-as-you-go scheme (i.e. unprivatizing the pension system). We compare politically stable as well as politically unstable reforms and show that even if the funded system is overall welfare enhancing, the cohort distribution of benefits along the transition path may turn privatizing social security politically unsustainable.