bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of an effective mechanism for staffing in the agricultural sector in the context of globalization and integration through the pedagogical conditions of increasing motivation in students of agricultural universities
Authors: Klimova S , Kondykov A , Mertsalov E
Published: June 2019

The relevance of the research topic is explained by the fact that agriculture belongs to high-risk production, and the modern agrarian sector of the economy requires qualitatively new young professionals who can be not only production technologists, but also entrepreneurs with marketing and production management. This article poses the problem that it is necessary to update the structure of the formation of an effective mechanism for staffing the agricultural sector of the economy in the context of globalization and integration through the pedagogical conditions of forming the motivation of students in agricultural universities. Currently, when preparing qualified personnel for the agro-industrial complex, it is necessary to focus on improving the competence and innovative activity of students. Insufficient study of students’ satisfaction with the activities of universities in modern conditions has led to high relevance and the need for this study within the university. The motivation of learning activities is quite widely studied and covered in the scientific-periodical literature, and the satisfaction of students with learning activities is little studied. The lack of knowledge of this issue predetermined the choice of the direction of research by the method of L. V. Mishchenko, where the goal is to clarify the views of students and the development of practical recommendations for improving the activities of the university. The method includes 7 scales and 70 questions of statements of emotional and evaluative nature and the presented answers (wrong, perhaps wrong, right and perhaps true). The article analyzes the level of satisfaction of students with the activities of the university, summarizes the main trends in quantitative and qualitative changes, analyzes the current mechanism as an institution for the formation of highly qualified personnel for the agro-industrial complex of the region.
Algorithm for the formation of personnel potential in the scientific and educational sector of the agrarian sector based on cluster and pedagogical approaches
Authors: Klimova S , Kondykov A , Mertsalov E
Published: June 2019

The main product of higher education is a young specialist of an educational institution, the preparation of which consumes significant financial resources. In this regard, the relevance of the formation of operational, reliable, and complete indicators of student labor activity in-creases. Obtaining operational, reliable, and complete indicators of satisfaction of students with senior university activities, as well as analysis of these indicators and the formation of indicators to evaluate the effectiveness of the educational process serves as a basis for identifying and forecasting the labor activity of students, forming a list of popular areas and specialties, including adjustments to educational programs. The article discusses the motivation of students of the Agrarian University, as a prerequisite for the manifestation of the intrasectoral structure of employment and differences in its effectiveness, as well as the level of satisfaction with the knowledge gained in various types of activities. In order to improve the educational process and its methodological support, surveys of graduates and employers are held, exhibitions and conferences devoted to the problems of innovative technologies in agricultural education. The activity on the development of an independent personality among students, the formation of entrepreneurial spirit, and the disclosure of research talent, leadership qualities. A study of the level of satisfaction with the educational activities of the university, focused on the formation of research competence among students according to the methodology of L. V. Mishchenko showed high results of satisfaction with the activities of the university, namely 84%, with an average level of 11% and the lowest level of 5%. Studying at the university, future young professionals (farmers) should get the best in order to adapt to the conditions of real production, and this in turn affects the level of key competencies of the future graduate. The article substantiates the directions for increasing the prestige of the agricultural professions, increasing the informational level of students on the possibilities of self-realization in the agro-industrial sphere, and measures to be taken in order to increase the motivation of students during the period of study and the post-graduate period.
The state support system for agriculture
Authors: Ragulina Yu , Zavalko N
Published: June 2019

In the modern market community, the issues of providing state support for agriculture, as well as the effective use of budgetary funds, are of particular relevance. The agro-industrial complex is a significant socio-economic priority for the development of the state. Currently, agriculture has a low yield, which depends on the climatic conditions and the seasonal nature of production. Agriculture is slower than other industries, adapting to the changing economic situation.
Digital economy of the Republic of Uzbekistan
Authors: Obidov Z , Abdullaev S , Shukurov B
Published: June 2019

The purpose of the article is to develop a conceptual model of the use of the mechanism of the digital economy in the Republic of Uzbekistan. The research methodology is based on the application of a systematic approach to the study of socio-economic phenomena and processes. As a result of the study, the authors conclude that radical reforms are needed for the development of the digital economy in Uzbekistan. The current stage of development of the digital economy in Uzbekistan is in a period of formation and is characterized by a high dynamics of development. It is necessary to introduce innovative services. The development strategy of the digital economy should take into account the experience of advanced foreign countries, especially Korea. Revolutionary changes in the global financial system associated with the growth of electronic payment services, cryptocurrency, and lending without intermediaries are also covered.
Rational economic behavior
Authors: Semenova E
Published: June 2019

Economic transformations, globalization, and localization of the world socioeconomic systems, the desire to institutionalize current processes in society have changed the perception of economic activity tasks by the business entities, approaches to their solution, motivation, norms and skills of rational management, ethical standards, etc. This determines the relevance of the research on this topic. The main theoretical approaches to rational human behavior in terms of economic theory and management are summarized. The rational behavior is analyzed in terms of the individual and organization. Conclusion about the limited rationality of the Russians are made.
Principles of the organization of wages of managers and specialists of agricultural enterprises
Authors: Yusipova A
Published: June 2019

The principal provisions of the organization of the remuneration of managers and specialists of agricultural organizations are discussed in the article. The main functional responsibilities of the managers and chief specialists of crop and livestock are marked. The dynamics of the number and labor costs of these workers is presented for the five years, covering 2011-2015. Indicators of the level of wages and labor productivity of managers and specialists, as well as profitability of sales, are evaluated as a criterion of the effectiveness of their activities. Author’s proposal on the coefficients of the wage levels of certain groups of specialists is given, which is aimed at the objectivity of assessing their work in the economy.
Management of the life cycle of the innovation apiproduct from drone larvae and its introduction in the food industry
Authors: Prokhoda I A , Eliseeva E V , Polesskaya O P , Potseluev E I , Zabenko D V
Published: June 2019

The articles summarizes the experience the small innovative enterprise “Apiproduct” (Open Company SIP “Apiproduct”) - the first Russian enterprise that manages a life cycle of the innovation apiproduct from drone larvae, and its introduction in the food industry for the enrichment of mass consumption products with high-grade protein, biologically active high-functional substances and complexes. The authors analyzed the key stages of the life cycle of the apiproduct that consist of the justification of the idea of utilization of products of the larval origin in the food industry, experimental scientific and practical research, technology of the apiproduct manufacturing in a powder form with the author’s name “Bilar”, and production of its pilot batch in the Open Company SIP “Apiproducts”. The authors’ technology of production of the apiproduct “Bilar” includes the following stages: cultivation, reception and grinding of larvae to biomass, sublimation vacuum drying of biomass and production of powder with a mass fraction of 2% moisture. To date, the Russian apiproduct “Bilar” passed the sanitary-hygienic examination and can be used in its pure form as a food processor, containing in addition to protein, vitamins b, β-carotene, α-tocopherol, additionally biotin, vitamins PP, 28 macro-and microelements, unsaturated fatty acids (linoleic and arachidonic), phenolic compounds with p-vitamin activity, 80 enzymes, biopolymers, growth factor, etc., that has a long shelf life due to removal of water from the structure. The practice of the SIP “Apiproduct” work demonstrates that manufacturing and introduction of this innovation product - apiproduct “Bilar” - to the market significantly increases the assortment and competitiveness of the enterprise.
Analytical solution for the vertical structure eigenfunction in diagnosis of the low frequency wave-type perturbations in primitive dynamics equation
Authors: Rainchik S E
Published: June 2019

This study presents an analytical solution to the problem of determining the vertical modal structure of low-frequency atmospheric oscillations. This analytical solution is critically compared with the numerical solution of this problem known in the literature, and good agreement for vertical normal modes with the wave number less than 9 is found. Applicability of the analytical solution for diagnosing the atmospheric climate variability and the quality of its simulation by contemporary GCM is briefly discussed.
Numerical modeling of the influence of different options for feeding fuel on the combustion process for turbine profiles
Authors: Dostiyarov A M , Umyshev D R , Katranova G S
Published: June 2019

The article presents the results of numerical modeling of the effect of various fuel supply options on the combustion processes behind the turbine profiles. The article considered three options for fuel supply. In the first option, (a) the fuel is supplied to the wide side of the profile; in the second option, (b) the fuel is sprayed directly into the recirculation zone formed between the plate and the profiles; in the third option, (c) the fuel is sprayed from the convex (back) part of the profile. On the basis of the analysis performed, it can be concluded that the profiles of the blades have rather high stabilization parameters. The best performance has the option of supplying fuel from the back of the turbine profile. This option provides the minimum concentration of nitrogen oxides, with all other factors being equal.
Blood Pressure, Chronic Kidney Disease Progression, and Kidney Allograft Failure in Kidney Transplant Recipients: A Secondary Analysis of the FAVORIT Trial
Authors: Malhotra Rakesh , Katz Ronit , Weiner Daniel E , Levey Andrew S , Cheung Alfred K , Bostom Andrew G , Ix Joachim H
Published: June 2019

BACKGROUND

In chronic kidney disease, intensive systolic blood pressure (SBP) control reduces mortality at a cost of greater acute kidney injury risk. Kidney transplantation involves implantation of denervated kidneys and immunosuppressive medications that increase acute kidney injury risk. The optimal blood pressure (BP) target in kidney transplant recipients (KTRs) is uncertain. Prior observational studies from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial demonstrate associations of lower SBP levels and reduced mortality risk, but the relationship of BP with kidney allograft function remains unknown. Thus, in FAVORIT, we investigated the relationship of SBP and diastolic blood pressure (DBP) with risk of kidney allograft failure and estimated glomerular filtration rate (eGFR) slope among stable KTRs.

METHODS

Cox proportional hazards and multivariable linear regression models adjusted for demographics, transplant characteristics, comorbidities, baseline eGFR, and urine albumin-to-creatinine ratio were used to determine associations of SBP and DBP with time to a composite kidney outcome of ≥50% eGFR decline or dialysis dependence, and with annualized eGFR change, respectively. Multivariable restricted cubic spline plots were developed to evaluate the functional form of the relationships.

RESULTS

Among 3,598 KTRs, mean age was 52 ± 9 years, SBP was 136 ± 20 mm Hg, DBP was 79 ± 12 mm Hg, and eGFR was 49 ± 18 ml/minute/1.73 m2. There were 369 events of ≥50% eGFR decline or dialysis dependence during a mean follow-up of 4.0 ± 1.5 years. There was no association of either SBP (compared with SBP 120 to <130 mm Hg, hazard ratio (HR) for the SBP < 110 was 1.01 (95% confidence interval (CI) 0.60 to 1.70) and 130 to <140 was 0.89 (0.64 to 1.24)) or DBP (compared with DBP 70 to <80 mm Hg, HR for the DBP 60 to <70 was 1.00 (95% CI 0.74 to 1.34) and 80 to <90 was 0.90 (0.68 to 1.18)) with the kidney failure outcome or annualized eGFR slope, and, when examined using restricted cubic splines, there was no evidence of “J”- or “U”-shaped relationships.

CONCLUSIONS

In a large sample of stable KTRs, we found no evidence of thresholds at which lower BPs were related to higher risk of allograft failure or eGFR decline. In light of prior findings of mortality benefit at low SBP, these observational findings suggest lower BP may be beneficial in KTRs. This important question requires confirmation in future randomized trials in KTRs.
What have we recently learned about song learning and social interactions?
Authors: García Natalia C
Published: June 2019

Vocal learning in birds is a complex animal behavior with several parallels to vocal learning in humans. Early experiments in the 70s showing that juvenile birds could learn their species’ normal song presented only through loudspeakers led to the general notion that social interactions are unnecessary for song learning. These views were soon challenged, and after decades of research we know that different social factors influence song learning. Here, I discuss recent research that is getting us closer to understanding how. Juvenile birds in the wild are exposed to both direct and indirect interactions with singing adults, which can be relevant to different aspects of the learning process. The exposure to a potential living tutor may trigger or enhance the learning process, but direct interaction with a tutor producing the song type that is finally learned or incorporated to the repertoire is not required. Social interactions that the learner witnesses may be more important in determining which songs are included in the final repertoire of an adult bird. Further research is also required to better understand the role of interactions with females, not by providing a model song to imitate but by exhibiting responses contingent to juveniles practicing their songs.
Smooth muscle cell-specific TMEM16A deletion does not alter Ca2+ signaling, uterine contraction, gestation length, or litter size in mice†
Authors: Qu Mingzi , Lu Ping , Bellve Karl , Fogarty Kevin , Lifshitz Lawrence , Shi Fangxiong , Zhuge Ronghua
Published: June 2019

Ion channels in myometrial cells play critical roles in spontaneous and agonist-induced uterine contraction during the menstrual cycle, pregnancy maintenance, and parturition; thus, identifying the genes of ion channels in these cells and determining their roles are essential to understanding the biology of reproduction. Previous studies with in vitro functional and pharmacological approaches have produced controversial results regarding the presence and role of TMEM16A Ca2+-activated Cl− channels in myometrial cells. To unambiguously determine the function of this channel in these cells, we employed a genetic approach by using smooth muscle cell-specific TMEM16A deletion (i.e. TMEM16ASMKO) mice. We found that myometrial cells from TMEM16ASMKO mice generated the same pattern and magnitude in Ca2+ signals upon stimulation with KCl, oxytocin, and PGF2α compared to the isogenic control myometrial cells. At the uterine tissue level, TMEM16A deletion also did not cause detectable changes in either spontaneous or agonist (i.e. KCl, oxytocin, and PGF2α)-induced contractions. Moreover, in vivo the TMEM16ASMKO mice gave birth at full term with the same litter size as genetically identical control mice. Finally, TMEM16A immunostaining in both control and TMEM16ASMKO mice revealed that this protein was highly expressed in the endometrial stroma, but did not co-localize with a smooth muscle specific marker MYH11. Collectively, these results unequivocally demonstrate that TMEM16A does not serve as a pacemaking channel for spontaneous uterine contraction, neither does it function as a depolarizing channel for agonist-evoked uterine contraction. Yet these two functions could underlie the normal gestation length and litter size in the TMEM16ASMKO mice.
Statistical inference of genetic pathway analysis in high dimensions
Authors: Liu Yang , Sun Wei , Reiner Alexander P , Kooperberg Charles , He Qianchuan
Published: June 2019

Genetic pathway analysis has become an important tool for investigating the association between a group of genetic variants and traits. With dense genotyping and extensive imputation, the number of genetic variants in biological pathways has increased considerably and sometimes exceeds the sample size $n$. Conducting genetic pathway analysis and statistical inference in such settings is challenging. We introduce an approach that can handle pathways whose dimension $p$ could be greater than $n$. Our method can be used to detect pathways that have nonsparse weak signals, as well as pathways that have sparse but stronger signals. We establish the asymptotic distribution for the proposed statistic and conduct theoretical analysis on its power. Simulation studies show that our test has correct Type I error control and is more powerful than existing approaches. An application to a genome-wide association study of high-density lipoproteins demonstrates the proposed approach.
A Mortality Analysis of Letermovir Prophylaxis for Cytomegalovirus (CMV) in CMV-seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation
Authors: Ljungman Per , Schmitt Michael , Marty Francisco M , Maertens Johan , Chemaly Roy F , Kartsonis Nicholas A , Butterton Joan R , Wan Hong , Teal Valerie L , Sarratt Kendra , Murata Yoshihiko , Leavitt Randi Y , Badshah Cyrus
Published: June 2019

Background

In a phase 3 trial, letermovir reduced clinically significant cytomegalovirus infections (CS-CMVi) and all-cause mortality at week 24 versus placebo in CMV-seropositive allogeneic hematopoietic cell transplantation (HCT) recipients. This post hoc analysis of phase 3 data further investigated the effects of letermovir on all-cause mortality.

Methods

Kaplan-Meier survival curves were generated by treatment group for all-cause mortality. Observations were censored at trial discontinuation for reasons other than death or at trial completion. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox modeling, adjusting for risk factors associated with mortality.

Results

Of 495 patients with no detectable CMV DNA at randomization, 437 had vital-status data available through week 48 post-HCT at trial completion (101 deaths, 20.4%). Following letermovir prophylaxis, the HR for all-cause mortality was 0.58 (95% CI, 0.35–0.98; P = .04) at week 24 and 0.74 (95% CI, 0.49–1.11; P = .14) at week 48 post-HCT versus placebo. Incidence of all-cause mortality through week 48 post-HCT in the letermovir group was similar in patients with or without CS-CMVi (15.8 vs 19.4%; P = .71). However, in the placebo group, all-cause mortality at week 48 post-HCT was higher in patients with versus those without CS-CMVi (31.0% vs 18.2%; P = .02). The HR for all-cause mortality in patients with CS-CMVi was 0.45 (95% CI, 0.21–1.00; P = .05) at week 48 for letermovir versus placebo.

Conclusions

Letermovir may reduce mortality by preventing or delaying CS-CMVi in HCT recipients.

Clinical Trials Registration

clinicaltrials.gov, NCT02137772.
Mantle-induced temperature anomalies do not reach the inner core boundary
Authors: Davies Christopher J , Mound Jon E
Published: June 2019

Temperature anomalies in Earth’s liquid core reflect the vigour of convection and the nature and extent of thermal core–mantle coupling. Numerical simulations suggest that longitudinal temperature anomalies forced by lateral heat flow variations at the core–mantle boundary (CMB) can greatly exceed the anomalies that arise in homogeneous convection (i.e. with no boundary forcing) and may even penetrate all the way to the inner core boundary. However, it is not clear whether these simulations access the relevant regime for convection in Earth’s core, which is characterized by rapid rotation (low Ekman number E) and strong driving (high Rayleigh number Ra). We access this regime using numerical simulations of non-magnetic rotating convection with imposed heat flow variations at the outer boundary (OB) and investigate the amplitude and spatial pattern of thermal anomalies, focusing on the inner and outer boundaries. The 108 simulations cover the parameter range 10−4 ≤ E ≤ 10−6 and Ra = 1−800 times the critical value. At each Ra and E we consider two heat flow patterns—one derived from seismic tomography and the hemispheric $Y_1^1$ spherical harmonic pattern—with amplitudes measured by the parameter q⋆ = 2.3, 5 as well as the case of homogeneous convection. At the OB the forcing produces strong longitudinal temperature variations that peak in the equatorial region. Scaling relations suggest that the longitudinal variations are weakly dependent on E and Ra and are much stronger than in homogeneous convection, reaching O(1) K at core conditions if q⋆ ≈ 35. At the inner boundary, latitudinal and longitudinal temperature variations depend weakly on Ra and q⋆ and decrease strongly with E, becoming practically indistinguishable between homogeneous and heterogeneous cases at E = 10−6. Interpreted at core conditions our results suggest that heat flow variations on the CMB are unlikely to explain the large-scale variations observed by seismology at the top of the inner core.
Key aspects for the sustainable coordination of a process to facilitate holistic well-being in South African schools
Authors: Kitching Ansie Elizabeth , van Rooyen Bianke
Published: June 2019

A holistic well-being approach, understood as an approach that pays attention to the promotion of individual, relational and collective well-being in a particular context, is proposed as a way to address the fragmented nature in which mental health and well-being programmes are implemented in school communities in South Africa. The goal of this paper is to indicate key aspects for sustainable coordination of a process to facilitate holistic well-being in South African schools. Research was conducted in six South African schools with the aim of developing an integrated, multilevel process to facilitate holistic well-being in these contexts. A participatory action learning and action research approach was applied. As part of this research, key aspects that could contribute to the sustainable coordination of holistic well-being were identified. The research comprised a cross-case analysis of the data gathered, as well as a focus group that was held with the coordinators who facilitated the development of the process in each school. In addition, the school principals completed a semi-structured questionnaire, and Skype interviews were conducted with four international experts. The five aspects identified as key to the sustainable coordination of well-being are: that ownership and responsibility should reside in the school context; that there should be a clear vision for the promotion of holistic well-being; that the connections between all involved should be deepened; that all efforts to promote holistic well-being should be integrated, and that the complexity of the process should be acknowledged.
Gene therapy for hearing loss
Authors: Omichi Ryotaro , Shibata Seiji B , Morton Cynthia C , Smith Richard J H
Published: June 2019

Sensorineural hearing loss (SNHL) is the most common sensory disorder. Its underlying etiologies include a broad spectrum of genetic and environmental factors that can lead to hearing loss that is congenital or late onset, stable or progressive, drug related, noise induced, age related, traumatic or post-infectious. Habilitation options typically focus on amplification using wearable or implantable devices; however exciting new gene-therapy-based strategies to restore and prevent SNHL are actively under investigation. Recent proof-of-principle studies demonstrate the potential therapeutic potential of molecular agents delivered to the inner ear to ameliorate different types of SNHL. Correcting or preventing underlying genetic forms of hearing loss is poised to become a reality. Herein, we review molecular therapies for hearing loss such as gene replacement, antisense oligonucleotides, RNA interference and CRISPR-based gene editing. We discuss delivery methods, techniques and viral vectors employed for inner ear gene therapy and the advancements in this field that are paving the way for basic science research discoveries to transition to clinical trials.
Long-term fluorescence hyperspectral imaging of on-chip treated co-culture tumour spheroids to follow clonal evolution
Authors: St-Georges-Robillard Amélie , Cahuzac Maxime , Péant Benjamin , Fleury Hubert , Lateef Muhammad Abdul , Ricard Alexis , Sauriol Skye Alexandre , Leblond Frédéric , Mes-Masson Anne-Marie , Gervais Thomas
Published: June 2019

Multicellular tumour spheroids are an ideal in vitro tumour model to study clonal heterogeneity and drug resistance in cancer research because different cell types can be mixed at will. However, measuring the individual response of each cell population over time is challenging: current methods are either destructive, such as flow cytometry, or cannot image throughout a spheroid, such as confocal microscopy. Our group previously developed a wide-field fluorescence hyperspectral imaging system to study spheroids formed and cultured in microfluidic chips. In the present study, two subclones of a single parental ovarian cancer cell line transfected to express different fluorophores were produced and co-culture spheroids were formed on-chip using ratios forming highly asymmetric subpopulations. We performed a 3D proliferation assay on each cell population forming the spheroids that matched the 2D growth behaviour. Response assays to PARP inhibitors and platinum-based drugs were also performed to follow the clonal evolution of mixed populations. Our experiments show that hyperspectral imaging can detect spheroid response before observing a decrease in spheroid diameter. Hyperspectral imaging and microfluidic-based spheroid assays provide a versatile solution to study clonal heterogeneity, able to measure response in subpopulations presenting as little as 10% of the initial spheroid.
MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis
Authors: Spec Andrej , Pullman John , Thompson George R , Powderly William G , Tobin Ellis H , Vazquez Jose , Wring Stephen A , Angulo David , Helou Silvia , Pappas Peter G ,   Mycoses Study Group, Vasquez Jose , Ostrosky-Zeichner Luis , Patterson Thomas , Alexander Barbara , Boucher Helen , Pappas Peter , Betts Robert , Schuster Mindy , Shoham Shmuel , Revankar Sanjay , Mushatt David , Bedimo Roger , Freifeld Alison , Nguyen Minh Hong , Mylonakis Eleftherios , Kett Daniel , Reboli Annette , Walsh Thomas , Pouch Stephanie , Almyroudis Nikolaos , Andes David , Hadley Susan , Barron Michelle , Mullane Katheen , Miller Loren
Published: June 2019

Objectives

To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 μM·h) in >80% of the intended population.

Methods

In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment.

Results

Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response.

Conclusions

The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.
Geriatric Research Policy: Japan Clinical Oncology Group (JCOG) policy
Authors: Mizutani Tomonori , Nakamura Kenichi , Fukuda Haruhiko , Ogawa Asao , Hamaguchi Tetsuya , Nagashima Fumio ,   Geriatric Study Committee/Japan Clinical Oncology Group
Published: June 2019

Due to the rapid aging of Japan’s population, clinical research focusing on older patients with cancer is urgently needed. The Japan Clinical Oncology Group (JCOG) has conducted several such clinical trials, but there has been no formal policy for geriatric research. We have therefore established a JCOG policy for geriatric cancer research.

We defined the patient selection policy based on treatment tolerance and chronological age. Older patients are categorized into three conceptual groups: ‘fit patients’ who can undergo the same standard treatment given to younger patients, ‘frail patients’ for whom best supportive or palliative care is indicated and ‘vulnerable patients’ who fall between the fit and frail categories. Unmet needs often exist for vulnerable patients.

The policy recommends that study endpoints include not only survival but also other endpoints such as physical and cognitive function because the objective of therapy in older patients is not only extended life expectancy but also maintenance of the patient’s general condition. In this viewpoint, co-primary or composite endpoints that incorporate geriatric assessment in the study design are often applicable.

Study design will differ depending on the study population, clinical question, and treatment. Even for older patients, a randomized clinical trial is still the gold standard when the clinical question asks which treatment is better. An observational study of a broader population is applicable for investigating actual conditions of older patients.

This JCOG Geriatric Research Policy includes several practical solutions for various issues in geriatric research. We plan to revise this policy periodically to guide future geriatric research.
Towards a radially resolved semi-analytic model for the evolution of disc galaxies tuned with machine learning
Authors: Forbes John C , Krumholz Mark R , Speagle Joshua S
Published: June 2019

We present a flexible, detailed model for the evolution of galactic discs in a cosmological context since z ≈ 4, including a physically motivated model for radial transport of gas and stars within galactic discs. This expansion beyond traditional semi-analytic models that do not include radial structure, or include only a prescribed radial structure, enables us to study the internal structure of disc galaxies and the processes that drive it. In order to efficiently explore the large parameter space allowed by this model, we construct a neural-network-based emulator that can quickly return a reasonable approximation for many observables we can extract from the model, e.g. the star formation rate or the half-mass stellar radius, at different redshifts. We employ the emulator to constrain the model parameters with Bayesian inference by comparing its predictions to 11 observed galaxy scaling relations at a variety of redshifts. The constrained models agree well with observations, both those used to fit the data and those not included in the fitting procedure. These models will be useful theoretical tools for understanding the increasingly detailed observational data sets from Integral Field Units (IFUs).
A critical assessment of turbulence models for 1D core-collapse supernova simulations
Authors: Müller Bernhard
Published: June 2019

It has recently been proposed that global or local turbulence models can be used to simulate core-collapse supernova explosions in spherical symmetry (1D) more consistently than with traditional approaches for parametrized 1D models. However, a closer analysis of the proposed schemes reveals important consistency problems. Most notably, they systematically violate energy conservation as they do not balance buoyant energy generation with terms that reduce potential energy, thus failing to account for the physical source of energy that buoyant convection feeds on. We also point out other non-trivial consistency requirements for viable turbulence models. The Kuhfuss model from the 1980s proves more consistent than the newly proposed approaches for supernovae, but still cannot account naturally for all the relevant physics for predicting explosion properties. We perform numerical simulations for a $20 \, \mathrm{M}_\odot$ progenitor to further illustrate problems of 1D turbulence models. If the buoyant driving term is formulated in a conservative manner, the explosion energy of ${\sim }2\times 10^{51}\, \mathrm{erg}$ for the corresponding non-conservative turbulence model is reduced to $\lt 10^{48} \, \mathrm{erg}$ even though the shock expands continuously. This demonstrates that the conservation problem cannot be ignored. Although plausible energies can be reached using an energy-conserving model when turbulent viscosity is included, it is doubtful whether the energy budget of the explosion is regulated by the same mechanism as in multidimensional models. We conclude that 1D turbulence models based on a spherical Reynolds decomposition cannot provide a more consistent approach to supernova explosion and remnant properties than other phenomenological approaches before some fundamental problems are addressed.
Galaxies in X-ray selected clusters and groups in Dark Energy Survey data – II. Hierarchical Bayesian modelling of the red-sequence galaxy luminosity function
Authors: Zhang Y , Miller C J , Rooney P , Bermeo A , Romer A K , Vergara Cervantes C , Rykoff E S , Hennig C , Das R , McKay T , Song J , Wilcox H , Bacon D , Bridle S L , Collins C , Conselice C , Hilton M , Hoyle B , Kay S , Liddle A R , Mann R G , Mehrtens N , Mayers J , Nichol R C , Sahlén M , Stott J , Viana P T P , Wechsler R H , Abbott T , Abdalla F B , Allam S , Benoit-Lévy A , Brooks D , Buckley-Geer E , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Castander F J , Crocce M , Cunha C E , D’Andrea C B , da Costa L N , Diehl H T , Dietrich J P , Eifler T F , Flaugher B , Fosalba P , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Honscheid K , James D J , Jeltema T , Kuehn K , Kuropatkin N , Lima M , Lin H , Maia M A G , March M , Marshall J L , Melchior P , Menanteau F , Miquel R , Ogando R L C , Plazas A A , Sanchez E , Schubnell M , Sevilla-Noarbe I , Smith M , Soares-Santos M , Sobreira F , Suchyta E , Swanson M E C , Tarle G , Walker A R ,   (DES Collaboration)
Published: June 2019

Using ∼100 X-ray selected clusters in the Dark Energy Survey Science Verification data, we constrain the luminosity function (LF) of cluster red-sequence galaxies as a function of redshift. This is the first homogeneous optical/X-ray sample large enough to constrain the evolution of the LF simultaneously in redshift (0.1 < z < 1.05) and cluster mass ($13.5 \le \rm {log_{10}}(M_{200crit}) \sim \lt 15.0$). We pay particular attention to completeness issues and the detection limit of the galaxy sample. We then apply a hierarchical Bayesian model to fit the cluster galaxy LFs via a Schechter function, including its characteristic break (m*) to a faint end power-law slope (α). Our method enables us to avoid known issues in similar analyses based on stacking or binning the clusters. We find weak and statistically insignificant (∼1.9σ) evolution in the faint end slope α versus redshift. We also find no dependence in α or m* with the X-ray inferred cluster masses. However, the amplitude of the LF as a function of cluster mass is constrained to ${\sim } 20{{\ \rm per\ cent}}$ precision. As a by-product of our algorithm, we utilize the correlation between the LF and cluster mass to provide an improved estimate of the individual cluster masses as well as the scatter in true mass given the X-ray inferred masses. This technique can be applied to a larger sample of X-ray or optically selected clusters from the Dark Energy Survey, significantly improving the sensitivity of the analysis.
A Network Autonomy Framework: Reconceptualizing Special District Autonomy in Polycentric Systems
Authors: Greer Robert A , Scott Tyler A
Published: June 2019

The widespread proliferation of special districts and their role in producing and delivering public goods and services has been well documented. Each new entity further fragments government authority, and thus their autonomy is a critical determinant of how local governance systems function. Existing theories of special district autonomy emphasize formal institutional attributes such as election structure and state restrictions. We argue that this approach does not fully incorporate how relational dynamics such as functional interdependence, interest alignment, and social capital affect how special districts fit within regional polycentric governance systems. We propose a Network Autonomy Framework for local governments that focuses on relational dynamics between co-located1 governments and demonstrate an example of how this framework can be applied to a metropolitan region. By understanding how co-located governments relate to one another, we can gain a deeper understanding of special districts’ role in local governance systems and advance propositions as to how they will affect a variety of local policy outcomes.
Efficacy and safety of apremilast for Behçet’s syndrome: a real-life single-centre Italian experience
Authors: De Luca Giacomo , Cariddi Adriana , Campochiaro Corrado , Vanni Daniele , Boffini Nicola , Tomelleri Alessandro , Cavalli Giulio , Dagna Lorenzo
Published: June 2019

Objectives

To evaluate the efficacy and safety of apremilast in treating oral ulcers (OUs), the cardinal and high-disabling feature of Behçet’s disease (BD).

Methods

Twelve consecutive patients affected by BD with recurrent/relapsing OUs resistant and/or intolerant to conventional therapy were enrolled and prospectively followed. The primary endpoint was the number of OUs at week 12. Secondary endpoints were modification from baseline to week 12 in Behçet’s Syndrome Activity Score (BSAS), Behçet’s Disease Current Activity Form (BDCAF) score, Behçet’s Disease Quality of Life (BDQOL) scale and pain of OUs, as measured by a visual analogue scale (VAS). All adverse events (AEs) were recorded during follow-up. Non-parametric tests (Wilcoxon rank test) were used and a P-value <0.05 was considered statistically significant.

Results

After 12 weeks of apremilast, there was a significant reduction in the number of OUs [0.58 (s.d. 0.67) vs 3.33 (s.d. 1.45) at baseline, P = 0.02] that was paralleled by improvement in disease activity: BSAS was 16.8 (s.d. 9.1) [from 45.9 (s.d. 19.6) at baseline] (P = 0.02), BDCAF score was 0.72 (s.d. 0.65) [vs 2.45 (s.d. 1.0) at baseline] (P = 0.04) and the VAS score for pain decreased to 23.3 (s.d. 13.7) [vs 67.9 (s.d. 17.2) at baseline] (P = 0.02). Consistently, an improvement of BDQOL was assessed (P = 0.02). Clinical improvement led to complete steroid discontinuation in six patients and a tapering of the prednisone dose in two patients (P = 0.016). Colchicine was discontinued in six of nine patients (P = 0.031). AEs related to apremilast occurred in four patients (mainly due to gastrointestinal AEs), leading to drug discontinuation in all of them.

Conclusion

Our preliminary real-world data support the use of apremilast as an effective therapeutic strategy against BD-related recurrent OUs resistant or intolerant to first-line therapy.
Vagabond Microbes, Leaky Laboratories and Epidemic Mapping: Alexandre Yersin and the 1898 Plague Epidemic in Nha Trang
Authors: Lynteris Christos
Published: June 2019

This article examines the epidemic mapping produced by the Pasteurian doctor Alexandre Yersin in the course of the outbreak of bubonic plague in the town of Nha Trang (French Indochina, 1898). Examining how Yersin responded to and reasoned about the outbreak as this unfolded around his laboratory, the article argues for a situated, processual approach of epidemic mapping. Considering four maps produced by Yersin during the outbreak, it is argued that these should not be simply seen as visual objects aimed at establishing and systematising epidemiological knowledge. Instead the changes evinced in and between these maps were driven by Yersin’s desire to distance plague from his laboratory, which stood accused as the origin of the epidemic. It is thus argued that, in this case, epidemic mapping acquires a distancing function, with its aim being to symbolically banish the source of the outbreak back to China.
Oscillatory patterns in the electroencephalogram at sleep onset
Authors: Achermann Peter , Rusterholz Thomas , Stucky Benjamin , Olbrich Eckehard
Published: June 2019

Falling asleep is a gradually unfolding process. We investigated the role of various oscillatory activities including sleep spindles and alpha and delta oscillations at sleep onset (SO) by automatically detecting oscillatory events. We used two datasets of healthy young males, eight with four baseline recordings, and eight with a baseline and recovery sleep after 40 h of sustained wakefulness. We analyzed the 2-min interval before SO (stage 2) and the five consecutive 2-min intervals after SO. The incidence of delta/theta events reached its maximum in the first 2-min episode after SO, while the frequency of them was continuously decreasing from stage 1 onwards, continuing over SO and further into deeper sleep. Interestingly, this decrease of the frequencies of the oscillations were not affected by increased sleep pressure, in contrast to the incidence which increased. We observed an increasing number of alpha events after SO, predominantly frontally, with their prevalence varying strongly across individuals. Sleep spindles started to occur after SO, with first an increasing then a decreasing incidence and a continuous decrease in their frequency. Again, the frequency of the spindles was not altered after sleep deprivation. Oscillatory events revealed derivation dependent aspects. However, these regional aspects were not specific of the process of SO but rather reflect a general sleep related phenomenon. No individual traits of SO features (incidence and frequency of oscillations) and their dynamics were observed. Delta/theta events are important features for the analysis of SO in addition to slow waves.
Adolescent SBIRT Practices Among Pediatricians in Massachusetts
Authors: Levy Sharon , Wiseblatt Aria , Straus John H. , Strother Heather , Fluet Christina , Harris Sion K.
Published: June 2019

Objectives:

Adolescent Screening, Brief Intervention, and Referral to Treatment (SBIRT) in primary care is a key strategy to prevent, identify, and respond to substance use problems and disorders, including opioid and other drug addictions. Despite substantial investment in recent years to increase its implementation, few studies have reported on recent levels of SBIRT implementation among pediatricians. We aimed to assess self-reported use of the SBIRT framework with adolescent patients among Massachusetts pediatricians, and describe trends since an earlier survey.

Methods:

We analyzed responses to a cross-sectional survey mailed in 2017 to a representative sample of pediatricians in Massachusetts. We computed response frequencies for all SBIRT practice questions. We used the chi-square test to compare current data to data collected in 2014, as we found no demographic differences between the 2 samples.

Results:

Nearly all pediatricians in the 2017 sample (n = 160) reported annual screening of their adolescent patients (99%). The majority reported giving positive reinforcement (87%), brief advice (92%), counseling (90%), and referral to treatment (66%) in response to screen results. Compared with 2014, a significantly higher proportion of pediatricians in 2017 referred patients who screened positively for problematic alcohol use, but perceived barriers to screening and follow-up remain, such as insufficient time to screen and patient refusal to return.

Conclusions:

Among respondents to a Massachusetts pediatrician survey, we found high rates of delivering SBIRT in accordance with published guidelines, though barriers remain. Whether the content of the counseling adheres to guidelines is unknown.